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Medical Studies

How to Write a Medical Case Study Report

Last Updated: April 18, 2024 Fact Checked

This article was medically reviewed by Mark Ziats, MD, PhD and by wikiHow staff writer, Jennifer Mueller, JD . Dr. Mark Ziats is an Internal Medicine Physician, Scientist, Entrepreneur, and the Medical Director of xBiotech. With over five years of experience, he specializes in biotechnology, genomics, and medical devices. He earned a Doctor of Medicine degree from Baylor College of Medicine, a Ph.D. in Genetics from the University of Cambridge, and a BS in Biochemistry and Chemistry from Clemson University. He also completed the INNoVATE Program in Biotechnology Entrepreneurship at The Johns Hopkins University - Carey Business School. Dr. Ziats is board certified by the American Board of Internal Medicine. There are 15 references cited in this article, which can be found at the bottom of the page. This article has been fact-checked, ensuring the accuracy of any cited facts and confirming the authority of its sources. This article has been viewed 186,984 times.

You've encountered an interesting and unusual case on your rounds, and a colleague or supervising physician says, "Why don't you write up a case study report?" If you've never written one before, that might sound intimidating, but it's a great way to get started in medical writing. Case studies always follow a standard structure and format, so the writing is very formulaic once you get the hang of it. Read on for a step-by-step guide to writing your first case study report.

What is a case study report?

Step 1 A case study report is an academic publication describing an unusual or unique case.

Medical students or residents typically do the bulk of the writing of the report. If you're just starting your medical career, a case study report is a great way to get a publication under your belt. [2] X Research source

Step 2 Your report discusses the case presented by one patient.

If the patient is a minor or is incapable of giving informed consent, get consent from their parents or closest relative. [4] X Trustworthy Source PubMed Central Journal archive from the U.S. National Institutes of Health Go to source
Your hospital likely has specific consent forms to use. Ask your supervising physician if you're not sure where to get one.
Some journals also have their own consent form. Check your target journal's author or submission information to make sure. [5] X Research source

How is a case study report structured?

Step 1 A typical report consists of an abstract, intro, case description, discussion, and conclusion.

Even though the introduction is the first part of a case study report, doctors typically write it last. You'll have a better idea of how to introduce your case study to readers after you've written it.
Your abstract comes at the top, before the introduction, and provides a brief summary of the entire report. Unless your case study is published in an open-access journal, the abstract is the only part of the article many readers will see.

Step 2 Check your target journal for possible variations.

Many journals offer templates and checklists you can use to make sure your case study includes everything necessary and is formatted properly—take advantage of these! Some journals, such as BMJ Case Reports , require all case studies submitted to use their templates.

Drafting Your Medical Case Study Report

Step 1 Pull all of the hospital records for the case.

Patient description
Chronological case history
Physical exam results
Results of any pathological tests, imaging, or other investigations
Treatment plan
Expected outcome of treatment
Actual outcome of treatment

Step 2 Write a draft of the case presentation.

Why the patient sought medical help (you can even use their own words)
Important information that helped you settle on your diagnosis
The results of your clinical examination, including diagnostic tests and their results, along with any helpful images
A description of the treatment plan
The outcome, including how and why treatment ended and how long the patient was under your care [11] X Trustworthy Source PubMed Central Journal archive from the U.S. National Institutes of Health Go to source

Step 3 Research the existing literature on the patient's condition and treatment.

You will need references to back up symptoms of the condition, common treatment, and the expected outcome of that common treatment.
Use your research to paint a picture of the usual case of a patient with a similar condition—it'll help you show how unusual and different your patient's case is.
Generally, aim for around 20 references—no fewer than 15, but no more than 25. [13] X Trustworthy Source PubMed Central Journal archive from the U.S. National Institutes of Health Go to source

Step 4 Write a section discussing the case in light of your research.

Close your discussion section with a summary of the lessons learned from the case and why it's significant to consider when treating similar cases in the future.
Outline any open questions that remain. You might also provide suggestions for future research.

Step 5 Complete your introduction and conclusion after you've written the body.

In your conclusion, you might also give suggestions or recommendations to readers based on what you learned as a result of the case.
Some journals don't want a separate conclusion section. If that's the case for one of your target journals, just move this paragraph to the end of your discussion section.

Polishing Your Report for Submission to Publishers

Step 1 Come up with a title for your case study.

Most titles are fewer than 10 words long and include the name of the disease or condition treated.
You might also include the treatment used and whether the outcome was successful. When deciding what to include, think about the reason you wrote the case study in the first place and why you think it's important for other clinicians to read.

Step 2 Identify the authors of the report on the title page.

Made a significant intellectual contribution to the case study report
Was involved in the medical care of the patient reported
Can explain and defend the data presented in the report
Has approved the final manuscript before submission for publication

Step 3 Write an abstract summarizing the entire article.

Keep in mind that the abstract is not just going to be the first thing people read—it will often be the only thing people read. Make sure that if someone is going to walk away having only read the abstract, they'll still get the same message they would have if they read the whole thing.
There are 2 basic types of abstract: narrative and structured. A narrative abstract is a single paragraph written in narrative prose. A structured abstract includes headings that correspond with the sections of the paper, then a brief summary of each section. Use the format preferred by your target journal.

Step 4 Choose keywords that will help readers find your case study.

Look for keywords that are relevant to your field or sub-field and directly related to the content of your article, such as the name of the condition or specific treatments you used.
Most journals allow 4-8 keywords but check the submission guidelines of your target journal to make sure.

Blur out the patient's face as well as any tattoos, birthmarks, or unrelated scars that are visible in diagnostic images.

Step 6 Include your acknowledgments and conflict of interest statement.

It's common to thank the patient, but that's up to you. Even if you don't, include a statement indicating that you have the patient's written, informed consent to publish the information.
Read the journal's submission guidelines for a definition of what that journal considers a conflict of interest. They're generally the same, but some might be stricter than others. [22] X Research source

Step 7 Compile and format your reference section.

If you're not familiar with the citation style used by your target journal, check online for a guide. There might also be one available at your hospital or medical school library.
Medical librarians can also help with citation style and references if you run into something tricky—don't just wing it! Correct citation style insures that readers can access the materials you cite.

Step 8 Get feedback on your final draft.

It's also a good idea to get a beta reader who isn't a medical professional. Their comments can help you figure out where you need to clarify your points.
Read a lot of case studies published in your target journals—it will help you internalize the tone and style that journal is looking for.

Submitting Your Report to Publishers

Step 1 Choose target journals that publish similar content.

Look into the background and reputation of journals before you decide to submit to them. Only seek publication from reputable journals in which articles go through a peer-review process.
Find out what publishing fees the journals charge. Keep in mind that open-access journals tend to charge higher publishing fees. [26] X Research source
Read each journal's submission and editorial guidelines carefully. They'll tell you exactly how to format your case study, how long each section should be, and what citation style to use. [27] X Research source
For electronic journals that only publish case reports, try BMJ Case Reports , Journal of Medical Case Reports , or Radiology Case Reports .

Step 2 Submit your manuscript according to the journal's requirements.

If your manuscript isn't suitable for the journal you submitted to, the journal might offer to forward it to an associated journal where it would be a better fit.
When your manuscript is provisionally accepted, the journal will send it to other doctors for evaluation under the peer-review process.
Most medical journals don't accept simultaneous submissions, meaning you'll have to submit to your first choice, wait for their decision, then move to the next journal on the list if they don't bite.

Step 3 Revise your manuscript based on peer review comments.

Along with your revised manuscript, include a letter with your response to each of the reviewer's comments. Where you made revisions, add page numbers to indicate where the revisions are that address that reviewer's comments.
Sometimes, doctors involved in the peer review process will indicate that the journal should reject the manuscript. If that's the case, you'll get a letter explaining why your case study report won't be published and you're free to submit it elsewhere.

Step 4 Complete final copy-editing if the editors approve your article.

Some journals require you to have your article professionally copy-edited at your own cost while others do this in-house. The editors will let you know what you're responsible for.

Step 5 Pay the article processing charge if your article is accepted.

With your acceptance letter, you'll get instructions on how to make payment and how much you owe. Take note of the deadline and make sure you pay it as soon as possible to avoid publication delays.
Some journals will publish for free, with an "open-access option" that allows you to pay a fee only if you want open access to your article. [32] X Research source

Through the publishing agreement, you assign your copyright in the article to the journal. This allows the journal to legally publish your work. That assignment can be exclusive or non-exclusive and may only last for a specific term. Read these details carefully!
If you published an open-access article, you don't assign the copyright to the publisher. The publishing agreement merely gives the journal the right to publish the "Version of Record." [33] X Research source

How do I find a suitable case for a report?

Step 1 Keep your eye out for unusual or interesting cases.

A rare disease, or unusual presentation of any disease
An unusual combination of diseases or conditions
A difficult or inconclusive diagnosis
Unexpected developments or responses to treatment
Personal impact
Observations that shed new light on the patient's disease or condition

Step 2 Discuss possible cases with your medical team.

There might be other members of your medical team that want to help with writing. If so, use one of these brainstorming sessions to divvy up writing responsibilities in a way that makes the most sense given your relative skills and experience.
Senior doctors might also be able to name some journals that would potentially publish your case study. [36] X Research source

Expert Q&A

↑ https://www.elsevier.com/connect/authors-update/the-dos-and-donts-of-writing-and-publishing-case-reports
↑ https://www.bmj.com/content/350/bmj.h2693
↑ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686928/
↑ https://health.usf.edu/medicine/internalmedicine/im-impact/~/media/B3A3421F4C144FA090AE965C21791A3C.ashx
↑ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597880/
↑ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476221/
↑ https://www.springer.com/gp/authors-editors/authorandreviewertutorials/writing-a-journal-manuscript/title-abstract-and-keywords/10285522
↑ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597880/
↑ https://thelancet.com/pb/assets/raw/Lancet/authors/tl-info-for-authors.pdf
↑ https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-017-1351-y
↑ https://guides.himmelfarb.gwu.edu/casereports
↑ https://casereports.bmj.com/pages/authors/
↑ https://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-7-239
↑ https://research.chm.msu.edu/students-residents/writing-a-case-report
↑ https://authorservices.taylorandfrancis.com/publishing-your-research/moving-through-production/copyright-for-journal-authors/#

About This Article

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The content of this article is not intended to be a substitute for professional medical advice, examination, diagnosis, or treatment. You should always contact your doctor or other qualified healthcare professional before starting, changing, or stopping any kind of health treatment.

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How to write a medical case report

Related content
Peer review
Seema Biswas , editor-in-chief, BMJ Case Reports, London, UK ,
Oliver Jones , student editor, BMJ Case Reports, London, UK

Two BMJ Case Reports journal editors take you through the process

This article contains...

- Choosing the right patient

- Choosing the right message

- Before you begin - patient consent

- How to write your case report

- How to get published

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 better and safer patient care.

For many medical students and junior doctors, a case report may be their first attempt at medical writing. A published case report will look impressive on your curriculum vitae, particularly if it is on a topic of your chosen specialty. Publication will be an advantage when applying for foundation year posts and specialty training, and many job applications have points allocated exclusively for publications in peer reviewed journals, including case reports.

The writing of a case report rests on skills that medical students acquire in their medical training, which they use throughout their postgraduate careers: these include history taking, interpretation of clinical signs and symptoms, interpretation of laboratory and imaging results, researching disease aetiology, reviewing medical evidence, and writing in a manner that clearly and effectively communicates with the reader.

If you are considering writing a case report, try to find a senior doctor who can be a supervising coauthor and help you decide whether you have a message worth writing about, that you have chosen the correct journal to submit to (considering the format that the journal requires), that the process is transparent and ethical at all times, and that your patient is not compromised in your writing. Indeed, try to include your patient in the process from the outset, and always gain consent.

A case report is the first line of medical evidence, and over time has become an important medium for sharing new findings (box 1). High quality case reports successfully bring together the various domains of medicine such as physiology, pathology, and anatomy. Using the patient as the focus, case reports provide a clinical “coat peg” on which to hang this knowledge.

Box 1: Notable case reports through the ages

Many case reports have changed the way clinicians view health and disease. For example, in 1861 the French surgeon Pierre Paul Broca reported the case of a dysphasic patient nicknamed “Tan”—owing to his inability to say any other words. After Tan’s death, Broca did an autopsy and discovered a syphilitic lesion in the frontal lobe of the brain, leading to the hypothesis of a speech centre in the brain—later known as Broca’s area. 1 Other notable case reports have documented the discovery of the Bence-Jones protein, 2 the first descriptions of Parkinson’s disease, 3 and AIDS. 4

Choosing the right patient

We can learn from all patients, but choose a patient from whom there is something new to learn. Search the literature and decide whether the topic you want to discuss, whether clinical or non-clinical (a radiological or microbiological finding, for example), has already been well discussed.

Your patient should ideally be someone who is not simply a willing participant in this process but someone who wants their story to be told to educate students, doctors, and other patients. Many journals have an option for patients to contribute to the manuscript.

Choosing the right message

Rare diseases are not in themselves a reason to write up a case, but unusual presentations of a common disease are important to communicate to the medical community. Early or subtle signs and symptoms that are easily missed are important for us to learn from. Indeed, the learning value of your case is the single most important factor in determining whether it is likely to be published.

Have in mind the journal that you want to submit your manuscript to before you begin to write. Your case and the message should fit with the style of the journal, whether a specialist journal, a case reports journal, or a journal that publishes case presentations in different formats. This may include question and answer formats, quizzes, or even interactive online educational formats useful for exam revision—for example, Endgames ( The BMJ ), Epilogue ( Archives of Disease in Childhood ), or Images ( New England Journal of Medicine ). These adapted formats are important, as most of these journals no longer accept case reports written in their traditional format.

Also, be careful in your claims about new diseases and new treatments. Case reports cannot make claims about the efficacy of novel treatments on the basis of individual cases and limited follow-up time. The most important message is a new or novel learning point—that is, the educational message.

Before you begin

Once you have chosen your patient and discussed with them what you would like to write, show them the case report so that they may give informed consent to your manuscript submission and familiarise themselves with the website.

It is important that a patient understands how their case will appear online or in print and that they truly give informed consent. You should do this under the supervision of the senior doctor who is the supervising coauthor of your manuscript; ideally, the senior doctor would obtain consent.

Writing the case report

Case presentation.

Begin with the case presentation (box 2): describe your encounter with the patient, their symptoms, and their signs. You should already have an idea what your take home messages will be. If the journal presentation of the case report allows, you can write these take home messages as bullet points (box 3).

Box 2: Case presentation

Acute pancreatitis and severe hypertriglyceridaemia masking unsuspected underlying diabetic ketoacidosis.

After 48 hours of anorexia, nausea, and non-bloody vomiting at home, the patient presented to her local hospital, where the diagnosis of moderate acute pancreatitis was made, based on an abdominal computed tomogram and ultrasound and serum chemistry. Ongoing symptoms, including left upper quadrant, 7/10 stabbing pain with generalised abdominal cramps, led to her transfer to the closest tertiary hospital for further management.

On admission to the tertiary hospital, the patient was treated as having uncomplicated pancreatitis. Immediate management included intravenous rehydration therapy, antiemetics, and narcotics for pain control with further orders for nothing to be ingested until the patient was re-evaluated. Initial assessment of the patient showed a temperature of 37.3ºC, heart rate 110 beats/min, blood pressure 126/68 mm Hg, respiratory rate 14 breaths/min, and oxygen saturation 98% on room air. She had a normal body habitus and was not in distress; however, she had a moderate amount of abdominal discomfort. Her physical examination showed no xanthalasmas or skin eruptions, nor was a fruity odour detected. Her gastrointestinal examination showed diffuse tenderness, with a soft, non-distended abdomen. Also, no organomegally was noted. Other than tachycardia, her cardiorespiratory examination was unremarkable with the notable absence of tachypnoea.

The patient was previously healthy without any medical history or surgical history. Her medication list was limited to the oral contraceptive pill (ethinyl oestradiol, norgestimate). The patient described only occasional social alcohol consumption (none within the last week) and no binge drinking or recreational drug use in the past. There were no recent surgeries, gastrointestinal endoscopic procedures, or abdominal trauma. She denied fever, chills, rigors, or recent unintended weight loss. There was no history of polyuria or polydipsia.

She did not have any prodromal abdominal symptoms There had been no similar episodes previously. There was no family history of dyslipidaemias, pancreatitis, or gallstones. Her family history was relevant for rectal carcinoma in her paternal grandfather and type 2 diabetes in her maternal grandmother. Six hours after her arrival at the tertiary hospital, and 12 hours from her first presentation and assessment at the local rural hospital, the patient began to decompensate with rapid progression of hypotension, tachycardia, and tachypnoea. The acute decompensation to hypotension and shock was assumed to be due to progression of the pancreatitis with potential infection complicating the pancreatitis. The patient was aggressively rehydrated and started on broad spectrum antibiotics. However, the hypotension failed to respond to fluid resuscitation and there was increased patient distress. She was urgently referred to the intensive care unit for supportive measures and management.

Aboulhosn K, Arnason T. Acute pancreatitis and severe hypertriglyceridaemia masking unsuspected underlying diabetic ketoacidosis. BMJ Case Rep 2013;2013, doi: 10.1136/bcr-2013-200431 .

Box 3: Learning points

Postpartum hellp syndrome and subcapsular liver haematoma.

Subcapsular liver haematoma is a potentially life threatening complication of severe pre-eclampsia and haemolysis, the breakdown of red blood cells; elevated liver enzymes; low platelet count syndrome.

The complication is rare but should be considered with severe upper abdominal pain in obstetric patients, especially in the presence of pre-eclampsia.

Real time ultrasound imaging of the liver is often diagnostic.

Messerschmidt L, Andersen LL, Sorensen MB. Postpartum HELLP syndrome and subcapsular liver haematoma. BMJ Case Rep 2014, doi: 10.1136/bcr-2013-202503 .

You should separate your case presentation section from the investigations and differential diagnoses. The key points to remember to include are your choice of investigations and how they helped you establish a working diagnosis (box 4).

Box 4: Investigations

Unilateral presentation of postpartum cardiomyopathy misdiagnosed as pneumonia.

On arriving at the emergency department, the patient had severe shortness of breath at rest 10 days after delivery. Her vital signs included an oral temperature of 36.7ºC, blood pressure 163/102 mmHg, pulse rate 146 beats/min, and oxygen saturation 88% in room air. Treatment with supplemental oxygen by mask yielded an increase in oxygen saturation to 95%. Her physical examination revealed no jugular venous distension, hepatic enlargement, or pedal oedema; heart sounds were fast and regular, with no evidence of murmurs or additional sounds. On lung auscultation bilateral crackles were present. Her laboratory analysis showed mild non-specific indicators of stress with a leucocyte count of 9.3×10 3 cells/mm 3 , haemoglobin value of 10.6 g/dL, and a platelet count of 791×10 3 cells/mm 3 . Her electrocardiogram was similar to the one obtained a day earlier showing T wave inversion in leads V4–V6; however, chest radiography showed a more bilateral presentation compared with the previous one showing both heart enlargement and pulmonary oedema. A chest computed tomography angiography performed to exclude pulmonary artery embolisation confirmed the presence of cardiomegaly and pulmonary oedema with bilateral effusions (fig 1). ⇓ An echocardiogram showed a diminished ejection fraction of 15-20% confirming the diagnosis of postpartum cardiomyopathy.

Amit BH, Marmor A, Hussein A. Unilateral presentation of postpartum cardiomyopathy misdiagnosed as pneumonia. BMJ Case Rep 2010, doi: 10.1136/bcr.05.2010.3039 .

Fig 1 Chest computed tomogram performed after deterioration showing heart enlargement, pulmonary oedema, and bilateral pleural effusions mainly on the right. From Amit BH et al. BMJ Case Rep 2010, doi: 10.1136/bcr.05.2010.3039 .

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Imagine that you are presenting at a grand round and have to explain your choices to your colleagues—this is essentially what you are doing as you write your case report. Do not simply list your differential diagnoses; describe how you worked through your list of differentials and how you established a final diagnosis.

Also, make sure you collect and include high quality and well annotated images that not only explain radiological findings but also show their importance in establishing your diagnosis.

Good quality annotated images

Fig 2 Craniocervical x ray film showing fusion of the posterior arch of C1 to the occiput. A fracture was not evident, but clinical suspicion prompted a computed tomography scan

Fig 3 Axial, left, and sagittal, right, computed tomography scans of the craniocervical junction at presentation showing fusion of the left occipital condyle with the lateral mass of C1 and a fracture involving both elements. The fracture is indicated by the arrowheads

Outcome and follow-up

The outcome and your follow-up of the patient are important. In both your case presentation and the section on patient outcome, you should describe what happened to your patient in terms of their specific symptoms, their general wellbeing, and their lifestyle and activity.

Some journals require you to write a summary of your case report. This usually has a word limit and appears in medical search engines, such as Pubmed/MEDLINE. It is the equivalent of the abstract of a research paper.

Ensure that your title is scientific and clinical. Cryptic and humorous titles translate poorly across a global audience and do not always accurately reflect the content of your case report. You may find that the word limit does not permit you to write all the detail you would want to include in the summary, but the background section allows you to do this. Try to make sure that the background section does not repeat the summary.

Publication process

Clinical videos and images are important alternatives or potential additions to clinical case reports which many journals encourage authors to submit. Again, prepare these in collaboration with clinical teachers or coauthors, who will help you annotate these images and point out important learning messages, and do this from the outset in the format of the journal that you have researched well and decided to submit your manuscript to.

All submitted case reports are usually sent for peer review. Reviewers are chosen according to their specialty and clinical or academic interests. Your choice of key words is therefore important as these are the basis for the assignment of reviewers. Keywords are also important for other authors doing literature searches who discover your case report and cite this in their own writing.

Decisions to accept, revise, or reject are based on editors’ and reviewers’ opinions together, and every attempt is made to ensure that criticism is constructive and useful.

Dependent on how quickly your manuscript is reviewed, you should receive a decision on your manuscript within three to six weeks of submission. Outright rejections for reasons such as the unsuitability of your manuscript for the particular journal and its audience, manuscripts in the wrong format, incomplete sections (especially the case presentation and differential diagnosis sections), and plagiarism tend to be prompt, and they would be easily avoided by following the steps above and choosing your patient, your topic, your journal, and your particular manuscript format well.

Rejections on the basis of the content of the case report tend to be at the peer review stage and may be a few weeks after submission. They could include reasons such as the lack of novelty or educational message, a poor literature search, or inconsistent clinical management. Again, this is avoidable by preparing well. It is unusual for a well thought out and well prepared manuscript to be rejected.

Autoformatting software, especially with references, may produce errors, so do double check these. Syntax errors, spelling mistakes, and poor grammar create a poor impression of an otherwise good case report. As always, first impressions matter, so be meticulous as you proofread your manuscript before you submit.

The entire process of publication depends on the number of revisions necessary and how quickly you submit a revised manuscript. For those of you aiming to submit in time to prepare for job applications, do take into account the time taken in the process of publication.

Article Contents

Format of the patient case report
Appendix A—Criteria for publishable case reports
Appendix B—Guidelines for writing patient case report manuscripts
< Previous

How to write a patient case report

Article contents
Figures & tables
Supplementary Data

Henry Cohen, How to write a patient case report, American Journal of Health-System Pharmacy , Volume 63, Issue 19, 1 October 2006, Pages 1888–1892, https://doi.org/10.2146/ajhp060182

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Purpose. Guidelines for writing patient case reports, with a focus on medication-related reports, are provided.

Summary. The format of a patient case report encompasses the following five sections: an abstract, an introduction and objective that contain a literature review, a description of the case report, a discussion that includes a detailed explanation of the literature review, a summary of the case, and a conclusion. The abstract of a patient case report should succinctly include the four sections of the main text of the report. The introduction section should provide the subject, purpose, and merit of the case report. It must explain why the case report is novel or merits review, and it should include a comprehensive literature review that corroborates the author’s claims. The case presentation section should describe the case in chronological order and in enough detail for the reader to establish his or her own conclusions about the case’s validity. The discussion section is the most important section of the case report. It ought to evaluate the patient case for accuracy, validity, and uniqueness; compare and contrast the case report with the published literature; derive new knowledge; summarize the essential features of the report; and draw recommendations. The conclusion section should be brief and provide a conclusion with evidence-based recommendations and applicability to practice.

Conclusion. Patient case reports are valuable resources of new and unusual information that may lead to vital research.

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How to Successfully Conclude a Case Study

Knowing how to successfully conclude a case study is one of the most important parts of every case interview. A strong conclusion shows how well you summarize the entire case solution into a couple of points. In addition, it proves that you can successfully back up your arguments with both quantitative and qualitative facts. It’s also the very last point of the case, thus the point clients remember the most.

How to Successfully Conclude a Case Study - Best Practice Approaches

Take approximately 30 seconds before concluding the case, and use this time to jot down key messages you want to touch on during your recommendation. You want to have your ideas sorted out in advance so that you speak clearly and concisely, covering each point without referring back to your notes.

Practice the art of the elevator pitch

Ideally, your final recommendation should not exceed more than one minute. It is a way to mimic day-to-day interactions with our clients when we are asked to give them key pointers in a short summary.

Answer first and answer focused

As you will see more in detail with Prepmatter cases, in many case types, you should start with the answer. However, in certain case types where the client has a business problem yet to be diagnosed (e.g., competitive response strategy, profitability, operations), it’s best to start with your diagnosis and then provide recovery solutions.

Allocate time correctly

Make sure to allocate most of your time to the delivery of a solution and its supporting evidence. Some candidates spend half - if not more - of their time in delivering risks and next steps, which dilutes the key messages in the recommendation. Conclude the case in the following structure:

Recommendation: Give a one-sentence action-oriented recommendation.
First supporting fact with figures (quantitative)
Second supporting fact with figures (quantitative)
Third supporting fact (qualitative)
Risks: Comment on the potential risks assessed during the case. Try to mention them in a way supporting your conclusion.
Next steps: Provide direction on how they should act going forward based on the recommendation.

Example of a Strong Conclusion

I suggest the client should go ahead with this investment and enter the cosmetics market with their new product.
With this investment, the client can make an $800M profit over the next three years, which is higher than our objective of $600M.
The cosmetics market is expected to grow at a 9% annual growth rate over the next 10 years, promising sustainable value in the long term.
We can create synergies by combining our back-end operations with our existing business.
Risks: There is a regulatory risk given that the authorities increase their health restrictions related to cosmetics products. The client should make sure that they spend additional effort to comply with all regulations.
Next steps: As the next step, I suggest the client design a detailed production plan for the new product.

How to Practice Case Conclusions

There are various ways to practice concluding a case. Practice with the Prepmatter cases or any other case you may have. You can change the numbers in the case to create hypothetical facts and draw a new conclusion. By doing so, you can also change the recommendation if the numbers change significantly. For instance, if you change the 3-year profits to $400M from $800M in the example above, the recommendation would change from ‘Go’ to ‘No-go’.

Knowing how to successfully conclude a case study is a critical part of each case interview, so we recommend you set aside specific time to review it with your coach or case partner. Take time to solve as many cases as possible to improve how well you summarize, support, and present your conclusion.

Open access
Published: 27 June 2011

The case study approach

Sarah Crowe 1 ,
Kathrin Cresswell 2 ,
Ann Robertson 2 ,
Guro Huby 3 ,
Anthony Avery 1 &
Aziz Sheikh 2

BMC Medical Research Methodology volume 11 , Article number: 100 ( 2011 ) Cite this article

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The case study approach allows in-depth, multi-faceted explorations of complex issues in their real-life settings. The value of the case study approach is well recognised in the fields of business, law and policy, but somewhat less so in health services research. Based on our experiences of conducting several health-related case studies, we reflect on the different types of case study design, the specific research questions this approach can help answer, the data sources that tend to be used, and the particular advantages and disadvantages of employing this methodological approach. The paper concludes with key pointers to aid those designing and appraising proposals for conducting case study research, and a checklist to help readers assess the quality of case study reports.

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Introduction

The case study approach is particularly useful to employ when there is a need to obtain an in-depth appreciation of an issue, event or phenomenon of interest, in its natural real-life context. Our aim in writing this piece is to provide insights into when to consider employing this approach and an overview of key methodological considerations in relation to the design, planning, analysis, interpretation and reporting of case studies.

The illustrative 'grand round', 'case report' and 'case series' have a long tradition in clinical practice and research. Presenting detailed critiques, typically of one or more patients, aims to provide insights into aspects of the clinical case and, in doing so, illustrate broader lessons that may be learnt. In research, the conceptually-related case study approach can be used, for example, to describe in detail a patient's episode of care, explore professional attitudes to and experiences of a new policy initiative or service development or more generally to 'investigate contemporary phenomena within its real-life context' [ 1 ]. Based on our experiences of conducting a range of case studies, we reflect on when to consider using this approach, discuss the key steps involved and illustrate, with examples, some of the practical challenges of attaining an in-depth understanding of a 'case' as an integrated whole. In keeping with previously published work, we acknowledge the importance of theory to underpin the design, selection, conduct and interpretation of case studies[ 2 ]. In so doing, we make passing reference to the different epistemological approaches used in case study research by key theoreticians and methodologists in this field of enquiry.

This paper is structured around the following main questions: What is a case study? What are case studies used for? How are case studies conducted? What are the potential pitfalls and how can these be avoided? We draw in particular on four of our own recently published examples of case studies (see Tables 1 , 2 , 3 and 4 ) and those of others to illustrate our discussion[ 3 – 7 ].

What is a case study?

A case study is a research approach that is used to generate an in-depth, multi-faceted understanding of a complex issue in its real-life context. It is an established research design that is used extensively in a wide variety of disciplines, particularly in the social sciences. A case study can be defined in a variety of ways (Table 5 ), the central tenet being the need to explore an event or phenomenon in depth and in its natural context. It is for this reason sometimes referred to as a "naturalistic" design; this is in contrast to an "experimental" design (such as a randomised controlled trial) in which the investigator seeks to exert control over and manipulate the variable(s) of interest.

Stake's work has been particularly influential in defining the case study approach to scientific enquiry. He has helpfully characterised three main types of case study: intrinsic , instrumental and collective [ 8 ]. An intrinsic case study is typically undertaken to learn about a unique phenomenon. The researcher should define the uniqueness of the phenomenon, which distinguishes it from all others. In contrast, the instrumental case study uses a particular case (some of which may be better than others) to gain a broader appreciation of an issue or phenomenon. The collective case study involves studying multiple cases simultaneously or sequentially in an attempt to generate a still broader appreciation of a particular issue.

These are however not necessarily mutually exclusive categories. In the first of our examples (Table 1 ), we undertook an intrinsic case study to investigate the issue of recruitment of minority ethnic people into the specific context of asthma research studies, but it developed into a instrumental case study through seeking to understand the issue of recruitment of these marginalised populations more generally, generating a number of the findings that are potentially transferable to other disease contexts[ 3 ]. In contrast, the other three examples (see Tables 2 , 3 and 4 ) employed collective case study designs to study the introduction of workforce reconfiguration in primary care, the implementation of electronic health records into hospitals, and to understand the ways in which healthcare students learn about patient safety considerations[ 4 – 6 ]. Although our study focusing on the introduction of General Practitioners with Specialist Interests (Table 2 ) was explicitly collective in design (four contrasting primary care organisations were studied), is was also instrumental in that this particular professional group was studied as an exemplar of the more general phenomenon of workforce redesign[ 4 ].

What are case studies used for?

According to Yin, case studies can be used to explain, describe or explore events or phenomena in the everyday contexts in which they occur[ 1 ]. These can, for example, help to understand and explain causal links and pathways resulting from a new policy initiative or service development (see Tables 2 and 3 , for example)[ 1 ]. In contrast to experimental designs, which seek to test a specific hypothesis through deliberately manipulating the environment (like, for example, in a randomised controlled trial giving a new drug to randomly selected individuals and then comparing outcomes with controls),[ 9 ] the case study approach lends itself well to capturing information on more explanatory ' how ', 'what' and ' why ' questions, such as ' how is the intervention being implemented and received on the ground?'. The case study approach can offer additional insights into what gaps exist in its delivery or why one implementation strategy might be chosen over another. This in turn can help develop or refine theory, as shown in our study of the teaching of patient safety in undergraduate curricula (Table 4 )[ 6 , 10 ]. Key questions to consider when selecting the most appropriate study design are whether it is desirable or indeed possible to undertake a formal experimental investigation in which individuals and/or organisations are allocated to an intervention or control arm? Or whether the wish is to obtain a more naturalistic understanding of an issue? The former is ideally studied using a controlled experimental design, whereas the latter is more appropriately studied using a case study design.

Case studies may be approached in different ways depending on the epistemological standpoint of the researcher, that is, whether they take a critical (questioning one's own and others' assumptions), interpretivist (trying to understand individual and shared social meanings) or positivist approach (orientating towards the criteria of natural sciences, such as focusing on generalisability considerations) (Table 6 ). Whilst such a schema can be conceptually helpful, it may be appropriate to draw on more than one approach in any case study, particularly in the context of conducting health services research. Doolin has, for example, noted that in the context of undertaking interpretative case studies, researchers can usefully draw on a critical, reflective perspective which seeks to take into account the wider social and political environment that has shaped the case[ 11 ].

How are case studies conducted?

Here, we focus on the main stages of research activity when planning and undertaking a case study; the crucial stages are: defining the case; selecting the case(s); collecting and analysing the data; interpreting data; and reporting the findings.

Defining the case

Carefully formulated research question(s), informed by the existing literature and a prior appreciation of the theoretical issues and setting(s), are all important in appropriately and succinctly defining the case[ 8 , 12 ]. Crucially, each case should have a pre-defined boundary which clarifies the nature and time period covered by the case study (i.e. its scope, beginning and end), the relevant social group, organisation or geographical area of interest to the investigator, the types of evidence to be collected, and the priorities for data collection and analysis (see Table 7 )[ 1 ]. A theory driven approach to defining the case may help generate knowledge that is potentially transferable to a range of clinical contexts and behaviours; using theory is also likely to result in a more informed appreciation of, for example, how and why interventions have succeeded or failed[ 13 ].

For example, in our evaluation of the introduction of electronic health records in English hospitals (Table 3 ), we defined our cases as the NHS Trusts that were receiving the new technology[ 5 ]. Our focus was on how the technology was being implemented. However, if the primary research interest had been on the social and organisational dimensions of implementation, we might have defined our case differently as a grouping of healthcare professionals (e.g. doctors and/or nurses). The precise beginning and end of the case may however prove difficult to define. Pursuing this same example, when does the process of implementation and adoption of an electronic health record system really begin or end? Such judgements will inevitably be influenced by a range of factors, including the research question, theory of interest, the scope and richness of the gathered data and the resources available to the research team.

Selecting the case(s)

The decision on how to select the case(s) to study is a very important one that merits some reflection. In an intrinsic case study, the case is selected on its own merits[ 8 ]. The case is selected not because it is representative of other cases, but because of its uniqueness, which is of genuine interest to the researchers. This was, for example, the case in our study of the recruitment of minority ethnic participants into asthma research (Table 1 ) as our earlier work had demonstrated the marginalisation of minority ethnic people with asthma, despite evidence of disproportionate asthma morbidity[ 14 , 15 ]. In another example of an intrinsic case study, Hellstrom et al.[ 16 ] studied an elderly married couple living with dementia to explore how dementia had impacted on their understanding of home, their everyday life and their relationships.

For an instrumental case study, selecting a "typical" case can work well[ 8 ]. In contrast to the intrinsic case study, the particular case which is chosen is of less importance than selecting a case that allows the researcher to investigate an issue or phenomenon. For example, in order to gain an understanding of doctors' responses to health policy initiatives, Som undertook an instrumental case study interviewing clinicians who had a range of responsibilities for clinical governance in one NHS acute hospital trust[ 17 ]. Sampling a "deviant" or "atypical" case may however prove even more informative, potentially enabling the researcher to identify causal processes, generate hypotheses and develop theory.

In collective or multiple case studies, a number of cases are carefully selected. This offers the advantage of allowing comparisons to be made across several cases and/or replication. Choosing a "typical" case may enable the findings to be generalised to theory (i.e. analytical generalisation) or to test theory by replicating the findings in a second or even a third case (i.e. replication logic)[ 1 ]. Yin suggests two or three literal replications (i.e. predicting similar results) if the theory is straightforward and five or more if the theory is more subtle. However, critics might argue that selecting 'cases' in this way is insufficiently reflexive and ill-suited to the complexities of contemporary healthcare organisations.

The selected case study site(s) should allow the research team access to the group of individuals, the organisation, the processes or whatever else constitutes the chosen unit of analysis for the study. Access is therefore a central consideration; the researcher needs to come to know the case study site(s) well and to work cooperatively with them. Selected cases need to be not only interesting but also hospitable to the inquiry [ 8 ] if they are to be informative and answer the research question(s). Case study sites may also be pre-selected for the researcher, with decisions being influenced by key stakeholders. For example, our selection of case study sites in the evaluation of the implementation and adoption of electronic health record systems (see Table 3 ) was heavily influenced by NHS Connecting for Health, the government agency that was responsible for overseeing the National Programme for Information Technology (NPfIT)[ 5 ]. This prominent stakeholder had already selected the NHS sites (through a competitive bidding process) to be early adopters of the electronic health record systems and had negotiated contracts that detailed the deployment timelines.

It is also important to consider in advance the likely burden and risks associated with participation for those who (or the site(s) which) comprise the case study. Of particular importance is the obligation for the researcher to think through the ethical implications of the study (e.g. the risk of inadvertently breaching anonymity or confidentiality) and to ensure that potential participants/participating sites are provided with sufficient information to make an informed choice about joining the study. The outcome of providing this information might be that the emotive burden associated with participation, or the organisational disruption associated with supporting the fieldwork, is considered so high that the individuals or sites decide against participation.

In our example of evaluating implementations of electronic health record systems, given the restricted number of early adopter sites available to us, we sought purposively to select a diverse range of implementation cases among those that were available[ 5 ]. We chose a mixture of teaching, non-teaching and Foundation Trust hospitals, and examples of each of the three electronic health record systems procured centrally by the NPfIT. At one recruited site, it quickly became apparent that access was problematic because of competing demands on that organisation. Recognising the importance of full access and co-operative working for generating rich data, the research team decided not to pursue work at that site and instead to focus on other recruited sites.

Collecting the data

In order to develop a thorough understanding of the case, the case study approach usually involves the collection of multiple sources of evidence, using a range of quantitative (e.g. questionnaires, audits and analysis of routinely collected healthcare data) and more commonly qualitative techniques (e.g. interviews, focus groups and observations). The use of multiple sources of data (data triangulation) has been advocated as a way of increasing the internal validity of a study (i.e. the extent to which the method is appropriate to answer the research question)[ 8 , 18 – 21 ]. An underlying assumption is that data collected in different ways should lead to similar conclusions, and approaching the same issue from different angles can help develop a holistic picture of the phenomenon (Table 2 )[ 4 ].

Brazier and colleagues used a mixed-methods case study approach to investigate the impact of a cancer care programme[ 22 ]. Here, quantitative measures were collected with questionnaires before, and five months after, the start of the intervention which did not yield any statistically significant results. Qualitative interviews with patients however helped provide an insight into potentially beneficial process-related aspects of the programme, such as greater, perceived patient involvement in care. The authors reported how this case study approach provided a number of contextual factors likely to influence the effectiveness of the intervention and which were not likely to have been obtained from quantitative methods alone.

In collective or multiple case studies, data collection needs to be flexible enough to allow a detailed description of each individual case to be developed (e.g. the nature of different cancer care programmes), before considering the emerging similarities and differences in cross-case comparisons (e.g. to explore why one programme is more effective than another). It is important that data sources from different cases are, where possible, broadly comparable for this purpose even though they may vary in nature and depth.

Analysing, interpreting and reporting case studies

Making sense and offering a coherent interpretation of the typically disparate sources of data (whether qualitative alone or together with quantitative) is far from straightforward. Repeated reviewing and sorting of the voluminous and detail-rich data are integral to the process of analysis. In collective case studies, it is helpful to analyse data relating to the individual component cases first, before making comparisons across cases. Attention needs to be paid to variations within each case and, where relevant, the relationship between different causes, effects and outcomes[ 23 ]. Data will need to be organised and coded to allow the key issues, both derived from the literature and emerging from the dataset, to be easily retrieved at a later stage. An initial coding frame can help capture these issues and can be applied systematically to the whole dataset with the aid of a qualitative data analysis software package.

The Framework approach is a practical approach, comprising of five stages (familiarisation; identifying a thematic framework; indexing; charting; mapping and interpretation) , to managing and analysing large datasets particularly if time is limited, as was the case in our study of recruitment of South Asians into asthma research (Table 1 )[ 3 , 24 ]. Theoretical frameworks may also play an important role in integrating different sources of data and examining emerging themes. For example, we drew on a socio-technical framework to help explain the connections between different elements - technology; people; and the organisational settings within which they worked - in our study of the introduction of electronic health record systems (Table 3 )[ 5 ]. Our study of patient safety in undergraduate curricula drew on an evaluation-based approach to design and analysis, which emphasised the importance of the academic, organisational and practice contexts through which students learn (Table 4 )[ 6 ].

Case study findings can have implications both for theory development and theory testing. They may establish, strengthen or weaken historical explanations of a case and, in certain circumstances, allow theoretical (as opposed to statistical) generalisation beyond the particular cases studied[ 12 ]. These theoretical lenses should not, however, constitute a strait-jacket and the cases should not be "forced to fit" the particular theoretical framework that is being employed.

When reporting findings, it is important to provide the reader with enough contextual information to understand the processes that were followed and how the conclusions were reached. In a collective case study, researchers may choose to present the findings from individual cases separately before amalgamating across cases. Care must be taken to ensure the anonymity of both case sites and individual participants (if agreed in advance) by allocating appropriate codes or withholding descriptors. In the example given in Table 3 , we decided against providing detailed information on the NHS sites and individual participants in order to avoid the risk of inadvertent disclosure of identities[ 5 , 25 ].

What are the potential pitfalls and how can these be avoided?

The case study approach is, as with all research, not without its limitations. When investigating the formal and informal ways undergraduate students learn about patient safety (Table 4 ), for example, we rapidly accumulated a large quantity of data. The volume of data, together with the time restrictions in place, impacted on the depth of analysis that was possible within the available resources. This highlights a more general point of the importance of avoiding the temptation to collect as much data as possible; adequate time also needs to be set aside for data analysis and interpretation of what are often highly complex datasets.

Case study research has sometimes been criticised for lacking scientific rigour and providing little basis for generalisation (i.e. producing findings that may be transferable to other settings)[ 1 ]. There are several ways to address these concerns, including: the use of theoretical sampling (i.e. drawing on a particular conceptual framework); respondent validation (i.e. participants checking emerging findings and the researcher's interpretation, and providing an opinion as to whether they feel these are accurate); and transparency throughout the research process (see Table 8 )[ 8 , 18 – 21 , 23 , 26 ]. Transparency can be achieved by describing in detail the steps involved in case selection, data collection, the reasons for the particular methods chosen, and the researcher's background and level of involvement (i.e. being explicit about how the researcher has influenced data collection and interpretation). Seeking potential, alternative explanations, and being explicit about how interpretations and conclusions were reached, help readers to judge the trustworthiness of the case study report. Stake provides a critique checklist for a case study report (Table 9 )[ 8 ].

Conclusions

The case study approach allows, amongst other things, critical events, interventions, policy developments and programme-based service reforms to be studied in detail in a real-life context. It should therefore be considered when an experimental design is either inappropriate to answer the research questions posed or impossible to undertake. Considering the frequency with which implementations of innovations are now taking place in healthcare settings and how well the case study approach lends itself to in-depth, complex health service research, we believe this approach should be more widely considered by researchers. Though inherently challenging, the research case study can, if carefully conceptualised and thoughtfully undertaken and reported, yield powerful insights into many important aspects of health and healthcare delivery.

Yin RK: Case study research, design and method. 2009, London: Sage Publications Ltd., 4

Google Scholar

Keen J, Packwood T: Qualitative research; case study evaluation. BMJ. 1995, 311: 444-446.

Article CAS PubMed PubMed Central Google Scholar

Sheikh A, Halani L, Bhopal R, Netuveli G, Partridge M, Car J, et al: Facilitating the Recruitment of Minority Ethnic People into Research: Qualitative Case Study of South Asians and Asthma. PLoS Med. 2009, 6 (10): 1-11.

Article Google Scholar

Pinnock H, Huby G, Powell A, Kielmann T, Price D, Williams S, et al: The process of planning, development and implementation of a General Practitioner with a Special Interest service in Primary Care Organisations in England and Wales: a comparative prospective case study. Report for the National Co-ordinating Centre for NHS Service Delivery and Organisation R&D (NCCSDO). 2008, [ http://www.sdo.nihr.ac.uk/files/project/99-final-report.pdf ]

Robertson A, Cresswell K, Takian A, Petrakaki D, Crowe S, Cornford T, et al: Prospective evaluation of the implementation and adoption of NHS Connecting for Health's national electronic health record in secondary care in England: interim findings. BMJ. 2010, 41: c4564-

Pearson P, Steven A, Howe A, Sheikh A, Ashcroft D, Smith P, the Patient Safety Education Study Group: Learning about patient safety: organisational context and culture in the education of healthcare professionals. J Health Serv Res Policy. 2010, 15: 4-10. 10.1258/jhsrp.2009.009052.

Article PubMed Google Scholar

van Harten WH, Casparie TF, Fisscher OA: The evaluation of the introduction of a quality management system: a process-oriented case study in a large rehabilitation hospital. Health Policy. 2002, 60 (1): 17-37. 10.1016/S0168-8510(01)00187-7.

Stake RE: The art of case study research. 1995, London: Sage Publications Ltd.

Sheikh A, Smeeth L, Ashcroft R: Randomised controlled trials in primary care: scope and application. Br J Gen Pract. 2002, 52 (482): 746-51.

PubMed PubMed Central Google Scholar

King G, Keohane R, Verba S: Designing Social Inquiry. 1996, Princeton: Princeton University Press

Doolin B: Information technology as disciplinary technology: being critical in interpretative research on information systems. Journal of Information Technology. 1998, 13: 301-311. 10.1057/jit.1998.8.

George AL, Bennett A: Case studies and theory development in the social sciences. 2005, Cambridge, MA: MIT Press

Eccles M, the Improved Clinical Effectiveness through Behavioural Research Group (ICEBeRG): Designing theoretically-informed implementation interventions. Implementation Science. 2006, 1: 1-8. 10.1186/1748-5908-1-1.

Article PubMed Central Google Scholar

Netuveli G, Hurwitz B, Levy M, Fletcher M, Barnes G, Durham SR, Sheikh A: Ethnic variations in UK asthma frequency, morbidity, and health-service use: a systematic review and meta-analysis. Lancet. 2005, 365 (9456): 312-7.

Sheikh A, Panesar SS, Lasserson T, Netuveli G: Recruitment of ethnic minorities to asthma studies. Thorax. 2004, 59 (7): 634-

CAS PubMed PubMed Central Google Scholar

Hellström I, Nolan M, Lundh U: 'We do things together': A case study of 'couplehood' in dementia. Dementia. 2005, 4: 7-22. 10.1177/1471301205049188.

Som CV: Nothing seems to have changed, nothing seems to be changing and perhaps nothing will change in the NHS: doctors' response to clinical governance. International Journal of Public Sector Management. 2005, 18: 463-477. 10.1108/09513550510608903.

Lincoln Y, Guba E: Naturalistic inquiry. 1985, Newbury Park: Sage Publications

Barbour RS: Checklists for improving rigour in qualitative research: a case of the tail wagging the dog?. BMJ. 2001, 322: 1115-1117. 10.1136/bmj.322.7294.1115.

Mays N, Pope C: Qualitative research in health care: Assessing quality in qualitative research. BMJ. 2000, 320: 50-52. 10.1136/bmj.320.7226.50.

Mason J: Qualitative researching. 2002, London: Sage

Brazier A, Cooke K, Moravan V: Using Mixed Methods for Evaluating an Integrative Approach to Cancer Care: A Case Study. Integr Cancer Ther. 2008, 7: 5-17. 10.1177/1534735407313395.

Miles MB, Huberman M: Qualitative data analysis: an expanded sourcebook. 1994, CA: Sage Publications Inc., 2

Pope C, Ziebland S, Mays N: Analysing qualitative data. Qualitative research in health care. BMJ. 2000, 320: 114-116. 10.1136/bmj.320.7227.114.

Cresswell KM, Worth A, Sheikh A: Actor-Network Theory and its role in understanding the implementation of information technology developments in healthcare. BMC Med Inform Decis Mak. 2010, 10 (1): 67-10.1186/1472-6947-10-67.

Article PubMed PubMed Central Google Scholar

Malterud K: Qualitative research: standards, challenges, and guidelines. Lancet. 2001, 358: 483-488. 10.1016/S0140-6736(01)05627-6.

Article CAS PubMed Google Scholar

Yin R: Case study research: design and methods. 1994, Thousand Oaks, CA: Sage Publishing, 2

Yin R: Enhancing the quality of case studies in health services research. Health Serv Res. 1999, 34: 1209-1224.

Green J, Thorogood N: Qualitative methods for health research. 2009, Los Angeles: Sage, 2

Howcroft D, Trauth E: Handbook of Critical Information Systems Research, Theory and Application. 2005, Cheltenham, UK: Northampton, MA, USA: Edward Elgar

Book Google Scholar

Blakie N: Approaches to Social Enquiry. 1993, Cambridge: Polity Press

Doolin B: Power and resistance in the implementation of a medical management information system. Info Systems J. 2004, 14: 343-362. 10.1111/j.1365-2575.2004.00176.x.

Bloomfield BP, Best A: Management consultants: systems development, power and the translation of problems. Sociological Review. 1992, 40: 533-560.

Shanks G, Parr A: Positivist, single case study research in information systems: A critical analysis. Proceedings of the European Conference on Information Systems. 2003, Naples

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Acknowledgements

We are grateful to the participants and colleagues who contributed to the individual case studies that we have drawn on. This work received no direct funding, but it has been informed by projects funded by Asthma UK, the NHS Service Delivery Organisation, NHS Connecting for Health Evaluation Programme, and Patient Safety Research Portfolio. We would also like to thank the expert reviewers for their insightful and constructive feedback. Our thanks are also due to Dr. Allison Worth who commented on an earlier draft of this manuscript.

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Sarah Crowe & Anthony Avery

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AS conceived this article. SC, KC and AR wrote this paper with GH, AA and AS all commenting on various drafts. SC and AS are guarantors.

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Frequently asked questions

How to write the conclusion of your case study

You worked on an amazing UX project. You documented every detail and deliverable and when the time came, you began to write a UX case study about it. In the case study, you highlighted how you worked through a Design Thinking process to get to the end result; so, can you stop there and now move on to the next thing? Well, no! There’s just one more bit left to finish up and make the perfect case study. So, get ready; we will now explore how you can write the perfect conclusion to wrap it all up and leave a lasting great impression.

Every start has an end – we’re not just repeating the famous quote here, because for case studies, a proper end is your last and final chance to leave a lasting great (at the very least, good) impression with whoever is reading your work (typically, recruiters!). Many junior UX designers often forget about the conclusion part of the case study, but this is a costly mistake to make. A well-written case study must end with an appropriate final section, in which you should summarize the key takeaways that you want others to remember about you and your work. Let’s see why.

Last impressions are just as important as first ones

We’ll go to some length here to convince you about the importance of last impressions, especially as we can understand the reason behind not wanting to pay very much attention to the end of your case study, after all the hard work you put into writing the process section. You are tired, and anyone who’s read your work should already have a good idea about your skills, anyway. Surely—you could be forgiven for thinking, at least—all that awesome material you put in the start and middle sections must have built up the momentum to take your work into orbit and make the recruiter’s last impression of you a lasting—and very good—one, and all you need to do now is take your leave. However, psychologist Saul McLeod (2008) explains how early work by experimental psychology pioneers Atkinson & Shriffin (1968) demonstrated that when humans are presented with information, they tend to remember the first and last elements and are more likely to forget the middle ones.

This is known as the “ serial position effect ” (more technically, the tendency to remember the first elements is known as the “ primacy effect ”, while the tendency to remember the last elements is known as the “ recency effect ”). Further work in human experiences discovered that the last few things we see or hear at the end of an experience can generate the most powerful memories that come back to us when we come across a situation or when we think about it. For example, let’s say you stayed in a hotel room that left a bit to be desired. Maybe the room was a little cramped, or the towels were not so soft. But if the receptionist, as you leave, shakes your hand warmly, smiles and thanks you sincerely for your custom, and goes out of his way to help you with your luggage, or to get you a taxi, you will remember that person’s kind demeanor more than you will remember the fact that the room facilities could be improved.

A good ending to your case study can help people forget some of the not-so-good points about your case study middle. For example, if you missed out a few crucial details but can demonstrate some truly interesting takeaways, they can always just ask you about these in an interview. Inversely, a bad ending leaves the recruiter with some doubt that will linger. Did this person learn nothing interesting from all this work? Did their work have no impact at all? Did they even write the case study themselves? A bad last impression can certainly undo much of the hard work you’ve put into writing the complicated middle part of your case study.

What to put in your case study conclusions

A case study ending is your opportunity to bring some closure to the story that you are writing. So, you can use it to mention the status of the project (e.g., is it ongoing or has it ended?) and then to demonstrate the impact that your work has had. By presenting some quantifiable results (e.g., data from end evaluations, analytics, key performance indicators ), you can demonstrate this impact. You can also discuss what you learned from this project, making you wiser than the next applicant – for example, something about a special category of users that the company might be interested in developing products for, or something that is cutting-edge and that advances the frontiers of science or practice.

As you can see, there are a few good ways in which you can end your case study. Next, we will outline four options that can be part of your ending: lessons learned, the impact of the project, reflections, and acknowledgements.

Lessons learned

A recruiter wants to see how you improve yourself by learning from the projects you work on. You can discuss interesting insights that you learned from user research or the evaluation of your designs – for example, surprising behaviors that you found out about the technology use in a group of users who are not typically considered to be big proponents of technology (e.g., older adults), or, perhaps, the reasons a particular design pattern didn’t work as well as expected under the context of your project.

Another thing you can discuss is your opinion on what the most difficult challenge of the project was, and comment on how you managed to overcome it. You can also discuss here things that you found out about yourself as a professional – for example, that you enjoyed taking on a UX role that you didn’t have previous experience with, or that you were able to overcome some personal limitations or build on your existing skills in a new way.

Impact of the project

Showing impact is always good. How did you measure the impact of your work? By using analytics, evaluation results, and even testimonials from your customers or users, or even your development or marketing team, you can demonstrate that your methodical approach to work brought about some positive change. Use before-after comparison data to demonstrate the extent of your impact. Verbatim positive quotes from your users or other project stakeholders are worth their weight (or rather, sentence length) in gold. Don’t go overboard, but mix and match the best evidence for the quality of your work to keep the end section brief and to the point.

User reviews from app stores are a great source of obtaining testimonials to include in your case studies. Overall app ratings and download volumes are also great bits of information to show impact.

An excerpt from a case study ending section. Here, text and accompanying charts are used to demonstrate the impact of the work done by the UX professional.

Reflections on your experiences

You can include some information that shows you have a clear understanding of how further work can build on the success of what you’ve already done. This demonstrates forward thinking and exploratory desire. Something else you can reflect on is your choices during the project. In every project, there might be things you could do differently or improve upon. But be aware that the natural question that follows such statements is this: “Well, so why haven’t you done it?”

Don’t shoot yourself in the foot by listing all the things you wish you could have done, but focus on what you’ve actually done and lay out future directions. For example, if you’ve done the user research in an ongoing project, don’t say, “ After all this user research, it would have been great to progress to a prototype, but it’s not yet done ”; instead, say, “ This user research is now enabling developers to quickly progress to the prototyping stage. ”

Acknowledgments

The end of the case study section is where you should put in your acknowledgments to any other members of your team, if this wasn’t a personal project. Your goal by doing so is to highlight your team spirit and humility in recognizing that great projects are most typically the result of collaboration . Be careful here, because it’s easy to make the waters muddy by not being explicit about what YOU did. So, for example, don’t write something like “ I couldn’t have done it without John X. and Jane Y. ”, but instead say this: “ My user research and prototype design fed into the development work carried out by John X. User testing was carried out by Jane Y., whose findings informed further re-design that I did on the prototypes. ”

What is a good length for a UX case study ending?

UX case studies must be kept short, and, when considering the length of your beginning, process and conclusion sections, it’s the beginning and the conclusion sections that should be the shortest of all. In some case studies, you can keep the ending to two or three short phrases. Other, longer case studies about more complex projects may require a slightly longer section.

Remember, though, that the end section is your chance for a last, short but impactful impression. If the hotel receptionist from our early example started to say goodbye and then went on and on to ask you about your experience, sharing with you the comments of other clients, or started talking to you about where you are going next, and why, and maybe if he had been there himself, started to tell you all about where to go and what to see, well… you get the point. Keep it short, sincere and focused. And certainly, don’t try to make the project sound more important than it was. Recruiters are not stupid – they’ve been there and done that, so they know.

Putting it all together

In the example below, we will show how you can address the points above using text. We are going to focus on the three main questions here, so you can see an example of this in action, for a longer case study.

An example ending section for a longer case study, addressing all aspects: Lessons, impact, reflection and acknowledgments.

Here is how we might structure the text for a shorter version of the same case study, focusing on the bare essentials:

An example ending section for a shorter case study, addressing the most critical aspects: Lessons, impact and reflection. Acknowledgments are being sacrificed for the sake of brevity here, but perhaps that’s OK – you might mention it in the middle part of the case study.

The Take Away

The end part of your case study needs as much care and attention as the rest of it does. You shouldn’t neglect it just because it’s the last thing in the case study. It’s not hard work if you know the basics, and here, we’ve given you the pointers you need to ensure that you don’t miss out anything important. The end part of the case study should leave your recruiters with a good (hopefully, very good) last impression of you and your work, so give it the thorough consideration it needs, to ensure it doesn’t undo all the hard work you’ve put into the case study.

References & Where to Learn More

Atkinson, R. C., & Shiffrin, R. M. (1968). Chapter: Human memory : A proposed system and its control processes. In Spence, K. W., & Spence, J. T. The psychology of learning and motivation (Volume 2). New York: Academic Press. pp. 89–195.

McLeod, S. (2008). Serial Position Effect

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Health Care Comes Home: The Human Factors (2011)

Chapter: 7 conclusions and recommendations.

7 Conclusions and Recommendations

Health care is moving into the home increasingly often and involving a mixture of people, a variety of tasks, and a broad diversity of devices and technologies; it is also occurring in a range of residential environments. The factors driving this migration include the rising costs of providing health care; the growing numbers of older adults; the increasing prevalence of chronic disease; improved survival rates of various diseases, injuries, and other conditions (including those of fragile newborns); large numbers of veterans returning from war with serious injuries; and a wide range of technological innovations. The health care that results varies considerably in its safety, effectiveness, and efficiency, as well as its quality and cost.

The committee was charged with examining this major trend in health care delivery and resulting challenges from only one of many perspectives: the study of human factors. From the outset it was clear that the dramatic and evolving change in health care practice and policies presents a broad array of opportunities and problems. Consequently the committee endeavored to maintain focus specifically on how using the human factors approach can provide solutions that support maximizing the safety and quality of health care delivered in the home while empowering both care recipients and caregivers in the effort.

The conclusions and recommendations presented below reflect the most critical steps that the committee thinks should be taken to improve the state of health care in the home, based on the literature reviewed in this report examined through a human factors lens. They are organized into four areas: (1) health care technologies, including medical devices and health information technologies involved in health care in the home; (2)

caregivers and care recipients; (3) residential environments for health care; and (4) knowledge gaps that require additional research and development. Although many issues related to home health care could not be addressed, applications of human factors principles, knowledge, and research methods in these areas could make home health care safer and more effective and also contribute to reducing costs. The committee chose not to prioritize the recommendations, as they focus on various aspects of health care in the home and are of comparable importance to the different constituencies affected.

HEALTH CARE TECHNOLOGIES

Health care technologies include medical devices that are used in the home as well as information technologies related to home-based health care. The four recommendations in this area concern (1) regulating technologies for health care consumers, (2) developing guidance on the structure and usability of health information technologies, (3) developing guidance and standards for medical device labeling, and (4) improving adverse event reporting systems for medical devices. The adoption of these recommendations would improve the usability and effectiveness of technology systems and devices, support users in understanding and learning to use them, and improve feedback to government and industry that could be used to further improve technology for home care.

Ensuring the safety of emerging technologies is a challenge, in part because it is not always clear which federal agency has regulatory authority and what regulations must be met. Currently, the U.S. Food and Drug Administration (FDA) has responsibility for devices, and the Office of the National Coordinator for Health Information Technology (ONC) has similar authority with respect to health information technology. However, the dividing line between medical devices and health information technology is blurring, and many new systems and applications are being developed that are a combination of the two, although regulatory oversight has remained divided. Because regulatory responsibility for them is unclear, these products may fall into the gap.

The committee did not find a preponderance of evidence that knowledge is lacking for the design of safe and effective devices and technologies for use in the home. Rather than discovering an inadequate evidence base, we were troubled by the insufficient attention directed at the development of devices that account, necessarily and properly, for users who are inadequately trained or not trained at all. Yet these new users often must

rely on equipment without ready knowledge about limitations, maintenance requirements, and problems with adaptation to their particular home settings.

The increased prominence of the use of technology in the health care arena poses predictable challenges for many lay users, especially people with low health literacy, cognitive impairment, or limited technology experience. For example, remote health care management may be more effective when it is supported by technology, and various electronic health care (“e-health”) applications have been developed for this purpose. With the spectrum of caregivers ranging from individuals caring for themselves or other family members to highly experienced professional caregivers, computer-based care management systems could offer varying levels of guidance, reminding, and alerting, depending on the sophistication of the operator and the criticality of the message. However, if these technologies or applications are difficult to understand or use, they may be ignored or misused, with potentially deleterious effects on care recipient health and safety. Applying existing accessibility and usability guidelines and employing user-centered design and validation methods in the development of health technology products designed for use in the home would help ensure that they are safe and effective for their targeted user populations. In this effort, it is important to recognize how the line between medical devices and health information technologies has become blurred while regulatory oversight has remained distinct, and it is not always clear into which domain a product falls.

Recommendation 1. The U.S. Food and Drug Administration and the Office of the National Coordinator for Health Information Technology should collaborate to regulate, certify, and monitor health care applications and systems that integrate medical devices and health information technologies. As part of the certification process, the agencies should require evidence that manufacturers have followed existing accessibility and usability guidelines and have applied user-centered design and validation methods during development of the product.

Guidance and Standards

Developers of information technologies related to home-based health care, as yet, have inadequate or incomplete guidance regarding product content, structure, accessibility, and usability to inform innovation or evolution of personal health records or of care recipient access to information in electronic health records.

The ONC, in the initial announcement of its health information technology certification program, stated that requirements would be forthcom-

ing with respect both to personal health records and to care recipient access to information in electronic health records (e.g., patient portals). Despite the importance of these requirements, there is still no guidance on the content of information that should be provided to patients or minimum standards for accessibility, functionality, and usability of that information in electronic or nonelectronic formats.

Consequently, some portals have been constructed based on the continuity of care record. However, recent research has shown that records and portals based on this model are neither understandable nor interpretable by laypersons, even by those with a college education. The lack of guidance in this area makes it difficult for developers of personal health records and patient portals to design systems that fully address the needs of consumers.

Recommendation 2. The Office of the National Coordinator for Health Information Technology, in collaboration with the National Institute of Standards and Technology and the Agency for Healthcare Research and Quality, should establish design guidelines and standards, based on existing accessibility and usability guidelines, for content, accessibility, functionality, and usability of consumer health information technologies related to home-based health care.

The committee found a serious lack of adequate standards and guidance for the labeling of medical devices. Furthermore, we found that the approval processes of the FDA for changing these materials are burdensome and inflexible.

Just as many medical devices currently in use by laypersons in the home were originally designed and approved for use only by professionals in formal health care facilities, the instructions for use and training materials were not designed for lay users, either. The committee recognizes that lack of instructional materials for lay users adds to the level of risk involved when devices are used by populations for whom they were not intended.

Ironically, the FDA’s current premarket review and approval processes inadvertently discourage manufacturers from selectively revising or developing supplemental instructional and training materials, when they become aware that instructional and training materials need to be developed or revised for lay users of devices already approved and marketed. Changing the instructions for use (which were approved with the device) requires manufacturers to submit the device along with revised instructions to the FDA for another 510(k) premarket notification review. Since manufacturers can find these reviews complicated, time-consuming, and expensive, this requirement serves as a disincentive to appropriate revisions of instructional or training materials.

Furthermore, little guidance is currently available on design of user

training methods and materials for medical devices. Even the recently released human factors standard on medical device design (Association for the Advancement of Medical Instrumentation, 2009), while reasonably comprehensive, does not cover the topic of training or training materials. Both FDA guidance and existing standards that do specifically address the design of labeling and ensuing instructions for use fail to account for up-to-date findings from research on instructional systems design. In addition, despite recognition that requirements for user training, training materials, and instructions for use are different for lay and professional users of medical equipment, these differences are not reflected in current standards.

Recommendation 3. The U.S. Food and Drug Administration (FDA) should promote development (by standards development organizations, such as the International Electrotechnical Commission, the International Organization for Standardization, the American National Standards Institute, and the Association for the Advancement of Medical Instrumentation) of new standards based on the most recent human factors research for the labeling of and ensuing instructional materials for medical devices designed for home use by lay users. The FDA should also tailor and streamline its approval processes to facilitate and encourage regular improvements of these materials by manufacturers.

Adverse Event Reporting Systems

The committee notes that the FDA’s adverse event reporting systems, used to report problems with medical devices, are not user-friendly, especially for lay users, who generally are not aware of the systems, unaware that they can use them to report problems, and uneducated about how to do so. In order to promote safe use of medical devices in the home and rectify design problems that put care recipients at risk, it is necessary that the FDA conduct more effective postmarket surveillance of medical devices to complement its premarket approval process. The most important elements of their primarily passive surveillance system are the current adverse event reporting mechanisms, including Maude and MedSun. Entry of incident data by health care providers and consumers is not straightforward, and the system does not elicit data that could be useful to designers as they develop updated versions of products or new ones that are similar to existing devices. The reporting systems and their importance need to be widely promoted to a broad range of users, especially lay users.

Recommendation 4. The U.S. Food and Drug Administration should improve its adverse event reporting systems to be easier to use, to collect data that are more useful for identifying the root causes of events

related to interactions with the device operator, and to develop and promote a more convenient way for lay users as well as professionals to report problems with medical devices.

CAREGIVERS IN THE HOME

Health care is provided in the home by formal caregivers (health care professionals), informal caregivers (family and friends), and individuals who self-administer care; each type of caregiver faces unique issues. Properly preparing individuals to provide care at home depends on targeting efforts appropriately to the background, experience, and knowledge of the caregivers. To date, however, home health care services suffer from being organized primarily around regulations and payments designed for inpatient or outpatient acute care settings. Little attention has been given to how different the roles are for formal caregivers when delivering services in the home or to the specific types of training necessary for appropriate, high-quality practice in this environment.

Health care administration in the home commonly involves interaction among formal caregivers and informal caregivers who share daily responsibility for a person receiving care. But few formal caregivers are given adequate training on how to work with informal caregivers and involve them effectively in health decision making, use of medical or adaptive technologies, or best practices to be used for evaluating and supporting the needs of caregivers.

It is also important to recognize that the majority of long-term care provided to older adults and individuals with disabilities relies on family members, friends, or the individual alone. Many informal caregivers take on these responsibilities without necessary education or support. These individuals may be poorly prepared and emotionally overwhelmed and, as a result, experience stress and burden that can lead to their own morbidity. The committee is aware that informational and training materials and tested programs already exist to assist informal caregivers in understanding the many details of providing health care in the home and to ease their burden and enhance the quality of life of both caregiver and care recipient. However, tested materials and education, support, and skill enhancement programs have not been adequately disseminated or integrated into standard care practices.

Recommendation 5. Relevant professional practice and advocacy groups should develop appropriate certification, credentialing, and/or training standards that will prepare formal caregivers to provide care in the home, develop appropriate informational and training materials

for informal caregivers, and provide guidance for all caregivers to work effectively with other people involved.

RESIDENTIAL ENVIRONMENTS FOR HEALTH CARE

Health care is administered in a variety of nonclinical environments, but the most common one, particularly for individuals who need the greatest level and intensity of health care services, is the home. The two recommendations in this area encourage (1) modifications to existing housing and (2) accessible and universal design of new housing. The implementation of these recommendations would be a good start on an effort to improve the safety and ease of practicing health care in the home. It could improve the health and safety of many care recipients and their caregivers and could facilitate adherence to good health maintenance and treatment practices. Ideally, improvements to housing design would take place in the context of communities that provide transportation, social networking and exercise opportunities, and access to health care and other services.

Safety and Modification of Existing Housing

The committee found poor appreciation of the importance of modifying homes to remove health hazards and barriers to self-management and health care practice and, furthermore, that financial support from federal assistance agencies for home modifications is very limited. The general connection between housing characteristics and health is well established. For example, improving housing conditions to enhance basic sanitation has long been part of a public health response to acute illness. But the characteristics of the home can present significant barriers to autonomy or self-care management and present risk factors for poor health, injury, compromised well-being, and greater dependence on others. Conversely, physical characteristics of homes can enhance resident safety and ability to participate in daily self-care and to utilize effectively health care technologies that are designed to enhance health and well-being.

Home modifications based on professional home assessments can increase functioning, contribute to reducing accidents such as falls, assist caregivers, and enable chronically ill persons and people with disabilities to stay in the community. Such changes are also associated with facilitating hospital discharges, decreasing readmissions, reducing hazards in the home, and improving care coordination. Familiar modifications include installation of such items as grab bars, handrails, stair lifts, increased lighting, and health monitoring equipment as well as reduction of such hazards as broken fixtures and others caused by insufficient home maintenance.

Deciding on which home modifications have highest priority in a given

setting depends on an appropriate assessment of circumstances and the environment. A number of home assessment instruments and programs have been validated and proven to be effective to meet this need. But even if needed modifications are properly identified and prioritized, inadequate funding, gaps in services, and lack of coordination between the health and housing service sectors have resulted in a poorly integrated system that is difficult to access. Even when accessed, progress in making home modifications available has been hampered by this lack of coordination and inadequate reimbursement or financial mechanisms, especially for those who cannot afford them.

Recommendation 6. Federal agencies, including the U.S. Department of Health and Human Services and the Centers for Medicare & Medicaid Services, along with the U.S. Department of Housing and Urban Development and the U.S. Department of Energy, should collaborate to facilitate adequate and appropriate access to health- and safety-related home modifications, especially for those who cannot afford them. The goal should be to enable persons whose homes contain obstacles, hazards, or features that pose a home safety concern, limit self-care management, or hinder the delivery of needed services to obtain home assessments, home modifications, and training in their use.

Accessibility and Universal Design of New Housing

Almost all existing housing in the United States presents problems for conducting health-related activities because physical features limit independent functioning, impede caregiving, and contribute to such accidents as falls. In spite of the fact that a large and growing number of persons, including children, adults, veterans, and older adults, have disabilities and chronic conditions, new housing continues to be built that does not account for their needs (current or future). Although existing homes can be modified to some extent to address some of the limitations, a proactive, preventive, and effective approach would be to plan to address potential problems in the design phase of new and renovated housing, before construction.

Some housing is already required to be built with basic accessibility features that facilitate practice of health care in the home as a result of the Fair Housing Act Amendments of 1998. And 17 states and 30 cities have passed what are called “visitability” codes, which currently apply to 30,000 homes. Some localities offer tax credits, such as Pittsburgh through an ordinance, to encourage installing visitability features in new and renovated housing. The policy in Pittsburgh was impetus for the Pennsylvania Residential VisitAbility Design Tax Credit Act signed into law on October 28, 2006, which offers property owners a tax credit for new construction

and rehabilitation. The Act paves the way for municipalities to provide tax credits to citizens by requiring that such governing bodies administer the tax credit (Self-Determination Housing Project of Pennsylvania, Inc., n.d.).

Visitability, rather than full accessibility, is characterized by such limited features as an accessible entry into the home, appropriately wide doorways and one accessible bathroom. Both the International Code Council, which focuses on building codes, and the American National Standards Institute, which establishes technical standards, including ones associated with accessibility, have endorsed voluntary accessibility standards. These standards facilitate more jurisdictions to pass such visitability codes and encourage legislative consistency throughout the country. To date, however, the federal government has not taken leadership to promote compliance with such standards in housing construction, even for housing for which it provides financial support.

Universal design, a broader and more comprehensive approach than visitability, is intended to suit the needs of persons of all ages, sizes, and abilities, including individuals with a wide range of health conditions and activity limitations. Steps toward universal design in renovation could include such features as anti-scald faucet valve devices, nonslip flooring, lever handles on doors, and a bedroom on the main floor. Such features can help persons and their caregivers carry out everyday tasks and reduce the incidence of serious and costly accidents (e.g., falls, burns). In the long run, implementing universal design in more homes will result in housing that suits the long-term needs of more residents, provides more housing choices for persons with chronic conditions and disabilities, and causes less forced relocation of residents to more costly settings, such as nursing homes.

Issues related to housing accessibility have been acknowledged at the federal level. For example, visitability and universal design are in accord with the objectives of the Safety of Seniors Act (Public Law No. 110-202, passed in 2008). In addition, implementation of the Olmstead decision (in which the U.S. Supreme Court ruled that the Americans with Disabilities Act may require states to provide community-based services rather than institutional placements for individuals with disabilities) requires affordable and accessible housing in the community.

Visitability, accessibility, and universal design of housing all are important to support the practice of health care in the home, but they are not broadly implemented and incentives for doing so are few.

Recommendation 7. Federal agencies, such as the U.S. Department of Housing and Urban Development, the U.S. Department of Veterans Affairs, and the Federal Housing Administration, should take a lead role, along with states and local municipalities, to develop strategies that promote and facilitate increased housing visitability, accessibil-

ity, and universal design in all segments of the market. This might include tax and other financial incentives, local zoning ordinances, model building codes, new products and designs, and related policies that are developed as appropriate with standards-setting organizations (e.g., the International Code Council, the International Electrotechnical Commission, the International Organization for Standardization, and the American National Standards Institute).

RESEARCH AND DEVELOPMENT

In our review of the research literature, the committee learned that there is ample foundational knowledge to apply a human factors lens to home health care, particularly as improvements are considered to make health care safe and effective in the home. However, much of what is known is not being translated effectively into practice, neither in design of equipment and information technology or in the effective targeting and provision of services to all those in need. Consequently, the four recommendations that follow support research and development to address knowledge and communication gaps and facilitate provision of high-quality health care in the home. Specifically, the committee recommends (1) research to enhance coordination among all the people who play a role in health care practice in the home, (2) development of a database of medical devices in order to facilitate device prescription, (3) improved surveys of the people involved in health care in the home and their residential environments, and (4) development of tools for assessing the tasks associated with home-based health care.

Health Care Teamwork and Coordination

Frail elders, adults with disabilities, disabled veterans, and children with special health care needs all require coordination of the care services that they receive in the home. Home-based health care often involves a large number of elements, including multiple care providers, support services, agencies, and complex and dynamic benefit regulations, which are rarely coordinated. However, coordinating those elements has a positive effect on care recipient outcomes and costs of care. When successful, care coordination connects caregivers, improves communication among caregivers and care recipients and ensures that receivers of care obtain appropriate services and resources.

To ensure safe, effective, and efficient care, everyone involved must collaborate as a team with shared objectives. Well-trained primary health care teams that execute customized plans of care are a key element of coordinated care; teamwork and communication among all actors are also

essential to successful care coordination and the delivery of high-quality care. Key factors that influence the smooth functioning of a team include a shared understanding of goals, common information (such as a shared medication list), knowledge of available resources, and allocation and coordination of tasks conducted by each team member.

Barriers to coordination include insufficient resources available to (a) help people who need health care at home to identify and establish connections to appropriate sources of care, (b) facilitate communication and coordination among caregivers involved in home-based health care, and (c) facilitate communication among the people receiving and the people providing health care in the home.

The application of systems analysis techniques, such as task analysis, can help identify problems in care coordination systems and identify potential intervention strategies. Human factors research in the areas of communication, cognitive aiding and decision support, high-fidelity simulation training techniques, and the integration of telehealth technologies could also inform improvements in care coordination.

Recommendation 8 . The Agency for Healthcare Research and Quality should support human factors–based research on the identified barriers to coordination of health care services delivered in the home and support user-centered development and evaluation of programs that may overcome these barriers.

Medical Device Database

It is the responsibility of physicians to prescribe medical devices, but in many cases little information is readily available to guide them in determining the best match between the devices available and a particular care recipient. No resource exists for medical devices, in contrast to the analogous situation in the area of assistive and rehabilitation technologies, for which annotated databases (such as AbleData) are available to assist the provider in determining the most appropriate one of several candidate devices for a given care recipient. Although specialists are apt to receive information about devices specific to the area of their practice, this is much less likely in the case of family and general practitioners, who often are responsible for selecting, recommending, or prescribing the most appropriate device for use at home.

Recommendation 9. The U.S. Food and Drug Administration, in collaboration with device manufacturers, should establish a medical device database for physicians and other providers, including pharmacists, to use when selecting appropriate devices to prescribe or recommend

for people receiving or self-administering health care in the home. Using task analysis and other human factors approaches to populate the medical device database will ensure that it contains information on characteristics of the devices and implications for appropriate care recipient and device operator populations.

Characterizing Caregivers, Care Recipients, and Home Environments

As delivery of health care in the home becomes more common, more coherent strategies and effective policies are needed to support the workforce of individuals who provide this care. Developing these will require a comprehensive understanding of the number and attributes of individuals engaged in health care in the home as well as the context in which care is delivered. Data and data analysis are lacking to accomplish this objective.

National data regarding the numbers of individuals engaged in health care delivery in the home—that is, both formal and informal caregivers—are sparse, and the estimates that do exist vary widely. Although the Bureau of Labor Statistics publishes estimates of the number of workers employed in the home setting for some health care classifications, they do not include all relevant health care workers. For example, data on workers employed directly by care recipients and their families are notably absent. Likewise, national estimates of the number of informal caregivers are obtained from surveys that use different methodological approaches and return significantly different results.

Although numerous national surveys have been designed to answer a broad range of questions regarding health care delivery in the home, with rare exceptions such surveys reflect the relatively limited perspective of the sponsoring agency. For example,

The Medicare Current Beneficiary Survey (administered by the Centers for Medicare & Medicaid Services) and the Health and Retirement Survey (administered by the National Institute on Aging) are primarily geared toward understanding the health, health services use, and/or economic well-being of older adults and provide no information regarding working-age adults or children or information about home or neighborhood environments.
The Behavioral Risk Factors Surveillance Survey (administered by the Centers for Disease Control and Prevention, CDC), the National Health Interview Survey (administered by the CDC), and the National Children’s Study (administered by the U.S. Department of Health and Human Services and the U.S. Environmental Protection Agency) all collect information on health characteristics, with limited or no information about the housing context.
The American Housing Survey (administered by the U.S. Department of Housing and Urban Development) collects detailed information regarding housing, but it does not include questions regarding the health status of residents and does not collect adequate information about home modifications and features on an ongoing basis.

Consequently, although multiple federal agencies collect data on the sociodemographic and health characteristics of populations and on the nation’s housing stock, none of these surveys collects data necessary to link the home, its residents, and the presence of any caregivers, thus limiting understanding of health care delivered in the home. Furthermore, information is altogether lacking about health and functioning of populations linked to the physical, social, and cultural environments in which they live. Finally, in regard to individuals providing care, information is lacking regarding their education, training, competencies, and credentialing, as well as appropriate knowledge about their working conditions in the home.

Better coordination across government agencies that sponsor such surveys and more attention to information about health care that occurs in the home could greatly improve the utility of survey findings for understanding the prevalence and nature of health care delivery in the home.

Recommendation 10. Federal health agencies should coordinate data collection efforts to capture comprehensive information on elements relevant to health care in the home, either in a single survey or through effective use of common elements across surveys. The surveys should collect data on the sociodemographic and health characteristics of individuals receiving care in the home, the sociodemographic attributes of formal and informal caregivers and the nature of the caregiving they provide, and the attributes of the residential settings in which the care recipients live.

Tools for Assessing Home Health Care Tasks and Operators

Persons caring for themselves or others at home as well as formal caregivers vary considerably in their skills, abilities, attitudes, experience, and other characteristics, such as age, culture/ethnicity, and health literacy. In turn, designers of health-related devices and technology systems used in the home are often naïve about the diversity of the user population. They need high-quality information and guidance to better understand user capabilities relative to the task demands of the health-related device or technology that they are developing.

In this environment, valid and reliable tools are needed to match users with tasks and technologies. At this time, health care providers lack the

tools needed to assess whether particular individuals would be able to perform specific health care tasks at home, and medical device and system designers lack information on the demands associated with health-related tasks performed at home and the human capabilities needed to perform them successfully.

Whether used to assess the characteristics of formal or informal caregivers or persons engaged in self-care, task analysis can be used to develop point-of-care tools for use by consumers and caregivers alike in locations where such tasks are encouraged or prescribed. The tools could facilitate identification of potential mismatches between the characteristics, abilities, experiences, and attitudes that an individual brings to a task and the demands associated with the task. Used in ambulatory care settings, at hospital discharge or other transitions of care, and in the home by caregivers or individuals and family members themselves, these tools could enable assessment of prospective task performer’s capabilities in relation to the demands of the task. The tools might range in complexity from brief screening checklists for clinicians to comprehensive assessment batteries that permit nuanced study and tracking of home-based health care tasks by administrators and researchers. The results are likely to help identify types of needed interventions and support aids that would enhance the abilities of individuals to perform health care tasks in home settings safely, effectively, and efficiently.

Recommendation 11. The Agency for Healthcare Research and Quality should collaborate, as necessary, with the National Institute for Disability and Rehabilitation Research, the National Institutes of Health, the U.S. Department of Veterans Affairs, the National Science Foundation, the U.S. Department of Defense, and the Centers for Medicare & Medicaid Services to support development of assessment tools customized for home-based health care, designed to analyze the demands of tasks associated with home-based health care, the operator capabilities required to carry them out, and the relevant capabilities of specific individuals.

Association for the Advancement of Medical Instrumentation. (2009). ANSI/AAMI HE75:2009: Human factors engineering: Design of medical devices. Available: http://www.aami.org/publications/standards/HE75_Ch16_Access_Board.pdf [April 2011].

Self-Determination Housing Project of Pennsylvania, Inc. (n.d.) Promoting visitability in Pennsylvania. Available: http://www.sdhp.org/promoting_visitability_in_pennsy.htm [March 30, 2011].

In the United States, health care devices, technologies, and practices are rapidly moving into the home. The factors driving this migration include the costs of health care, the growing numbers of older adults, the increasing prevalence of chronic conditions and diseases and improved survival rates for people with those conditions and diseases, and a wide range of technological innovations. The health care that results varies considerably in its safety, effectiveness, and efficiency, as well as in its quality and cost.

Health Care Comes Home reviews the state of current knowledge and practice about many aspects of health care in residential settings and explores the short- and long-term effects of emerging trends and technologies. By evaluating existing systems, the book identifies design problems and imbalances between technological system demands and the capabilities of users. Health Care Comes Home recommends critical steps to improve health care in the home. The book's recommendations cover the regulation of health care technologies, proper training and preparation for people who provide in-home care, and how existing housing can be modified and new accessible housing can be better designed for residential health care. The book also identifies knowledge gaps in the field and how these can be addressed through research and development initiatives.

Health Care Comes Home lays the foundation for the integration of human health factors with the design and implementation of home health care devices, technologies, and practices. The book describes ways in which the Agency for Healthcare Research and Quality (AHRQ), the U.S. Food and Drug Administration (FDA), and federal housing agencies can collaborate to improve the quality of health care at home. It is also a valuable resource for residential health care providers and caregivers.

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Cost-effectiveness of PCV20 to Prevent Pneumococcal Disease in the Pediatric Population: A German Societal Perspective Analysis

Original Research
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Published: 11 May 2024

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An Ta ORCID: orcid.org/0000-0003-0929-6365 1 ,
Felicitas Kühne ORCID: orcid.org/0000-0001-9762-3842 2 ,
Maren Laurenz 2 ,
Christof von Eiff 2 ,
Sophie Warren 3 &
Johnna Perdrizet ORCID: orcid.org/0000-0002-4260-7607 4

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Introduction

Since 2009, a pneumococcal conjugate vaccine (PCV) covering 13 serotypes (PCV13) has been included by Germany’s Standing Committee on Vaccinations for infants, resulting in major reductions in pneumococcal disease (PD). Higher-valent vaccines may further reduce PD burden. This cost-effectiveness analysis compared 20-valent PCV (PCV20) under a 3+1 schedule with 15-valent PCV (PCV15) and PCV13, both under 2+1 schedule, in Germany’s pediatric population.

A Markov model with annual cycles over a 10-year time horizon was adapted to simulate the clinical and economic impact of pediatric vaccination with PCV20 versus lower-valent PCVs in Germany. The model used PCV13 clinical effectiveness and impact studies as well as PCV7 efficacy studies for vaccine direct and indirect effect estimates. Epidemiologic, utility, and medical cost inputs were obtained from published sources. Benefits and costs were discounted at 3% from a German societal perspective. Outcomes included PD cases, deaths, costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs).

In the base case, PCV20 provided greater health benefits than PCV13, averting more cases of invasive pneumococcal disease (IPD; 15,301), hospitalized and non-hospitalized pneumonia (460,197 and 472,365, respectively), otitis media (531,634), and 59,265 deaths over 10 years. This resulted in 904,854 additional QALYs and a total cost saving of €2,393,263,611, making PCV20 a dominant strategy compared with PCV13. Compared to PCV15, PCV20 was estimated to avert an additional 11,334 IPD, 704,948 pneumonia, and 441,643 otitis media cases, as well as 41,596 deaths. PCV20 was associated with a higher QALY gain and lower cost (i.e., dominance) compared with PCV15. The robustness of the results was confirmed through scenario analyses as well as deterministic and probabilistic sensitivity analyses.

PCV20 3+1 dominated both PCV13 2+1 and PCV15 2+1 over 10 years. Replacing lower-valent PCVs with PCV20 would result in greater clinical and economic benefits, given PCV20’s broader serotype coverage.

Plain Language Summary

Pneumococcal diseases (e.g., ear infections, pneumonia, bloodstream infections) are among the leading causes of illness and death in children worldwide. The pneumococcal conjugate vaccine protects against pneumococcal diseases and has significantly reduced the number of newly diagnosed cases. Higher-valent vaccines (which provide coverage for a greater number of disease-causing serotypes) have recently received European Commission approval for use in adults and children. This study examined costs and health benefits associated with the 20-valent pneumococcal conjugate vaccine (PCV20) under a 3+1 (i.e., three primary doses and one booster dose) schedule in Germany’s childhood vaccination program compared with 13-valent pneumococcal conjugate vaccine (PCV13) and the 15-valent pneumococcal conjugate vaccine (PCV15), both under a 2+1 (two primary doses, one booster) schedule. PCV20 was estimated to result in greater health benefits from avoiding more cases in pneumococcal diseases and lower costs compared with both PCV13 and PCV15. PCV20, therefore, is considered the best option among the three vaccines for children in Germany.

Avoid common mistakes on your manuscript.

Streptococcus pneumoniae is the leading cause of bacterial pneumonia and global mortality in children [ 2 , 3 , 4 , 5 ]. In 2016, S. pneumoniae has been estimated to account for approximately 197 million cases of pneumonia and 1.1 million deaths [ 6 ]. This encapsulated bacterium is the major cause of pneumococcal diseases ranging from otitis media (OM) and pneumonia to life-threatening invasive pneumococcal diseases (IPDs), including sepsis and meningitis.

Pneumococcal conjugate vaccines (PCV) elicit robust and durable immune responses in both pediatric and adult populations [ 4 ]. They have noticeably reduced IPD incidence across all age groups due to indirect effects (i.e., herd effects or the effect on the unvaccinated population) [ 7 , 8 ]. The 7-valent PCV (PCV7) was first approved in Europe in 2001 [ 9 ], and was recommended for high-risk children in July 2001 by Germany’s Standing Committee on Vaccinations [Ständige Impfkommission (STIKO)] with a schedule of three priming doses in infancy plus one booster (3+1) [ 10 ]. The recommendation was extended to the entire infant population (< 2 years of age) in July of 2006 [ 11 ].

The 13-valent PCV (PCV13) and 10-valent PCV (PCV10) replaced PCV7 and were introduced in 2009, and administered based on physician’s choice [ 12 ]. In 2015, STIKO changed its recommendations for full-term infants from a 3+1 schedule with the priming series administered at 2, 3, and 4 months and a booster at 11–14 months, to a 2+1 vaccination schedule with a priming series administered at 2 months and 4 months plus a booster at 11 months [ 3 , 13 ]. The 3+1 schedule remains in place for preterm infants [ 14 ].

Next-generation PCVs with increased serotype coverage [15-valent PCV (PCV15) and 20-valent PCV (PCV20)] were approved for adults aged 18 years and older by the European Commission in October 2021 and February 2022, respectively [ 15 , 16 ]. Since September 2023, PCV20 is recommended in Germany for all individuals aged 60 years and older and for all individuals aged 18‒59 years with underlying diseases. A cost-effectiveness analysis (CEA) in the German adult population concluded that a single dose of PCV20 for adults aged ≥ 60 years and adults aged 18‒59 years with moderate- and high-risk conditions would prevent pneumococcal disease cases, save lives, and would be cost-saving compared to the pneumococcal polysaccharide vaccine (PPSV23) alone, PCV13 followed by PPSV23, or PCV15 followed by PPSV23 [ 17 ].

Prior to the licensure of PCV15 in October of 2022, PCV13 was considered as the standard of care. With the inclusion of PCV15 in the STIKO recommendation for infants in Germany, the current clinical practice includes a market basket of PCV13 and PCV15. PCV20 covers all PCV15 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) and five additional serotypes (8, 10A, 11A, 12F, and 15B). On January 25, 2024, the Committee for Medicinal Products for Human Use adopted a positive opinion for the higher-valent option of PCV20 for the use in children [ 18 ] PCV20 was approved by the European Commission in a 3+1 schedule on March 12, 2024 [ 16 ]. The purpose of this CEA was to examine the health benefits and costs of implementing a PCV20 vaccination program under a 3+1 schedule in Germany’s pediatric population compared with PCV13 and PCV15, both administered in a 2+1 schedule.

Conceptual Framework and Model Structure

The CEA was structured in Microsoft Excel ® (Redmond, WA, US) using a decision-analytic Markov (state-transition) cohort model. The Markov model estimated pneumococcal disease-related events in both unvaccinated and vaccinated individuals (Fig. 1 ). The model captured an individual’s possible transition to several clinical events, including IPD (developing into either meningitis or sepsis/bacteremia), all-cause pneumonia (non-hospitalized or hospitalized), all-cause OM, no pneumococcal disease state, and death. Death captured both general mortality and case fatality, which could occur in any disease state and non-disease state. The transition occurred on an annual cycle and was age- and vaccination-specific. The non-mutually exclusive nature of pneumococcal disease was reflected through each 12-month interval during which persons could transition to one or more disease states or remain in a non-disease state. In the case of more than one pneumococcal disease, costs and quality-adjusted life year (QALY) decrements associated with all events were considered. At the beginning of each annual cycle, a new cohort of children (i.e., incoming birth cohort) entered the model and was eligible for vaccination.

Model structure. IPD invasive pneumococcal disease, mo months, OM otitis media, SoC standard of care, yrs years

The full health benefit of vaccination was applied to the entire German population, of which the vaccinated cohort experienced the direct effects of vaccination immediately, while the rest of the unvaccinated population gradually received indirect effects over the model time horizon.

Target Population and Subgroups

The target population was composed of infants aged < 2 years (i.e., ,a vaccination cohort), while the model assumed that the groups aged 2–4 years, 5–17 years, and 18–49 years were not vaccinated with the higher-valent PCVs. In clinical practice, a proportion of the group ≥ 60 years is vaccinated under the adult immunization program [ 19 , 20 ]; hence, within this pediatric model, that proportion of adults was excluded from receiving indirect effects, while the remainder of the population ≥ 60 years remained unvaccinated and benefitted from indirect effects of pediatric vaccination.

Intervention and Comparator Strategies

STIKO currently recommends PCV10, PCV13, and PCV15 for infants and children in Germany [ 21 ]. However, PCV13 was shown to avoid more cases than PCV10 [ 22 ] and accounts for the majority of vaccination rate, at more than 90%, in children, remaining the most used PCV in the past decade in Germany [ 13 , 23 ]. Therefore, PCV10, although included in the STIKO recommendation, was not considered among comparators in this analysis. The analysis evaluated the clinical and economic outcomes of PCV20 in a 3+1 schedule as a potential vaccination strategy compared with PCV13 (i.e., standard of care) and PCV15, both in a 2+1 schedule.

Perspective, Time Horizon, Cycle Length, and Discount Rate

The base-case analysis was conducted from a German societal perspective using a 3% annual discount rate for both costs and benefits, according to the recommendations of the Institute for Quality and Efficiency in Health Care and STIKO [ 24 , 25 ]. The model used an annual cycle length over a 10-year time horizon to capture relevant costs and outcomes. The 10-year time horizon sufficiently captures the health benefits of the PCV vaccination program, based on the observation of the accrual and stabilization of indirect effects over a 5- to 10-year period following the introduction of PCV7 and PCV13 [ 26 , 27 ]. The life years and QALY loss is accumulated over the time loss between death occurrence and life expectancy (with the QALYs being age-dependent and discounted from the year the death occurs). Lifetime long-term costs related to a clinical event, such as sequalae following meningitis, were incorporated in the model as a one-time discounted cost in the cycle in which the event happens.

This study was based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors; as such, ethical approval was not required.

Population and Epidemiology Data

Population data were obtained from the German Federal Statistical Office to determine the size of the stratified population age groups [ 28 ] (Table S1 ; Supplementary Material) and the incoming birth cohort each year [ 29 ] (Table S2; Supplementary Material).

Age-specific disease incidence rates per 100,000 individuals were informed by German-specific published literature [ 30 , 31 , 32 , 33 ], adjusted for relevant age groups using population size from the German Federal Statistical Office [ 28 ] (Table 1 ).

Mortality in the analysis was considered as a combination of general mortality [ 34 ] and case fatality, which were applied to meningitis, sepsis/bacteremia, and all-cause hospitalized and non-hospitalized pneumonia (Table 1 ), while no mortality was assumed for OM [ 22 , 31 ].

The model considered sequela following meningitis (i.e., deafness and non-deafness) in the base case as sequela following meningitis are quite common among patients with IPD [ 22 ]. The data for the proportion of patients developing complications with IPD were sourced from published literature [ 22 ] (Table S3; Supplementary Material).

IPD serotype-specific distribution by each PCV stratified by age groups was obtained from [ 35 , 36 ] (Table 2 ). The serotype coverage for PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F) was incorporated as one input, while the coverage for each additional serotype included in higher valent vaccines was input separately for each age group. The analysis did not consider cross-reactive serotypes. Non-invasive serotype distributions (i.e., for pneumonia and OM) were assumed to be the same as IPD serotype distribution.

Vaccine Effectiveness and Efficacy

The direct effect of PCVs against IPD for a complete vaccine schedule was assumed to be equivalent to the adjusted PCV13 effectiveness against PCV13-type IPD, of which 78.2% [95% confidence interval (CI) 56.0, 89.0] was applied for vaccines in a 2+1 schedule while 89.7% (95% CI 82.0, 94.0) was used for PCV20 in 3+1 schedule (Table 3 ) [ 37 ]. To estimate the direct effects of the higher-valent PCVs against all-cause pneumonia (non-hospitalized and hospitalized) and OM, the model adopted an approach commonly used in CEAs [ 38 , 39 , 40 , 41 , 42 ], in which the effectiveness of higher-valent PCVs against non-invasive disease was assumed to be the same as the reported trial-based efficacy data of PCV7, which was then adjusted based on study design, period, and country-specific factors. These results demonstrated an efficacy of 25.5% (95% CI 4.4, 34.0) [ 43 ], 6.0% (95% CI − 1.5, 11.0) [ 44 ], and 7.8% (95% CI 5.2, 10.5) [ 45 ] against radiographically confirmed non-invasive hospitalized pneumonia, non-hospitalized pneumonia, and OM, respectively (Table 3 ).

In addition, a < 12-month effect modifier was used to account for potential reduced effectiveness in the first year of life during which children have only received the priming series of the full vaccination schedule [i.e., at two-thirds (~ 67%) of the full effect for vaccination with a 2+1 schedule for PCV13 and PCV15, and at 75.6% for PCV20 3+1 based on the Advisory Committee on Immunization Practices’ assumption [ 46 ]]. Vaccine coverage was set at 89.9% for the priming series and at 76.8% for the booster dose [ 47 ].

Evidence has shown that direct effects of PCVs remain stable for a few years after the final dose. For example, the efficacy of PCV13 was steady for up to 4 years in infants after vaccination was completed [ 37 ] and for more than 5 years in people aged ≥ 65 years after a single dose [ 48 ]. Therefore, in the base case, a full direct effect for the first 5 years after the booster dose was assumed for all vaccines, followed by an annual waning of 10% from year 6 through year 10.

The analysis considered indirect effects in unvaccinated individuals since they are an important benefit from pediatric PCV national immunization programs. The indirect effect against serotypes covered represents the maximum protection the unvaccinated population could receive from a vaccine regimen. This was modeled as a percent reduction in the expected age-specific disease incidence. Indirect effect was not realized immediately and was only applied to newly covered serotypes in PCV15 and PCV20, as the indirect effect for PCV13 serotypes was assumed to have already reached a steady state. These benefits accrued gradually until a new steady state was reached for additional serotypes. Indirect effect for PCV15 and PCV20 was assumed to have no added effects on PCV13 steady-state serotypes. The model assumed that incidence trends for all newly covered serotypes would decrease consistently across ages. For IPD and non-hospitalized and hospitalized pneumonia, indirect effect was assumed for all age groups, while for OM, indirect effect was assumed only for the < 5 years age group. To estimate indirect effects, the model incorporated the reduction in incidence of the newly covered serotypes and the accrual of the indirect effects of higher-valent PCVs (see Supplementary Material, Appendix A).

Resource Use and Costs

Vaccine costs for PCV13, PCV20, and PCV15 were derived from retail pharmacy price per dose [ 49 ], and the administration cost were from [ 22 ], inflated to 2022 Euros (€). Additional vaccine cost and administration cost, which accounted for an additional visit, were applied to the extra dose under 3+1 schedule for PCV20. Medical costs per episode related to each disease state sourced from [ 22 ] were included for all relevant age groups in the model [ 22 ]. Lifetime medical costs per episode of sequela were assumed to be the same across all age groups for deafness and non-deafness [ 22 ]. Societal costs considered productivity loss per episode of meningitis, sepsis/bacteremia, inpatient and outpatient pneumonia and OM, as well copayment for adult patients. All costs were in Euros (€) and obtained from German published sources and the literature, then inflated to 2022 prices using the healthcare component of the consumer price index [ 50 ] where relevant. The summary of cost inputs is listed in Table 3 .

The model used baseline utility for the general population [ 51 ] minus disutilities related to disease states and acute events to assess quality of life related to each vaccination strategy (Table 3 ) [ 42 , 52 , 53 , 54 , 55 , 56 , 57 ].

Assessment of Uncertainty

Uncertainty around the analyses was evaluated using deterministic sensitivity analyses (DSA), probabilistic sensitivity analyses (PSA), and scenario analyses. DSA assessed uncertainty around the following variables: disease incidence, breakdown of IPD cases, case fatality rate (CFR), serotype distribution by age, vaccine effectiveness and utilities.

In the PSA, all parameters subject to any degree of uncertainty were assessed The incremental results for costs, QALYs, and incremental cost-effectiveness ratios (ICER) were recorded for each simulation of a total of 1000 simulations to examine the stability of the model findings.

Several scenarios were conducted, the description and results of which are reported in Table 6 . In addition to the scenario assessments, threshold analyses were conducted to assess the price per dose of PCV20 under a 3+1 schedule. These analyses aim to determine the price range at which PCV20 stays a cost-saving strategy compared to PCV13 2+1 and PCV15 2+1, assuming consistent input parameters for other variables (including the prices of PCV13 and PCV15).

Base-case Results

Over the 10-year time horizon, compared to both PCV13 2+1 and PCV15 2+1, PCV20 3+1 provided substantially greater health benefits and broader protection (Table 4 ). Compared to PCV13, PCV20 is estimated to result in greater health benefits due to a greater number of cases averted and total QALYs gained (Table 4 ). Compared with PCV13, PCV20 averted an additional 15,301 cases of IPD; 460,197 and 472,365 cases of hospitalized and non-hospitalized pneumonia, respectively; 531,634 cases of OM; and 59,265 deaths due to disease across all ages. Consequently, PCV20 was estimated with a higher QALY gain of 904,854. In comparison with PCV15, the number of additional cases averted by PCV20 were 11,334, 335,937, 369,012, and 441,643 in IPD, hospitalized pneumonia, non-hospitalized pneumonia, and OM, respectively. Additionally, an estimation of a reduction of 41,596 deaths due to disease was estimated for PCV20 versus PCV15, and PCV20 was associated with an incremental QALY of 646,235.

PCV20 was associated with higher direct vaccine costs, at €525,362,283 and €522,747,819 more than that of PCV13 and PCV15, respectively. This is the result of the higher price per dose considered for PCV20 and the additional dose included in PCV20 under the 3+1 schedule. However, it resulted in significant cost savings from lower direct costs of disease and lifetime costs of sequela compared to both comparators (Table 4 ) due to broader serotype coverage compared to PCV13 and PCV15. PCV20 was the dominant strategy in both comparisons, with a total cost saving of €2,393,263,611 versus PCV13 and of €1,628,000,506 versus PCV15.

The breakdown results by age groups were mostly consistent with the overall results where more cases were avoided related to PCV20 in all included age groups for IPD, hospitalized pneumonia, and OM than to PCV13, especially in the oldest group of 65+ year olds. Similarly, PCV20 is estimated to prevent more cases of non-hospitalized pneumonia than PCV13 in children less than 5 years old. The higher valent vaccines showed an increasing number of prevented non-invasive pneumonia. One could observe a shift from severe cases (i.e., hospitalized cases) in the lower valent vaccine strategies to less severe cases (i.e., non-hospitalized pneumonia) in the higher valent vaccine strategies. Furthermore, better health outcomes from PCV20 were shown by a reduction in deaths due to disease in all age groups, with the greatest reduction observed in those 65 years old and above (50,064 deaths averted) (Table S4; Supplementary Material). Similar results broken down by age groups were also observed when comparing PCV20 with PCV15 (Figs. 1 , 2 , 3 , 4 , 5 ; Table S4; Supplementary Material).

Estimated number of IPD cases stratified by age groups. IPD invasive pneumococcal disease, PCV13 13-valent pneumococcal conjugate vaccine, PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine

Estimated number of hospitalized pneumonia cases stratified by age groups. PCV13 13-valent pneumococcal conjugate vaccine, PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine

Estimated number of non-hospitalized pneumonia cases stratified by age groups. PCV13 13-valent pneumococcal conjugate vaccine, PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine

Estimated number of otitis media cases stratified by age groups. PCV13 13-valent pneumococcal conjugate vaccine, PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine

Sensitivity Analyses

The results from DSA, where one parameter was varied in one direction while all other inputs were held constant, are reported in Fig. 6 for costs and Fig. 7 for QALYs. When compared to PCV13, the key drivers for costs included maximum indirect effect against hospitalized pneumonia (PCV20), serotype distribution by age, incidence of hospitalized pneumonia and medical costs of per episode of hospitalized pneumonia.

DSA results in costs: PCV20 versus PCV13. DSA deterministic sensitivity analysis, PCV13 13-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine

DSA results in QALYs: PCV20 versus PCV13. DSA, deterministic sensitivity analysis; PCV13 13-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine, QALY quality-adjusted life years

The DSA of PCV20 versus PCV13 also illustrated that the top five most impactful parameters on QALYs were maximum indirect effects on hospitalized pneumonia (PCV20) and serotype distribution by age, baseline utilities, followed by hospitalized pneumonia incidence and CFR for hospitalized pneumonia. When comparing PCV20 and PCV15, the results were largely similar (Figs. 8 and 9 ).

DSA results in costs: PCV20 versus PCV15. DSA deterministic sensitivity analysis; PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine

DSA results in QALYs: PCV20 versus PCV15. DSA deterministic sensitivity analysis, PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine, QALY quality-adjusted life years

Probabilistic results from the PSA based on 1,000 iterations aligned with the base case results, confirming robust findings with PCV20 being dominant in all simulations. Compared with PCV13, PCV20 was the dominant strategy in all iterations, while PCV20 dominated PCV15 in 98.40% of the total 1000 iterations (Table 5 ). The cost-effectiveness plane plots are reported in Figs. 10 and 11 .

PSA cost-effectiveness plane versus baseline of PCV13. PCV13 13-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine, PSA probabilistic sensitivity analysis

PSA cost-effectiveness plane versus baseline PCV15. PCV15 15-valent pneumococcal conjugate vaccine, PCV20 20-valent pneumococcal conjugate vaccine, PSA probabilistic sensitivity analysis

Scenario Analyses

Scenario analysis results are summarized in Table 6 . In the three scenarios where different discount rates were applied for costs and benefits, the qualitative conclusion of PCV20 being the dominant strategy compared to both comparators remained robust. When reducing indirect effects (i.e., maximum reduction in disease incidence) by half, PCV20 was still estimated to have better health benefits and lower costs compared to both PCV13 and PCV15. Similarly, extending time to realize indirect effects (i.e., accrual data in the first 2 years at 0%) and increased vaccination uptake in adults 65+ years old aligned with the base case results of PCV20 being the dominant strategy versus both comparators. Using a payer perspective led to a decrease by 15% and 17% in ICER in the comparison between PCV20 versus PCV13 and PCV20 versus PCV15, respectively. However, the qualitative conclusion remained the same. Other scenarios testing a different waning assumption (i.e., reducing duration of full protection to 3 years) and serotype replacement were in line with the base case with minimal change in ICER. Overall, the results and conclusion were relatively robust. When assuming a high vaccine uptake in infant (90%), ICERs increased slightly, at less than 1%, for both PCV20 versus PCV13 and PCV20 versus PCV15. Considering disutility related to adverse events related to the administration of all vaccines (e.g., local reaction and systematic reaction or fever) resulted in the same conclusion of PCV20 3+1 being the dominant strategy among the three PCVs. In the threshold analyses, threshold prices per dose for PCV20 3+1 were €170 versus PCV13 2+1 and €135 versus PCV15 2+1. Given that all price ranges exceed double the current list price per dose of PCV20 for cost-saving analyses, it is reasonable to conclude that changes in the price per dose are unlikely to impact the study's conclusions.

This article is based on previously conducted studies or collected published data and does not contain any new studies with human participants or animals performed by any of the authors.

The introduction of next-generation PCVs with increased serotype coverage in Europe has provided options to be considered in national childhood immunization programs. This study examined the cost and health outcomes related to PCV20 under a 3+1 schedule compared with PCV13 and PCV15, both under a 2+1 schedule, in the pediatric population in Germany.

The base-case results demonstrated PCV20 as the dominant strategy over both lower-valent alternative vaccines. PCV20 was estimated to have greater health benefits than both PCV13 and PCV15 by averting more cases of pneumococcal diseases, including IPD, pneumonia, and OM, over a 10-year time horizon. This resulted in higher QALY gained and lower total costs related to PCV20, implying dominance of PCV20 compared with PCV13 and PCV15. Several scenarios assessed additional uncertainty, such as effects of different discount rates for costs and outcomes, several assumptions on vaccine effects (i.e., reduction in indirect effects and extension in accrual time of indirect effects), and waning duration. In addition, serotype replacement assumptions were examined to test how sensitive the results were to reduction in vaccine-type serotype coverage over time. Finally, payer perspective and an assumption of higher vaccine uptake in infant were explored. The results were robust across all sensitivity analyses including PSA and DSA.

Our findings are consistent with published studies comparing PCV20 to PCV13 and PCV15 in other settings. In Canada [ 58 ] and Greece [ 59 ], PCV20 was estimated to be cost-saving compared with PCV15 in a 2+1 schedule. In the United Kingdom, PCV20 2+1 was estimated to be cost-saving compared to PCV13 1+1 and cost-effective compared with PCV20 1+1 [ 60 ]. Moreover, a public health impact analysis in the Netherlands estimated that PCV20 could avert 45,127 pneumococcal cases compared to PCV10 over 5 years [ 61 ]. Our findings are also consistent with a historic economic evaluation in Germany comparing higher-valent versus lower-valent PCVs, in which PCV13 dominated both PCV10 and PCV7 [ 56 ]. The PCV13 infant immunization program in Germany was expected to have a substantial public health impact because of its broader serotype coverage compared with both PCV7 and PCV10, similar to our findings for PCV20 compared with both PCV13 and PCV15. Differences in disease incidence have been noted; for example, Strutton et al. 2012 [ 56 ] used an IPD incidence among those aged < 2 years of 43.35 per 100,000 individuals, whereas our analysis uses 15.8 per 100,000. The lower incidence values in our economic evaluation reflect the historic impact of PCV13 on disease incidence; however, substantial disease associated with PCV20-unique serotypes remains in Germany.

Our analyses have several limitations. Firstly, a Markov cohort model was considered appropriate for the decision problem based on previous cost-effectiveness assessments of PCVs [ 62 ]. Static models are commonly used for economic evaluations of PCVs in Germany [ 56 , 63 ] and globally [ 42 , 64 , 65 , 66 , 67 , 68 ]. While dynamic models are known to capture indirect effects, the decision-analytic Markov cohort model in this study utilizes the simplistic static Markov framework and incorporates components such as indirect effects. This notable improvement in the modeling approach helps quantify the far-reaching effects of vaccination at the population level while maintaining the clarity and transparency of the model.

The methodological framework adopted in this study was based on the examination of overall vaccine-type serotypes rather than individual serotypes, owing to the limited data suitable for modeling clinical outcomes at the individual serotype level, in particular non-invasive disease. While the analysis encompassed diverse distributions in serotype coverage pertaining to additional serotypes facilitated by higher-valent PCVs in contrast to PCV7, the capacity to scrutinize outcomes specific to distinct serotypes within this paradigm remained constrained. Future modeling endeavors could attempt to explore the nuanced dynamics inherent to pneumococcal serotypes, especially for IPD for which data are more readily available.

German data were prioritized to parameterize the model. When German data were not available, data were sourced from other high-income European countries with similar health care systems. Direct effects were estimated from different sources using PCV13 and PCV7 studies, given no studies have measured the effectiveness of PCV15 or PCV20 against pneumococcal disease outcomes. Differential herd effects were not modeled based on a PCV schedule but have been observed in countries that have implemented PCV13 in infant national immunization programs (i.e., increase in disease reduction under a 3+1 vs. 2+1) [ 26 , 69 ]. There are potential confounding factors, such as the rate of reduction and time to stabilization of IPD incidence across age groups and countries may be associated with multiple factors, including vaccine uptake, implementation of a catch-up program, duration of PCV use, availability of an adult pneumococcal vaccination program, serotypes in circulation, and general epidemiologic variability. To assess the uncertainty around the indirect effect estimations for IPD and non-invasive disease, extensive sensitivity analyses were conducted, such as PSA, DSA, and several scenarios.

The base-case analysis did not include serotype replacement. It is difficult to predict how the characteristics or composition of non-vaccine serotypes will change following higher-valent PCV introduction. Model simulations suggest that replacement may be less for high-valency PCVs [ 70 , 71 ]. To address uncertainty, we tested the impact of increasing non-vaccine serotypes over time, which all led to similar directional results as the base-case (i.e., PCV20 remained dominant).

We did not consider adverse events originating from vaccination by PCV20, PCV15, or PCV13 in our base-case analysis. Although adverse events after pneumococcal vaccination resulting in healthcare seeking are rare and event rates are similar for the different pneumococcal vaccines, PCV20, licensed in a 3+1 schedule, is likely to result in more adverse events than PCV15 and PCV13, both under a 2+1 schedule. We tested this scenario and found that, although PCV20 3+1 was estimated with slightly higher disutility related to the extra dose, the strategy still provides higher total QALY gain compared to lower-valent alternatives and remained dominant.

Despite a numerically higher immunological response reported against serotype 3 for PCV15, we did not model higher vaccine effectiveness against this serotype for PCV15, as data on clinical effectiveness of PCV15 against serotype 3 are unknown. In contrast, a meta-analysis of observational studies supports direct PCV13 protection against serotype 3 IPD in children. Without any real-world effectiveness data for PCV15, there is no way to assess the actual impact of PCV15 on serotype 3. For that reason, PCV15 and PCV20 are assumed to provide comparable protection to PCV13 against serotype 3 disease.

Recently, STIKO recommended PCV20 for adults aged 60 years and older and for adult patients with underlying diseases [ 19 ]. Vaccination rates among adults may increase in the future as PCV20 is only administered once in adults. However, given the recent recommendation and implementation (since January 2024), we were not able to draw conclusions regarding the full impact of adult PCV20 vaccination on epidemiology at this time. To account for the direct impact of adult vaccination, we assumed a proportion of adults received a PCV and therefore received no additional benefit of indirect effects from the pediatric program. We also tested the impact of less pronounced herd effects associated with higher-valent PCVs. Changes to the assumptions resulted in fewer cases avoided and smaller life expectancy gains under a PCV20 pediatric program. However, PCV20 under a 3+1 program remained the dominant strategy avoiding more cases, increasing life expectancy while costing less than PCV13 or PCV15 under a 2+1 program.

Indirect cost estimates were not based on a rigorous German database cost assessment. We applied estimates based on published assumptions. To avoid assumptions on the indirect costs, we carried out a scenario from the payer perspective, not accounting for any indirect costs. This is a very conservative approach given that parents stay at home or have another caregiver for their child. Even under conservative assumptions, PCV20 vaccination strategy was clearly dominating PCV15 and PCV13 strategies resulting in fewer cases and fewer costs.

The results of this CEA estimated that the implementation of PCV20 under a 3+1 schedule into the German immunization recommendation would be less costly and more effective than PCV13 and PCV15, both under a 2+1 schedule. PCV20 has the potential to substantially decrease the clinical and economic burden of pneumococcal diseases in Germany by providing substantially broader protection compared with lower-valent vaccines.

Data Availability

All data generated or analyzed during this study are included in this published article/as supplementary information files.

Ta A, et al. Cost-effectiveness of PCV20 to prevent pneumococcal disease in the pediatric population—a German societal perspective analysis. medRxiv. 2024.03.14.24304296; https://doi.org/10.1101/2024.03.14.24304296 .

Dadonaite, B. and M. Roser, Pneumonia. 2019. OurWorldInData.org.

European Centre for Disease Prevention and Control, Factsheet about pneumococcal disease. 2023.

Ganaie F, et al. A new pneumococcal capsule type, 10D, is the 100th serotype and has a large cps fragment from an oral streptococcus. mBio. 2020. https://doi.org/10.1128/mbio.00937-20 .

Article PubMed PubMed Central Google Scholar

World Health Organization. Pneumococcal Disease. [cited 2023 June]; Available from: https://www.who.int/teams/health-product-policy-and-standards/standards-and-specifications/vaccine-standardization/pneumococcal-disease .

Troeger C, et al. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis. 2018;18(11):1191–210.

Article Google Scholar

Ladhani SN, et al. Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000–17: a prospective national observational cohort study. Lancet Infect Dis. 2018;18(4):441–51.

Article PubMed Google Scholar

Wahl B, et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000–15. Lancet Glob Health. 2018;6(7):e744–57.

Tin Tin Htar M, Christopoulou D, Schmitt H-J. Pneumococcal serotype evolution in Western Europe. BMC Infect Dis. 2015;15(1):419.

Empfehlungen der Ständigen Impfkommission (STIKO) am Robert Koch-Institut. Begründung der STIKO-Empfehlungen zur Impfung gegen Pneumokokken und Meningokokken vom Juli 2006. Epidemiologisches Bulletin 2006;4(31).

Robert-Koch-Institut. Impfempfehlungen der Ständigen, I., Begründungen zur allgemeinen Empfehlung der Impfungen gegen Pneumokokken und Meningokokken im Säuglings- und Kindesalter, in Epidemiologisches Bulletin. Robert Koch-Institut. 2006.

van der Linden M, et al. Four years of universal pneumococcal conjugate infant vaccination in Germany: Impact on incidence of invasive pneumococcal disease and serotype distribution in children. Vaccine. 2012;30(40):5880–5.

Perniciaro S, et al. Regional variations in serotype distribution and vaccination status in children. PLoS One. 2019;14(1932-6203(electronic)):e0210278.

Article CAS PubMed PubMed Central Google Scholar

Robert Koch-Instituts (RKI). Epidemiologisches Bulletin. Robert Koch-Institut. 2015.

European Medicines Agency. European public assessment report. Vaxneuvance. 2021 [cited 2024 March]; Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/vaxneuvance .

European Medicines Agency. European public assessment report. Prevenar 20 (previously Apexxnar). [cited 2024 March]; Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/prevenar-20-previously-apexxnar .

Kühne Felicitas, et al. Cost-effectiveness of use of 20-valent pneumococcal conjugate vaccine among adults in Germany. Expert Rev Vacc. 2023;22(1):921–32. https://doi.org/10.1080/14760584.2023.2262575 .

Article CAS Google Scholar

European Medicines Agency. Apexxnar—opinion on variation to marketing authorisation. [cited 2024 February]; Available from: https://www.ema.europa.eu/en/medicines/human/variation/apexxnar .

Robert-Koch-Institut. STIKO: Aktualisierung der Empfehlungen zur Pneumokokken-Impfung in Epidemiologisches Bulletin. Robert-Koch-Institut. 2023.

Robert-Koch-Institut. Impfquoten bei Erwachsenen in Deutschland in Epidemiologisches Bulletin. Robert-Koch-Institut. 2022.

Robert-Koch-Institut. Impfempfehlungen der Ständigen, I., Stellungnahme der STIKO zum Einsatz von Pneumokokken-Konjugatimpfstoffen im Säuglings-, Kindes- und Jugendalter, in Epidemiologisches Bulletin. Robert Koch-Institut. 2023.

Kuhlmann A, von der Schulenburg JMG. Modeling the cost-effectiveness of infant vaccination with pneumococcal conjugate vaccines in Germany. Eur J Health Econ. 2017;18(3):273–92.

Weiss S, et al. Impact of 10-and 13-valent pneumococcal conjugate vaccines on incidence of invasive pneumococcal disease in children aged under 16 years in Germany, 2009 to 2012. Eurosurveillance. 2015. https://doi.org/10.2807/1560-7917.ES2015.20.10.21057 .

Institut für Qualität und Wirtschaftlichkeit im, G., Allgemeine Methoden. 2022.

Ständige Impfkommission am Robert-Koch-Institut, Standardvorgehensweise (SOP) der Ständigen Impfkommission (STIKO) für die systematische Entwicklung von Impfempfehlungen Version 3.1 (Stand: 14.11.2018). Berlin. 2018.

Shiri T, et al. Indirect effects of childhood pneumococcal conjugate vaccination on invasive pneumococcal disease: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(1):e51–9.

Centers for Disease Control and Prevention. 2019. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Streptococcus pneumoniae, 2019. [cited 2024 March]; Available from: https://www.cdc.gov/abcs/downloads/SPN_Surveillance_Report_2019.pdf .

Statistisches Bundesamt (Destatis), Population: Germany Reporting date, age years. 2022.

Destatis Statistiches B. Current population of Germany. 2023 13 June 2023]; Available from: https://www.destatis.de/EN/Themes/Society-Environment/Population/Current-Population/_node.html .

Weinberger R, et al. Invasive pneumococcal disease in children under 16 years of age: Incomplete rebound in incidence after the maximum effect of PCV13 in 2012/13 in Germany. Vaccine. 2018;36(4):572–7.

Deb A, et al. Clinical and economic burden of pneumococcal disease among individuals aged 16 years and older in Germany. Epidemiol Infect. 2022;150: e204.

Kuhlmann A, von der Schulenburg JMG. Authors’ reply to Gandjour: “Modeling the cost-effectiveness of infant vaccination with pneumococcal conjugate vaccines in Germany.” Eur J Health Econ. 2018;19(3):473–81.

Hu T, et al. Incidence of acute otitis media in children < 16 years old in Germany during 2014–2019. BMC Pediatr. 2022;22(1):204.

van der Linden M, Itzek A. Invasive pneumococcal disease among adults in Germany. Reporting period: 1 July 1992–30 June 2022, in Report for Pfizer Pharma GmbH. 2022, data on file.

van der Linden M, Itzek A. Invasive pneumococcal disease among adults in Germany. Reporting period: 1 July 1992–30 June 2022, in Report for Pfizer Pharma GmbH. 2022.

van der Linden M, Itzek A. Effects of the National Immunization Program for Pneumococcal Conjugate Vaccination (PCV7, PCV10, PCV13) on invasive pneumococcal disease among children in Germany. Reporting period: 1 July 1997–30 June 2022. Pfizer data on file. 2022.

Savulescu C, et al. Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: SpIDnet observational multicentre study. Vaccine. 2022;40(29):3963–74.

Article CAS PubMed Google Scholar

Ansaldi F, et al. Estimating the clinical and economic impact of switching from the 13-valent pneumococcal conjugate vaccine (PCV13) to the 10-valent pneumococcal conjugate vaccine (PCV10) in Italy. Pathogens. 2020. https://doi.org/10.3390/pathogens9020076 .

Kim H-Y, et al. Cost-effectiveness of a national immunization program with the 13-valent pneumococcal conjugate vaccine compared with the 10-valent pneumococcal conjugate vaccine in South Korea. Hum Vaccin Immunother. 2021;17(3):909–18.

Klok RM, et al. Cost-effectiveness of a 10- versus 13-valent pneumococcal conjugate vaccine in Denmark and Sweden. Clin Ther. 2013;35(2):119–34.

Kulpeng W, et al. Cost-utility analysis of 10- and 13-valent pneumococcal conjugate vaccines: protection at what price in the Thai context? Vaccine. 2013;31(26):2839–47.

Rozenbaum MH, et al. Cost effectiveness of pneumococcal vaccination among Dutch infants: economic analysis of the seven valent pneumococcal conjugated vaccine and forecast for the 10 valent and 13 valent vaccines. BMJ. 2010;340: c2509.

Hansen J, et al. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than 5 years of age for prevention of pneumonia: updated analysis using world health organization standardized interpretation of chest radiographs. Pediat Infect Dis J. 2006;25(9):779–81.

Black SB, et al. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia. Pediatr Infect Dis J. 2002;21(9):810–5.

Black S, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J. 2000;19(3):187–95.

Stoecker C. Economic assessment of PCV15 &PCV20. In: Advisory Committee on Immunization Practices. Atlanta, GA. 2021.

Schley K, et al. Did the change of the vaccination schedule effect pneumococcal conjugate vaccination compliance and adherence of premature and mature born infants in Germany? Answers from a claims database analysis. Vaccine. 2023;41(28):4081–91. https://doi.org/10.1016/j.vaccine.2023.05.045 .

Patterson S, et al. A post hoc assessment of duration of protection in CAPiTA (Community Acquired Pneumonia immunization Trial in Adults). Trials Vaccinol. 2016;5:92–6.

Lauer-Fischer GmbH. LAUER-TAXE® Kompetenz online. 2023.

Statistisches Bundesamt (Destatis), Consumer Price Index: Germany Reporting date, application [Table 61111]. 2022. [cited 2024 March]. Available from: https://www.destatis.de/EN/Home/_node.html .

Grochtdreis T, et al. Health-related quality of life measured with the EQ-5D-5L: estimation of normative index values based on a representative German population sample and value set. Eur J Health Econ. 2019;20(6):933–44.

Mangen M-JJ, et al. Cost-effectiveness of adult pneumococcal conjugate vaccination in the Netherlands. Eur Respir J. 2015;46(5):1407.

Melegaro A, Edmunds WJ. Cost-effectiveness analysis of pneumococcal conjugate vaccination in England and Wales. Vaccine. 2004;22(31):4203–14.

Rozenbaum MH, et al. Vaccination of risk groups in England using the 13 valent pneumococcal conjugate vaccine: economic analysis. BMJ Br Med J. 2012;345: e6879.

Stoecker C, et al. Cost-Effectiveness of Using 2 vs 3 Primary Doses of 13-Valent Pneumococcal Conjugate Vaccine. Pediatrics. 2013;132(2):e324–32.

Strutton DR, et al. Cost-effectiveness of 13-valent pneumococcal conjugate vaccine: Germany, Greece, and The Netherlands. J Infect. 2012;64(1):54–67.

Mangen M-JJ, Bonten MJM, de Wit GA. Rationale and design of the costs, health status and outcomes in community-acquired pneumonia (CHO-CAP) study in elderly persons hospitalized with CAP. BMC Infect Dis. 2013;13(1):597.

Lytle D, et al. Cost-effectiveness analysis of PCV20 to prevent pneumococcal disease in the Canadian pediatric population. Hum Vaccin Immunother. 2023;19(2):2257426.

Warren S, et al. Estimating the clinical and economic impact of switching from the 13-valent pneumococcal conjugate vaccine (PCV13) to higher-valent options in Greek infants. Vaccines. 2023;11(8):1369.

Wilson M, et al. Estimating the cost-effectiveness of switching to higher-valency pediatric pneumococcal conjugate vaccines in the United Kingdom. Vaccines. 2023;11(7):1168.

Wilson M, et al. Assessing public health impact of four pediatric pneumococcal conjugate vaccination strategies in the Netherlands. Infect Dis Ther. 2023;12(7):1809–21. https://doi.org/10.1007/s40121-023-00828-8 .

Løchen A, Anderson RM. Dynamic transmission models and economic evaluations of pneumococcal conjugate vaccines: a quality appraisal and limitations. Clin Microbiol Infect. 2020;26(1):60–70.

Talbird SE, et al. Outcomes and costs associated with PHiD-CV, a new protein D conjugate pneumococcal vaccine, in four countries. Vaccine. 2010;28:G23–9.

Wilson M, et al. Clinical and economic impact of a potential switch from 13-valent to 10-valent pneumococcal conjugate infant vaccination in Canada. Infect Dis Ther. 2018;7(3):353–71.

Chuck AW, et al. Pharmacoeconomic evaluation of 10- and 13-valent pneumococcal conjugate vaccines. Vaccine. 2010;28(33):5485–90.

Earnshaw SR, et al. Cost-effectiveness of 2 + 1 dosing of 13-valent and 10-valent pneumococcal conjugate vaccines in Canada. BMC Infect Dis. 2012;12(1):101.

Wals P, et al. Simulation model for comparing the costs and effectiveness of different pneumococcal conjugate vaccines. Proc Vaccinol. 2009;1:67–72.

Syeed MS, et al. Pneumococcal vaccination in children: a systematic review and meta-analysis of cost-effectiveness studies. Value Health. 2023;26(4):598–611.

Perdrizet J, et al. Historical population-level impact of infant 13-valent pneumococcal conjugate vaccine (PCV13) National immunization programs on invasive pneumococcal disease in Australia, Canada, England and Wales, Israel, and the United States. Infect Dis Ther. 2023;12(5):1351–64.

Croucher NJ, Løchen A, Bentley SD. Pneumococcal vaccines: host interactions, population dynamics, and design principles. Annu Rev Microbiol. 2018;72:521–49.

Masala GL, et al. Exploring the role of competition induced by non-vaccine serotypes for herd protection following pneumococcal vaccination. J R Soc Interface. 2017;14(136):20170620.

Robert Koch Institut; 2016. available from: RKI - Abgeschlossene Projekte - Evaluation unterschiedlicher Impfstrategien zur Prävention von Pneumokokken-Infektionen bei älteren Erwachsenen: Ergebnisse eines dynamischen Transmissionsmodells.

Levy C, et al. Impact of PCV13 on community-acquired pneumonia by C-reactive protein and procalcitonin levels in children. Vaccine. 2017;35(37):5058–64.

Rodrigo C, et al. Impact of infant 13-valent pneumococcal conjugate vaccine on serotypes in adult pneumonia. Eur Respir J. 2015;45(6):1632.

Lau WCY, et al. Impact of pneumococcal conjugate vaccines on childhood otitis media in the United Kingdom. Vaccine. 2015;33(39):5072–9.

Claes C, Reinert RR, von der Schulenburg J-MG. Cost effectiveness analysis of heptavalent pneumococcal conjugate vaccine in Germany considering herd immunity effects. Eur J Health Econ. 2009;10:25–38.

Statistisches Bundesamt (destatis.de). 40% der Mütter von Kindern unter drei Jahren sind erwerbstätig. 2023: destatis.de.

Mangen M-JJ, et al. The impact of community-acquired pneumonia on the health-related quality-of-life in elderly. BMC Infect Dis. 2017;17(1):208.

Erickson LJ, et al. Complications of meningococcal disease in college students. Clin Infect Dis. 2001;33(5):737–9.

Oostenbrink R, Henriëtte AM, Essink-Bot ML. The EQ-5D and the health utilities index for permanent sequelae after meningitis: a head-to-head comparison. J Clin Epidemiol. 2002;55(8):791–9.

Janoir C, et al. Insight into resistance phenotypes of emergent non 13-valent pneumococcal conjugate vaccine type pneumococci isolated from invasive disease after 13-valent pneumococcal conjugate vaccine implementation in France. In: Open forum infectious diseases. Oxford: Oxford University Press; 2016.

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Medical Writing/Editorial Assistance

The original model was developed by Des Dillon-Murphy, PhD, and Ruth Chapman, PhD, of Evidera. Writing support for this manuscript was provided by Colleen Dumont and Sally Neath of Cytel Inc, Waltham, MA, US and by Allison Brackley, PhD, and Elizabeth Hubscher, PhD, who were employed by Cytel Inc, Waltham, MA, US at the time of the manuscript development. This support was funded by Pfizer. We thank Mark van der Linden for providing IPD data. An Ta is an employee of Cytel, which received funding from Pfizer in connection with the development of this manuscript.

Sponsorship for this study and Rapid Service Fee were funded by Pfizer Inc.

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Felicitas Kühne, Maren Laurenz, Christof von Eiff, Johnna Perdrizet and Sophie Warren contributed to the study conceptualization, investigation, and methodology. An Ta conducted the formal analysis and was responsible for project administration. Johnna Perdrizet was responsible for funding acquisition. Johnna Perdrizet and Felicitas Kühne provided supervision and validation. All authors contributed to writing the original draft, as well as reviewing and editing subsequent drafts, and approving the final version.

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Felicitas Kühne, Maren Laurenz, Christof von Eiff, and Johnna Perdrizet are employees of Pfizer. Sophie Warren was employed by Pfizer at the time of the manuscript development (current affiliation: Adelphi Values, UK). An Ta is an employee of Cytel, which received consulting fees from Pfizer for the study and manuscript development.

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Ta, A., Kühne, F., Laurenz, M. et al. Cost-effectiveness of PCV20 to Prevent Pneumococcal Disease in the Pediatric Population: A German Societal Perspective Analysis. Infect Dis Ther (2024). https://doi.org/10.1007/s40121-024-00977-4

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The clinical case report: a review of its merits and limitations

Trygve nissen.

1 Department of Clinical Medicine, University of Tromsø, N-9038 Tromsø, Norway

2 Division of General Psychiatry, University Hospital of North Norway, N-9291 Tromsø, Norway

3 Division of Addictions and Specialized Psychiatry, University Hospital of North Norway, N-9291 Tromsø, Norway

The clinical case report has a long-standing tradition in the medical literature. While its scientific significance has become smaller as more advanced research methods have gained ground, case reports are still presented in many medical journals. Some scholars point to its limited value for medical progress, while others assert that the genre is undervalued. We aimed to present the various points of view regarding the merits and limitations of the case report genre. We searched Google Scholar, PubMed and select textbooks on epidemiology and medical research for articles and book-chapters discussing the merits and limitations of clinical case reports and case series.

The major merits of case reporting were these: Detecting novelties, generating hypotheses, pharmacovigilance, high applicability when other research designs are not possible to carry out, allowing emphasis on the narrative aspect (in-depth understanding), and educational value. The major limitations were: Lack of ability to generalize, no possibility to establish cause-effect relationship, danger of over-interpretation, publication bias, retrospective design, and distraction of reader when focusing on the unusual.

Conclusions

Despite having lost its central role in medical literature in the 20th century, the genre still appears popular. It is a valuable part of the various research methods, especially since it complements other approaches. Furthermore, it also contributes in areas of medicine that are not specifically research-related, e.g. as an educational tool. Revision of the case report genre has been attempted in order to integrate the biomedical model with the narrative approach, but without significant success. The future prospects of the case report could possibly be in new applications of the genre, i.e. exclusive case report databases available online, and open access for clinicians and researchers.

Throughout history the clinical case report and case report series have been integral components of medical literature [ 1 ]. The case report genre held a strong position until it was sidelined in the second half of the 20 th century [ 2 , 3 ]. New methodologies for research articles paved the way for evidence-based medicine. Editors had to make space for these research articles and at the same time signaled less enthusiasm for publishing case reports [ 4 ]. This spurred some heated debates in medical journals as readers were worried that the traditional case report was in jeopardy [ 5 , 6 ]. Those who welcomed the new trend with fewer case reports being published pointed mainly to their low quality and inclination to emphasize mere curiosa [ 7 - 9 ]. Some of the proponents of the genre claimed that the case report had been and still was indispensible for furthering medical knowledge and that it was unique in taking care of the detailed study of the individual patient as opposed to the new research methods with their “…nomothetic approach [taking] precedence…” [ 5 ]. Still, the case report got a low ranking on the evidence hierarchy. After a decline in popularity a new interest for the case report emerged, probably beginning in the late 1990s [ 2 ]. A peer-reviewed ‘Case reports’ section was introduced in the Lancet in 1995 [ 10 ]. In 2007, the first international, Pubmed-listed medical journal publishing only case reports was established [ 11 , 12 ]. In the following years, several similar journals, for the most part online and open-access, have been launched.

The present debate is not so much focused on whether case reporting is obsolete or not. Some of the discussions after the turn of the century have been about adapting the case report genre to new challenges. One example is the suggestion of incorporating the narrative, i.e. “… stressing the patient’s story”, in the case report [ 13 ]. The authors termed their initiative “The storied case report”. Their endeavor was not met with success. In analyzing the causes for this, they wondered if “… junior trainees find it too hard to determine what is relevant and senior trainees find it too hard to change their habits” [ 13 ]. A similar attempt was done when the editors of the Journal of Medical Case Reports in 2012 encouraged authors to include the patients’ perspectives by letting patients describe their own experiences [ 14 ].

Notwithstanding, we feel there is much to be gained from having an ongoing discussion highlighting the indications and contraindications for producing case reports. This can to some degree be facilitated by getting an understanding of the merits and limitations of the genre. The objective of this article is to present the merits and limitations of case reports and case series reports.

We adopted Taber’s Cyclopedic Medical Dictionary’s definition of the case report : “A formal summary of a unique patient and his or her illness, including the presenting signs and symptoms, diagnostic studies, treatment course and outcome” [ 15 ]. A case report consists of one or two cases, most often only one. The case series or case series report usually consists of three to ten cases [ 16 ]. (In the following we use the term case report to denote both case reports and case series report). Case reports are most often naturalistic and descriptive. Sometimes, however, they can be prospective and experimental.

As literature specifically dealing with the case report genre seemed harder to elicit from the databases than the vast amount of particular case reports, we performed iterative searches. We searched Google Scholar and PubMed using the search terms ‘case report(s)’, ‘case series’, ‘case series report(s)’, ‘case reporting’ in various combinations with ‘clinical’, ‘medical’, ‘anecdotal’, ‘methodology’, ‘review’, ‘overview’, ‘strengths’, ‘weaknesses’, ‘merits’, and ‘limitations’. Further references were identified by examining the literature found in the electronic searches. We also consulted major textbooks on epidemiology [ 17 , 18 ], some scholars of medical genres [ 19 , 20 ] and a monograph on case reporting by the epidemiologist M. Jenicek [ 16 ]. We delimited our review to the retrospective, naturalistic, and descriptive case report, also labeled the “traditional” or “classic” case report, and case series including such reports. Thus we excluded other types, such as the planned, qualitative case study approach [ 21 ] and simulated cases [ 22 - 24 ]. Finally, we extracted the relevant data and grouped the merits and limitations items in rank order with the items we judged to be the most important first.

New observations

The major advantage of case reporting is probably its ability to detect novelties [ 16 ]. It is the only way to present unusual, uncontrolled observations regarding symptoms, clinical findings, course of illness, complications of interventions, associations of diseases, side effects of drugs, etc. In short, anything that is rare or has never been observed previously might be important for the medical community and ought to be published. A case report might sensitize readers and thus facilitate detection of similar or identical cases.

Generating hypotheses

From a single, or preferably several single case reports or a case series, new hypotheses could be formulated. These could then be tested with formal research methods that are designed to refute or confirm the hypotheses, i.e. comparative (observational and experimental) studies.

There are numerous examples of new discoveries or major advancements in medicine that started with a case report or, in some cases, as humbly as a letter to the editor. The first concern from the medical community about the devastating side effect of thalidomide, i.e. the congenital abnormalities, appeared as a letter to the editor in the Lancet in 1961 [ 25 ]. Soon thereafter, several case reports and case series reports were published in various journals. Case reporting is thus indispensable in drug safety surveillance (pharmacovigilance) [ 26 ].

Sometimes significant advancements in knowledge have come not from what researchers were pursuing, but from “accidental discoveries”, i.e. by serendipity. The story of Alexander Fleming’s discovery of penicillin in 1928 is well known in the medical field [ 27 ]. Psychiatry has profited to a large degree from this mode of advancing medical science as many of the drugs used for mental disorders have been discovered serendipitously [ 27 ]. One notable example is the discovery of the effect of lithium on manic episodes in patients with manic-depressive disorder [ 28 ]. A more recent discovery is the successful treatment of infantile hemangiomas with systemic propranolol. This discovery was published, as a case series report, in the correspondence section in New England Journal of Medicine [ 29 ]. However, the evidence for the effect of this treatment is still preliminary, and several randomized trials are under way [ 30 , 31 ].

Clear and operational entities are prerequisites for doing medical research. Descriptions must come before understanding. Clinical observations that lead to new disorders being described are well suited for case reporting. The medical literature is replete with case-based articles describing new diseases and syndromes. One notable example is the first description of neurasthenia by G. Beard in Boston Medical and Surgical Journal in 1869 [ 32 ].

Researching rare disorders

For rare disorders randomized controlled trials (RCTs) can be impossible to run due to lack of patients to be enrolled. Research on drug treatment and other kinds of interventions must therefore be based on less rigorous methodologies, among them case series and case reports. This would be in accordance with the European Commission’s recommendation to its members to improve health care for those with rare disorders [ 33 ].

Solving ethical constraints

Case reporting can be valuable when ethical constraints prohibit experimental research. Take as an example the challenge of how to manage the side effects of accidental extravasation of cytotoxic drugs. As RCTs on humans seem unethical in this clinical situation the current guidelines rest on small observational studies, case reports and animal studies [ 34 ]. Or another example: Physical restraint is sometimes associated with sudden, unexpected death. The cause or causes for this are to some degree enigmatic, and it is hard to conceive of a controlled study that could be ethical [ 35 , 36 ]. Case reports and case series being “natural experiments” might be the only evidence available for guiding clinical practice.

In-depth narrative case studies

Case reporting can be a way of presenting research with an idiographic emphasis. As contrasted to nomothetic research, an idiographic approach aims at in-depth understanding of human phenomena, especially in the field of psychology and psychiatry. The objective is not generalizable knowledge, but an understanding of meaning and intentionality for an individual or individuals. Sigmund Freud’s case studies are relevant examples. This usage of case reports borders on qualitative research. Qualitative studies, although developed in the social sciences, have become a welcome contribution within health sciences in the last two decades.

Educational value

Clinical medical learning is to a large degree case-based. Typical case histories and vignettes are often presented in textbooks, in lectures, etc. Unusual observations presented as published case reports are important as part of doctors’ continuing medical education, especially as they demonstrate the diversity of manifestations both within and between medical diseases and syndromes [ 37 , 38 ]. Among the various medical texts, the case report is the only one that presents day-to-day clinical practice, clinicians’ diagnostic reasoning, disease management, and follow-up. We believe that some case reports that are written with the aim of contributing to medical knowledge turn out to be of most value educationally because the phenomena have already been described elsewhere. Other case reports are clearly primarily written for educational value [ 37 ]. Some journals have regular sections dedicated to educational case reports, e.g. The Case Records of the Massachusetts General Hospital in the New England Journal of Medicine and the Clinical Case Conference found in the American Journal of Psychiatry.

The cost of doing a case report is low compared to planned, formal studies. Most often the necessary work is probably done in the clinical setting without specific funding. Larger studies, for instance RCTs, will usually need an academic setting.

Fast publication

The time span from observation to publication can be much shorter than for other kinds of studies. This is obviously a great advantage as a case report can be an important alert to the medical community about a serious event. The unexpected side effects of the sedative-antinauseant thalidomide on newborn babies is a telling story. The drug had been prescribed during pregnancy to the babies’ mothers. After the first published observation of severe abnormalities in babies appeared as a letter to the editor of the Lancet in December 16 th , 1961 [ 25 ], several case reports and series followed [ 39 , 40 ]. It should be mentioned though that the drug company had announced on December 2 nd , 1961, i.e. two weeks before the letter from McBride [ 25 ], that it would withdraw the drug form the market immediately [ 41 ].

Flexible structure

Riaz Agha, editor of the International Journal of Surgery Case Reports suggests that the case report, with its less rigid structure is useful as it “… allows the surgeon(s) to discuss their diagnostic approach, the context, background, decision-making, reasoning and outcomes” [ 42 ]. Although the editor is commenting on the surgical case report, the argument can be applied for the whole field of clinical medicine. It should be mentioned though, that other commentators have argued for a more standardized, in effect more rigid, structure [ 43 ].

Clinical practice can be changed

Case reporting can lead to or contribute to a change in clinical practice. A drug might be withdrawn from the market. Or a relabeling might change the attitude to and treatment of a condition. During Word War I the shell shock syndrome was labeled and described thoroughly in several articles in the Lancet , the first of them appearing in February 1915 [ 44 ]. The author was the British captain and military doctor Charles S. Myers. Before his efforts to bring good care and treatment to afflicted soldiers there had been a common misconception that many of these dysfunctional soldiers were malingerers or cowards.

Exercise for novice researchers

The case report format is well suited for young doctors not yet trained as researchers. It can be an opportunity for a first exercise in authoring an article and a preparation for a scientific career [ 37 , 45 , 46 ].

Communication between the clinical and academic fields

Articles authored by clinicians can promote communication between practicing clinicians and academic researchers. Observations published can generate ideas and be a trigger for further studies. For instance, a case series consisting of several similar cases in a short period can make up the case-group for a case–control study [ 47 ]. Clinicians could do the observation and publish the case series while the case–control study could be left to the academics.

Entertainment

Some commentators find reading case reports fun. Although a rather weak argument in favor of case reporting, the value of being entertained should not be dismissed altogether. It might inspire physicians to spend more time browsing and reading scientific literature [ 48 ].

Studying the history of medicine

Finally, we present a note on a different and unintended aspect of the genre. The accumulated case reports from past eras are a rich resource for researching and understanding medical history [ 49 , 50 ]. A close study of old case reports can provide valuable information about how medicine has been practiced through the centuries [ 50 , 51 ].

Limitations

No epidemiological quantities.

As case reports are not chosen from representative population samples they cannot generate information on rates, ratios, incidences or prevalences. The case or cases being the numerator in the equation, has no denominator. However, if a case series report consists of a cluster of cases, it can signal an important and possibly causal association, e.g. an epidemic or a side effect of a newly marketed drug.

Causal inference not possible

Causality cannot be inferred from an uncontrolled observation. An association does not imply a cause-effect relationship. The observation or event in question could be a mere coincidence. This is a limitation shared by all the descriptive studies [ 47 ]. Take the thalidomide tragedy already mentioned as an example; Unusual events such as congenital malformations in some of the children born to mothers having taken a specific drug during pregnancy does not prove that the drug is the culprit. It is a mere hypothesis until further studies have either rejected or confirmed it. Cause-effect relationships require planned studies including control groups that to the extent possible control for chance, bias and confounders [ 52 ].

Generalization not possible

From the argument above, it follows that findings from case reports cannot be generalized. In order to generalize we need both a cause-effect relationship and a representative population for which the findings are valid. A single case report has neither. A case series, on the other hand, e.g. many “thalidomide babies” in a short time period, could strengthen the suspicion of a causal relationship, demanding further surveillance and research.

Publication bias could be a limiting factor. Journals in general favor positive-outcome findings [ 53 ]. One group of investigators studying case reports published in the Lancet found that only 5% of case reports and 10% of case series reported treatment failures [ 54 ]. A study of 435 case reports from the field of dentistry found that in 99.1%, the reports “…clearly [had] a positive outcome and the intervention was considered and described as successful by the authors” [ 55 ].

Overinterpretation

Overinterpretation or misinterpretation is the tendency or temptation to generalize when there is no justification for it. It has also been labeled “the anecdotal fallacy” [ 56 ]. This is not a shortcoming intrinsic to the method itself. Overinterpretation may be due to the phenomenon of case reports often having an emotional appeal on readers. The story implicitly makes a claim to truth. The reader might conclude prematurely that there is a causal connection. The phenomenon might be more clearly illustrated by the impact of the clinician’s load of personal cases on his or her practice. Here exemplified by a young doctor’s confession: “I often tell residents and medical students, ‘The only thing that actually changes practice is adverse anecdote.’” [ 57 ].

Emphasis on the rare

As case reporting often deals with the rare and atypical, it might divert the readers’ attention from common diseases and problems [ 58 ].

Confidentiality

Journals today require written informed consent from patients before publishing case reports. Both authors and publishers are responsible for securing confidentiality. A guarantee for full confidentiality is not always possible. Despite all possible measures taken to preserve confidentiality, sometimes the patient will be recognized by someone. This information should be given to the patient. An adequately informed patient might not consent to publication. In 1995 in an Editorial in the British Journal of Psychiatry one commentator, Isaac Marks, feared that written consent would discourage case reports being written [ 59 ]. Fortunately, judged form the large number of reports being published today, it seems unlikely that the demand for consent has impeded their publication.

Other methodological limitations

Case reports and series are written after the relevant event, i.e. the observation. Thus, the reports are produced retrospectively. The medical record might not contain all relevant data. Recall bias might prevent us from getting the necessary information from the patient or other informants such as family members and health professionals.

It has also been held against case reporting that it is subjective. The observer’s subjectivity might bias the quality and interpretation of the observation (i.e. information bias).

Finally, the falsification criterion within science, which is tested by repeating an experiment, cannot be applied for case reports. We cannot design another identical and uncontrolled observation. However, unplanned similar “experiments” of nature can be repeated. Several such observations can constitute a case series that represents stronger indicative evidence than the single case report.

The major advantages of case reporting are the ability to make new observations, generate hypotheses, accumulate scientific data about rare disorders, do in-depth narrative studies, and serve as a major educational tool. The method is deficient mainly in being unable to deliver quantitative data. Nor can it prove cause-effect relationship or allow generalizations. Furthermore, there is a risk of overinterpretation and publication bias.

The traditional case report does not fit easily into the qualitative-quantitative dichotomy of research methods. It certainly shares some characteristics with qualitative research [ 16 ], especially with regard to the idiographic, narrative perspective – the patient’s “interior world” [ 60 ] – that sometimes is attended to. Apart from “The storied case report” mentioned in the Background-section, other innovative modifications of the traditional case report have been tried: the “evidence-based case report” [ 61 ], the “interactive case report” [ 62 ] and the “integrated narrative and evidence based case report” [ 63 ]. These modifications of the format have not made a lasting impact on the way case reports in general are written today.

The method of case reporting is briefly dealt with in some textbooks on epidemiology [ 17 , 18 ]. Journals that welcome case reports often put more emphasis on style and design than on content in their ‘instruction to authors’ section [ 64 ]. As a consequence, Sorinola and coworkers argue for more consensus and more consistent guidance on writing case reports [ 64 ]. We feel that a satisfactory amount of guidance concerning both style and content now exists [ 12 , 16 , 65 , 66 ]. The latest contribution, “The CARE guidelines”, is an ambitious endeavor to improve completeness and transparency of reports [ 66 ]. These guidelines have included the “Patient perspective” as an item, apparently a bit half-heartedly as this item is placed after the Discussion section, thus not allowing this perspective to influence the Discussion and/or Conclusion section. We assume this is symptomatic of medicine’s problem with integrating the biomedical model with “narrative-based medicine”.

In recent years the medical community has taken an increased interest in case reports [ 2 ], especially after the surge of online, exclusive case report journals started in 2007 with the Journal of Medical Case Reports (which was the first international, Pubmed-listed medical journal publishing only case reports) as the first of this new brand. The climate of skepticism has been replaced by enthusiasm and demand for more case reports. A registry for case reports, Cases Database, was founded in 2012 [ 67 ]. On the condition that it succeeds in becoming a large, international database it could serve as a register being useful for clinicians at work as well as for medical research on various clinical issues. Assuming Pamela P. Powell’s assertion that “[a]lmost all practicing physicians eventually will encounter a case worthy of being reported” [ 60 ] is valid, there should be no shortage of potential cases waiting to be reported and filed in various databases, preferably online and open access.

Limitations of this review

There are several limitations to this study. It is a weakness that we have not been able to review all the relevant literature. The number of publications in some way related to case reports and case report series is enormous, and although we have attempted to identify those publications relevant for our purpose (i.e. those that describe the merits and limitations of the case report genre), we might have missed some. It was difficult to find good search terms for our objective. Still, after repeated electronic searches supplemented with manual searches in reference lists, we had a corpus of literature where essentially no new merits or limitations emerged.

As we point out above, the ranking of merits and limitations represents our subjective opinion and we acknowledge that others might rank the importance of the items differently.

The perspective on merits and limitations of case reporting has been strictly medical. As a consequence we have not analyzed or discussed the various non-medical factors affecting the publication of case reports in different medical journals [ 2 ]. For instance, case reports are cited less often than other kinds of medical research articles [ 68 ]. Thus they can lower a journal’s impact factor, potentially making the journal less attractive. This might lead some high-impact journals to publish few or no case reports, while other journals have chosen to specialize in this genre.

Before deciding on producing a case report or case series based on a particular patient or patients at hand, the observant clinician has to determine if the case report method is the appropriate article type. This review could hopefully assist in that judgment and perhaps be a stimulus to the continuing debate in the medical community on the value of case reporting.

Competing interests

The authors declare that there are no competing interests.

Authors’ contributions

TN contributed to the conception, drafting, and revision of the article. RW contributed to the conception, drafting, and revision of the article. Both authors approved the final manuscript.

Acknowledgements

There was no specific funding for this study.

Cabán-Martinez AJ, Beltrán WF. Advancing medicine one note at a time: the educational value in clinical case reports. BMC Res Notes. 2012; 5 :293. doi: 10.1186/1756-0500-5-293. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Nissen T, Wynn R. The recent history of the clinical case report: a narrative review. JRSM Sh Rep. 2012; 3 :87. doi: 10.1258/shorts.2012.012046. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Nissen T, Wynn R. The history of the case report: a selective review. JRSM Open. 2014; 5 :4. [ PMC free article ] [ PubMed ] [ Google Scholar ]
Wilkinson G. Fare the well – the Editor’s last words. Br J Psychiatry. 2003; 182 :465–466. doi: 10.1192/bjp.182.6.465. [ CrossRef ] [ Google Scholar ]
Williams DDR. In defence of case of the case report (Letter) Br J Psychiatry. 2004; 184 :84. doi: 10.1192/bjp.184.1.84. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Enoch MD. Case reports (Letter) Br J Psychiatry. 2005; 185 :169. [ PubMed ] [ Google Scholar ]
Nahum AM. The clinical case report: “Pot boiler” or scientific literature? Head Neck Surg. 1979; 1 :291–292. doi: 10.1002/hed.2890010402. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Doherty M. What value case reports? (Editorial) Ann Rheum Dis. 1994; 53 :1–2. doi: 10.1136/ard.53.1.1. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Procopio M. Publication of case reports. Br J Psychiatry. 2005; 187 :91. [ PubMed ] [ Google Scholar ]
Bignall J, Horton R. Learning from stories – Lancet’s case reports. Lancet. 1995; 346 :1256. [ PubMed ] [ Google Scholar ]
Kidd M, Hubbard C. Introducing Journal of Medical Case Reports. J Med Case Rep. 2007; 1 :1. doi: 10.1186/1752-1947-1-1. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Rison RA. A guide to writing case reports for the Journal of Medical Case Reports and BioMed Central Research Notes. J Med Case Reports. 2013; 7 :239. doi: 10.1186/1752-1947-7-239. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Bayoumi AM, Kopplin PA. The storied case report. CMAJ. 2004; 171 :569–570. doi: 10.1503/cmaj.1031503. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Kidd MR, Saltman D. Case reports at the vanguard of the 21 st century medicine (Editorial) J Med Case Rep. 2012; 6 :156. doi: 10.1186/1752-1947-6-156. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Venes D. Taber’s Cyclopedic Medical Dictionary. 21. Philadelphia: F.A. Davis Company; 2009. [ Google Scholar ]
Jenicek M. Clinical case reporting in evidence-based medicine. Oxford: Butterworth Heinemann; 1999. [ Google Scholar ]
Fletcher RH, Fletcher SW. Clinical epidemiology: The essentials. 4. Philadelphia: Lippincott Williams & Wilkins; 2005. [ Google Scholar ]
Sackett DL, Brian Haynes R, Tugwell P. Clinical epidemiology. Boston: Little, Brown and Company; 1985. [ Google Scholar ]
Berkencotter C. Patient tales. Case histories and the uses of narrative in psychiatry. Columbia: University of South Carolina Press; 2008. [ Google Scholar ]
Hunter KM. Doctors’ stories. The narrative structure of medical knowledge. Princeton: Princeton University Press; 1991. [ Google Scholar ]
Crowe S, Cresswell K, Robertson A, Huby G, Avery A, Sheikh A. The case study approach. BMC Med Res Methodol. 2011; 11 :100. doi: 10.1186/1471-2288-11-100. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Wynn R, Kvalvik AM, Hynnekleiv T. Attitudes to coercion at two Norwegian psychiatric units. Nord J Psychiatry. 2011; 65 :133–137. doi: 10.3109/08039488.2010.513068. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Wynn R, Myklebust LH, Bratlid T. Psychologists and coercion: decisions regarding involuntary psychiatric admission and treatment in a group of Norwegian psychologists. Nord J Psychiatry. 2007; 61 :433–437. doi: 10.1080/08039480701773139. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Aaker E, Knudsen A, Wynn R, Lund A. General practitioners’ reactions to non-compliant patients. Scand J Prim Health Care. 2001; 19 :103–106. doi: 10.1080/028134301750235330. [ PubMed ] [ CrossRef ] [ Google Scholar ]
McBride WG. Thalidomide and congenital abnormalities. (Letter) Lancet. 1961; 278 :1358. [ Google Scholar ]
Chakra CAN, Pariente A, Pinet M, Nkeng L, Moore N, Moride Y. Case series in drug safety. A review to determine characteristics and quality. Drug Saf. 2010; 33 :1081–1088. doi: 10.2165/11539300-000000000-00000. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Ban TA. The role of serendipity in drug discovery. Dialogues Clin Neurosci. 2006; 8 :335–344. [ PMC free article ] [ PubMed ] [ Google Scholar ]
Cade JFJ. Lithium salts in the treatment of psychotic excitement. Med J Aust. 1949; 2 :349–352. [ PubMed ] [ Google Scholar ]
Léauté-Labrèze C, de la Roque Dumas E, Hubiche T, Boralevi F. Propranolol for severe hemangiomas of infancy. (Letter to the editor) N Engl J Med. 2008; 358 :2649–2651. doi: 10.1056/NEJMc0708819. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Fretheim A. Godt nok dokumentert? (Sufficiently documented?) (Editorial) Tidsskr Nor Legeforen. 2010; 130 :1806. [ PubMed ] [ Google Scholar ]
U.S. National Institutes of Health. Studies found for the search 'propanolol and hemangiomas' in the ClinicalTrials.gov database. Accessed on 22 April, 2014 at: http://www.clinicaltrials.gov/ct2/results?term=propanolol+and+hemangiomas&Search=Search .
Beard G. Neurasthenia, or nervous exhaustion. Boston Med Surg J. 1869; 80 :217–221. doi: 10.1056/NEJM186904290801301. [ CrossRef ] [ Google Scholar ]
Taylor DM. Developing a strategy for the management of rare disorders. BMJ. 2012; 344 :e2417. doi: 10.1136/bmj.e2417. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Bjånes TK. Lokale bivirkninger ved parenteral administrering av legemidler. (Localized side effects caused by parenteral administration of drugs) Tidsskr Nor Legeforen. 2011; 131 :472–474. [ PubMed ] [ Google Scholar ]
Nissen T, Rørvik P, Haugslett L, Wynn R. Physical restraint and near death of a psychiatric patient. J Forensic Sci. 2013; 58 :259–262. doi: 10.1111/j.1556-4029.2012.02290.x. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Wynn R. Coercion in psychiatric care: clinical, legal, and ethical controversies. Int J Psychiatry Clin Pract. 2006; 10 :247–251. doi: 10.1080/13651500600650026. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Lundh A, Christensen M, Jørgensen AW. International or national publication of case reports. Dan Med Bul. 2011; 58 :A4242. [ PubMed ] [ Google Scholar ]
Grønli O, Wynn R. Normocalcemic hyperparathyroidism and treatment resistant depression. Psychosomatics. 2013; 54 :493–497. doi: 10.1016/j.psym.2012.10.008. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Ward SP. Thalidomide and congenital abnormalities. BMJ. 1962; 2 (5305):646–647. doi: 10.1136/bmj.2.5305.646. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Coodin FJ, Uchida CM, Murphy CH. Phocomelia: report of three cases. CMAJ. 1962; 87 :735–739. [ PMC free article ] [ PubMed ] [ Google Scholar ]
Heyman DJ. Managing director of the Destillers Company Ltd. (Letter) Lancet. 1961; 278 :1262. [ Google Scholar ]
Agha R, Rosin RD. Time for a new approach to case reports. (Editorial) Int J Surg Case Rep. 2010; 1 :1–3. doi: 10.1016/j.ijscr.2010.04.001. doi:10.1016/j.ijscr.2010.04.001. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Aronson JA. Anecdotes as evidence. (Editorial) BMJ. 2003; 326 :1346. doi: 10.1136/bmj.326.7403.1346. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Myers CS. A contribution to the study of the shell shock. Being an account of three cases of loss of memory, vision, smell and taste, admitted into the Duchess of Westminster’s War Hospital, Le Touquet. Lancet. 1915; 185 :316–320. doi: 10.1016/S0140-6736(00)52916-X. [ CrossRef ] [ Google Scholar ]
Morris BA. The importance of case reports. (Letter to the Editor) CMAJ. 1989; 141 :875–876. [ PMC free article ] [ PubMed ] [ Google Scholar ]
Rison RA. Neurology case reports: a call for all. J Med Case Rep. 2011; 5 :113. doi: 10.1186/1752-1947-5-113. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Grimes DA, Schulz KF. Descriptive studies: what they can and cannot do. Lancet. 2002; 359 :145–149. doi: 10.1016/S0140-6736(02)07373-7. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Kang S. Anecdotes in medicine - 15 years of Lancet case reports. Lancet. 2010; 376 :1448–1449. doi: 10.1016/S0140-6736(10)60624-1. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Rose JC, Corn M. Dr. E. and other patients: new lessons from old case reports. J Hist Med Allied Sci. 1984; 39 :3–32. doi: 10.1093/jhmas/39.1.3. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Álvarez Millán C. Practice versus theory: tenth-century case histories from Islamic Middle East. Soc Hist Med. 2000; 13 :293–306. doi: 10.1093/shm/13.2.293. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Álvarez Millán C. The case history in Medieval Islamic medical literature: Tajarib and Mujarrabat as source. Med Hist. 2010; 54 :195–214. doi: 10.1017/S0025727300006712. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Hulley SB, Cummings SR, Browner WS, Grady DG, Newman TB. Designing clinical research. 3. Philadelphia: Lippincott Williams & Wilkins; 2007. [ Google Scholar ]
Easterbrook PJ, Gopalan R, Berlin JA, Matthews DR. Publication bias in clinical research. Lancet. 1991; 337 :867–872. doi: 10.1016/0140-6736(91)90201-Y. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Albrecht J, Meves A, Bigby M. Case reports and case series from the Lancet had significant impact on medical literature. J Clin Epidemiol. 2005; 58 :1227–1232. doi: 10.1016/j.jclinepi.2005.04.003. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Oliveira GJ, Leles CR. Critical appraisal and positive outcome bias in case reports published in Brazilian dental journals. J Dent Educ. 2006; 70 :869–874. [ PubMed ] [ Google Scholar ]
Charlton BG, Walston F. Individual case studies in clinical research. J Eval Clin Practice. 1998; 4 :147–155. doi: 10.1111/j.1365-2753.1998.tb00081.x. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Stuebe AM. Level IV evidence – adverse anecdote and clinical practice. N Engl J Med. 2011; 365 :8–9. doi: 10.1056/NEJMp1102632. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Hoffman JR. Rethinking case reports. West J Med. 1999; 170 :253–254. [ PMC free article ] [ PubMed ] [ Google Scholar ]
Wilkinson G, Fahy T, Russell G, Healy D, Marks I, Tantam D, Dimond B. Case reports and confidentiality. (Editorial) Br J Psychiatry. 1995; 166 :555–558. doi: 10.1192/bjp.166.5.555. [ PubMed ] [ CrossRef ] [ Google Scholar ]
Powell PP. The single-case report in medical literature: the ‘Elephant man’ serves as an exellent example. J Am Med Writers Assoc. 1990; 5 :9–12. [ Google Scholar ]
Glasziou P. Evidence based case report: twenty year cough in a non-smoker. BMJ. 1998; 316 :1660–1661. doi: 10.1136/bmj.316.7145.1660. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Harker N, Montgomery A, Fahey T. Interactive case report. Treating nausea and vomiting during pregnancy: case outcome. BMJ. 2004; 328 :276. doi: 10.1136/bmj.328.7434.276. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Reis S, Hermoni D, Livingstone P, Borkan J. Integrated narrative and evidence based case report: case report of paroxysmal atrial fibrillation and anticoagulation. BMJ. 2002; 325 :1018–1020. doi: 10.1136/bmj.325.7371.1018. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Sorinola O, Olufowobi O, Coomarasamy A, Khan KS. Instructions to authors for case reporting are limited: a review of a core journal list. BMC Med Educ. 2004; 4 :4. doi: 10.1186/1472-6920-4-4. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
Rossor MN. In: How to write a paper. 4. Hall GM, editor. London: Blackwell Publishing; 2008. How to write a case report; pp. 71–75. [ Google Scholar ]
Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D. CARE group. The CARE guidelines: consensus-based clinical case reporting guideline development. J Med Case Rep. 2013; 7 :223. doi: 10.1186/1752-1947-7-223. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]
BioMed Central. Cases Database. Accessed on 22 April, 2014 at: http://www.casesdatabase.com .
Mason RA. The case report – an endangered species? (Editorial) Anesthesia. 2001; 56 :99–102. doi: 10.1046/j.1365-2044.2001.01919.x. [ PubMed ] [ CrossRef ] [ Google Scholar ]

Open access
Published: 09 May 2024

Genetic markers of cardiac autonomic neuropathy in the Kazakh population

Nazira Bekenova 1 na1 ,
Ainur Sibagatova 1 na1 ,
Alisher Aitkaliyev 1 na1 ,
Tamara Vochshenkova 1 na1 ,
Balzhan Kassiyeva 1 na1 &
Valeriy Benberin 1 na1

BMC Cardiovascular Disorders volume 24 , Article number: 242 ( 2024 ) Cite this article

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Metrics details

Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes.

Materials and methods

A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE “Medical Center Hospital of the President’s Affairs Administration of the Republic of Kazakhstan”. 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0. Results: Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09–3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63–1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04–9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19–5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09–0.68), p = 0.007, and OR 0.43, CI (0.22–0.84), p = 0.02, respectively). Conclusion: The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.

Peer Review reports

It’s generally accepted that Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that disrupts cardiac innervation and increases the risk of morbidity and mortality [ 1 , 2 , 3 ]. Some sources describe CAN as an autonomic control disorder of the cardiovascular system specifically associated with DM, after excluding other factors [ 4 , 5 ]. However, emerging evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome being potential precursors [ 5 ]. Prediabetes, as classified by the World Health Organization, encompasses impaired fasting glucose levels and impaired glucose tolerance [ 6 , 7 ]. Moreover, some researchers propose that early-onset CAN is more characteristic of insulin-dependent diabetes [ 8 ].

Due to limited research on the disease, prevalence data varies, and analysis is primarily based on systematic reviews and meta-analyses. Some studies indicate that CAN may occur in approximately 90% of individuals with DM [ 3 , 9 ]. Other sources report prevalence rates ranging from 2 to 91% in type 1 diabetes mellitus (DM1) and 25–75% in type 2 diabetes (DM2) [ 10 , 11 ].

Mortality rates associated with CAN are also significant, as there is a risk of death even at the asymptomatic stage [ 12 ]. Studies have demonstrated that the five-year mortality from CAN ranges from 15 to 60% [ 3 , 13 ].

Regarding gender differences, the incidence of CAN was higher in women compared to men (2.2% and 1.4% in severe cases, 4.7% and 2.6% in moderate cases, respectively) [ 14 ]. However, it is crucial to understand the incidence of CAN by gender, especially in the early stages. Since early-stage CAN is often underdiagnosed, available information mainly focuses on differences in heart rate variability (HRV) between men and women, showing that a decrease in HRV is more frequently observed in women [ 15 ]. Decreased HRV is considered an early sign of cardiac dysautonomia [ 1 , 10 ].

As neuropathy originates in the longest nerve fibres, early manifestations of CAN result from impaired innervation of the parasympathetic nervous system, leading to changes in HRV [ 12 , 16 ]. While many studies emphasize the primary inhibition of the parasympathetic nervous system [ 6 , 17 ], the disruption of parasympathetic innervation subsequently leads to sympathetic nervous system dominance. It is worth noting that sympathetic dominance is also influenced by dysglycemia [ 5 ] and contributes to insulin resistance and hyperinsulinemia in prediabetes [ 18 ]. These changes in the sympathetic and parasympathetic nerve fibres innervating the heart and blood vessels result in reduced HRV [ 19 ]. Higher resting heart rate and reduced HRV correlate with the risk of developing components of metabolic syndrome and subsequent cardiovascular mortality [ 20 ].

Additionally, the denervation of sympathetic nerve fibres starts from the apex of the ventricles and progresses toward the base. Importantly, the reversibility of CAN disorders decreases as the disease advances [ 6 , 12 ]. Consequently, early markers for the disease are crucial to identify.

It is known that in the pathogenesis of cardiac autonomic neuropathy, not only hyperglycemia and insulin deficiency play a role but also disruptions in lipid metabolism [ 21 ], which subsequently influence the reduction of neural blood flow, leading to a decrease in conductivity in the heart. Atrophy of axons and demyelination of nerve fibres, developed due to reduced neural blood flow, also contribute to decreased conductivity in the heart. In this context, it would be interesting to consider certain polymorphisms that have important functional significance in lipid metabolism, myelination of nerve fibres, and insulin resistance.

Among all genes associated with fat mass and obesity, the FTO gene (FTO alpha-ketoglutarate-dependent dioxygenase) stands out with the strongest correlation. According to GWAS studies, it is practically linked to disruptions in lipid metabolism in almost all populations. According to some data, it is considered a predisposition gene for obesity [ 22 , 23 ].

Following GWAS studies, most obesity loci have been examined in individuals of European descent [ 22 ]. Recent studies conducted in an Asian population among 62,245 East Asian participants found a significant association with the rs12149832 polymorphism of the FTO gene ( p = 4.8 × 10–22) [ 24 ].

Participation in the processes of insulin resistance is due to epigenetic modifications of the FTO gene, in particular DNA methylation, which have an inhibitory effect on the PPARG gene [ 25 ].

PPARG improves insulin sensitivity by increasing fatty acid stores in fat cells (decreasing lipotoxicity), enhancing the release of adiponectin from fat cells and gain of production nicotinic acid adenine dinucleotide phosphate due to enzyme CD 38 activation [ 26 ].

It is known that mutations in this gene, that is, single-nucleotide substitutions, impair insulin sensitivity. Polymorphism rs1801282 of the PPARG gene leads to the replacement of proline with alanine in codon 12 of exon B (C > G; Pro 12 Ala) and causes conformational changes in the protein, and the presence of a minor allele is associated with a decrease in PPARG activity. The C allele of this polymorphism is associated with increased PPARG transcriptional activity and, consequently, insulin hypersensitivity. Although, it’s important to note that there are conflicting opinions about the connection between the rs1801282 polymorphism and diabetes. Studies of its relationship with gestational diabetes showed that rs1801282 reduced the risk of the disease in 50% of cases in the French population, while the studies conducted in Turkey report that rs1801282 did not affect the prevalence of gestational diabetes. However, in both populations, it was associated with excess weight [ 27 , 28 , 29 , 30 ].

It is known that there are common mechanisms in the pathogenesis of neurodegenerative diseases and complications of diabetes mellitus since these diseases are characterized by autonomic disorders [ 31 , 32 ]. Polymorphisms rs2736990 and rs2737029 in the SNCA gene are important in the pathogenesis of Parkinson’s disease [ 33 , 34 ]. However, it has not been studied in other diseases, particularly in CAN.

The understudied polymorphisms rs1108775 and rs1799782 were of great interest due to their investigation in the Kazakh population and their association with ischemic heart disease [ 35 ] and reduced risk of thyroid cancer [ 36 ], respectively. This study aims to investigate the Single Nucleotide Polymorphisms (polymorphisms) of specific genes to identify genetic markers associated with CAN development in the Kazakh population.

Patients’ selection

The case-control study included 82 patients with CAN (cases) and 100 patients with no CAN (controls). The statistical software Epi Info was used to calculate the sample size. The estimated frequency in the control group was 30%, with an odds ratio of 2.0, confidence level of 95%, and statistical power of 80%. The selection into the group of cases was carried out continuously among the patients from the therapeutic department of the Medical Centre Hospital of the President’s Affairs Administration of the Republic of Kazakhstan consecutively for the period from September 2017 to August 2019 (with the hospital’s turnover at the beginning of the study (2017) being 25,454 people). The control group was also formed from persons who underwent preventive examinations in the same hospital, and in whom the diagnosis of CAN was excluded.

Criteria for inclusion in the group of cases were an established diagnosis of CAN, age of 18 years and older, and Kazakh nationality. Exclusion criteria were a history of genetic disease, hypothyroidism or hyperthyroidism, rhythmic disturbances in the electrical activity of the heart, LVAD placement within the last 3 months, regular alcohol consumption (more than 80 mg/day), anemia (Hb < 110), cancer, kidney disease, severe CVD, liver, end-stage blood, autoimmune diseases that can affect autonomic nerve fibres such as systemic lupus erythematosus, concomitant degenerative disease (e.g., Parkinson’s disease or multiple system atrophy), drugs that can affect the frequency heart contractions such as beta-blockers, verapamil, diltiazem, amiodarone or nitrates, pregnant and lactating women.

The inclusion criteria for the control group were excluding the diagnosis of CAN, age 18 years and older, and the Kazakh population. Exclusion criteria were like those in the case group.

Out of the entire patient population, 82 individuals exhibited indications of CAN based on the daily Electrocardiogram (ECG) monitoring conducted through Holter monitoring. The Medilog DARWIN ECG Holter monitoring system from Switzerland was utilized to perform 24-hour Holter monitoring. Data collection focused on the following parameters:

Average Standard Deviation of NN Intervals (SDNN av) (ref. interval 53–279 m/sec).

Median of Standard Deviation of NN Intervals (SDNN med) (ref. interval > 53.8 m/sec).

Average Standard Deviation of Average NN Intervals (SDANN av) (ref. interval 45–261 m/sec).

Average Root Mean Square of Successive Differences (RMSSD av) (ref. interval 7–103 m/sec).

Median of Root Mean Square of Successive Differences (RMSSD med) (ref. interval 28.8–71.9) m/sec)

Average Percentage of NN Intervals differing by more than 50 ms (pNN50 av) (ref. interval 0-137%).

Median Percentage of NN Intervals differing by more than 50 ms (pNN50 med) (ref. interval 6.0-44.1%).

High-Frequency Power (HF) (> 56.4).

Low-Frequency Power (LF) (< 43.6).

The ratio of High-Frequency Power to Low-Frequency Power (HF/LF) (< 0.8).

The above values were used as normal values and were used to select patients for the control group, and deviations from these values were used for the diagnosis of CAN and selection for the case group. CAN was characterized as deviations in three or more Heart Rate Variability (HRV) measurements (such as SDNN, RMSSD, HF, LF, and HF/LF) [ 37 , 38 ].

HT was determined by observing an elevation in systolic blood pressure (SBP) equal to or greater than 140 mm Hg, and/or diastolic blood pressure (DBP) equal to or greater than 90 mm Hg, either through daily monitoring of blood pressure or by assessing the consistent use of antihypertensive medication. The BTL-08 ABPM ambulatory blood pressure recorder, manufactured in Great Britain, was used for the daily monitoring of blood pressure.

The diagnosis of DM2 was determined based on the clinical protocol established by the Ministry of Health of the Republic of Kazakhstan [ 39 ]. Specifically, laboratory parameters including fasting glucose concentration (≥ 6.1 mmol/l) and glycosylated hemoglobin (≥ 6.5% or 48 mmol/mol) were utilized for diagnosis.

BMI was calculated by dividing weight in kilograms by the square of height in meters.

The following anamnestic data were analyzed: Age, Sex, and a habit of smoking. Clinical data were also evaluated (glucose concentration, triglyceride level). Glucose level was determined under fasted conditions from venous blood. Blood samples were collected from the cubital vein in the treatment room after a 12-hour fast. The plasma was separated by spinning at 1000×g (4 C) for 10 min. To conduct further biochemical analysis, the plasma was stored at -30 C. The serum obtained after centrifugation was used for analysis on the same day as the blood collection. The levels of glucose, total cholesterol, TG, HDL, and LDL were measured using the enzymatic method on an Architect’s 8000 automatic biochemical analyzer manufactured by Abbott Laboratories in the USA.

Isolation of DNA

DNA extraction from blood samples was carried out using kits from the DSMZ-German Collection of Microorganisms and Cell Cultures (Germany, catalogue number ACC11) following the manufacturer’s instructions. DNA extraction was performed automatically using the AutoMate Express™ Instrument. The iPrep™ Purelink™ gDNA Blood Kit was used for this purpose. Initially, tubes were prepared and labelled according to the DNA samples. Subsequently, the Qubit® working solution was created by diluting the Qubit® dsDNA BR Reagent in the Qubit® dsDNA BR Buffer at a ratio of 1:200 for each patient. Then, 2 µl of the buffer and reagent mix were combined with 2 µl of DNA. The concentration of DNA was assessed using the Qubit™ 4 Fluorometer with the Qubit® dsDNA BR Assay Kits.

Considering that gene polymorphisms in CAN are poorly studied, the selection of candidate genes and their polymorphisms was carried out from the genetic markers involved in the pathogenesis of age-associated diseases: neurodegenerative diseases, atherosclerosis, DM, obesity, arterial hypertension, breast cancer and prostate in the database of GWAS studies.

All study participants were genotyped for 120 polymorphisms that were identified through a genome-wide search. After a preliminary analysis of 120 polymorphisms with cardiac autonomic neuropathy, an association of 7 polymorphisms was shown: rs12149832 of the FTO gene, rs2737029, rs2736990 of the SNCA gene, rs1801282 of the PPARG gene, rs1799782 of the XRCC 1 gene, rs13016963 of the gene FLACC 1, rs1108775 LINCO 1924, which were further analyzed using logistic regression with adjustment for age and sex. Genotyping was carried out using the innovative OpenArray technology, which enables reactions in very small volumes. Specifically designed OpenArray slides, each containing 3,072 data points, were utilized in this process. To perform genotyping, the previously extracted DNA samples were combined with the reaction mixture in a 384-well sample plate. For each sample, 3.0 µl of OppenArray Real-time master mix and 2.0 µl of DNA sample with a concentration of 50 ng/µl were required. The total volume of the reaction mixture per well was 5 µl, and each sample was duplicated. The plate was thoroughly mixed using a shaker and then centrifuged. Probes were designed using the QuantStudio OpenArray AccuFill Plate Configurator and dried assays were provided in the designated throughholes of the genotyping plates. These plates were specifically designed with two allele-specific probes, a minor groove binder, and two PCR primers to ensure accurate and precise genotyping calls. The OpenArray technology utilizes nanoliter fluidics and can be customized with up to 3,072 through-holes in six different formats.

A plate setup file was created to outline the protocol for the applied samples, including analysis information. This protocol was uploaded into the QuantStudio™ 12 K Flex software to generate and conduct the experiment. The prepared chips were inserted into the QuantStudio 12 K Flex using disposable genotyping blocks. Subsequently, the amplification reaction took place using real-time PCR microfluidic technology. The obtained data from the amplification reaction were analyzed using the online tools provided by the Thermo Fisher Cloud service. The results of the bioinformatic analysis allowed for the classification of the studied genes as homozygotes for the major allele, homozygotes for the minor allele, or heterozygotes.

Statistical analysis

The dataset for the analysis consisted of personal information, laboratory data, and genotyping data from a total of 182 individuals. The analysis was performed using SPSS (IBM) version 26.0. Quantitative data were presented as means, medians, upper and lower quartiles (M + SD), and Me (Q1, Q3) and were used as continuous variables. Qualitative data is presented as frequencies and proportions. Were dichotomized: gender (male/female), smoking (smoker/non-smoker), and presence of diabetes mellitus (yes/no).

Quantitative data with non-normal distribution were analyzed using the non-parametric Mann–Whitney test for independent groups, and the results were reported as median (Q1; Q3). The normality of the data distribution was assessed using the Shapiro-Wilks criterion. Dichotomous and categorical variables were analyzed using the Chi-square test. A significance level of p < 0.05 was considered for determining statistically significant differences.

The association of CAN with gene polymorphisms was performed by comparing groups of patients with CAN (case) and without a diagnosis of CAN (control) using binary logistic regression. The association was appreciated using four inheritance models: dominant, co-dominant, recessive, and log-additive models. Adjustments were made for age and gender since there were no significant differences between the case and control groups in terms of the studied parameters. The analysis was performed using SPSS (IBM) version 26.0.

The mean patients’ age in groups with and without CAN did not differ significantly and amounted to 54.6 ± 9.1 and 54.7 ± 10.6 years old, respectively. There were no differences between the groups in terms of gender, BMI, and the number of smokers and non-smokers. There were no differences in cholesterol levels, low-density lipoprotein (LDL), high-density lipoprotein (HDL), glucose and glycated haemoglobin and triglycerides among the groups. Moreover, there were no significant differences in heart rate, respiratory rate, diastolic blood pressure, and systolic blood pressure. As for the prevalence of CAN in the population of patients with DM2, it occurred in 1/3 of patients (Table 1 ).

Alleles and genotypes distribution of in hardy- weinberg equilibrium

As a result of the study, out of 120 polymorphisms in a preliminary genetic analysis, 7 polymorphisms were associated with cardiovascular autonomic neuropathy: rs2736990, rs12149832, rs1108775, rs2737029, rs1801282, rs1799782, rs 13,016,963. All 7 polymorphisms were in Hardy- Weinberg equilibrium both in the case group and in the control group ( p > 0.05). These polymorphisms were further analyzed using four models: codominant, dominant, recessive, and additive.

The binary logistic regression analysis was performed under different inheritance models (codominant, dominant, recessive, and log-additive) in addition; adjustments for gender and age were made (Table 2 )).

Association rs12149832 and FTO gene (FTO alpha-ketoglutarate dependent dioxygenase) with CAN

During the study, it was found that the AA genotype of the rs12149832 FTO gene polymorphism nearly triples the risk of developing CAN in the codominant model ( p = 0.05). Furthermore, after adjusting for sex and age, BMI the risk increases to 3.2 times ( p = 0.04). When analyzed in the recessive model, the risk of developing CAN in carriers of the AA genotype was also increased, but to a lesser extent than in the codominant model, both before correction and after correction (2.18(1.19–3.95), p = 0.01) and (2.31(1.26–4.25), p = 0.007), respectively. The results from the additive model also suggest that this polymorphism may contribute to the predisposition to CAN (Table 2 ).

rs1801282 association with PPARG gene (peroxisome proliferator-activated receptor gamma) with CAN

According to the results of our study shown in Table 2 , rs1801282 of the PPARG gene was also associated with CAN. In the codominant model, the heterozygous CG variant more than doubled the risk of developing CAN ( p = 0.03). In the dominant model, CG and GG genotypes also increased the risk of developing CAN ( p = 0.03). After adjusting for age and sex, BMI the OR indicators in the codominant and dominant models did not change, and it was also found that CG and GG genotypes increase the risk of developing CAN in the respective models ( p = 0.02).

Association of the SNCA gene (synuclein alfa gene) SNP with CAN

Of the two SNCA gene polymorphisms, only rs2737029 was associated with CAN (the results are demonstrated in Table 2 ). According to the results, the CC genotype increases the risk of development of CAN two times (1.93 (1.06–3.53), p = 0.03). After adjusting for age and gender, BMI the scores did not change significantly. However, in other models, no statistically significant association of CAN with rs2737029 of the SNCA gene was found.

The study of the rs2736990 polymorphism did not reveal a statistically significant association with CAN in any of the models.

Association of rs1108775 with CAN in patients

In codominant and recessive models, the GG genotype of the rs1108775 acted as a protective factor and reduced the risk of developing CAN (0.24(0.09–0.68), p = 0.007 and 0.30(0.12–0.75), p = 0.009, respectively) shown in Table 2 . However, no statistically significant association of CAN with rs1108775 was found in dominant models. The additive model showed that this SNP reduces the chances of developing CAN (0.51 (0.32–0.82), p = 0.01 after correction).

The XRCC 1 gene (X-ray repair cross-complementing 1) with CAN

In the codominant model, the study of the rs1799782 polymorphism of the XRCC 1 gene showed that the presence of the AG genotype reduced the risk of developing CAN (0.43 (0.22–0.84), p = 0.02) after correction. In the dominant model, it was found that carriers of the AA and AG genotypes had low chances of developing CAN (0.41 (0.21–0.80), p = 0.009). The results of the additive model also show that this polymorphism may reduce the chances of developing CAN (0.45 (0.24–0.82), p = 0.01) (Table 2 ).

Association of rs13016963 of the FLACC 1 (flagellum associated containing coiled-coil domains 1) gene with CAN

In the codominant model, the rs13016963 polymorphism was not associated with cardiac autonomic neuropathy. However, after correction for gender, age, and BMI, a statistically significant association was observed, with the AA genotype increasing the risk of developing CAN by more than 2 times (2.34 (1.00-5.46), p = 0.05).

The rs13016963 of the FLACC 1 gene showed that the AA and AG genotypes in the dominant model increase the risk of developing CAN almost two times (2.06 (1.09–3.85), p = 0.03) according to the results in Table 2 . The additive model shows that with an increase in the number of risk alleles by one, the chances increase by 1.5 times (1.56 (1.04–2.36) p = 0.032).

Polymorphisms rs2737029 of the SNCA Gene, rs12149832 of the FTO Gene, rs1801282 of the PPARG GENE, rs13016963 of FLACC1 can be predisposition factors to the development of CAN, and resistance factors can be polymorphisms rs1108775 and rs1799782 of XRCC 1 gene.

According to our data, the rs2737029 polymorphism of the SNCA gene was associated with CAN. There are only a small number of studies in the literature on the rs2737029 of the SNCA gene, according to which it is associated with a susceptibility to Parkinson’s disease [ 33 ]. There is some evidence that HRV is altered when dopamine signalling is deficient in the brain [ 40 ]. In addition, animal studies have shown that electrical stimulation of the substantia nigra increases blood pressure and heart rate in awake and anesthetized animals. The important role of dopamine in the work of the heart is also evidenced by the receptors for serotonin and dopamine found on myocardial cells and the walls of blood vessels, on the terminals of cholinergic, noradrenergic, and other nerve fibres, in the nerve centres that regulate the work of the heart and other visceral functions. However, this is not a statement that the rs2737029 affects the decrease or increase in dopamine in cells. All these data motivate further research aimed at studying the rs2737029 polymorphism of the SNCA gene in the pathogenesis of CAN, particularly HRV about dopamine receptors.

Moreover, according to the results of our study, the AA genotype of rs12149832 of the FTO gene is associated with a predisposition to CAN. Unfortunately, there are no studies aimed at studying the rs12149832 polymorphism of the FTO gene in CAN, but there is evidence that the AG genotype of rs12149832 predisposes to obesity [ 24 ]. However, there is evidence that an elevated BMI is closely associated with CAN [ 41 ]. CAN reduces the ability of the autonomic nervous system to provide effective communication between the peripheral (including the gastrointestinal tract) and the central nervous system, which may contribute to further weight gain, obesity, and deterioration of autonomic function by reducing postprandial neurohumoral stimuli that impair satiety [ 42 ]. However, in our study, patients with CAN were not identified as obese based on mean BMI values. Though, as it was mentioned this gene is involved in the processes of insulin sensitivity in conjunction with the PPARG gene.

In our study, the CG genotype of the rs1801282 polymorphism of the PPARG gene increases the risk of developing CAN. Although to date there are no studies aimed at studying this polymorphism with CAN, there is evidence that the C allele of this polymorphism increases insulin sensitivity by increasing the transcriptional activity of PPARG, while the presence of the minor allele has the opposite effect [ 27 ].

It is believed that HRV is more related to insulin sensitivity than to the presence of diabetes [ 43 ]. This is particularly true in Asian populations, who tend to have low body weight and reduced insulin sensitivity compared to European populations. Possibly, in patients with cardiac neuropathy in our sample, there is dysfunction in insulin sensitivity, with a tendency towards a decrease of insulin sensitivity. Conducting further research may allow us to elucidate the association of this gene with cardiac neuropathy through insulin sensitivity. It should be noted that the presence of diabetes in only 1/3 of the patients may indicate that the reduction in heart rate variability in our sample was not always associated with diabetes.

We found that the rs1108775 in our population reduced the risk of developing CAN. At the same time, according to some authors, the rs1108775 polymorphism was not associated with the risk of developing coronary heart disease in the Kazakh population.

Furthermore, in our investigation, we observed a significant association between two polymorphisms, rs1799782 and rs13016963, and the CAN signs. Previous research has identified these polymorphisms as factors contributing to the development of various types of cancer. Specifically, rs1799782 has been linked to breast [ 44 ], colorectal [ 45 ], thyroid [ 36 ], and lung cancer, and has been shown to impact cancer treatment and overall survival rates [ 46 ]. In addition, there is a study that demonstrates a general association of this polymorphism with a combination of various oncological diseases. Arg194Trp (C > T, rs1799782) variant is associated with altered DNA repair activity [ 47 ]. Such polymorphisms resulting in amino acid changes can potentially impact the efficiency of DNA repair and hold functional significance. Although the precise functional consequences of these polymorphisms remain unclear, certain studies suggest that amino acid substitutions within evolutionarily conserved regions can influence protein capabilities [ 48 ].

rs13016963 has also been implicated in several studies as a genetic factor associated with oral squamous cell carcinoma [ 49 ], melanoma [ 50 ], esophageal squamous cell carcinoma [ 51 ], and lung cancer [ 52 ]. Genetic variations that affect the expression or function of caspase-8 may potentially influence tumorigenesis through these mechanisms [ 53 ].

At this stage of knowledge, comprehending how rs1799782 and rs13016963 are associated with CAN is challenging. However, it is known that the development of DM2 and oncogenesis are interconnected processes. Publications exist that discuss shared genetic, phenotypic, and environmental factors between DM2 and cancer s [ 54 , 55 ]. Furthermore, in the pursuit of new targets for DM treatment, articles have been published identifying CASP8 as a potential therapeutic target [ 56 ]. Additionally, there is evidence linking XRCC1 to an association with DM2 through its role in DNA repair [ 57 ]. Hence, the XRCC1 and CASP8 genes are involved in fundamental cellular processes, namely DNA repair and apoptosis. Consequently, there is evidence supporting the involvement of these proteins in the processes accompanying DM2, which could potentially explain their association with CAN.

The limitations of our study include a small sample size, which makes it possible to identify only relatively strong relationships. However, even this sample size allowed us to identify statistically significant differences. It should also be noted that the recruitment of patients was carried out only within the same medical organization. Because of this, we cannot extrapolate our results to the entire population. The third drawback can be attributed to the fact that different SNPs of different genes that are not related to each other have been studied. The study of several polymorphisms of one gene, located close to each other, and their influence on protein production makes it possible to identify certain patterns in the pathogenesis of the disease.

Although our study may have certain limitations, it also possesses notable strengths. For the first time, the genetic markers of CAN in Kazakhs have been studied and identified as factors of predisposition to CAN based on gene polymorphisms.

Thus, the genetic markers identified in our study may have functional significance in the pathogenesis of cardiac autonomic neuropathy. These patterns are likely to be explained by individual insulin sensitivity and impaired conductivity in nerve endings. All of this needs the conduction of further research in this direction, which could contribute to the prevention of the disease through individually tailored therapy.

Data availability

Underlying data OSF: Genetic Markers of cardiac autonomic neuropathy in the Kazakh population. Identifier: DOI https://doi.org/10.17605/OSF.IO/Y3U85 This project contains the following underlying data: https://osf.io/y3u85/ Data file 1. Database of Dependent and Independent Variables.xlsx. Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication). Software: The presented analysis was performed using SPSS (IBM) version 26.0. the software is available from: https://www.ibm.com/products/spss-statistics .

Acknowledgements

We express our gratitude to the nurses for their help in recruiting patients.

This research has been funded by the Ministry of Science and Higher Education of the Republic of Kazakhstan, Grant No. AR14871525.

Author information

Nazira Bekenova, Ainur Sibagatova, Alisher Aitkaliyev, Tamara Vochshenkova, Balzhan Kassiyeva and Valeriy Benberin have contributed equally.

Authors and Affiliations

Gerontology Center, Medical Centre Hospital of President’s Affairs Administration of the Republic of Kazakhstan, Mangilik El 80, Astana City, 010000, Kazakhstan

Nazira Bekenova, Ainur Sibagatova, Alisher Aitkaliyev, Tamara Vochshenkova, Balzhan Kassiyeva & Valeriy Benberin

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N.B. worked hypothesis formation, statistical data processing, writing sections “Introduction”, “Results”, and “Discussion”. She is the corresponding author of the research article. A.S. worked on statistical processing of data, wring of sections “Materials and Methods”, partially “Discussion”. A.A worked on preparation of an article according to technical requirements. T.V. was responsible for project management, research funding acquiring, and study protocol preparation. B.K. was responsible for patient recruitment, database formation. V.B. is the leader of the project, responsible for funding acquiring and hypothesis formation. All authors reviewed the manuscript.

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The study was conducted in adherence to ethical guidelines and received approval from the LocalEthics Commission of The Medical Center Hospital of the President’s Affairs Administration of the Republic of Kazakhstan, with permission note No. 5 issued on September 18, 2017. All medical tests and examinations were carried out following the approved standard operating procedures of the Hospital. Before participating in the study, all individuals willingly agreed to be part of the research and provided their informed consent by signing appropriate documentation.

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Bekenova, N., Sibagatova, A., Aitkaliyev, A. et al. Genetic markers of cardiac autonomic neuropathy in the Kazakh population. BMC Cardiovasc Disord 24 , 242 (2024). https://doi.org/10.1186/s12872-024-03912-0

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Determinants of severe maternal outcome in Keren hospital, Eritrea: An unmatched case-control study

Roles Conceptualization, Formal analysis, Investigation, Methodology, Resources, Supervision, Visualization, Writing – original draft, Writing – review & editing

* E-mail: [email protected]

Affiliation Departement of Family and Community Health, Ministry of Health Anseba Province, Keren, Anseba, Eritrea

Henos Kiflom Zewde

Published: May 13, 2024
https://doi.org/10.1371/journal.pone.0299663
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In the past few decades, several studies on the determinants and risk factors of severe maternal outcome (SMO) have been conducted in various developing countries. Even though the rate of maternal mortality in Eritrea is among the highest in the world, little is known regarding the determinants of SMO in the country. Thus, the aim of this study was to identify determinants of SMO among women admitted to Keren Provincial Referral Hospital.

A facility based unmatched case-control study was conducted in Keren Hospital. Women who encountered SMO event from January 2018 to December 2020 were identified retrospectively from medical records using the sub-Saharan Africa maternal near miss (MNM) data abstraction tool. For each case of SMO, two women with obstetric complication who failed to meet the sub-Saharan MNM criteria were included as controls. Bivariate and multivariate logistic regression analyses were employed using SPSS version-22 to identify factors associated with SMO.

In this study, 701 cases of SMO and 1,402 controls were included. The following factors were independently associated with SMO: not attending ANC follow up (AOR: 4.53; CI: 3.15–6.53), caesarean section in the current pregnancy (AOR: 3.75; CI: 2.69–5.24), referral from lower level facilities (AOR: 11.8; CI: 9.1–15.32), residing more than 30 kilometers away from the hospital (AOR: 2.97; CI: 2.29–3.85), history of anemia (AOR: 2.36; CI: 1.83–3.03), and previous caesarean section (AOR: 3.49; CI: 2.17–5.62).

In this study, lack of ANC follow up, caesarean section in the current pregnancy, referral from lower facilities, distance from nearest health facility, history of anaemia and previous caesarean section were associated with SMO. Thus, improved transportation facilities, robust referral protocol and equitable distribution of emergency facilities can play vital role in reducing SMO in the hospital.

Citation: Zewde HK (2024) Determinants of severe maternal outcome in Keren hospital, Eritrea: An unmatched case-control study. PLoS ONE 19(5): e0299663. https://doi.org/10.1371/journal.pone.0299663

Editor: Mergan Naidoo, University of Kwazulu-Natal, SOUTH AFRICA

Received: October 16, 2022; Accepted: February 14, 2024; Published: May 13, 2024

Copyright: © 2024 Henos Kiflom Zewde. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The complete data set supporting the conclusion of this manuscript have been provided as a supporting information in this manuscript.

Funding: The author(s) received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: MNM, maternal near miss; CEmOC, comprehensive emergency obstetric care; WHO, world health organization; SMO, severe maternal outcome; ANC, antenatal care; SPSS, statistical package for social sciences; OR, odds ratio; CI, confidence interval

Introduction

An important target of Sustainable Development Goals (SDGs), which urges the international community to reduce maternal mortality rate (MMR) to less than 70 per 100,000 live births by 2030, [ 1 ] is still far from reach. Despite huge international efforts to reduce its incidence, maternal mortality remains one of the most important public health problems. Even though the global maternal mortality rate fell from 442 to 211 per 100,000 live births within the past twenty years [ 2 ], the number of maternal deaths is still high in most developing countries. Sub-Saharan Africa countries bear the highest burden of maternal mortality contributing to 66% of the total maternal deaths reported globally [ 2 ].

The high burden of adverse maternal events in some resource-poor areas of the world is a clear manifestation of the inequalities in health service access, and highlights the gap between the rich and poor. Four largely preventable obstetric complications (bleeding, infections, preeclampsia/eclampsia, and unsafe abortion) account for 80% of all maternal deaths [ 3 ]. Most maternal deaths are avoidable since there are well-established healthcare solutions to prevent and manage obstetric complications [ 4 ]. Yet, majority of maternal deaths that occur in developing countries are largely preventable [ 5 , 6 ].

Information on the determinants of MNM and mortality is crucial for general assessment of resource requirements, appropriate policy formulation, as well as prioritization and effective implementation of interventions. Previously a number of distant (socio-economic and demographic characteristics of women) and intermediate (obstetric history, preexisting medical conditions, and reproductive health characteristics) factors were revealed as determinants of maternal mortality and morbidity [ 7 – 10 ].

The WHO MNM tool [ 11 ] recommends investigation of all cases of MNM and maternal death to gain better understanding of the circumstances surrounding maternal death and severe maternal morbidity. This principle is based on the assumption that all maternal deaths experience at least one life threatening condition (organ dysfunction), and therefore are similar to cases of MNM in every aspect except for the ultimate outcome of interest. Even though there are several studies in the literature that focus on the determinants of either maternal mortality [ 12 , 13 ] or MNM, [ 7 , 8 , 14 ] there is still scarcity of research focusing on potential factors associated with severe maternal outcome (SMO).

Eritrea is one of the sub-Saharan countries with high rate of maternal mortality. Despite this fact, studies on the subject of maternal morbidity and mortality are virtually inexistent in the country. Hence, there is lack of knowledge regarding factors associated with SMO in Eritrea. The aim of this study was, therefore, to assess determinants of SMO among mothers admitted to Keren Regional Referral Hospital.

Study design, setting and source population

To address the objectives of this study, unmatched case-control study was conducted in Keren regional referral hospital. Located in the town of Keren, this hospital is the only reference hospital for high complexity obstetric care in the entire Anseba region. The hospital serves both self-referred women and those referred from community hospitals, health centers, and health stations across all subzones of Anseba Region. It provides comprehensive emergency obstetric and newborn care (CEmOC) services. Approximately 549,000 people who reside within its immediate catchment area are served in the hospital. All women who were in labor, delivered or aborted, or within 42 days of postpartum and admitted in maternity or emergency wards of this hospital from January 2018 to December 2020 were the source population for this study.

Inclusion criteria

All women admitted to Keren Hospital during the study period for the treatment of pregnancy related complications, having delivered, or within 42 days of termination of pregnancy, and who fulfilled at least one of the conditions stated in the MNM tool adapted for sub-Saharan Africa [ 15 ] were enrolled as cases in the current study. Similarly, women who died while pregnant, during childbirth, or within 42 days of termination of pregnancy, irrespective of the duration and the site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes were also included as cases.

Women admitted to the hospital with obstetric complications who failed to satisfy the sub-Saharan MNM criteria were enrolled as controls for the present study. For each case of SMO, two controls who were admitted in the same day were randomly selected.

Exclusion criteria

Women whose medical records were unavailable at the time of data collection were excluded from the study. Moreover, any woman whose medical record contains missing information on two or more variables was left out from the study.

Data collection process and materials

First, the data collectors identified all cases of MNM and maternal death that occurred during the entire study period. They used the sub-Saharan MNM data abstraction tool to identify women who experienced MNM event. Then, information regarding the potential proximate and distant determinants of SMO was collected from all cases of SMO and their respective controls using a structured data abstraction tool. The tool was prepared after thorough review of literature. Data were collected from the medical records and registries of antenatal care ward, delivery ward, obstetric ward and emergency ward. For every woman, data related to socio-demographic characteristics, obstetric history, obstetric conditions, history of comorbidities, and underlying complications were collected. Prior to the commencement of the actual study, pretest was conducted in the hospital using 10% of the sample size to ensure the appropriateness of the tool. Moreover, each data collector completed the data abstraction tool for all women who were selected in the pretest to ensure that there is substantial agreement amongst them. The Cohen’s Kappa Statistic was then used to evaluate the inter-observer agreement, and its value was above 0.9 indicating a near perfect concordance between the data collectors.

Sample size determination

The sample size for this study was calculated using Epi info-7 software employing a method for unmatched case-control studies. While calculating the sample size the following assumptions were made: confidence level of 97%, power of 80%, case to control ratio of 1:2, proportion of controls exposed 1.5%, and proportion of cases exposed 15.3%. The proportion of exposure among cases and controls was taken from an Ethiopian study [ 7 ]. After careful consideration of all exposure variables included in the study, the one yielding the largest sample size (no ANC follow up) was considered in the sample size calculation for the current study. Based on the above assumptions, a minimum sample size of 188 cases and 376 controls was required. After adding 10% for data unavailability, the final sample size was calculated to be 207 cases and 414 controls. However, we opted to include all SMO cases identified during the entire study period along with their controls in order to increase the power of the study.

Data analysis

The collected data was coded, entered and cleaned using Epi info-7 software program and analyzed using SPSS Version-22 computer software. SMO was the dependent variable for the present study. The following variables, on the other hand, were the independent variables: age, parity, antenatal care attendance, birth interval, gestational age, mode of delivery, mode of admission, proximity of residence to hospital, preexisting chronic medical conditions, history of anemia, history of caesarean section, and history of abortion. Descriptive statistics were used to summarize baseline characteristics of cases and controls. Potential differences between cases and controls with regard to the distribution of independent variables were assessed using Pearson’s Chi square test (χ 2 ). Binary logistic regression analysis was also employed to determine the influence of each independent variable on SMO individually. Multivariate analysis was then employed to find out whether the factors that were found to be significant in the bivariate analysis remain independently associated with SMO. Only variables that showed statistical significance at p<0.25 were considered in the multivariate logistic regression model. For each variable the crude and adjusted odds ratio, confidence interval, and p-value were reported. The level of significance for the bivariate and multivariate logistic regression analysis was set at 0.05.

Fitness of the final model was assessed using the Hosmer-Lemeshow (HL) test. This test suggested that the model was best fit for the data as the HL Statistic was found to be insignificant (>0.05). Values of Tolerance and Variance Inflation factor (VIF) were also checked to ascertain the absence of multicollinearity between the independent variables involved in this study.

Data quality assurance

Data for the current study was collected by three competent nurse midwives who have been providing CEmOC services for more than five years in the hospital. They were given training on how to identify relevant registers, how to extract information from them, and how to handle unclear and missing data. Clear and detailed definition of every criterion in the SSA MNM tool [ 15 ] was given to all data collectors to minimize errors in identifying cases of MNM. Likewise, the International Classification of Diseases (ICD-10) definition of maternal death [ 16 ] was used to include eligible cases of maternal death. Data collectors were strictly informed to contact the principal researcher in case of any ambiguity or uncertainty; such ambiguities were then resolved based on consensus reached between the researcher and the data collectors. The principal researcher closely monitored the entire data collection process, and registers were revisited in case of any doubt.

Ethical consideration

The entire study process was strictly abided by acceptable ethical standards. Approval was sought and granted from the Provincial and National Health Research Review and Ethics Committees. Adequate explanation was given to all concerned bodies regarding the purpose and benefits of the study. The study was conducted in accordance with the guidelines for research outlined by the National Research and Ethics Committee and the Helsinki declaration of 1975, as revised in 1983. Written consent to review medical records was obtained from the medical director of Keren Hospital. The need to obtain informed consent was waived by the Research and Ethics Committee as this is the standard procedure for research activities entirely based on routinely collected data. In order to revise records in case of doubt and to avoid repetition of cases recorded in multiple registers in different wards, essential participants’ identifiers were recorded in a logbook. The logbook was kept in a secure cabinet until data collection period was over, and all recorded information was destroyed soon after the completion of the study. Likewise, all data obtained using the data abstraction tool were de-identified following completion of the study, so that none of the collected information could be tracked back to any individual woman.

During the 3-year period reviewed, 701 (SMO) cases were identified (662 cases of MNM and 39 maternal deaths). We also included 1,402 women who delivered without any notable complications during the same period to be used as controls in this study.

Socio-demographic, obstetric, prenatal and perinatal characteristics of study participants

There was no significant difference between mean age of SMO cases (27.6) and controls (28.2). Larger proportion of women with SMO did not attend antenatal care services compared to controls (p<0.001). Moreover, compared to the control group, cases of SMO tended to have higher parity, have premature delivery, experience abortion, be referred from lower facilities, and reside 30 kilometers or further from the hospital, all of which were statistically significant ( Table 1 ).

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https://doi.org/10.1371/journal.pone.0299663.t001

Past obstetric and medical characteristics of study participants

The percentage of women with SMO who had history of anemia, caesarean section, and stillbirth was significantly higher than controls. Higher proportion of SMO cases had preexisting medical conditions compared to controls as well; this difference, however, did not reach statistical significance. Slightly higher percentage of women in the control group also had history of abortion compared to the SMO group, although the difference proved to be statistically insignificant ( Table 2 ).

https://doi.org/10.1371/journal.pone.0299663.t002

Determinants of severe maternal outcome

In the bivariate binary logistic regression analysis, we assessed the association of 12 distant and proximate variables with maternal outcome. The following variables were significantly associated with SMO: parity of four or more, not attending ANC, lower gestational age, caesarean section in the current pregnancy, referral from lower level facilities, longer distance from the hospital, history of anemia, previous caesarean section and history of stillbirth. All variables considered in the bivariate analysis were significant at p = 0.25, and therefore, were eligible to be include in the multivariate binary logistic regression analysis.

In the final multivariate logistic regression model, the following variables remained independently associated with SMO: not attending ANC follow up (AOR: 4.54; CI: 3.15–6.54), caesarean section in the current pregnancy (AOR: 3.70; CI: 2.44–5.17), referral from lower level facilities (AOR: 11.71; CI: 9.01–15.23), residing more than 30 kilometers away from the hospital (AOR: 2.93; CI: 2.25–3.80), history of anemia (AOR: 2.38; CI: 1.84–3.07), and previous caesarean section (AOR: 3.33; CI: 2.06–5.38) ( Table 3 ).

https://doi.org/10.1371/journal.pone.0299663.t003

In the present study, ANC follow up, caesarean section in the current pregnancy, referral from lower level facilities, proximity of residence to hospital, history of anemia, and history of caesarean section were the major determinants of SMO.

In our study, we found that women who did not attend ANC were more likely to experience SMO. Studies from Ethiopia [ 7 , 8 , 14 , 17 – 20 ] and Brazil [ 9 , 10 ] also reported similar findings. There is overwhelming evidence regarding the effectiveness of ANC in preventing undesirable outcomes of pregnancy [ 21 ]. ANC provides opportunity to early detect and treat risk factors such as iron deficiency anemia and hypertensive disorders of pregnancy that can increase the odds of complication during late stage of pregnancy and delivery. Moreover, women who attend ANC tend to have better knowledge of obstetric danger signs [ 22 ] and are more likely to give birth at health facilities [ 23 ], and therefore have better chances of avoiding the occurrence of first and second delays. This suggests that a substantial number of SMO incidents can be avoided through improvements in ANC services.

Our findings further revealed that Women who underwent caesarean section in the current pregnancy had higher odds of SMO compared to women who had spontaneous vaginal delivery. This result was in line with similar studies from Brazil [ 24 , 25 ] that reported a three-fold increase in the risk of SMO among women who undertook caesarean section. Caesarean section is associated with several risk factors including thromboembolism, postoperative adhesion, hysterectomy, incisional hernia, and wound infections (especially if performed without administering prophylactic antibiotics) [ 26 ]. In addition, caesarean section might cause severe hemorrhage that can be threatening to the mother’s life, and may require blood transfusion [ 27 ]. However, these findings should be interpreted with caution. Most of the time, women who require caesarean section are those with higher risk pregnancies or severe medical conditions. Hence, it is difficult to distinguish problems caused by the caesarean section itself from the problems caused by the conditions that require it. It has been reported that annually millions of unnecessary caesarean section are performed throughout the world [ 28 ]. Therefore, ensuring caesarean section rates stay within the recommended range (15%) [ 29 ] through promoting evidence-based practices is crucial.

This study also revealed that women who previously had caesarean section were at higher risk of developing SMO compared to women who had normal delivery in their preceding pregnancies. This finding was in agreement with previous researches from Ethiopia [ 8 , 14 , 19 ]. Studies have shown that women who had multiple caesarean sections were more likely to have problems with later pregnancies. Previous caesarean section has been recognized as a strong risk factor of uterine rupture [ 30 ]. Caesarean section leaves a scar in the uterus that weakens the elastic property of the myometrium, making the uterus easily ruptured. Moreover, the risk of placenta accrete, a potentially life threatening condition, dramatically increases with each caesarean section performed [ 27 , 31 ]. Previous caesarean section is also a strong risk factor for placenta previa, abruption placenta, and hysterectomy [ 31 ]. Obstetricians have different opinions on the relative advantages of vaginal birth and caesarean section following a caesarean delivery. However, in accordance with WHO recommendation, the rate of caesarean section should be restrained within the ideal range of 5–15% [ 29 ] through efforts to reduce caesarean sections performed for reasons other than medical necessity.

Consistent with previous studies from Ethiopia, the current study also found that women who had history of anemia were more prone to SMO event [ 7 , 14 ]. Anemia increases the mother’s risk to complications of pregnancy including placenta previa, abruption placenta, postpartum hemorrhage, shock, uterine sub-involution, and caesarean delivery morbidity [ 32 ]. Anemia also contributes to SMO through its negative impact on immune functions. It has been documented that anemia increases susceptibility or severity of infections [ 33 ]. Early detection and treatment of anemia through quality and accessible antenatal care services is imperative to reduce the effect of anemia on adverse maternal outcome.

Among all factors, referral from lower-level health facilities had the strongest link to SMO in this study. Women referred from lower level facilities had more than twelve-fold higher odds of ending up with SMO compared to self-referred women. The scientific literature has documented a number of challenges in the emergency referral system that compromise the chances of survival in women referred due to obstetric complications. Distance from CEmOC facility and poor quality roads are the main challenges faced by referring facilities in transporting women with obstetric complication in most developing countries [ 34 ]. Most peripheral health facilities do not have readily available ambulance and will often have to rely on unreliable sources of transportation such as private vehicles [ 34 – 36 ]. Poor communication between the referring and receiving health facilities is another factor that negatively affects the effectiveness of referral system. In most instances, referring facilities fail to inform staff members of the recipient hospital in advance when referring a woman with obstetric complication [ 35 , 37 ]. As a result, valuable time is often lost to make necessary preparations once the woman reaches the hospital. Clinical skill of health workers in the referring facilities could also have profound effect on the efficiency of referral system [ 37 ]. Health workers may fail to recognize danger signs on time or may refer the woman without proper resuscitation and stabilization [ 35 ]. Effectiveness of the referral system can be enhanced by improving the transportation systems, raising technical skills of health workers, and establishing standard referral protocol [ 35 , 38 , 39 ].

This study also identified distance from the hospital as a risk factor for SMO. Accordingly, women residing more than 30 kilometers away from the hospital were found to be at higher odds of developing SMO. Similarly, two studies done in Ethiopia [ 17 , 20 ] reported that mothers who travelled 10 Kilometers or more to reach the hospital were twice as likely to develop SMO. In their classic three delays model [ 40 ], Maine and Thaddeus have clearly outlined how distance from health facility can cause both first and second delays. Long distances not only hinder reaching healthcare but also discourage women from seeking it in the first place. Women who reside in remote villages often wait until their illness gets serious before they decide to seek care, hopping that it will resolve by itself. The effect of distance is even more catastrophic when coupled with lack of transportation and poor quality roads. In addition, in most developing countries including Eritrea, specialized obstetric facilities are concentrated in the urban centers [ 40 ]. This means that women who reside in remote villages will have difficulty to reach the closest health facility, leave alone a CEmOC facility. Ensuring equitable distribution of specialist obstetric care facilities and enhancing maternity waiting home services are the most feasible solutions to mitigate the negative impact of long distance on maternal health outcome.

In the present study, we could not establish significant association between preexisting medical conditions and SMO. However, previous studies from Brazil [ 24 ] and Ethiopia [ 7 , 8 , 19 ] reported that women with preexisting medical conditions were more likely to have SMO. The proportion of women with medical comorbidities was very low in both SMO and control groups in this study. Therefore, the fact that our study was underpowered for this particular variable might be the most plausible explanation for the observed inconsistency.

Strengths and limitations

As far as the author’s knowledge is concerned, this study is the first one to assess the determinants of SMO in Eritrean setting. The sample size was large enough to give the study enough power to identify all factors associated with SMO. The sub-Saharan Africa MNM criteria was also used instead of the WHO organ dysfunction criteria, which enabled us to identify more cases of SMO in light of the limited resources in our hospital. However, the present study had some limitations as well. Data were collected from medical registers of the hospital. Hence, potential data errors in medical records could introduce some bias. Moreover, a number of important variables including religion, ethnicity, educational level and income level were left out from this study since information on these variables is not routinely recorded in the registers. The retrospective nature of this study also prevented us from collecting data on the ‘Three Delays Model’ despite its importance as a determinant of SMO. Finally, even though WHO suggests a follow-up period of 42 days postpartum, we were not able to identify women who encountered SMO subsequent to hospital discharge.

In this study, ANC follow up, caesarean section in the current pregnancy, referral from lower level facilities, proximity of residence to hospital, history of anemia, and history of caesarean section were found to be independently associated with SMO. These findings imply that improving access to antenatal care services will have a remarkable impact in preventing SMO. Quality ANC service is critical for early identification and correction of obstetric complications in general and iron deficiency anemia in particular. Health authorities should also be committed to reduce the rate of caesarean sections performed without sound medical indications. Moreover, improving transportation facilities, establishing robust referral protocol as well as ensuring equitable distribution of CEmOC facilities can play crucial role in reducing the incidence of SMO in Keren Hospital.

Supporting information

S1 data. raw data supporting the findings of this study..

https://doi.org/10.1371/journal.pone.0299663.s001

Acknowledgments

I would like to thank the research and ethics committee of ministry of health Anseba region for granting me permission to conduct this study. I would also like to extend my gratitude to staff members of Keren Hospital who participated in the process of data collection.

1. United Nations. Transforming our world: the 2030 agenda for sustainable development. New York: United Nations; 2015. https://sustainabledevelopment.un.org/post2015/transformingourworld/publication . [Accessed 21 June 2023].
2. World Health Organization. Trends in maternal mortality 2000 to 2017: estimates by WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division. Geneva: World Health Organization; 2019. https://iris.who.int/handle/10665/327595 [Accessed 21 June 2023].
3. World health organization. Maternal mortality: evidence brief (No. WHO/RHR/19.20). World Health Organization; 2019. https://iris.who.int/bitstream/handle/10665/329886/WHO-RHR-19.20-eng.pdf [Accessed 22 June 2023].
4. World Health Organization. Strategies towards ending preventable maternal mortality (EPMM). Geneva: World Health Organizaiton; 2015. https://iris.who.int/bitstream/handle/10665/153544/9789241508483_eng.pdf . [Accessed 21 June 2023].
View Article
PubMed/NCBI
Google Scholar
11. The World Health Organization. Evaluating the quality of care for severe pregnancy complications: the WHO near-miss approach for maternal health. Geneva: World Health Organization; 2011. https://apps.who.int/iris/bitstream/handle/10665/44692/9789241502221_eng.pdf . [Accessed 20 March 2023].
16. World Health Organization. WHO Library Cataloguing-in-Publication Data. The WHO application of ICD-10 to deaths during pregnancy, childbirth and puerperium: ICD-MM. Geneva: World Health Organization; 2012. https://iris.who.int/bitstream/handle/10665/70929/9789241548458_eng.pdf [Accessed 25 June 2023].
28. World Health Organization. WHO statement on caesarean section rates. Geneva: World health organization; 2015. https://www.who.int/publications/i/item/WHO-RHR-15.02 [Accessed 23 June 2023].
29. World Health Organization, United Nations Population Fund, Mailman School of Public Health. Averting Maternal Death and Disability & United Nations Children’s Fund (UNICEF). Monitoring Emergency Obstetric Care: A Handbook. Geneva: World Health Organizaiton; 2009. https://www.who.int/publications/i/item/9789241547734 [Accessed 23 June 2023].
36. Rajé F. Rural transport interventions to improve maternal health outcomes. K4D Helpdesk Report. Brighton, UK: Institute of Development Studies; 2018. https://e-space.mmu.ac.uk/627563/ [Accessed 24 th June 2023].

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In Medicine, the Morally Unthinkable Too Easily Comes to Seem Normal

A photograph of two forceps, placed handle to tip against each other.

By Carl Elliott

Dr. Elliott teaches medical ethics at the University of Minnesota. He is the author of the forthcoming book “The Occasional Human Sacrifice: Medical Experimentation and the Price of Saying No,” from which this essay is adapted.

Here is the way I remember it: The year is 1985, and a few medical students are gathered around an operating table where an anesthetized woman has been prepared for surgery. The attending physician, a gynecologist, asks the group: “Has everyone felt a cervix? Here’s your chance.” One after another, we take turns inserting two gloved fingers into the unconscious woman’s vagina.

Had the woman consented to a pelvic exam? Did she understand that when the lights went dim she would be treated like a clinical practice dummy, her genitalia palpated by a succession of untrained hands? I don’t know. Like most medical students, I just did as I was told.

Last month the Department of Health and Human Services issued new guidance requiring written informed consent for pelvic exams and other intimate procedures performed under anesthesia. Much of the force behind the new requirement came from distressed medical students who saw these pelvic exams as wrong and summoned the courage to speak out.

Whether the guidance will actually change clinical practice I don’t know. Medical traditions are notoriously difficult to uproot, and academic medicine does not easily tolerate ethical dissent. I doubt the medical profession can be trusted to reform itself.

What is it that leads a rare individual to say no to practices that are deceptive, exploitative or harmful when everyone else thinks they are fine? For a long time I assumed that saying no was mainly an issue of moral courage. The relevant question was: If you are a witness to wrongdoing, will you be brave enough to speak out?

But then I started talking to insiders who had blown the whistle on abusive medical research. Soon I realized that I had overlooked the importance of moral perception. Before you decide to speak out about wrongdoing, you have to recognize it for what it is.

This is not as simple as it seems. Part of what makes medical training so unsettling is how often you are thrust into situations in which you don’t really know how to behave. Nothing in your life up to that point has prepared you to dissect a cadaver, perform a rectal exam or deliver a baby. Never before have you seen a psychotic patient involuntarily sedated and strapped to a bed or a brain-dead body wheeled out of a hospital room to have its organs harvested for transplantation. Your initial reaction is often a combination of revulsion, anxiety and self-consciousness.

To embark on a career in medicine is like moving to a foreign country where you do not understand the customs, rituals, manners or language. Your main concern on arrival is how to fit in and avoid causing offense. This is true even if the local customs seem backward or cruel. What’s more, this particular country has an authoritarian government and a rigid status hierarchy where dissent is not just discouraged but also punished. Living happily in this country requires convincing yourself that whatever discomfort you feel comes from your own ignorance and lack of experience. Over time, you learn how to assimilate. You may even come to laugh at how naïve you were when you first arrived.

A rare few people hang onto that discomfort and learn from it. When Michael Wilkins and William Bronston started working at the Willowbrook State School in Staten Island as young doctors in the early 1970s, they found thousands of mentally disabled children condemned to the most horrific conditions imaginable: naked children rocking and moaning on concrete floors in puddles of their own urine; an overpowering stench of illness and filth; a research unit where children were deliberately infected with hepatitis A and B.

“It was truly an American concentration camp,” Dr. Bronston told me. Yet when he and Dr. Wilkins tried to enlist Willowbrook doctors and nurses to reform the institution, they were met with indifference or hostility. It seemed as if no one else on the medical staff could see what they saw. It was only when Dr. Wilkins went to a reporter and showed the world what was happening behind the Willowbrook walls that anything began to change.

When I asked Dr. Bronston how it was possible for doctors and nurses to work at Willowbrook without seeing it as a crime scene, he told me it began with the way the institution was structured and organized. “Medically secured, medically managed, doctor-validated,” he said. Medical professionals just accommodated themselves to the status quo. “You get with the program because that’s what you’re being hired to do,” he said.

One of the great mysteries of human behavior is how institutions create social worlds where unthinkable practices come to seem normal. This is as true of academic medical centers as it is of prisons and military units. When we are told about a horrific medical research scandal, we assume that we would see it just as the whistle-blower Peter Buxtun saw the Tuskegee syphilis study : an abuse so shocking that only a sociopath could fail to perceive it.

Yet it rarely happens this way. It took Mr. Buxtun seven years to convince others to see the abuses for what they were. It has taken other whistle-blowers even longer. Even when the outside world condemns a practice, medical institutions typically insist that the outsiders don’t really understand.

According to Irving Janis, a Yale psychologist who popularized the notion of groupthink, the forces of social conformity are especially powerful in organizations that are driven by a deep sense of moral purpose. If the aims of the organization are righteous, its members feel, it is wrong to put barriers in the way.

This observation helps explain why academic medicine not only defends researchers accused of wrongdoing but also sometimes rewards them. Many of the researchers responsible for the most notorious abuses in recent medical history — the Tuskegee syphilis study, the Willowbrook hepatitis studies, the Cincinnati radiation studies , the Holmesburg prison studies — were celebrated with professional accolades even after the abuses were first called out.

The culture of medicine is notoriously resistant to change. During the 1970s, it was thought that the solution to medical misconduct was formal education in ethics. Major academic medical centers began establishing bioethics centers and programs throughout the 1980s and ’90s, and today virtually every medical school in the country requires ethics training.

Yet it is debatable whether that training has had any effect. Many of the most egregious ethical abuses in recent decades have taken place in medical centers with prominent bioethics programs, such as the University of Pennsylvania , Duke University , Columbia University and Johns Hopkins University , as well as my own institution, the University of Minnesota .

One could be forgiven for concluding that the only way the culture of medicine will change is if changes are forced on it from the outside — by oversight bodies, legislators or litigators. For example, many states have responded to the controversy over pelvic exams by passing laws banning the practice unless the patient has explicitly given consent.

You may find it hard to understand how pelvic exams on unconscious women without their consent could seem like anything but a terrible invasion. Yet a central aim of medical training is to transform your sensibility. You are taught to steel yourself against your natural emotional reactions to death and disfigurement; to set aside your customary views about privacy and shame; to see the human body as a thing to be examined, tested and studied.

One danger of this transformation is that you will see your colleagues and superiors do horrible things and be afraid to speak up. But the more subtle danger is that you will no longer see what they are doing as horrible. You will just think: This is the way it is done.

Carl Elliott ( @FearLoathingBTX ) teaches medical ethics at the University of Minnesota. He is the author of the forthcoming book “The Occasional Human Sacrifice: Medical Experimentation and the Price of Saying No,” from which this essay is adapted.

The Times is committed to publishing a diversity of letters to the editor. We’d like to hear what you think about this or any of our articles. Here are some tips . And here’s our email: [email protected] .

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Guidelines To Writing A Clinical Case Report
A case report is a detailed report of the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient. Case reports usually describe an unusual or novel occurrence and as such, remain one of the cornerstones of medical progress and provide many new ideas in medicine. Some reports contain an extensive review of the relevant ...
Guideline on writing a case report
5. Background: what does this case report add to the medical literature? 6. Case summary: chief complaint, diagnosis, intervention, and outcome: 7. Conclusion: what is the main "take-away" lesson from this case? Keyword Introduction Patient information: 8. 4-7 key words-include "case report" as one of the key words: 9.
Writing a Medical Case Study: From Inspiration to Publication
5. Complete your introduction and conclusion after you've written the body. Since these sections summarize key points of your case study, it's best to write them last. The introduction gives a brief overview of the basic condition of your patient and the problem you'll address in your case study.
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 ...
PDF How to Write & Publish a Medical Case Report Using CARE Guidelines
Step 2 - Select a Journal. What target audience (doctors & patients) would best benefit from the info? If indexed in PubMed, it is peer reviewed and locatable. Some journals do NOT publish case reports. FIRST double-check the journal's "Author's Guidelines," or "Author's Instructions" to see "Types of Articles".
How to write a medical case report
Writing a case report is an excellent way of documenting these findings for the wider medical community—sharing new knowledge that will lead to better and safer patient care. For many medical students and junior doctors, a case report may be their first attempt at medical writing. A published case report will look impressive on your ...
How to write a patient case report
Case reports should contain an abstract and four sections—an introduction, case presentation, discussion, and conclusion. The introduction provides the subject, purpose, and merit of the case report and the strategy used for the literature review. The patient case presentation should be descriptive, organized chronologically, accurate ...
A young researcher's guide to writing a clinical case report
A clinical case report or case study is a means of disseminating new knowledge gained from clinical practice. Clinical case reports are the first-line evidence in medical literature as they present original observations. This article provides detailed guidance on how to identify, write, and publish a case report.
PDF 10. Guideline and Template for Writing a Case Report/Case Series
2. With these seven steps, you have the "core" of your case report. Now you need to write your Background, Discussion, and Conclusion Sections. Step 8: What is the main message of your case report on the basis of this "core"? In face of symptoms such as those described, health care providers should think of initiating anti-
A Guide to Writing Quality Case Reports
Word count limits vary by journal, with some as low as 500 words or as high as 3000 words. The word count of a case report submitted to the HCA Healthcare Journal of Medicine should be around 2000 words from the introduction to the conclusion, excluding references, tables, figures, and figure legends. The number of ta-bles, figures, or images ...
Writing Medical Case Reports
Generally, patient case studies begin with a concise statement of the pathology/medical/clinical area of the case, then provide a key significance statement, followed by a brief overview of the patients being presented. The body is made up of the case example itself with analysis relevant to the purpose of the article (see 1-3 above).
PDF How to write a case study
This guide explains how to write a descriptive case study. A descriptive case study describes how an organization handled a specific issue. Case studies can vary in length and the amount of details provided. They can be fictional or based on true events. Why should you write one? Case studies can help others (e.g., students, other organizations,
How to Write Discussions and Conclusions
Begin with a clear statement of the principal findings. This will reinforce the main take-away for the reader and set up the rest of the discussion. Explain why the outcomes of your study are important to the reader. Discuss the implications of your findings realistically based on previous literature, highlighting both the strengths and ...
How to Conclude a Case Study
Conclude the case in the following structure: Recommendation: Give a one-sentence action-oriented recommendation. Three reasons for this recommendation: List two quantitative and qualitative facts you generated while solving the case. Make sure the facts complement each other and do not overlap (MECE).
The case study approach
A case study is a research approach that is used to generate an in-depth, multi-faceted understanding of a complex issue in its real-life context. It is an established research design that is used extensively in a wide variety of disciplines, particularly in the social sciences. A case study can be defined in a variety of ways (Table 5 ), the ...
Case 22-2020: A 62-Year-Old Woman with Early Breast Cancer during the
Communication is at the core of the medical profession, and effective and empathic communication can have a positive effect on a patient's quality of life, satisfaction with care, and medical ...
A guide to writing case reports for the Journal of Medical Case Reports
Introduction: the importance of case reports. Case reports are a time-honored tradition in the medical profession. From Hippocrates (460 B.C. to 370 B.C.), and even arguably further back since the papyrus records of ancient Egyptian medicine (c. 1600 B.C.) to modern day, physicians of all specialties have described interesting cases involving all specialties [1,2].
How to write the conclusion of your case study
UX case studies must be kept short, and, when considering the length of your beginning, process and conclusion sections, it's the beginning and the conclusion sections that should be the shortest of all. In some case studies, you can keep the ending to two or three short phrases. Other, longer case studies about more complex projects may ...
7 Conclusions and Recommendations
training methods and materials for medical devices. Even the recently released human factors standard on medical device design (Association for the Advancement of Medical Instrumentation, 2009), while reasonably comprehensive, does not cover the topic of training or training materials.
(PDF) A Case Study: Pneumonia
Our main ndings and conclusion were: Citation: Zafar MZ (2016) A Case Study: Pneumonia. Occup Med Health Aff 4: 242. ... students identify chemical education topics in published medical case ...
AHRQ Seeks Examples of Impact for Development of Impact Case Studies
Since 2004, the agency has developed more than 400 Impact Case Studies that illustrate AHRQ's contributions to healthcare improvement. Available online and searchable via an interactive map , the Impact Case Studies help to tell the story of how AHRQ-funded research findings, data and tools have made an impact on the lives of millions of ...
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We present a case of a neonate born with prenatal diagnosis of Cantrell syndrome and ectopia cordis. This extremely rare congenital disorder underscores the significant need for multimodality imaging to plan further management. The aim of the study was to present the thoracoabdominal syndrome using a three-dimensional computed tomography angiography. The CT scans confirmed complex intracardiac ...
Cost-effectiveness of PCV20 to Prevent Pneumococcal Disease ...
Streptococcus pneumoniae is the leading cause of bacterial pneumonia and global mortality in children [2,3,4,5].In 2016, S. pneumoniae has been estimated to account for approximately 197 million cases of pneumonia and 1.1 million deaths [].This encapsulated bacterium is the major cause of pneumococcal diseases ranging from otitis media (OM) and pneumonia to life-threatening invasive ...
The clinical case report: a review of its merits and limitations
Background. Throughout history the clinical case report and case report series have been integral components of medical literature [].The case report genre held a strong position until it was sidelined in the second half of the 20 th century [2,3].New methodologies for research articles paved the way for evidence-based medicine.
Genetic markers of cardiac autonomic neuropathy in the Kazakh
A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA ...
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Background In the past few decades, several studies on the determinants and risk factors of severe maternal outcome (SMO) have been conducted in various developing countries. Even though the rate of maternal mortality in Eritrea is among the highest in the world, little is known regarding the determinants of SMO in the country. Thus, the aim of this study was to identify determinants of SMO ...
In Medicine, the Morally Unthinkable Too Easily Comes to Seem Normal
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