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• 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.

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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

Centre for Population Health Sciences, The University of Edinburgh, Edinburgh, UK

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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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Case Reports, Case Series – From Clinical Practice to Evidence-Based Medicine in Graduate Medical Education

Jerry w sayre.

1 Family Medicine, North Florida Regional Medical Center

Hale Z Toklu

2 Graduate Medical Education, North Florida Regional Medical Center

Joseph Mazza

3 Department of Clinical Research, Marshfield Clinic Research Foundation

Steven Yale

4 Internal Medicine, University of Central Florida College of Medicine

Case reports and case series or case study research are descriptive studies that are prepared for illustrating novel, unusual, or atypical features identified in patients in medical practice, and they potentially generate new research questions. They are empirical inquiries or investigations of a patient or a group of patients in a natural, real-world clinical setting. Case study research is a method that focuses on the contextual analysis of a number of events or conditions and their relationships. There is disagreement among physicians on the value of case studies in the medical literature, particularly for educators focused on teaching evidence-based medicine (EBM) for student learners in graduate medical education. Despite their limitations, case study research is a beneficial tool and learning experience in graduate medical education and among novice researchers. The preparation and presentation of case studies can help students and graduate medical education programs evaluate and apply the six American College of Graduate Medical Education (ACGME) competencies in the areas of medical knowledge, patient care, practice-based learning, professionalism, systems-based practice, and communication. A goal in graduate medical education should be to assist residents to expand their critical thinking, problem-solving, and decision-making skills. These attributes are required in the teaching and practice of EBM. In this aspect, case studies provide a platform for developing clinical skills and problem-based learning methods. Hence, graduate medical education programs should encourage, assist, and support residents in the publication of clinical case studies; and clinical teachers should encourage graduate students to publish case reports during their graduate medical education.

Introduction

Case reports and case series or case study research   are descriptive studies to present patients in their natural clinical setting. Case reports, which generally consist of three or fewer patients, are prepared to illustrate features in the practice of medicine and potentially create new research questions that may contribute to the acquisition of additional knowledge in the literature. Case studies involve multiple patients; they are a qualitative research method and include in-depth analyses or experiential inquiries of a person or group in their real-world setting. Case study research focuses on the contextual analysis of several events or conditions and their relationships [ 1 ]. In addition to their teaching value for students and graduate medical education programs, case reports provide a starting point for novice investigators, which may prepare and encourage them to seek more contextual writing experiences for future research investigation. It may also provide senior physicians with clues about emerging epidemics or a recognition of previously unrecognized syndromes. Limitations primarily involve the lack of generalizability and implications in clinical practice, which are factors extraneous to the learning model (Table ​ (Table1 1 ).

There is disagreement among physicians on the value of case reports in the medical literature and in evidence-based medicine (EBM) [ 2 ]. EBM aims to optimize decision-making by using evidence from well-conducted research. Therefore, not all data has the same value as the evidence. The pyramid (Figure ​ (Figure1) 1 ) classifies publications based on their study outlines and according to the power of evidence they provide [ 2 - 3 ]. In the classical pyramid represented below, systematic reviews and a meta-analysis are expected to provide the strongest evidence. However, a recent modification of the pyramid was suggested by Murad et al. [ 2 ]: the meta-analysis and systematic reviews are removed from the pyramid and are suggested to be a lens through which evidence is viewed (Figure 1 ). 

Modified from Murad et al. [ 2 ]

Because case reports do not rank highly in the hierarchy of evidence and are not frequently cited, as they describe the clinical circumstances of single patients, they are seldom published by high-impact medical journals. However, case reports are proposed to have significant educational value because they advance medical knowledge and constitute evidence for EBM. In addition, well-developed publication resources can be difficult to find, especially for medical residents; those that do exist vary in quality and may not be suitable for the aim and scope of the journals. Over the last several years, a number (approximately 160) of new peer-reviewed journals that focus on publishing case reports have emerged. These are mostly open-access journals with considerably high acceptance rates [ 4 ]. Packer et al. reported a 6% publication rate for case reports [ 5 ]; however, they did not disclose the number of papers submitted but rejected and neither did they state whether any of the reported cases were submitted to open-access journals.

The development of open-access journals has created a new venue for students and faculty to publish. In contrast to subscription-based and peer-reviewed e-journals, many of these new case report journals are not adequately reviewed and, instead, have a questionably high acceptance rate [ 4 ]. There, however, remains the issue of the fee-based publication of case reports in open-access journals without proper peer reviews, which increases the burden of scientific literature. Trainees should be made aware of the potential for academic dilution, particularly with some open-access publishers. While case reports with high-quality peer reviews are associated with a relatively low acceptance rate, this rigorous process introduces trainees to the experience and expectations of peer reviews and addresses other issues or flaws not considered prior to submission. We believe that these are important skills that should be emphasized and experienced during training, and authors should seek these journals for the submission of their manuscripts.

Importance of Case Reports and Case Series in Graduate Medical Education

The Accreditation Council for Graduate Medical Education (ACGME) has challenged faculties to adapt teaching methodologies to accommodate the different learning modalities of the next generation of physicians. As evidenced by its implementation by ACGME, competency-based medical education is rapidly gaining international acceptance, moving from classic didactic lectures to self-directed learning opportunities with experiential learning aids in the development of critical cognitive and scholarly skills. As graduate medical educators, we are in agreement with Packer et al. about the value of the educational benefits resulting from student-generated case reports [ 5 ]. Case study assignments help residents develop a variety of key skills, as previously described. EBM is an eventual decision-making process for executing the most appropriate treatment approach by using the tools that are compatible with the national health policy, medical evidence, and the personal factors of physician and patient (Figure ​ (Figure2). The 2 ). The practice of identifying and developing a case study creates a learning opportunity for listening skills and appreciation for the patient’s narrative as well as for developing critical learning and thinking skills that are directly applicable to the practice of EBM. This critically important process simultaneously enhances both the medical and the humanistic importance of physician-patient interaction. In addition, case-based learning is an active learner-centered approach for medical students and residents. It serves as a curricular context, which can promote the retention of information and evidence-based thinking.

Modified from Toklu et al. 2015 [ 3 ]

The value of case studies in the medical literature is controversial among physicians. Despite their limitations, clinical case reports and case series are beneficial tools in graduate medical education. The preparation and presentation of case studies can help students and residents acquire and apply clinical competencies in the areas of medical knowledge, practice-based learning, systems-based practice, professionalism, and communication. In this aspect, case studies provide a tool for developing clinical skills through problem-based learning methods. As a result, journals should encourage the publication of clinical case studies from graduate medical education programs through a commonly applied peer-review process, and clinical teachers should promote medical residents to publish case reports during their graduate medical education.

The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.

The authors have declared that no competing interests exist.

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Doege-Potter syndrome due to a solitary fibrous tumor of the pleura: a case report

• Juan Estrada-Maya   ORCID: orcid.org/0000-0003-3543-6958 1 , 2 ,
• Juan Sebastián Montejo   ORCID: orcid.org/0000-0002-1598-5637 1 , 2 ,
• Katerin Dayana Báez López   ORCID: orcid.org/0000-0002-9182-9417 3 &
• Juan Carlos Garzón 4  

Journal of Medical Case Reports volume  18 , Article number:  383 ( 2024 ) Cite this article

Metrics details

Doege-Potter syndrome is a rare paraneoplastic phenomenon associated with solitary fibrous tumors of the pleura (SFTPs). It is characterized by the presence of severe, sustained, and treatment-refractory hypoglycemia. Hypoglycaemia, which may be the sole symptom at disease onset, is mediated by the secretion of high-molecular-weight insulin-like growth factor (IGF-2). Most tumors exhibit benign behavior, with a 100% survival rate at 5 years. However, 10% of these tumors may display aggressive behavior with local or metastatic recurrence. We present a clinical case of a patient with a benign solitary fibrous tumor of the pleura who presented with symptomatic hypoglycemia and required pulmonary and pleural surgical resection to control the paraneoplastic phenomenon.

Case presentation

A Hispanic 46-year-old man presented with a 15-day history of transient alterations in consciousness worsened by fasting. The relevant medical history included obstructive sleep apnea treated with continuous positive air pressure (CPAP) and previous smoking. In-hospital studies revealed noninsulinemic hypoglycemia and a benign SFTP. Complete surgical resection was performed while the patient received dextrose fluids and corticosteroids perioperatively for hypoglycemia. Subsequently, the hypoglycemia resolved, and the patient was followed-up without disease recurrence.

Doege-Potter syndrome is challenging to recognize. However, effective treatment can be achieved with a high survival rate. Raising awareness among healthcare professionals about the recognition of this paraneoplasic syndrome patients will improve diagnostic suspicion, biochemical confirmation, the development of diagnostic and therapeutic guidelines, and the creation of predictive indices for aggressive presentations requiring closer monitoring.

Peer Review reports

Non-Islet Cell Tumor Hypoglycemia (NICTH) is an uncommon paraneoplastic condition caused by the synthesis of insulin-like growth factor type 2 (IGF-2) by benign and malignant nonpancreatic tumors [ 1 ]. This condition, first described by Karl Doege and Roy Potter in 1930 is characterized by recurrent and refractory hypoglycemia in the presence of an intrathoracic solitary fibrous tumor [ 2 ]. Doege-Potter syndrome is attributed to non-insulin-induced hypoglycemia caused on by fibrous tumors, while it can also be seen in mesotheliomas, liposarcoma, rhabdomyosarcoma, leukemia, lymphoma, and teratoma [ 3 ].

Solitary fibrous tumors are mesenchymal neoplasms that make up 2% of soft tissue tumors [ 4 ]. While they typically develop in the pleura, they can also affect the peritoneum, pericardium, and mediastinum [ 5 ]. Although rare, they occur at a rate of 2.8 per 100,000 people and usually have an indolent and benign course in 90% of cases [ 6 ]. However, about 5% of patients develop difficult-to-manage non-insulin-induced hypoglycemia [ 7 , 8 ].

Doege-Potter syndrome patients are difficult to identify since their condition is rarely taken into account while making a differential diagnosis of hypoglycemia. Case reports and short series make up the majority of the literature on Doege-Potter syndrome [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. By sharing our experience and highlighting interesting aspects of the pathophysiology, our case report seeks to advance understanding of this syndrome.

We present the case of a Hispanic 46-year-old male from Bogotá, Colombia, with a 15-day history of disorientation, altered thought content, stereotyped movements of the upper limbs, and episodes of heteroaggressive behavior. The patient, who was diagnosed with obstructive sleep apnea (OSA) using continuous positive air pressure (CPAP), had a history of smoking cessation (5 pack-years) and a recently identified suspicious right lung mass on outpatient chest computed tomography (CT). There was no other relevant personal or family history.

Upon admission to the CardioInfantil Foundation-Cardiology Institute, the patient was in good condition with all vital signs at normal ranges. Physical examination revealed digital clubbing (Fig.  1 ) in both hands, skin thickening between the eyes, also known as pachydermoperiostosis, absence of breath sounds in the right hemithorax, and a normal neurological examination.

Image of the patient highlighting physical examination findings: digital clubbing indicated by a red arrow. The patient's face has been obscured to protect his identity

Mixed delirium was considered the initial working diagnosis. The admission laboratory results are presented in Table  1 . Neurologic services ruled out structural central nervous system components through cranial CT and contrast-enhanced cerebral magnetic resonance imaging (MRI), both of which were normal. Twelve-hour electroencephalography showed no ictal activity. According to the described history and semiological findings, a chest X-ray (Fig.  2 ) revealed a radiopaque mass occupying the right hemithorax. Thoracic surgeons indicated that an incisional biopsy after a chest CT scan (Fig.  3 ) revealed a pleura-dependent mass affecting the right hemithorax and compressing the ipsilateral lung parenchyma.

Anteroposterior (AP) and lateral chest radiographs, highlighting a radiodense space-occupying lesion with ill-defined borders and mild ipsilateral pleural effusion, accompanied by subsegmental atelectasis in the ipsilateral hilar regions

Chest computerized tomography (CT) of axial (left) and coronal (right) sections revealed a large solid mass with extrapulmonary features, demonstrating mild heterogeneous enhancement and some coarse calcifications in its lower portion, measuring approximately 229 by 204 by 124 mm, occupying nearly the entire right hemithorax. An apparent vascular supply was observed from branches of the right middle adrenal artery and right internal mammary artery

During the procedure, the patient experienced a relapse of neurological symptoms, including stupor, upwards gaze deviation, and profuse diaphoresis, which were identical to what family members had reported. A glucometer reading of 35 mg/dl indicated severe symptomatic hypoglycemia. Intravenous correction with 10% dextrose in distilled water resulted in full symptom reversal, recovery of consciousness with amnesia of the incident, and further biochemical investigations (Table  1 ).

Despite a constant intravenous 10% dextrose infusion rate of 20 cc/h, the patient continued to experience episodes of hypoglycemia. The addition of 10 mg of prednisolone resulted in the remission of neuroglycopenic episodes and glycemic control (Fig.  4 ).

Hospitalized serum fasting glucose patterns

An open approach involving right thoracotomy was used for tumor removal, and paraneoplastic phenomena due to the intrathoracic mass were considered. Nonanatomic lung resection of the anterobasal segment of the right lower lobe was used to remove the entire tumor. The infiltrative involvement and secondary adhesions of the tumor pose difficulties for surgical treatment, especially when releasing the vascular pedicle. In the end, a total resection of the 25 × 18 × 20 cm mass was obtained (Fig.  5 ). A solitary fibrous tumor of the pleura was confirmed by histopathological investigation (Fig.  6 ) and classified as low risk by modified risk stratification criteria proposed by DEMICCO et al. in 2017 [ 17 ].

(Left) Large right intrathoracic mass measuring 25 by 18 by 20 cm, originating from the medial and subpulmonary aspects of the right lower lobe, with multiple adhesions. (Right) Complete lung expansion after mass removal without lung compromise

Fusocellular tumors with moderately dense collagenous stroma, delicate and branching vasculature, devoid of mitotic activity, necrosis, cellular atypia, or areas of hypercellularity. Low-risk solitary fibrous tumor stratification was performed according to the 2017 DEMICCO et al. [ 17 ] criteria

Adequate lung re-expansion was observed on postoperative chest X-ray (Fig.  7 ). The patient maintained good glycemic control during the postoperative period. Consequently, he was discharged after 5 days with a nasal cannula for oxygen after five days, along with orders for follow-up visits with Thoracic Surgery, Endocrinology, and Pulmonology. The patient had a Follow-up check up at3, 6, and 12 months post-discharge, during which blood glucose levels were evaluated and found to be within normal range. Additionally, there was an improvement in digital clubbing (Fig.  8 ), as evidenced by the previously described images. The patient was still free of tumor recurrence.

Postoperative anteroposterior (AP) and lateral chest radiography demonstrating lung re-expansion, with clear costophrenic and cardiophrenic angles

Image of the patient during the ambulatory follow-up period, revealing evidence of resolution of cutaneous changes

A classic instance of Doege-Potter syndrome was documented, with a solitary fibrous tumor of the pleura causing difficult-to-treat severe symptomatic hypoglycemia. Despite having all neuroglycopenic (behavioral changes, drowsiness, confusion), adrenergic (anxiety, tremor, palpitations), and autonomic (hunger, diaphoresis) symptoms, hypoglycemia is rarely diagnosed in non-diabetic patients [ 15 ]. And if it is suspected, generally it is considered to have more common causes outside of insulin, like drug side effects (sulfonylureas, antibiotics), alcohol, malnutrition, liver or kidney failure, and endocrine causes (endogenous hyperinsulinism and adrenal insufficiency) [ 15 ]. As a result, non-pancreatic malignancies are seldom considered to cause hypoglycemia, yet it can be the only manifestation of the disease [ 12 ].

Solitary fibrous tumors (SFTs) are rare soft tissue neoplasms that develop from submesothelial mesenchymal cells with fibroblastic differentiation [ 18 ]. Although first described as intrathoracic, the majority of instances come from the visceral pleura, accounting for less than 5% of all pleural malignancies. They may additionally arise within the lungs from the parenchyma, mediastinum, or diaphragm. Other common tumor sites are the retroperitoneum, pelvis, liver, and mediastinum [ 18 , 19 ]. They are typically benign tumors with slow growth that become symptomatic only when they reach a significant size, resulting in cough, dyspnea, chest discomfort, pleural effusion, or digital clubbing [ 16 ], as shown in our instance.

Hypoglycemia associated with these tumors is infrequent and is known as Doege-Potter syndrome, accounting for less than 5% of all cases [ 5 , 20 ]. In this condition, changes in IGF-2 folding result in the generation of bigger peptides, which impede cellular receptors signaling pathways of counterregulatory hormones, favoring hypoglycemia states [ 21 ]. However, the presence of "large" IGF-2 does not guarantee a relationship with NICTH episodes. Lloyd et al. found that 83.3% of fibrous tumors expressed IGF-2 mRNA, while only 7.1% of patients experienced hypoglycemia [ 22 ]. Predictors for the biochemical diagnosis of NICTH include an IGF-2/IGF-1 ratio greater than 3 and inhibition of IGF-1 expression [ 14 , 23 ]. Although these tests were not done on our patient due to study constraints, other non-insulin-induced hypoglycemia diagnostic criteria, such as reduced insulin levels and undetectable C-peptide, were present [ 20 , 24 , 25 ].

Currently, there are no clinical practice guidelines for NICTH patients. The initial therapy is usually symptomatic, with an intravenous dextrose bolus or infusion while waiting for surgery. In this example, a continuous infusion of dextrose fluids was employed to treat hypoglycemia as an interim measure for tumor removal. Previous research found that corticosteroids at dosages greater than 25 mg/day of prednisolone reduced hypoglycemia episodes by 75% in medically treated individuals by decreasing "large" IGF-2 [ 26 ]. Bourciguax et al. demonstrated the efficacy of combination corticosteroid and growth hormone therapy in treating hypoglycemic episodes [ 27 ]. The use of glucagon is more controversial, with inconsistent outcomes [ 14 ].

The definitive treatment is a full surgical excision of the tumor with clear margins [ 18 , 25 ]. The histological report of the neoplasia has no bearing on the curative surgical technique. Tumor size determines the type of surgery performed: thoracotomy for large tumors orthoracoscopy for small tumors. Complete mass excision has a 5-year survival rate of 100%, with a recurrence risk of 20% [ 28 ]. In our case, nonanatomic excision of the anterobasal portion of the lower right lobe was done by thoracotomy. Vascular pedicle inscision was made for total tumor mass release and subsequent linear mechanical suturing. Adequate postprocedural lung re-expansion was demonstrated, indicating the likelihood of total excision (Fig.  2 ). Other therapeutic options for cytoreduction, such as glucocorticoids, chemotherapy, and radiotherapy, were not investigated in this case, as surgery was provided as a curative attempt [ 25 ]. Anthracycline-based chemotherapy regimens [ 29 ] are available for individuals whose cancers are unresectable or have metastatic disease. In other cases, combination therapy with temozolomide and bevacizumab may be recommended [ 20 ]. There is currently insufficient data to support the use of radiotherapy, and there are few descriptive studies and case reports using brachytherapy and photodynamic therapy during the preoperative period [ 25 ].

When compared to other recorded Doege-Potter syndrome cases around the world and in Colombia, some epidemiological points stand out. The patient's age at clinical presentation was lower than that documented in the literature, with the disease peaking between the sixth and eighth decades of life [ 10 ]. Furthermore, this is the first recorded male incidence in Colombia in contrast to two prior cases in females [ 15 , 16 ], for a syndrome in which it is uncertain if women are more affected than men [ 9 ]. Additionally, it is a case of non-insulin-induced hypoglycemia (NICTH) caused by a benign tumor, which is generally associated with malignancies in up to 56% of situations [ 14 ]. Finally, a right-sided pleural tumor with a right-to-left ratio larger than 2 was found, which is indicative of a tumor linked to hypoglycemia [ 14 ].

Regarding the strengths and limitations of our approach, it is worth noting that the previous medical record of lung mass skewed the initial approach, which aimed to rule out intracerebral metastases while overlooking metabolic causes on admission analytics. Yet, once hypoglycemia was identified, interdisciplinary collaboration across internal medicine, thoracic surgery, and endocrinology allowed recognition and medical attention of Doege-Potter syndrome, highlighting the value of teamwork. We acknowledge that the measurement of IGF-2 was not performed, and this laboratory result could have supported the diagnosis and served as a prognostic biomarker to define the risk of recurrence in light of the available literature. Aside from that, we believe our experience will be extremely beneficial to other healthcare professionals by raising awareness of Doege-Potter syndrome, enhancing early detection and effective patient management, and motivating future clinical research for evidence-based treatment guidelines.

Conclusions

As previously stated, NICTH is a difficult metabolic illness characterized by aggressive disease behavior, local recurrence, and metastatic involvement [ 26 ]. Counterregulatory hormones are frequently used to offset the endogenous activity of paraneoplastic hormones, but there is limited evidence. The relevance of prognostic biochemical, histological, and imaging parameters, such as IGF-2 levels, vimentin, CD34, bcl-2, or CD99 positivity but cytokeratin negativity, and tumor size > 10 cm, is unclear [ 13 ]. Raising knowledge among healthcare providers about Doege-Potter syndrome patients may serve to improve diagnostic suspicion, biochemical confirmation, and the creation of diagnostic and treatment guidelines. Future advancements are expected in developing models that can forecast aggressive disease presentations that necessitate closer monitoring.

Availability of data and materials

All data generated and analysed during the current study are included in this published article [and its supplementary information files].

Abbreviations

Continuous positive air pressure

Computed tomography

Insulin-like growth factor

Magnetic resonance imaging

Nonislet cell tumor hypoglycemia

Solitary fibrous tumors of the pleura

Solitary fibrous tumors

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Acknowledgements

The authors wish to thank the Research Center of Fundación Cardioinfantil-Instituto de Cardiología, Bogotá, Colombia, for their contribution to the publication costs of this manuscript.

There was no funding for the work associated with this publication.

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Internal Medicine, Fundación Cardioinfantil-Instituto de Cardiología, Calle 163ª#13B-60, Bogotá, Colombia

Juan Estrada-Maya & Juan Sebastián Montejo

School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia

General Medicine, Fundación Cardioinfantil-Instituto de Cardiología, Bogotá, Colombia

Katerin Dayana Báez López

Thoracic Surgery, Fundación Cardioinfantil-Instituto de Cardiología, Bogotá, Colombia

Juan Carlos Garzón

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Contributions

JSM and DKB were responsible for patient care, obtaining images, and reviewing the case literature. The JCG was the attending surgeon in the patient's care and provided the surgical descriptions and images. JPE designed the case report and led the manuscript development along with JSM and DKB. All the authors have read and approved the final manuscript.

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Correspondence to Juan Estrada-Maya .

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Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

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The authors declare no competing interests.

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Estrada-Maya, J., Montejo, J.S., Báez López, K.D. et al. Doege-Potter syndrome due to a solitary fibrous tumor of the pleura: a case report. J Med Case Reports 18 , 383 (2024). https://doi.org/10.1186/s13256-024-04658-1

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GLP-1RA vs DPP-4i Use and Rates of Hyperkalemia and RAS Blockade Discontinuation in Type 2 Diabetes

• 1 Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China
• 2 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
• 3 Department of Clinical Epidemiology, Centre for Research in Epidemiology and Population Health, Paris-Saclay University, Paris, France
• 4 Division of Precision Medicine, Department of Medicine, New York University Grossman School of Medicine, New York
• 5 Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
• 6 Nephrology Clinic, Danderyd University Hospital, Stockholm, Sweden

Question   Is the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) vs dipeptidyl peptidase-4 inhibitors (DPP-4is) associated with different rates of hyperkalemia or prolonged renin-angiotensin system (RAS) inhibitor use in people with type 2 diabetes (T2D)?

Findings   In this cohort study of 33 280 patients with T2D, the use of GLP-1RAs was associated with a lower rate of hyperkalemia and prolonged RAS inhibitor use compared with the use of DPP-4is.

Meaning   These findings confirm that the use of GLP-1RAs in routine care is associated with a lower risk of hyperkalemia in people with T2D and that GLP-1RA use may enable the use of guideline-recommended RAS inhibitors, thus contributing to their overall cardioprotective and renoprotective effect.

Importance   Hyperkalemia is a common complication in people with type 2 diabetes (T2D) that may limit the use of guideline-recommended renin-angiotensin system inhibitors (RASis). Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) increase urinary potassium excretion, which may translate into reduced hyperkalemia risk.

Objective   To compare rates of hyperkalemia and RASi persistence among new users of GLP-1RAs vs dipeptidyl peptidase-4 inhibitors (DPP-4is).

Design, Setting, and Participants   This cohort study included all adults with T2D in the region of Stockholm, Sweden, who initiated GLP-1RA or DPP-4i treatment between January 1, 2008, and December 31, 2021. Analyses were conducted between October 1, 2023, and April 29, 2024.

Exposures   GLP-1RAs or DPP-4is.

Main Outcomes and Measures   The primary study outcome was time to any hyperkalemia (potassium level >5.0 mEq/L) and moderate to severe (potassium level >5.5 mEq/L) hyperkalemia. Time to discontinuation of RASi use among individuals using RASis at baseline was assessed. Inverse probability of treatment weights served to balance more than 70 identified confounders. Marginal structure models were used to estimate per-protocol hazard ratios (HRs).

Results   A total of 33 280 individuals (13 633 using GLP-1RAs and 19 647 using DPP-4is; mean [SD] age, 63.7 [12.6] years; 19 853 [59.7%] male) were included. The median (IQR) time receiving treatment was 3.9 (1.0-10.9) months. Compared with DPP-4i use, GLP-1RA use was associated with a lower rate of any hyperkalemia (HR, 0.61; 95% CI, 0.50-0.76) and moderate to severe (HR, 0.52; 95% CI, 0.28-0.84) hyperkalemia. Of 21 751 participants who were using RASis, 1381 discontinued this therapy. The use of GLP-1RAs vs DPP-4is was associated with a lower rate of RASi discontinuation (HR, 0.89; 95% CI, 0.82-0.97). Results were consistent in intention-to-treat analyses and across strata of age, sex, cardiovascular comorbidity, and baseline kidney function.

Conclusions   In this study of patients with T2D managed in routine clinical care, the use of GLP-1RAs was associated with lower rates of hyperkalemia and sustained RASi use compared with DPP-4i use. These findings suggest that GLP-1RA treatment may enable wider use of guideline-recommended medications and contribute to clinical outcomes in this population.

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Huang T , Bosi A , Faucon A, et al. GLP-1RA vs DPP-4i Use and Rates of Hyperkalemia and RAS Blockade Discontinuation in Type 2 Diabetes. JAMA Intern Med. Published online August 12, 2024. doi:10.1001/jamainternmed.2024.3806

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Common antibiotics linked to severe skin reactions, study warns doctors to choose wisely

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In a recent study published in the journal JAMA , researchers investigated the link between commonly prescribed oral antibiotics and the subsequent development of serious cutaneous adverse drug reactions (cADRs). They used long-term (20 years) records from a large dataset of elderly participants (age > 66, n = 3,257,181) who suffered antibiotic-related cARDs (n = 21,758) compared to controls that did not (n = 87,025).

Study findings revealed that commonly consumed oral antibiotics, particularly sulfonamides (aOR = 2.9), cephalosporins (aOR = 2.6), nitrofurantoins (aOR = 2.2), penicillins (aOR = 1.4), and fluoroquinolones (aOR = 1.3) resulted in significantly higher cADRs, hospitalizations, and mortality rates compared to macrolides. These findings highlight the need for medical practitioners to select lower-risk antibiotic prescriptions wherever clinically possible.

Cutaneous adverse drug reactions (cARDs), commonly named ‘toxidermia,’ are a group of rare but life-threatening hypersensitivity reactions affecting the skin, mucous membranes, and adnexa. Common examples of serious cARDs include toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), the former of which has a known mortality rate of 20-40%.

Previous research has identified numerous drugs, particularly antibiotics, as risk factors in the development of cARDs. Unfortunately, no studies have investigated the differential contributions of different antibiotic classes of cARD risk. This knowledge would be essential for medical practitioners, allowing them to preferentially select low-risk antibiotics when patients’ clinical symptoms allow for multiple treatment options.

Optimal antibiotic selection is instrumental in older patient populations, given their disproportionately high antibiotic consumption, comorbidity risk, and polypharmacy.

About the study

The present study follows a population-based study design to explore the associations between different classes of oral antibiotics and their relative subsequent cARDs risk. Data for the study was obtained from the administrative health databases of Ontario, Canada, between April 2002 and March 2022. Specifically, the Ontario Drug Benefit database was perused for antibiotic data, the Canadian Institute for Health Information (CIHI) National Ambulatory Care Reporting System for hospitalization data, and the Registered Persons Database for participants’ demographic information.

The study methodology follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and Reporting of Studies Conducted Using Observational Routinely Collected Health Data Statement for Pharmacoepidemiology (RECORD-PE) guidelines. Participants were included in the study if they were at least 65 at the time of study enrolment, had completed medical and demographic records, and (for the cARD/case cohort) were hospitalized for serious cARDs with confirmed antibiotic prescriptions in the 60 days before admission.

Each case (cARD hospitalization) was age- and sex-matched with up to four controls (patients who received antibiotic interventions but did not develop cARDs). Patients undergoing more than one simultaneous antibiotic course were excluded from the study to prevent cross-reactivity-associated complications. The outcome under focus was a serious antibiotic-associated cARD requiring hospitalization, wherein the class of prescribed antibiotics comprised the exposure.

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Previous research has established the low risk of macrolide-based antibiotics in triggering cARDs, and they were hence used as a reference group for comparisons between antibiotic classes. Statistical analyses included multivariable logistic regressions. All models were adjusted for age, sex, demographics, socioeconomics, and presence of chronic diseases.

Study findings

Over the 20-year study period, 3,257,181 participants (median age = 75), collectively representing 21,758 cARD-associated hospital admissions, were identified and included in the analysis dataset. These individuals were age, sex, and demographics matched to 87,025 controls. The average latency between antibiotic prescription and hospitalization was revealed to be 14 days.

Penicillin was observed to be the most commonly prescribed antibiotic across both cohorts (n = 42,323; 28.9%). Cephalosporins, fluoroquinolones (16.5%), macrolides (14.8%), nitrofurantoin (8.6%), and sulfonamides (6.2%) followed. Antibiotic prescriptions of classes excluding those already mentioned were collectively classified as ‘others’ and comprised 6.9% of prescriptions.

Cumulatively, 34,114,254 antibiotics courses were associated with 72,449 serious cARDs (2.12 cARDs per 1,000 prescriptions). Following corrections, multivariable analyses revealed sulfonamides as the drugs most associated with cARD risk (OR = 2.9; 3.22 cARD per 1,000 prescriptions), followed by cephalosporins (OR = 2.6; 4.92), ‘others’ (OR = 2.3), nitrofurantoin (OR = 2.2), penicillins (OR = 1.4), and fluoroquinolones (OR = 1.3).

“During the study period, 2852 (13.1%) of the 21 758 case patients were hospitalized for a cADR within 60 days of outpatient antibiotics; of these, only 50 (1.8%)were explicitly identified as having SJS/TEN. In-hospital mortality was low for all serious cADRs (n = 150; 5.3%) but higher for the SJS/TEN subtype (n = 10; 20.0%)”

Conclusions

The present study verifies the association between antibiotic consumption and subsequent cARD risk. Notably, it highlights the differential risk contributions of different antibiotic classes. Sulfonamides and cephalosporins were identified as the most harmful antibiotics, though all classes were observed to increase cARD-associated hospitalizations to varying extents.

This study emphasizes the need for medical practitioners to take note of the potential cARD contributions of different antibiotics and preferentially select the lowest-risk antibiotic class wherever clinically possible.

• Lee EY, Gomes T, Drucker AM, et al. Oral Antibiotics and Risk of Serious Cutaneous Adverse Drug Reactions.  JAMA.  Published online August 08, 2024, DOI – 10.1001/jama.2024.11437, https://jamanetwork.com/journals/jama/fullarticle/2822097

Posted in: Medical Research News | Medical Condition News | Pharmaceutical News

Tags: Antibiotic , Chronic , Drugs , Epidemiology , Hospital , Hypersensitivity , Mortality , Penicillin , Pharmacoepidemiology , Research , Skin , Syndrome

Hugo Francisco de Souza

Hugo Francisco de Souza is a scientific writer based in Bangalore, Karnataka, India. His academic passions lie in biogeography, evolutionary biology, and herpetology. He is currently pursuing his Ph.D. from the Centre for Ecological Sciences, Indian Institute of Science, where he studies the origins, dispersal, and speciation of wetland-associated snakes. Hugo has received, amongst others, the DST-INSPIRE fellowship for his doctoral research and the Gold Medal from Pondicherry University for academic excellence during his Masters. His research has been published in high-impact peer-reviewed journals, including PLOS Neglected Tropical Diseases and Systematic Biology. When not working or writing, Hugo can be found consuming copious amounts of anime and manga, composing and making music with his bass guitar, shredding trails on his MTB, playing video games (he prefers the term ‘gaming’), or tinkering with all things tech.

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Health Care Access & Coverage

How For-Profit Hospitals Billed More Aggressively Than Nonprofits For Medicare Outlier Payments: A Case Study From the Early 2000s

For-profits were also likelier to spend new revenue on executive pay and share buybacks, atul gupta, phd.

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American hospitals account for the largest nonprofit sector in the United States, but while most U.S. hospitals are nonprofit, a significant portion are for-profit. Policymakers and researchers long have questioned whether nonprofit hospitals behave differently than for-profit hospitals. In a recently released National Bureau of Economic Research working paper that examines this question, we made use of a now-resolved loophole in Medicare payment policy to understand how nonprofit and for-profit hospitals exploited this loophole, and what they did with the resulting financial windfall.

What was the loophole? Medicare used hospitals’ list prices (also called “charges”) to determine how much hospitals should get in “outlier payments” — which reimbursed hospitals beyond Medicare’s usual fixed-price contract for providing especially resource-intensive care. Because the Centers for Medicare and Medicaid Services could not observe the true costs of this treatment, they relied on those list prices, giving hospitals the opportunity to inflate them.

We used a novel approach to find hospitals that gamed the system with inflated charges for outlier payments during this time period and identified 180 such hospitals. The gain for these hospitals was substantial, resulting in a windfall of $3 billion in Medicare payments and $12 billion when including all insurers’ payments over this time period. (For perspective, consider that the total spending on the Women, Infants and Children’s (WIC) program in 2022 was $6 billion.)

Both for-profit and nonprofit hospitals took advantage of the loophole. But we found that the type of ownership was highly predictive of gaming, with the for-profit hospitals more likely to exploit the loophole than the nonprofit hospitals. The for-profit hospitals also were more likely to pocket the money rather than reinvesting it in patient care.

Hospitals That Gamed the System Derived Direct and Indirect Revenue Benefits

We found that weaknesses in government contracts can produce ripple or “spillover” effects that may far exceed in magnitude the direct revenue increases, based on our comparison of the revenue trends of the “gamer” hospitals versus those of a matched set of hospitals that did not inflate list prices for outlier payments. As our analysis showed, the impact of the loophole extended beyond the increased payments from Medicare to include increased payments from private insurance too.

This spillover — adding up to $12 billion — perhaps resulted from private insurers using similar payment designs and negotiating contracts based on list prices. The higher spending by private insurers, which then likely was passed on to employers in the form of higher insurance premiums, greater cost sharing for employees, and even salary decreases, highlights the importance of considering spillover effects when determining whether investments in oversight or enforcement actions are justified.    

Nonprofit Hospitals More Likely to Use Extra Money on Operating Costs

It is unclear exactly why the for-profit hospitals were more likely to take advantage of the Medicare outlier payment loophole. We hypothesize that managers of for-profit hospitals had more incentive to maximize revenue since they could distribute profits to themselves. We also hypothesize that managers who joined nonprofits versus for-profits differed in their financial motivation.      

What is clear, though, is that the nonprofit and for-profit gamers spent the extra revenue in different ways, consistent with predictions from organizational theory. Nonprofits directed about 75% of the gaming revenue to operating costs, with no increase in compensation for senior executives. We detected a modest but statistically significant improvement in the mortality rate at these nonprofit hospitals.

In contrast, for-profit hospitals transferred all of the excess revenue off their balance sheets, with no effect on patient care. For the largest and most important gamer, the Tenet Corporation, we showed that the excess revenue dramatically increased compensation for its highest-paid executives at the peak of gaming. Compensation more than doubled, from $6 million to $12 million and stock options ballooned to $92.5 million.

The system also engaged in stock buybacks, which resulted in nearly a billion dollars transferred to shareholders. In the case of for-profit hospital systems, this evidence strongly suggests that investing in more stringent oversight is likely to carry high social value.

Loopholes Will be Exploited and For-Profit Hospitals May Warrant Greater Scrutiny

Although the findings look back to a loophole closed two decades ago, they are particularly salient now. According to the US GAO, Medicaid and Medicare made more than $100 billion in improper payments in 2023.

The issue of improper payments has taken on additional policy significance in the aftermath of large payouts to hospitals for care related to the COVID-19 pandemic. Congress authorized nearly $200 billion in pandemic-related emergency assistance for healthcare providers.

There are concerns that some hospitals and other entities abused this and other COVID-era relief programs. The appropriate policy responses — in response to such “gaming” — depend on how the marginal dollar of excess revenue ends up being allocated.

For example, if hospitals direct excess revenue to patient care, policymakers may have less to fear from loopholes. However, if the excess revenue has limited benefits for patients and workers, it would support devoting greater resources to contract design and payment oversight.

The working paper, “Turbocharging Profits? Contract Gaming and Revenue Allocation in Healthcare,” was published June 2024 by the National Bureau of Economic Research and authored by Atul Gupta , Ambar La Forgia, and Adam Sacarny.

Assistant Professor, Health Care Management, Wharton School

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• Open access
• Published: 06 August 2024

A case report about anorexia nervosa and ischemic stroke: what can we learn?

• F. Marcolini 1 ,
• G. Arnone 2 ,
• C. Weston 1 ,
• S. Tempia Valenta 1 ,
• A. Zini 2 ,
• D. De Ronchi 1 &
• A. R. Atti 1  

Journal of Eating Disorders volume  12 , Article number:  111 ( 2024 ) Cite this article

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Introduction

Anorexia Nervosa (AN) is a complex psychiatric illness, characterized by a high risk of developing cardiovascular complications. Given the high risk of vascular diseases in patients with AN, we can assume that patients with severe AN have a high risk of developing ischemic stroke. However, to the best of our knowledge, no reports of patients with AN presenting with ischemic stroke have been published, other than a report of the development of IS during refeeding therapy in patients with severe AN.

Case presentation

The present case report is aimed at describing the characteristics of an ischemic stroke occurring in a 19-year-old university student who had a 6-month history of AN. She was a non-smoker, had no relevant medical history and no family history of stroke. Upon hospital admission due to symptoms of stroke (aphasia and facial droop), she exhibited severe malnutrition with a BMI of 12.8 kg/m 2 . Computerized tomography imaging revealed occlusion of the left M2 branch and a congruous extensive area of hypoperfusion. Further investigations ruled out all common causes of stroke: she had no vascular stenosis, no heart diseases or arrhythmias, and no shunts, and gave negative results in autoimmune, toxicological and thrombophilia screenings.

Clinicians should suspect development of severe complications, including ischemic stroke, in patients with severe AN. Further extensive group studies or group-based studies are needed to elucidate the etiology of ischemic stroke in patients with severe AN. This will enable us to develop more precise and effective interventions.

Graphical Abstract

Stroke remains nowadays one of the leading causes of death and disability worldwide [ 1 , 2 ]. There are two main types of stroke: ischemic and hemorrhagic strokes [ 3 ]. Ischemic strokes (IS) are more frequent and are caused by a disruption of blood supply to certain brain regions, leading to a lack of oxygen and subsequent loss of function and death of brain tissue [ 4 ]. In general, the causes of IS are classified under four categories: atherosclerosis, cardiac embolism, small vessel disease, and others [ 4 ]. Stroke in young people, defined as stroke occurring in patients younger than 55 years, represents an estimated 10–15% of all strokes, resulting in about two million young adults affected by stroke worldwide every year [ 5 , 6 , 7 ]. Yet, in up to 35% of all cases with ischemic stroke at a young age, no clear cause can be identified through clinical work-up or the use of stroke TOAST classification [ 8 , 9 ], resulting in the diagnosis of cryptogenic stroke. Cryptogenic stroke is characterized by higher rates of recurrence than those with other causes [ 10 , 11 ].

Anorexia nervosa (AN) is a complex psychiatric illness characterized by severe nutritional restriction that can pose a risk to the individual’s life [ 12 ]. Patients affected by AN frequently develop severe complications, including hepatic dysfunction, respiratory failure, and cardiac disease [ 13 , 14 , 15 , 16 ]. Complications related to AN seem to also involve the circulatory system, occurring in up to 87% of patients at some stage of the illness [ 17 ]. This seems to reflect the body’s attempt to preserve energy and compensate for poor nutrition and a lower blood volume [ 18 ]. Cardiovascular complications involve functional and structural cardiac abnormalities, as well as aberrations of heart rate and rhythm [ 19 ]. Peripheral vascular anomalies are also frequently seen in patients with AN, mostly related to cold intolerance and poor peripheral circulation, suggesting heat-preserving vasoconstriction [ 17 , 19 ]. Recent studies in fact suggest that patients with severe AN frequently have arteriosclerotic damage and experience venous thromboembolism [ 20 , 21 ]. Some complications eventually lead to fatal outcomes despite careful treatments [ 22 ].

Considering the high risk of vascular disease in patients with AN, we can assume that patients with severe AN also have a high risk of developing IS. However, to the best of our knowledge, no reports of patients with AN presenting with IS have been published, other than a report of the development of IS during refeeding therapy in patients with severe AN [ 23 ].

This case report offers a brief overview of a case of hospital admission due to a stroke in a 19-year-old patient suffering from AN, in the absence of other organic risk factors or laboratory findings that could justify the event.

The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. Written informed consent was obtained from the patients for publication of this report and any accompanying images.

Case report

We present the case of a female patient, university student and classical ballet dancer, of 19 years old. Her social network was described as stable and she lived with her family. Non-smoker. She denied using alcohol or other substances. No past history of neurological or cardiovascular diseases. She had no family history of stroke. She denied taking chronic medications. She had been treated for AN, Restrictive type, by a private psychotherapist and nutritionist for about six months. The onset of the symptoms of the eating disorder was reported around the age of 13, when in her ballet class environment food rules were imposed with the aim of encouraging thinness. In the six months prior to hospital admission there had been a weight loss of approximately 22 kg. At the moment of the admission, she suffered from severe malnutrition: her BMI was 12.8 kg/m2 (height, 174.5 cm; weight, 39 kg). She was not known to the local public psychiatric services. The case is graphically summarized in Fig.  1 .

Case summary

The patient arrived at the local hospital emergency department (Maggiore Hospital, Bologna, Italy) by ambulance, accompanied by her parents. About an hour and a half earlier, in her home, she had suddenly presented a speech disorder and an asymmetrical mouth droop. Upon entering the emergency room, she had a blood pressure of 110/80 mmHg, a heart rate of 44 beats per minute and an oxygen saturation in the ambient area of 98%. Her electrocardiogram showed sinus bradycardia, with prolonged QT and nonspecific junctional ST depression. According to the neurological objective examination (performed at the bedside) she appeared alert and able to carry out simple orders in the absence of stenic, sensory or coordination deficits in her limbs. She evidently had a deficit in the right VII cranial nerve, severe motor aphasia and dysarthria. No deficits in ocular movements and vision, nor hemi-neglect, emerged. According to the National Institute of Health Stroke Scale (NIHSS) she had a score 7. The blood tests carried out at the time of access revealed no significant anomalies other than hypercholesterolemia, which had already been diagnosed in routine blood tests (total cholesterol 354 mg/dL with LDL 237 mg/dL).

According to protocol, she underwent an encephalic computerized tomography (CT) without contrast, followed by a perfusion CT with contrast and a triphasic CT angiography of the neck and intracranial vessels. This procedure showed the absence of intracranial hemorrhages and occlusion of the left M2 branch with a congruous and extensive area of hypoperfusion, with a favorable perfusion pattern. In the absence of contraindications, she was treated with intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) 0.9 mg/kg (10% in bolus and the remaining in infusion over one hour), followed by angiography with thrombectomy by aspiration of the clot in the occluded vessel which led to complete revascularization. She was later admitted to the stroke unit.

Upon admission to the stroke unit, she had an NIHSS score of 2 and a persisting deficit affecting the VII cranial nerve. This picture rapidly improved until normalization with an NIHSS score of 0. The neuroradiological investigations, in particular the brain magnetic resonance imaging (MRI), showed an ischemic lesion in the left insulae and fronto-opercolar cortex, no longer symptomatic at the time of the scan. In figures reported below diffusion MRI and perfusion CT results are shown (Figs.  2 and 3 ).

MRI diffusion imaging that shows the appearance of an ischemic lesion in the left insulae and fronto-opercolar cortex

Perfusion CT imaging RAPID software showing “penumbra”. (CBF, cerebral blood flow; Tmax, time to maximum)

The patient underwent multiple tests aimed at defining the origin of the ischemic stroke. An angiogram of the neck and intracranial vessels showed no significant stenosis. No signs of heart disease or arrhythmias with potential for embolism were found, as assessed via transthoracic and transesophageal echocardiogram and 24 h and 7 day Holter ECG recording (MYATRIA study approved by the hospital ethics committee for which the patient gave her consent). Right to left shunts were also ruled out with a transcranial color doppler ultrasound, and toxicological, autoimmune and thrombophilia screening tests gave negative results.

Antiplatelet therapy with acetylsalicylic acid (100 mg/die) and atorvastatin (20 mg/die) was started for secondary prevention of ischemic stroke of undetermined origin. On the sixth day of hospitalization, she was transferred to Internal Medicine.

Hospitalization in internal medicine lasted 74 days, in which the primary objective was to contrast malnutrition and dehydration by monitoring refeeding. Nutritional therapy was administered both orally and parenterally. For the entire duration of hospitalization, as well as upon discharge, the patient firmly refused to take psychopharmacological drugs; both antidepressants, prescribed to manage mood swings and significant anxiety crises triggered by meals, and sedatives, prescribed to counteract persistent insomnia. From the clinical interviews carried out, it was not possible to fully understand the reason for such strong opposition to psychiatric therapy, leaving only the hypothesis of the presence of stigma towards the status of psychiatric patient. After reaching a weight of 43 kg (BMI 14.2 kg/m2), the patient was transferred to a local residential center specialized in the treatment of EDs.

In this case report, we presented a young patient with severe AN who had an ischemic stroke defined as cryptogenic.

Recent studies have reported wide variation in the geographic incidence of stroke in young adults, with results ranging from 5/100,000 cases per year in Europe, to 20/100,000 in North America, and up to 100/100,000 in Africa [ 24 ]. The higher incidence of stroke in low-income countries compared to high-income countries may be partially explained by geographically dependent etiological differences (including the presence of rheumatic heart disease) and by lower identification of vascular risk factors due to limited resources [ 7 , 8 , 25 ]. Several studies have shown an increased incidence in recent years of stroke in those younger than 55 years of age [ 26 , 27 , 28 , 29 ]. Possible causes for increased incidence, as proposed by Farah and colleagues, are an increased prevalence of certain risk factors and of illicit drug use in the general population [ 30 ]. At the same time, the introduction of MRI scans and increased awareness of stroke symptoms may also have contributed to higher incidence [ 30 ]. Identification of causes and risk factors of ischemic stroke in young adults is key to speed up diagnosis and optimize treatment. Conventional risk factors such as hypertension, central obesity, dyslipidemia, cardiac causes, smoking, drinking alcohol, and psychosocial stress are also important for stroke in those younger than 45 years of age [ 31 ]. A recent study conducted by Ekker and colleagues identified Coca-Cola consumption, vigorous physical exercise, sexual activity, illicit drug use, and a feverish state as specific potential trigger factors for stroke in the young population [ 32 ].

The patient presented in this report underwent multiple tests aimed at defining the cause of the ischemic stroke, but they all gave negative results. Our extensive work-up revealed no source of embolism. Given the absence of smoking and other behaviors considered at risk for the development of stroke, as well as the absence of elements such as obesity, hypertension, and previous cardiovascular diseases, we hypothesize that the condition of AN is at the basis of this ischemic manifestation. In particular, AN, in its restrictive form, can lead to dehydration dependent on the reduction of fluid intake and the marked suppression of the thirst stimulus [ 33 , 34 ]. Dehydration, leading to high plasma osmolality, is a potential contributing factor for cerebral ischemia [ 35 , 36 ]. High plasma osmolality may manifest as orthostatic intolerance and may cause a decreased cerebral blood flow with orthostatic changes [ 37 , 38 ]. This is accentuated by possible concomitant bradycardia (defined by the 2018 bradycardia guidelines as a non-physiological sinus rate lower than 50 bpm), an element that often characterizes the clinical picture of AN, which is considered a compensatory adaptation within the starved body, mediated by increased vagal tone, in order to preserve energy [ 17 , 39 , 40 ]. In fact, the patient described accessed the emergency room with a heart rate of 44 beats per minute. High tonicity can also lead to an increase in blood viscosity, due to an increase of the hematocrit. As the Hagen-Poiseuille equation states, high blood viscosity translates into an impaired cerebral blood flow, which can be linked to an increased risk of ischemic stroke [ 41 , 42 ]. Dehydration could also trigger the coagulation cascade by activating the autonomic sympathetic system [ 43 ].

An altered lipid profile (in the form of hypercholesterolemia) in AN is associated with increased cardiovascular risk [ 44 , 45 ]. High serum total cholesterol has been found in patients with AN since 1965 [ 46 ]. It has been discovered that hypercholesterolemia in AN patients does not depend on de novo synthesis, even if a secondary synthesis linked to the hyperglycemia consequent to the increased level of cortisol is considered possible [ 47 , 48 ]. Nestel and colleagues related hypercholesterolemia in AN to diminished cholesterol and bile acid turnover as a mechanism that compensates reduced caloric intake [ 49 ]. Moreover, a high level of cholesterol esterase transfer protein activity was demonstrated [ 50 ]. Elevated cholesterol levels are associated to an increased risk of stroke incidence since, in addition to extracranial atherosclerosis, hyperlipidemia promotes cervical and coronary atherosclerosis, which predisposes to atherothrombotic and cardioembolic stroke [ 51 ]. In our patient, no alterations in the hematocrit or coagulation cascade were found, just as no evidence of atherosclerosis was found.

In order to prevent the development of organic complications, which can be so complex as to threaten the survival of the individual, it becomes of primary importance to attempt to prevent AN from evolving into severe or enduring forms. Indeed, approximately 20% of individuals diagnosed with AN are estimated to relapse into a long-lasting disorder [ 52 , 53 ]. Therefore, it is of paramount importance to identify and diagnose the disorder as early as possible [ 54 , 55 ] and to initiate an integrated and patient-centred approach that can effectively address the multiple challenges posed by AN [ 56 , 57 , 58 ].

In conclusion, we report here the case of a patient with severe AN who had an episode of ischemic stroke. Our extensive clinical workup was not able to determine the etiology of ischemia. The etiology of the event remains undetermined at this time. This case provides novel insights: clinicians should suspect development of severe complications, including ischemic stroke, in patients with severe AN. Further extensive group studies or group-based studies are needed to elucidate the etiology of ischemic stroke in patients with severe AN. This will enable us to develop more precise and effective interventions.

Availability of data and materials

The data used during the current study are available from the corresponding author on reasonable request.

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Marcolini, F., Arnone, G., Weston, C. et al. A case report about anorexia nervosa and ischemic stroke: what can we learn?. J Eat Disord 12 , 111 (2024). https://doi.org/10.1186/s40337-024-01074-0

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After private equity takes over hospitals, they are less able to care for patients, top medical researchers say

After private-equity firms acquire hospitals , the facilities’ assets and resources diminish significantly, leaving the facilities less equipped to care for patients, according to a new study by physician researchers at the University of California at San Francisco, Harvard Medical School and the City University of New York’s Hunter College.

Published Tuesday in the  Journal of the American Medical Association,  the research highlights a pattern of asset stripping at health care facilities purchased by private-equity firms, its researchers said, and is the first study to analyze the activity nationwide. 

“It’s a very striking finding and should change the way people think about private equity in hospitals,” said Dr. Stephanie  Woolhandler , a distinguished professor of public health at Hunter, part of CUNY, and one of seven authors of the study. “The PE firms say, ‘We bring new capital into hospitals.’ It turns out that’s not quite true.”

Assets studied in the research consist of land, buildings, major hospital equipment and information technology. The study found that during the two years after a private-equity acquisition, total capital assets at private equity-acquired hospitals declined by 15% on average while assets rose by an average of 9% at other hospitals. That makes for a net difference of 24%, the researchers found, equivalent to a loss of $28 million in total assets per hospital.The research studied 156 hospitals acquired by private-equity firms from 2010 to 2019 comparing them with 1,560 hospitals of similar size in similar communities that were not bought by private equity. The pattern of diminished assets persisted and widened five years after acquisition, the study reported.

Depleted assets translate to a reduced level of care, Woolhandler told NBC News, noting that equipment, buildings and technology are resources needed for patient care. “There are real dangers to the health care that people get if you deplete all the capital from a hospital,” she added.

Private-equity firms borrow money to buy companies that they hope to sell in a few years at a profit. Independent academic research shows that such leveraged buyouts result in far more bankruptcies than acquisitions that do not use so much debt and the deals can result in significant job losses for rank-and-file workers.Health care has been a primary focus of private-equity purchases in recent years, with over $500 billion invested in the industry by firms such as Apollo Global Management, The Blackstone Group, The Carlyle Group and KKR. The  American Investment Council , the industry lobbying group, says private equity improves health care. 

But increased patient falls and infections follow private-equity takeovers of hospitals, recent research shows, and residents of nursing homes owned by private-equity firms experience 10% greater mortality rates than those owned by other types of entities.

“Previous studies have found that patients are endangered and costs increase in the wake of private-equity acquisitions,” said Dr. Elizabeth Schrier, a resident physician at the University of California, San Francisco, and a lead author of the new research.

The report on asset-stripping in private equity-owned hospitals comes amid the collapse of Steward Health Care, a hospital chain recently owned by private equity that filed for bankruptcy in May, leaving patients and workers at 31 facilities adrift. Last  week , the Senate’s Health, Education, Labor and Pensions committee announced an investigation into the Steward crisis. 

Until 2020, Steward was owned by Cerberus Capital, a private-equity firm led by Steve Feinberg. In 2010, Cerberus bought a nonprofit chain known as Caritas Christi Health Care for around $250 million. The firm and its investor partners reaped an $800 million profit when it divested a decade later.

Along the way, Steward sold the land under its hospitals, generating a gain for investors but increasing the company’s costs significantly.

A Cerberus spokesman said in a  statement that it’s unfair and incorrect to characterize the Steward land sale as “looting” the company, as Sens. Ed Markey and Elizabeth Warren, both Massachusetts Democrats, have done. “During our nearly 11-year ownership of Steward, we supported the revitalization of failing community hospitals into a leading healthcare system,” the statement continued. “Cerberus’ long-term investment made it possible for Steward to continue to serve its communities, employ tens of thousands of professionals, and positively impact millions of patients’ lives.”

Amid rising numbers of health care takeovers by private equity, at least 10 states are ramping up  scrutiny  on the transactions to prevent patient harm, such as rising health care costs or the effects of monopolization. On July 1, Indiana began requiring that private-equity partnerships proposing transactions with health care companies valued at $10 million or more to notify the state’s attorney general 90 days before the proposed deal. While approval of the transaction is not mandatory, the attorney general can analyze antitrust concerns or issue a civil investigative demand for more information.

California, Connecticut, Illinois and Nevada are among the other states enacting new laws bringing scrutiny to private equity’s health care acquisitions.

Health care is not the only industry in which some private-equity owners have stripped companies’ assets. The Red Lobster restaurant chain  failed  in part because its private-equity owner sold off the company’s prime real estate, generating gains for itself. Meanwhile, Red Lobster had to pay rent on the properties, raising its costs and ultimately hobbling its operations.

Gretchen Morgenson is the senior financial reporter for the NBC News Investigative Unit. A former stockbroker, she won the Pulitzer Prize in 2002 for her "trenchant and incisive" reporting on Wall Street.