study vs research

Find Master ’ s degrees in Europe now

💡 Taught Masters vs Research Masters:

There are many types of Master’s degrees, and most of these are Taught Masters . In the United Kingdom, such programmes are also called postgraduate taught or PGT for short. They typically require completing a set number of modules and a thesis (also called dissertation), plus sometimes work experience through a placement. The type of dissertation you will undertake will depend on the type of Master’s degree you are enrolled in, and might for example include your own small research project. Most postgraduate taught degrees have these elements of independent work and research to varying extents.

In contrast, a Research Master ’ s degree will focus on, you guessed it, research. In the UK, such programmes are also called postgraduate research or PGR (although this term may also refer to doctorate programmes). Rather than attending classes every semester and completing module assignments, you will need to focus on an independent research project – under supervision, of course. The course will still include a few taught modules, most often on research methodologies, but it will require you to work independently for most of the time.

Master’s degrees in the UK are usually one year full-time or two years part-time, but in other countries the duration may differ.

Remember: A final dissertation will be compulsory for all Master ’ s degrees. However, a dissertation for an MRes will typically be longer than that for an MA or MSc.

Typically, Research Masters will lead to an MRes degree. At some universities, however, you'll instead be awarded an MPhil (Master of Philosophy) or MLitt (Master of Letters). For more information, have a look at our detailed glossary.

🤔 Is a Research Master’s the same as a PhD?

No, a Research Master’s degree is not the same as a PhD. Although for both degrees you will need to complete a dissertation based on an independent research project, there are notable differences:

• The first difference is the duration : A Master’s degree will typically last one to two years, while a PhD usually takes up about three to five years. The research project you’ll undertake during a doctorate degree will therefore be longer and broader than one you would pursue in a Master’s degree.
• As a PhD student, you’re expected to publish research papers in journals before you are awarded your degree. MRes students might occasionally do that during or after their studies, but it’s rarely obligatory.
• As a PhD student, you’ll most often be expected to take on other duties , such as teaching.

If you wish to pursue doctoral research and a career in academia, a research Master’s degree could be a great option for you as it will allow you to get to grips with and gather valuable experience and training on independent research early on in your studies.

👀 Overview: What’s the difference?

There are a few differences between Taught Masters and Research Masters , and not all of them are obvious.

The table below outlines some of the main elements to consider when choosing which of the two degrees to pursue after your Bachelor’s degree:

Study in Europe: Find your Master ’ s degrees

🏛️ Which should you choose?

The choice between a taught Master’s and a research Master’s depends on a few factors.

• First of all, do you enjoy research more than coursework? Then an MRes may be more suitable – but remember that any Master’s degree, especially an MSc, will have a research component.
• Then, it’s crucial to understand how you like to work and study. Do you particularly enjoy working independently? Perhaps then you can consider an MRes. In a taught Master’s, you’ll have a more solid structure, timetables and regular deadlines to keep you on track, but these may not be as readily available during an MRes, so consider which environment you are more likely to thrive in.  
• Another important consideration is what you want to do after your Master’s degree. If you want to enter the labour market immediately, and you are not particularly interested in focusing on research training, then perhaps a taught Master’s degree is more suited.

💸 Is there a difference in fees between Taught and Research Masters?

No, normally, you won’t find a huge difference in tuition fees between taught and research Master’s degrees. Only in some instances, Postgraduate Research Masters tend to be cheaper.

📝 Can I do a PhD after taking a Taught Master’s Degree?

Yes, you can pursue a PhD after any type of Master’s course, provided that you have a degree in a relevant subject. All taught postgraduate degrees involve some independent work and research, especially for your dissertation, which will prepare you for further research should you choose to pursue a PhD.

Some taught Masters require more independent research work than others, particularly when it comes to the dissertation after completing the taught modules. Consult the curriculum or ask admissions staff to get a better idea of what to expect.

While a taught Master’s degree won’t prevent you from doing a PhD further down the line, it’s vital that you have a good idea of what requirements you will have to fulfil in order to be admitted to the PhD, and how you can best prepare.

If you already have a clear idea of what field you’d like to conduct your doctoral research in, you could take advantage of the joint Master’s – PhD programmes on offer at some universities.

These four-year programmes – also called “combined” or “integrated” degrees – offer the chance to complete a Master’s degree in the first year and to progress seamlessly to PhD research in the next three.

Looking for Masters in Europe? Have a look at these English-taught degrees 👀

Author: Claudia Civinini

Claudia has many years of experience as a reporter and writer on international education and student mobility. Originally from Italy, she holds a BA in Communication and Media Studies from the University of Genova; a Graduate Diploma in Education, Secondary Education and Teaching from the Australian Catholic University; and a joint MSc in Educational Neuroscience from UCL and Birkbeck, University of London. Claudia has previously worked as Chief Reporter for the English Language Gazette, as Senior Reporter for the PIE News (Professionals in International Education), and as Reporter for Tes.

You might be interested in this:

Case Study vs. Research

What's the difference.

Case study and research are both methods used in academic and professional settings to gather information and gain insights. However, they differ in their approach and purpose. A case study is an in-depth analysis of a specific individual, group, or situation, aiming to understand the unique characteristics and dynamics involved. It often involves qualitative data collection methods such as interviews, observations, and document analysis. On the other hand, research is a systematic investigation conducted to generate new knowledge or validate existing theories. It typically involves a larger sample size and employs quantitative data collection methods such as surveys, experiments, or statistical analysis. While case studies provide detailed and context-specific information, research aims to generalize findings to a broader population.

Further Detail

Introduction.

When it comes to conducting studies and gathering information, researchers have various methods at their disposal. Two commonly used approaches are case study and research. While both methods aim to explore and understand a particular subject, they differ in their approach, scope, and the type of data they collect. In this article, we will delve into the attributes of case study and research, highlighting their similarities and differences.

A case study is an in-depth analysis of a specific individual, group, event, or phenomenon. It involves a detailed examination of a particular case to gain insights into its unique characteristics, context, and dynamics. Case studies often employ multiple sources of data, such as interviews, observations, and documents, to provide a comprehensive understanding of the subject under investigation.

One of the key attributes of a case study is its focus on a specific case, which allows researchers to explore complex and nuanced aspects of the subject. By examining a single case in detail, researchers can uncover rich and detailed information that may not be possible with broader research methods. Case studies are particularly useful when studying rare or unique phenomena, as they provide an opportunity to deeply analyze and understand them.

Furthermore, case studies often employ qualitative research methods, emphasizing the collection of non-numerical data. This qualitative approach allows researchers to capture the subjective experiences, perspectives, and motivations of the individuals or groups involved in the case. By using open-ended interviews and observations, researchers can gather rich and detailed data that provides a holistic view of the subject.

However, it is important to note that case studies have limitations. Due to their focus on a specific case, the findings may not be easily generalized to a larger population or context. The small sample size and unique characteristics of the case may limit the generalizability of the results. Additionally, the subjective nature of qualitative data collection in case studies may introduce bias or interpretation challenges.

Research, on the other hand, is a systematic investigation aimed at discovering new knowledge or validating existing theories. It involves the collection, analysis, and interpretation of data to answer research questions or test hypotheses. Research can be conducted using various methods, including surveys, experiments, and statistical analysis, depending on the nature of the study.

One of the primary attributes of research is its emphasis on generating generalizable knowledge. By using representative samples and statistical techniques, researchers aim to draw conclusions that can be applied to a larger population or context. This allows for the identification of patterns, trends, and relationships that can inform theories, policies, or practices.

Research often employs quantitative methods, focusing on the collection of numerical data that can be analyzed using statistical techniques. Surveys, experiments, and statistical analysis allow researchers to measure variables, establish correlations, and test hypotheses. This objective approach provides a level of objectivity and replicability that is crucial for scientific inquiry.

However, research also has its limitations. The focus on generalizability may sometimes sacrifice the depth and richness of understanding that case studies offer. The reliance on quantitative data may overlook important qualitative aspects of the subject, such as individual experiences or contextual factors. Additionally, the controlled nature of research settings may not fully capture the complexity and dynamics of real-world situations.

Similarities

Despite their differences, case studies and research share some common attributes. Both methods aim to gather information and generate knowledge about a particular subject. They require careful planning, data collection, analysis, and interpretation. Both case studies and research contribute to the advancement of knowledge in their respective fields.

Furthermore, both case studies and research can be used in various disciplines, including social sciences, psychology, business, and healthcare. They provide valuable insights and contribute to evidence-based decision-making. Whether it is understanding the impact of a new treatment, exploring consumer behavior, or investigating social phenomena, both case studies and research play a crucial role in expanding our understanding of the world.

In conclusion, case study and research are two distinct yet valuable approaches to studying and understanding a subject. Case studies offer an in-depth analysis of a specific case, providing rich and detailed information that may not be possible with broader research methods. On the other hand, research aims to generate generalizable knowledge by using representative samples and quantitative methods. While case studies emphasize qualitative data collection, research focuses on quantitative analysis. Both methods have their strengths and limitations, and their choice depends on the research objectives, scope, and context. By utilizing the appropriate method, researchers can gain valuable insights and contribute to the advancement of knowledge in their respective fields.

Comparisons may contain inaccurate information about people, places, or facts. Please report any issues.

• Rules/Help/FAQ Help/FAQ
• Members Current visitors
• Interface Language

Follow along with the video below to see how to install our site as a web app on your home screen.

Note: This feature may not be available in some browsers.

• English Only

study vs research

• Thread starter muskulpesent
• Start date May 20, 2020

muskulpesent

• May 20, 2020

Can study and research be used interchangeably? Is there any difference?  

Senior Member

Are you asking about the nouns or the verbs? Please give us a sentence in which you think that study and research are or possibly are interchangeable.  

Nouns. For example: This research aims to investigate studies about online counseling both in Turkey and USA. Can i use study instead of research in this sentence?  

You have already used studies in your sentence, so you would not use it twice. Research can sometimes mean a study. I think of study as a paper, i.e. the result of a study published in a journal. In this sense a study is part of research into something. Research is a broader term involving making investigations into a subject, and may include looking at various studies. A scientist may carry out research in an area and his or her research may encompass a number of studies.  

• Skip to main content
• Keyboard shortcuts for audio player

Your Health

• Treatments & Tests
• Health Inc.
• Public Health

Why writing by hand beats typing for thinking and learning

Jonathan Lambert

If you're like many digitally savvy Americans, it has likely been a while since you've spent much time writing by hand.

The laborious process of tracing out our thoughts, letter by letter, on the page is becoming a relic of the past in our screen-dominated world, where text messages and thumb-typed grocery lists have replaced handwritten letters and sticky notes. Electronic keyboards offer obvious efficiency benefits that have undoubtedly boosted our productivity — imagine having to write all your emails longhand.

To keep up, many schools are introducing computers as early as preschool, meaning some kids may learn the basics of typing before writing by hand.

But giving up this slower, more tactile way of expressing ourselves may come at a significant cost, according to a growing body of research that's uncovering the surprising cognitive benefits of taking pen to paper, or even stylus to iPad — for both children and adults.

Is this some kind of joke? A school facing shortages starts teaching standup comedy

In kids, studies show that tracing out ABCs, as opposed to typing them, leads to better and longer-lasting recognition and understanding of letters. Writing by hand also improves memory and recall of words, laying down the foundations of literacy and learning. In adults, taking notes by hand during a lecture, instead of typing, can lead to better conceptual understanding of material.

"There's actually some very important things going on during the embodied experience of writing by hand," says Ramesh Balasubramaniam , a neuroscientist at the University of California, Merced. "It has important cognitive benefits."

While those benefits have long been recognized by some (for instance, many authors, including Jennifer Egan and Neil Gaiman , draft their stories by hand to stoke creativity), scientists have only recently started investigating why writing by hand has these effects.

A slew of recent brain imaging research suggests handwriting's power stems from the relative complexity of the process and how it forces different brain systems to work together to reproduce the shapes of letters in our heads onto the page.

Your brain on handwriting

Both handwriting and typing involve moving our hands and fingers to create words on a page. But handwriting, it turns out, requires a lot more fine-tuned coordination between the motor and visual systems. This seems to more deeply engage the brain in ways that support learning.

Shots - Health News

Feeling artsy here's how making art helps your brain.

"Handwriting is probably among the most complex motor skills that the brain is capable of," says Marieke Longcamp , a cognitive neuroscientist at Aix-Marseille Université.

Gripping a pen nimbly enough to write is a complicated task, as it requires your brain to continuously monitor the pressure that each finger exerts on the pen. Then, your motor system has to delicately modify that pressure to re-create each letter of the words in your head on the page.

"Your fingers have to each do something different to produce a recognizable letter," says Sophia Vinci-Booher , an educational neuroscientist at Vanderbilt University. Adding to the complexity, your visual system must continuously process that letter as it's formed. With each stroke, your brain compares the unfolding script with mental models of the letters and words, making adjustments to fingers in real time to create the letters' shapes, says Vinci-Booher.

That's not true for typing.

To type "tap" your fingers don't have to trace out the form of the letters — they just make three relatively simple and uniform movements. In comparison, it takes a lot more brainpower, as well as cross-talk between brain areas, to write than type.

Recent brain imaging studies bolster this idea. A study published in January found that when students write by hand, brain areas involved in motor and visual information processing " sync up " with areas crucial to memory formation, firing at frequencies associated with learning.

"We don't see that [synchronized activity] in typewriting at all," says Audrey van der Meer , a psychologist and study co-author at the Norwegian University of Science and Technology. She suggests that writing by hand is a neurobiologically richer process and that this richness may confer some cognitive benefits.

Other experts agree. "There seems to be something fundamental about engaging your body to produce these shapes," says Robert Wiley , a cognitive psychologist at the University of North Carolina, Greensboro. "It lets you make associations between your body and what you're seeing and hearing," he says, which might give the mind more footholds for accessing a given concept or idea.

Those extra footholds are especially important for learning in kids, but they may give adults a leg up too. Wiley and others worry that ditching handwriting for typing could have serious consequences for how we all learn and think.

What might be lost as handwriting wanes

The clearest consequence of screens and keyboards replacing pen and paper might be on kids' ability to learn the building blocks of literacy — letters.

"Letter recognition in early childhood is actually one of the best predictors of later reading and math attainment," says Vinci-Booher. Her work suggests the process of learning to write letters by hand is crucial for learning to read them.

"When kids write letters, they're just messy," she says. As kids practice writing "A," each iteration is different, and that variability helps solidify their conceptual understanding of the letter.

Research suggests kids learn to recognize letters better when seeing variable handwritten examples, compared with uniform typed examples.

This helps develop areas of the brain used during reading in older children and adults, Vinci-Booher found.

"This could be one of the ways that early experiences actually translate to long-term life outcomes," she says. "These visually demanding, fine motor actions bake in neural communication patterns that are really important for learning later on."

Ditching handwriting instruction could mean that those skills don't get developed as well, which could impair kids' ability to learn down the road.

"If young children are not receiving any handwriting training, which is very good brain stimulation, then their brains simply won't reach their full potential," says van der Meer. "It's scary to think of the potential consequences."

Many states are trying to avoid these risks by mandating cursive instruction. This year, California started requiring elementary school students to learn cursive , and similar bills are moving through state legislatures in several states, including Indiana, Kentucky, South Carolina and Wisconsin. (So far, evidence suggests that it's the writing by hand that matters, not whether it's print or cursive.)

Slowing down and processing information

For adults, one of the main benefits of writing by hand is that it simply forces us to slow down.

During a meeting or lecture, it's possible to type what you're hearing verbatim. But often, "you're not actually processing that information — you're just typing in the blind," says van der Meer. "If you take notes by hand, you can't write everything down," she says.

The relative slowness of the medium forces you to process the information, writing key words or phrases and using drawing or arrows to work through ideas, she says. "You make the information your own," she says, which helps it stick in the brain.

Such connections and integration are still possible when typing, but they need to be made more intentionally. And sometimes, efficiency wins out. "When you're writing a long essay, it's obviously much more practical to use a keyboard," says van der Meer.

Still, given our long history of using our hands to mark meaning in the world, some scientists worry about the more diffuse consequences of offloading our thinking to computers.

"We're foisting a lot of our knowledge, extending our cognition, to other devices, so it's only natural that we've started using these other agents to do our writing for us," says Balasubramaniam.

It's possible that this might free up our minds to do other kinds of hard thinking, he says. Or we might be sacrificing a fundamental process that's crucial for the kinds of immersive cognitive experiences that enable us to learn and think at our full potential.

Balasubramaniam stresses, however, that we don't have to ditch digital tools to harness the power of handwriting. So far, research suggests that scribbling with a stylus on a screen activates the same brain pathways as etching ink on paper. It's the movement that counts, he says, not its final form.

Jonathan Lambert is a Washington, D.C.-based freelance journalist who covers science, health and policy.

• handwriting

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Dtsch Arztebl Int
• v.106(15); 2009 Apr

Types of Study in Medical Research

Bernd röhrig.

1 MDK Rheinland-Pfalz, Referat Rehabilitation/Biometrie, Alzey

Jean-Baptist du Prel

2 Zentrum für Präventive Pädiatrie, Zentrum für Kinder- und Jugendmedizin, Mainz

Daniel Wachtlin

3 Interdisziplinäres Zentrum Klinische Studien (IZKS), Fachbereich Medizin der Universität Mainz

Maria Blettner

4 Institut für Medizinische Biometrie, Epidemiologie und Informatik (IMBEI), Johannes Gutenberg Universität Mainz

The choice of study type is an important aspect of the design of medical studies. The study design and consequent study type are major determinants of a study’s scientific quality and clinical value.

This article describes the structured classification of studies into two types, primary and secondary, as well as a further subclassification of studies of primary type. This is done on the basis of a selective literature search concerning study types in medical research, in addition to the authors’ own experience.

Three main areas of medical research can be distinguished by study type: basic (experimental), clinical, and epidemiological research. Furthermore, clinical and epidemiological studies can be further subclassified as either interventional or noninterventional.

Conclusions

The study type that can best answer the particular research question at hand must be determined not only on a purely scientific basis, but also in view of the available financial resources, staffing, and practical feasibility (organization, medical prerequisites, number of patients, etc.).

The quality, reliability and possibility of publishing a study are decisively influenced by the selection of a proper study design. The study type is a component of the study design (see the article "Study Design in Medical Research") and must be specified before the study starts. The study type is determined by the question to be answered and decides how useful a scientific study is and how well it can be interpreted. If the wrong study type has been selected, this cannot be rectified once the study has started.

After an earlier publication dealing with aspects of study design, the present article deals with study types in primary and secondary research. The article focuses on study types in primary research. A special article will be devoted to study types in secondary research, such as meta-analyses and reviews. This article covers the classification of individual study types. The conception, implementation, advantages, disadvantages and possibilities of using the different study types are illustrated by examples. The article is based on a selective literature research on study types in medical research, as well as the authors’ own experience.

Classification of study types

In principle, medical research is classified into primary and secondary research. While secondary research summarizes available studies in the form of reviews and meta-analyses, the actual studies are performed in primary research. Three main areas are distinguished: basic medical research, clinical research, and epidemiological research. In individual cases, it may be difficult to classify individual studies to one of these three main categories or to the subcategories. In the interests of clarity and to avoid excessive length, the authors will dispense with discussing special areas of research, such as health services research, quality assurance, or clinical epidemiology. Figure 1 gives an overview of the different study types in medical research.

Classification of different study types

*1 , sometimes known as experimental research; *2 , analogous term: interventional; *3 , analogous term: noninterventional or nonexperimental

This scheme is intended to classify the study types as clearly as possible. In the interests of clarity, we have excluded clinical epidemiology — a subject which borders on both clinical and epidemiological research ( 3 ). The study types in this area can be found under clinical research and epidemiology.

Basic research

Basic medical research (otherwise known as experimental research) includes animal experiments, cell studies, biochemical, genetic and physiological investigations, and studies on the properties of drugs and materials. In almost all experiments, at least one independent variable is varied and the effects on the dependent variable are investigated. The procedure and the experimental design can be precisely specified and implemented ( 1 ). For example, the population, number of groups, case numbers, treatments and dosages can be exactly specified. It is also important that confounding factors should be specifically controlled or reduced. In experiments, specific hypotheses are investigated and causal statements are made. High internal validity (= unambiguity) is achieved by setting up standardized experimental conditions, with low variability in the units of observation (for example, cells, animals or materials). External validity is a more difficult issue. Laboratory conditions cannot always be directly transferred to normal clinical practice and processes in isolated cells or in animals are not equivalent to those in man (= generalizability) ( 2 ).

Basic research also includes the development and improvement of analytical procedures—such as analytical determination of enzymes, markers or genes—, imaging procedures—such as computed tomography or magnetic resonance imaging—, and gene sequencing—such as the link between eye color and specific gene sequences. The development of biometric procedures—such as statistical test procedures, modeling and statistical evaluation strategies—also belongs here.

Clinical studies

Clinical studies include both interventional (or experimental) studies and noninterventional (or observational) studies. A clinical drug study is an interventional clinical study, defined according to §4 Paragraph 23 of the Medicines Act [Arzneimittelgesetz; AMG] as "any study performed on man with the purpose of studying or demonstrating the clinical or pharmacological effects of drugs, to establish side effects, or to investigate absorption, distribution, metabolism or elimination, with the aim of providing clear evidence of the efficacy or safety of the drug."

Interventional studies also include studies on medical devices and studies in which surgical, physical or psychotherapeutic procedures are examined. In contrast to clinical studies, §4 Paragraph 23 of the AMG describes noninterventional studies as follows: "A noninterventional study is a study in the context of which knowledge from the treatment of persons with drugs in accordance with the instructions for use specified in their registration is analyzed using epidemiological methods. The diagnosis, treatment and monitoring are not performed according to a previously specified study protocol, but exclusively according to medical practice."

The aim of an interventional clinical study is to compare treatment procedures within a patient population, which should exhibit as few as possible internal differences, apart from the treatment ( 4 , e1 ). This is to be achieved by appropriate measures, particularly by random allocation of the patients to the groups, thus avoiding bias in the result. Possible therapies include a drug, an operation, the therapeutic use of a medical device such as a stent, or physiotherapy, acupuncture, psychosocial intervention, rehabilitation measures, training or diet. Vaccine studies also count as interventional studies in Germany and are performed as clinical studies according to the AMG.

Interventional clinical studies are subject to a variety of legal and ethical requirements, including the Medicines Act and the Law on Medical Devices. Studies with medical devices must be registered by the responsible authorities, who must also approve studies with drugs. Drug studies also require a favorable ruling from the responsible ethics committee. A study must be performed in accordance with the binding rules of Good Clinical Practice (GCP) ( 5 , e2 – e4 ). For clinical studies on persons capable of giving consent, it is absolutely essential that the patient should sign a declaration of consent (informed consent) ( e2 ). A control group is included in most clinical studies. This group receives another treatment regimen and/or placebo—a therapy without substantial efficacy. The selection of the control group must not only be ethically defensible, but also be suitable for answering the most important questions in the study ( e5 ).

Clinical studies should ideally include randomization, in which the patients are allocated by chance to the therapy arms. This procedure is performed with random numbers or computer algorithms ( 6 – 8 ). Randomization ensures that the patients will be allocated to the different groups in a balanced manner and that possible confounding factors—such as risk factors, comorbidities and genetic variabilities—will be distributed by chance between the groups (structural equivalence) ( 9 , 10 ). Randomization is intended to maximize homogeneity between the groups and prevent, for example, a specific therapy being reserved for patients with a particularly favorable prognosis (such as young patients in good physical condition) ( 11 ).

Blinding is another suitable method to avoid bias. A distinction is made between single and double blinding. With single blinding, the patient is unaware which treatment he is receiving, while, with double blinding, neither the patient nor the investigator knows which treatment is planned. Blinding the patient and investigator excludes possible subjective (even subconscious) influences on the evaluation of a specific therapy (e.g. drug administration versus placebo). Thus, double blinding ensures that the patient or therapy groups are both handled and observed in the same manner. The highest possible degree of blinding should always be selected. The study statistician should also remain blinded until the details of the evaluation have finally been specified.

A well designed clinical study must also include case number planning. This ensures that the assumed therapeutic effect can be recognized as such, with a previously specified statistical probability (statistical power) ( 4 , 6 , 12 ).

It is important for the performance of a clinical trial that it should be carefully planned and that the exact clinical details and methods should be specified in the study protocol ( 13 ). It is, however, also important that the implementation of the study according to the protocol, as well as data collection, must be monitored. For a first class study, data quality must be ensured by double data entry, programming plausibility tests, and evaluation by a biometrician. International recommendations for the reporting of randomized clinical studies can be found in the CONSORT statement (Consolidated Standards of Reporting Trials, www.consort-statement.org ) ( 14 ). Many journals make this an essential condition for publication.

For all the methodological reasons mentioned above and for ethical reasons, the randomized controlled and blinded clinical trial with case number planning is accepted as the gold standard for testing the efficacy and safety of therapies or drugs ( 4 , e1 , 15 ).

In contrast, noninterventional clinical studies (NIS) are patient-related observational studies, in which patients are given an individually specified therapy. The responsible physician specifies the therapy on the basis of the medical diagnosis and the patient’s wishes. NIS include noninterventional therapeutic studies, prognostic studies, observational drug studies, secondary data analyses, case series and single case analyses ( 13 , 16 ). Similarly to clinical studies, noninterventional therapy studies include comparison between therapies; however, the treatment is exclusively according to the physician’s discretion. The evaluation is often retrospective. Prognostic studies examine the influence of prognostic factors (such as tumor stage, functional state, or body mass index) on the further course of a disease. Diagnostic studies are another class of observational studies, in which either the quality of a diagnostic method is compared to an established method (ideally a gold standard), or an investigator is compared with one or several other investigators (inter-rater comparison) or with himself at different time points (intra-rater comparison) ( e1 ). If an event is very rare (such as a rare disease or an individual course of treatment), a single-case study, or a case series, are possibilities. A case series is a study on a larger patient group with a specific disease. For example, after the discovery of the AIDS virus, the Center for Disease Control (CDC) in the USA collected a case series of 1000 patients, in order to study frequent complications of this infection. The lack of a control group is a disadvantage of case series. For this reason, case series are primarily used for descriptive purposes ( 3 ).

Epidemiological studies

The main point of interest in epidemiological studies is to investigate the distribution and historical changes in the frequency of diseases and the causes for these. Analogously to clinical studies, a distinction is made between experimental and observational epidemiological studies ( 16 , 17 ).

Interventional studies are experimental in character and are further subdivided into field studies (sample from an area, such as a large region or a country) and group studies (sample from a specific group, such as a specific social or ethnic group). One example was the investigation of the iodine supplementation of cooking salt to prevent cretinism in a region with iodine deficiency. On the other hand, many interventions are unsuitable for randomized intervention studies, for ethical, social or political reasons, as the exposure may be harmful to the subjects ( 17 ).

Observational epidemiological studies can be further subdivided into cohort studies (follow-up studies), case control studies, cross-sectional studies (prevalence studies), and ecological studies (correlation studies or studies with aggregated data).

In contrast, studies with only descriptive evaluation are restricted to a simple depiction of the frequency (incidence and prevalence) and distribution of a disease within a population. The objective of the description may also be the regular recording of information (monitoring, surveillance). Registry data are also suited for the description of prevalence and incidence; for example, they are used for national health reports in Germany.

In the simplest case, cohort studies involve the observation of two healthy groups of subjects over time. One group is exposed to a specific substance (for example, workers in a chemical factory) and the other is not exposed. It is recorded prospectively (into the future) how often a specific disease (such as lung cancer) occurs in the two groups ( figure 2a ). The incidence for the occurrence of the disease can be determined for both groups. Moreover, the relative risk (quotient of the incidence rates) is a very important statistical parameter which can be calculated in cohort studies. For rare types of exposure, the general population can be used as controls ( e6 ). All evaluations naturally consider the age and gender distributions in the corresponding cohorts. The objective of cohort studies is to record detailed information on the exposure and on confounding factors, such as the duration of employment, the maximum and the cumulated exposure. One well known cohort study is the British Doctors Study, which prospectively examined the effect of smoking on mortality among British doctors over a period of decades ( e7 ). Cohort studies are well suited for detecting causal connections between exposure and the development of disease. On the other hand, cohort studies often demand a great deal of time, organization, and money. So-called historical cohort studies represent a special case. In this case, all data on exposure and effect (illness) are already available at the start of the study and are analyzed retrospectively. For example, studies of this sort are used to investigate occupational forms of cancer. They are usually cheaper ( 16 ).

Graphical depiction of a prospective cohort study (simplest case [2a]) and a retrospective case control study (2b)

In case control studies, cases are compared with controls. Cases are persons who fall ill from the disease in question. Controls are persons who are not ill, but are otherwise comparable to the cases. A retrospective analysis is performed to establish to what extent persons in the case and control groups were exposed ( figure 2b ). Possible exposure factors include smoking, nutrition and pollutant load. Care should be taken that the intensity and duration of the exposure is analyzed as carefully and in as detailed a manner as possible. If it is observed that ill people are more often exposed than healthy people, it may be concluded that there is a link between the illness and the risk factor. In case control studies, the most important statistical parameter is the odds ratio. Case control studies usually require less time and fewer resources than cohort studies ( 16 ). The disadvantage of case control studies is that the incidence rate (rate of new cases) cannot be calculated. There is also a great risk of bias from the selection of the study population ("selection bias") and from faulty recall ("recall bias") (see too the article "Avoiding Bias in Observational Studies"). Table 1 presents an overview of possible types of epidemiological study ( e8 ). Table 2 summarizes the advantages and disadvantages of observational studies ( 16 ).

1 = slight; 2 = moderate; 3 = high; N/A, not applicable.

*Individual cases may deviate from this pattern.

Selecting the correct study type is an important aspect of study design (see "Study Design in Medical Research" in volume 11/2009). However, the scientific questions can only be correctly answered if the study is planned and performed at a qualitatively high level ( e9 ). It is very important to consider or even eliminate possible interfering factors (or confounders), as otherwise the result cannot be adequately interpreted. Confounders are characteristics which influence the target parameters. Although this influence is not of primary interest, it can interfere with the connection between the target parameter and the factors that are of interest. The influence of confounders can be minimized or eliminated by standardizing the procedure, stratification ( 18 ), or adjustment ( 19 ).

The decision as to which study type is suitable to answer a specific primary research question must be based not only on scientific considerations, but also on issues related to resources (personnel and finances), hospital capacity, and practicability. Many epidemiological studies can only be implemented if there is access to registry data. The demands for planning, implementation, and statistical evaluation for observational studies should be just as high for observational studies as for experimental studies. There are particularly strict requirements, with legally based regulations (such as the Medicines Act and Good Clinical Practice), for the planning, implementation, and evaluation of clinical studies. A study protocol must be prepared for both interventional and noninterventional studies ( 6 , 13 ). The study protocol must contain information on the conditions, question to be answered (objective), the methods of measurement, the implementation, organization, study population, data management, case number planning, the biometric evaluation, and the clinical relevance of the question to be answered ( 13 ).

Important and justified ethical considerations may restrict studies with optimal scientific and statistical features. A randomized intervention study under strictly controlled conditions of the effect of exposure to harmful factors (such as smoking, radiation, or a fatty diet) is not possible and not permissible for ethical reasons. Observational studies are a possible alternative to interventional studies, even though observational studies are less reliable and less easy to control ( 17 ).

A medical study should always be published in a peer reviewed journal. Depending on the study type, there are recommendations and checklists for presenting the results. For example, these may include a description of the population, the procedure for missing values and confounders, and information on statistical parameters. Recommendations and guidelines are available for clinical studies ( 14 , 20 , e10 , e11 ), for diagnostic studies ( 21 , 22 , e12 ), and for epidemiological studies ( 23 , e13 ). Since 2004, the WHO has demanded that studies should be registered in a public registry, such as www.controlled-trials.com or www.clinicaltrials.gov . This demand is supported by the International Committee of Medical Journal Editors (ICMJE) ( 24 ), which specifies that the registration of the study before inclusion of the first subject is an essential condition for the publication of the study results ( e14 ).

When specifying the study type and study design for medical studies, it is essential to collaborate with an experienced biometrician. The quality and reliability of the study can be decisively improved if all important details are planned together ( 12 , 25 ).

Acknowledgments

Translated from the original German by Rodney A. Yeates, M.A., Ph.D.

Conflict of interest statement

The authors declare that there is no conflict of interest in the sense of the International Committee of Medical Journal Editors.

• U.S. Department of Health & Human Services

• Virtual Tour
• Staff Directory
• En Español

You are here

Nih research matters.

May 14, 2024

Understanding how exercise affects the body

At a glance.

• A study of endurance training in rats found molecular changes throughout the body that could help explain the beneficial effects of exercise on health.
• Large differences were seen between male and female rats, highlighting the need to include both women and men in exercise studies.

Exercise is one of the most beneficial activities that people can engage in. Regular exercise reduces the risk of heart disease, diabetes, cancer, and other health problems. It can even help people with many mental health conditions feel better.

But exactly how exercise exerts its positive effects hasn’t been well understood. And different people’s bodies can respond very differently to certain types of exercise, such as aerobic exercise or strength training.

Understanding how exercise impacts different organs at the molecular level could help health care providers better personalize exercise recommendations. It might also lead to drug therapies that could stimulate some of the beneficial effects of a workout for people who are physically unable to exercise.

To this end, researchers in the large, NIH-funded Molecular Transducers of Physical Activity Consortium (MoTrPAC) have been studying how endurance exercise and strength training affect both people and animals. The team is examining gene activity, protein alterations, immune cell function, metabolite levels, and numerous other measures of cell and tissue function. The first results, from rat studies of endurance exercise, were published on May 2, 2024, in Nature and several related journals.

Both male and female rats underwent progressive exercise training on a treadmill over an 8-week period. By the end of training, male rats had increased their aerobic capacity by 18%, and females by 16%. Tissue samples were collected from 18 different organs, plus the blood, during the training period and two days after the final bout of exercise. This let the researchers study the longer-term adaptations of the body to exercise.

Changes in gene activity, immune cell function, metabolism, and other cellular processes were seen in all the tissues studied, including those not previously known to be affected by exercise. The types of changes differed from tissue to tissue.

Many of the observed changes hinted at how exercise might protect certain organs against disease. For example, in the small intestines, exercise decreased the activity of certain genes associated with inflammatory bowel disease and reduced signs of inflammation in the gut. In the liver, exercise boosted molecular changes associated with improved tissue health and regeneration.

Some of the effects differed substantially between male and female rats. For example, in male rats, the eight weeks of endurance training reduced the amount of a type of body fat called subcutaneous white adipose tissue (scWAT). The same amount of exercise didn’t reduce the amount of scWAT in female rats. Instead, endurance exercise caused scWAT in female rats to alter its energy usage in ways that are beneficial to health. These and other results highlight the importance of including both women and men in exercise studies.

The researchers also compared gene activity changes in the rat studies with those from human samples taken from previous studies and found substantial overlap. They identified thousands of genes tied to human disease that were affected by endurance exercise. These analyses show how the MoTrPAC results from rats can be used to help guide future research in people.

“This is the first whole-organism map looking at the effects of training in multiple different organs,” says Dr. Steve Carr, a MoTrPAC investigator from the Broad Institute. “The resource produced will be enormously valuable, and has already produced many potentially novel biological insights for further exploration.”

Human trials are expected in the next few years. Information on participating can be found here .

—by Sharon Reynolds

Related Links

• Gut Microbes May Affect Motivation to Exercise
• Exercise-Induced Molecule Reduces Obesity in Mice
• Testing Ways to Encourage Exercise
• Hormone Links Exercise with Cognitive Benefits
• Exercise-Induced Protein May Reverse Age-Related Cognitive Decline
• Getting Active Later in Life Brings Benefits
• Get Active Together: Social Support Can Help Keep You Moving
• Personalized Exercise? How Biology Influences Fitness
• Maintain Your Muscle: Strength Training at Any Age
• Molecular Transducers of Physical Activity Consortium (MoTrPAC)
• Participating in MoTrPAC

References:  Temporal dynamics of the multi-omic response to endurance exercise training. MoTrPAC Study Group; Lead Analysts; MoTrPAC Study Group. Nature . 2024 May;629(8010):174-183. doi: 10.1038/s41586-023-06877-w. Epub 2024 May 1. PMID: 38693412. Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue. Many GM, Sanford JA, Sagendorf TJ, Hou Z, Nigro P, Whytock KL, Amar D, Caputo T, Gay NR, Gaul DA, Hirshman MF, Jimenez-Morales D, Lindholm ME, Muehlbauer MJ, Vamvini M, Bergman BC, Fernández FM, Goodyear LJ, Hevener AL, Ortlund EA, Sparks LM, Xia A, Adkins JN, Bodine SC, Newgard CB, Schenk S; MoTrPAC Study Group. Nat Metab . 2024 May 1. doi: 10.1038/s42255-023-00959-9. Online ahead of print. PMID: 38693320. The impact of exercise on gene regulation in association with complex trait genetics. Vetr NG, Gay NR; MoTrPAC Study Group; Montgomery SB. Nat Commun . 2024 May 1;15(1):3346. doi: 10.1038/s41467-024-45966-w. PMID: 38693125.

Funding:  NIH’s Office of the Director (OD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute on Aging (NIA), National Human Genome Research Institute (NHGRI), National Heart, Lung, and Blood Institute (NHLBI), and National Library of Medicine (NLM); Knut and Alice Wallenberg Foundation; National Science Foundation (NSF).

Connect with Us

• More Social Media from NIH

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Published: 08 May 2024

Accurate structure prediction of biomolecular interactions with AlphaFold 3

• Josh Abramson   ORCID: orcid.org/0009-0000-3496-6952 1   na1 ,
• Jonas Adler   ORCID: orcid.org/0000-0001-9928-3407 1   na1 ,
• Jack Dunger 1   na1 ,
• Richard Evans   ORCID: orcid.org/0000-0003-4675-8469 1   na1 ,
• Tim Green   ORCID: orcid.org/0000-0002-3227-1505 1   na1 ,
• Alexander Pritzel   ORCID: orcid.org/0000-0002-4233-9040 1   na1 ,
• Olaf Ronneberger   ORCID: orcid.org/0000-0002-4266-1515 1   na1 ,
• Lindsay Willmore   ORCID: orcid.org/0000-0003-4314-0778 1   na1 ,
• Andrew J. Ballard   ORCID: orcid.org/0000-0003-4956-5304 1 ,
• Joshua Bambrick   ORCID: orcid.org/0009-0003-3908-0722 2 ,
• Sebastian W. Bodenstein 1 ,
• David A. Evans 1 ,
• Chia-Chun Hung   ORCID: orcid.org/0000-0002-5264-9165 2 ,
• Michael O’Neill 1 ,
• David Reiman   ORCID: orcid.org/0000-0002-1605-7197 1 ,
• Kathryn Tunyasuvunakool   ORCID: orcid.org/0000-0002-8594-1074 1 ,
• Zachary Wu   ORCID: orcid.org/0000-0003-2429-9812 1 ,
• Akvilė Žemgulytė 1 ,
• Eirini Arvaniti 3 ,
• Charles Beattie   ORCID: orcid.org/0000-0003-1840-054X 3 ,
• Ottavia Bertolli   ORCID: orcid.org/0000-0001-8578-3216 3 ,
• Alex Bridgland 3 ,
• Alexey Cherepanov   ORCID: orcid.org/0000-0002-5227-0622 4 ,
• Miles Congreve 4 ,
• Alexander I. Cowen-Rivers 3 ,
• Andrew Cowie   ORCID: orcid.org/0000-0002-4491-1434 3 ,
• Michael Figurnov   ORCID: orcid.org/0000-0003-1386-8741 3 ,
• Fabian B. Fuchs 3 ,
• Hannah Gladman 3 ,
• Rishub Jain 3 ,
• Yousuf A. Khan   ORCID: orcid.org/0000-0003-0201-2796 3 ,
• Caroline M. R. Low 4 ,
• Kuba Perlin 3 ,
• Anna Potapenko 3 ,
• Pascal Savy 4 ,
• Sukhdeep Singh 3 ,
• Adrian Stecula   ORCID: orcid.org/0000-0001-6914-6743 4 ,
• Ashok Thillaisundaram 3 ,
• Catherine Tong   ORCID: orcid.org/0000-0001-7570-4801 4 ,
• Sergei Yakneen   ORCID: orcid.org/0000-0001-7827-9839 4 ,
• Ellen D. Zhong   ORCID: orcid.org/0000-0001-6345-1907 3 ,
• Michal Zielinski 3 ,
• Augustin Žídek   ORCID: orcid.org/0000-0002-0748-9684 3 ,
• Victor Bapst 1   na2 ,
• Pushmeet Kohli   ORCID: orcid.org/0000-0002-7466-7997 1   na2 ,
• Max Jaderberg   ORCID: orcid.org/0000-0002-9033-2695 2   na2 ,
• Demis Hassabis   ORCID: orcid.org/0000-0003-2812-9917 1 , 2   na2 &
• John M. Jumper   ORCID: orcid.org/0000-0001-6169-6580 1   na2  

Nature ( 2024 ) Cite this article

215k Accesses

1 Citations

1150 Altmetric

Metrics details

We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

• Drug discovery
• Machine learning
• Protein structure predictions
• Structural biology

The introduction of AlphaFold 2 1 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design 2–6 . In this paper, we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture, which is capable of joint structure prediction of complexes including proteins, nucleic acids, small molecules, ions, and modified residues. The new AlphaFold model demonstrates significantly improved accuracy over many previous specialised tools: far greater accuracy on protein-ligand interactions than state of the art docking tools, much higher accuracy on protein-nucleic acid interactions than nucleic-acid-specific predictors, and significantly higher antibody-antigen prediction accuracy than AlphaFold-Multimer v2.3 7,8 . Together these results show that high accuracy modelling across biomolecular space is possible within a single unified deep learning framework.

You have full access to this article via your institution.

Similar content being viewed by others

Highly accurate protein structure prediction with AlphaFold

De novo generation of multi-target compounds using deep generative chemistry

Augmenting large language models with chemistry tools

Author information.

These authors contributed equally: Josh Abramson, Jonas Adler, Jack Dunger, Richard Evans, Tim Green, Alexander Pritzel, Olaf Ronneberger, Lindsay Willmore

These authors jointly supervised this work: Victor Bapst, Pushmeet Kohli, Max Jaderberg, Demis Hassabis, John M. Jumper

Authors and Affiliations

Core Contributor, Google DeepMind, London, UK

Josh Abramson, Jonas Adler, Jack Dunger, Richard Evans, Tim Green, Alexander Pritzel, Olaf Ronneberger, Lindsay Willmore, Andrew J. Ballard, Sebastian W. Bodenstein, David A. Evans, Michael O’Neill, David Reiman, Kathryn Tunyasuvunakool, Zachary Wu, Akvilė Žemgulytė, Victor Bapst, Pushmeet Kohli, Demis Hassabis & John M. Jumper

Core Contributor, Isomorphic Labs, London, UK

Joshua Bambrick, Chia-Chun Hung, Max Jaderberg & Demis Hassabis

Google DeepMind, London, UK

Eirini Arvaniti, Charles Beattie, Ottavia Bertolli, Alex Bridgland, Alexander I. Cowen-Rivers, Andrew Cowie, Michael Figurnov, Fabian B. Fuchs, Hannah Gladman, Rishub Jain, Yousuf A. Khan, Kuba Perlin, Anna Potapenko, Sukhdeep Singh, Ashok Thillaisundaram, Ellen D. Zhong, Michal Zielinski & Augustin Žídek

Isomorphic Labs, London, UK

Alexey Cherepanov, Miles Congreve, Caroline M. R. Low, Pascal Savy, Adrian Stecula, Catherine Tong & Sergei Yakneen

You can also search for this author in PubMed   Google Scholar

Corresponding authors

Correspondence to Max Jaderberg , Demis Hassabis or John M. Jumper .

Supplementary information

Supplementary information.

This Supplementary Information file contains the following 9 sections: (1) Notation; (2) Data pipeline; (3) Model architecture; (4) Auxiliary heads; (5) Training and inference; (6) Evaluation; (7) Differences to AlphaFold2 and AlphaFold-Multimer; (8) Supplemental Results; and (9) Appendix: CCD Code and PDB ID tables.

Reporting Summary

Rights and permissions.

Reprints and permissions

About this article

Cite this article.

Abramson, J., Adler, J., Dunger, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature (2024). https://doi.org/10.1038/s41586-024-07487-w

Download citation

Received : 19 December 2023

Accepted : 29 April 2024

Published : 08 May 2024

DOI : https://doi.org/10.1038/s41586-024-07487-w

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

This article is cited by

Major alphafold upgrade offers boost for drug discovery.

• Ewen Callaway

Nature (2024)

By submitting a comment you agree to abide by our Terms and Community Guidelines . If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

More From Forbes

Exercise changes perception of time, says new study.

• Share to Facebook
• Share to Twitter
• Share to Linkedin

According to a new study, the perception of time slowed down while people were exercising.

Exercise has long been touted for both its physical and mental health benefits, but recent research adds an intriguing twist to the understanding of its effects, indicating it can also alter the perception of time.

The study, published in the journal Brain and Behavior and led by researchers from the U.K. and The Netherlands indicates that time seems to slow down when people engage in physical activity.

The study involved 33 active adults who participated in controlled experiments where they cycled in virtual environments for 4 kilometres at a time. These environments were designed to be both engaging and challenging, including the presence of virtual competitors to test if social dynamics could influence time perception. The participants then completed time perception tasks at three different intervals: before, during, and after their exercise sessions.

The findings revealed a significant distortion in the participants' perception of time during exercise. Specifically, time appeared to stretch, making periods of physical activity feel longer than they actually were. This phenomenon was consistent regardless of the presence of virtual competitors, indicating that the act of exercising itself, rather than whether other individuals were preset, was responsible for this time-warping effect.

"Our findings have important implications for healthy exercise choices, enjoyment levels and also for how we use this information to optimise performance,” said Professor Andrew Edwards, co-lead author of the work from Canterbury Christ Church University in Kent, U.K. in a press release .

Fallout Dethroned In Amazon Prime Video s Top 10 List By A New Offering

Google chrome gets second emergency update in a week as new exploit confirmed, metallica makes history with their new no 1 single.

The paper suggests that if time perception can be manipulated to make workouts feel less burdensome or lengthy, more people could be encouraged to engage in regular physical activity, improving overall health and fitness levels. For example, shorter, high-intensity workouts that feel longer could be integrated into fitness regimes, providing the benefits of extended exercise sessions without the associated time commitment. The researchers also suggest that understanding how time perception changes during exercise could help in developing new strategies to make physical activity more enjoyable, potentially increasing adherence to exercise routines.

"The main strands of the work are to see how we can motivate people to engage with exercise, avoid/mitigate negative associations with time appearing to move slowly and perhaps see if we can use this apparent slowing of time to our advantage," said Edwards.

However, the researchers are keen to point out the limitations of the study, including that the participants in the study were all quite fit and exercised regularly to start with, so they can't say whether the results would be similar for people who are less fit and don't partake in regular exercise.

"It's still unclear whether the results are generalizable. The sample size of 33 people offer an intriguing first glimpse into how our perception of time can be warped — and perhaps a clue as to how to take things to the next level while exercising,” said Edwards.

The research team plans to expand their studies to include a more diverse range of participants, exploring how different demographics and fitness levels experience time distortion during exercise. They are also planning to investigate how various types of physical activity, beyond cycling, impact time perception and how their findings can be applied to specific populations, such as athletes seeking to optimize their training or individuals undergoing rehabilitation who might benefit from more engaging exercise experiences.

• Editorial Standards
• Reprints & Permissions

Join The Conversation

One Community. Many Voices. Create a free account to share your thoughts. 

Forbes Community Guidelines

Our community is about connecting people through open and thoughtful conversations. We want our readers to share their views and exchange ideas and facts in a safe space.

In order to do so, please follow the posting rules in our site's  Terms of Service.   We've summarized some of those key rules below. Simply put, keep it civil.

Your post will be rejected if we notice that it seems to contain:

• False or intentionally out-of-context or misleading information
• Insults, profanity, incoherent, obscene or inflammatory language or threats of any kind
• Attacks on the identity of other commenters or the article's author
• Content that otherwise violates our site's  terms.

User accounts will be blocked if we notice or believe that users are engaged in:

• Continuous attempts to re-post comments that have been previously moderated/rejected
• Racist, sexist, homophobic or other discriminatory comments
• Attempts or tactics that put the site security at risk
• Actions that otherwise violate our site's  terms.

So, how can you be a power user?

• Stay on topic and share your insights
• Feel free to be clear and thoughtful to get your point across
• ‘Like’ or ‘Dislike’ to show your point of view.
• Protect your community.
• Use the report tool to alert us when someone breaks the rules.

Thanks for reading our community guidelines. Please read the full list of posting rules found in our site's  Terms of Service.

• Download PDF
• Share X Facebook Email LinkedIn
• Permissions

Mortality in Patients Hospitalized for COVID-19 vs Influenza in Fall-Winter 2023-2024

• 1 Clinical Epidemiology Center, VA St Louis Health Care System, St Louis, Missouri

In the first year of the COVID-19 pandemic, risk of death in people hospitalized for COVID-19 was substantially higher than in people hospitalized for seasonal influenza. 1 , 2 The risk of death due to COVID-19 has since declined. In fall-winter 2022-2023, people hospitalized for COVID-19 had a 60% higher risk of death compared with those hospitalized for seasonal influenza. 3 New variants of SARS-CoV-2 have continued to appear, including the emergence of JN.1, the predominant variant in the US since December 24, 2023. 4 This study evaluated the risk of death in a cohort of people hospitalized for COVID-19 or seasonal influenza in fall-winter 2023-2024.

Read More About

Xie Y , Choi T , Al-Aly Z. Mortality in Patients Hospitalized for COVID-19 vs Influenza in Fall-Winter 2023-2024. JAMA. Published online May 15, 2024. doi:10.1001/jama.2024.7395

Manage citations:

© 2024

Artificial Intelligence Resource Center

Cardiology in JAMA : Read the Latest

Browse and subscribe to JAMA Network podcasts!

Others Also Liked

Select your interests.

Customize your JAMA Network experience by selecting one or more topics from the list below.

• Academic Medicine
• Acid Base, Electrolytes, Fluids
• Allergy and Clinical Immunology
• American Indian or Alaska Natives
• Anesthesiology
• Anticoagulation
• Art and Images in Psychiatry
• Artificial Intelligence
• Assisted Reproduction
• Bleeding and Transfusion
• Caring for the Critically Ill Patient
• Challenges in Clinical Electrocardiography
• Climate and Health
• Climate Change
• Clinical Challenge
• Clinical Decision Support
• Clinical Implications of Basic Neuroscience
• Clinical Pharmacy and Pharmacology
• Complementary and Alternative Medicine
• Consensus Statements
• Coronavirus (COVID-19)
• Critical Care Medicine
• Cultural Competency
• Dental Medicine
• Dermatology
• Diabetes and Endocrinology
• Diagnostic Test Interpretation
• Drug Development
• Electronic Health Records
• Emergency Medicine
• End of Life, Hospice, Palliative Care
• Environmental Health
• Equity, Diversity, and Inclusion
• Facial Plastic Surgery
• Gastroenterology and Hepatology
• Genetics and Genomics
• Genomics and Precision Health
• Global Health
• Guide to Statistics and Methods
• Hair Disorders
• Health Care Delivery Models
• Health Care Economics, Insurance, Payment
• Health Care Quality
• Health Care Reform
• Health Care Safety
• Health Care Workforce
• Health Disparities
• Health Inequities
• Health Policy
• Health Systems Science
• History of Medicine
• Hypertension
• Images in Neurology
• Implementation Science
• Infectious Diseases
• Innovations in Health Care Delivery
• JAMA Infographic
• Law and Medicine
• Leading Change
• Less is More
• LGBTQIA Medicine
• Lifestyle Behaviors
• Medical Coding
• Medical Devices and Equipment
• Medical Education
• Medical Education and Training
• Medical Journals and Publishing
• Mobile Health and Telemedicine
• Narrative Medicine
• Neuroscience and Psychiatry
• Notable Notes
• Nutrition, Obesity, Exercise
• Obstetrics and Gynecology
• Occupational Health
• Ophthalmology
• Orthopedics
• Otolaryngology
• Pain Medicine
• Palliative Care
• Pathology and Laboratory Medicine
• Patient Care
• Patient Information
• Performance Improvement
• Performance Measures
• Perioperative Care and Consultation
• Pharmacoeconomics
• Pharmacoepidemiology
• Pharmacogenetics
• Pharmacy and Clinical Pharmacology
• Physical Medicine and Rehabilitation
• Physical Therapy
• Physician Leadership
• Population Health
• Primary Care
• Professional Well-being
• Professionalism
• Psychiatry and Behavioral Health
• Public Health
• Pulmonary Medicine
• Regulatory Agencies
• Reproductive Health
• Research, Methods, Statistics
• Resuscitation
• Rheumatology
• Risk Management
• Scientific Discovery and the Future of Medicine
• Shared Decision Making and Communication
• Sleep Medicine
• Sports Medicine
• Stem Cell Transplantation
• Substance Use and Addiction Medicine
• Surgical Innovation
• Surgical Pearls
• Teachable Moment
• Technology and Finance
• The Art of JAMA
• The Arts and Medicine
• The Rational Clinical Examination
• Tobacco and e-Cigarettes
• Translational Medicine
• Trauma and Injury
• Treatment Adherence
• Ultrasonography
• Users' Guide to the Medical Literature
• Vaccination
• Venous Thromboembolism
• Veterans Health
• Women's Health
• Workflow and Process
• Wound Care, Infection, Healing
• Register for email alerts with links to free full-text articles
• Access PDFs of free articles
• Manage your interests
• Save searches and receive search alerts

Pro-Palestinian posts significantly outnumbered pro-Israeli posts on TikTok, new Northeastern research shows

• Search Search

The pattern of pro-Palesitinian posts is consistent with a prolonged social movement, the research suggests, while the pattern of pro-Israeli posts is typical of what follows a major news event.

• Copy Link Link Copied!

With millions of users across the globe, including the Middle East, TikTok has become a popular source of information and commentary on the Israel-Hamas war.

But pro-Palestinian posts to the social media app significantly outnumber pro-Israeli posts and follow a very different pattern, new research from Northeastern University reveals.

The pattern of pro-Palestinian posts is consistent with a prolonged social movement, the research suggests, while the pattern of pro-Israeli posts is typical of what follows a major news event.

The number of pro-Israeli content posted to TikTok has steadily declined since Hamas’ Oct. 7 attack on Israel, the research shows.

“There’s a lot of posting activity initially, and then there’s a gradual decline over time,” says Laura Edelson, an assistant professor at Northeastern’s Khoury College of Computer Sciences.

Northeastern Global News, in your inbox.

Sign up for NGN’s daily newsletter for news, discovery and analysis from around the world.

The opposite has happened with pro-Palestinian content.

“What we see with pro-Palestine posting activity — it grows organically over time, it culminates and then it has a symmetric decline,” says Edelson, a computer scientist who studies large online platforms. “That’s the kind of pattern that is more commonly associated with social movements.”

Edelson was granted access to the TikTok Research API , which allows independent and academic researchers who work for nonprofit institutions to access certain data to support their work. 

She collected data on more than 280,000 TikTok posts from the United States that had specific hashtags related to the Israel-Hamas war. Examples include political statements such as #IStandWithIsrael or #SavePalestine, as well as more general apolitical tags like #Gaza or #Israel.

The data was gathered from 12 three-day windows — beginning Oct. 7 to Oct. 9, 2023, and ending Jan. 26 to Jan. 29, 2024. 

Edelson examined the data in three major ways.

First was the number of posts. There were 170,430 pro-Palestinian posts, 8,843 pro-Israeli posts and 101,706 neutral or general posts.

Edelson also looked at the posts’ page views — there were 236 million views for pro-Palestinian posts, 14 million for pro-Israeli posts and 492 million views for neutral or general posts.

Finally, Edelson compared whether the number of posts and the post views were proportionate — this enabled Edelson to conclude whether TikTok was amplifying certain types of posts.

“It’s not enough to look at content,” Edelson says. “Big differences in how people experience content come from differences in amplification too.”

Content was amplified on both sides, the research suggests.

“There’s periods of time when TikTok is disproportionately amplifying pro-Palestine content, and there’s times when it’s disproportionately amplifying pro-Israel content,” Edelson says. “When you sum up everything over the entire study period, they amplify those two things equally, but it changes over time, initially.”

Featured Stories

Researchers are translating ‘whale-speak’ — accents included — and this Northeastern network scientist is leading the way

This former cheerleader is aiming to be a ‘world-class star’ in hammer throw

‘Challengers’ is where tennis meets love. But what happens in real life if you date someone in your field?

What are vampire facials? Do they work? And what went wrong in the procedures linked to HIV?

Edelson thus divides the data into three “phases.” In the first phase, the 3½ weeks following the Oct. 7 Hamas attack, neutral or general content is both most posted and most seen. 

Edelson says the high number of general posts and views per general post is “fairly similar” to what happens on the platform following any major news event. She notes that TikTok is unique among social media platforms. Rather than amplifying the most extreme voices, it is “majoritarian,” she says.

“TikTok wants to find the most popular thing and then show that most popular thing as widely as possible,” Edelson says.

She also notes that neutral or general content is predominantly higher in quality — in terms of production value — which means it is more likely to be amplified by TikTok. 

Pro-Israeli content follows the same pattern as general news: it is highest in this phase as well, but it steadily declines after the first week.

Pro-Palestinian content, on the other hand, jumps significantly in the second week and continues to grow steadily.

But things begin to change on Oct. 27 when the number page views on pro-Israel posts skyrockets — 2,555 views per post compared to 336 views per post previously.

Edelson says she doesn’t know why this occurred. But it lasts through the return of some Israeli hostages during a ceasefire that began Nov. 24 and into the first half of December.

The final phase begins on Dec. 15 when views per post for all categories fall dramatically.

“Interest in topics declines over time, that’s very normal,” Edelson says. “But the speed of the fall off is striking and not well explained by other events.”

Recent Stories

Myocardial work in chronic kidney disease: insights from the CPH-CKD ECHO Study

• Original Paper
• Open access
• Published: 15 May 2024

Cite this article

You have full access to this open access article

• Flemming Javier Olsen   ORCID: orcid.org/0000-0001-9511-8375 1 , 2 ,
• Nino Emanuel Landler 1 , 2 ,
• Jacob Christensen 1 , 2 ,
• Bo Feldt-Rasmussen 3 , 4 ,
• Ditte Hansen 4 , 5 ,
• Christina Christoffersen 2 , 6 ,
• Ellen Linnea Freese Ballegaard 3 , 4 ,
• Ida Maria Hjelm Sørensen 3 ,
• Sasha Saurbrey Bjergfelt 2 , 3 ,
• Eline Seidelin 5 ,
• Susanne Bro 3 &
• Tor Biering-Sørensen 1 , 2 , 7 , 8  

Myocardial work is a novel echocardiographic measure that offers detailed insights into cardiac mechanics. We sought to characterize cardiac function by myocardial work in patients with chronic kidney disease (CKD).

We prospectively enrolled 757 patients with non-dialysis-dependent CKD and 174 age- and sex-matched controls. Echocardiographic pressure-strain loop analysis was performed to acquire the global work index (GWI). Linear regressions were performed to investigate the association between estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) to GWI.

Patients with CKD had a mean age of 57 years, 61% were men, and median eGFR was 42 mL/min/1.73 m 2 . Overall, no difference in GWI was observed between patients and controls (1879 vs. 1943 mmHg%, p  = 0.06). However, a stepwise decline in GWI was observed for controls vs. patients with CKD without left ventricular hypertrophy vs. patients with CKD and left ventricular hypertrophy (GWI, 1943 vs. 1887 vs. 1789 mmHg%; p for trend = 0.030). In patients with CKD, eGFR was not associated with GWI by linear regression. However, diabetes modified this association ( p for interaction = 0.007), such that per 10 mL/min/1.73 m 2 decrease in eGFR, GWI decreased by 22 (9–35) mmHg% ( p  = 0.001) after multivariable adjustments in patients without diabetes, but with no association between eGFR and GWI in patients with diabetes. No association was observed between UACR and GWI.

Patients with CKD and left ventricular hypertrophy exhibited lower myocardial work compared to matched controls. Furthermore, decreasing eGFR was associated with decreasing myocardial work only in patients without diabetes. No association to UACR was observed.

Graphical Abstract

Avoid common mistakes on your manuscript.

Introduction

Chronic kidney disease (CKD) is increasing worldwide, with an estimated prevalence of 13% [ 1 , 2 ]. Patients with CKD face an elevated risk of heart failure (HF) and those who develop HF have a high risk of HF readmissions, CKD progression, and all-cause death [ 3 , 4 , 5 ]. This emphasizes the importance of timely recognition of patients at risk of HF who may benefit from close monitoring to guide preventive measures. Transthoracic echocardiography could be valuable in this regard as it is a cost-effective, harmless, and readily available tool in the clinic. Although cardiac abnormalities are frequently observed with echocardiography in patients with CKD, systolic dysfunction is overall not a common finding with quite diverging prevalence estimates of 2–18% [ 6 , 7 , 8 ].

This may reflect that systolic dysfunction has conventionally been defined from the left ventricular ejection fraction (LVEF), which has several technical limitations [ 9 ]. Consequently, novel techniques have been developed to provide a more detailed evaluation of systolic function. One such technique contemplates the use of pressure-strain loop analyses as a non-invasive method to estimate myocardial work [ 10 ]. This method provides a direct assessment of myocardial tissue function in a highly reproducible manner while also taking afterload into consideration, thus potentially superior to global longitudinal strain (GLS) [ 11 ]. This method may therefore provide a more nuanced characterization of myocardial contraction in patients with CKD as a means to identify patients at risk of HF. Consequently, in this study, we sought to provide a detailed characterization of systolic function. We hypothesized that patients with CKD exhibited more abnormal myocardial work compared to controls and that myocardial work measures worsened with decreasing renal function.

We performed a cross-sectional analysis based on participants who were prospectively enrolled in the Copenhagen Chronic Kidney Disease Echocardiographic (CPH-CKD ECHO) Study. The study has previously been described in detail [ 12 , 13 ]. Briefly, the CPH-CKD ECHO Study was a dual-centre study that comprised patients with non-dialysis-dependent CKD ( n , 825) and age- and sex-matched control individuals ( n , 175). Patients with CKD were enrolled from the outpatient clinic at the Departments of Nephrology at Rigshospitalet and Herlev-Gentofte Hospital in Denmark. Controls were recruited through posts in local newspapers and on a Danish website (forsoegsperson.dk) dedicated to highlighting ongoing research studies seeking voluntary individuals. The inclusion phase ran from October 2015 through October 2018. Inclusion criteria were known CKD and age between 30 and 75 years. CKD was defined as either kidney injury (albuminuria, renal cyst, or other structural abnormalities in the kidneys) or an eGFR < 60 mL/min/1.73 m 2 lasting more than 3 months [ 14 ]. Exclusion criteria were as follows: kidney transplantation with a functioning graft, pregnancy, intellectual disability, dementia or psychosis, active malignancy, and retraction of informed consent.

The controls were not allowed to have known cardiovascular disease, kidney disease, malignant disease, or chronic disease, apart from mild hypertension, thyroid disease, mild depression, or hypercholesterolemia. Subjects were excluded if they had kidney damage or an eGFR < 60 mL/min/1.73 m 2 .

The total study population thus included 1000 individuals. Of these, 9 were excluded because they had aortic valve stenosis since the myocardial work analysis assumes that there is no obstruction between the left ventricle and the aorta [ 10 ]. In addition, 5 were excluded because they had severe aortic regurgitation since myocardial work analysis assumes negligible diastolic pressures, which is not the case with severe aortic regurgitation [ 10 ]. Finally, 55 were excluded because the myocardial work analysis was not technically feasible, leaving 931 for final analysis (757 patients with CKD and 174 controls).

The study was approved by the regional scientific ethics committee (ID: H-3–2011-069) and the Danish Data Protection Agency (ID: 30–0840). Informed consent was obtained from all participants, and the study adhered to the 2 nd Helsinki Declaration.

Clinical characteristics

Data on medical history and clinical characteristics were collected at an outpatient baseline visit upon inclusion. Medical history was obtained by interview and review of hospital medical records. A physical examination was performed to measure anthropometrics, heart rate, and brachial artery blood pressure. Hypertension was defined as a systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg, or the use of antihypertensive medication. Urinary samples were collected to determine the degree of albuminuria (urine albumin-creatinine ratio, UACR). Details on UACR were available in 733/757 patients. Venous blood samples were drawn to acquire plasma creatinine level and for storage in a biobank. A 12-lead electrocardiogram was also performed at the visit.

eGFR was calculated from plasma creatinine level with the CKD-EPI formula [ 15 ]. The patients were grouped into eGFR categories in accordance with the 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines [ 14 ]. In line with our previous publications, we also collated patients into three eGFR groups as follows: G1 + G2 (eGFR ≥ 60 mL/min/1.73 m 2 ), G3 (eGFR 30–59 mL/min/1.73 m 2 ), and G4 + G5 (eGFR ≤ 29 mL/min/1.73 m 2 ) [ 13 ].

Albuminuria was characterized as follows: normoalbuminuria with UACR < 30 mg/g, microalbuminuria with UACR of 30–300 mg/g, and macroalbuminuria with UACR > 300 mg/g.

Standard echocardiography

All echocardiographic examinations were performed using a GE Vivid E9 ultrasound machine according to a dedicated protocol. All images were acquired over three consecutive cycles. For individuals in sinus rhythm, measurements were performed in a single cardiac cycle — the one with the most optimal image quality — whereas all measurements were performed in three cardiac cycles for patients who had atrial fibrillation during the examination. All standard measures were performed with commercially available post-processing software (EchoPAC BT 203, GE Healthcare) by a single experienced investigator blinded to clinical information according to the 2015 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) guidelines [ 16 ]. The analysis process has been described meticulously elsewhere [ 13 ].

Valve disease was quantified according to the most recent guidelines [ 17 , 18 ]. Significant valve disease was defined as either moderate aortic valve regurgitation, moderate or severe mitral regurgitation, or moderate or severe mitral stenosis.

Pressure-strain loop analysis

Analyses of pressure-strain loops were performed according to published directions [ 19 ]. The analysis process and definition of work parameters are shown in Fig.  1 . Pressure-strain loops were acquired by first analyzing myocardial speckle tracking in the three apical projections (minimum frame rate of 40 frames per second, mean ± SD, 58 ± 5 frames per second). The left ventricular myocardium was automatically traced using automated function imaging. This created a region of interest that covered the endocardial throughout the myo-epicardial layer. The tracing and region of interest could be adjusted at the discretion of the investigator. Segments could be excluded if the tracing did not follow the myocardial speckles adequately, however, only one segment in total could be excluded, otherwise, the analysis was considered infeasible. Speckle tracking analysis was feasible in 941 (94%). Pressure-strain loops were then created by inputting blood pressure and visually estimating valvular event timing. The following myocardial work parameters were derived from the pressure-strain loop analyses: global work index (GWI), global work efficiency (GWE), global constructive work (GCW), and global wasted work (GWW).

The pressure-strain loop analysis process used to obtain myocardial work measures. First, left ventricular speckle tracking is performed (top left panel), then the brachial artery blood pressure is added, and then the timing of valvular opening and closure is visually estimated (top right panel with orange arrow at the mitral valve and green arrow at the aortic valve). The results are depicted in the bottom left panel and include a pressure-strain loop with the area reflecting global myocardial work index, the bulls-eye plot shows segmental values of myocardial work, and bar charts show the relative distribution of constructive and wasted work. The bottom right panel presents definitions of the four work measures derived from the pressure-strain loop analysis 

Abnormal work indices were defined as follows according to published reference material [ 20 ]: GWI < 1576 mmHg%, GCW < 1708 mmHg%, GWW > 159 mmHg%, GWE < 93.0%.

In line with our previous publication, GLS below 18% (numerical value) was considered abnormal [ 13 ].

Clinical and echocardiographic characteristics were compared for the patients with CKD stratified by normal vs. abnormal GWI. Furthermore, myocardial work measures were compared between patients with CKD and controls. For these comparisons, Gaussian-distributed continuous variables were analyzed with Student’s T -test and reported as mean with standard deviation. Non-Gaussian distributed variables were compared with the Wilcoxon rank-sum test and reported as median with interquartile ranges. Gaussian distribution was assessed from histograms. Categorical variables were compared with either the chi 2 test or Fisher’s exact test as appropriate and reported as total numbers with percentages.

Linear multivariable regressions were made to account for confounders between patients with CKD and controls and calculate predicted means. Adjustments were made for body mass index, diabetes, hypertension, smoking status, alcohol consumption, eGFR, UACR, heart rate, left bundle branch block, atrial fibrillation, heart failure, ischemic heart disease, significant valve disease, and left ventricular mass index. For all regression analyses involving work measures, the GWW and GWE variables were log- and logit-transformed, respectively.

Comparisons were further made across groups of left ventricular remodeling (controls vs. patients with CKD without and with left ventricular hypertrophy (LVH), respectively), across eGFR groups (G1, G2, G3, G4, G5), strata of albuminuria (normoalbuminuria, microalbuminuria, and macroalbuminuria). For these comparisons, the ANOVA test was applied for Gaussian-distributed variables, and non-Gaussian distributed variables were compared with a non-parametric trend test.

Linear regression analysis was also applied to examine the association between eGFR and myocardial work measures and between UACR and myocardial work measures. For all regression analyses, UACR underwent a log-transformation. Multivariable adjustments were made for relevant confounders: age, sex, hypertension, diabetes, heart rate, significant valve disease, ischemic heart disease, smoking status, alcohol consumption, body mass index, known heart failure, and left ventricular mass index. For the analyses concerning the association between UACR and work measures, the multivariable model also included adjustment for eGFR and vice versa. The same analyses were carried out in a subgroup of patients with CKD who exhibited current signs of functional kidney disease (defined as either reduced eGFR (< 60 mL/min/1.73 m 2 ) or albuminuria (UACR > 30 mg/g)).

Logistic regression was applied to investigate which stages of CKD were associated with increased likelihood of abnormal work. Multivariable adjustments were similar to the linear regressions.

Tests for interactions from diabetes, hypertension, and CKD etiology, respectively, were applied in both linear and logistic regression analysis. Since diabetes significantly modified the association between eGFR and work measures, these regression analyses were stratified by diabetes status.

All statistical analyses were performed using STATA v. 15 SE (StataCorp LP, College Station, TX). p -values < 0.05 were considered significant in all analyses.

Table 1 outlines clinical baseline characteristics for all patients with CKD included in the present analysis. Briefly, these patients had a mean age of 57 years, 61% were of male sex, and the median eGFR was 42 mL/min/1.73 m 2 . Comparisons between controls and patients with CKD in terms of clinical characteristics have previously been published [ 13 ]. Per study design, known cardiovascular disease and diabetes were absent in controls, who more frequently were non-smokers and had lower BMI, but similar blood pressure compared with patients with CKD.

Table 1 also outlines baseline characteristics for patients with CKD as stratified by abnormal GWI. In brief, those who had abnormal GWI were slightly older, more frequently men, had lower systolic blood pressure, higher heart rate, and an overall higher proportion of cardiovascular risk factors and disease. In terms of renal function, they exhibited slightly lower eGFR, whereas no significant difference in UACR was noted. In terms of echocardiographic characteristics, those with abnormal GWI exhibited lower ejection fraction and higher left ventricular mass index, but similar diastolic function.

Myocardial work in chronic kidney disease

When comparing patients with CKD to controls, no differences were noted in GWI (1879 vs. 1943 mmHg%, p  = 0.06) nor GCW (2193 vs. 2249 mmHg%, p  = 0.11). However, they did exhibit higher GWW (133 vs. 107 mmHg%, p  < 0.001) and lower GWE (94.3 vs. 95.2%, p  < 0.001). These findings were unchanged after multivariable adjustments. However, when stratified according to left ventricular geometry, we observed a stepwise increase in GWW and decrease in GWI and GWE for patients with CKD and hypertrophy vs. patients with CKD without hypertrophy vs. controls (GWI: 1789 vs. 1887 vs. 1943 mmHg%, p for trend = 0.030; GWW: 194 vs. 130 vs. 107 mmHg%, p for trend < 0.001; GWE: 91.6 vs. 94.5 vs. 95.2%, p for trend < 0.001) with no differences in GCW ( p for trend = 0.20). These differences persisted after multivariable adjustments.

Among patients with CKD, 325 (45%) were considered to have abnormal GLS, whereas 144 (19%) were considered to have abnormal GWI. Accordingly, 216 (66%) of those with abnormal GLS had normal myocardial work. The distribution of values for GLS and GWI according to groups of abnormal strain and work is shown in Fig.  2 .

Distribution of myocardial work and longitudinal strain. Separated scatter plot illustrating how measures of global longitudinal strain and myocardial work were distributed according to abnormalities in strain and work

Myocardial work in relation to eGFR

Table 2 shows absolute values for myocardial work measures as well as the proportion of abnormal work measures according to eGFR groups. A significant trend of higher GWW and lower GWE was observed across the groups. By extension, the proportion of patients with abnormal GWW and GWE increased significantly across the groups. No differences in either GWI or GCW were observed across eGFR groups; however, the proportion of abnormal work indices increased significantly across the groups, being notably higher in the G3, G4, and G5 compared to the G1 and G2 groups.

Linear regression analysis did not reveal any continuous association between eGFR and either GWI or GCW ( p  = 0.33 and 0.81, respectively) but did show that GWW increased and GWE decreased with decreasing eGFR ( p  < 0.001 for both). However, these associations did not persist after multivariable adjustments ( p  = 0.50 and 0.17 for GWW and GWE, respectively).

No effect modification from hypertension or CKD etiology was identified; however, diabetes did significantly modify the association between eGFR and both GWI and GCW ( p for interaction = 0.007 and 0.033, respectively) but not for GWW nor GWE ( p for interaction > 0.05). These effect modifications persisted in multivariable adjustments ( p for interaction = 0.010 and 0.036 for GWI and GCW, respectively), such that per 10 mL/min/1.73 m 2 decrease in eGFR, GWI decreased by 22 (9–35) mmHg% ( p  = 0.001) and GCW decreased by 21 (8–34) mmHg% ( p  = 0.001) in patients without diabetes, whereas no significant associations were observed in patients with diabetes (Fig.  3 ). In a subgroup of patients with current signs of functional kidney disease ( n , 670), similar observations were made for GWI but not for GCW (Supplementary Results).

The association between eGFR and the global work index in patients without diabetes (top left panel) and patients with diabetes (top right panel). In addition, the association between eGFR and global constructive work is also depicted in patients without diabetes (bottom left panel) and patients with diabetes (bottom right panel). CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate

Logistic regression revealed that decreasing eGFR was associated with an increased likelihood of abnormalities in all work measures. However, diabetes modified the associations between eGFR and abnormal GWI ( p for interaction = 0.001), abnormal GWW ( p for interaction = 0.032), and abnormal GWE ( p for interaction = 0.002) but not for abnormal GCW ( p for interaction = 0.32). The associations were modified such that decreasing eGFR was associated with an elevated likelihood of abnormal GWI (OR 1.13 (1.04–1.23), per 10 mL/min/1.73 m 2 decrease, p  = 0.005) in patients without diabetes but a lower likelihood in patients with diabetes (Supplemental Fig. 1 ). Decreasing eGFR was also associated with an elevated likelihood of abnormal GCW (OR 1.14 (1.02–1.29), per 10 mL/min/1.73 m 2 decrease, p  = 0.027), GWW (OR 1.21 (1.12–1.29), per 10 mL/min/1.73 m 2 decrease, p  < 0.001), and GWE (OR 1.18 (1.10–1.27), per 10 mL/min/1.73 m 2 decrease, p  < 0.001) in patients without diabetes whereas no association between eGFR and abnormal GCW, GWW, and GWE were observed in patients with diabetes ( p  > 0.05).

These effect modifications persisted in multivariable regression models (abnormal GWI, p for interaction = 0.002; abnormal GWW, p for interaction = 0.043; abnormal GWE, p for interaction = 0.009). After multivariable adjustments, decreasing eGFR remained significantly associated with an increased likelihood of having abnormal GWI and GCW but not GWW nor GWE (Fig.  4 ), whereas no association between eGFR and abnormal work measures were observed in patients with diabetes ( p  > 0.05 in all analyses).

Based on logistic regression, these figures illustrate the association between eGFR and the probability of having abnormal GWI (top left panel), GCW (top right panel), GWW (bottom left panel), and GWE (bottom right panel) after multivariable adjustments in patients without diabetes. eGFR, estimated glomerular filtration rate; GWI, global work index; GCW, global constructive work; GWW, global wasted work; GWE, global work efficiency

In logistic regression, we observed that both eGFR groups G3 and G4 + 5 were significantly associated with an increased likelihood of having abnormal GWI, GCW, GWW, and GWE as compared to the G1 + 2 group in patients without diabetes but not in patients with diabetes (Supplementary Table  1 ). After multivariable adjustment, these associations persisted for abnormal GWI and GCW in the patients without diabetes (Supplementary Table 1).

Myocardial work in relation to albuminuria

When stratified by degree of albuminuria, we did not observe any differences in myocardial work measures across the categories of normo-, micro-, or macroalbuminuria (Table  3 ). Similarly, no associations between UACR and work measures were observed in linear regression analyses (Supplementary Fig. 2).

By extension, logistic regression revealed that neither the presence of micro- or macroalbuminuria was associated with an elevated likelihood of having abnormal GWI, GCW, GWW, nor GWE as compared to normoalbuminuria ( p  > 0.05 in all analyses).

Of note, tests for interaction did not reveal any effect modification from hypertension, CKD etiology, or diabetes in either linear or logistic regression analyses.

Based on the largest prospective study on myocardial work in patients with CKD, we observed the following: Patients with CKD exhibited a higher amount of wasted work, resulting in reduced work efficiency, as compared to controls. While no differences were observed in myocardial work (the global work index), the findings were influenced by left ventricular geometry such that myocardial work indeed decreased in patients with LVH. In addition, decreasing eGFR was associated with lower myocardial work in patients without diabetes, and eGFR < 60 mL/min/1.73 m 2 was associated with increased likelihood of abnormal myocardial work parameters. Finally, albuminuria was not associated with myocardial work measures.

Myocardial work in CKD

The recent technological advancement allowing for the acquisition of myocardial work indices has provided a promising tool to detect subclinical systolic dysfunction by incorporating the strengths of the robust marker, GLS, while accounting for afterload [ 19 ]. Indeed myocardial work parameters have shown potential value beyond GLS in other studies [ 21 ], and given the altered afterload conditions often observed with CKD, exploration into measures of ventriculo-arterial coupling is warranted.

A handful of studies have already investigated myocardial work in CKD, primarily by comparing myocardial work in a case–control design (number of patients with CKD ranging from 68 to 144). These have repeatedly shown that patients with CKD have higher wasted work and lower work efficiency compared to controls [ 22 , 23 , 24 ], consistent with our findings. Since work efficiency is a derivative of wasted and constructive work, this finding is driven by the higher amount of wasted work. Wasted work represents the amount of work generated that does not translate into cardiac output. Although this can be observed in the presence of electromechanical dyssynchrony [ 25 ], our findings remained unchanged after adjusting for presence of left bundle branch block, suggesting other mechanisms behind our finding. Two predominant mechanisms contribute to wasted work, early systolic lengthening and post-systolic shortening [ 11 ]. Historically, these features have been considered signs of myocardial ischemia, frequently observed throughout the entire cascade of myocardial ischemia, with their presence indicating an elevated risk of cardiovascular events [ 26 , 27 , 28 ]; hence, the finding of a higher amount of wasted work may suggest presence of coronary artery disease, a well-established comorbidity associated with CKD.

Even though no differences were noted in myocardial work, it is interesting to note that several studies — ours included — have suggested that left ventricular geometry influences myocardial work measures in patients with CKD but diverging results have been reported on this.

In 33 patients on chronic hemodialysis with LVH vs. 35 controls, Liu et al. observed lower GWI consistent with our findings [ 22 ]. However, another study of patients with CKD (defined as eGFR < 60 mL/min/1.73 m 2 for over 3 months) that included 46 patients with LVH patients, 59 patients without LVH, and 33 healthy controls revealed higher GWI in those with CKD and LVH than those without LVH and the healthy controls [ 24 ]. Several aspects may contribute to these diverging findings. The differences in study populations in particular make it difficult to compare the studies since the duration, degree, and underlying cause of CKD could influence the findings (details that are not available in all related studies). The discrepancy in findings may, however, reflect differences in duration of LVH, since shorter-lasting LVH could indicate that the left ventricle was compensating by performing more work against an increased workload. In our study and in the study on hemodialysis patients [ 22 ], the remodeling process may have lasted longer and resulted in hypertrophy with myocyte disarray and interstitial fibrosis precipitating decompensation and worsening systolic function [ 29 ]. However, further studies, in particular longitudinal and outcome studies, are needed to substantiate this hypothesis by examining how myocardial work measures develop with changes in left ventricular geometry and whether this translates into worse prognosis, which has been suggested from community-based cohort studies [ 30 ].

A notable finding in our study was that eGFR was associated with GWI and GCW in patients without diabetes, whereas no association between eGFR and any myocardial work measure was observed in patients with diabetes. No other study has previously examined the interplay between eGFR and diabetes in relation to myocardial work and it is unclear why decreasing eGFR would not lead to deterioration in work measures in patients with diabetes, particularly considering that the cardiorenal syndrome in diabetes is well-established [ 31 ]. Our findings therefore require external validation and deeper exploration into diabetes characteristics to shed further light on this finding.

Even though the effect modification from diabetes is previously unrecognized, the previously mentioned studies on myocardial work in CKD have explored the potential association between eGFR and myocardial work. Liu et al. investigated clinical correlates to myocardial work measures and reported that eGFR was associated with GWW and GWE [ 24 ]. This is consistent with our observations; however, we did not find that these associations were independent of confounders. Whether this also pertains to the findings from Liu et al. is unclear since multivariable analyses were not reported. By contrast, Liu et al. reported independent associations between eGFR and GWW [ 23 ]. However, whether GWW was appropriately transformed for regression analysis is unclear. In addition, our study had markedly greater power that allowed for more extensive adjustments. Finally, it is unclear whether a sole finding of higher GWW — that does not translate into lower GWE — is clinically relevant. In fact, only the study by Ke et al. that evaluated 93 patients with CKD observed an association between eGFR and GWI [ 32 ], similar to our study. Our findings further extend those findings to suggest that decreasing eGFR below 60 mL/min/1.73 m 2 may be used to indicate the presence of abnormal myocardial work. However, it is still unclear whether the identification of this abnormality in myocardial work also indicates an elevated likelihood of cardiovascular outcome in patients with CKD. It is also unclear whether treatment with heart failure medication would improve myocardial work in patients with CKD, even though this has been alluded to in a prospective, but non-randomized study of patients with end-stage renal disease [ 33 ].

Interestingly, we did not find albuminuria to be associated with myocardial work measures, which extends our previous findings also showing a lack of association between both standard echocardiographic measures of cardiac function and GLS to UACR. Possible explanations have been discussed in our previous report [ 13 ], but a principal reason for this may be that our study included a heterogeneous sample of patients with CKD, some with etiologies that may not lead to albuminuria. However, no previous studies have examined the relationship between myocardial work and UACR, and further studies are consequently needed to validate our findings.

Limitations

Since we did not include patients on dialysis, our findings cannot be extrapolated to these patients. Similarly, our findings cannot be applied to patients with aortic valve stenosis nor severe aortic regurgitation as the non-invasive pressure estimation does not apply in this setting. Due to the observational nature of the study and lack of relevant parameters, including NT-proBNP, Cystatin C, and SGLT2-inhibitor usage, our study may be subject to residual and uncorrected confounding. This also pertains to the fact that heart failure may be underestimated in this study, since heart failure with preserved ejection fraction may be an underdiagnosed condition in Denmark [ 34 ]. The study was conducted before SGLT2-inhibitors became standard of care in CKD, making our findings less generalizable to contemporary patients with CKD.

Furthermore, since approximately a third of the controls presented with hypertension, we cannot exclude that this could have influenced our findings; however, we sought to account for this through multivariable adjustments.

Patients with CKD and left ventricular hypertrophy exhibited poorer systolic function by myocardial work compared to matched controls. Furthermore, patients with CKD exhibited lower work efficiency and a higher amount of wasted work.

In patients without diabetes, decreasing eGFR was associated with decreasing myocardial work, which was not the case for patients with diabetes, and eGFR below 60 mL/min/1.73 m 2 could indicate abnormal myocardial work in patients with CKD without diabetes.

No association between albuminuria and myocardial work was observed in patients with CKD.

Data Availability

The data underlying this study contains sensitive patient information and can therefore not be shared publicly according to Danish legislation. Methodology will be shared upon reasonable request.

Eknoyan G, Levey AS, Levin NW, Keane WF (2001) The national epidemic of chronic kidney disease. What we know and what we can do. Postgrad Med 110:23–29

Article   CAS   PubMed   Google Scholar  

Lv J-C, Zhang L-X (2019) Prevalence and disease burden of chronic kidney disease. Adv Exp Med Biol 1165:3–15

Zelnick LR, Shlipak MG, Soliman EZ et al (2022) Prediction of incident heart failure in CKD: the CRIC study. Kidney Int Rep 7:708–719

Article   PubMed   PubMed Central   Google Scholar  

Kottgen A, Russell SD, Loehr LR et al (2007) Reduced kidney function as a risk factor for incident heart failure: the Atherosclerosis Risk in Communities (ARIC) study. J Am Soc Nephrol 18:1307–1315

Bansal N, Zelnick L, Bhat Z et al (2019) Burden and outcomes of heart failure hospitalizations in adults with chronic kidney disease. J Am Coll Cardiol 73:2691–2700

Matsushita K, Kwak L, Sang Y et al (2017) Kidney disease measures and left ventricular structure and function: the Atherosclerosis Risk in Communities study. J Am Heart Assoc 6:e006259

Cai Q-Z, Lu X-Z, Lu Y, Wang AY-M (2014) Longitudinal changes of cardiac structure and function in CKD (CASCADE study). J Am Soc Nephrol 25:1599–1608

Article   CAS   PubMed   PubMed Central   Google Scholar  

Park M, Hsu C, Li Y et al (2012) Associations between kidney function and subclinical cardiac abnormalities in CKD. J Am Soc Nephrol 23:1725–1734

Cikes M, Solomon SD (2016) Beyond ejection fraction: an integrative approach for assessment of cardiac structure and function in heart failure. Eur Heart J 37:1642–1650

Article   PubMed   Google Scholar  

Russell K, Eriksen M, Aaberge L et al (2012) A novel clinical method for quantification of regional left ventricular pressure-strain loop area: a non-invasive index of myocardial work. Eur Heart J 33:724–733

Boe E, Skulstad H, Smiseth OA (2019) Myocardial work by echocardiography: a novel method ready for clinical testing. Eur Heart J Cardiovasc Imaging 20:18–20

Sørensen IMH, Saurbrey SAK, Hjortkjær HØ et al (2020) Regional distribution and severity of arterial calcification in patients with chronic kidney disease stages 1–5: a cross-sectional study of the Copenhagen chronic kidney disease cohort. BMC Nephrol 21:534

Landler NE, Olsen FJ, Christensen J et al (2022) Associations between albuminuria, estimated GFR and cardiac phenotype in a cohort with chronic kidney disease: the CPH-CKD ECHO study. J Card Fail 28:1615–1627

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2013) KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3:1–150

Google Scholar  

Levey AS, Stevens LA, Schmid CH et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612

Lang RM, Badano LP, Mor-Avi V et al (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 16:233–270

Lancellotti P, Tribouilloy C, Hagendorff A et al (2013) Recommendations for the echocardiographic assessment of native valvular regurgitation: an executive summary from the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 14:611–644

Baumgartner H, Hung J, Bermejo J et al (2009) Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr 10:1–25

Smiseth OA, Donal E, Penicka M, Sletten OJ (2021) How to measure left ventricular myocardial work by pressure-strain loops. Eur Heart J Cardiovasc Imaging 22:259–261

Olsen FJ, Skaarup KG, Lassen MCH et al (2022) Normal values for myocardial work indices derived from pressure-strain loop analyses: from the CCHS. Circ Cardiovasc Imaging 15:e013712

Edwards NFA, Scalia GM, Shiino K et al (2019) Global myocardial work is superior to global longitudinal strain to predict significant coronary artery disease in patients with normal left ventricular function and wall motion. J Am Soc Echocardiogr 32:947–957

Liu C, Feng Y-P, Yan Z-N et al (2021) Value of quantitative analysis of left ventricular systolic function in patients on maintenance hemodialysis based on myocardial work technique. BMC Cardiovasc Disord 21:76

Liu F-Z, Wang X-L, Zhang C-Q (2021) Quantitative assessment of left ventricular myocardial work in chronic kidney disease patients by a novel non-invasive pressure-strain loop analysis method. Int J Cardiovasc Imaging 37:1567–1575

Liu X, Chen L, Zhong X et al (2022) Noninvasive evaluation of myocardial work in patients with chronic kidney disease using left ventricular pressure-strain loop analysis. Diagnostics (Basel) 12:856

Vecera J, Penicka M, Eriksen M et al (2016) Wasted septal work in left ventricular dyssynchrony: a novel principle to predict response to cardiac resynchronization therapy. Eur Heart J Cardiovasc Imaging 17:624–632

Brainin P, Hoffmann S, Fritz-Hansen T et al (2018) Usefulness of postsystolic shortening to diagnose coronary artery disease and predict future cardiovascular events in stable angina pectoris. J Am Soc Echocardiogr 31:870-879.e3

Brainin P, Haahr-Pedersen S, Olsen FJ et al (2020) Early systolic lengthening in patients with ST-segment-elevation myocardial infarction: a novel predictor of cardiovascular events. J Am Heart Assoc 9:e013835

Brainin P, Skaarup KG, Iversen AZ et al (2019) Post-systolic shortening predicts heart failure following acute coronary syndrome. Int J Cardiol 276:191–197

Tadic M, Cuspidi C, Marwick TH (2022) Phenotyping the hypertensive heart. Eur Heart J 43:3794–3810

Olsen FJ, Skaarup KG, Lassen MCH et al (2024) Association between myocardial work indices and cardiovascular events according to hypertension in the general population. Eur Heart J Cardiovasc Imaging 25:413–424

Méndez Fernández AB, Vergara Arana A, Olivella San Emeterio A et al (2023) Cardiorenal syndrome and diabetes: an evil pairing. Front Cardiovasc Med 10:1185707

Ke Q-Q, Xu H-B, Bai J et al (2020) Evaluation of global and regional left ventricular myocardial work by echocardiography in patients with chronic kidney disease. Echocardiography 37:1784–1791

Wang B, Wang G-H, Ding X-X et al (2022) Effects of sacubitril/valsartan on resistant hypertension and myocardial work in hemodialysis patients. J Clin Hypertens (Greenwich) 24:300–308

Madelaire C, Gustafsson F, Køber L et al (2020) Identification of patients with new-onset heart failure and reduced ejection fraction in Danish administrative registers. Clin Epidemiol 12:589–594

Download references

Open access funding provided by Copenhagen University. The study received funding from the Capital Region of Denmark (Region Hovedstaden).

Author information

Authors and affiliations.

Cardiovascular Non-Invasive Imaging Research Laboratory, Department of Cardiology, Copenhagen University Hospital – Herlev and Gentofte, Gentofte Hospitalsvej 8, 2900, Hellerup, Denmark

Flemming Javier Olsen, Nino Emanuel Landler, Jacob Christensen & Tor Biering-Sørensen

Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Flemming Javier Olsen, Nino Emanuel Landler, Jacob Christensen, Christina Christoffersen, Sasha Saurbrey Bjergfelt & Tor Biering-Sørensen

Department of Nephrology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

Bo Feldt-Rasmussen, Ellen Linnea Freese Ballegaard, Ida Maria Hjelm Sørensen, Sasha Saurbrey Bjergfelt & Susanne Bro

Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

Bo Feldt-Rasmussen, Ditte Hansen & Ellen Linnea Freese Ballegaard

Department of Nephrology, Copenhagen University Hospital – Herlev and Gentofte, Herlev, Denmark

Ditte Hansen & Eline Seidelin

Department of Clinical Biochemistry, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

Christina Christoffersen

Department of Cardiology, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

Tor Biering-Sørensen

Steno Diabetes Center Copenhagen, Herlev, Denmark

You can also search for this author in PubMed   Google Scholar

Corresponding author

Correspondence to Flemming Javier Olsen .

Ethics declarations

Conflict of interest.

D.H.: Steering Committee member of the Boehringer Ingelheim financed SHARP3 trial. Advisory Board: GSK. Lecture fee: Astra Zeneca and UCB Nordic. E.L.F.B.: Received non-related research grants from AstraZeneca. T.B-S.: Steering Committee member of the Amgen financed GALACTIC-HF trial. Primary investigator of the Sanofi Pasteur financed “NUDGE-FLU” trial. Primary investigator of the Sanofi Pasteur financed “DANFLU-1” trial. Primary investigator of the Sanofi Pasteur financed “DANFLU-2” trial. Steering Committee member of “LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System” trial. Steering Committee member of the Boehringer Ingelheim financed SHARP3 trial. Advisory Board: Sanofi Pasteur, Amgen, and GSK. Speaker Honorarium: Novartis, Sanofi Pasteur, GE Healthcare, and GSK. Research grants: GE Healthcare, AstraZeneca, Novo Nordisk and Sanofi Pasteur. The other authors declare no conflict of interest.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 197 KB)

Rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .

Reprints and permissions

About this article

Olsen, F.J., Landler, N.E., Christensen, J. et al. Myocardial work in chronic kidney disease: insights from the CPH-CKD ECHO Study. Clin Res Cardiol (2024). https://doi.org/10.1007/s00392-024-02459-6

Download citation

Received : 31 January 2024

Accepted : 03 May 2024

Published : 15 May 2024

DOI : https://doi.org/10.1007/s00392-024-02459-6

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Myocardial work
• Pressure-strain
• Kidney disease
• Chronic nephropathy
• Find a journal
• Publish with us
• Track your research