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Research Topics & Ideas: Healthcare

100+ Healthcare Research Topic Ideas To Fast-Track Your Project

Finding and choosing a strong research topic is the critical first step when it comes to crafting a high-quality dissertation, thesis or research project. If you’ve landed on this post, chances are you’re looking for a healthcare-related research topic , but aren’t sure where to start. Here, we’ll explore a variety of healthcare-related research ideas and topic thought-starters across a range of healthcare fields, including allopathic and alternative medicine, dentistry, physical therapy, optometry, pharmacology and public health.

NB – This is just the start…

The topic ideation and evaluation process has multiple steps . In this post, we’ll kickstart the process by sharing some research topic ideas within the healthcare domain. This is the starting point, but to develop a well-defined research topic, you’ll need to identify a clear and convincing research gap , along with a well-justified plan of action to fill that gap.

If you’re new to the oftentimes perplexing world of research, or if this is your first time undertaking a formal academic research project, be sure to check out our free dissertation mini-course. In it, we cover the process of writing a dissertation or thesis from start to end. Be sure to also sign up for our free webinar that explores how to find a high-quality research topic.

Overview: Healthcare Research Topics

• Allopathic medicine
• Alternative /complementary medicine
• Veterinary medicine
• Physical therapy/ rehab
• Optometry and ophthalmology
• Pharmacy and pharmacology
• Public health
• Examples of healthcare-related dissertations

Allopathic (Conventional) Medicine

• The effectiveness of telemedicine in remote elderly patient care
• The impact of stress on the immune system of cancer patients
• The effects of a plant-based diet on chronic diseases such as diabetes
• The use of AI in early cancer diagnosis and treatment
• The role of the gut microbiome in mental health conditions such as depression and anxiety
• The efficacy of mindfulness meditation in reducing chronic pain: A systematic review
• The benefits and drawbacks of electronic health records in a developing country
• The effects of environmental pollution on breast milk quality
• The use of personalized medicine in treating genetic disorders
• The impact of social determinants of health on chronic diseases in Asia
• The role of high-intensity interval training in improving cardiovascular health
• The efficacy of using probiotics for gut health in pregnant women
• The impact of poor sleep on the treatment of chronic illnesses
• The role of inflammation in the development of chronic diseases such as lupus
• The effectiveness of physiotherapy in pain control post-surgery

Topics & Ideas: Alternative Medicine

• The benefits of herbal medicine in treating young asthma patients
• The use of acupuncture in treating infertility in women over 40 years of age
• The effectiveness of homoeopathy in treating mental health disorders: A systematic review
• The role of aromatherapy in reducing stress and anxiety post-surgery
• The impact of mindfulness meditation on reducing high blood pressure
• The use of chiropractic therapy in treating back pain of pregnant women
• The efficacy of traditional Chinese medicine such as Shun-Qi-Tong-Xie (SQTX) in treating digestive disorders in China
• The impact of yoga on physical and mental health in adolescents
• The benefits of hydrotherapy in treating musculoskeletal disorders such as tendinitis
• The role of Reiki in promoting healing and relaxation post birth
• The effectiveness of naturopathy in treating skin conditions such as eczema
• The use of deep tissue massage therapy in reducing chronic pain in amputees
• The impact of tai chi on the treatment of anxiety and depression
• The benefits of reflexology in treating stress, anxiety and chronic fatigue
• The role of acupuncture in the prophylactic management of headaches and migraines

Topics & Ideas: Dentistry

• The impact of sugar consumption on the oral health of infants
• The use of digital dentistry in improving patient care: A systematic review
• The efficacy of orthodontic treatments in correcting bite problems in adults
• The role of dental hygiene in preventing gum disease in patients with dental bridges
• The impact of smoking on oral health and tobacco cessation support from UK dentists
• The benefits of dental implants in restoring missing teeth in adolescents
• The use of lasers in dental procedures such as root canals
• The efficacy of root canal treatment using high-frequency electric pulses in saving infected teeth
• The role of fluoride in promoting remineralization and slowing down demineralization
• The impact of stress-induced reflux on oral health
• The benefits of dental crowns in restoring damaged teeth in elderly patients
• The use of sedation dentistry in managing dental anxiety in children
• The efficacy of teeth whitening treatments in improving dental aesthetics in patients with braces
• The role of orthodontic appliances in improving well-being
• The impact of periodontal disease on overall health and chronic illnesses

Tops & Ideas: Veterinary Medicine

• The impact of nutrition on broiler chicken production
• The role of vaccines in disease prevention in horses
• The importance of parasite control in animal health in piggeries
• The impact of animal behaviour on welfare in the dairy industry
• The effects of environmental pollution on the health of cattle
• The role of veterinary technology such as MRI in animal care
• The importance of pain management in post-surgery health outcomes
• The impact of genetics on animal health and disease in layer chickens
• The effectiveness of alternative therapies in veterinary medicine: A systematic review
• The role of veterinary medicine in public health: A case study of the COVID-19 pandemic
• The impact of climate change on animal health and infectious diseases in animals
• The importance of animal welfare in veterinary medicine and sustainable agriculture
• The effects of the human-animal bond on canine health
• The role of veterinary medicine in conservation efforts: A case study of Rhinoceros poaching in Africa
• The impact of veterinary research of new vaccines on animal health

Topics & Ideas: Physical Therapy/Rehab

• The efficacy of aquatic therapy in improving joint mobility and strength in polio patients
• The impact of telerehabilitation on patient outcomes in Germany
• The effect of kinesiotaping on reducing knee pain and improving function in individuals with chronic pain
• A comparison of manual therapy and yoga exercise therapy in the management of low back pain
• The use of wearable technology in physical rehabilitation and the impact on patient adherence to a rehabilitation plan
• The impact of mindfulness-based interventions in physical therapy in adolescents
• The effects of resistance training on individuals with Parkinson’s disease
• The role of hydrotherapy in the management of fibromyalgia
• The impact of cognitive-behavioural therapy in physical rehabilitation for individuals with chronic pain
• The use of virtual reality in physical rehabilitation of sports injuries
• The effects of electrical stimulation on muscle function and strength in athletes
• The role of physical therapy in the management of stroke recovery: A systematic review
• The impact of pilates on mental health in individuals with depression
• The use of thermal modalities in physical therapy and its effectiveness in reducing pain and inflammation
• The effect of strength training on balance and gait in elderly patients

Topics & Ideas: Optometry & Opthalmology

• The impact of screen time on the vision and ocular health of children under the age of 5
• The effects of blue light exposure from digital devices on ocular health
• The role of dietary interventions, such as the intake of whole grains, in the management of age-related macular degeneration
• The use of telemedicine in optometry and ophthalmology in the UK
• The impact of myopia control interventions on African American children’s vision
• The use of contact lenses in the management of dry eye syndrome: different treatment options
• The effects of visual rehabilitation in individuals with traumatic brain injury
• The role of low vision rehabilitation in individuals with age-related vision loss: challenges and solutions
• The impact of environmental air pollution on ocular health
• The effectiveness of orthokeratology in myopia control compared to contact lenses
• The role of dietary supplements, such as omega-3 fatty acids, in ocular health
• The effects of ultraviolet radiation exposure from tanning beds on ocular health
• The impact of computer vision syndrome on long-term visual function
• The use of novel diagnostic tools in optometry and ophthalmology in developing countries
• The effects of virtual reality on visual perception and ocular health: an examination of dry eye syndrome and neurologic symptoms

Topics & Ideas: Pharmacy & Pharmacology

• The impact of medication adherence on patient outcomes in cystic fibrosis
• The use of personalized medicine in the management of chronic diseases such as Alzheimer’s disease
• The effects of pharmacogenomics on drug response and toxicity in cancer patients
• The role of pharmacists in the management of chronic pain in primary care
• The impact of drug-drug interactions on patient mental health outcomes
• The use of telepharmacy in healthcare: Present status and future potential
• The effects of herbal and dietary supplements on drug efficacy and toxicity
• The role of pharmacists in the management of type 1 diabetes
• The impact of medication errors on patient outcomes and satisfaction
• The use of technology in medication management in the USA
• The effects of smoking on drug metabolism and pharmacokinetics: A case study of clozapine
• Leveraging the role of pharmacists in preventing and managing opioid use disorder
• The impact of the opioid epidemic on public health in a developing country
• The use of biosimilars in the management of the skin condition psoriasis
• The effects of the Affordable Care Act on medication utilization and patient outcomes in African Americans

Topics & Ideas: Public Health

• The impact of the built environment and urbanisation on physical activity and obesity
• The effects of food insecurity on health outcomes in Zimbabwe
• The role of community-based participatory research in addressing health disparities
• The impact of social determinants of health, such as racism, on population health
• The effects of heat waves on public health
• The role of telehealth in addressing healthcare access and equity in South America
• The impact of gun violence on public health in South Africa
• The effects of chlorofluorocarbons air pollution on respiratory health
• The role of public health interventions in reducing health disparities in the USA
• The impact of the United States Affordable Care Act on access to healthcare and health outcomes
• The effects of water insecurity on health outcomes in the Middle East
• The role of community health workers in addressing healthcare access and equity in low-income countries
• The impact of mass incarceration on public health and behavioural health of a community
• The effects of floods on public health and healthcare systems
• The role of social media in public health communication and behaviour change in adolescents

Examples: Healthcare Dissertation & Theses

While the ideas we’ve presented above are a decent starting point for finding a healthcare-related research topic, they are fairly generic and non-specific. So, it helps to look at actual dissertations and theses to see how this all comes together.

Below, we’ve included a selection of research projects from various healthcare-related degree programs to help refine your thinking. These are actual dissertations and theses, written as part of Master’s and PhD-level programs, so they can provide some useful insight as to what a research topic looks like in practice.

• Improving Follow-Up Care for Homeless Populations in North County San Diego (Sanchez, 2021)
• On the Incentives of Medicare’s Hospital Reimbursement and an Examination of Exchangeability (Elzinga, 2016)
• Managing the healthcare crisis: the career narratives of nurses (Krueger, 2021)
• Methods for preventing central line-associated bloodstream infection in pediatric haematology-oncology patients: A systematic literature review (Balkan, 2020)
• Farms in Healthcare: Enhancing Knowledge, Sharing, and Collaboration (Garramone, 2019)
• When machine learning meets healthcare: towards knowledge incorporation in multimodal healthcare analytics (Yuan, 2020)
• Integrated behavioural healthcare: The future of rural mental health (Fox, 2019)
• Healthcare service use patterns among autistic adults: A systematic review with narrative synthesis (Gilmore, 2021)
• Mindfulness-Based Interventions: Combatting Burnout and Compassionate Fatigue among Mental Health Caregivers (Lundquist, 2022)
• Transgender and gender-diverse people’s perceptions of gender-inclusive healthcare access and associated hope for the future (Wille, 2021)
• Efficient Neural Network Synthesis and Its Application in Smart Healthcare (Hassantabar, 2022)
• The Experience of Female Veterans and Health-Seeking Behaviors (Switzer, 2022)
• Machine learning applications towards risk prediction and cost forecasting in healthcare (Singh, 2022)
• Does Variation in the Nursing Home Inspection Process Explain Disparity in Regulatory Outcomes? (Fox, 2020)

Looking at these titles, you can probably pick up that the research topics here are quite specific and narrowly-focused , compared to the generic ones presented earlier. This is an important thing to keep in mind as you develop your own research topic. That is to say, to create a top-notch research topic, you must be precise and target a specific context with specific variables of interest . In other words, you need to identify a clear, well-justified research gap.

Need more help?

If you’re still feeling a bit unsure about how to find a research topic for your healthcare dissertation or thesis, check out Topic Kickstarter service below.

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15 Comments

I need topics that will match the Msc program am running in healthcare research please

Hello Mabel,

I can help you with a good topic, kindly provide your email let’s have a good discussion on this.

Can you provide some research topics and ideas on Immunology?

Thank you to create new knowledge on research problem verse research topic

Help on problem statement on teen pregnancy

This post might be useful: https://gradcoach.com/research-problem-statement/

can you provide me with a research topic on healthcare related topics to a qqi level 5 student

Please can someone help me with research topics in public health ?

Hello I have requirement of Health related latest research issue/topics for my social media speeches. If possible pls share health issues , diagnosis, treatment.

I would like a topic thought around first-line support for Gender-Based Violence for survivors or one related to prevention of Gender-Based Violence

Please can I be helped with a master’s research topic in either chemical pathology or hematology or immunology? thanks

Can u please provide me with a research topic on occupational health and safety at the health sector

Good day kindly help provide me with Ph.D. Public health topics on Reproductive and Maternal Health, interventional studies on Health Education

may you assist me with a good easy healthcare administration study topic

May you assist me in finding a research topic on nutrition,physical activity and obesity. On the impact on children

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Top 100 Disease Research Topics For Paper Writing

Students have many disease research topics to consider when writing research papers and essays. A disease occurs when the body undergoes some changes. Science philosophy has pointed at pathogens and the causes of illness. Today, medicine focus on biochemical factors, nutrition, immunology levels, and environmental toxins as the causes of diseases. Research papers on disease topics can focus on specific illnesses independently or in groups. You can also write about infectious diseases like COVID-19 and HIV or non-communicable diseases. Non-communicable diseases are also known as chronic illnesses. These are diseases that you can’t get from a sick person. They include heart disease, cancer, stroke, and lung disease. These diseases account for up to 70% of global deaths. Nevertheless, whether you opt to write about advanced topics in Lyme disease or something simple like flu, research will be paramount. You  can also buy research papers cheap, if you don’t have time for it. So, d on’t put your grade at risk and get research paper online help .  

Why Choose Our Disease Research Topics?

Educators want you to convince them that you have taken the time to think about your topic and research it extensively. What’s more, your research should make a meaningful contribution to your study field. Therefore, select a good topic and research it extensively before you start writing. Analyze your information to determine what will make it to your research paper. Here is a list of 100 disease research paper topics worth considering for your paper or essay.

Top Disease Research Topics

Maybe you want to research and write a research paper on a topic that anybody will find interesting to read. In that case, consider ideas in this list of disease research topics.

• How NSAIDS lead to peptic ulcers
• What are pandemic diseases?
• What is the role of pandemic diseases in the mankind history?
• What are the symptoms of acute lung disease?
• Explain how Attention Deficit Hyperactivity Disorder affects children
• Discuss the AIDS pandemic in third world countries
• Describe the main causes of AIDS
• Explain how AIDS affects children
• Discuss the treatment of AIDS
• Is alcohol addiction a disease?
• Discuss the Alzheimer’s disease scope and how it affects the elderly persons’ brain
• How can you help dementia or Alzheimer’s disease patients and caregivers?
• What are the symptoms of Alzheimer’s disease?
• What is autoimmune disease?
• Explain how autoimmune thyroiditis begins
• Examine acute protective membrane inflammation in bacterial meningitis
• Compare pathology of AIDS and black death
• Discuss the effects of cancer in today’s society
• Autism and its causes
• Different types of cancer and their prevalence

These are topics disease experts will recommend researching and writing about. And because students can write about these topics without getting complex, anybody will find them interesting. If you’re searching for research topics on Alzheimer’s disease, this list also has some ideas for you to consider.

Infectious Disease Topics for Research Papers

Are you interested in infectious disease research topics? If yes, you will find this list interesting. This category comprises hot topics in infectious disease fields. Consider some of these ideas for your research paper.

• The virology, epidemiology, and prevention of COVID-19
• The diagnosis of COVID-19
• Prevention vaccines for SARS-CoV-2 infection
• Questions people ask about COVID-19
• Clinical features of COVID-19
• COVID-19 management in a hospital setting
• Infection control for COVID-19 in homes and healthcare settings
• Skin abscess and cellulitis in adults
• Clinical manifestation, diagnosis, and epidemiology of yellow fever
• Transmission and epidemiology of measles
• Role of untreated inflammation of genital tract in HIV transmission
• Racial inequities of COVID-19 and HIV in black communities
• Community-acquired pneumonia overview in adults
• The use of procalcitonin in the infections of lower respiratory tract
• Herpes simplex virus prevention and treatment
• Uncomplicated Neisseria gonorrhea treatment
• Society guidelines for COVID-19
• Why public education is crucial in fighting COVID-19
• Overview of Ebola over the last two decades
• Investigations into the use of monoclonal antibody in treating Ebola

This category also has some of the best infectious disease presentation topics. Nevertheless, learners should prepare to research extensively before writing academic papers on these topics.

Interesting Disease Topics

Maybe you want to research and write a research paper on a topic that most people find interesting. In that case, consider these disease topics for research paper.

• Discuss bulimia as a common eating disorder
• Why are so many young people suffering from anorexia?
• What causes most eating disorders
• How serious are sleep disorders
• Discuss rabies treatment- The Milwaukee protocol
• Is assisted suicide a way to treat terminal diseases?
• What are the effects of brain injuries?
• What are professional diseases?
• Is autism a norm variant or a disease?
• The history of pandemics and epidemics
• The role of antibiotics in treating diseases
• What causes insomnia?
• What are the effects of insomnia?
• How to cope with insomnia
• Can sleeping pills cure insomnia?
• Explain what causes long-term insomnia
• Using traditional medicine to fight insomnia
• How to deal with bulimia and nervosa
• How eating disorders affect self-harm behavior
• How feminism affect anorexic women phenomenon

This is a list of easy disease topics for papers. What’s more, most people will find these research paper disease topics interesting to read about. Nevertheless, students should take time to research their preferred topics to come up with brilliant papers on any of these human disease research paper topics.

Cardiovascular Disease Research Topics

Maybe you’re interested in topic ideas on heart disease. Perhaps, you want to write about an illness of the respiratory system. In that case, consider these heart disease research topics.

• An investigation of hypertrophic cardiomyopathy
• A research of the causes of coronary artery disease
• Antithrombotic therapy in surgical valve and prosthetic heart valve repair
• Intervention choice for severe cases of calcific aortic stenosis
• Prognosis and treatment of heart failure using preserved fraction of injection
• Infective endocarditis management in adults
• Risk assessment for cardiovascular disease for primary prevention
• Prognosis and treatment of acute pericarditis
• Treatment of reflex syncope in adolescents and adults
• Anticoagulant therapy for preventing thromboembolism in atrial fibrillation
• Cardiac manifestations of COVID-19 in adults
• Acute decompensated heart failure treatment
• What is hypertriglyceridemia?
• How to manage elevated low-density lipoprotein-cholesterol in cardiovascular disease
• Management and evaluation of cardiac disease
• Conduction system and arrhythmias disease and COVID-19
• Myocardial infarction in COVID-19
• Can somebody inherit a cardiac disease?
• How effective are treatments for irregular heartbeat?
• How to determine the risk for a sudden cardiac death

This list comprises some of the best special disease topics. That’s because most people reading about these topics might not have heard about them before. Nevertheless, this category also has interesting research topics for disease control that may help individuals that want to avoid or manage some illnesses.

Research Topics for Chronic Disease

You probably know somebody living with a chronic illness. Unlike controversial topics in infectious disease, people don’t talk much about chronic illnesses. And for this reason, some people don’t know about these illnesses. When writing about non-communicable illnesses, you can settle for human genetic disease topics or even research topics for sickle cell disease. Here are some of the topics about non-communicable diseases that you can write about.

• The risk of breast cancer after childbirth
• Postpartum PTSD- Effective preventative measures
• Experiences of females suffering from cardiac disease during pregnancy- A systematic review
• Husbands attendance and knowledge of wives’ postpartum care in rural areas
• Postpartum depression screening by perinatal nurses in hospitals
• Gestational diabetes mellitus screening from the rural perspective
• Maternal mortality- How to help cardiac and pregnant patients
• Sex differences in cardio metabolic disorders and major depression- Effect of immune exposures and prenatal stress
• Determinants and prevalence of anxiety and antepartum depressive symptoms in fathers and expectant mothers- Outcomes from perinatal psychiatric morbidity
• Evaluating the effect of community health workers on non-communicable diseases, tuberculosis, malnutrition, antenatal care, and family planning
• History of women with postpartum affective disorder and the risk of future pregnancies recurrence
• New self-care guide package and its effect on neonatal and maternal results in gestational diabetes
• Depressive symptoms and life events in pregnant women- Moderating the resilience role and social support
• Gestational diabetes and ethnic disparities
• Pregnancy and diabetes- Opportunities and risks
• Cardiovascular disease maternal death reduction- A pragmatic investigation
• Meta-analysis and systematic review of gestational diabetes mellitus diagnosis with a two-step or one-step associations and approaches with negative pregnancy outcomes
• Gestational diabetes mellitus treatment in women- A Cochrane systematic overview
• Research in non-communicable diseases in Africa- A strategic investment
• How to finance the national response to non-communicable diseases

Whether you opt to write about research paper topics in Huntington’s disease or non-communicable liver disease topics, you have to engage in extensive research to come up with a brilliant paper. We have more health research topics for you, so don’t hesitate to check them. Therefore, select an idea you will be comfortable researching and writing about. That way, you will avoid enduring a boring process of investing your topic and writing the paper. If you want to hire someone to help you with your assignment, just c ontact us with a “ do my research paper now ” request and we’ll get your papers done. 

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Defining the Question: Foreground & Background Questions

In order to most appropriately choose an information resource and craft a search strategy, it is necessary to consider what  kind  of question you are asking: a specific, narrow "foreground" question, or a broader background question that will help give context to your research?

Foreground Questions

A "foreground" question in health research is one that is relatively specific, and is usually best addressed by locating primary research evidence. 

Using a structured question framework can help you clearly define the concepts or variables that make up the specific research question. 

 Across most frameworks, you’ll often be considering:

• a who (who was studied - a population or sample)
• a what (what was done or examined - an intervention, an exposure, a policy, a program, a phenomenon)
• a how ([how] did the [what] affect the [who] - an outcome, an effect). 

PICO is the most common framework for developing a clinical research question, but multiple question frameworks exist.

PICO (Problem/Population, Intervention, Comparison, Outcome)

Appropriate for : clinical questions, often addressing the effect of an intervention/therapy/treatment

Example : For adolescents with type II diabetes (P) does the use of telehealth consultations (I) compared to in-person consultations  (C) improve blood sugar control  (O)?

Framing Different Types of Clinical Questions with PICO

Different types of clinical questions are suited to different syntaxes and phrasings, but all will clearly define the PICO elements.  The definitions and frames below may be helpful for organizing your question:

Intervention/Therapy

Questions addressing how a clinical issue, illness, or disability is treated.

"In__________________(P), how does__________________(I) compared to_________________(C) affect______________(O)?"

Questions that address the causes or origin of disease, the factors which produce or predispose toward a certain disease or disorder.

"Are_________________(P), who have_________________(I) compared with those without_________________(C) at_________________risk for/of_________________(O) over_________________(T)?" 

Questions addressing the act or process of identifying or determining the nature and cause of a disease or injury through evaluation.

In_________________(P) are/is_________________(I) compared with_________________(C) more accurate in diagnosing_________________(O)?

Prognosis/Prediction:

Questions addressing the prediction of the course of a disease.

In_________________(P), how does_________________(I) compared to_________________ (C) influence_________________(O)?

Questions addressing how one experiences a phenomenon or why we need to approach practice differently.

"How do_________________(P) with_________________(I) perceive_________________(O)?" 

Adapted from: Melnyk, B. M., & Fineout-Overholt, E. (2011). Evidence-based practice in nursing & healthcare: A guide to best practice. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins.

Beyond PICO: Other Types of Question Frameworks

PICO is a useful framework for clinical research questions, but may not be appropriate for all kinds of reviews.  Also consider:

PEO (Population, Exposure, Outcome)

Appropriate for : describing association between particular exposures/risk factors and outcomes

Example : How do  preparation programs (E) influence the development of teaching competence  (O) among novice nurse educators  (P)?

SPIDER (Sample, Phenomenon of Interest, Design, Evaluation, Research Type)

Appropriate for : questions of experience or perspectives (questions that may be addressed by qualitative or mixed methods research)

Example : What are the experiences and perspectives (E) of  undergraduate nursing students  (S)  in clinical placements within prison healthcare settings (PI)?

SPICE (Setting, Perspective, Intervention/phenomenon of Interest, Comparison, Evaluation)

Appropriate for : evaluating the outcomes of a service, project, or intervention

Example : What are the impacts and best practices for workplace (S) transition support programs (I) for the retention (E) of newly-hired, new graduate nurses (P)?

PCC (Problem/population, Concept, Context)

Appropriate for : broader (scoping) questions

Example : How do nursing schools  (Context) teach, measure, and maintain nursing students ' (P)  technological literacy  (Concept))throughout their educational programs?

Background Questions

To craft a strong and reasonable foreground research question, it is important to have a firm understanding of the concepts of interest.  As such, it is often necessary to ask background questions, which ask for more general, foundational knowledge about a disorder, disease, patient population, policy issue, etc. 

For example, consider the PICO question outlined above:

"For adolescents with type II diabetes does the use of telehealth consultations compared to in-person consultations  improve blood sugar control ?

To best make sense of the literature that might address this PICO question, you would also need a deep understanding of background questions like:

• What are the unique barriers or challenges related to blood sugar management in adolescents with TII diabetes?
• What are the measures of effective blood sugar control?
• What kinds of interventions would fall under the umbrella of 'telehealth'?
• What are the qualitative differences in patient experience in telehealth versus in-person interactions with healthcare providers?
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Participating in Health Research Studies

What is health research.

• Is Health Research Safe?
• Is Health Research Right for Me?
• Types of Health Research

The term "health research," sometimes also called "medical research" or "clinical research," refers to research that is done to learn more about human health. Health research also aims to find better ways to prevent and treat disease. Health research is an important way to help improve the care and treatment of people worldwide.

Have you ever wondered how certain drugs can cure or help treat illness? For instance, you might have wondered how aspirin helps reduce pain. Well, health research begins with questions that have not been answered yet such as:

"Does a certain drug improve health?"

To gain more knowledge about illness and how the human body and mind work, volunteers can help researchers answer questions about health in studies of an illness. Studies might involve testing new drugs, vaccines, surgical procedures, or medical devices in clinical trials . For this reason, health research can involve known and unknown risks. To answer questions correctly, safely, and according to the best methods, researchers have detailed plans for the research and procedures that are part of any study. These procedures are called "protocols."

An example of a research protocol includes the process for determining participation in a study. A person might meet certain conditions, called "inclusion criteria," if they have the required characteristics for a study. A study on menopause may require participants to be female. On the other hand, a person might not be able to enroll in a study if they do not meet these criteria based on "exclusion criteria." A male may not be able to enroll in a study on menopause. These criteria are part of all research protocols. Study requirements are listed in the description of the study.

A Brief History

While a few studies of disease were done using a scientific approach as far back as the 14th Century, the era of modern health research started after World War II with early studies of antibiotics. Since then, health research and clinical trials have been essential for the development of more than 1,000 Food and Drug Administration (FDA) approved drugs. These drugs help treat infections, manage long term or chronic illness, and prolong the life of patients with cancer and HIV.

Sound research demands a clear consent process. Public knowledge of the potential abuses of medical research arose after the severe misconduct of research in Germany during World War II. This resulted in rules to ensure that volunteers freely agree, or give "consent," to any study they are involved in. To give consent, one should have clear knowledge about the study process explained by study staff. Additional safeguards for volunteers were also written in the Nuremberg Code and the Declaration of Helsinki .

New rules and regulations to protect research volunteers and to eliminate ethical violations have also been put in to place after the Tuskegee trial . In this unfortunate study, African American patients with syphilis were denied known treatment so that researchers could study the history of the illness. With these added protections, health research has brought new drugs and treatments to patients worldwide. Thus, health research has found cures to many diseases and helped manage many others.

Why is Health Research Important?

The development of new medical treatments and cures would not happen without health research and the active role of research volunteers. Behind every discovery of a new medicine and treatment are thousands of people who were involved in health research. Thanks to the advances in medical care and public health, we now live on average 10 years longer than in the 1960's and 20 years longer than in the 1930's. Without research, many diseases that can now be treated would cripple people or result in early death. New drugs, new ways to treat old and new illnesses, and new ways to prevent diseases in people at risk of developing them, can only result from health research.

Before health research was a part of health care, doctors would choose medical treatments based on their best guesses, and they were often wrong. Now, health research takes the guesswork out. In fact, the Food and Drug Administration (FDA) requires that all new medicines are fully tested before doctors can prescribe them. Many things that we now take for granted are the result of medical studies that have been done in the past. For instance, blood pressure pills, vaccines to prevent infectious diseases, transplant surgery, and chemotherapy are all the result of research.

Medical research often seems much like standard medical care, but it has a distinct goal. Medical care is the way that your doctors treat your illness or injury. Its only purpose is to make you feel better and you receive direct benefits. On the other hand, medical research studies are done to learn about and to improve current treatments. We all benefit from the new knowledge that is gained in the form of new drugs, vaccines, medical devices (such as pacemakers) and surgeries. However, it is crucial to know that volunteers do not always receive any direct benefits from being in a study. It is not known if the treatment or drug being studied is better, the same, or even worse than what is now used. If this was known, there would be no need for any medical studies.

• Next: Is Health Research Safe? >>
• Last Updated: May 27, 2020 3:05 PM
• URL: https://guides.library.harvard.edu/healthresearch

• Library databases
• Library website

Evidence-Based Research: Phrasing Research Questions

The researchable question.

The first step in doing evidence-based practice research is forming a researchable question. Questions that are too broad or too narrow can make your research difficult, if not impossible.

Clinical example:

• This topic is so broad that you'd have difficulty wading through all of the results.
• This question is so specific that there probably hasn't been anything published on that specific location regarding that specific population.
• Just right : In the NICU, what is the effect of hand washing on infection control compared with hand sanitizers, over 6 months?

Non-clinical example:

• This topic is so broad that you'd have difficulty wading through all of the results.  Also the wording in the question has to be more specific (use synonyms to include all possible versions).  For instance, heart disease is better known in the literature as cardiovascular disease, so search both ways. 
• This question is so specific that there probably hasn't been anything published on that specific location regarding that specific population. It can be only be determined by accessing the electronic medical records in the hospital and finding the rate.
• This question is just right because the variable name like “cardiovascular mortality” are descriptive and reflective of what is found in the literature.  Additionally, there are some control variables included to make sure that even if each group of race had individuals with different ages or different incomes, this would not explain away the differences in cardiovascular mortality impacted by race.

PICOT and other models

PICOT is a mnemonic that helps you remember the key components of a well-focused question. It stands for:

• P = Patient, Population or Problem
• I = Intervention, Prognostic Factor, or Exposure
• C = Comparison (optional)
• O = Outcome

PICOT examples:

Intervention/therapy

In _______(P), what is the effect of _______(I) on ______(O) compared with _______(C) within ________ (T)? 

In the aged population, what is the effect of exercise programs on accidental falls, as compared with no exercise?  

Are ____ (P) who have _______ (I) at ___ (Increased/decreased) risk for/of_______ (O) compared with ______ (P) with/without ______ (C) over _____ (T)?

Are adult smokers with a history of childhood asthma at increased risk of COPD compared to adult smokers with no history of asthma?  

Diagnosis or diagnostic test

Are (is) _________ (I) more accurate in diagnosing ________ (P) compared with ______ (C) for _______ (O)? 

Is the Hemoglobin A1C test more accurate in diagnosing diabetes as compared with fasting blood sugar levels?  

For ________ (P) does the use of ______ (I) reduce the future risk of ________ (O) compared with _________ (C)? 

For people with type 2 diabetes, does zinc supplementation reduce the future risk of foot ulcers compared with placebo?  

Prognosis/Predictions 

Does __________ (I) influence ________ (O) in patients who have _______ (P) over ______ (T)? 

In adults with osteoarthritis, does low vitamin D levels in the bloodstream predict the rate of future hip fractures?  

Meaning 

How do ________ (P) diagnosed with _______ (I) perceive ______ (O) during _____ (T)? 

How do cancer patients diagnosed with alopecia perceive their self-esteem during and after chemotherapy?

Public Health:

PICO(T) is commonly used to formulate research questions, sometimes referred to as ‘PI/ECO’ (Population/participants, Intervention/Exposure, Comparison, Outcome). The PI/ECO structure can be readily amended for different question types ( NHMRC Guidelines, 2019 ). A simple example might be:   

• Population / participants: Non-institutionalized civilian residents of the United States   
• Intervention (or Exposure): Hypertension (or Low Socioeconomic Status)  
• Comparison: Respondents without hypertension   
• Outcomes: Cardiovascular disease or cardiovascular mortality   
• Types of studies: Cross-sectional, Longitudinal

Alternate Models:

• PECO  – Population | Environment | Comparison | Outcome Very similar to PICO but looking at the effect of exposure to something e.g. smoky atmosphere
• SPICE  - Setting | Population | Intervention | Comparison | Evaluation Another variant of PICO but this time including the setting (where? in what context?)
• ECLIPSE  - Expectation | Client group | Location | Impact | Professionals | Service Recommended for health policy/management searches
• SPIDER  – Sample | Phenomenon of Interest | Design | Evaluation | Research Type Developed to create effective search strategies of qualitative and mixed-methods research - more specific than PICO/PECO

Search terms

Once you've developed your question, it's time to find keywords or search terms that you can use in the Library databases to find articles relevant to your question. Remember that each article does not necessarily need to address ALL the aspects of your question.

To learn more about selecting and combining appropriate search terms, please see our guides:

• Keyword Searching: Keyword Search Strategy
• Guide: Keyword Searching: Boolean
• Previous Page: Overview
• Next Page: Levels of Evidence Pyramid
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55 research questions about mental health

Last updated

11 March 2024

Reviewed by

Brittany Ferri, PhD, OTR/L

Research in the mental health space helps fill knowledge gaps and create a fuller picture for patients, healthcare professionals, and policymakers. Over time, these efforts result in better quality care and more accessible treatment options for those who need them.

Use this list of mental health research questions to kickstart your next project or assignment and give yourself the best chance of producing successful and fulfilling research.

• Why does mental health research matter?

Mental health research is an essential area of study. It includes any research that focuses on topics related to people’s mental and emotional well-being.

As a complex health topic that, despite the prevalence of mental health conditions, still has an unending number of unanswered questions, the need for thorough research into causes, triggers, and treatment options is clear.

Research into this heavily stigmatized and often misunderstood topic is needed to find better ways to support people struggling with mental health conditions. Understanding what causes them is another crucial area of study, as it enables individuals, companies, and policymakers to make well-informed choices that can help prevent illnesses like anxiety and depression.

• How to choose a strong mental health research topic

As one of the most important parts of beginning a new research project, picking a topic that is intriguing, unique, and in demand is a great way to get the best results from your efforts.

Mental health is a blanket term with many niches and specific areas to explore. But, no matter which direction you choose, follow the tips below to ensure you pick the right topic.

Prioritize your interests and skills

While a big part of research is exploring a new and exciting topic, this exploration is best done within a topic or niche in which you are interested and experienced.

Research is tough, even at the best of times. To combat fatigue and increase your chances of pushing through to the finish line, we recommend choosing a topic that aligns with your personal interests, training, or skill set.

Consider emerging trends

Topical and current research questions are hot commodities because they offer solutions and insights into culturally and socially relevant problems.

Depending on the scope and level of freedom you have with your upcoming research project, choosing a topic that’s trending in your area of study is one way to get support and funding (if you need it).

Not every study can be based on a cutting-edge topic, but this can be a great way to explore a new space and create baseline research data for future studies.

Assess your resources and timeline

Before choosing a super ambitious and exciting research topic, consider your project restrictions.

You’ll need to think about things like your research timeline, access to resources and funding, and expected project scope when deciding how broad your research topic will be. In most cases, it’s better to start small and focus on a specific area of study.

Broad research projects are expensive and labor and resource-intensive. They can take years or even decades to complete. Before biting off more than you can chew, consider your scope and find a research question that fits within it.

Read up on the latest research

Finally, once you have narrowed in on a specific topic, you need to read up on the latest studies and published research. A thorough research assessment is a great way to gain some background context on your chosen topic and stops you from repeating a study design. Using the existing work as your guide, you can explore more specific and niche questions to provide highly beneficial answers and insights.

• Trending research questions for post-secondary students

As a post-secondary student, finding interesting research questions that fit within the scope of your classes or resources can be challenging. But, with a little bit of effort and pre-planning, you can find unique mental health research topics that will meet your class or project requirements.

Examples of research topics for post-secondary students include the following:

How does school-related stress impact a person’s mental health?

To what extent does burnout impact mental health in medical students?

How does chronic school stress impact a student’s physical health?

How does exam season affect the severity of mental health symptoms?

Is mental health counseling effective for students in an acute mental crisis?

• Research questions about anxiety and depression

Anxiety and depression are two of the most commonly spoken about mental health conditions. You might assume that research about these conditions has already been exhausted or that it’s no longer in demand. That’s not the case at all.

According to a 2022 survey by Centers for Disease Control and Prevention (CDC), 12.5% of American adults struggle with regular feelings of worry, nervousness, and anxiety, and 5% struggle with regular feelings of depression. These percentages amount to millions of lives affected, meaning new research into these conditions is essential.

If either of these topics interests you, here are a few trending research questions you could consider:

Does gender play a role in the early diagnosis of anxiety?

How does untreated anxiety impact quality of life?

What are the most common symptoms of anxiety in working professionals aged 20–29?

To what extent do treatment delays impact quality of life in patients with undiagnosed anxiety?

To what extent does stigma affect the quality of care received by people with anxiety?

Here are some examples of research questions about depression:

Does diet play a role in the severity of depression symptoms?

Can people have a genetic predisposition to developing depression?

How common is depression in work-from-home employees?

Does mood journaling help manage depression symptoms?

What role does exercise play in the management of depression symptoms?

• Research questions about personality disorders

Personality disorders are complex mental health conditions tied to a person’s behaviors, sense of self, and how they interact with the world around them. Without a diagnosis and treatment, people with personality disorders are more likely to develop negative coping strategies during periods of stress and adversity, which can impact their quality of life and relationships.

There’s no shortage of specific research questions in this category. Here are some examples of research questions about personality disorders that you could explore:

What environments are more likely to trigger the development of a personality disorder?

What barriers impact access to care for people with personality disorders?

To what extent does undiagnosed borderline personality disorder impact a person’s ability to build relationships?

How does group therapy impact symptom severity in people with schizotypal personality disorder?

What is the treatment compliance rate of people with paranoid personality disorder?

• Research questions about substance use disorders

“Substance use disorders” is a blanket term for treatable behaviors and patterns within a person’s brain that lead them to become dependent on illicit drugs, alcohol, or prescription medications. It’s one of the most stigmatized mental health categories.

The severity of a person’s symptoms and how they impact their ability to participate in their regular daily life can vary significantly from person to person. But, even in less severe cases, people with a substance use disorder display some level of loss of control due to their need to use the substance they are dependent on.

This is an ever-evolving topic where research is in hot demand. Here are some example research questions:

To what extent do meditation practices help with craving management?

How effective are detox centers in treating acute substance use disorder?

Are there genetic factors that increase a person’s chances of developing a substance use disorder?

How prevalent are substance use disorders in immigrant populations?

To what extent do prescription medications play a role in developing substance use disorders?

• Research questions about mental health treatments

Treatments for mental health, pharmaceutical therapies in particular, are a common topic for research and exploration in this space.

Besides the clinical trials required for a drug to receive FDA approval, studies into the efficacy, risks, and patient experiences are essential to better understand mental health therapies.

These types of studies can easily become large in scope, but it’s possible to conduct small cohort research on mental health therapies that can provide helpful insights into the actual experiences of the people receiving these treatments.

Here are some questions you might consider:

What are the long-term effects of electroconvulsive therapy (ECT) for patients with severe depression?

How common is insomnia as a side effect of oral mental health medications?

What are the most common causes of non-compliance for mental health treatments?

How long does it take for patients to report noticeable changes in symptom severity after starting injectable mental health medications?

What issues are most common when weaning a patient off of an anxiety medication?

• Controversial mental health research questions

If you’re interested in exploring more cutting-edge research topics, you might consider one that’s “controversial.”

Depending on your own personal values, you might not think many of these topics are controversial. In the context of the research environment, this depends on the perspectives of your project lead and the desires of your sponsors. These topics may not align with the preferred subject matter.

That being said, that doesn’t make them any less worth exploring. In many cases, it makes them more worthwhile, as they encourage people to ask questions and think critically.

Here are just a few examples of “controversial” mental health research questions:

To what extent do financial crises impact mental health in young adults?

How have climate concerns impacted anxiety levels in young adults?

To what extent do psychotropic drugs help patients struggling with anxiety and depression?

To what extent does political reform impact the mental health of LGBTQ+ people?

What mental health supports should be available for the families of people who opt for medically assisted dying?

• Research questions about socioeconomic factors & mental health

Socioeconomic factors—like where a person grew up, their annual income, the communities they are exposed to, and the amount, type, and quality of mental health resources they have access to—significantly impact overall health.

This is a complex and multifaceted issue. Choosing a research question that addresses these topics can help researchers, experts, and policymakers provide more equitable and accessible care over time.

Examples of questions that tackle socioeconomic factors and mental health include the following:

How does sliding scale pricing for therapy increase retention rates?

What is the average cost to access acute mental health crisis care in [a specific region]?

To what extent does a person’s environment impact their risk of developing a mental health condition?

How does mental health stigma impact early detection of mental health conditions?

To what extent does discrimination affect the mental health of LGBTQ+ people?

• Research questions about the benefits of therapy

Therapy, whether that’s in groups or one-to-one sessions, is one of the most commonly utilized resources for managing mental health conditions. It can help support long-term healing and the development of coping mechanisms.

Yet, despite its popularity, more research is needed to properly understand its benefits and limitations.

Here are some therapy-based questions you could consider to inspire your own research:

In what instances does group therapy benefit people more than solo sessions?

How effective is cognitive behavioral therapy for patients with severe anxiety?

After how many therapy sessions do people report feeling a better sense of self?

Does including meditation reminders during therapy improve patient outcomes?

To what extent has virtual therapy improved access to mental health resources in rural areas?

• Research questions about mental health trends in teens

Adolescents are a particularly interesting group for mental health research due to the prevalence of early-onset mental health symptoms in this age group.

As a time of self-discovery and change, puberty brings plenty of stress, anxiety, and hardships, all of which can contribute to worsening mental health symptoms.

If you’re looking to learn more about how to support this age group with mental health, here are some examples of questions you could explore:

Does parenting style impact anxiety rates in teens?

How early should teenagers receive mental health treatment?

To what extent does cyberbullying impact adolescent mental health?

What are the most common harmful coping mechanisms explored by teens?

How have smartphones affected teenagers’ self-worth and sense of self?

• Research questions about social media and mental health

Social media platforms like TikTok, Instagram, YouTube, Facebook, and X (formerly Twitter) have significantly impacted day-to-day communication. However, despite their numerous benefits and uses, they have also become a significant source of stress, anxiety, and self-worth issues for those who use them.

These platforms have been around for a while now, but research on their impact is still in its infancy. Are you interested in building knowledge about this ever-changing topic? Here are some examples of social media research questions you could consider:

To what extent does TikTok’s mental health content impact people’s perception of their health?

How much non-professional mental health content is created on social media platforms?

How has social media content increased the likelihood of a teen self-identifying themselves with ADHD or autism?

To what extent do social media photoshopped images impact body image and self-worth?

Has social media access increased feelings of anxiety and dread in young adults?

• Mental health research is incredibly important

As you have seen, there are so many unique mental health research questions worth exploring. Which options are piquing your interest?

Whether you are a university student considering your next paper topic or a professional looking to explore a new area of study, mental health is an exciting and ever-changing area of research to get involved with.

Your research will be valuable, no matter how big or small. As a niche area of healthcare still shrouded in stigma, any insights you gain into new ways to support, treat, or identify mental health triggers and trends are a net positive for millions of people worldwide.

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Health information on the Internet — Can NIH offer any advice when searching for health information on the Internet?

The National Institutes of Health (NIH) has no official role in policing the quality of health information found on the Internet. Nevertheless, we can offer some advice.

• Web information should not be used as an alternative to seeking professional medical help. Don't use the information you find to make a self-diagnosis.
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The NIH Web site does not offer personalized medical advice to individuals about their condition or treatment. The resources on this site should not be used as a substitute for professional medical care and we urge you to work with your medical care providers for answers to your personal health questions.

If you have a medical question, please visit the Health Information on the NIH Web site. You should also visit MEDLINEplus.

If you have questions that relate to specific foods, or prescription, or over-the-counter drugs, you should visit the Food and Drug Administration (FDA) Web site .

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NIH is a medical research organization. As such, we only enroll patients who are participating in one of our clinical studies. These trials span a wide range of diseases and conditions. For information about clinical trials .

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No. However, please visit Healthfinder for information on choosing quality care.

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NIH's National Library of Medicine provides a guide to over 9,000 prescription and over-the-counter medications on its MEDLINEplus Web site . For the latest information on drug approvals and safety warnings, consult the Food and Drug Administration (FDA) Web site. For information about drug abuse and addiction, visit the National Institute on Drug Abuse (NIDA).

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The mission of National Center for Complementary and Integrative Health (NCCIH) is to define, through rigorous scientific investigation, the usefulness and safety of complementary and integrative health interventions and their roles in improving health and health care.

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The NIH Clinical Center provides an opportunity for healthy volunteers to participate in medical research studies (sometimes called protocols or trials). Healthy volunteers provide researchers with important information for comparison with people who have specific illnesses. Every year, nearly 3,500 healthy volunteers participate in studies at NIH. Visit the Clinical Research Volunteer Program to learn about the benefits of volunteering.

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Some NIH Institutes have established special on-line areas to provide statistical information. Visit the following links for information on: cancer, complementary and alternative medicine, deafness and communication disorders, dental health, diabetes, digestive diseases, kidney and urologic diseases, obesity, drug abuse, eye disease, and mental health.

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Visit our Research Training Opportunities page. This site brings together information about the intramural and extramural training opportunities offered by all of NIH's Institutes and Centers.

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NIH LRPs are a vital component of our nation's efforts to attract health professionals to careers in clinical, pediatric, health disparity, or contraceptive and infertility research. Visit https://www.lrp.nih.gov for all the details and to complete an online application for NIH Loan Repayment benefits.

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The HHS Office of Research Integrity (ORI) promotes integrity in biomedical and behavioral research supported by the U. S. Public Health Service (PHS) at about 4,000 institutions worldwide. ORI monitors institutional investigations of research misconduct and facilitates the responsible conduct of research through educational, preventive, and regulatory activities.

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Founded in 1887, the National Institutes of Health today is one of the world's foremost medical research centers, and the Federal focal point for medical research in the United States. The NIH, comprising 27 separate Institutes and Centers, is one of eight health agencies of the Public Health Service which, in turn, is part of the U.S. Department of Health and Human Services.

Simply described, the goal of NIH research is to acquire new knowledge to help prevent, detect, diagnose, and treat disease and disability, from the rarest genetic disorder to the common cold. The NIH mission is to uncover new knowledge that will lead to better health for everyone. NIH works toward that mission by: conducting research in its own laboratories; supporting the research of non-Federal scientists in universities, medical schools, hospitals, and research institutions throughout the country and abroad; helping in the training of research investigators; and fostering communication of medical and health sciences information.

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• Published: 22 December 2022

Rare diseases and space health: optimizing synergies from scientific questions to care

• Maria Puscas   ORCID: orcid.org/0000-0002-5880-5157 1   na1   nAff13 ,
• Gabrielle Martineau   ORCID: orcid.org/0000-0003-3980-4631 1   na1   nAff14 ,
• Gurjot Bhella 1   nAff15 ,
• Penelope E. Bonnen 2 ,
• Phil Carr 3 ,
• Robyn Lim 4 ,
• John Mitchell   ORCID: orcid.org/0000-0002-6055-6858 5 ,
• Matthew Osmond 6 ,
• Emmanuel Urquieta 7 ,
• Jaime Flamenbaum   ORCID: orcid.org/0000-0002-8473-5551 8 ,
• Giuseppe Iaria 9 ,
• Yann Joly 10 ,
• Étienne Richer   ORCID: orcid.org/0000-0002-5814-5777 11 ,
• Joan Saary 12 ,
• David Saint-Jacques 1   nAff16 ,
• Nicole Buckley 1   nAff17 &
• Etienne Low-Decarie   ORCID: orcid.org/0000-0002-0413-567X 1   nAff18  

npj Microgravity volume  8 , Article number:  58 ( 2022 ) Cite this article

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Knowledge transfer among research disciplines can lead to substantial research progress. At first glance, astronaut health and rare diseases may be seen as having little common ground for such an exchange. However, deleterious health conditions linked to human space exploration may well be considered as a narrow sub-category of rare diseases. Here, we compare and contrast research and healthcare in the contexts of rare diseases and space health and identify common barriers and avenues of improvement. The prevalent genetic basis of most rare disorders contrasts sharply with the occupational considerations required to sustain human health in space. Nevertheless small sample sizes and large knowledge gaps in natural history are examples of the parallel challenges for research and clinical care in the context of both rare diseases and space health. The two areas also face the simultaneous challenges of evidence scarcity and the pressure to deliver therapeutic solutions, mandating expeditious translation of research knowledge into clinical care. Sharing best practices between these fields, including increasing participant involvement in all stages of research and ethical sharing of standardized data, has the potential to contribute to humankind’s efforts to explore ever further into space while caring for people on Earth in a more inclusive fashion.

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Introduction.

For tackling complex issues, the value of bridging across disciplines is recognized for addressing scientific questions of pressing societal significance 1 . As such, domains that share more commonalities may advance faster than disparate areas 1 . Rare disease and space health are two health domains for which interdisciplinary collaboration may appear challenging, as they are at first glance fairly disparate, whether spatially (terrestrial vs. celestial environments), etiologically, demographically, methodologically, or ethically (Table 1 ). With just around 600 people having reached Earth orbit, astronaut health in space could be considered a niche research subject 2 . While this number increases significantly when taking into account participants in ground analogs, it can be difficult to accurately mimic the physiological and psychological responses to spaceflight. In contrast, rare diseases, though individually rare, are estimated to affect upwards of 300 million people across the thousands of known rare diseases 3 . This is reflected in the research output in terms of the number of scientific publications referencing rare diseases which is proportionally larger than for space health (Fig. 1 ). Whereas rare diseases are predominately characterized as permanent genetic disorders, conditions linked to space exploration are often transient results of exposure to occupational health hazards among predominantly healthy adults 4 , 5 . These differences lead to variation in the approaches to research and therapeutic care, between rare diseases and space health and even to the process of how research topics are selected and how knowledge is converted into health solutions. This contrast is reflected in the coverage of genetic and occupational consideration in the linked scientific literature (Figs. 1 and 2 ). Despite striking differences, there are clear avenues for exchange between rare disease and space health research and care.

Rare disease, despite being individually rare collectively affect a significant proportion of the population and thus elicit a higher research output than space health. Even with the revolutions in genomics, genetic studies in astronauts remain rare. Despite commonality of genetic basis for rare disease, genetic studies have increased in the field of rare diseases but they do not represent a dominant research topic in the scientific literature nor even, surprisingly, a growing proportion of the scientific literature. Consideration of “natural history” seems mostly absent from the space health literature but appears as often as genetic in the rare disease literature. The number of annual publications for the keywords “rare disease” (blue) and “astronaut” + “health” (orange) from 1990 to present day (2021). Data was additionally generated for keyword combinations such as “rare disease” and “natural history” (green), “genetic” and “astronaut” + “health” (yellow), and “genetic” and “rare disease” (red). No publications were found for the “astronaut” + “health” and “natural history”. All data was generated using Web of Science. Data in Source data 1.

Despite a common focus on health, the fields of rare diseases and space health have little overlap in terms of dominant research topics. Space health appears to be technology or engineering oriented, while rare disease integrates a more medical focus. The top 26 most common research categories based on number of publications were generated from Web of Science for the keyword’s “astronaut” + “health” and “rare disease”. The top 10 categories based on publications were graphed for both “astronaut health” and “rare disease”. Five out of 52 total research topics found in common between both keywords were also graphed and denoted with * (Multidisciplinary Sciences, Oncology, Neurosciences Public Environmental Occupation, and Radiology Nuclear Medicine). Data in Source data 2.

There are examples of valuable knowledge transfers between the fields of rare diseases and space health. Overlaps exist in terms of terrestrial prevention strategies, as well as underlying physiological explanations. For example, investigators have unveiled a genetic predisposition for astronauts to develop ophthalmologic issues such as choroidal folds, lines in the posterior pole of the eye, similar to women suffering from polycystic ovary syndrome (PCOS) 6 . Initial studies have shown an association of one-carbon metabolism pathway polymorphisms with ophtalmic changes 7 , 8 , which could lead to potential terrestrial prevention strategies 7 . From a neurovestibular perspective, the changes in gravity fields may also cause a decline in the ability of astronauts to orient in the surrounding 9 , a phenomenon similar to the one experienced by individuals affected by a rare familial disease 10 known as developmental topographical disorientation (DTD) 11 , 12 .

Commonalities between rare diseases and space health are not limited to specific overlaps in physiological explanations for phenomena. Notably, both areas are characterized by a lack of comprehensive, diverse, and validated personal data in order to derive novel scientific solutions. Moreover, rare disease and space health research often entail small sample sizes that influence the types of trials that can be used and, subsequently, the methods of data analysis adopted 13 . Indeed, some types of research trial designs are ethically and statistically inappropriate in these circumstances. General universal ethical principles mandate that with a paucity of participants in both fields, it is crucial to ensure that participants are consulted about the choice of available research topics, their priorities, and therapeutic options in order to align participants’ and researchers’ priorities to research outcomes. In order to minimize some of the identified barriers to conducting research in a rare disease or space health context, increasing collaborative data sharing and open model research is lauded for potentially establishing a foundation for future experimentation 14 .

To better guide our evaluation and discussion, we conducted a baseline literature search to identify synergies and discrepancies between the 2 areas of research (rare disease and astronaut health). We searched PubMed using the keywords “astronaut” “health” and separately “rare disease” from the years 2000–2021. In order to have the most similar sample sizes for both searches, all “astronaut” “health” articles were included, while “rare disease” articles were sorted by “Best Match” in descending order, and the top 5 original research articles for each year (2000–2021) were included. Articles were then reviewed and original articles were included per the protocol outlined in the Supplementary Materials, which includes the data collected. The results from the PubMed search are referenced in text. Bibliometric data for Figs. 1 and 2 used in figures was obtained separately from Web of Knowledge, which provides category information. Data is provided in Source data 1 , 2, and 3 and further details about data collection are provided in Supplementary Methods.

Here, in an effort to identify areas of translational opportunity where one area could benefit from the other, or in which both fields could derive benefit, we first expand on the definition of rare disease and space health and elaborate on how defining differences could lead to contrasts in the selection of research topics to be investigated. Then, we delve into shared challenges found across rare disease and space health areas (i.e., limited long-term knowledge and small sample sizes) and highlight the opportunity of implementing collaborative data-centric strategies, as well as individualized approaches in both research and care.

Definitions and participants at hand

Definitions of what constitutes a rare disease depend on the incidence rate of the specific disorder in the population. These rates often coincide with the pharmaceutical regulations surrounding orphan drugs (drugs for rare diseases) and vary from country to country. In the United States, rare diseases have been defined as affecting 200,000 individuals or less while Canada has proposed to define it as <5 in 10,000 15 , 16 . Out of over 7,000 rare diseases, 72% are linked to a genetic condition and 70% primarily affect children 17 . Given how many rare conditions are inherited and the permanent nature of those conditions, a substantial proportion of rare disease research aims to develop effective therapeutics by investigating the genetic targets/pathways of the disease (Fig. 1 ). Health conditions linked to human space exploration may well be considered as a narrow sub-category of rare diseases, as these conditions only affect a subset of the already small population of astronauts. However, in contrast to the majority of rare disease, conditions linked to human space exploration are seen as resulting from occupational health hazards present in an environment in which generally healthy, highly-screened adults have decided to take certain calculated risks, generally, in the context of employment. This etiology is reflected in the space flight-associated scientific literature in terms of reference to occupational considerations (Fig. 1 ). More recently less screened civilians flying with commercial spaceflight companies have also had increasing access to the space environment. Evidence reviewed by NASA through the Human Research Program (HRP) has categorized the risks of space exploration missions into the categories of Human Factors and Behavioral Health Performance, Space Radiation, Exercise and Extravehicular Activity, and Exploration Medical Capabilities 18 . Similar categories for space biomedical research are adopted by the Canadian Space Agency (CSA), Japan Aerospace Exploration Agency (JAXA), and the European Space Agency (ESA) to guide research topics 19 , 20 , 21 .

Both rare disease and space health research and care are hindered by the deficiency of diversity or representativeness of the people who engage with the research as subjects and the wider communities affected. In the rare disease context, there is high heterogeneity in both phenotypic expression of rare diseases and treatment effects, representing a practical challenge to measuring the success of clinical treatments 22 , 23 . Despite this, the genomic information available in rare disease databases overwhelmingly comes from individuals with European ancestry with other ancestries underrepresented in population studies 24 . A lack of comprehensive genomic data can make it more challenging to differentiate between a ‘rare’ disease and a condition that is more common amongst individuals that are not of European ancestry. Astronaut cohorts have historically been mainly homogeneous and typically consisting of middle-aged men of European descent who maintain exceptional physical fitness and fit within a certain height range. While physical fitness remains a requirement for NASA and International Partner astronauts, there has been an increasingly diverse population of flyers including more women and those of non-European descent that will continue to grow with the possibility of more accessible commercial spaceflight opportunities 25 . Certain conditions pertaining to space flight also impact individuals differently based on sex, including references to how women have greater loss of blood plasma volume than men during spaceflight and women’s stress response includes heart rate increase while men respond with increase in vascular resistance. Similarly, race, ethnic groups, and sex can have varying space radiation cancer risk predictions, with Asian-Pacific Islanders and Hispanic populations having the lowest overall cancer risks, and White females having the highest 26 .

Differences in the etiology of conditions associated with space health and rare diseases lead to differences in care. Health research conducted in space has been focused on characterizing the physiological responses to living in the extremes of space and on prevention of those deleterious to crew health and performance 18 . Space agencies have implemented preventive measures (countermeasures) to ensure that astronauts maintain a good health during and after space missions, and to reduce the impact of known space-related physiological adaptive processes such as loss of bone density and muscle and changes in neurovestibular function 27 . In juxtaposition, rare disease clinical care is primarily focused on diagnostic treatments and therapeutics that rely on both valid applicable evidence in tandem with clinical expertise 28 . With greater recognition of environmental influences on the onset and phenotypic presentation of rare disorders, increased population genetic screening may reveal that there are identifiable preventative measures such as avoiding exposure to toxins and lifestyle changes that one can take to reduce the onset of certain disorders 29 .

Selection of research topics

Likely due to the contrast in etiology and focus of care, rare disease and space health fields identify and prioritize research questions differently (Fig. 2 ). Rare disease research appears to have a researcher-led nation-agnostic development of questions, which is common to most life science fields of research. While space health research has a more centrally-guided research mandate put forward by national space agencies based on solving issues that could impact astronaut health, and that would negatively impacting lengthy and costly space missions.

In addition to the government programs that commonly fund health research, large foundations such as the National Organization for Rare Disorders (NORD) and the Rare Disease Foundation as well as many disease-specific not-for-profits and charities, also fund rare disease research 30 , 31 . Some efforts are made by the rare disease research communities and these foundations, to identify common questions and ways forward 32 . Of the articles reviewed, 8% of rare disease articles reported receiving funding from a foundation. The rare disease research community has pioneered the involvement of patients and their families at the very onset of research to identify worthy research topics and ensure that research priorities align with what is considered clinically important to the family or the patient. In light of many rare disease patients having shortened lifespans and limited treatment options, patient involvement in research and trial design greatly enhances a sense of self-efficacy and the ultimate quality of care provided 33 .

In comparison, space health research questions are generally driven by the mission risks and the engineering mitigation measures to alleviate those risks as identified by national space agencies (Fig. 2 ). The reason for this focus is likely in part driven by the source of funding for this research, with 70% of astronaut health articles reported receiving funding from a space agency and 45% received funding from government bodies. In sharp contrast, only 14% of rare disease articles reported funding from government bodies and topics were generally medical. Space health research may benefit from a diversification of sources of funding, including more generalist health or science funding agencies, and from research that goes beyond evaluating engineering solutions to health risks to greater integration of topics common in rare disease research, particularly genetic heredity. On the other hand, rare disease research may find value in engaging engineering solutions to mitigate the triggers or effects of rare diseases. Also, we have preferred the use of the term space health, where others may have used space medicine, to reflect that the focus of most of this work is not medical in nature.

As of November 2020, 3000 experiments had been conducted onboard the International Space Station (ISS), mostly by astronauts, with 300 of these experiments involving human research. This participation highlights the high degree of skill among astronauts required to perform innovative life science experiments, among the dominating physical and material sciences experiments 34 . Despite their involvement in the execution of research experiments, astronauts are not always involved in the process of generating research questions and designing experimental protocol to better tailor the space health focus on both their needs and interests 35 . Increased astronaut involvement in research, mainly through greater stakeholder power in determining experiments (i.e., ensure research addresses what matters to the astronaut not only to the researcher) could increase the relevance and uptake of the research outcomes. Both rare disease and space health communities could achieve greater participant satisfaction by prioritizing participant involvement throughout the research process and ensuring a ‘real’ partnership with participants prior to enrollment in research clinical trials.

The sample size issue: how small is small?

Research involving distinct populations, such as rare disease patients and astronauts, are associated with small sample sizes. For space health, approximately 600 humans have travelled to space, with a limited number of participants available for research this far 36 , 37 , 38 . Moreover, the limited number of flight opportunities associated with the high cost of space travel is often cited as a fundamental obstacle to carrying out experiments in the near-Earth orbit 39 . While hundreds of millions of people worldwide are affected by rare diseases, the number of patients developing a particular disease is low compared to other prevalent diseases, and often vary in frequency from less than a dozen documented cases to millions globally 28 . Moreover, as for any disease and treatment, genotypic and demographic variability within rare diseases further reducing the population that can be targeted with a given therapy, as patients may have vastly different responses to treatments 40 . Of the articles we reviewed, the median [interquartile range] study sample size for astronaut health was 13 [7–26] participants while the median rare disease sample size was 1 [1–16]. Despite the low incidence rate of rare diseases, cross-national collaboration and extensive database information can allow rare disease researchers to obtain larger sample sizes. The target size (number of study participants that are either people with rare diseases or astronauts) in the articles we reviewed was significantly lower, with astronaut health having a median of 1 [0–12] participants and rare disease with 1 [1–9.5]. The requirement for substantial sample sizes impacts the study design of prospective research trials.

Typically, when it comes to choosing a design to test the effectiveness of an intervention, randomized-control trials (RCTs) have long been regarded as the gold standard to producing reliable evidence. However, rare disease researchers have found that RCTs have questionable reliability in rare disease research, largely in part due to small sample sizes 41 . When trial designs do not contain a sufficient sample size and statistical power, alternative designs and analyses can allow research to proceed on the grounds that the research question has great clinical significance 13 . Bayesian approaches can permit the incorporation of real-time knowledge into the ongoing clinical trial and analysis. This provides an opportunity for rare disease researchers to pivot when encountering novel information and to enhance the trial design as opposed to starting from scratch. Such approaches include adaptive design that makes use of ongoing trial data to modify trial design aspects as need be 42 . Proposed designs include the use of sequential multiple assignment randomized trials (SMARTs) that can allow comprehensive testing of the efficacy of multiple drugs for a particular rare disease to determine which drug can best serve as the standard therapy for a particular disorder 43 . Moreover, implementation of “N-of-1” trials in which an individual participant undergoes consecutive periods of treatment(s) or placebo, have been published in both the rare disease and space health literature 41 , 44 . In the articles reviewed, we found that 63% of the rare disease articles were case studies ( n  = 1) while only 5% of the astronaut health studies were classified as case studies. For both rare disease and space health, experimental design and statistical approaches are likely to continue to evolve to better address the challenges of small populations, with the need for regulation to follow.

One of the main barriers to conducting clinical trials in the setting of orphan drugs for rare diseases is the recruitment of patients. To combat low patient recruitment, involving rare disease patients and astronauts in the experimental design process has been proposed 13 . Involving research participants in the experimental design has great potential, however, the burden (i.e., time, travel, and financial considerations) associated with participation may prove to strain the development of research, especially in communities that are seeking larger sample sizes 45 . Longitudinal, extensive follow-up evaluations commonly associated with rare disease trials can deter otherwise willing participants and families from participation.

In order to overcome this challenge, it has been suggested that clinical trials be carried out with multicenter involvement instead of using one facility to conduct all research experiments 46 . Of the articles reviewed, 29% of astronaut health studies involved a multicenter layout, while only 11% of rare disease articles were designated as multicenter. To continue to do so, technological advances can be used to stimulate patient participation through gathering sporadic and continuous patient information from home through modern methods of data capture 47 . These advancements can encourage patient registration in research, especially for families and patients that are reluctant to participate due to financial and psychological concerns over long-term travel and follow-up. Similarly to rare diseases, astronaut participation in research is voluntary, however, due to the occupational nature of the health concerns being addressed, ongoing surveillance of occupational health hazards may serve as a requirement for employment 48 .

In an attempt to alleviate the burden of research participation placed on astronauts, alternative environments, such as analog environments and simulation facilities, have been proposed 18 , 49 . While there are limitations to using ground-based analogs, this often remains the most feasible and viable alternative to best prepare for space exploration-class missions and obtain relevant data when space travel is not a possibility 18 . For space health, microgravity analogs such as parabolic flight have been used. Facilities with “analog” relevance for rare diseases include organ-on-a-chip micro-scale systems that are designed to simulate human tissues can be instrumental in advancing rare disease research, especially when intervention therapy is not a possibility 49 . Utilizing analog approaches from space health research may prove to be instrumental in rare disease research, especially concerning rare diseases with short lifespans and ones where unstable patient conditions do not allow for human research to be performed.

Small sample size research demands a methodological high standard for data analyses 14 . Rare disease researchers must in turn be able to produce statistically significant results that adhere to regulator standards in order to use the data to get approval for therapeutics 42 . Moreover, the lack of replicability of current space health research poses a significant problem in the area 50 . For both communities, it can be concluded that a small sample size highlights the limitations of applying traditional statistical methods to conduct research and is the major challenge for the need to generate evidence and find curative treatments.

Given the challenges implied in meeting statistical requirements, many have raised the issue of relaxing standard margins for statistical significance in regard to designing clinical trials, pending careful considerations of the cost/benefits for all stakeholders 42 . As an alternative, authors suggest that the main criteria for publication should revolve around the pertinence of the study in adding knowledge of clinical or public health, as well as on the validity of the methodology and the experimental rigor of the study design. The US Food and Drug Administration (FDA)’s popularly used Guidance for Industry on Enrichment Strategies for Clinical Trial to Support Approval Of Human Drugs And Biological Products outlines flexible evidence standards to show drug efficacy for low-frequency molecular alterations by using those “mutations” to identify patients with specific biomarkers and patients with a greater chance of prominent worsening conditions 51 . This is part of the FDA’s efforts to advance the development and availability of effective treatments for rare diseases 40 . To atone for the lower empirical standard, the FDA recommends detailed, transparent labeling information for drugs, especially pertaining to information about the level of evidence supporting the therapeutic 40 , 51 . Consequently, this change could assess gaps in knowledge and stimulate beneficial collaborations between scientists to share and combine data to increase sample size.

Natural history as a mitigating factor to small sample size and knowledge gaps

Numerous challenges to rare disease research and therapeutic development include: (1) relatively rare viable and tailored treatments or approved therapies, (2) uncertainties in diagnostic detection and (3) in establishing robust endpoints, and (4) the existence of large knowledge gaps in natural history 42 , 50 . Defining the right variables and parameters for rare disease clinical trials is especially challenging, since the understanding of underlying mechanisms and conditions for disease development and treatment remain poorly understood 52 . Research in space health faces similar issues as the high costs of space missions, methodological constraints and specifics associated with conducting research in an isolated, confined, and extreme (ICE) environment, complicating the mobilization of knowledge into action 39 . Amongst other challenges in the design of space health experiments, the high cost and difficulty associated with transporting equipment into space, as well as the necessity to develop protocols that are tailored to the ICE environment are often regarded as contributing factors to the lack of consistent information in the field. Rare disease and space health fields are often tasked with experiments that cannot be easily reproduced, which is problematic, as reproducibility (along with predictability and falsifiability) are the cornerstone principles of experimental research.

Space health research often focuses on countermeasure development, which can be insufficient in addressing all space health risks, as seen by the limited progress in areas such as risk of cancer caused by HZE, high atomic number and high energy, charged particle radiation 4 . In order to achieve better astronaut health and performance mitigation strategies, promoting and providing high-value applied research concerning the efficiency of treatments and consideration of novel treatments should be taken into consideration 18 .

The scarcity of individuals affected by individual rare diseases and of astronauts who have travelled to space, as well as the heterogeneity of those individuals, has contributed to the knowledge gaps in both fields (Fig. 1 ). As few as 70 articles include data collected during space flight addressing psychological, behavioral challenges and performance of astronauts arising from space exposure 38 . Improving natural history studies has been proposed to address small n sample sizes and replication concerns, thus helping refine questions and fill knowledge gaps in space health and rare disease research 53 . A natural history study collects health information over time to understand how the medical condition or disease develops and to give insight into how it might be treated 53 . The study of natural history can provide a foundation for informing future treatments, biomarker identification, and facilitating the translation of research into therapy 54 . The long-term diagnosis associated with the majority of rare diseases requires in-depth knowledge on biological mechanisms at every stage in disorder progression, thus natural history studies play a prominent role in identifying gaps in existing scientific knowledge 55 .

Comprehensive natural histories, particularly before or long after space flight, have been notably rare in this field (Fig. 1 ), however, long-term monitoring of astronauts has been used for decades to better inform research questions. Regardless of spaceflight experience or time in the astronaut corps, long-term health data has been captured and is at least theoretically available for research pending consent for all NASA astronauts ( n  = 360) (information valid as of August 5, 2022 provided by the NASA Lifetime Surveillance of Astronaut Health -LSAH-). These long-term monitoring initiatives are akin to natural history studies for rare diseases, but would benefit through greater international implementation. Along those lines, the integration of research evidence suggests that, in order to achieve better astronaut health and performance mitigation strategies, performing a constant monitoring of astronaut’s health, validating the current astronaut selection process and refining and improving the selection system should be taken into consideration 18 .

Tailored approaches

As more scientific knowledge is being harnessed in both areas of research, we now understand the relevance of more tailored approach to research and care, factoring in spatial, genetic, and environmental heterogeneity for rare disease and space health research participants. New rare diseases are being discovered or characterized annually. As approaches to research and care need to be adapted to individual rare disease 56 , new approaches need to be continuously developed 56 . Heterogeneity (including in terms root cause, symptom presentation, therapeutic course, and response to treatment) within and among rare diseases can contribute to the difficulties associated with the efficacy of treatments. While genetic variation is high among various rare diseases, genotypic and phenotypic divergence exists even within individuals affected by the same rare disease. For rare diseases, the variation that is addressed is primarily physical differences between individuals and their clinical condition, though consideration of environmental factors is beneficial. Tailoring approaches in the context of space health requires consideration of variations between individuals, but also differences in mission variables (dose exposures, mission length, destination, and occurrence) and the interaction between these two factors 18 .

Next-generation sequencing (NGS) has been an important factor in increasing the capacity for identifying the genetic basis for rare diseases, allowing people to receive tailored research and care, that takes into consideration genetic variations that distinguish rare diseases and variations within specific rare diseases 57 . Space health research and care does not appear to have benefitted to the same extent from advancements in genomics, potentially because of the pervasive issue of genetic data regulations for employment when it comes to research and development involving human genetics 58 . It is NASA’s policy to only voluntarily obtain and use human research genetic testing for risk identification related to space exploration and informing clinical care 59 . The responsibility to protect the privacy of astronaut genetic information to the fullest extent of the law as per GINA (the Genetic Information and Non-discrimination Act) is outlined in NASAs Policy Directive and prohibits the use of human genetic information for employment decisions related to astronaut selection, training, and missions 59 .

However, the European Space Agency recently found that the individual response to approximately one-third of drugs available on the International Space Station are substantially affected by heritable polymorphic metabolizing enzymes 60 . This shows how standardized screening and testing may have significant benefit for tailoring astronaut countermeasure regimes to reflect individual need. The field of space health research could reap benefits of adopting genetic screening approaches from the rare disease field to improve clinical outcomes. Future technological advancements in the space exploration field will allow for the production of therapeutic molecules tailored to the needs of a patient, potentially implemented aboard spaceships for long-duration cosmic missions. Such adapted approaches include experimental designs that align treatments to specific subgroups in a larger sample size, allowing for a generally more efficient allocation of health resources.

In the context of rare diseases, since treatment options are often uncertain and are greatly influenced by patients and their families’ preferences regarding treatment avenues, incorporating patients as active decision-makers can reveal important considerations for trial designs 33 , 45 . Furthermore, patients can provide invaluable insight into treatment effectiveness and potential side-effects, allowing researchers to optimize both existing and future therapeutics. Taking into consideration the variety of physiological responses/symptoms manifesting in rare diseases and astronaut health, personalized approaches can more effectively utilize existing treatment regimens and tailor them to specific individuals/groups.

Personalized clinical care brings a new outlook to the table which includes predictive and tailored therapeutics, earlier interventions and better clinical endpoints, and hence greater general effectiveness 23 . Integrating the evaluation of various patient characteristics and interactive feedback between patients and clinicians throughout the entire process of clinical trials could be of highest value to define tailored clinical outcomes and to enhance our understanding of the most suitable treatment administration for both patients and clinicians 22 . Moreover, a recent review study suggested that the enrollment of participants in clinical trials as decision-makers as opposed to solely study volunteers can optimize interpretation of clinical outcomes 61 . Personalized approaches, whether in the form of dynamic variables or tailored care, represent an area for space health and rare disease fields to invest in.

Collaborative data management

Due to the complex issues faced in rare disease and space health research, stakeholders have much to gain through comparable approaches to data management. After experiments are conducted, great pressure is placed on ensuring the viability of the samples and subsequent data analysis procedures. The collection, processing, and storage of resources and samples associated with space health and rare disease research require comprehensive data standardization processes. Moreover, compiling global or multinational standards to how evidence is collected while increasing data sharing among communities can mitigate the reproducibility and validity concerns associated with rare disease and space health studies 46 . The design of the Core Outcome Measures in Effectiveness Trials (COMET), while not specific to either field, could serve as a crucial tool in establishing a minimum foundation of outcomes to be included in future trials around the world 62 . Global initiatives that bring experts in their respective communities together can be employed to maximize the use of generated scientific data while taking into consideration the limited resources available to both communities 14 , 35 . That being said, establishing international partnerships in rare diseases and space health research and development represent an additional challenge, given the plurality and heterogeneity of participants encountered in those fields.

Promoting international efforts to create standardized regulatory and ethical data governance policies would be highly beneficial for rare diseases research and development. Such policies would promote collaborative research and thus prevent knowledge duplication. Fostering collaborations between countries can also lower the expenses of translational research for many stakeholders, and guarantee an easier, faster access to therapeutics to patients 23 .

Similarly, for the space health community, collaboration between individuals and research groups is truly important 63 . The fact that the ISS is an international research facility, which is also the main platform available to scientists to gather space health in-flight data, ensures collaborations between various space agencies. As ISS partner nations conduct their research programs, international collaboration and exchange among scientists worldwide is growing rapidly. The many research projects based onboard the ISS are often the results of cooperation between many ISS partners. Japan (JAXA) and Russia (Roscosmos) teamed up to study new treatment options for Duchenne Muscular Dystrophy through a protein crystal growth experiment in 2009, providing insights into potential biological pathway targets for treatment, which underpins the value of multinational collaborations in the investigation of novel treatment avenues 64 . Moreover, NASA reiterates that such partnerships initiated between research groups are key elements to promote and instill collaboration and teamwork values amongst stakeholders and to work toward efficient problem solving 65 . Recently, the exponential growth in civilian commercial spaceflight will bring new opportunities to collect more diverse data in a high throughput fashion.

In parallel, there is evidence of a collective effort and interest toward data standardization in the rare diseases’ community as the case of Myotonic Dystrophy (i.e., DM), where health care professionals took part in an international collaboration initiative that is the D-M Scope patient registries 66 . In the rare disease community, the increased use of extensive databases such as Orphanet, serves as a model for international data collection 67 . As a further example, The Matchmaker Exchange (MME) has shown how international data sharing in the rare disease realm can be optimized by enabling searches of multiple databases at once, while allowing for quicker identification of rare genotypes and phenotypes in a manner respectful of participants confidentiality right 68 . Matching algorithms of the MME have shown promising success in rare disease gene discovery by using participant(s) genotype and phenotypic features to retrieve similar cases 69 , 70 , 71 , 72 . The implementation of core outcomes for rare disease registries, as seen in COMET, can further standardize existing databases, and eliminate fundamental discrepancies among and/or within registries.

In order to maximize the benefits associated with data exchange between researchers, establishing a common language for data standardization is crucial to ensuring data is easily and accurately interpreted. Data standardization comes about through different implemented approaches. In space health, researchers have resorted to the lowest common denominator approach as a means to define the variables contained in the omics datasets 73 . Rare disease and space health researchers must work with a finite number of resources; therefore, quality data collection standards are essential to preserving quality evidence.

Over the past years, NASA’s Life Sciences Data Archive (LSDA), PubSpace, NASA NTRS as well as GeneLab initiatives, have sought to improve data availability and thus can be regarded as a great leap forward in working with sensitive data 74 , 75 . Along those lines, a recent review revisiting the implications of open model research suggested that NASA’s open innovation research model, involving open peer-production, fostering collaboration amongst research, and development professionals, has spurred the development of scientific knowledge 76 . Of the articles reviewed, 29% of the astronaut health articles reported using databases in their research and 16% of the articles had open access availability.

Primarily given the wide array of rare diseases and low incidence rate, it is highly unlikely for a single group to advance research alone 77 . Data sharing may be a valuable resource in understanding natural history, disease progression, and providing an adequate sample size to work with. Of the articles reviewed, only 8% of rare disease articles used public databases. Given that pathophysiology occurring in astronauts can be characterized as occupational-based, crew members are not able to opt out of occupational surveillance as it is intended for use only within the organization to better understand the hazards associated with spaceflight 18 . While participation in research is voluntary, space organizations are aware of the potential for coercion and thus have rigorous informed consent procedures 48 . Due to the small number of individuals available for research, international data sharing can lead to direct identification of participants, even with privacy regulations in place. Individuals with rare diseases who seek support through patient support forums found on rare disease foundation sites or webpages are at high risk of re-identification in hospital datasets due to their unique identifier combinations (e.g., age, sex, rare disease, marital status) 78 . Astronauts face additional privacy concerns about identifiability due to their visibility in the public eye.

In the context of rare diseases, participant enrollment in clinical trials, is driven by the physical, financial, and emotional burden and day-to-day impacts of rare diseases on the patient and their communities 45 . A sense of commitment to the research cause is present in participants from both scientific fields, however, for many rare disease patients this is often an urgent effort to discover new possible quality of life-preserving treatments. Ensuring that rare disease patients and their families receive in-depth information, are supported prior to enrollment, and are able to give and revoke consent for participation at any point is crucial to successful and non-exploitative research.

Data privacy laws are increasing in sophistication globally to allow for a transition into the big data era of mass data sharing, often resulting in tightened laws with higher consent standards and safeguards in place, allowing for less flexibility to share samples and data internationally 77 . In order to achieve a balance between too lenient and too rigid privacy laws, increased patient involvement in research design, security protections and transparency about how data sharing occurs have been recommended 48 , 77 . The extent of the experimental information collected and the degree of privacy that’s regulated will remain a topic that requires further discussion among stakeholders in both communities.

Summary and future outlook

As humankind strives to explore ever-further into space while caring for people on Earth in a more comprehensive and individualized fashion, we will need to continue to enhance our approaches to both science and healthcare. Monitoring the physiological and psychological effects of space in a manner similar to what is done for tracking the life history of a rare disease may provide unique insights into health outcomes for astronauts. Across all research and care, ensuring that the people most directly affected are enabled to partake and that they have their voices heard throughout the process is crucial. This participation of astronauts or an individuals affected by rare diseases both empowers these people and improves the outcomes of research and care. Important advancements in digital technologies will enable the sharing of precious data in ways that increase reproducibility and reuse. This transformation should at the same time be leveraged to offer greater protection of individuals’ autonomy and privacy rights. Specifically, these improvements may change the approaches to astronaut personal information, including genetic data. Research in this area may be enabled and astronauts may receive information on individual level risks and better-tailored mitigations to spaceflight stressors in ways that does not compromise their choices and privacy. Future initiatives in space health and rare disease areas should involve outlining a clear path forward, with area-specific goals and a timeline by which they hope to be accomplished. By overcoming logistical and practical barriers, the space health and rare disease communities may catalyze wider changes in both health research and care.

Reporting summary

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

Data availability

The authors declare that the data supporting the findings of this study are available in the source data files. Source data are provided with this paper.

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Acknowledgements

E.U. was supported by the Translational Research Institute for Space Health through NASA NNX16AO69A.

Author information

Maria Puscas

Present address: The School of Health Sciences, University of Western Ontario, London, Canada

Gabrielle Martineau

Present address: Hawaii Institute of Marine Biology (HIMB), Kaneohe, HI, USA

Gurjot Bhella

Present address: University of Waterloo, Waterloo, Canada

David Saint-Jacques

Present address: Astronauts, Life Sciences and Space Medicine Canadian Space Agency, Government of Canada, Longueil, Canada

Nicole Buckley

Present address: Directorate of Human Spaceflight and Robotic Exploration, European Space Agency, Noordwijk, Holland

Etienne Low-Decarie

Present address: Agriculture and Agri-Food Canada, Government of Canada, Montreal, Canada

These authors contributed equally: Maria Puscas, Gabrielle Martineau.

Authors and Affiliations

Astronauts, Life Sciences and Space Medicine Canadian Space Agency, Government of Canada, Longueil, Canada

Maria Puscas, Gabrielle Martineau, Gurjot Bhella, David Saint-Jacques, Nicole Buckley & Etienne Low-Decarie

Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

Penelope E. Bonnen

The Strategic Review Group Inc., Ottawa, Canada

Legislative and Regulatory Modernization, Health Canada, Ottawa, Canada

Pediatric Endocrinology and Biochemical Genetics, Montreal Children’s Hospital-McGill University, Human Genetics and Pediatrics, McGill University, Montreal, Canada

John Mitchell

Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada

Matthew Osmond

Translational Research Institute for Space Health (TRISH) and Department of Emergency Medicine and Center for Space Medicine, Baylor College of Medicine, Houston, TX, USA

Emmanuel Urquieta

Canadian Institutes of Health Research Ethics Office, Ottawa, Canada

Jaime Flamenbaum

Department of Psychology, Hotchkiss Brain Institute, and Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Canada

Giuseppe Iaria

Centre of Genomics and Policy, Faculty of Medicine, Human Genetics, McGill University, Montreal, Canada

Canadian Institutes of Health Research Institute of Genetics, Ottawa, Canada

Étienne Richer

Department of Medicine, Division of Occupational Medicine, University of Toronto, Toronto, Canada

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N.B. launched the initiative and led the workshop resulting in this article. G.B., P.E.B., P.C., R.L., J.M., M.O., E.U., J.F., G.I., Y.J., É.R., J.S., D.S.-J., N.B., and E.L.-D. partook in and contributed material to the workshop. P.C. led the workshop as facilitator and drafted the workshop report. M.P., G.M., and E.L.-D. drafted the manuscript. All authors provided comments on the manuscript and approved it for publication.

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Correspondence to Nicole Buckley or Etienne Low-Decarie .

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Puscas, M., Martineau, G., Bhella, G. et al. Rare diseases and space health: optimizing synergies from scientific questions to care. npj Microgravity 8 , 58 (2022). https://doi.org/10.1038/s41526-022-00224-5

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Identifying research questions for HIV, tuberculosis, tuberculosis-HIV, malaria, and neglected tropical diseases through the World Health Organization guideline development process: a retrospective analysis, 2008–2018

S. hargreaves.

a Institute for Infection and Immunity, St George's, University of London, UK

L.B. Nellums

b World Health Organization, Geneva, Switzerland

A.F. Gabrielli

N. gebreselassie, d. schellenberg, s.l. norris, associated data.

World Health Organization (WHO) guidelines for health programmes and healthcare delivery are the foundation of its technical leadership in public health and essential to decision-making globally. A key function of guideline development is to identify areas in which further evidence is needed because filling these gaps will lead to future improvements in population health. The objective of this study was to examine the knowledge gaps and research questions for addressing those gaps generated through the WHO guideline development process, with the goal of informing future strategies for improving and strengthening the guideline development process.

Study design

We did a systematic, retrospective analysis of research questions identified in the published guidelines.

We analyzed guidelines published between January 1, 2008, and December 31, 2018, by the Communicable Diseases Cluster in five disease areas: tuberculosis (TB), HIV, malaria, TB-HIV, and neglected tropical diseases (NTDs). Research questions were extracted independently by two researchers. We analyzed the distribution of research questions by disease and by topic category and did a qualitative assessment of optimum practice for research question generation during the guideline development process.

A total of 48 guidelines were included: 26 on HIV, 1 on malaria, 11 on TB, 5 on TB/HIV, and 5 on NTDs. Overall, 36 (75%) guidelines encompassed a total of 360 explicit research questions; the remainder did not contain specific research questions. The number of research questions that focused on TB was 49, TB/HIV was 38, HIV was 250, and NTDs was 23. The number of research questions that focused on diagnosis was 43 (11.9%) of 360, prevention was 62 (17.2%), treatment was 103 (28.6%), good practice was 12 (3.3%), service delivery was 86 (23.8%), and other areas was 54 (15%). Research questions were often not formulated in a specific or actionable way and were hard to identify in the guideline. Examples of good practice identified by the review team involved the generation of specific and narrowly defined research questions, with accompanying recommendations for appropriate study design.

Conclusions

The WHO must strengthen its approach to identifying and presenting research questions during the guideline development process. Ensuring access to research questions is a key next step in adding value to the guideline development process.

• • We examined the knowledge gaps generated through the World Health Organization (WHO) guideline development process to inform future strategies.
• • We focused on five disease areas: tuberculosis (TB), HIV, malaria, TB-HIV, and neglected tropical diseases.
• • Research questions were often not formulated in a specific or actionable way and were hard to be identified.
• • The WHO must strengthen its approach in identifying research questions during the guideline development process.

Introduction

One of the most important normative roles of the World Health Organization (WHO) is to develop guidelines for health programmes to support best practice in healthcare delivery. Producing robust guidelines is essential to inform decisions regarding diagnosis, management, and treatment, in support of evidence-based approaches to the prevention and control of diseases. 1 , 2 , 3 , 4 WHO guidelines aim to promote the achievement of the Sustainable Development Goals and access to universal health coverage and reflect the core WHO value of the ‘right to health.’ 3 , 4

The WHO and other national and international guideline development groups strive to ensure that their guidelines meet the highest international standards and are impactful at the country level. In 2007, the WHO Guidelines Review Committee (GRC) was established to oversee the processes and methods used to develop WHO guidelines and to ensure the quality of all published guidelines. The GRC re-established a set of guideline development standards and adopted the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach in formulating evidence-based recommendations. 5 The guideline development process involves carrying out systematic reviews of the evidence for each of the key questions underpinning recommendations in a guideline, with assessment of the quality or certainty of the body of evidence, and the explicit and transparent formulation of recommendations based on the balance of benefits and harms of an intervention and other important considerations such as acceptability, resource use, and effects on equity. In addition, guideline development groups should formulate research questions needed to address identified gaps in knowledge. 6 , 7

There has been significant improvement within the WHO in developing public health guidelines. 8 , 9 However, there has been little emphasis on the opportunity provided by the guideline development process to identify, formulate, and compile relevant research questions that address knowledge gaps. This approach has been promoted for informing the development of a public health research agenda for the WHO. 6 , 7 Since 2014, the WHO Handbook for Guideline Development has included the following advice: ‘When gaps in the evidence are such that significant uncertainty exists with respect to the balance of an intervention's benefits and harms, such knowledge gaps should be described and questions and methods for addressing the gaps should be suggested.’ 4 Answering the research questions identified through the guideline development process fills knowledge gaps directly relevant to programmes and contributes to improved delivery of interventions and better health. Systematically compiling and disseminating the research questions identified through the WHO guideline development process can therefore help maximize public health relevance of future research. 7 , 10 , 11 , 12

For a selected set of WHO guidelines, i.e., those developed by the WHO Communicable Diseases Cluster on tuberculosis (TB), HIV, malaria, TB-HIV, and neglected tropical diseases (NTDs) between 2008 and 2018, we therefore assessed the extent to which the guideline development process identifies research questions that address knowledge gaps. The objective of this study was to examine the research questions generated through the WHO guideline development process with the goal of informing future strategies for improving and collating these questions into an open-access online directory.

Inclusion and exclusion criteria

We did a systematic, retrospective analysis of research questions contained in all WHO guidelines approved by the GRC and published between January 1, 2008, and December 31, 2018, by the CDS at WHO headquarters in Geneva, Switzerland. This unit produces guidelines on TB, HIV, malaria, TB-HIV, and NTDs. A research question was defined as an answerable or actionable enquiry generated through the guideline development process describing an identified knowledge gap or where it was explicitly stated in the guideline to be a research question.

The GRC Secretariat provided a database containing all WHO guidelines published during the relevant time period. From this database, we identified guidelines related to the five disease areas of interest (TB, HIV, malaria, TB-HIV, and NTDs). The most recent guidelines were used when multiple guidelines were available on the same topic.

Data extraction

Research questions were extracted from the published guideline documents independently and in duplicate by J.H. and S.H. This involved a systematic search of the guideline for the following terms: research, research questions, research gaps, research needs, research priorities, knowledge gaps, outstanding research, quality of evidence, and implications of research. Research questions were extracted verbatim into an Excel file and assigned to the relevant disease area. Where research questions were present in paragraphs of text pertaining to research gaps or research questions, we disaggregated the text into separate research questions, wherever possible.

Analysis and validation

We categorized research questions into six broad areas: diagnosis, prevention, treatment, specific procedural/operational needs to establish good practice, service delivery, and ‘other.’ Once all data had been extracted from the guidelines and categorized, we analyzed the number of guidelines for each disease and the distribution of research questions by disease grouping and by topic area. We did a qualitative assessment of optimum approaches for defining actionable research questions, which involved two researchers doing an in-depth reading of all included guidelines to explore areas of good and bad practice in the generation of research questions and knowledge gaps during the guideline development process. The researchers took detailed notes during the process, which were discussed during a face-to-face review team meeting to agree on optimum approaches, to inform the guideline development process going forward.

Because we planned to use the identified research questions to populate an open-access online directory, identified research questions underwent an internal validation process by senior WHO technical staff with responsibility for each of the five disease areas under study to assess which research questions were still relevant to the current disease context. An Excel (Microsoft, Redmond, WA, USA) spreadsheet of research questions identified from the guidelines was sent via email to each of the staff members who then coordinated a discussion within their department to assess which research questions were still relevant. Irrelevant and outdated questions were removed.

Distribution of guidelines and research questions by disease

A total of 48 guidelines were included in total (2008–2018), including 26 on HIV, 1 on malaria, 11 on TB, 5 on TB-HIV, and 5 on NTDs (see Fig. 1 ). Among the 48 guidelines reviewed, 30 (62.5%) were developed before the updated guidance 4 on identifying research questions in 2014.

Included guidelines by disease area. NTD = neglected tropical disease; TB = tuberculosis.

There was considerable heterogeneity across the guidelines in terms of research questions generated, with some disease areas showing a higher emphasis than others on generating a set of defined research questions as part of the guideline development process ( Fig. 2 ). Of the 48 guidelines, 36 (75%) encompassed explicit research questions, including 360 research questions in total: HIV, 250 (69.4%); TB, 49 (13.6%); TB-HIV, 38 (10.6%); NTDs, 23 (6.4%), and malaria, 0 ( Fig. 2 ). Only one guideline was identified for malaria, which did not explicitly state any research questions. Rarely did the guideline development groups propose an appropriate study design to accompany a defined research question.

Research questions by disease area (%). NTD = neglected tropical disease; TB = tuberculosis.

Distribution of research questions by category

Of the 360 research questions, the focus was on diagnosis in 43 (11.9%), prevention in 62 (17.2%), treatment in 103 (28.6%), good practice in 12 (3.3%), service delivery in 86 (23.8), and ‘other’ in 54 (15%) questions.

There was variation in the emphasis of questions generated by research area across the disease categories. Among the 250 research questions on HIV, the most commonly reported were those on treatment ( n  = 82), followed by service delivery ( n  = 64). Among the 49 research questions on TB, those on treatment were also most frequently reported ( n  = 16). The main focus of the 38 TB/HIV research questions was on service delivery ( n  = 14), followed by prevention ( n  = 10). The main focus of the 23 research questions on NTDs was on prevention ( n  = 15).

Validation of research questions

Table 1 shows the number of validated research questions. The full data set of extracted research questions is available as Supplementary Information . The key reasons cited by Disease Leads as to why research questions were removed from the list of identified research questions include the following:

• (i) The guideline from which the research question was extracted is no longer valid.
• (ii) Research questions were reframed and incorporated into a newer guideline.
• (iii) The research question is now obsolete or no longer relevant.
• (iv) The research question is not well formulated.

Table 1

Included guidelines and research questions after validation.

NTD = neglected tropical disease; TB = tuberculosis.

Qualitative assessment of optimum approaches

We found that research questions were commonly dispersed across the guideline in various sections, making it difficult for the reader to clearly see the research gaps generated by the guideline development process. Research questions were often not formulated in a specific or actionable way, with interventions not specified, study design not defined, and research questions too broad.

In many cases, guideline development groups did not specify explicit research questions or knowledge gaps but rather opted for paragraphs of interconnected text containing a broad discussion on research gaps, which makes it difficult for the reader to clearly identify the research questions. In guidelines published after the 2014 guidance—in which guideline development groups (GDGs) were specifically asked to address the issue of research question generation—we found that guideline development groups began to generate a defined section of ‘research questions,’ ‘research gaps,’ or ‘research priorities.’

We noted a number of good examples of research questions in the cohort of guidelines that we examined, with specific and narrowly defined questions, accompanied by recommendations regarding study design. Examples include the following:

“Large RCTs are needed to compare the effectiveness of topical amorolfine and butenafine in order to establish an alternative to oral treatments for toenail infections, in both HIV-infected and the general population.”

“Field evaluations of commercially available point-of-care technologies are needed to confirm the accuracy of results and the strategic placement of this technology within national programmes.”

The ‘Consolidated and Updated Guidelines on the Programmatic Management of Latent Tuberculosis Infection’ published in 2018 13 was highlighted by the review team as an example of good practice in research question generation. The guideline concludes with the research questions based on existing knowledge gaps, to support the improvement of quality of care ( Table 2 ), with recommended study designs stated.

Table 2

Research questions extracted from a WHO guideline: 13 an example of good practice in research question generation.

WHO = World Health Organization; LTBI = latent tuberculosis infection; TB = tuberculosis; IGRA = interferon gamma release assay; TB = tuberculosis; TST = tuberculin skin tests; RCT = randomised controlled trial; MDR-TB= multidrug-resistant TB.

The cohort of guidelines on infectious diseases that we assessed varied considerably in the extent to which they identified research questions as part of the guideline development process. Of the included guidelines, 75% contained explicit research questions, most frequently focusing on disease treatment. A relevant study design accompanying the research questions was rarely proposed. The better examples involved the generation of specific and narrowly defined research questions, in its own defined section of the guideline that is easily accessible to the reader, with accompanying recommendations for appropriate study design.

This analysis provides evidence of the lack of a systematic approach in identifying research questions during the guideline development process, which is relevant to the WHO's guideline development groups and other organizations generating guidelines in the field of public health. Explicit guidance on how to identify knowledge gaps and actionable research questions and to present them in WHO guidelines would add value to each guideline and to the setting of evidence-informed public health research agendas. This guidance could build on existing work on the generation of research agendas through systematic reviews. 14

Guidance is needed on when in the guideline process, developers should start thinking about research questions and how reseach question formulation can be better integrated into the guideline development process. Consideration must be given to what expertise is needed to identify and formulate optimal questions and to the approaches that may be useful for subsequent prioritization among these research questions.

There were limitations identified with respect to this review. Primarily, the review team may have missed regional guidelines or research questions within these guidelines. However working directly with disease leads for each disease means that this would have been unlikely. We are not aware of any other organizations involved in guideline development that have analyzed and assessed their approach to research question generation through the guideline development process. Nor were we able to identify any published or gray literature from other organizations on how to generate research questions. Organizations such as the Guidelines International Network ( https://www.g-i-n.net/ ) may be well placed to strengthen approaches in generating research questions and highlighting evidence gaps during guideline development.

This review has generated some key new considerations to inform the standardized and systematic identification and compilation of research questions for guideline development in the future, which may be relevant to other health guideline development groups. There should be sufficient expertise in research among members of the guideline group to help generate research questions. In addition, research questions are more easily accessible to guideline end users if they are short and clearly defined and in a defined section of the published guideline.

Opportunities for the WHO to ensure the research questions identified through its guideline development process are made more widely available, including the compilation of an online directory of research questions hosted by the WHO Global Observatory on Health R&D 15 and presentation on the WHO website where guidelines are published. 16 Work is currently underway to disseminate research questions using these fora.

This analysis shows the variable extent to which the WHO guideline development process identifies research questions. The results indicate the need for the WHO to strengthen its guideline development process by systematically identifying and compiling research questions that address key knowledge gaps. Such an approach will facilitate the formulation of relevant and impactful research agendas that will ultimately help to improve health programmes and achieve the Sustainable Development Goals for health.

Author statements

Ethical approval.

None sought.

The study was funded by the Special Programme for Research and Training in Tropical Diseases (TDR).

Competing interests

S.L.N. was the Secretary of the World Health Organization (WHO) Guidelines Review Committee, until 2020 and in that position, she was responsible for supporting and overseeing the methods used and standards implemented for WHO guidelines, including for many of the guidelines included in the study cohort. She was the lead author of WHO Handbook for Guideline Development (2nd edition, 2014). All other authors report no competing interests.

Availability of data sets

The data set supporting the conclusions of this article is included as an additional supplementary file.

Author contributions

D.M., N.F., and S.L.N. conceived the idea for this study. S.H. led the investigation and data analysis, with input from L.B.N. and J.H. G.B., A.F.G., N.G., and M.Z. validated the data extraction. S.H. and D.M. drafted the manuscript, and all authors provided input and approved the final manuscript.

Appendix A Supplementary data to this article can be found online at https://doi.org/10.1016/j.puhe.2020.03.028 .

Appendix A. Supplementary data

The following are the Supplementary data to this article:

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SDOH Research by CDC Authors: Frequently Asked Questions

To answer questions related to the CDC research database. Including, how articles were chosen for research selection, what research article topics are included, and how to find them.

How did you select articles for the research section?

We included articles on this website that have at least one CDC author and were published in 2016 or later. This list will be updated periodically to add articles published after this website was developed. We include articles that:

• Focus substantively on SDOH in their underlying research
• Expand the SDOH scientific evidence and knowledge base
• Analyze health outcomes in the context of social and structural factors
• Describe actions that address SDOH to improve health and achieve health equity

Some articles related to SDOH may not have been included because they did not meet these criteria. Examples of excluded articles include:

• Research that primarily describes varying rates of disease in particular populations (e.g., descriptive pieces that do not assign causal connections to social and structural influences)
• Research that mentions social or structural factors in a conclusion but not in the research
• Research focused on mental health or behaviors without explicit linkage to structural or social factors

How can I find research articles on particular SDOH topics?

Articles can be found by keywords using the search function. They are also organized by Healthy People 2030 domains: Economic Stability, Education, Social/Community Context, Health and Health Care, and Neighborhood and Built Environment. There are also articles listed under a general category that do not fit neatly under one of the domains because they discuss cross-cutting topics such as methods, data access, general practices, or other areas unrelated to domains. However, given the nature of social determinants, articles can easily fall under more than one category. For example:

• Articles that largely focus on high levels of incarceration (a social contextual issue) might also discuss challenges in economic stability.
• Articles about the effects of characteristics such as crime levels, which fall under the category of neighborhood and built environment, could also contain content about housing stability. Therefore, such articles could also fall under the economic stability category.

Is research on workplace conditions included in SDOH?

While it is neither a separate domain nor listed as a "key issue" under any of the HP2030 domains, this website has listed research related to workplace conditions under the social and community context domain because:

• Work is a central part of people's lives that affects the physical, psychological, and social well-being of workers and their families.
• Understanding the influence job or career has on health goes beyond the physical, emotional and social hazards, risks, and conditions faced at work.
• A person's job or career also exerts a significant influence over other aspects of life that contribute to or detract from personal health and health of family members. For example, work often determines workers' type of health care, the kind of neighborhood in which they can afford to live, how much money they have to meet their families' needs, and the time they have to spend with their families.

Is research on violence included?

Yes, articles with a focus on violence are included because violence is strongly determined by social and community contextual factors (e.g., limited economic, housing, and educational opportunities; residential segregation; high density of alcohol outlets; systemic inequities; structural racism). These contextual factors can put people at risk for violence or protect them from experiencing or perpetrating violence. Violence research is included under these Healthy People 2030 domains:

• Social and Community Context: Research under this domain helps us better understand the connection between social determinants and the risk of violence such as child abuse and neglect, intimate partner violence, and sexual violence.
• Neighborhood and Built Environment: Research under this domain helps us better understand how structural racism and other forms of oppression in communities can increase inequities in risk for violence, undermining power and trust among community members (e.g., social capital). Reductions in social capital can make it harder for communities to mobilize collective efforts to improve their health. For example, high levels of violence in a community can create conditions in which individuals risk their safety in order to walk or exercise outdoors. In turn, these conditions can also undermine a healthy lifestyle, increasing risk for chronic diseases.

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Rain, rain, go away, come again another day: do climate variations enhance the spread of COVID-19?

• Masha Menhat 1 ,
• Effi Helmy Ariffin   ORCID: orcid.org/0000-0002-8534-0113 2 ,
• Wan Shiao Dong 3 ,
• Junainah Zakaria 2 ,
• Aminah Ismailluddin 3 ,
• Hayrol Azril Mohamed Shafril 4 ,
• Mahazan Muhammad 5 ,
• Ahmad Rosli Othman 6 ,
• Thavamaran Kanesan 7 ,
• Suzana Pil Ramli 8 ,
• Mohd Fadzil Akhir 2 &
• Amila Sandaruwan Ratnayake 9  

Globalization and Health volume  20 , Article number:  43 ( 2024 ) Cite this article

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The spread of infectious diseases was further promoted due to busy cities, increased travel, and climate change, which led to outbreaks, epidemics, and even pandemics. The world experienced the severity of the 125 nm virus called the coronavirus disease 2019 (COVID-19), a pandemic declared by the World Health Organization (WHO) in 2019. Many investigations revealed a strong correlation between humidity and temperature relative to the kinetics of the virus’s spread into the hosts. This study aimed to solve the riddle of the correlation between environmental factors and COVID-19 by applying RepOrting standards for Systematic Evidence Syntheses (ROSES) with the designed research question. Five temperature and humidity-related themes were deduced via the review processes, namely 1) The link between solar activity and pandemic outbreaks, 2) Regional area, 3) Climate and weather, 4) Relationship between temperature and humidity, and 5) the Governmental disinfection actions and guidelines. A significant relationship between solar activities and pandemic outbreaks was reported throughout the review of past studies. The grand solar minima (1450-1830) and solar minima (1975-2020) coincided with the global pandemic. Meanwhile, the cooler, lower humidity, and low wind movement environment reported higher severity of cases. Moreover, COVID-19 confirmed cases and death cases were higher in countries located within the Northern Hemisphere. The Blackbox of COVID-19 was revealed through the work conducted in this paper that the virus thrives in cooler and low-humidity environments, with emphasis on potential treatments and government measures relative to temperature and humidity.

• The coronavirus disease 2019 (COIVD-19) is spreading faster in low temperatures and humid area.

• Weather and climate serve as environmental drivers in propagating COVID-19.

• Solar radiation influences the spreading of COVID-19.

• The correlation between weather and population as the factor in spreading of COVID-19.

Graphical abstract

Introduction

The revolution and rotation of the Earth and the Sun supply heat and create differential heating on earth. The movements and the 23.5° inclination of the Earth [ 1 ] separate the oblate-ellipsoid-shaped earth into northern and southern hemispheres. Consequently, the division results in various climatic zones at different latitudes and dissimilar local temperatures (see Fig.  1 ) and affects the seasons and length of a day and night in a particular region [ 2 ]. Global differential heating and climate variability occur due to varying solar radiation received by each region [ 3 ]. According to Trenberth and Fasullo [ 4 ] and Hauschild et al. [ 5 ] the new perspective on the issue of climate change can be affected relative to the changes in solar radiation patterns. Since the study by Trenberth and Fasullo [ 4 ] focused on climate model changes from 1950 to 2100, it was found that the role of changing clouds and trapped sunlight can lead to an opening of the aperture for solar radiation.

The annual average temperature data for 2021 in the northern and southern hemispheres ( Source: meteoblue.com ). Note: The black circles mark countries with high Coronavirus disease 2019 (COVID-19) infections

Furthermore, the heat from sunlight is essential to humans; several organisms could not survive without it. Conversely, the spread of any disease-carrying virus tends to increase with less sunlight exposure [ 6 ]. Historically, disease outbreaks that led to epidemic and pandemic eruptions were correlated to atmospheric changes. Pandemic diseases, such as the flu (1918), Asian flu (1956–1958), Hong Kong flu (1968), and recently, the coronavirus disease 2019 (COVID-19) (2019), recorded over a million death toll each during the winter season or minimum temperature conditions [ 7 ]. The total number of COVID-19 cases is illustrated in Fig.  2 .

A graphical representation of the total number of COVID-19 cases across various periods between 2020 and 2021. ( Source : www.worldometers.info ). Note: The black circles indicate countries with high numbers COVID-19-infections

In several previous outbreaks, investigations revealed a significant association between temperature and humidity with a particular focus on the transmission dynamics of the infection from the virus into the hosts [ 8 , 9 , 10 ]. Moreover, disease outbreaks tended to heighten in cold temperatures and low humidity [ 11 ]. Optimal temperature and sufficient relative humidity during evaporation are necessary for cloud formation, resulting in the precipitated liquid falling to the ground as rain, snow, or hail due to the activity of solar radiation balancing [ 4 ].

Consequently, the radiation balancing processes in the atmosphere are directly linked to the living beings on the earth, including plants and animals, and as well as viruses and bacterias. According to Carvalho et al. [ 12 ]‘s study, the survival rate of the Coronaviridae Family can decrease during summer seasons. Nevertheless, numerous diseases were also developed from specific viruses, such as influenza, malaria, and rubella, and in November 2019, a severe health threat originated from a 125 nm size of coronavirus, had resulted in numerous deaths worldwide.

Transmission and symptoms of COVID-19

The COVID-19, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease caused by a newly discovered pathogenic virus from the coronavirus family, the novel coronavirus (2019-nCoV) [ 13 ]. The first case was recorded in Wuhan, China, in December 2019 [ 14 ]. The pathogenic virus is transmitted among humans when they breathe in air contaminated with droplets and tiny airborne particles containing the virus [ 14 , 15 , 16 , 17 , 18 ].

According to the World Health Organization (WHO), the most common symptoms of COVID-19 infection include fever, dry cough, and tiredness. Nevertheless, older people and individuals with underlying health problems (lung and heart problems, high blood pressure, diabetes, or cancer) are at higher risk of becoming seriously ill and developing difficulty breathing [ 19 ]. The COVID-19 was initially only predominant in China but rapidly spread to other countries globally. The remarkably swift acceleration of the number of infections and mortality forced WHO to declare COVID-19 a global public health emergency on the 30th of January 2020, which was later declared as a pandemic on the 11th of March 2020 [ 20 ].

Since no vaccine was available then, WHO introduced the COVID-19 preventative measures to reduce the chances of virus transmission. The guideline for individual preventative included practising hand and respiratory hygiene by regularly cleaning hands with soap and water or alcohol-based sanitisers, wear a facemask and always maintaining at least a one-meter physical distance [ 21 ]. Nevertheless, the worldwide transmission of COVID-19 has resulted in fear and forced numerous countries to impose restrictions rules, such as lockdown, travel bans, closed country borders, restrictions on shipping activities, and movement limitations, to diminish the spread of COVID-19 [ 22 ].

According to WHO, by the 2nd of December 2020, 63,379,338 confirmed cases and 1,476,676 mortalities were recorded globally. On the 3rd of December 2021, 263,655,612 confirmed cases and deaths were recorded, reflecting increased COVID-19 infections compared to the previous year. The American and European regions documented the highest COVID-19 patients with 97,341,769 and 88,248,591 cases, respectively (see Fig. 2 ), followed by Southeast Asia with 44,607,287, Eastern Mediterranean accounted 16,822,791, Western Pacific recorded 6,322,034, and Africa reported the lowest number of cases at 6,322,034 [ 19 ].

Recently, an increasing number of studies are investigating the association between environmental factors (temperature and humidity) and the viability, transmission, and survival of the coronavirus [ 23 , 24 , 25 , 26 ]. The results primarily demonstrated that temperature was more significantly associated with the transmission of COVID-19 [ 27 , 28 , 29 ] and its survival period on the surfaces of objects [ 30 ]. Consequently, the disease was predominant in countries with low temperature and humidity [ 31 ], which was also proven by Diao et al. [ 32 ]‘s study demonstrating higher rates of COVID-19 transmission in China, England, Germany, and Japan.

A comprehensive systematic literature review (SLR) is still lacking despite numerous research on environmental factors linked to coronavirus. Accordingly, this article aimed to fill the gap in understanding and identifying the correlation between environmental factors and COVID-19 by analysing existing reports. Systematically reviewing existing literature is essential to contribute to the body of knowledge and provide beneficial information for public health policymakers.

Methodology

The present study reviewed the protocols, formulation of research questions, selection of studies, appraisal of quality, and data abstraction and analysis.

The protocol review

The present SLR was performed according to the reporting standards for systematic evidence syntheses (ROSES) and followed or adapted the guidelines as closely as possible. Thus, in this study, a systematic literature review was guided by the ROSES review protocol (Fig.  3 ). Compared to preferred reporting items for systematic review and meta-analysis (PRISMA), ROSES is a review protocol specifically designed for a systematic review in the conservation or environment management fields [ 33 ]. Compared to PRISMA, ROSES offers several advantages, as it is tailored to environmental systematic review, which reduces emphasis on quantitative synthesis (e.g. meta-analysis etc.) that is only reliable when used with appropriate data [ 34 ].

The flow diagram guide by ROSES protocol and Thematical Analysis

The current SLR started by determining the appropriate research questions, followed by the selection criteria, including the review, specifically on the keywords employed and the selection of journals database. Subsequently, the appraisal quality process and data abstraction and analysis were conducted.

Formulation of research questions

The entire process of this SLR was guided by the specific research questions, while sources to be reviewed and data abstraction and analysis were in line with the determined research question [ 35 , 36 ]. In the present article, a total of five research questions were formed, namely:

What the link between solar activity and COVID-19 pandemic outbreaks?

Which regions were more prone to COVID-19?

What were the temporal and spatial variabilities of high temperature and humidity during the spread of COVID-19?

What is the relationship between temperature and humidity in propagating COVID-19?

How did the government’s disinfection actions and guidelines can be reducing the spread of COVID-19?

Systematic searching strategies

Selection of studies.

In this stage of the study, the appropriate keywords to be employed in the searching process were determined. After referring to existing literature, six main keywords were chosen for the searching process, namely COVID-19, coronavirus, temperature, humidity, solar radiation and population density. The current study also utilised the boolean operators (OR, AND, AND NOT) and phrase searching.

Scopus was employed as the main database during the searching process, in line with the suggestion by Gusenbauer and Haddaway [ 37 ], who noted the strength of the database in terms of quality control and search and filtering functions. Furthermore, Google Scholar was selected as the supporting database. Although Halevi et al. [ 38 ] expressed concerns about its quality, Haddaway et al. [ 39 ] reported that due to its quantity, Google Scholar was suitable as a supporting database in SLR studies.

In the first stage of the search, 2550 articles were retrieved, which were then screened. The suitable criteria were also determined to control the quality of the articles reviewed [ 40 ]. The criteria are: any documents published between 2000 to 2022, documents that consist previously determined keywords, published in English, and any environment-related studies that focused on COVID-19. Based on these criteria, 2372 articles were excluded and 178 articles were proceeded to the next step namely eligibility. In the eligibility process, the title and the abstract of the articles were examined to ensure its relevancy to the SLR and in this process a total of 120 articles were excluded and only 58 articles were processed in the next stage.

Appraisal of the quality

The study ensured the rigor of the chosen articles based on best evidence synthesis. In the process, predefined inclusion criteria for the review were appraised by the systematic review team based on previously established guidelines and the studies were then judged as being scientifically admissible or not [ 40 ]. Hence, by controlling the quality based on the best evidence synthesis, the present SLR controls its quality by including articles that are in line with the inclusion criteria. It means that any article published within the timeline (in the year 2000 and above), composed of predetermined keywords, in English medium, and environment-related investigations focusing on COVID-19 are included in the review. Based on this process, all 58 articles fulfilled all the inclusion criteria and are considered of good quality and included in the review.

Data abstraction and analysis

The data abstraction process in this study was performed based on five research questions (please refer to 2.2, formulation of research questions). The data that was able to answer the questions were abstracted and placed in a table to ease the data analysis process. The primary data analysis technique employed in the current study was qualitative and relied on thematic analysis.

The thematic technique is a descriptive method that combines data flexibly with other information evaluation methods [ 41 ], aiming to identify the patterns in studies. Any similarities and relationships within the abstracted data emerge as patterns. Subsequently, suitable themes and sub-themes would be developed based on obtained patterns [ 42 ]. Following the thematic process, five themes were selected in this study.

Background of the selected articles

The current study selected 58 articles for the SLR. Five themes were developed based on the thematic analysis from the predetermined research questions: the link between solar activity and pandemic outbreaks, regional area, climate and weather, the relationship between temperature and humidity, and government disinfection action guidelines. Among the articles retrieved between 2000 and 2022; two were published in 2010, one in 2011, four in 2013, three in 2014, two in 2015, six in 2016 and 2017, respectively, one in 2018, six in 2019, twelve in 2020, eight in 2021, and seven in 2022.

Temperature- and humidity-related themes

The link between solar activity and pandemic outbreaks.

Numerous scientists have investigated the relationship between solar activities and pandemic outbreaks over the years ([ 43 ]; A [ 27 , 44 , 45 ].). Nuclear fusions from solar activities have resulted in minimum and maximum solar sunspots. Maximum solar activities are characterised by a high number of sunspots and elevated solar flare frequency and coronal mass injections. Minimum solar sunspot occurrences are identified by low interplanetary magnetic field values entering the earth [ 1 ].

A diminished magnetic field was suggested to be conducive for viruses and bacteria to mutate, hence the onset of pandemics. Nonetheless, Hoyle and Wickramasinghe [ 46 ] reported that the link between solar activity and pandemic outbreaks is only speculative. The literature noted that the data recorded between 1930 and 1970 demonstrated that virus transmissions and pandemic occurrences were coincidental. Moreover, no pandemic cases were reported in 1979, when minimum solar activity was recorded [ 47 ].

Chandra Wickramasinghe et al. [ 48 ] suggested a significant relationship between pandemic outbreaks and solar activities as several grand solar minima, including Sporer (1450–1550 AD), Mounder (1650–1700 AD), and Dalton (1800–1830) minimums, were recorded coinciding with global pandemics of diseases, such as smallpox, the English sweat, plague, and cholera pandemics. Furthermore, since the Dalton minimum, which recorded minimum sunspots, studies from 2002 to 2015 have documented the reappearance of previous pandemics. For example, influenza subtype H1N1 1918/1919 episodically returned in 2009, especially in India, China, and other Asian countries. Zika virus, which first appeared in 1950, flared and became endemic in 2015, transmitted sporadically, specifically in African countries. Similarly, SARS-CoV was first recorded in China in 2002 and emerged as an outbreak, MERS-CoV, in middle east countries a decade later, in 2012.

In 2020, the World Data Centre Sunspot Index and Long-term Solar Observations ( http://sidc.be ) confirmed that a new solar activity was initiated in December 2019, during which a novel coronavirus pandemic also occurred, and present a same as the previous hypothesis. Nevertheless, a higher number of pandemic outbreaks were documented during low minimum solar activities, including Ebola (1976), H5N1 (Nipah) (1967–1968), H1N1 (2009), and COVID-19 (2019–current). Furthermore, Wickramasinghe and Qu [ 49 ] reported that since 1918 or 1919, more devastating and recurrent pandemics tend to occur, particularly after a century. Consequently, within 100 years, a sudden surge of influenza was recorded, and novel influenza was hypothesised to emerge.

Figure  4 demonstrates that low minimum solar activity significantly reduced before 2020, hence substantiating the claim that pandemic events are closely related to solar activities. Moreover, numerous studies (i.e. [ 43 ], Chandra [ 46 , 47 , 48 ]) reported that during solar minimums, new viruses could penetrate the surfaces of the earth and high solar radiation would result in lower infection rates, supporting the hypothesis mentioned above.

The number of sunspots in the last 13 years. Note : The yellow curve indicates the daily sunspot number and the 2010–2021 delineated curve illustrates the minimum solar activity recorded (source: http://sidc.be/silso )

Regional area

In early December 2019, Wuhan, China, was reported as the centre of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak [ 50 ]. Chinese health authorities immediately investigated and controlled the spread of the disease. Nevertheless, by late January 2020, the WHO announced that COVID-19 was a global public health emergency. The upgrade was due to the rapid rise in confirmed cases, which were no longer limited to Wuhan [ 28 ]. The disease had spread to 24 other countries, which were mainly in the northern hemisphere, particularly the European and Western Pacific regions, such as France, United Kingdom, Spain, South Korea, Japan, Malaysia, and Indonesia [ 51 , 52 ]. The migration or movement of humans was the leading agent in the spread of COVID-19, resulting in an almost worldwide COVID-19 pandemic [ 53 ].

The first hotspots of the epidemic outspread introduced by the Asian and Western Pacific regions possessed similar winter climates with an average temperature and humidity rate of 5–11 °C and 47–79%. Consequently, several publications reviewed in the current study associated the COVID-19 outbreak with regional climates (i.e. [ 1 , 29 , 54 , 55 ]) instead of its close connection to China. This review also discussed the effects of a range of specific climatological variables on the transmission and epidemiology of COVID-19 in regional climatic conditions.

America and Europe documented the highest COVID-19 cases, outnumbering the number reported in Asia [ 19 ] and on the 2nd of December 2020, the United States of America (USA) reported the highest number of confirmed COVID-19 infections, with over 13,234,551 cases and 264,808 mortalities (Da S [ 56 ].). The cases in the USA began emerging in March 2020 and peaked in late November 2020, during the wintertime in the northern hemisphere (December to March) [ 53 ]. Figure  5 demonstrates the evolution of the COVID-19 pandemic in several country which represent comparison two phase of summer and one phase of winter. Most of these countries tend to increase of COVID cases close to winter season. Then, it can be worsening on phase two of summer due to do not under control of human movement although the normal trend it is presenting during winter phase.

The evolution of the COVID-19 pandemic from the 15th of February 2020 to the 2nd of December 2020 ( Source: https://www.worldometers.info/coronavirus )

The coronavirus spread aggressively across the European region, which recorded the second highest COVID-19 confirmed cases after America. At the end of 2020, WHO reported 19,071,275 Covid-19 cases in the area, where France documented 2,183,275 cases, the European country with the highest number of confirmed cases, followed by the United Kingdom (1,629,661 cases) and Spain (1,652,801 cases) [ 19 ]. Europe is also located in the northern hemisphere and possesses a temperate climate.

The spatial and temporal transmission patterns of coronavirus infection in the European region were similar to America and the Eastern Mediterranean, where the winter season increased COVID-19 cases. Typically, winter in Europe occurs at the beginning of October and ends in March. Hardy et al. [ 57 ] also stated that temperature commonly drops below freezing (approximately − 1 °C) when snow accumulates between December to mid-March, resulting in an extreme environment. Figure 5 indicates that COVID-19 cases peaked in October when the temperature became colder [ 21 ]. Similarly, the cases were the highest in the middle of the year in Australia and South Asian countries, such as India, that experience winter and monsoon, respectively, during the period.

In African regions, the outbreak of COVID-19 escalated rapidly from June to October before falling from October to March, as summer in South Africa generally occurs from November to March, while winter from June to August. Nevertheless, heavy rainfall generally transpires during summer, hence the warm and humid conditions in South Africa and Namibia during summer, while the opposite happens during winter (cold and dry). Consequently, the outbreak in the region recorded an increasing trend during winter and subsided during the summer, supporting the report by Gunthe et al. [ 58 ]. Novel coronavirus disease presents unique and grave challenges in Africa, as it has for the rest of the world. However, the infrastructure and resources have limitations for Africa countries facing COVID-19 pandemic and the threat of other diseases [ 59 ].

Conclusively, seasonal and regional climate patterns were associated with COVID-19 outbreaks globally. According to Kraemer et al. [ 60 ], they used real-time mobility data in Wuhan and early measurement presented a positive correlation between human mobility and spread of COVID-19 cases. However, after the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases were still indicative of local chains of transmission outside of Wuhan.

Climate and weather

The term “weather” represents the changes in the environment that occur daily and in a short period, while “climate” is defined as atmospheric changes happening over a long time (over 3 months) in specific regions. Consequently, different locations would experience varying climates. Numerous reports suggested climate and weather variabilities as the main drivers that sped or slowed the transmission of SARS-CoV-2 worldwide [ 44 , 61 , 62 , 63 ].

From a meteorological perspective, a favourable environment has led to the continued existence of the COVID-19 virus in the atmosphere [ 64 ]. Studies demonstrated that various meteorological conditions, such as the rate of relative humidity (i.e. [ 28 ]), precipitation (i.e. [ 65 ]), temperature (i.e. [ 66 ]), and wind speed factors (i.e. [ 54 ]), were the crucial components that contributed to the dynamic response of the pandemic, influencing either the mitigation or exacerbation of novel coronavirus transmission. In other words, the environment was considered the medium for spreading the disease when other health considerations were put aside. Consequently, new opinions, knowledge, and findings are published and shared to increase awareness, thus encouraging preventive measures within the public.

The coronavirus could survive in temperatures under 30 °C with a relative humidity of less than 80% [ 67 ], suggesting that high temperatures and lower relative humidity contributed to the elicitation of COVID-19 cases [ 18 , 51 , 58 , 68 ]. Lagtayi et al. [ 7 ] highlighted temperature as a critical factor, evidently from the increased transmission rate of MERS-Cov in African states with a warm and dry climate. Similarly, the highest COVID-19 cases were recorded in dry temperate regions, especially in western Europe (France and Spain), China, and the USA, while the countries nearer to the equator were less affected. Nevertheless, the temperature factor relative to viral infections depends on the protein available in the viruses. According to Chen and Shakhnovich [ 69 ], there is a good correlation between decreasing temperature and the growth of proteins in virus. Consequently, preventive measures that take advantage of conducive environments for specific viruses are challenging.

Precipitation also correlates with influenza [ 43 ]. A report demonstrated that regions with at least 150 mm of monthly precipitation threshold level experienced fewer cases than regions with lower precipitation rates. According to Martins et al. [ 70 ], influenza and COVID-19 can be affected by climate, where virus can be spread through the respiratory especially during rainfall season. The daily spread of Covid-19 cases in tropical countries, which receive high precipitation levels, are far less than in temperate countries [ 27 ]. Likewise, high cases of COVID-19 were reported during the monsoon season (mid-year) in India during which high rainfall is recorded [ 71 ]. Moreover, the majority of the population in these regions has lower vitamin D levels, which may contribute to weakened immune responses during certain seasons [ 27 ].

Rainfall increases the relative atmospheric humidity, which is unfavourable to the coronaviruses as its transmission requires dry and cold weather. Moreover, several reports hypothesised that rain could wash away viruses on object surfaces, which is still questioned. Most people prefer staying home on rainy days, allowing less transmission or close contact. Conversely, [ 72 ] exhibited that precipitation did not significantly impact COVID-19 infectiousness in Oslo, Norway due the location in northern hemisphere which are during winter season presenting so cold.

Coşkun et al. [ 54 ] and Wu et al. [ 29 ] claimed that wind could strongly correlate with the rate of COVID-19 transmission. Atmospheric instability (turbulent occurrences) leads to increased wind speed and reduces the dispersion of particulate matter (PM 2.5 and PM 10 ) in the environment and among humans. An investigation performed in 55 cities in Italy during the COVID-19 outbreak proved that the areas with low wind movement (stable atmospheric conditions) possessed a higher correlation coefficient and exceeded the threshold value of the safe level of PM 2.5 and PM 10 . Resultantly, more individuals were recorded infected with the disease in the regions. As mentioned in Martins et al. [ 70 ] the COVID-19 can be affected by climate and the virus can be spread through respiratory which is the virus moving in the wind movement.

The relationship between temperature and humidity

Climatic parameters, such as temperature and humidity, were investigated as the crucial factors in the epidemiology of the respiratory virus survival and transmission of COVID-19 ([ 61 ]; S [ 73 , 74 ].). The rising number of confirmed cases indicated the strong transmission ability of COVID-19 and was related to meteorological parameters. Furthermore, several studies found that the disease transmission was associated with the temperature and humidity of the environment [ 55 , 64 , 68 , 75 ], while other investigations have examined and reviewed environmental factors that could influence the epidemiological aspects of Covid-19.

Generally, increased COVID-19 cases and deaths corresponded with temperature, humidity, and viral transmission and mortality. Various studies reported that colder and dryer environments favoured COVID-19 epidemiologically [ 45 , 76 , 77 ]. As example tropical region, the observations indicated that the summer (middle of year) and rainy seasons (end of the year) could effectively diminish the transmission and mortality from COVID-19. High precipitation statistically increases relative air humidity, which is unfavourable for the survival of coronavirus, which prefers dry and cold conditions [ 32 , 34 , 78 , 79 ]. Consequently, warmer conditions could reduce COVID-19 transmission. A 1 °C increase in the temperature recorded a decrease in confirmed cases by 8% increase [ 45 ].

Several reports established that the minimum, maximum, and average temperature and humidity correlated with COVID-19 occurrence and mortality [ 55 , 80 , 81 ]. The lowest and highest temperatures of 24 and 27.3 °C and a humidity between 76 and 91% were conducive to spreading the virulence agents. The propagation of the disease peaked at the average temperature of 26 °C and humidity of 55% before gradually decreasing with elevated temperature and humidity [ 78 ].

Researchers are still divided on the effects of temperature and humidity on coronavirus transmission. Xu et al. [ 26 ] confirmed that COVID-19 cases gradually increased with higher temperature and lower humidity, indicating that the virus was actively transmitted in warm and dry conditions. Nevertheless, several reports stated that the spread of COVID-19 was negatively correlated with temperature and humidity [ 10 , 29 , 63 ]. The conflicting findings require further investigation. Moreover, other factors, such as population density, elderly population, cultural aspects, and health interventions, might potentially influence the epidemiology of the disease and necessitate research.

Governmental disinfection actions and guidelines

The COVID-19 is a severe health threat that is still spreading worldwide. The epidemiology of the SAR-CoV-2 virus might be affected by several factors, including meteorological conditions (temperature and humidity), population density, and healthcare quality, that permit it to spread rapidly [ 16 , 17 ]. Nevertheless, in 2020, no effective pharmaceutical interventions or vaccines were available for the diagnosis, treatment, and epidemic prevention against COVID-19 [ 73 , 82 ]. Consequently, after 2020 the governments globally have designed and executed non-pharmacological public health measures, such as lockdown, travel bans, social distancing, quarantine, public place closure, and public health actions, to curb the spread of COVID-19 infections and several studies have reported on the effects of these plans [ 13 , 83 ].

The COVID-19 is mainly spread via respiratory droplets from an infected person’s mouth or nose to another in close contact [ 84 ]. Accordingly, WHO and most governments worldwide have recommended wearing facemasks in public areas to curb the transmission of COVID-19. The facemasks would prevent individuals from breathing COVID-19-contaminated air [ 85 ]. Furthermore, the masks could hinder the transmission of the virus from an infected person as the exhaled air is trapped in droplets collected on the masks, suspending it in the atmosphere for longer. The WHO also recommended adopting a proper hand hygiene routine to prevent transmission and employing protective equipment, such as gloves and body covers, especially for health workers [ 86 ].

Besides wearing protective equipment, social distancing was also employed to control the Covid-19 outbreak [ 74 , 87 ]. Social distancing hinders the human-to-human transmission of the coronavirus in the form of droplets from the mouth and nose, as evidenced by the report from Sun and Zhai [ 88 ]. Conversely, Nair & Selvaraj [ 89 ] demonstrated that social distancing was less effective in communities and cultures where gatherings are the norm. Nonetheless, the issue could be addressed by educating the public and implementing social distancing policies, such as working from home and any form of plague treatment.

Infected persons, individuals who had contact with confirmed or suspected COVID-19 patients, and persons living in areas with high transmission rates were recommended to undergo quarantine by WHO. The quarantine could be implemented voluntarily or legally enforced by authorities and applicable to individuals, groups, or communities (community containment) [ 90 ]. A person under mandatory quarantine must stay in a place for a recommended 14-day period, based on the estimated incubation period of the SARS-CoV-2 [ 19 , 91 ]. According to Stasi et al. [ 92 ], 14-days period for mandatory quarantine it is presenting a clinical improvement after they found 5-day group and 10-day group can be decrease number of patient whose getting effect of COVID-19 from 64 to 54% respectively. This also proven by Ahmadi et al. [ 43 ] and Foad et al. [ 93 ], quarantining could reduce the transmission of COVID-19.

Lockdown and travel bans, especially in China, the centre of the coronavirus outbreak, reduced the infection rate and the correlation of domestic air traffic with COVID-19 cases [ 17 ]. The observations were supported by Sun & Zhai [ 88 ] and Sun et al. [ 94 ], who noted that travel restrictions diminished the number of COVID-19 reports by 75.70% compared to baseline scenarios without restrictions. Furthermore, example in Malaysia, lockdowns improved the air quality of polluted areas especially in primarily at main cities [ 95 ]. As additional, Martins et al. [ 70 ] measure the Human Development Index (HDI) with the specific of socio-economic variables as income, education and health. In their study, the income and education levels are the main relevant factors that affect the socio-economic.

A mandatory lockdown is an area under movement control as a preventive measure to stop the coronavirus from spreading to other areas. Numerous governments worldwide enforced the policy to restrict public movements outside their homes during the pandemic. Resultantly, human-to-human transmission of the virus was effectively reduced. The lockdown and movement control order were also suggested for individuals aged 80 and above or with low or compromised immunities, as these groups possess a higher risk of contracting the disease [ 44 ].

Governments still enforced movement orders even after the introduction of vaccines by Pfizer, Moderna, and Sinovac, as the vaccines only protect high-risk individuals from the worst effects of COVID-19. Consequently, in most countries, after receiving the first vaccine dose, individuals were allowed to resume life as normal but were still required to follow the standard operating procedures (SOP) outlined by the government.

The government attempted to balance preventing COVID-19 spread and recovering economic activities, for example, local businesses, maritime traders, shipping activities, oil and gas production and economic trades [ 22 , 96 ]. Nonetheless, the COVID-19 cases demonstrated an increasing trend during the summer due to the higher number of people travelling and on vacation, primarily to alleviate stress from lockdowns. Several new variants were discovered, including the Delta and Omicron strains, which spread in countries such as the USA and the United Kingdom. The high number of COVID-19 cases prompted the WHO to suggest booster doses to ensure full protection.

As mentioned in this manuscript, the COVID-19 still uncertain for any kind factors that can be affected on spreading of this virus. However, regarding many sources of COVID-19 study, the further assessment on this factor need to be continue to be sure, that we ready to facing probably in 10 years projection of solar minimum phase can be held in same situation for another pandemic.

The sun has an eleven-year cycle known as the solar cycle, related to its magnetic field, which controls the activities on its surface through sunspots. When the magnetic fields are active, numerous sunspots are formed on its surface, hence the sun produces more radiation energy emitted to the earth. The condition is termed solar maximum (see Fig.  6 , denoted by the yellow boxes). Alternatively, as the magnetic field of the sun weakens, the number of sunspots decreases, resulting in less radiation energy being emitted to the earth. The phenomenon is known as the solar minimum (see Fig. 6 , represented by the blue boxes).

The emergence and recurrence of pandemics every 5 years in relation to solar activities ( Source: www.swpc.noaa.gov/ ). Note: The yellow boxes indicate the solar maximum, while the blue boxes represent the solar minimum

The magnetic field of the sun protects the earth from cosmic or galactic cosmic rays emitted by supernova explosions, stars, and gamma-ray bursts [ 97 ]. Nevertheless, galactic cosmic rays could still reach the earth during the solar minimum, the least solar radiation energy period. In the 20th and early 21st centuries, several outbreaks of viral diseases that affected the respiratory system (pneumonia or influenza), namely the Spanish (1918–1919), Asian (1957–1958) and Hong Kong (1968) flu, were documented. Interestingly, the diseases that claimed numerous lives worldwide occurred at the peak of the solar maximum.

Figure  6 illustrates the correlation between the number of sunspots and disease outbreaks from 1975 to 2021, including COVID-19, that began to escalate in December 2019. Under the solar minimum conditions, the spread of Ebola (1976), H5N1 (1997–1998), H1N1 (2009), and COVID-19 (2019-2020) were documented, while the solar maximum phenomenon recorded SARS (2002) and H7N9 (2012–2013) or MERS outbreaks. Nonetheless, solar activity through the production of solar sunspots began to decline since the 22nd solar cycle. Accordingly, further studies are necessary to investigate the influence such solar variations could impart or not on pandemic development.

Despite the findings mentioned above, the sun and cosmic radiations could influence the distribution or outspread of disease-spreading viruses. The rays could kill the viruses via DNA destruction or influence their genetic mutations, which encourage growth and viral evolution. Nevertheless, the connection between radiation and the evolutionary process requires further study by specialists in the field it is become true or not.

The spread of viral diseases transpires naturally in our surroundings and occurs unnoticed by humans. According to records, the spread of pandemic diseases, including the Black Death (fourteenth century) and the Spanish flu (1919), was significantly influenced by the decline and peak of solar activities. Furthermore, in the past 20 years, various diseases related to the influenza virus have been recorded. According to the pattern observed, if all diseases were related to the solar cycle (solar maximum and minimum), the viral diseases would reoccur every 5 to 6 years since they first appeared between 1995 and 2020. Accordingly, the next pandemic might occur around 2024 or 2025 and need to have a proper study for prove these statements. Nonetheless, the activities on the surface of the sun have been weakening since the 23rd solar cycle and it can be proven later after the proper study can be make it.

The beginning of the COVID-19 spread, only several countries with the same winter climate with an average temperature of 5–11 °C and an average humidity rate of 47–79% located at latitudes 30–50 N reported cases. The areas included Wuhan distribution centres in China, the United Kingdom, France, Spain, South Korea, Japan, and the USA (see Fig.  5 ). Other than biological aspects, the higher number of confirmed cases recorded in colder environments was due to the human body secreting less lymphoproliferative hormone, leading to decreased immunogenicity effects and increased risk of infection [ 24 ]. Consequently, the virus could attack and rapidly infect humans during the period [ 1 , 54 ].

The lymphoproliferative response is a protective immune response that plays a vital role in protecting and eradicating infections and diseases. On the other hand, staying in warm conditions or being exposed to more sunlight would lower the risks of infection. According to Asyary and Veruswati [ 98 ], sunlight triggers vitamin D, which increases immunity and increases the recovery rates of infected individuals.

Researchers believe that viruses could survive in the environment for up to 3 to 4 years or even longer. The survival rate of the microorganisms is relatively high, which is related to their biological structures, adaptability on any surfaces, and transmission medium to spread diseases. Viruses possess simple protein structures, namely the spike, membrane, and envelope protein; therefore, when they enter living organisms (such as through the respiratory system), the viruses are easily transmitted.

Once they have entered a host, the viruses duplicate exponentially and swarm the lungs. Subsequently, after the targeted organs, such as the lungs, are invaded, the viruses attack the immune system and create confusion in protective cells to destroy healthy cells. The situation is still considered safe in younger and healthy individuals as their immune systems could differentiate and counter-attack the viruses, curing them. Nonetheless, in elders and individuals with several chronic diseases, most of their protective cells are dead, hence their immune system is forced to work hard to overcome the infection. Pneumonia and death tend to occur when the situation is overwhelming [ 85 ]. Consequently, the viruses are harmful to humans as they could multiply in a short period, enter the blood, and overrun the body.

The coronavirus could attach to surfaces without a host, including door knobs and steel and plastic materials. The microorganisms could survive alone, but virologists have yet to determine how long. If someone touches any surface with the virus, the individual would then be infected. The situation would worsen if the infected person contacted numerous people and became a super spreader. A super spreader does not exhibit any symptoms and continuously transmits the virus without realising it. An infected individual transmits the coronavirus via droplets from coughs or sneezes. Nevertheless, scientists have yet to determine if coronavirus is spread via airborne or droplets, hence requiring thorough evaluation [ 99 ].

The COVID-19 virus mutates over time, and it can be changing any times. Mutations alter the behaviour and genetic structure of the virus, resulting in a new strain. Numerous research have been conducted to procure vaccines and anti-viral medications, but mutations have led to evolutionary disadvantages. The novel strains are more infectious than the original ones. As of November 2020, approximately six new coronavirus strains have been detected, each displaying different transmission behaviours [ 100 ].

Recent studies demonstrated that the mutated viruses exhibit little variability, allowing scientists to produce viable vaccines [ 71 ]. Furthermore, different types of vaccines are manufactured by different countries, which could be advantageous. Currently, most countries also recommend booster doses to attain extra protection after receiving the mandatory two vaccine doses. In same time, the social and physical interactions between humans also necessitate to be aware.

The COVID-19 virus is primarily transmitted through droplets produced by an infected person. Accordingly, physical distancing, a one-metre minimum distance between individuals [ 19 ], and following the SOP might prevent or avoid spreading the disease. Moreover, self-quarantine, school closures, working from home, cancelling large events, limiting gatherings, and avoiding spending long periods in crowded places are essential strategies in enforcing physical distancing at a community level. The policies are essential precautions that could reduce the further spreading of coronavirus and break the chain of transmission.

Government support also need to control the spread of COVID-19 with the strict SOP. The SOP enforcement in public places would enhance adherence to the new practice among the public and the community, aiding in curbing disease transmission. Practising limited meetings and social gatherings, avoiding crowded places, workplace distancing, preventing non-necessary travels of high-risk family members, especially those with chronic disease, and adhering to the recommended SOP could reduce coronavirus outbreaks. Nonetheless, individual awareness is also necessary to achieve COVID-19 spread prevention.

Many researchers are focused on identifying the primary drivers of pandemic outbreaks. Seasonal, temperature, and humidity differences significantly impacted COVID-19 growth rate variations. It is crucial to highlight the potential link between the recurrence of pandemics every 5 years and solar activities, which can influence temperature and humidity variations. Notable variations in COVID-19 mortality rates were observed between northern and southern hemisphere countries, with the former having higher rates. One hypothesis suggests that populations in the northern hemisphere may receive insufficient sunlight to maintain optimal vitamin D levels during winter, possibly leading to higher mortality rates.

The first COVID-19 case was detected in Wuhan, China, which is in the northern hemisphere. The number of cases rapidly propagated in December during the winter season. At the time, the temperature in Wuhan was recorded at 13–18 °C. Accordingly, one theory proposes that the survival and transmission of the coronavirus were due to meteorological conditions, namely temperatures between 13 and 18 °C and 50–80% humidity.

Daily rainfall directly impacts humidity levels. The coronavirus exhibited superior survival rates in cold and dry conditions. Furthermore, transmissible gastroenteritis (TGEV) suspensions and possibly other coronaviruses remain viable longer in their airborne states, which are more reliably collected in low relative humidity than in high humidity. Consequently, summer rains would effectively reduce COVID-19 transmission in southern hemisphere regions.

In southern hemisphere regions, the summer seasons are accompanied by a high average temperature at the end and beginning of the year. Countries with temperatures exceeding 24 °C reported fewer infections. As temperatures rise from winter to summer, virus transmission is expected to decline. Nonetheless, the activities and transmission of the virus were expected to decrease during winter to summer transitions, when the countries would be warmer. The peak intensity of infections strongly depends on the level of seasonal transmissions.

Social distancing plays a critical role in preventing the overload of healthcare systems. Many respiratory pathogens, including those causing mild common cold-like syndromes, show seasonal fluctuations, often peaking in winter. This trend can be attributed to increased indoor crowding, school reopening, and climatic changes during autumn.

The spread of COVID-19 to neighbouring regions can be attributed to population interactions. Migration patterns, such as the movement from northern to southern regions during the warmer months, have significant epidemiological impacts. This trend mirrors the behavior of influenza pandemics where minor outbreaks in spring or summer are often followed by major waves in autumn or winter.

Availability of data and materials

Not applicable.

Abbreviations

Novel coronavirus

Coronavirus disease 2019

Deoxyribonucleic acid

Swine influenza

Influenza A virus subtype H5N1

Asian Lineage Avian Influenza A(H7N9) Virus

Middle East respiratory syndrome

Middle East respiratory syndrome Coronavirus

Particulate matter

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

RepOrting standards for Systematic Evidence Syntheses

Severe Acute Respiratory Syndrome

Severe Acute Respiratory Syndrome Coronavirus

Syndrome coronavirus 2

Systematic literature review

Standard operating procedure

Transmissible gastroenteritis Virus

United States of America

World Health Organization

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The authors would also like to acknowledge the Editors and an anonymous reviewer, who contributed immensely to improving the quality of this publication and a special thanks to Muhammad Hafiy Nauwal Effi Helmy, that contributed an excellent idea through singing during the COVID-19 lockdown period.

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Menhat, M., Ariffin, E.H., Dong, W.S. et al. Rain, rain, go away, come again another day: do climate variations enhance the spread of COVID-19?. Global Health 20 , 43 (2024). https://doi.org/10.1186/s12992-024-01044-w

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DOI : https://doi.org/10.1186/s12992-024-01044-w

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Clinical characteristics and valve lesions in rheumatic heart disease among children admitted to a selected tertiary teaching hospital in eastern Ethiopia

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Background Rheumatic heart disease remains a significant public health concern, especially among children in resource-limited settings like Ethiopia. Despite effective prevention strategies, RHD persists due to factors such as poverty and limited healthcare access. Understanding the clinical characteristics and valve lesions of rheumatic heart disease is crucial for improving diagnosis and management.

Objective This study aimed to characterize the clinical features and valve lesions in children with rheumatic heart disease admitted to a tertiary teaching hospital in Eastern Ethiopia.

Methods A hospital-based cross-sectional study was conducted from September 1, 2020, to August 31, 2021, at Hiwot Fana Comprehensive Specialized Hospital. Data were collected from medical records, clinical assessments, echocardiography reports, and laboratory tests. Descriptive statistics were used for analysis.

Results A total of 39 children with rheumatic heart disease were included, predominantly females (71.8%). Shortness of breath (53.9%) and cough (38.5%) were common presenting symptoms. Acute decompensated heart failure (ADHF) was prevalent (89.7%). Mitral regurgitation (94.9%) and aortic regurgitation (66.7%) were frequent valve lesions. Other findings included mitral stenosis (56.4%) and left atrial enlargement (86.1%). Laboratory results showed mean hemoglobin of 10.29 g/dL and mean ESR of 45 mm/hr.

Conclusions This study highlights the burden of RHD in Eastern Ethiopia, with advanced disease at presentation. Mitral and aortic valve lesions were predominant, emphasizing the need for early detection and comprehensive management strategies. Collaboration among healthcare providers and policymakers is essential to address the challenges of RHD in resource-limited settings.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was funded by Haramaya University.

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I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethical clearance was obtained from Haramaya University College of Health and Medical Sciences Institution Health Research Ethical Review Committee (with ethical approval ref.no: IHRERC/245/2020). An official letter was sent to Hiwot Fana Comprehensive Specialized Hospital.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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Diversity is a source of strength, creativity, and innovation for UW-Madison. We value the contributions of each person and respect the profound ways their identity, culture, background, experience, status, abilities, and opinion enrich the university community. We commit ourselves to the pursuit of excellence in teaching, research, outreach, and diversity as inextricably linked goals. The University of Wisconsin-Madison fulfills its public mission by creating a welcoming and inclusive community for people from every background - people who as students, faculty, and staff serve Wisconsin and the world. For more information on diversity and inclusion on campus, please visit: Diversity and Inclusion

Preferred Bachelor's Degree Biological or social sciences or health-related field preferred

Qualifications:

At least 1 year of experience in clinical, health or social research environment preferred. Applicants with relevant experience in a clinical or community/public health role with direct participant are also encouraged to apply. REDCap experience preferred. Experience in providing project management or staff support to multidisciplinary teams preferred.

Full or Part Time: 50% - 100% This position may require some work to be performed in-person, onsite, at a designated campus work location. Some work may be performed remotely, at an offsite, non-campus work location.

Appointment Type, Duration:

Ongoing/Renewable

Minimum $45,000 ANNUAL (12 months) Depending on Qualifications The expected salary range for this position is $45,000 up to $65,000 for highly experienced candidates. Actual pay will depend on experience and qualifications. Employees in this position can expect to receive benefits such as generous vacation, holidays, and sick leave; competitive insurances and savings accounts; retirement benefits. Benefits information can be found at ( https://hr.wisc.edu/benefits/ ).

Additional Information:

It is anticipated that this will be filled as a 50% FTE position, with higher FTE possible in the future depending upon program needs and funding availability. University sponsorship is not available for this position, including transfers of sponsorship. The selected applicant will be responsible for ensuring their continuous eligibility to work in the United States (i.e. a citizen or national of the United States, a lawful permanent resident, a foreign national authorized to work in the United States without the need of an employer sponsorship) on or before the effective date of appointment. This position is an ongoing position that will require continuous work eligibility. UW-Madison is not an E-Verify employer, and therefore, is not eligible to employ F1-OPT STEM Extension participants. If you are selected for this position you must provide proof of work authorization and eligibility to work. This position has been identified as a position of trust with access to vulnerable populations. The selected candidate will be required to pass an initial caregiver check to be eligible for employment under the Wisconsin Caregiver Law and every four years.

How to Apply:

To apply for this position, please click on the "Apply Now" button. You will be asked to upload a current resume/CV and a cover letter briefly describing your qualifications and experience. You will also be asked to provide contact information for three (3) references, including your current/most recent supervisor during the application process. References will not be contacted without prior notice.

Jacqueline Giese [email protected] 608-263-1326 Relay Access (WTRS): 7-1-1. See RELAY_SERVICE for further information.

Official Title:

Research Specialist(RE047)

Department(s):

A53-MEDICAL SCHOOL/MEDICINE/GASTROENT

Employment Class:

Academic Staff-Renewable

Job Number:

The university of wisconsin-madison is an equal opportunity and affirmative action employer..

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Kratom: unsafe and ineffective.

Users swear by kratom for mood enhancement and fatigue reduction, but safety issues and questions about its effectiveness abound.

If you read health news or visit vitamin stores, you may have heard about kratom, a supplement that is sold as an energy booster, mood enhancer, pain reliever and antidote for opioid withdrawal. However, the truth about kratom is more complicated, and the safety problems related to its use are concerning.

Kratom is an herbal extract that comes from the leaves of an evergreen tree (Mitragyna speciosa) grown in Southeast Asia. Kratom leaves can be chewed, and dry kratom can be swallowed or brewed. Kratom extract can be used to make a liquid product. The liquid form is often marketed as a treatment for muscle pain, or to suppress appetite and stop cramps and diarrhea. Kratom is also sold as a treatment for panic attacks.

Kratom is believed to act on opioid receptors. At low doses, kratom acts as a stimulant, making users feel more energetic. At higher doses, it reduces pain and may bring on euphoria. At very high doses, it acts as a sedative, making users quiet and perhaps sleepy. Some people who practice Asian traditional medicine consider kratom to be a substitute for opium.

Some people take kratom to avoid the symptoms of opioid withdrawal and because kratom may be bought more easily than prescription drugs.

Kratom is also used at music festivals and in other recreational settings. People who use kratom for relaxation report that because it is plant-based, it is natural and safe. However, the amount of active ingredient in kratom plants can vary greatly, making it difficult to gauge the effect of a given dose. Depending on what is in the plant and the health of the user, taking kratom may be very dangerous. Claims about the benefits of kratom can't be rated because reliable evidence is lacking.

Side effects and safety concerns

Although people who take kratom believe in its value, researchers who have studied kratom think its side effects and safety problems more than offset any potential benefits. Poison control centers in the United States received about 1,800 reports involving use of kratom from 2011 through 2017, including reports of death. About half of these exposures resulted in serious negative outcomes such as seizures and high blood pressure. Five of the seven infants who were reported to have been exposed to kratom went through withdrawal. Kratom has been classified as possibly unsafe when taken orally.

Kratom has a number of known side effects, including:

• Weight loss
• Chills, nausea and vomiting
• Changes in urine and constipation
• Liver damage
• Muscle pain

Kratom also affects the mind and nervous system:

• Hallucinations and delusion
• Depression and delusion
• Breathing suppression
• Seizure, coma and death

Kratom takes effect after five to 10 minutes, and its effects last two to five hours. The effects of kratom become stronger as the quantity taken increases. In animals, kratom appears to be more potent than morphine. Exposure to kratom has been reported in an infant who was breastfed by a mother taking kratom.

Many of the problems that occur with pain medications happen when these drugs are used at high doses or over a long period of time. It's not known exactly what level of kratom is toxic in people, but as with pain medications and recreational drugs, it is possible to overdose on kratom.

Research shows little promise

At one time, some researchers believed that kratom might be a safe alternative to opioids and other prescription pain medications. However, studies on the effects of kratom have identified many safety concerns and no clear benefits.

Kratom has been reported to cause abnormal brain function when taken with prescription medicines. When this happens, you may experience a severe headache, lose your ability to communicate or become confused.

In a study testing kratom as a treatment for symptoms of opioid withdrawal, people who took kratom for more than six months reported withdrawal symptoms similar to those that occur after opioid use. Too, people who use kratom may begin craving it and require treatments given for opioid addiction, such as naloxone (Narcan) and buprenorphine (Buprenex).

Kratom also adversely affects infant development. When kratom is used during pregnancy, the baby may be born with symptoms of withdrawal that require treatment.

In addition, substances that are made from kratom may be contaminated with salmonella bacteria. As of April 2018, more than 130 people in 38 states became ill with Salmonella after taking kratom. Salmonella poisoning may be fatal, and the U.S. Food and Drug Administration has linked more than 35 deaths to Salmonella-tainted kratom. Salmonella contamination has no obvious signs, so the best way to avoid becoming ill is to avoid products that may contain it.

Kratom is not currently regulated in the United States, and federal agencies are taking action to combat false claims about kratom. In the meantime, your safest option is to work with your doctor to find other treatment options.

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• Kruegel AC, et al. The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse. Neuropharmacology. In press. Accessed May 2, 2018.
• Ismail I, et al. Kratom and future treatment for the opioid addiction and chronic pain: Periculo beneficium? Current Drug Targets. In press. Accessed May 2, 2018.
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• Food and Drug Administration. Statement from FDA Commissioner Scott Gottlieb, M.D., on FDA advisory about deadly risks associated with kratom. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm584970.htm. Accessed April 17, 2018.
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• Post S. Kratom exposures reported to United States poison control centers: 2011-2017. Clinical Toxicology. Published online February 20, 2019.
• Drug Enforcement Administration. Kratom—drug fact sheet. https://www.dea.gov/sites/default/files/2020-06/Kratom-2020.pdf. Accessed January 26, 2022.
• Therapeutic Research Center. Kratom. https://naturalmedicines.therapeuticresearch.com/databases/food,-herbs-supplements/professional.aspx?productid=1513. Accessed January 26, 2022.
• Umbehr G, et al. Acute liver injury following short-term use of the herbal supplement kratom. JAAPA. 2022;35:39.
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