Severely stressful events worsen symptoms of long COVID

The death of a loved one, financial or food insecurity, or a newly developed disability were some of the strongest predictors of whether a patient hospitalized for COVID-19 would experience symptoms of long COVID a year later, a new study finds.
Led by researchers from NYU Grossman School of Medicine, the study found that adult patients with such “major life stressors” — present in more than 50% of those followed — were at least twice as likely to struggle with depression, brain fog, fatigue, sleep problems, and other long-term COVID-19 symptoms, say the study authors.
Published online this week in the Journal of the Neurological Sciences (JNS), the analysis also confirmed the contribution of traditional factors to greater long COVID risk as shown by past studies — older age, disability level to start with, and a more severe initial case of COVID-19.
“Our study is unique in that it explores the impact of life stressors — along with demographic trends and neurological events — as predictors of long-term cognitive and functional disabilities that affected quality of life in a large population,” says lead study author Jennifer A. Frontera, MD, professor in the Department of Neurology at NYU Langone Health. “Therapies that lessen the trauma of the most stress-inducing life events need to be a central part of treatment for long COVID, with more research needed to validate the best approaches.”
The research used standard telephone survey tools in the field — the modified Rankin Scale (mRS), the Barthel Index, the Montreal Cognitive Assessment (t-MoCA), and the NIH/PROMIS Neurological Quality Of Life (NeuroQoL) batteries — to measure level of daily function, clear thinking (cognition), anxiety, depression, fatigue and sleep quality. The team attempted follow-up with each of 790 patients six months and a year after COVID-19 hospitalization within NYU Langone Health between March 10, 2020 and May 20, 2020.
Of these surviving patients, 451(57%) completed 6-month and/or 12-month follow-up, and of them, 17% died between discharge and 12-month follow-up and 51% reported significant life stressors at 12-months.

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Autism research: Understanding reluctance to make eye contact with others

A hallmark of autism spectrum disorder, ASD, is the reluctance to make eye contact with others in natural conditions. Although eye contact is a critically important part of everyday interactions, scientists have been limited in studying the neurological basis of live social interaction with eye-contact in ASD because of the inability to image the brains of two people simultaneously.
However, using an innovative technology that enables imaging of two individuals during live and natural conditions, Yale researchers have identified specific brain areas in the dorsal parietal region of the brain associated with the social symptomatology of autism. The study, published Nov. 9 in the journal PLOS ONE, finds that these neural responses to live face and eye-contact may provide a biomarker for the diagnosis of ASD as well as provide a test of the efficacy of treatments for autism.
“Our brains are hungry for information about other people, and we need to understand how these social mechanisms operate in the context of a real and interactive world in both typically developed individuals as well as individuals with ASD,” said co-corresponding author Joy Hirsch, Elizabeth Mears and House Jameson Professor of Psychiatry, Comparative Medicine, and of Neuroscience at Yale.
The Yale team, led by Hirsch and James McPartland, Harris Professor at the Yale Child Study Center, analyzed brain activity during brief social interactions between pairs of adults — each including a typical participant and one with ASD — using functional near-infrared spectroscopy, a non-invasive optical neuroimaging method. Both participants were fitted with caps with many sensors that emitted light into the brain and also recorded changes in light signals with information about brain activity during face gaze and eye-to-eye contact.
The investigators found that during eye contact, participants with ASD had significantly reduced activity in a brain region called the dorsal parietal cortex compared to those without ASD. Further, the more severe the overall social symptoms of ASD as measured by ADOS (Autism Diagnostic Observation Schedule, 2nd Edition) scores, the less activity was observed in this brain region. Neural activity in these regions was synchronous between typical participants during real eye-to-eye contact but not during gaze at a video face. This typical increase in neural coupling was not observed in ASD, and is consistent with the difficulties in social interactions.
“We now not only have a better understanding of the neurobiology of autism and social differences, but also of the underlying neural mechanisms that drive typical social connections,” Hirsch said.
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Materials provided by Yale University. Original written by Bill Hathaway. Note: Content may be edited for style and length.

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Early diagnosis tool for childhood kidney disease

Early diagnosis of chronic kidney disease (CKD) is key to managing progression of the disease. A new technique analyzing urine extracellular vesicles (uEVs) — cell-derived nanoscale spherical structures involved in multiple biological functions — in urine samples identifies changes in the kidneys earlier than conventional methods and can also predict renal function decline. A team at the University of Tokyo studied urine samples from children with and without CKD. They found that the size and content of uEVs change with decreasing kidney function. This proof of concept could help with developing new urine tests that can catch the disease earlier, as well as the development of similar tests for other diseases.
Kidneys are our body’s essential filtration system. These bean-shaped, fist-sized organs are made up of millions of tiny filtration units called nephrons working hard to keep our blood clear of waste. Unfortunately, 9% of the global population is affected by chronic kidney disease (CKD) and the number of cases is on the rise. CKD develops when nephrons are damaged, whether through lifestyle, inherited and congenital diseases, or injury. Many people will not experience severe symptoms, and therefore not seek help, until the condition is more advanced. As it is difficult to completely regenerate damaged nephrons, the earlier the diagnosis the better the possible outcome.
A urine or blood test can typically tell doctors if a patient has kidney damage. However, these tests can still miss the very early stages of nephron loss which signal the start of CKD. Researchers at the University of Tokyo wanted to find out if there might be other early markers of kidney disease, especially to aid identification in young children.
“We found that changes in tiny structures called extracellular vesicles in urine are valuable in the diagnosis of kidney disease,” explained Associate Professor Yutaka Harita from the Graduate School of Medicine. “The percentage of larger vesicles increased with decreased kidney function. We were also surprised to learn that we can use changes in the molecules contained in the vesicles to diagnose and predict renal function decline.”
Extracellular vesicles are particles that are released from almost all types of cells in our bodies and serve a range of functions. Urinary extracellular vesicles (uEVs) contain proteins from nephrons, which means they could be used as a source of biomarkers (molecules that are signs of normal or abnormal processes) for various related diseases. The team looked at uEVs in urine samples from 26 children with healthy kidneys and 94 children who have various types of CKD, including those born with smaller than typical kidneys, containing fewer nephrons. In children, the causes of CKD are less likely to be due to acquired factors and more likely to be due to structural abnormalities. This made it easier for the researchers to identify and unravel the changes in uEVs, which are associated with abnormal kidney structure.
“To collect extracellular vesicles in urine, we used nanoscale magnetic microbeads (made up of iron oxide particles) coated with a molecule that binds to EVs,” explained Harita. “This method enabled efficient collection of uEVs even from patients with kidney disease who could only produce diluted urine. The size of the purified extracellular vesicles and the amount of protein contained in them were analyzed. We found several unique changes in uEVs from children with CKD. For example, children with CKD had lower levels of a protein called MUC1, important for kidney function, in their uEVs.”
These results offer proof of concept and a first step towards using uEVs for early identification of CKD and to complement existing methods. Next, Harita and the team hope to scale up the project. “We want to conduct studies on a larger scale to establish a new urine test using extracellular vesicles. We would also like to examine the utility of combining the new methods with existing tests for various diseases and age groups.”
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Materials provided by University of Tokyo. Note: Content may be edited for style and length.

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Toxic cooking fumes cause life-threatening complications in pregnant women with high blood pressure

Researchers from King’s College London explored the link between the rate of eclampsia (a serious condition during pregnancy where high blood pressure results in life-threatening seizures) and the number of deaths caused by indoor household pollution.
Indoor household pollution is more commonly seen in low- and middle-income countries because of cooking and heating with solid fuels, such as wood and charcoal, and has been proven to increase the risk of adverse birth outcomes, including placental hypoxia (when the fetus does not get enough oxygen).
The researchers evaluated more than 2,690 cases of eclampsia in Ethiopia, Haiti, India, Malawi, Sierra Leone, Uganda, Zambia and Zimbabwe, and found a significant correlation between deaths due to indoor household pollution and eclampsia rates — and the correlation was even more prominent when eclampsia occurred at home.
King’s College London’s Professor Andrew Shennan, one of the lead authors on the paper published in the International Journal of Gynecology & Obstetrics, said the findings demonstrate how air pollution can impact vulnerable populations the most.
“In-house cooking and household pollution may increase the risk of seizures. We believe that less oxygen will get to the mother’s brain, and this may trigger a fit in women who already have pre-eclampsia” he said.
“We are lucky to have such a large dataset of women with eclampsia, as it only occurs in 1% of women with pre-eclampsia. This has allowed us to uncover this new finding.
“This could help explain observed inequalities in maternal healthcare in low- and middle-income countries.”
In a previous study by King’s College London, scientists found that ninety-four percent of maternal deaths occur in low- and middle-income countries, with 22% due to hypertensive (high blood pressure) disorders like eclampsia.
Professor Shennan added: “Knowing why women have these severe outcomes allows us to reduce the risk of eclampsia and work out how to save lives.
“We have large programmes of work in India, Sierra Leone and Zambia where many women have complications related to high blood pressure. Our current research is aimed at identifying the women at risk but now we are looking at ways to reduce risk, including earlier delivery. This data will help us to give advice about avoiding risk at home.”
Researchers will next examine whether climate change increases the prevalence of pre-eclampsia or increases the morbidity from serious manifestations such as eclampsia.
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Materials provided by King’s College London. Note: Content may be edited for style and length.

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Trust in experts, media literacy connected to COVID-19 vaccine intention

An early pandemic survey found that respondents’ intentions to receive COVID-19 vaccines were linked more to their media literacy and opinion of health experts than knowledge of the virus or previous vaccination behavior.
In the study, published in the American Journal of Health Promotion, Washington State University researchers also found that for respondents who had recently refused a flu vaccine, higher COVID-19 knowledge actually correlated with lower future vaccine intentions.
“We have known for some time that knowledge and previous behavior can provide helpful clues to what people will do, but that is often insufficient to reliably predict behavior,” said Erica Austin, director of the WSU Murrow Center for Media and Health Promotion. “What we found was that measurements of trust in experts, the ability to identify reliable media sources and the ability to critically evaluate those media sources were more powerful predictors than either previous vaccine behavior or previous knowledge.”
For this study, the researchers conducted an online survey of 1,264 U.S. adults. The results indicate that people were engaging in what’s called motivated reasoning: the psychological process by which people consciously and selectively use facts to lead to a conclusion that reinforces their desired beliefs rather than rationally analyzing the evidence.
According to the authors, such processes are heavily influenced by the constantly changing news environment. It is a maze of information, misinformation, which is unintentionally incorrect, and disinformation, which is intentionally false.
“There are people out there who are motivated to take that little bit of misinformation and build a whole bunch of misinformation or even disinformation to try to sell you an idea or product based around it,” Austin said. “Most often they’re selling you both, but they’re probably not out there to do something good for you; they’re usually out there to do something that’s good for themselves.”
The results have important implications for health promotion practice and research, Austin added. It highlights the significance of individuals’ attempts to independently verify information and the need to cultivate their trust in health experts. The researchers also recommend that public health campaigns make sure to respect individuals’ freedom to make decisions for themselves while helping them make those decisions based on accurate information from credible sources.
In addition to Austin, co-authors on the study include Bruce Austin from WSU’s College of Education, Porismita Borah and Shawn Domgaard from WSU’s Murrow College of Communication as well as Sterling McPherson from WSU’s Elson S. Floyd College of Medicine.
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Materials provided by Washington State University. Original written by Thomas Evans, WSU Murrow College of Communication. Note: Content may be edited for style and length.

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Temperature, nearby species could affect avian flu transmission in migrating birds

Finding a turkey this holiday season could be difficult because of avian flu outbreaks on farms. Migratory wild birds could be to blame for transmitting the virus to commercial flocks, but no one has looked closely at this wandering population until now. In ACS’ Environmental Science & Technology, researchers report that cooler temperatures and certain species gathering in the same winter habitat could increase the circulation of H7 and H9 strains.
Avian flu is currently monitored in the air at many poultry farms and live markets, where large outbreaks are likely to occur. But many of the deadliest outbreaks have been linked to migratory birds infected by H5, H7 or H9 strains. These wild birds live in spread-out populations where, even if there are infected individuals, the levels of viruses in the ambient air are quite low, making them hard to measure. Previously, Pei-Shih Chen and colleagues determined how to measure low levels of airborne avian flu virus RNA in the environment. Using this method, Chen, Chen-Chih Chen and a new team wanted to collect first-of-its-kind information on virus strains that are likely to be circulating among migratory birds at a winter habitat and assess which factors could be influencing the transmission risks within the wild flock.
The researchers collected air samples regularly for two years near a large wetland in east Asia and filtered the samples through very fine membranes. Viral RNA was extracted from the filters, amplified and analyzed for influenza strains A, H5, H7 and H9 by quantitative real-time polymerase chain reaction. Then the team compared the results to weather data and their log of bird species present during the migratory season. Lower daily temperatures were linked to higher levels of influenza A, H7 and H9 in the air. In addition, the presence of certain migratory bird species, including ones from the orders Anseriformes, Charadriiformes and Pelecaniformes, was linked to periods of elevated amounts of H7 and H9 viral copies. By demonstrating that ambient air sampling can detect airborne avian flu, the researchers say they’ve identified potential factors that impact the strains of the disease circulating in the winter among migratory birds.
The authors acknowledge funding from the Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan from The Featured Areas Research Center Program within the Higher Education Sprout Project by the Ministry of Education in Taiwan; Kaohsiung Medical University Research Center Grants; the Council of Agriculture, Executive Yuan, Republic of China; Taiwan’s Ministry of Science and Technology, Republic of China; and the NPUST-KMU joint research project.
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Materials provided by American Chemical Society. Note: Content may be edited for style and length.

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Monoclonal antibodies preserve stem cells in mouse brains, bring promise for future studies

A new approach to stem cell therapy that uses antibodies instead of traditional immunosuppressant drugs robustly preserves cells in mouse brains and has potential to fast-track trials in humans, a Michigan Medicine study suggests.
For this study, researchers used monoclonal antibodies to suppress the immune system in mice and compared the results to traditional immunosuppression with the medications tacrolimus and mycophenolate mofetil. They tracked implanted human neural stem cell survival using luciferase, the protein that makes fireflies glow.
Results published in Clinical and Translational Medicine reveal that suppression with monoclonal antibodies enabled long-term survival of human stem cell transplants in mouse brains for at least six to eight months, while the cell grafts did not survive more than two weeks in most animals when using standard immunosuppressant drugs.
“This study makes it clear that using monoclonal antibodies is better for the study of stem cell transplants in the brain and spinal cord over the long term,” said lead author Kevin Chen, M.D., a neurosurgeon at University of Michigan Health and clinical assistant professor of neurosurgery at U-M Medical School. “The cells survived for so long with fewer injections and less toxicity from immunosuppression when using monoclonal antibodies. This will enable more experiments and studies of stem cell therapies, bringing more promise for their future in the neurosciences.”
Researchers sought to combat a longstanding obstacle for stem cell therapy in neurological disease of keeping cells alive when testing them in pre-clinical animal models. Many scientists have relied on immunosuppressant medications to keep the animals’ immune systems from rejecting stem cells, Chen says, but they eventually fail and torpedo the process.
“In many of these experiments, we would only see around a third of animals have cells survive and have no way to interpret the results,” he said. “It gets expensive in stem cell therapy to conduct these experiments and not have the cells survive.”
Traditional immunosuppressant drugs are less selective than monoclonal antibodies, which, in this study, targeted two immune proteins. The antibodies have only been analyzed in a handful of stem cell therapy studies for the nervous system. However, this study tracked cell survival for as long as eight months — one of the longest time points published for stem cells in the brain and spinal cord.
This study lays the groundwork for understanding how transplanted stem cells integrate into the brain, says senior author Eva Feldman, M.D., Ph.D., James W. Albers Distinguished Professor at U-M, the Russell N. DeJong Professor of Neurology and director of the NeuroNetwork for Emerging Therapies at Michigan Medicine.
“Our new findings continue to support advancing stem cell therapies into human clinical trials,” Feldman said. “Stem cell therapy remains a beacon of hope for neurological diseases.”
Additional authors include Lisa M. McGinley, Ph.D., Shayna N. Mason, B.S., DianaM. Rigan, B.S., Jacquelin F. Kwentus, B.S., John M. Hayes, B.A., Emily D. Glass, B.S., Evan L. Reynolds, Ph.D., Geoffrey G. Murphy, Ph.D., all of University of Michigan
This study was supported by the National Institute on Aging, The Handleman Emerging Scholar Program, The Robert E. Nederlander Sr. Program for Alzheimer’s Research, The Sinai Medical Staff Foundation, and and The NeuroNetwork for Emerging Therapies

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New hope for patients with severe bone loss

An innovative technology developed at Tel Aviv University will enable bone regeneration to correct large bone defects by means of a special hydrogel. Following successful tests in an animal model, the researchers now plan to move forward to clinical trials.
The groundbreaking study was conducted by experts from TAU’s Maurice and Gabriela Goldschleger School of Dental Medicine, led by Prof. Lihi Adler-Abramovich and Dr. Michal Halperin-Sternfeld, in collaboration with Prof. Itzhak Binderman, Dr. Rachel Sarig, Dr. Moran Aviv, and researchers from the University of Michigan in Ann Arbor. The paper was published in the Journal of Clinical Periodontology.
Prof. Adler-Abramovich: “Small bone defects, such as fractures, heal spontaneously, with the body restoring the lost bone tissue. The problem begins with large bone defects. In many cases, when substantial bone loss results from tumor resection (removal by surgery) , physical trauma, tooth extraction, gum disease or inflammation around dental implants, the bone is unable to renew itself. In the current study, we developed a hydrogel that mimics the natural substances in the extracellular matrix of bones, stimulating bone growth and reactivating the immune system to accelerate the healing process.”
The researchers explain that the extracellular matrix is the substance surrounding our cells, providing them with structural support. Every type of tissue in our body has a specific extracellular matrix consisting of suitable substances with the right mechanical properties. The new hydrogel has a fibrillary structure that mimics that of the extracellular matrix of the natural bone. Furthermore, it is rigid, thus enabling the patient’s cells to differentiate into bone-forming cells.
“As can be expected, the extracellular matrix of our bones is quite rigid,” says Prof. Adler-Abramovich. “In our study, we produced a hydrogel that mimics this specific matrix in both chemical and physical properties. At the nanometric level, the cell can attach itself to the gel, gaining structural support and receiving relevant mechanical signals from the fibers. At first, to test these properties, we grew cells in a 3D model of the gel. Then we examined the impact of the hydrogel on model animals with large bone defects that could not heal spontaneously. We monitored them for two months with various methods, including Micro C.T. To our delight, the bone defects were fully corrected through regeneration, with the bones regaining their original thickness, and generating new blood vessels.”
According to Prof. Adler-Abramovich, the innovative gel has extensive clinical applications in both orthopedic and dental medicine: “When we lose teeth due to extensive damage or bacterial infections, the standard treatment is dental implants. Implants, however, must be anchored in a sufficient amount of bone, and when bone loss is too substantial, physicians implant additional bone from a healthy part of the body — a complex medical procedure. Another option is adding bone substitutes from either human or animal sources, but these might generate an immune response. I hope that in the future the hydrogel we have developed will enable faster, safer, and simpler bone restoration.”
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Materials provided by Tel-Aviv University. Note: Content may be edited for style and length.

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Silicon nanochip could treat traumatic muscle loss

Technology developed by researchers at the Indiana University School of Medicine that can change skin tissue into blood vessels and nerve cells has also shown promise as a treatment for traumatic muscle loss.
Tissue nanotransfection is a minimally invasive nanochip device that can reprogram tissue function by applying a harmless electric spark to deliver specific genes in a fraction of a second.
A new study, published in Nature Partner Journals Regenerative Medicine, tested tissue nanotransfection-based gene therapy as a treatment, with the goal of delivering a gene known to be a major driver of muscle repair and regeneration. They found that muscle function improved when tissue nanotransfection was used as a therapy for seven days following volumetric muscle loss in rats. It is the first study to report that tissue nanotransfection technology can be used to generate muscle tissue and demonstrates its benefit in addressing volumetric muscle loss.
Volumetric muscle loss is the traumatic or surgical loss of skeletal muscle that results in compromised muscle strength and mobility. Incapable of regenerating the amount of lost tissue, the affected muscle undergoes substantial loss of function, thus compromising quality of life. A 20 percent loss in mass can result in an up to 90 percent loss in muscle function.
Current clinical treatments for volumetric muscle loss are physical therapy or autologous tissue transfer (using a person’s own tissue), the outcomes of which are promising but call for improved treatment regimens.
“We are encouraged that tissue nanotransfection is emerging as a versatile platform technology for gene delivery, gene editing and in vivo tissue reprogramming,” said Chandan Sen, director of the Indiana Center for Regenerative Medicine and Engineering, associate vice president for research and Distinguished Professor at the IU School of Medicine. “This work proves the potential of tissue nanotransfection in muscle tissue, opening up a new avenue of investigational pursuit that should help in addressing traumatic muscle loss. Importantly, it demonstrates the versatility of the tissue nanotransfection technology platform in regenerative medicine.”
Sen also leads the regenerative medicine and engineering scientific pillar of the IU Precision Health Initiative and is lead author on the new publication.
The Indiana Center for Regenerative Medicine and Engineering is home to the tissue nanotransfection technology for in vivo tissue reprogramming, gene delivery and gene editing. So far, tissue nanotransfection has also been achieved in blood vessel and nerve tissue. In addition, recent work has shown that topical tissue nanotransfection can achieve cell-specific gene editing of skin wound tissue to improve wound closure.
Other study authors include Andrew Clark, Subhadip Ghatak, Poornachander Reddy Guda, Mohamed S. El Masry and Yi Xuan, all of IU, and Amy Y. Sato and Teresita Bellido of Purdue University.
This work was supported by Department of Defense Discovery Award W81XWH-20-1-251. It is also supported in part by NIH grant DK128845 and Lilly Endowment INCITE (Indiana Collaborative Initiative for Talent Enrichment).
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Materials provided by Indiana University. Note: Content may be edited for style and length.

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Mindfulness-based stress reduction is as effective as an antidepressant drug for treating anxiety disorders, study finds

A guided mindfulness-based stress reduction program was as effective as use of the gold-standard drug — the common antidepressant drug escitalopram — for patients with anxiety disorders, according to results of a first-of-its-kind, randomized clinical trial led by researchers at Georgetown University Medical Center.
The findings appear in JAMA Psychiatry on November 9, 2022, and follow the October 11, 2022, announcement by the United States Preventive Services Task Force that, for the first time, recommended screening for anxiety disorders due to the high prevalence of these disorders.
“Our study provides evidence for clinicians, insurers, and healthcare systems to recommend, include and provide reimbursement for mindfulness-based stress reduction as an effective treatment for anxiety disorders because mindfulness meditation currently is reimbursed by very few providers,” says Elizabeth Hoge, MD, director of the Anxiety Disorders Research Program and associate professor of psychiatry at Georgetown and first author. “A big advantage of mindfulness meditation is that it doesn’t require a clinical degree to train someone to become a mindfulness facilitator. Additionally, sessions can be done outside of a medical setting, such as at a school or community center.”
Anxiety disorders can be highly distressing; they include generalized anxiety, social anxiety, panic disorder and fear of certain places or situations, including crowds and public transportation, all of which can lead to an increased risk for suicide, disability and distress and therefore are commonly treated in psychiatric clinics. Drugs that are currently prescribed for the disorders can be very effective, but many patients either have difficulty getting them, do not respond to them, or find the side effects (e.g., nausea, sexual dysfunction and drowsiness) as a barrier to consistent treatment. Standardized mindfulness-based interventions, such as mindfulness-based stress reduction (MBSR), can decrease anxiety, but prior to this study, the interventions had not been studied in comparison to effective anti-anxiety drugs. Of note, approximately 15% of the U.S. population tried some form of meditation in 2017.
The clinicians recruited 276 patients between June 2018 and February 2020 from three hospitals in Boston, New York City and Washington, D.C., and randomly assigned people to either MBSR or escitalopram. MBSR was offered weekly for eight weeks via two and a half-hour in-person classes, a day-long retreat weekend class during the 5th or 6th week, and 45-minute daily home practice exercises. Patients’ anxiety symptoms were assessed upon enrollment and again at completion of the intervention at 8 weeks, along with post-treatment assessments at 12 and 24 weeks after enrollment. The assessments were conducted in a blinded manner — the trained clinical evaluators did not know whether the patients they were assessing received the drug or MBSR.
At the end of the trial, 102 patients had completed MBSR and 106 had completed their medication course. The patients were relatively young, with a mean age of 33 and included 156 women, which comprised 75% of the enrollees, mirroring the disease prevalence in the U.S.

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