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Pregnancy can increase the risk of morbidity and mortality in women with cardiovascular disease; however, many cardiologists are not having pre-pregnancy contraception discussions with their patients of child-bearing age. There is a need to provide evidence-based guidance for contraceptive safety and effectiveness and pregnancy planning options for this high-risk patient group, according to a paper published in the Journal of the American College of Cardiology (JACC). This paper is one of a five-part JACC focus seminar series addressing a wide range of topics in the emerging cardio-obstetrics field.

Prior research has found that 68% of females have had sex at least once by the time they were 17, and a study of congenital heart disease (CHD) patients identified that 26% of all adolescents (age 15-18 years) and 74% of all young adults (age 19-25 years) with CHD report ever having sex. For reproductive-age women with cardiovascular disease, planning for if they want to become pregnant is vital for the health of both the mother and fetus. Many of these women are prescribed medications to treat cardiovascular disease that could potentially harm the fetus, and pregnancy may cause significant morbidity and mortality among women with pre-existing cardiovascular disease. Despite rising rates of acquired cardiovascular disease in women of this age group, the frequency of reproductive planning discussions between cardiologists and these patients is unknown.

Authors of the paper said they urge women with cardiovascular disease to develop reproductive goals that include deciding whether and when to become pregnant and encourage shared decision-making with their obstetrician, cardiologist and primary care provider to create an action plan. The paper also stresses that cardiovascular clinicians need to educate their patients about how their heart conditions impact contraceptive and medical decision-making for pregnancy.

"It is important for cardiovascular clinicians to assess for the need for contraception and appropriateness of contraceptive method both at the time of initial assessment and at subsequent annual encounters in all reproductive age women (age 15-44) with cardiovascular disease," said Kathryn J. Lindley, MD, FACC, chair of the ACC's Cardiovascular Disease in Women Committee and member of the ACC's Cardio-Obstetrics Work Group, and lead author of the paper. "If a patient identified to be at increased risk for pregnancy complications is also noted to be using a contraceptive method with low effectiveness, a discussion of reproductive goals and safe and effective methods of contraception is recommended."

Another barrier to optimal care discussed in the paper are the significant disparities that exist in access to contraception and risk of unintended pregnancy among certain minority populations, including women with high cardiovascular disease burden. According to the paper, over 19 million women in the US, particularly in the South, Midwest and Mountain West live in "contraception deserts" and lack access to a contraceptive care facility in their county.

"Given the significant barriers to and the importance of obtaining safe and effective contraception, ensuring contraceptive access is an important part of providing comprehensive cardiovascular care," Lindley said.

Recommendations for the different types of contraception methods, which are divided into three tiers of effectiveness, are provided in the paper: Tier 1 methods (permanent sterilization and long-acting reversible contraceptives), Tier II methods (combined hormonal contraceptives, progestin-only pills and the depot medroxyprogesterone acetate injection) and Tier III methods (barrier methods, withdrawal and natural family planning).

What The Study Did: Electronic health record data were used to examine whether the transition to remote cardiology clinic visits during COVID-19 is associated with disparities in patient use of care, diagnostic test ordering and medication prescribing.

Authors: Neal Yuan, M.D., of Cedars-Sinai Medical Center in Los Angeles, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.4157)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

March 10, 2021 - Hackensack, NJ - Convalescent plasma, the use of survivors' antibodies transfused into sick COVID-19 patients is safe and significantly improves clinical outcomes when using high levels of antibodies, according to a new publication by scientists at Hackensack Meridian Health, New Jersey's largest and most comprehensive health network.

The treatment was safe, transferred the survivors' antibodies, and did not prevent the recipients from making their own antibodies, according to the results published recently in the journal JCI Insights.

"We have developed this technique and methodology to save the lives of patients," said Michele Donato, M.D., FACP, CPE, chief of Stem Cell Transplantation and Cellular Therapy at John Theurer Cancer Center at Hackensack University Medical Center, and who is leading the study. "We believe our hard work is paying off."

"The know-how is really crucial for this kind of treatment," said David S. Perlin, Ph.D., the chief scientific officer and senior vice president of the Hackensack Meridian Center for Discovery and Innovation (CDI). "We have demonstrated that when you rigorously qualify donors, and deliver their antibodies into the right patients, it can make a huge difference."

Fifty-one patients were enrolled to receive the plasma. They were split into two groups: one that was hospitalized but not needing mechanical breathing assistance, and one that was receiving such assistance.

The non-mechanically ventilated patients survived at a significantly higher rate (88.9 percent) at the 30-day mark than a comparative group elsewhere in the health network (72.5 percent).

The convalescent plasma program at Hackensack University Medical Center identifies "super donors" - those with the highest levels of neutralizing antibodies - through methodology developed by experts from the CDI.

These plasma patients received high levels (titers) of antibodies, with almost all receiving viral neutralizing anti-spike protein levels at a proportion of 1:1000, or even greater. This compares with some other plasma programs which have not set elevated thresholds for antibody levels from donors.

Since the antibodies come from survivors who have developed immune responses to the latest strains, plasma may also keep up with the rise of "variants" of the SARS-CoV-2 virus where other interventions may not, according to some experts.

The promising results for the early intervention has led to an ongoing outpatient program at Hackensack University Medical Center, supported by a Department of Defense grant. The approximately $5.5 million will allow the researchers at Hackensack Meridian John Theurer Cancer Center at Hackensack University Medical Center, and their colleagues at the Hackensack Meridian Center for Discovery and Innovation (CDI) to continue phase 2 testing of the clinical treatments.

The goal of this outpatient work is to treat infected patients in the first 96 hours of symptoms with the antibodies found in plasma collected from COVID-19 survivors - with the aim to prevent hospitalization.

"This is an example of how our health network leverages excellent laboratory work into clinical interventions," said Ihor Sawczuk, M.D., FACS, president of Hackensack Meridian Health's Northern Market, and the chief research officer of the network. "Scientific research is helping to make a difference in this global pandemic."

People with ovarian cancer frequently receive aggressive end-of-life care despite industry guidelines that emphasize quality of life for those with advanced disease, according to a recent study.

In fact, by 2016, ICU stays and emergency department visits in the last month of life had become more common for people with ovarian cancer than they were in 2007, the earliest year from which researchers analyzed data.

The proportion of non-Hispanic Black people who turned to the emergency department for care was even higher -- double that of non-Hispanic whites. Black people were also nearly twice as likely to undergo intensive treatment, including life-extending measures such as resuscitation or the insertion of a feeding tube.

"Although the early integration of palliative care and the reduction of intensive and invasive end-of-life care have been included more and more in guidelines, these recommendations are not making enough of a difference in the type of care people with ovarian cancer receive at the end of their lives, especially for people of color," says Megan Mullins, Ph.D., M.P.H., first author of the study.

Both the American Society of Clinical Oncology and the National Academy of Medicine recommend palliative care, which focuses on relieving symptoms and elevating quality of life, for those with a prognosis of less than six months to live.

Palliative care is particularly relevant for people with ovarian cancer because they're often diagnosed once their cancer has already progressed to an advanced stage. By that point, survival is unlikely; just 17% of those with stage IV ovarian cancer live for at least five years after diagnosis.

ASCO had set a goal for cancer centers to incorporate palliative care into their treatment plans by 2020. Yet this study's findings, published in Cancer, highlight how much work remains to be done to ensure widespread adoption of such practices.

Researchers used the National Cancer Institute's cancer registries, known as Surveillance, Epidemiology, and End Results, or SEER, to examine the medical histories of close to 8,000 people who died between 2007 and 2016. All were over the age of 66 and on Medicare, and ovarian cancer was their only cancer diagnosis.

The research team found that some end-of-life measures are trending in a positive direction: Hospice enrollment has gone up over time, and the proportion of people with ovarian cancer who undergo invasive procedures, such as surgery that requires anesthesia, has decreased.

Yet the number of months they spend in hospice as well as the proportion receiving chemotherapy in their last two weeks of life did not change significantly from 2007 to 2016 (longer hospice stays are a sign that patients feel comfortable with palliative care).

And the overall increase in emergency department visits and ICU stays, plus the notable disparities in certain end-of-life measures for Black people, are disappointing, says Mullins, who's also a postdoctoral research fellow at the University of Michigan Rogel Cancer Center and the Center for Improving Patient and Population Health at the University of Michigan School of Nursing.

"Prognostication is difficult," Mullins says. "But being honest about the risks and benefits of treatment is important. Engaging in conversations with patients about the goals of their care allows them to consider how they would like to spend the time they have left."

Mullins says further research is needed to explore why aggressive end-of-life care persists for people with ovarian cancer. Explanations could include:

emotional toll of end-of-life conversations on physicians

lack of patient understanding about the impact of continuing certain cancer treatments on their quality of life

presence of additional chronic conditions that could worsen symptoms enough to require hospitalization

patients' cultural preferences or providers' perceptions of them

"It's very important that we actually understand why these preferences exist and how we can address them," Mullins says.

DALLAS, April 5, 2021 -- When people with human immunodeficiency virus (HIV) develop high blood pressure, the type of medication chosen for their initial treatment may influence their risk of heart disease, stroke and heart failure, according to new research published today in Hypertension, an American Heart Association journal.

With current anti-retroviral medications, people with HIV are able to live longer. However, people with HIV receiving anti-retroviral therapy (ART) are more likely to develop high blood pressure (hypertension) and hypertension-related heart problems than people who do not have the virus. The current study is the first to examine how the choice of blood pressure medications influences the long-term risk of heart disease, stroke and heart failure in this population that has a higher risk of CVD.

"We suspected there could be differences in risk based on which medications providers select to treat hypertension among people with HIV due to potential interactions between blood pressure medications and some therapies used to treat the virus. Additionally, factors such as how the body handles salt, inflammation and the accelerated aging of blood vessels may affect the risk of cardiac events in people with HIV differently than people who do not have HIV, which could be influenced by which blood pressure medication is used," said the study's senior author Jordana B. Cohen, M.D., M.S.C.E., assistant professor of medicine and epidemiology in the renal-electrolyte and hypertension division in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

In the current study, the researchers reviewed records of 8,041 veterans with HIV (average age 53 years, 97% male, 49% Black adults) who developed high blood pressure between 2000-2018; 6,516 had never been diagnosed with heart or blood vessel problems. At baseline, of the 8,041 patients, 5,979 (74%) were on anti-retroviral medication therapy and 6,582 (82%) were prescribed single antihypertensive medication therapy: 1,025 (13%) on beta blockers, 848 (11%) on calcium channel blockers, 1,905 (24%) on ACEi/ARBs and 1,865 (23%) on diuretics. The occurrence of heart disease (heart attack, heart-related chest pain, or need for a procedure to open narrowed arteries supplying blood to the heart), stroke or heart failure over the next 6.5 years was compared among the study participants based on the different types of blood pressure medications.

Researchers found:

In this study, 13% of the veterans with HIV were prescribed beta-blockers as their initial hypertension treatment. Single-medication treatment was started with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEi/ARBs) in 24% of patients; thiazide or similar diuretics in 23%; and calcium channel blockers (CCBs) in 11%.

During the mean 6.5 years follow-up period, 25% of the veterans experienced a cardiovascular event. Among veterans who had not been diagnosed with heart disease at the beginning of the study, the risk of developing heart disease, heart failure or stroke for the first time was 90% higher among those taking beta-blockers compared to the veterans who were taking ACEi/ARBs, the most frequently prescribed type of high blood pressure medication. The increased risk was present whether or not blood pressure was under control. Thiazide diuretics and CCBs did not increase risk.

Among veterans with HIV who did not have chronic kidney disease, the use of ACEi/ARBs was associated with a lower risk of developing heart failure, compared to those patients taking other medications who were found to have about a 50% higher risk of heart failure.

"Blood pressure and heart disease risk in patients who have HIV can be safely managed with first-line treatment of hypertension with ACEis, ARBs, CCBs and thiazide diuretics and may have added benefit from initial treatment with ACEis and ARBs," Cohen said.

Although CCBs are among the medications recommended for the initial treatment of hypertension, in this study beta-blockers were prescribed more frequently than CCBs.

"We were surprised by the high rates of beta-blockers prescribed for first-line hypertension treatment since they are not recommended as first-line agents," Cohen said. "We suspect this may be due to the fact that many people with HIV receive primary care from their infectious disease team, who do an amazing job at managing HIV but may not be focused on blood pressure treatment guidelines and contraindications. Ideally, a patient's primary care and infectious disease team should work together for the best possible outcomes."

Cohen said the results also highlight that there is possible harm from sing beta-blockers as first-line treatment for hypertension whether a person has HIV or not.

"While many people are appropriately treated with beta-blockers for various reasons, if you think you are taking them only for hypertension and aren't on any other blood pressure medications, I'd recommend talking to your doctor to make sure it's the best medication for you," she said.

As a retrospective analysis, the study cannot establish a cause-and-effect relationship between medication choice and heart disease events. The study results may also be affected by factors the researchers were unable to measure, such as some sociodemographic factors and patient preferences in medication choice. Although the results were the same in men and women in the study, the large proportion of men in the sample limits the ability to generalize the findings to women. Results from this study of veterans receiving care through the Veterans Health Administration also may not be generalizable to non-veterans or people who do not have health insurance or access to routine medical care.

"Patients with HIV need heightened attention to their elevated risk of heart disease. More dedicated research studying the unique needs for people with HIV and those taking ARTs is needed in order to optimize cardiovascular prevention," Cohen said.

Researchers at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center have developed DeepTCR, a software package that employs deep-learning algorithms to analyze T-cell receptor (TCR) sequencing data. T-cell receptors are found on the surface of immune T cells. These receptors bind to certain antigens, or proteins, found on abnormal cells, such as cancer cells and cells infected with a virus or bacteria, to guide the T cells to attack and destroy the affected cells.

"DeepTCR is an open-source software that can be used to answer questions in research into infectious disease, cancer immunology and autoimmune disease; any place where the immune system has a role through its T-cell receptors," said lead study author John-William Sidhom, an M.D./Ph.D. student at the Johns Hopkins University School of Medicine and Department of Biomedical Engineering working in the Bloomberg~Kimmel Institute for Cancer Immunotherapy.

The research was published March 11 in Nature Communications.

Sidhom was inspired to develop the software after attending a presentation on the use of deep learning for the medical sciences at the 2017 meeting of the American Association for Cancer Research. "I was doing research on T-cell receptor sequencing, and it struck me that this was the right technology to better analyze T-cell sequencing data," he says.

Deep learning is a form of artificial intelligence that roughly mimics the workings of the human brain in terms of pattern recognition. "Deep learning is a very flexible and powerful way to do pattern recognition on any kind of data. In this paper, we use deep learning to identify patterns in sequencing data of the T-cell receptor," says Sidhom, adding that the way the software explores T-cell receptors is analogous to an internet search. "When someone performs an internet search for an image of cats or dogs, the query doesn't involve looking for images that have a caption that labels the image as a cat or dog, but rather applies an algorithm that explores the features of the images and recognizes patterns that identify the images as a cat or dog. This is deep learning."

DeepTCR is a comprehensive deep-learning framework that includes both unsupervised and supervised deep learning models that can be applied at the sequence and sample level. Sidhom says the unsupervised approaches allow investigators to analyze their data in an exploratory fashion, where there may not be known immune exposures, and the supervised approaches will allow investigators to leverage known exposures to improve the learning of the models. As a result, he says, DeepTCR will enable investigators to study the function of the T-cell immune response in basic and clinical sciences by identifying the patterns in the receptors that confer the function of the T cell to recognize and kill pathological cells.

One of the main challenges of analyzing TCR sequencing data is distinguishing meaningful sequencing data from inconsequential data, and DeepTCR helps perform this analysis. "There are a lot of sequences in someone's immune repertoire. There are a lot of pathogens that someone can be infected by, so the immune response is very broad. As a result, there is a sea of noise in the immune response, and only parts of it are important at a certain time for a certain infection," Sidhom explains. "I may have T-cell responses to a thousand different viruses, but when the flu impacts me, I only need to utilize a small subset of those T cells to fight the flu. The main thing that the algorithm can do is isolate and match the right T cells to specific responses."

The software package, which employs a type of deep-learning architecture called a convolutional neural network, provides users the ability to find T-cell sequencing patterns that are relevant to a specific exposure, like a flu infection, a cancer or an autoimmune disease.

"When presented with a lot of data, our algorithms can learn rules of these TCR sequence patterns. For example, we may not know the rules for how the body responds to flu, but with enough data, our software can learn those rules and then teach us what they are," says Sidhom. "It is very well-suited to identify complex patterns in a very, very large immune repertoire to identify the interacting partners between a T-cell receptor and its antigen."

WHO Ingrid Katz, MD, MHS, Associate Physician, Department of Medicine, Brigham and Women's Hospital; lead author of a new Perspective piece published in the New England Journal of Medicine.

WHAT While the U.S. has begun to vaccinate millions of Americans each day, COVID-19 vaccine supplies around the world remain scarce. Experts estimate that 80 percent of people in low-resource countries will not receive a vaccine in 2021. At the time of the paper's writing, the global vaccination rate was 6.7 million doses per day -- a rate at which it would take 4.6 years to achieve global herd immunity. In a new Perspective piece in the New England Journal of Medicine, Katz and colleagues highlight the need to treat essential medical services as public goods, rather than market commodities. To truly protect U.S. residents and their neighbors, they urge the federal government to reinforce global vaccine distribution efforts.

"The early competitive procurement of vaccines by the United States and purchases by other high-resource countries have fed a widespread assumption that each country will be solely responsible for its own population," the authors write. "Such vaccine nationalism perpetuates the long history of powerful countries securing vaccines and therapeutics at the expense of less-wealthy countries; it is short-sighted, ineffective, and deadly."

Through the COVID-19 Vaccines Global Access (COVAX) program, the U.S. and the G7 nations have committed to vaccinating at least 20 percent of the populations of participating low- and middle-income countries by the end of 2021. But this falls far below the broader goal of achieving herd immunity by vaccinating at least 70 to 85 percent of the population and substantially increases the likelihood that new viral variants will emerge.

Drawing upon lessons learned from the HIV pandemic, when most low-resource countries could not access lifesaving therapies, the authors argue that the government should invest in what some experts are calling the President's Emergency Plan for Vaccine Access and Relief (PEPVAR), a spin-off of the 2003 President's Emergency Plan for AIDS Relief (PEPFAR). This latter plan was founded to deliver antiretroviral therapies globally, and a program like PEPVAR could draw upon pre-existing strategies to scale up the delivery of vaccines beyond COVAX's commitments. Like the plan for AIDS relief, it could leverage partnerships with governmental and multilateral organizations to improve vaccine access. Equally important is ensuring vaccine supply, and the authors posit that the World Trade Organization may be justified in temporarily waiving pharmaceutical patent protections to substantially reduce the costs of manufacturing vaccines.

"The United States has an unusual and urgent opportunity to ensure that COVID-19 vaccines are available to all," the authors write. "By investing in multilateral partnerships with a sense of shared commitment and employing a global allocation strategy that increases supply and manufacturing, we can meet the urgent challenge of COVID-19, while creating sustainable infrastructures and health systems for the future."

In 2020, the International Agency for Research on Cancer of the World Health Organization stated that breast cancer accounts for most cancer morbidities and mortalities in women worldwide. This alarming statistic not only necessitates newer methods for the early diagnosis of breast cancer, but also brings to light the importance of risk prediction of the occurrence and development of this disease. Ultrasound is an effective and noninvasive diagnostic procedure that truly saves lives; however, it is sometimes difficult for ultrasonologists to distinguish between malignant tumors and other types of benign growths. In particular, in China, breast masses are classified into four categories: benign tumors, malignant tumors, inflammatory masses, and adenosis (enlargement of milk-producing glands). When a benign breast mass is misdiagnosed as a malignant tumor, a biopsy usually follows, which puts the patient at unnecessary risk. The correct interpretation of ultrasound images is made even harder when factoring in the large workload of medical specialists.

Could deep learning algorithms be the solution to this conundrum? Professor Wen He (Beijing Tian Tan Hospital, Capital Medical University, China) thinks so. "Artificial intelligence is good at identifying complex patterns in images and quantifying information that humans have difficulty detecting, thereby complementing clinical decision making," he states. Although much progress has been made in the integration of deep learning algorithms into medical image analysis, most studies in breast ultrasound deal exclusively with the differentiation of malignant and benign diagnoses. In other words, existing approaches do not try to categorize breast masses into the four abovementioned categories.

To tackle this limitation, Dr. He, in collaboration with scientists from 13 hospitals in China, conducted the largest multicenter study on breast ultrasound yet in an attempt to train convolutional neural networks (CNNs) to classify ultrasound images. As detailed in their paper published in Chinese Medical Journal, the scientists collected 15,648 images from 3,623 patients and used half of them to train and the other half to test three different CNN models. The first model only used 2D ultrasound intensity images as input, whereas the second model also included color flow Doppler images, which provide information on blood flow surrounding breast lesions. The third model further added pulsed wave Doppler images, which provide spectral information over a specific area within the lesions.

Each CNN consisted of two modules. The first one, the detection module, contained two main submodules whose overall task was to determine the position and size of the breast lesion in the original 2D ultrasound image. The second module, the classification module, received only the extracted portion from the ultrasound images containing the detected lesion. The output layer contained four categories corresponding to each of the four classifications of breast masses commonly used in China.

First, the scientists checked which of the three models performed better. The accuracies were similar and around 88%, but the second model including 2D images and color flow Doppler data performed slightly better than the other two. The reason the pulsed wave Doppler data did not contribute positively to performance may be that few pulsed wave images were available in the overall dataset. Then, researchers checked if differences in tumor size caused differences in performance. While larger lesions resulted in increased accuracy in benign tumors, size did not appear to have an effect on accuracy when detecting malignancies. Finally, the scientists put one of their CNN models to the test by comparing its performance to that of 37 experienced ultrasonologists using a set of 50 randomly selected images. The results were vastly in favor of the CNN in all regards, as Dr. He remarks: "The accuracy of the CNN model was 89.2%, with a processing time of less than two seconds. In contrast, the average accuracy of the ultrasonologists was 30%, with an average time of 314 seconds."

This study clearly showcases the capabilities of deep learning algorithms as complementary tools for the diagnosis of breast lesions through ultrasound. Moreover, unlike previous studies, the researchers included data obtained using ultrasound equipment from different manufacturers, which hints at the remarkable applicability of the trained CNN models regardless of the ultrasound devices present at each hospital. In the future, the integration of artificial intelligence into diagnostic procedures with ultrasound could speed up the early detection of cancer. It would also bring about other benefits, as Dr. He explains: "Because CNN models do not require any type of special equipment, their diagnostic recommendations could reduce predetermined biopsies, simplify the workload of ultrasonologists, and enable targeted and refined treatment."

Let us hope artificial intelligence soon finds a home in ultrasound image diagnostics so doctors can work smarter, not harder.

Up to one in five employees at an academic medical institution are considering leaving their professions due to the strains of coping with the pandemic in their own lives, according to a new University of Utah Health study. Individuals who had caregiving responsibilities were among those most likely to contemplate leaving or reducing hours.

The findings suggest that retaining highly trained doctors, nurses, and scientists in the aftermath of the COVID-19 pandemic could be the next great health care challenge.

"It's sobering to learn that, during a time of economic recession, at least one-fifth of our workforce were considering leaving their jobs because of the severe levels of stress they were experiencing," says Angela Fagerlin, Ph.D., the study's senior author and professor and chair of the Department of Population Health Sciences at the University of Utah School of Medicine. "Many of these are people who have spent five to ten years of their adult lives training to do this kind of work. Yet, it's so overwhelming and burdensome that they were potentially thinking about giving it all up."

Although conducted at a single health care system, the researchers say these findings could have broader implications.

"We suspect these disturbing trends likely exist within other health care systems nationwide," says Rebecca Delaney, Ph.D., the study's lead author and a postdoctoral research fellow at the U of U School of Medicine. "These findings are alarming and a warning sign about the morale and well-being of doctors and nurses, as well as non-clinical health care scientists and staff."

The study appears in JAMA Network Open.

Several studies have examined the effects of burnout, stress, depression, and anxiety on frontline medical staff during the global pandemic. However, most have only included frontline workers or physician trainees. Few of these studies have addressed important family-work balance issues, such as childcare needs during the pandemic, which contribute significantly to the stress and burnout of staff.

To remedy this oversight, Delaney and her colleagues distributed a web-based survey of all 27,700 clinical and non-clinical U of U Health faculty, staff, and trainees in August 2020. Survey items measured childcare needs, work-life balance needs, career development impact, and stress related to the pandemic.

Overall, 18 percent (n=5,030) completed the entire survey. The data was consistent across clinical and non-clinical respondents, confirming that everyone--men, women, those with and without children--were struggling with the impact of COVID-19, Delaney says.

Nearly half (48 percent) reported having at least one child 18 years old or younger. In addition, the researchers found:

49 percent of those who had children reported that parenting and managing virtual education for children was causing them stress

Faculty (55 percent) and trainees (60 percent) reported decreased productivity

47 percent of participants expressed concern about COVID-19 affecting their career development, with 64 percent of trainees being highly concerned

30 percent reported considering reducing hours

21 percent reported considering leaving the workforce

In addition to being a single health care system survey, other study limitations included the possibility of selection bias among those who chose to complete the survey. It's also possible that more employees with children aged 18 or younger responded than those without children.

Although the researchers found that burnout, depression, and anxiety were important, they concluded that greater emphasis on work-life balance, accessibility to dependent care, and ongoing psychological and social support could prevent thousands of medical caregivers from joining this potentially devastating exodus.

"Health care systems must develop effective ways to ensure that well-trained clinicians, support staff, and non-clinical scientists are supported during this unprecedented time as well as after it," Fagerlin says. "If they do that, then health systems will be more likely to retain a diverse and effective workforce."

What The Study Did: Researchers compared rates of health maintenance organization (HMO) enrollment, by race and ethnicity, for children with commercial and public coverage with the use of national survey data.

Authors: Alon Peltz, M.D., M.B.A., M.H.S., of Harvard Medical School in Boston, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2021.4162)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

More than 60% of U.S. adults who vape are interested in quitting, according to a study published today in JAMA Network Open by MUSC Hollings Cancer Center researchers. And among those who vape to help them to quit smoking, some are successful while others continue smoking and using electronic cigarettes.

The study, which analyzed longitudinal survey data from more than 30,000 adults across the country, aimed to provide the most up-to-date estimate of how many Americans are interested in stopping their use of e-cigarettes or have made past attempts to quit.

According to the findings, former cigarette smokers had the highest intentions and interest in quitting. This is likely due to an increasing number of smokers using e-cigarettes to transition away from cigarettes, said the study's authors.

While evidence has shown that switching to e-cigarettes can be as effective as medication-based treatments for smoking cessation in some cases, many people continue to vape even after they've quit smoking. Those who aren't able to stop smoking often end up using both cigarettes and e-cigarettes simultaneously, increasing potential risks to their health.

"One of the best things you can do for your health is to stop smoking. While e-cigarettes may work for some people, they're hindering quit attempts for other people," said Amanda Palmer, Ph.D., a postdoctoral fellow in MUSC's Department of Public Health Sciences and the study's first author.

"What's interesting about the people who keep using e-cigarettes after they've quit smoking is that we don't really see that effect with other types of nicotine replacement drugs. It's rare to see someone still using a nicotine patch or nicotine gum months or years after they've quit smoking, so there's something special about e-cigarettes, even though they're delivering the same drug."

From one addictive habit to another

Unlike other nicotine replacement therapies, e-cigarettes are created to be addictive and have a similar nicotine curve to regular cigarettes, making it difficult for people to quit. People who use both cigarettes and e-cigarettes often report feeling more addicted and have trouble quitting either product.

To make matters worse, there are currently no evidence-based treatments that help people who want to quit vaping. Psychologists like Benjamin Toll, Ph.D., chief of Tobacco Cessation and Health Behaviors at Hollings and the study's senior author, can only offer methods that are proven to help people to quit smoking, which may not be relevant to adults who vape.

"I think we're doing patients a disservice by not having rigorous research to give these patients appropriate evidence-based care," said Toll, who also co-directs Hollings' Lung Cancer Screening Program. "Many of my patients who have switched to e-cigarettes find it challenging to stop using them. I would like to have data supporting the methods I share with them, and we currently don't have those in any of our clinical practice guidelines."

Smoking cessation is best achieved through a combination of medication and behavioral counseling that helps people to break the habit with coping skills and substituted behaviors. But because there may be different reasons and situations that cause people to pick up an e-cigarette versus a cigarette, the methods that help people to quit successfully may vary.

Palmer explained it this way. "If you use cigarettes, you're probably smoking for a short duration 10 to 20 times per day, whereas a lot of our e-cigarette users are vaping continuously all day and in situations where they might not otherwise be smoking," she said. "That's evidence that there needs to be different behavioral treatments, because the coping strategies I would recommend to someone who smokes are not the same for someone using e-cigarettes."

A growing need for data

Aside from uncovering how many people want to quit vaping, this study sheds light on the urgent need to understand e-cigarette use among adults more fully. Recent estimates show that roughly 3% of U.S. adults vape, but the popularity of these products may be rising.

"A lot of the press and attention around e-cigarette use has to do with youth and adolescents, but it feels like a lot of people older than 25 who use e-cigarettes tend to be left out of that conversation," said Palmer, who noted that adults are likely vaping for different reasons than those age 18 and younger.

Young people are more likely to vape on an experimental basis, whereas adults - especially those who are using e-cigarettes to quit smoking - are often using them consistently, resulting in a need for tailored interventions.

Now that they know that most adults who vape want to quit eventually, Hollings researchers plan to focus on developing data-driven interventions to help people to achieve that goal.

Palmer is beginning a new pilot study to test basic self-help kits that combine tailored medications and behavioral support that providers can offer to patients who express interest in quitting e-cigarettes. The study will also solicit feedback from providers and adults who vape about what they think they may need to quit or to help their patients to quit.

Until more data is available, Palmer and Toll recommend that people who want to use e-cigarettes as a method to stop smoking weigh the pros and cons of all available interventions before making that decision. They also urge patients to speak with their medical providers to determine which approach may be best for them.

"E-cigarettes are addictive and are not 100% safe," said Palmer. "If you're considering vaping as a method to quit smoking, consider some of the risks and benefits, and be aware that many people continue to vape after they quit smoking."

A personalized tumor cell vaccine strategy targeting Myc oncogenes combined with checkpoint therapy creates an effective immune response that bypasses antigen selection and immune privilege, according to a pre-clinical study for neuroblastoma and melanoma. The neuroblastoma model showed a 75% cure with long-term survival, researchers at Children's National Hospital found.

Myc is a family of regulator genes and proto-oncogenes that help manage cell growth and differentiation in the body. When Myc mutates to an oncogene, it can promote cancer cell growth. The Myc oncogenes are deregulated in 70% of all human cancers.

Myc mutations, like the amplification of c-MYC and MYCN, are associated with host immune suppression in melanoma and neuroblastoma tumors, according to the study published in The Journal for Immunotherapy of Cancer.

"Paradoxically, from an immunotherapeutic perspective, a lack of an immune response may offer an opportunity to target those tumors [melanoma and neuroblastoma] that would be less resistant to host immunity assuming potent cellular immunity can be generated against the tumor," said Wu et al.

The findings suggest that small molecule inhibitors--I-BET726 and JQ1--suppress Myc's uncontrolled cellular proliferation and enhance the immune response against tumor cells themselves, enabling their use as a tumor cell vaccine. The combination of cell vaccine and available therapies that keep the immune responses in check, also known as checkpoint inhibitor therapy, can help inform a personalized therapeutic tumor vaccine in the future.

"The work is pre-clinical and although we have seen excellent responses in these models, we need to determine whether this will also be effective in humans," said Xiaofang Wu, staff scientist III at Sheikh Zayed Institute for Pediatric Surgical Innovation and lead author. "For this purpose we have started laboratory testing in human cells. Our eventual hope is to translate these basic science findings to clinical application."

There is a need for more effective therapies for neuroblastoma and melanoma, given the poor outcome of patients experiencing high-risk or advanced disease through traditional chemotherapy methods. While the field has developed tumor vaccines and immune-based therapies, c-MYC and MYCN seem to protect the tumor against an immune response, so they often evade cure.

The researchers cautioned that both models induced potent immunity but draw different results, which means that this novel therapeutic vaccine is more effective in the mouse neuroblastoma model than in the melanoma model. The neuroblastoma model resulted in a remarkable 75% cure and significantly improved long-term survival despite a larger initial tumor challenge.

"In contrast, the melanoma tumor gained adaptive resistance that is associated with an imbalance between tumor cell growth and cytotoxic killing and thus the vaccine failed to eradicate the tumor," said Wu et al. "Despite potent immune effects from the vaccine, other immunosuppressive molecules will need to be targeted to see the full effects of the vaccine protocol in the melanoma model."

The study proposes a framework that could be translated for therapeutic patient-specific vaccines for MYCN-amplified neuroblastoma tumors resistant to available therapies.

To understand the exact role of c-Myc and MYCN amplification and their association with immune suppression, the researchers examined 21 human neuroblastoma samples--the majority with metastatic disease--and 324 melanoma samples where only 30 were categorized as MYC amplified. Based on the oncogene's capability to suppress the immune response, the researchers combined checkpoint inhibitors with pharmacologic molecules--I-BET726 and JQ1--to target Myc oncogenes in mouse neuroblastoma and melanoma models. They also tested for the effects of different doses, drug combinations and incubation times on tumor cell proliferation, differentiation and gene alteration.

WEST LAFAYETTE, Ind. -- If you walk with your spouse or partner on a regular basis, you might want to speed up. Or tell them to.

A new study by Purdue University nursing, health and kinesiology, and human development and family studies researchers shows that couples often decreased their speed when walking together. Speed further decreased if they were holding hands.

The study looked at walking times and gait speeds of 141 individuals from 72 couples. The participants ranged from age 25-79 and were in numerous settings, including clear or obstacle-filled pathways, walking together, walking together holding hands and walking individually.

"In our study, we focused on couples because partners in committed relationships often provide essential support to promote one another's healthy lifestyle behaviors, including exercise," says Melissa Franks, associate professor of human development and family studies.

Libby Richards, associate professor of nursing, says, "We were hoping that there would not be a reduction in speed where partners walked together. We hoped that slower partners would speed up to match the faster partner, but that was not the case. However, it's important to note that any physical activity or walking - regardless of speed - is better than none."

Richards says it is common for people to walk or exercise with a spouse, partner or friend, as it increases one's likelihood to be active, especially as Americans are encouraged to meet a goal of 150 minutes of moderate activity every week.

"If someone substantially slows down when they are walking with someone else, that could negate some of the health benefits recognized if they walked alone at a faster pace," Richards says.

Shirley Rietdyk, professor of health and kinesiology who specializes in biomechanics, says there are many reasons to measure gait speed.

"Gait speed is important to measure because it is related to overall health. Typical gait speed is predictive of fall risk, functional ability, disability recovery and mortality," Rietdyk says.

"Common exercise interventions, including strength, coordination and multimodal training, are all effective in increasing gait speed. These interventions can also delay the onset of slower gait speed and help slow the loss of gait speed. No one type of training is better than the other, so do the activity you are most likely to stick with."

While walking is one of the easiest activities, people tend to walk slower as they get older and may have to find other fitness routines to stay active.

"Older adults who are more active tend to maintain their gait speed," Rietdyk says. "In other words, slower gait speed is not an inevitable aspect of aging. Older adults who walk slower tend to have poorer health and lower functional status."

New research led by investigators from Boston Medical Center and Grady Memorial Hospital demonstrates the significant decline in hospitalizations for neurological emergencies during the COVID-19 pandemic. The rate of Subarachnoid hemorrhage (SAH) - bleeding in the space between the brain and the tissue covering the brain - hospitalizations declined 22.5 percent during the study period, which is consistent with the other reported decreases in emergencies such as stroke or heart attacks.

Published in Stroke & Vascular Neurology, the study compares subarachnoid hemorrhage hospital admissions for the months following throughout the initial COVID surge, in hospitals that bore a greater burdened by COVID-19, and those that did not.

"SAH is a global health burden, with high fatality and permanent disability rates, representing a potential impact of these emergent situations," said lead co-author Thanh N Nguyen, MD, FRCPc, a vascular and interventional neurologist at Boston Medical Center, and a professor of neurology and radiology at Boston University School of Medicine. "These neurological conditions can be life-threatening if care is not being promptly sought."

Other important data from this study includes the rate of embolization of ruptured aneurysms and aneurysmal SAH hospitalizations, which declined by 11.5 percent and 24.6 respectively.

Hospitals with a higher COVID-19 hospitalization burden were found to be more vulnerable to the decline in SAH admissions and ruptured aneurysm coiling volume. However, even hospitals with lower COVID-19 hospitalization burden were found to have decreases in SAH admissions, suggesting that access to hospital care was not the main factor for these decreases.

The cross-sectional, retrospective, observational study was done including data from six continents, 37 countries, and 140 comprehensive stroke centers. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm in need of coiling interventions, and COVID-19 were identified through prospective aneurysm databases and ICD-10 codes. Monthly and weekly admission volume data were collected over three periods of time: March 1, 2020, to May 31, 2020 (pandemic months), November 1, 2019, to February 29, 2020 (immediately preceding pandemic months), and March 1, 2019, to May 31, 2019 (equivalent period one year prior to pandemic). The findings are similar to reported decreases in SAH city-wide in Paris during a two-week period of the pandemic, and decreases in a Toronto hospital, whereas other cities such as Berlin and Joinville (South Brazil) reported no decreases in SAH during the COVID-19 pandemic.

High and intermediate procedural volume centers were more affected by declines in SAH hospitalizations and ruptured aneurysm embolization than low volume SAH coiling centers during the pandemic. However, hospitals with low SAH coiling volumes demonstrated an increase in the coiling of ruptured aneurysms during the pandemic, despite a significant decrease in total SAH admissions.

"This suggests a shift towards treating more patients with ruptured aneurysms with endovascular techniques during the pandemic to potentially shorten hospitalization times and mitigate risks of perioperative infection to the patient or provider," says Raul Nogueira, MD, director of neuroendovascular service at the Marcus Stroke & Neuroscience Center - Grady Memorial Hospital, lead co-investigator and professor of neurology and radiology at Emory University School of Medicine.

BOSTON - In the first study to use whole genome sequencing (WGS) to discover rare genomic variants associated with Alzheimer's disease (AD), researchers have identified 13 such variants (or mutations). In another novel finding, this study establishes new genetic links between AD and the function of synapses, which are the junctions that transmit information between neurons, and neuroplasticity, or the ability of neurons to reorganize the brain's neural network. These discoveries could help guide development of new therapies for this devastating neurological condition. Researchers at Massachusetts General Hospital (MGH), the Harvard T. H. Chan School of Public Health, and Beth Israel Deaconess Medical Center report these findings in Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

Over the last four decades, MGH has pioneered research on the genetic origins of AD, led by Rudolph Tanzi, PhD, vice chair of Neurology and director of the hospital's Genetics and Aging Research Unit. Notably, Tanzi and colleagues co-discovered genes that cause early onset (prior to age 60) familial AD (that is, a form that runs in families), including the amyloid protein (A4) precursor (APP), and the presenilin genes (PSEN1 and PSEN2). Mutations in these genes lead to accumulation of amyloid plaques in the brain, a hallmark of AD.

The next 30 AD gene variants that were discovered are primarily linked to chronic inflammation in the brain (or neuroinflammation), which also increases the risk for this cognitive disease. However, loss of synapses is the neurological change that is most closely correlated with the severity of dementia in Alzheimer's disease, yet no clear genetic links between the disease and these vital connections had previously been identified. "It was always kind of surprising that whole-genome screens had not identified Alzheimer's genes that are directly involved with synapses and neuroplasticity," says Tanzi.

Prior to this paper, the genome-wide association study (GWAS) was the primary tool used for identifying AD genes. In a GWAS, the genomes of many individuals are scanned in search of common gene variants that occur more frequently in people who have a given disease, such as AD. But to date, common Alzheimer's-associated gene variants have accounted for less than half of the heritability of AD. A standard GWAS misses the rare gene variants (those occurring in less than 1% of the population), a problem solved by the WGS, which scans every bit of DNA in a genome.

"This paper brings us to the next stage of disease-gene discovery by allowing us to look at the entire sequence of the human genome and assess the rare genomic variants, which we couldn't do before," says Dmitry Prokopenko, PhD, of MGH's McCance Center for Brain Health, who is lead author of the study.

Identifying less-common gene mutations that increase the risk for AD is important because they may hold critical information about the biology of the disease, says Tanzi. "Rare gene variants are the dark matter of the human genome," he says, and there are lots of them: Of the three billion pairs of nucleotide bases that form a complete set of DNA, each person has 50 to 60 million gene variants--and 77% are rare.

In their quest to find rare AD gene variants, Tanzi, Prokopenko and their colleagues performed WGS analyses on the genomes of 2,247 individuals from 605 families that include multiple members who have been diagnosed with AD. They also analyzed WGS datasets on 1,669 unrelated individuals. The study identified 13 previously unknown rare gene variants associated with AD. Strikingly, these gene variants were associated with functioning of synapses, development of neurons, and neuroplasticity.

"With this study, we believe we have created a new template for going beyond standard GWAS and association of disease with common genome variants, in which you miss much of the genetic landscape of the disease," says Tanzi, who sees potential for their methods to be used to study the genetics of many other conditions. Moreover, he plans to use "Alzheimer's in a dish"--three-dimensional cell culture models and brain organoids he and his colleagues have developed over the past decade--to explore what happens when the rare mutations this paper identified are inserted in neurons. "That could help guide us in novel drug discovery," says Tanzi.