Publisher Health

The first large-scale trial to test the long-term effects of a cocoa flavanol supplement to prevent cardiovascular disease offers promising signals that cocoa flavanols could have protective cardiovascular effects. In papers published in The American Journal of Clinical Nutrition, a team led by Howard Sesso, ScD, MPH, and JoAnn Manson, MD, DrPH, both of the Division of Preventive Medicine at Brigham and Women’s Hospital, unpacks the main outcomes of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS), a randomized, placebo-controlled trial that tested a cocoa flavanol supplement and a multivitamin in the prevention of cardiovascular disease and cancer. While neither supplement significantly reduced the primary outcome of total cardiovascular events, people randomized to receive the cocoa flavanol supplement had a 27 percent lower rate of cardiovascular death, a pre-specified secondary endpoint.
“When we look at the totality of evidence for both the primary and secondary cardiovascular endpoints in COSMOS, we see promising signals that a cocoa flavanol supplement may reduce important cardiovascular events, including death from cardiovascular disease,” said Sesso. “These findings merit further investigation to better understand the effects of cocoa flavanols on cardiovascular health.”
“Previous studies have suggested health benefits of flavanols — compounds in several plant-based foods including cocoa, tea, grapes, and berries,” said Manson. “COSMOS was not a chocolate trial — rather, it’s a rigorous trial of a cocoa extract supplement that contains levels of cocoa flavanols that a person could never realistically consume from chocolate without adding excessive calories, fat, and sugar to their diet.”
Smaller, short-term trials have found cardiovascular benefits for cocoa flavanols on blood pressure and blood vessel dilation. COSMOS offered the first opportunity to study if a cocoa flavanol supplement might also lead to longer-term reductions in clinical cardiovascular events. Investigators also looked for reductions in risk of cancer. In addition, the trial was designed to test a common multivitamin in the prevention of cancer and cardiovascular disease.
The primary cardiovascular outcome for the cocoa flavanol intervention was a composite of total cardiovascular events, including heart attacks, stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina. More than 21,000 participants were randomized to take daily capsules that contained 500 mg cocoa flavanols (donated by Mars Edge), a multivitamin tablet (donated by GSK Consumer Healthcare), neither or both.
The study found that cocoa flavanols reduced total cardiovascular events by 10 percent, but this was not statistically significant. However, several secondary analyses provided broader support for a potential benefit of cocoa flavanols on cardiovascular events. First, those receiving the cocoa flavanol supplement had a significant 27 percent reduction in death from cardiovascular disease. Second, when the study team took adherence to study pills into account (by looking at those taking their study pills regularly), the team saw a stronger, 15 percent reduction in total cardiovascular events and a 39 percent reduction in death from cardiovascular disease. Third, a composite endpoint of major cardiovascular events (heart attacks, strokes, and cardiovascular deaths), although not a trial focus, was also significantly reduced. The authors note in their report that their promising results on cocoa flavanols and cardiovascular events warrant cautious interpretation and underscore the need for additional research.
A daily multivitamin had no significant effect on total or individual cardiovascular events. There were no safety concerns for either cocoa flavanols or a multivitamin.
COSMOS concluded after about 3.6 years, which was likely too short to detect whether the supplements could have affected cancer risk. Although a daily multivitamin improved levels of several nutritional biomarkers, it had no significant effect on total invasive cancer, the primary outcome for the multivitamin analyses. Cocoa flavanols also had no significant effect on total invasive cancer. The authors note that continuing to follow COSMOS participants may help to clarify any longer-term effects on cancer and death. The investigators and collaborators are also leveraging COSMOS to study cognitive decline, falls, eye disease, and other aging-related outcomes that may be influenced by the supplements.
“Although our study suggests intriguing signals for cardiovascular protection with cocoa flavanols, any health benefits due to taking these supplements will need confirmation in a future trial,” said Manson. Adds Sesso: “Our message for consumers is to eat a healthy, balanced diet, rich in natural food sources of flavanols, and to stay tuned as we further evaluate other important health outcomes in COSMOS.”
Sesso and Manson reported receiving investigator-initiated grants from Mars Edge, a segment of Mars Incorporated dedicated to nutrition research and products, for infrastructure support and donation of COSMOS study pills and packaging, and Pfizer Consumer Healthcare (now part of GSK Consumer Healthcare) for donation of COSMOS study pills and packaging during the conduct of the study. Dr. Sesso additionally reported receiving investigator-initiated grants from Pure Encapsulations and Pfizer Inc., and honoraria and/or travel for lectures from the Council for Responsible Nutrition, BASF, NIH, and American Society of Nutrition during the conduct of the study.
Funding: The Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) is supported by an investigator-initiated grant from Mars Edge, a segment of Mars dedicated to nutrition research and products, which included infrastructure support and the donation of cocoa extract-containing study pills and packaging. Pfizer Consumer Healthcare (now part of GSK Consumer Healthcare) provided support through the partial provision of study pills (Centrum Silver) and packaging. COSMOS is also supported in part by grants AG050657, AG071611, EY025623, and HL157665 from the National Institutes of Health, Bethesda, MD. The Women’s Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005. Neither company had a role in the trial design or conduct, data collection (other than blinded assays supported by Mars Edge and completed independently), data analysis, or manuscript preparation or review.

Stroke can have many causes. An atherothrombotic stroke is caused by a clot that forms from plaques that build up within blood vessels in the brain. A new study suggests that people who have this type of stroke who also have higher levels of triglycerides, a type of fat, in their blood may have a higher risk of having another stroke or other cardiovascular problems one year later, compared to people who had a stroke but have lower triglyceride levels. The research is published in the March 16, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study found an association even when people were taking statin drugs meant to lower triglycerides and protect against heart attack and stroke.
Elevated triglyceride levels are thought to contribute to hardening of the arteries and increased risk of heart attack, heart disease and stroke.
“Our study suggests that for people who had atherothrombotic stroke, having elevated levels of triglycerides in their blood is a risk factor for having another stroke or other cardiovascular problems in the future, and we found that to be true even if the person is on statin therapy,” said study author Takao Hoshino, MD, of the Tokyo Women’s Medical University in Japan. “The good news is that statin medications are just one therapy for high triglycerides — diet and exercise can also be effective ways to reduce the levels in your blood at little or no cost.”
The study looked at 870 people who had a stroke or transient ischemic attack. Their average age was 70. Of those, 217, or 25%, had elevated triglyceride levels, defined as fasting triglycerides levels 150 milligrams per deciliter or higher.
Researchers followed up with the participants one year later to find out if there was an association between high triglyceride levels and having another stroke, acute coronary syndrome, which is any condition caused by a sudden reduction of blood flow to the heart, or death due to vascular causes.
After adjusting for factors like cholesterol level and statin use, researchers found that people who had high triglyceride levels had a 21% greater risk of death, stroke or heart condition one year, compared to 10% greater risk for those with lower levels.
When researchers looked specifically at people who had another stroke after an atherothrombotic stroke, they found that 14 out of 114 people with normal triglyceride levels, or 12%, had one during the study, compared to 33 out of 217 people, or 16%, of those with elevated levels.
For acute coronary syndrome, one out of 114 people, or 0.9%, with normal triglyceride levels developed the heart condition one year after an atherothrombotic stroke, compared to five out of 60, or 8%, of those with elevated levels.
Hoshino notes the study did not find an association between higher triglyceride levels and future cardiovascular problems in people who had a different type of stroke called cardioembolic stroke.
“More research is needed, but for people who have had an atherothrombotic stroke, triglyceride levels may emerge as a key target for preventing future strokes and other cardiovascular problems,” Hoshino said. “Statin therapy is still an effective treatment for people with high triglyceride levels, but our study highlights how important it is to look at all the tools a person can use to lower their triglycerides, including diet modifications, exercise and taking omega-3 fatty acids.”
The study does not prove that lowering high triglyceride levels will prevent people with atherothrombotic strokes from having cardiovascular problems later; it only shows an association.
A limitation of the study is that researchers considered only the participants’ fasting levels of triglycerides.
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Materials provided by American Academy of Neurology. Note: Content may be edited for style and length.

New research in mice has identified neurons in the brain that influence competitive interactions between individuals and that play a critical role in shaping the social behavior of groups. Published in Nature by a team led by investigators at Massachusetts General Hospital (MGH), the findings will be useful not only for scientists interested in human interactions but also for those who study neurocognitive conditions such as autism spectrum disorder and schizophrenia that are characterized by altered social behavior.
“Social interactions in humans and animals occur most commonly in large groups, and these group interactions play a prominent role in sociology, ecology, psychology, economics and political science,” says lead author S. William Li, an MD/PhD student at MGH. “What processes in the brain drive the complex dynamic behavior of social groups remains poorly understood, in part because most neuroscience research thus far has focused on the behaviors of pairs of individuals interacting alone. Here, we were able to study the behavior of groups by developing a paradigm in which large cohorts of mice were wirelessly tracked across thousands of unique competitive group interactions.”
Li and his colleagues found that the animals’ social ranking in the group was closely linked to the results of competition, and by examining recordings from neurons in the brains of mice in real time, the team discovered that neurons in the anterior cingulate region of the brain store this social ranking information to inform upcoming decisions.
“Collectively, these neurons held remarkably detailed representations of the group’s behavior and their dynamics as the animals competed together for food, in addition to information about the resources available and the outcome of their past interactions,” explains senior author Ziv M. Williams, MD, a neurosurgical oncologist at MGH. “Together, these neurons could even predict the animal’s own future success well before competition onset, meaning that they likely drove the animals’ competitive behavior based on whom they interacted with.”
Manipulating the activity of these neurons, on the other hand, could artificially increase or decrease an animal’s competitive effort and therefore control their ability to successfully compete against others. “In other words, we could tune up and down the animal’s competitive drive and do so selectively without affecting other aspects of their behavior such as simple speed or motivation,” says Williams.
The findings indicate that competitive success is not simply a product of an animal’s physical fitness or strength, but rather, is strongly influenced by signals in the brain that affect competitive drive. “These unique neurons are able to integrate information about the individual’s environment, social group settings, and reward resources to calculate how to best behave under specific conditions,” says Li.
In addition to providing insights into group behavior and competition in different sociologic or economic situations and other settings, identifying the neurons that control these characteristics may help scientists design experiments to better understand scenarios in which the brain is wired differently. “Many conditions manifest in aberrant social behavior that spans many dimensions, including one’s ability to understand social norms and to display actions that may fit the dynamical structure of social groups,” says Williams. “Developing an understanding of group behavior and competition holds relevance to these neurocognitive disorders, but until now, how this happens in the brain has largely remained unexplored.”
Additional co-authors include Omer Zeliger, Leah Strahs, Raymundo Báez-Mendoza, Lance M. Johnson, and Adian McDonald Wojciechowski.
Funding for this research was provided by the National Institutes of Health, the Autism Science Foundation, an MGH-ECOR Fund for Medical Discovery Fellowship, and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation.
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Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.

A small preliminary study from Northwestern Medicine has shown that a blood test may identify risk of stillbirth and placentitis in pregnant individuals who have had COVID-19. The finding builds on another study with similar results and could have implications in how physicians screen for and address high-risk pregnancies.
Research has shown pregnant people with COVID-19 have a higher risk of stillbirths and other pregnancy complications. Anecdotal reports have also reported potentially higher cases of stillbirths caused by certain variants, leading to increased concern in the scientific community. Scientists identified a link between COVID placentitis, in which the virus infects the placenta, and these poor outcomes, but can only diagnose instances of placentitis after delivery by examining the placenta.
The new paper, published this week in the journal PLACENTA, illuminates a link between placentitis and circulating SARS-CoV-2 virus.
“Right now, we don’t know if there’s placentitis until after the fact,” said Northwestern’s Dr. Leena Mithal, the paper’s first author. “We’re laying groundwork for further studies so that in the future, people who are diagnosed with COVID during pregnancy may be able to get a test that will help identify pregnancies that may be at higher risk of stillbirth or fetal distress.”
Mithal is an assistant professor of pediatric infectious diseases at Northwestern University Feinberg School of Medicine and an attending physician at Ann & Robert H. Lurie Children’s Hospital of Chicago. Dr. Jeffery Goldstein, the director of perinatal pathology at Feinberg, led the study and is the corresponding author.
Placentitis affects between 1% and 2% of pregnant people infected with COVID-19. Unlike many pregnancy complications, the risk of placentitis and stillbirth isn’t linked to the severity of the virus. Dr. Elisheva Shanes, a co-investigator of the study and assistant professor of perinatal and autopsy pathology at Feinberg, said that makes predicting which placentas are at risk next to impossible, because an asymptomatic infection could just as easily have complications as a very sick person.

An inhalable ‘aerogel’ loaded with DNA that encodes for the SARS-CoV-2 spike protein successfully induces an immune response against COVID-19 in the lungs of mice, according to new research conducted at Penn State. The team said its aerogel could be used to create an inhalable vaccine that blocks SARS-CoV-2 transmission by preventing the virus from establishing an infection in the lungs.
“There are many potential advantages of an inhalable formulation compared to an injectable vaccine,” said Atip Lawanprasert, graduate student in biomedical engineering and a lead author of the study, which published recently in the journal Biomacromolecules. “One is avoidance of needles. Inhalable vaccines might be able to help increase the rate of vaccination because so many people are afraid of injections. No matter how high the efficacy of a vaccine, if people don’t get it, then it’s not useful.”
Scott Medina, assistant professor of biomedical engineering, Penn State, added that inhalable vaccines may be more shelf stable than traditional vaccines.
“Importantly,” Medina said, “inhalable vaccines may induce an antibody response locally in the lungs where it can potentially neutralize and clear the virus before it fully infects the host and causes symptoms.”
By contrast, Girish Kirimanjeswara, associate professor of veterinary and biomedical sciences, explained that the injectable COVID-19 vaccines induce a systemic immune response, which is effective at fighting infections with SARS-CoV-2, but not as potent as an inhalable vaccine would be in stopping the infection at the location of the virus’s entry into the body.
“The current vaccines are not very good at preventing transmission because they allow the virus to replicate in the body, even for a short period, and then transmit to other individuals,” said Kirimanjeswara. “An inhalable vaccine would elicit local immunity at the primary site of infection, where SARS-CoV-2 could be rapidly neutralized and eliminated without the inflammatory response characteristic of systemic vaccination.”
Previously, the team had developed and patented a gel-like material, called an ‘aerogel,’ as a vehicle for delivering antimicrobials to the lungs to treat bacterial respiratory infections, particularly tuberculosis.

In a first-of-its-kind study, research from the University of Vermont Cancer Center has linked phthalates, commonly called the “everywhere chemical,” to higher incidence of specific childhood cancers.
Phthalates are chemical additives used to enhance the durability or consistency of plastics and a wide range of consumer products. Humans are routinely exposed to these compounds when they leach out of the products and into the environment. They are also used as inactive ingredients in some medications, especially those that require extended or delayed drug release to work properly, for example, some anti-inflammatory drugs and antibiotics.
The study, published in the Journal of the National Cancer Institute, suggests that exposure to medication-associated phthalates may contribute to the development of some childhood cancers, and that minimizing exposure to phthalates may help prevent some childhood cancers in the future.
The study measured the association between gestational and childhood phthalate exposures and childhood cancer incidence. Lead investigator Thomas Ahern, PhD, MPH, an associate professor at the University of Vermont’s Larner College of Medicine, teamed with colleagues at Aarhus University and Odense University Hospital in Denmark. Using data from the Danish Medical Birth Registry, the Danish Medicines Agency, and the Danish Cancer Registry, all supported by the country’s universal healthcare system, investigators studied all live births between 1997 and 2017, totaling nearly 1.3 million children.
Among the 2,027 cases of childhood cancer, researchers measured associations between gestational and childhood phthalate exposure and the incidence of specific cancers.
Childhood, but not gestational (in utero) phthalate exposure was associated with 20% higher rate of childhood cancer overall, with a nearly three-fold higher rate of osteosarcoma diagnosis, a bone cancer, and a two-fold higher rate of lymphoma diagnosis, cancer of the blood.
“These results add to a growing body of evidence suggesting that these ubiquitous chemicals have a negative impact on human health,” said Ahern.
“Our study characterized phthalate exposure based on prescription fills for phthalate-containing medications. While such exposures are typically much higher magnitude than what we would call ‘background’ environmental exposure, our findings warrant concern,” he said.
Fellow Cancer Center member, American Association for the Advancement of Science (AAAS) fellow, and UVM Larner College of Medicine professor Frances Carr, PhD, notes that phthalates are now recognized endocrine disruptors because they interfere with hormonal systems and may affect thyroid function. “Although more studies are needed, exposure to phthalates has been linked to thyroid, breast, and other solid tumors. Phthalates, like other plasticizers such as bisphenol A (BPA), are ubiquitous in the environment; age of exposure, as well as chronic low dose exposures, are significant risk factors for adverse health effects,” said Carr.
“While no direct correlation has been made between phthalates in our region and increased cancer risk, this study highlights the importance of environmental exposures and their relationship to cancer risk,” said UVM Cancer Center director Randall Holcombe, MD, MBA. The study’s authors suggest that future research will explore which specific phthalate (or combination of phthalates) poses the greatest risk, and by what mechanism(s) phthalates might drive risk of osteosarcoma and lymphoma. “Ultimately, research like this will lead to a better understanding of how to mitigate the risks of environmental phthalates,” said Holcombe.
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Materials provided by University of Vermont. Original written by Kate Strotmeyer. Note: Content may be edited for style and length.

High-grade serous carcinoma is the most aggressive form of ovarian cancer and accounts for the majority of advanced-stage cases. The poor outcomes associated with the disease underscore the need for more effective treatments. A research team led by Kunle Odunsi, MD, PhD, director of the University of Chicago Medicine Comprehensive Cancer Center, has discovered novel metabolic mechanisms that contribute to how ovarian cancer escapes from immune attack, and how combination therapies can exploit these pathways to improve ovarian cancer treatment, as reported in a paper published March 16, 2022, in Science Translational Medicine.
Over the past several years, investigators from the University of Chicago, Roswell Park Comprehensive Cancer Center and other leading institutions have teamed up to address one of the most pressing questions that stymies breakthroughs in the treatment for ovarian cancer — why does immunotherapy for ovarian cancer often fail? More specifically, they explored the underlying mechanisms that result in tumors being able to evade destruction by the immune system.
The researchers focused on targeting an enzyme called indoleamine 2,3-dioxygenase 1 (IDO1), which is responsible for degrading the amino acid tryptophan, to generate break-down products that can suppress cancer-fighting immune cells (T cells) within the tumor environment. Because tumors have realized that T cells are critically dependent on tryptophan for their survival, the tumors make high amounts of IDO1 in order to deprive T cells of tryptophan. Previous studies indicated that targeting the IDO1 pathway with a drug that blocks its action, known as epacadostat (EPA), can switch back on the T cells that the tumor shut off. Paradoxically, IDO1 blockade in combination with immunotherapy has shown limited success in clinical trials, indicating a gap in knowledge of IDO1 biology and the consequences of blocking it.
To better understand how ovarian cancer escapes from immune attack, the research team wanted to see exactly what goes on in the tumor microenvironment (TME) — the surrounding normal cells, molecules, and blood vessels that support a tumor’s growth — when IDO1 is blocked. Their search began in the clinic, where they collected tissue samples from patients with newly diagnosed advanced ovarian cancer who had not undergone surgery or chemotherapy. They collected samples again after the patients received treatment with a two-week course of EPA and surgery to remove the tumor.
In the laboratory, they ran experiments to study the effects of EPA on the TME from multiple angles. Their analyses revealed EPA was effective at blocking the IDO1 pathway of tryptophan degradation, but also revealed that this action triggered a separate chain of events. The tumor microenvironment adapted to these new conditions by redirecting the breakdown of tryptophan toward the serotonin pathway and increasing production of nicotinamide adenine dinucleotide (NAD+). The elevated NAD+ was the key culprit in reducing anti-tumor activity by T cells. The finding that NAD+, a component of key metabolism pathways, affects immune responses opens a new window for understanding anti-tumor immune responses.
The next question was how to use this information to improve therapy for patients with ovarian cancer. The researchers had a hunch. Because NAD+ metabolites could bind to purinergic receptors that communicate with the immune system, they investigated the impact of blocking these receptors on T cell proliferation and function in a mouse model of ovarian cancer.
The results were fascinating. The combination of IDO inhibition with EPA and an antagonist drug designed to interfere with the purinergic receptors “rescued” T cell proliferation and led to improved survival in a preclinical mouse model of ovarian cancer. Together they deliver a one-two punch to increase anti-tumor activity.
“These findings highlight the potential downside of IDO1 inhibition and suggest that IDO1 inhibitor therapy will require a combination with NAD+ signaling blockade,” said Odunsi, lead author of the study.
The study is a prime example of translational research, which involves taking observations from the clinic and studying them in the lab to uncover vulnerable therapeutic targets. Also, the study illustrates the advantages of the team science approach, whereby a group of diverse researchers working together could lead to more breakthroughs faster than any one researcher working alone.
“This work represents a highly collaborative effort spanning a broad range of expertise using cutting-edge technologies, from clinical expertise to statistics, metabolism, gene expression, advanced cell characterization and visualization, and a preclinical model of ovarian cancer,” he said. “This body of work encapsulates a tremendous amount of effort, knowledge, and expertise from a total of 36 researchers focused on understanding how we can improve ovarian cancer immunotherapy.”
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Materials provided by University of Chicago Medical Center. Original written by Jane Kollmer. Note: Content may be edited for style and length.

Individual Candida albicans yeast strains in the human gut are as different from each other as the humans that carry them, and some C. albicans strains may damage the gut of patients with inflammatory bowel disease (IBD), according to a new study from researchers at Weill Cornell Medicine. The findings suggest a possible way to tailor treatments to individual patients in the future.
The researchers, who report their findings March 16 in Nature, used an array of techniques to study strains, or genetic variants, of Candida from the colons of people with or without ulcerative colitis, a chronic, relapsing and remitting inflammatory disorder of the colon and rectum and one of the main forms of IBD. They found that certain strains, which they call “high-damaging,” produce a potent toxin called candidalysin that damages immune cells.
“Such strains retained their “high-damaging” properties when they were removed from the patient’s gut and triggered pro-inflammatory immunity when colonized in mice, replicating certain disease hallmarks,” said senior author Dr. Iliyan Iliev, an associate professor of immunology in medicine in the Division of Gastroenterology and Hepatology and a scientist in the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.
IBD affects approximately 3.1 million people in the United States and can greatly impair patients’ quality of life. Such patients rely on a handful of available therapies, but treatments may not always be effective. The new study has suggested one reason steroids, a commonly used treatment, may not work; treating mice with the drug to suppress intestinal inflammation failed in the presence of “high-damaging” C. albicans strains.
“Our findings suggest that C. albicans strains do not cause spontaneous intestinal inflammation in a host with intact immunity,” Dr. Iliev said. “But they do expand in the intestines when inflammation is present and can be a factor that influences response to therapy in our models and perhaps in patients.”
Most studies of the human microbiome in healthy individuals and those with IBD have focused on bacteria and viruses, but recent research by Dr. Iliev and others has illuminated the contributions of fungi to the effects of microbes on humans and mice. They have found that intestinal fungi play an important role in regulating immunity at surfaces exposed to the outside, such as the intestines and lungs, due to their potent immune-stimulating characteristics. While the collective community of fungi in the body, known as the mycobiota, has been linked to several diseases, including IBD, researchers previously had not understood the mechanisms by which the mycobiota contribute to inflammation in the gut.

Raising taxes on tobacco is associated with a reduction in neonatal and infant mortality, according to an analysis of 159 countries published this week in the open-access journal PLOS Global Public Health by Anthony Laverty of Imperial College London, UK, and colleagues.
Exposure of pregnant women and babies to smoking and second-hand smoke is known to increase the risks of neonatal and infant mortality. Raising taxation on tobacco has been shown to be the most effective measure of reducing tobacco use and associated health risks, especially among low-income populations. A tobacco tax rate of 75% or greater is recommended by the World Health Organization (WHO).
In the new study, the researchers used data spanning 2008 through 2018 from 159 countries on neonatal and infant mortality, tobacco taxation, and other related variables including gross domestic product, fertility rate, education and access to drinking water.
On average across all countries studied, the neonatal mortality rate was 14.4 and the infant mortality rate was 24.9 per 1,000 live births. Worldwide between 2008-2018, the average neonatal and infant mortality rates were 14.4 and 24.9 deaths per 1,000 live births, respectively. These rates were higher in LMICs than HICs — with 33 children aged under one, including 19 newborns, in every 1,000 dying each year in LMICs, compared to 4 newborns and 6 under-ones in every 1,000 in HICs. The average total tax on cigarettes relative to retail price was 49.1%, with only 11.2% of low- and middle-income countries and 42.1% of high-income countries achieving the recommended 75% taxation. The team found that a ten percentage-point increase in total cigarette tax was associated with a 2.6% decrease in neonatal mortality (95% CI 1.9- 3.2) and a 1.9% decrease in infant mortality (95% CI 1.3- 2.6). Based on the findings, an estimated 231,220 (95% CI 152,658- 307,655) infant deaths, including 181,970 (95% CI: 135,679 to 226,377) neonatal deaths, might have been averted in 2018 if all countries had at least a 75% cigarette tax rate.
The study was not able to control for all potential confounders, but the authors suggest that the health impacts of taxation are likely mediated through decreases in prenatal and postnatal second-hand smoke exposure and decreased smoking during pregnancy.
The authors add: “We know that tobacco smoking continues to kill more than 8 million people per year, and that increasing taxes on tobacco is an effective way to bring this number down. This study highlights that if everywhere taxed tobacco at the levels recommended by the WHO, we would substantially reduce neonatal and infant deaths.”
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The American College of Cardiology has issued an expert consensus decision pathway for the evaluation and management of adults with key cardiovascular consequences of COVID-19. The document discusses myocarditis and other types of myocardial involvement, patient-centered approaches for long COVID and guidance on resumption of exercise following COVID-19. The clinical guidance was published today in the Journal of the American College of Cardiology.
“The best means to diagnose and treat myocarditis and long COVID following SARS-CoV-2 infection continues to evolve,” said Ty Gluckman, MD, MHA, co-chair of the expert consensus decision pathway. “This document attempts to provide key recommendations for how to evaluate and manage adults with these conditions, including guidance for safe return to play for both competitive and non-competitive athletes.”
Myocarditis
Myocarditis, or inflammation of the heart, is a condition defined by the presence of cardiac symptoms (chest pain, shortness of breath, palpitations), an elevated cardiac troponin (biomarker of cardiac injury), and abnormal electrocardiographic (ECG), cardiac imaging (echocardiogram, cardiac magnetic resonance imaging) and/or cardiac biopsy findings.
Although rare, myocarditis with COVID-19 is more commonly seen in men. Because myocarditis is associated with a higher risk of cardiac complications, a proactive management plan should be in place to care for these individuals. For patients with mild or moderate forms of myocarditis, hospitalization is recommended to closely monitor for worsening symptoms, while undergoing follow-up testing and treatment. Patients with severe myocarditis should ideally be hospitalized at centers with expertise in advanced heart failure, mechanical circulatory support and other advanced therapies.
Myocarditis following COVID-19 mRNA vaccination is also rare. As of May 22, 2021, the U.S. Vaccine Adverse Event Reporting System noted rates of 40.6 cases per million after the second vaccine dose among male individuals aged 12-29 years and 2.4 cases per million among male individuals aged >30 years. Corresponding rates in female individuals were 4.2 and 1 cases per million, respectively. Although most cases of myocarditis following COVID-19 mRNA vaccination are mild, it should be diagnosed and treated similarly to myocarditis following COVID-19 infection. Currently approved COVID-19 mRNA vaccines are highly effective, and the benefit-to-risk ratio is very favorable across all demographic groups evaluated thus far.