Body

What The Study Did: The results of incorporating HIV screening into COVID-19 testing at an emergency department in Chicago are reported in this study.

Authors: David Pitrak, M.D., of the University of Chicago Medicine, 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/jamainternmed.2021.0839)

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.

What The Study Did: This modeling study estimates COVID-19-related changes in rates of colorectal cancer screenings and associated outcomes and estimates the degree to which expanded fecal immunochemical testing could potentially mitigate these outcomes.

Authors: Rachel B. Issaka, M.D., M.A.S., of the Fred Hutchinson Cancer Research Center in Seattle, 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.2021.6454)

Editor's Note: The article includes conflict 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.

New research from CU Cancer Center member Scott Cramer, PhD, and his colleagues could help in the treatment of men with certain aggressive types of prostate cancer.

Published this week in the journal Molecular Cancer Research, Cramer's study specifically looks at how the loss of two specific prostate tumor-suppressing genes -- MAP3K7 and CHD1 --increases androgen receptor signaling and makes the patient more resistant to the anti-androgen therapy that is typically administered to reduce testosterone levels in prostate cancer patients.

"Doctors don't normally stratify patients based on this subtype and say, 'We're going to have to treat these people differently,' but we think this should be considered before treating them with anti-androgen therapy because they appear to be already inherently resistant to the therapy," says Cramer, professor in the Department of Pharmacology. "They're less likely to respond to the treatment."

Cramer was the corresponding author on the paper. Lauren Jillson, a graduate student in the Cancer Biology Graduate Program at CU Anschutz, was the lead author on the study. Other CU Cancer Center members included M. Scott Lucia, MD, and James Costello, PhD. The 11 other authors were a mix of CU School of Medicine Department of Pharmacology and Department of Pathology researchers, as well as Stanford University and University of California researchers.

Elsewhere in the paper, Cramer and his co-researchers show that the loss of the expression of the MAP3K7 gene, in particular, is associated with poor outcomes, making it even more vital to treat patients who show the loss of the gene. Cramer notes that the majority of men diagnosed with prostate cancer have slow-growing tumors that are at low risk for metastasis, but about 20% of patients will eventually develop aggressive metastatic disease. Knowing that the lack of MAP3K7 and CHD1 is a signal of a more aggressive disease, and that treatments such as surgery, radiation, chemotherapy, and hormonal therapy all have side effects that can be significant, Cramer hopes eventually doctors can use the deletion as a marker for men who would benefit most from aggressive treatment strategies and spare those who are less likely to succumb to their disease.

"Those patients should be treated more aggressively than other patients because they're more likely to die from the disease," he says. "And we know that 50% of patients with loss of MAP3K7 and CHD1 are likely to recur after their primary treatment with recurrent disease."

An earlier study by Cramer showed that of prostate cancer patients with combination MAP3K7 and CHD1 deletions, about half will have recurrent prostate cancer, which ultimately leads to death. About 10-15% of all prostate cancers harbor combined MAP3K7-CHD1 deletions. He and his team are now investigating alternative treatment methods for patients resistant to anti-androgen therapy due to the deletions.

"Our ultimate goal is better treatment," he says. "There is a lot more work that needs to be done to reproduce our findings, validate them, and then extend them into preclinical models. If those all look good, then patients could potentially be stratified based on their expression of these proteins, and then hopefully we'll have better ways to treat them."

Using laboratory-grown roundworms as well as human and mouse eye tissue, University of Maryland School of Medicine (UMSOM) researchers have identified a new potential mechanism for age-related macular degeneration--the leading cause of blindness among older adults. The UMSOM researchers say that the findings suggest a new and distinct cause that is different from the previous model of a problematic immune system, showing that the structural organization of the eye's light-detecting cells may be affected by the disease.

The discovery offers the potential to identify new molecular targets to treat the disease. Their discovery was published on April 12 in the Proceedings of the National Academy of Sciences (PNAS).

According to the National Eye Institute, more than 14 percent of Americans over the age of 80 have age-related macular degeneration--a condition that leads to the progressive loss of vision with no known cure. Treatment exists for the "wet" version of the disease affecting only 10% of those with the condition, meaning most have no options.

"In order to find a cure for a disease, you have to fully understand what causes it, and we identified potential new contributors that were not known before," says Bruce Vogel, PhD, Assistant Professor of Physiology and Scientist at the UMSOM's Center for Biomedical Engineering and Technology (BioMET).

Several years ago, researchers had identified genetic mutations in the protein complement factor H as a contributor in large number of macular degeneration cases. Complement factor H marks cells in the body as self and protects them from attack by the immune system, whose job it is to eliminate invading pathogens and cells that do not belong. As a result, due to complement factor H's role in this process, it was thought that macular degeneration was likely due to the immune system attacking its own body's cells that were not marked properly as "self."

According to Dr. Vogel, since identifying effective new therapies for the disease has been slow, he wanted to see if his team could find new insights from studying the disease components in his laboratory model of the roundworm, C. elegans.

Dr. Vogel's team found a worm version of complement factor H protein located in the sensory neurons that help the worms detect chemicals, food, touch, and temperature. The protein appeared specifically in the middle region of the sensory neuron's little antennas, known as cilia (that do the work of sensing the environment), just next to another known important antenna protein called inversin. However, in worms bred to lack complement factor H, they found the inversin spread throughout the antennas rather than remaining in the middle of the antennas.

Next, the researchers confirmed their results in the light-detecting cells in tissue from human retinas. Complement factor H and inversin had the same positioning next to each other in the antenna of light-detecting cells from healthy samples. Yet in people with complement factor H mutations (i.e. people genetically predisposed to macular degeneration), they found the inversin spread around, no longer restricted to its neat banding pattern on the antenna.

"Our findings suggest that complement factor H plays a role in maintaining the organization of photoreceptor cilia and this process may be defective in age-related macular degeneration," says Vogel. "We plan to continue this work to determine how this structural disruption affects vision and to determine whether we can reverse the disruption and restore photoreceptor function."

"Age-related blindness is a vastly untreated condition that will only become more common as our population continues to age," says Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, University of Maryland Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "Studies like these are key to laying the groundwork needed to eventually develop treatments in order to treat blindness keeping older adults living independently and maintaining their quality of life."

Tsukuba, Japan - Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide, affecting as much as a quarter of humanity. It is characterized by fat accumulation in liver cells and may progress to inflammation, cirrhosis and liver failure. Now, researchers at the University of Tsukuba reveal the positive effects, beyond the expected weight-loss benefit, of exercise on the liver.

NAFLD is associated with unhealthy behaviors such as overeating and a sedentary lifestyle. In Japan 41% of middle-aged men have NAFLD and 25% will progress to non-alcoholic steatohepatitis (NASH) and hepatic dysfunction.

Weight reduction is fundamental to NAFLD management. Unfortunately, achieving a targeted bodyweight without supervision is difficult, and maintaining this over time even more so. Hitherto, exercise was considered adjunctive to dietary restrictions for weight loss but the other benefits such as reduced hepatic steatosis (fatty change) and stiffness are being increasingly recognized. However, the underlying mechanisms remain unclear.

"We compared data from obese Japanese men with NAFLD on a 3-month exercise regimen with those on dietary restriction targeting weight loss," senior author Professor Junichi Shoda explains. "We tracked hepatic parameters, reduction in adipose tissue, increase in muscle strength, reductions in inflammation and oxidative stress, changes in organokine concentrations, and expression of target genes of Nrf2, an oxidative stress sensor."

The researchers found that exercise preserved muscle mass better, though with modest decrease of body and fat mass. Remarkably, ultrasound elastography revealed that the exercise regimen reduced liver steatosis by an additional 9.5%, liver stiffness by an additional 6.8%, and the FibroScan-AST Score (a measure of liver fibrosis) by an additional 16.4% over the weight-loss regimen.

Additionally, the exercise regimen altered the circulating concentrations of specific organokines and apparently induced anti-inflammatory and anti-oxidative stress responses through activation of the Nrf2 (nuclear factor E2-related factor 2), an oxidative stress sensor. It also enhanced the phagocytic capacity of Kupffer cells which help maintain liver function.

Professor Shoda explains the relevance of their findings. "Our research shows how exercise prevents liver steatosis and fibrosis in NAFLD and clarifies that this benefit is compounded by preservation of muscle mass and is independent of weight changes. Patients on exercise regimens may become demotivated and drop out if they do not experience significant weight loss. Therefore, moderate to vigorous intensity exercise should be integrated in all NAFLD therapeutic regimens, and patients at risk for NASH should be encouraged to persevere with moderate to high intensity exercise regardless of whether or not they lose weight."

Tsukuba, Japan--Liver disease, from metabolic and bacterial causes, is a growing concern. What connects these dots? The gut, or more specifically, bacteria in the gut. Bacteria that cause inflammation in the mouth are transported through the digestive tract to the gut and liver, where they can cause liver inflammation. Lipopolysaccharides, important structural molecules in some bacteria, act as endotoxins, producing systemic effects that can manifest as non-alcoholic fatty liver disease (NAFLD). Now, a multidisciplinary team from the University of Tsukuba show that exercise could be used to improve the oral environment in people with NAFLD, potentially leading to a new treatment for the disease.

These researchers previously demonstrated that exercise benefits patients with NAFLD by reducing fat, inflammation, and scarring in the liver; improving the liver's response to and clearance of the endotoxin; and reducing gum disease. With the latest study in their series, they add another signpost to uncharted territory:

"We know that exercise has innumerable benefits to health overall and for these specific conditions," says corresponding author Professor Junichi Shoda. "With this study, we sought to characterize underlying mechanisms--that is, show how exercise alters physiology and how altered physiology induces changes in oral bacteria."

The researchers carried out biochemical and genetic analyses on saliva from overweight men with NAFLD and gum disease before and after 12-week exercise or diet programs. Men in both groups were able to lose fat mass, but those following dietary restrictions also lost muscle mass, whereas those following the exercise program gained muscle mass. "More importantly, we found that reductions in lactoferrin, lipopolysaccharide, and IgA concentrations were only evident in the men who followed the exercise regimen," Professor Shoda explains, "which suggested that the oral environment had been significantly altered by exercise."

The samples from the exercise group also showed increased bacterial diversity and changes in the relative constituent bacterial populations. In the overall population, more bacteria expressed genes related to environmental information processing, and less bacteria expressed genes related to genetic information processing and metabolism. In fact, bacteria expressed fewer genes for producing lipopolysaccharides.

"Therefore, it seems that, in people with both non-alcoholic liver disease and gum disease, exercise causes a biochemical shift in the environment of the mouth that favors the survival of less harmful bacteria," explains Professor Shoda.

A greater understanding of how to reduce the population or harmful effects of certain bacteria in patients with liver and periodontal disease could potentially lead to the development of new and improved treatment strategies for these diseases and other conditions thought to be influenced by bacteria, such as inflammatory bowel disease.

New Orleans, LA - A study led by Hui-Yi Lin, Ph.D., Professor of Biostatistics, and a team of researchers at LSU Health New Orleans Schools of Public Health and Medicine has found that adequate levels of five antioxidants may reduce infection with the strains of the human papillomavirus (HPV) associated with cervical cancer development. Findings are published in the Journal of Infectious Diseases.
Although previous studies have suggested that the onset of HPV-related cancer development may be activated by oxidative stress, the association had not been clearly understood. This study evaluated associations between 15 antioxidants and vaginal HPV infection status -- no, low-risk, and oncogenic/high-risk HPV (HR-HPV) -- in 11,070 women aged 18-59 who participated in the 2003-2016 National Health and Nutrition Examination Survey.

Study results showed that lower levels of serum albumin and four dietary antioxidants - vitamins A, B2, E, and folate -- were associated with a higher risk of HR-HPV infection. Albumin is the most bountiful circulating protein in plasma, and decreased serum albumin was found to be associated with increased systemic inflammation and impaired immune response. Based on the four dietary antioxidants, the researchers developed a nutritional antioxidant score.

"Our results showed that the women with the lowest quartile of the nutritional antioxidant score had a higher chance of both high-risk and low-risk HPV infection compared with the women with the highest quartile score after adjusting for other factors such as age, race, smoking, alcohol, and the number of sexual partners in past 12 months," notes the paper's lead author Hui-Yi Lin, PhD, Professor of Biostatistics at LSU Health New Orleans School of Public Health.

Human Papillomavirus is a well-known risk factor for cervical cancer, which is the fourth most common female cancer and contributed to 7.5% of cancer deaths for women worldwide in 2018. Certain HPV strains are more likely to trigger precursor events leading to cancer development. These strains are called oncogenic or high-risk [HR] HPV strains. Almost all cervical cancers are directly linked to previous infection with one or more HR-HPV infections.

"Currently, there is no effective antiviral therapy to clear genital HPV infection," adds Dr. Lin. "It is important to identify modifiable factors, such as antioxidants, associated with oncogenic HPV infection in order to prevent HPV carcinogenesis onset."

Cancer is one of the top causes of death worldwide. The cancer burden is related not only to genetic predisposition, but also to environmental pollution and socioeconomic factors such as lifestyle. Consequently, the burden of this disease is not uniform across all countries. In fact, the public health of China, a country known for the rapid change in its development status in the last few decades, has undergone a paradigm shift with respect to cancer incidence and mortality.

To better understand the cancer burden of the country, a team of researchers from Chinese Academy of Medical Sciences and Peking Union Medical College reviewed the data of GLOBOCAN 2020, an online database of cancer incidence and mortality compiled by the International Agency for Research on Cancer. They then compared the data for 2020 with that for 2018. "The trajectory of country-specific cancer trend is complex, and given the heterogeneity in social and demographical context, a 'one-size-fits-all' recipe would not work," says lead researcher Dr. Wanqing Chen of the Chinese Academy of Medical Sciences and Peking Union Medical College, China. The findings of Dr. Chen's team have been published recently in the Chinese Medical Journal.

Their investigation into how the ranks of 14 leading types of cancer--based on the number of new cancer cases and deaths--changed globally revealed that in 2020, breast cancer surpassed lung cancer to become the most frequently diagnosed cancer. The reasons for this rise may include increasing obesity or changing reproductive practices. While lung, liver, stomach, breast, and colon cancers were found to be the top five leading causes of cancer-related death, interestingly, the cases of stomach cancer showed a notable reduction.

The comparative assessment of the cancer incidence and mortality of 185 countries revealed some intriguing facts about the unique cancer scenario of China. It highlighted that 24% of all newly diagnosed cases and 30% of the cancer-related deaths in the world were reported from China. The high incidence of cancer might be partially attributed to the vast population of the country. The country-wise assessment of the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) further emphasized the severity of the cancer burden in China. Well above the global average, the high ASIR (204.8 per 100,000) and ASMR (129.4 per 100,000) of the country made it rank 65th and 13th in these categories, respectively. Strikingly, Japan and Korea, both China's neighboring countries, had higher ASIRs but lower ASMRs than China.

The gender-wise distribution of the most common cancer types in China painted a different picture. Among Chinese men, lung cancer was the most common cancer type, accounting for 38% of the global lung cancer cases in men. In contrast, following the global trend, breast cancer was the most common cancer type in Chinese women, accounting for 18% of global cases. However, lung cancer remained the leading cause of cancer-related deaths in both sexes in China, covering 40% of global lung cancer deaths.

Gastrointestinal cancers, including stomach, colorectal, liver, and esophageal cancers, also contributed to high incidence and mortality. Among Chinese males, gastrointestinal cancer ranked in the top five common cancer types after lung cancer and accounted for 47% of global gastrointestinal cancer deaths. Accounting for 38% of global new cases, thyroid cancer ranked as ninth and fourth in the list of most common types of cancer among men and women, respectively.

Going by the current trend of the global cancer burden, the researchers depict a grim future as the incidence and mortality due to cancer will continue to increase over the next 20 years, with a relatively high magnitude in Asia. With an already high cancer mortality rate, along with a predicted 6.85 million new cancer cases and 5.07 million deaths in 2040, China is in urgent need of targeted intervention for cancer control.

However, Dr. Chen is hopeful that dissemination of knowledge on China's cancer epidemiology would help to raise public awareness of cancer risk and promote a healthier lifestyle. He surmises, "An overview of the updated national cancer epidemiology will help renew our understanding of the recent cancer burden. Comprehensive strategies, including health education, dissemination of essential knowledge about cancer, advocating healthy lifestyles, effective screening, vaccination programs, and tobacco-control policies need to be customized to target China's cancer burden."

The insights from this study would definitely aid the policymakers of the country in tailoring preventive measures to mitigate the burden of cancer.

High blood pressure, the most important cause of disease worldwide, accelerates atherosclerosis but the mechanism is unknown. Using gene modified minipigs, researchers from the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Aarhus University (Denmark), demonstrate that high blood pressure alters the structure of arteries leading to more accumulation of LDL cholesterol and faster development of atherosclerosis. The study has been published in The Journal of the American College of Cardiology (JACC).

Blood pressure-lowering drugs are routinely used to prevent the development of atherosclerosis and heart disease, but the mechanism of this effect is still unknown. People suffering from high blood pressure (hypertension) often have accompanying changes in the hormones that control blood pressure and it has been unclear whether the pressure itself or the hormonal changes are the driver of accelerated atherosclerosis.

To investigate this, researchers from the CNIC and Aarhus University analyzed the development of atherosclerosis in minipigs that were genetically engineered to have high blood cholesterol and develop atherosclerosis.

Minipigs have arteries that are very similar in structure to human arteries and like humans they develop atherosclerosis in the heart when exposed to high blood cholesterol, Dr. Jacob Fog Bentzon comments, coordinator of the study published in JACC. As is also the case in humans, the development of the early stages of the disease is asymptomatic and therefore experiments on atherosclerosis can be conducted in minipigs with high animal welfare.

By manipulating blood pressure in the pigs and by analyzing the effects on arteries in the heart, the researchers found that the direct forces of pressure on arteries leads to structural changes that facilitate the development of atherosclerosis. "Arteries become denser and allow less passage of molecules from the blood. This includes the LDL particles that carry blood cholesterol, which instead accumulate in the innermost layer of arteries, where they drive the development of atherosclerosis", Dr. Jacob Fog Bentzon explains.

This finding uncovers an intimate relationship between the most important risk factors for atherosclerosis, LDL cholesterol and high blood pressure. While it has been known for decades that accumulation of LDL particles in arteries lead to atherosclerosis, the new research shows that high blood pressure accelerates the accumulation of LDL. Therefore, high blood pressure aggravates the effect of having high LDL cholesterol in the blood.

The new insight supports the need to keep both LDL cholesterol and blood pressure low throughout life by healthy diet choices, weight control, exercise, and, when needed, by drug therapy. "It could also pave the way for the development of more effective therapies to offset the detrimental effects of hypertension on atherosclerosis", the researchers conclude.

BOSTON - Exercise training may slow tumor growth and improve outcomes for females with breast cancer - especially those treated with immunotherapy drugs - by stimulating naturally occurring immune mechanisms, researchers at Massachusetts General Hospital (MGH) and Harvard Medical School (HMS) have found.

Tumors in mouse models of human breast cancer grew more slowly in mice put through their paces in a structured aerobic exercise program than in sedentary mice, and the tumors in exercised mice exhibited an increased anti-tumor immune response.

"The most exciting finding was that exercise training brought into tumors immune cells capable of killing cancer cells known as cytotoxic T lymphocytes (CD8+ T cells) and activated them. With more of these cells, tumors grew more slowly in mice that performed exercise training," says co-corresponding author Dai Fukumura, MD, PhD, deputy director of the Edwin L. Steele Laboratories in the Department of Radiation Oncology at MGH.

As Fukumura and colleagues report in the journal Cancer Immunology Research
, the beneficial effects of exercise training are dependent on CD8+ T cells; when the researchers depleted these cells in mice, tumors in mice that exercised no longer grew at a slower rate.

They also found evidence that recruitment of CD8+ T cells to tumors was dependent on two chemical recruiters (chemokines) labeled CXCL9 and CXCL11. Levels of these chemokines were increased in mice that exercised, and mice that were genetically engineered to lack the receptor (docking site) for these chemokines did not recruit CD8+ T cells and did not have an anti-tumor benefit.

"Humans whose tumors have higher levels of CD8+ T cells tend to have a better prognosis, respond better to treatment, and have reduced risk of cancer recurrence compared with patients whose tumors have lower levels of the immune cells, effects that were echoed by a reduced incidence of metastasis, or spread, of the cancers in mice that exercised," says co-corresponding author Rakesh K. Jain, PhD, director of the Steele Labs at MGH and Andrew Werk Cook Professor of Radiation Oncology at HMS.

CD8+ T cells are also essential for the success of drugs known as immune checkpoint inhibitors, such as Keytruda (pembrolizumab), Opdivo (nivolumab) and Yervoy (ipilimumab), which have revolutionized therapy for many types of cancer, but have to date had only limited success in breast cancer. The researchers found that exercise-trained mice displayed a much better response to immune checkpoint blockade, while the drugs did not work at all in sedentary mice.

"We showed that daily sessions of a moderate-to-vigorous intensity, continuous aerobic exercise training, lasting 30-45 minutes per session, induces a profound reprogramming of the tumor microenvironment that rewires tumor immunity, recruiting and activating CD8+ T cells to an unprecedented level with a non-pharmacological approach. Similar exercise training could be prescribed to a patient referred to an exercise oncology program," says Igor L. Gomes-Santos, PhD, lead author and exercise physiologist and post-doctoral fellow in the Steele Labs.

He notes that current clinical guidelines focus on general wellness, improved fitness levels and quality of life, but not necessarily on improved cancer treatment, especially immunotherapy, and that this lack of evidence limits its application in clinical practice.

More convincing, mechanism-based data are needed to motivate oncologists to discuss exercise training with their patients, to motivate patients to become more active and to expand implementation of outpatient exercise oncology programs, the investigators say.

Philadelphia, April 12, 2021 - Electronic cigarette (EC) use, or vaping, has both gained incredible popularity and generated tremendous controversy, but although they may be less harmful than tobacco cigarettes (TCs), they have major potential risks that may be underestimated by health authorities, the public, and medical professionals. Two cardiovascular specialists review the latest scientific studies on the cardiovascular effects of cigarette smoking versus ECs in the Canadian Journal of Cardiology, published by Elsevier. They conclude that young non-smokers should be discouraged from vaping, flavors targeted towards adolescents should be banned, and laws and regulations restricting their availability to our youth should be passed and strictly enforced.

Arash Nayeri, MD, and Holly Middlekauff, MD, of the David Geffen School of Medicine at UCLA, Department of Medicine, Division of Cardiology, Los Angeles, CA, USA, have written this review to provide physicians with an objective, rather than emotional, assessment of the available scientific data about ECs so that these physicians can help their patients make informed and thoughtful decisions.

TCs are lethal, killing up to half the people who use them. They are a leading cause of preventable cardiovascular morbidity and mortality around the globe, projected to account for an estimated eight million deaths annually worldwide by 2030, most of which resulting from cardiovascular disease.

ECs have gained popularity since 2007, both among long-term TC smokers and youth who have never smoked tobacco. There is evidence that ECs are less harmful than TCs, and the absence of a number of known toxic byproducts of TCs has helped cultivate the perception that ECs are healthy (or at least benign).

A recent review of more than 50 scientific studies involving over 12,000 participants concluded that ECs are more effective for smoking cessation than certified nicotine replacement therapy (NRT) like patches or gum and were also more effective than behavioral support alone, thereby providing a potential alternative to lethal cigarettes for adult smokers addicted to nicotine. However, there is growing concern that some of their constituents, including nicotine, and their thermal degradation byproducts, may have adverse effects.

"EC vaping by our youth has become so popular that it is approaching a public health crisis," explain the authors. "Fast on its heels is the recent rapid rise in vaping marijuana. In fact, more youth use marijuana, including vaping it, than currently smoke cigarettes. We have got to get this under control, and the first step in doing so is to know the facts."

Dr. Nayeri and Dr. Middlekauff evaluate:

Evolution in devices and nicotine delivery of ECs

Cardiovascular effects of nicotine

Non-nicotine constituents and byproducts and biomarkers of cardiovascular risk

Effects of ECs on hemodynamics, arrhythmogenicity, oxidative stress and Inflammation, thrombogenesis, and vascular health

ECs as effective tools to reduce tobacco smoking

Public health implications of tobacco smoking versus vaping

Emergence of pod-like devices

EVALI (EC, or vaping, product use associated lung injury)

It has been calculated that 1.6 to 6.6 million American lives could be saved over 10 years by switching from TCs to ECs. However, the authors point out that the long-term risks of ECs are still unknown and recommend use for the shortest effective time. They also note that fourth generation devices, "pods," can deliver similar amounts of nicotine as combustible cigarettes by employing "nicotine salts." Each pod may contain a nicotine load equivalent to a pack of cigarettes, and thus may pose a greater risk of addiction to non-smokers than earlier generation devices. On the other hand, these pod-like devices replicate the nicotine delivery of combustible cigarettes, and thus may have more appeal to smokers addicted to nicotine who want to quit tobacco cigarettes.

The authors point out that smoking one to three cigarettes a day has almost the same cardiovascular risk as smoking one to three packs per day, so using ECs to cut down on smoking (rather than eliminate it) is not an effective strategy. Therefore, they recommend that TC smokers who want to quit and who have failed certified, conventional therapies may consider ECs, but should use them to replace TCs completely.

"Only with great caution and after exhausting all other smoking cessation strategies should we consider recommending that our TC smoking patients switch to ECs," comments Dr. Nayeri. "Switching to unregulated ECs, with all their promise as smoking cessation devices, may lead to unforeseen, potentially fatal consequences. As currently marketed without quality control, ECs are no panacea," caution the authors.

Since ECs are not harmless, non-smokers, especially adolescents and young adults, should not use them, say the authors. "The direct marketing to young never smokers and the development of thousands of dessert and candy flavored liquids have unconscionably attracted millions of children to try them," notes Dr. Middlekauff. To discourage young non-smokers from vaping, the authors propose that flavors should be banned, public health anti-vaping campaigns should be supported, and laws and regulations restricting their availability to young people should be passed and strictly enforced. They also strongly recommend that people should stay away from bootlegged or black-market nicotine- or marijuana-based EC products.

"Look before you leap," writes Andrew L. Pipe, CM, MD, Division of Cardiac Prevention and Rehabilitation, University of Ottawa Heart Institute, Ottawa, ON, Canada, in an accompanying editorial.

Dr. Pipe points out that despite limited evidence to support the use of electronic nicotine delivery systems (ENDS) for smoking cessation in recent clinical studies, evidence of successful cessation in "real world" settings is not apparent. "Nonetheless, the use of ENDS containing known quantities of nicotine and limited flavoring might facilitate their use for smoking cessation, however, in the absence of appropriate product regulation such clinical use is unlikely in the near future."

Commenting on the policy vacuum in Canada that allowed the virtually unregulated entry of ENDS into Canada in contrast to the situation in other jurisdictions, Dr. Pipe notes the government's lack of consideration of their attractiveness to youth and limited regulation of their content, marketing and merchandising, contributing factors to widespread use and abuse of ENDS in Canada. Outcries from parents, educators, clinicians, and health organizations like the Heart and Stroke Foundation of Canada are now resulting in regulatory proposals.

"Will we be replacing the burden of lung- and other smoking-related cancers with an unanticipated burden of differing forms of chronic, incapacitating respiratory disease in years to come?" concludes Dr. Pipe. "Many who anticipated the arrival of ENDS with an optimistic curiosity now recognize the unfortunate realities that have surrounded their largely unregulated arrival. Perhaps some leapt - before they looked."

PHILADELPHIA - Residents in majority-Black neighborhoods experience higher rates of severe pregnancy-related health problems than those living in predominantly-white areas, according to a new study of pregnancies at a Philadelphia-based health system, which was led by researchers in the Perelman School of Medicine at the University of Pennsylvania. The findings, published today in Obstetrics and Gynecology, suggest that neighborhood-level public health interventions may be necessary in order to lower the rates of severe maternal morbidity -- such as a heart attack, heart failure, eclampsia, or hysterectomy -- and mortality in the United States.

The researchers retrospectively analyzed deliveries during a seven-year period at four hospitals within the University of Pennsylvania Health System and compared health outcomes to U.S. Census data. They found that the rate of severe maternal morbidity within a neighborhood increased by 2.4 percent with every 10 percent increase in the percentage of individuals in a Census tract who identified as Black or African American.

"Severe maternal morbidity disproportionately affects Black women. We know these differences are not genetic in etiology, but most likely due to structural racism and neighborhood-level risk factors," said senior author Jessica R. Meeker, PhD, MPH, who led the research as a third-year doctoral candidate in Epidemiology in the Perelman School of Medicine. "We wanted to explore this further and discovered that where you live is a key factor that affects maternal health outcomes."

Pregnancy-related deaths in the United States have doubled between 1987 and 2014, according to the Centers for Disease Control and Prevention (CDC). Severe maternal morbidity -- defined as "unexpected outcomes of labor and delivery that result in significant short- or long-term consequences to a woman's health" -- has risen by 75 percent over the past decade in the U.S., affecting more than 52,000 women annually.

While past studies have shown that the risk of severe maternal morbidity and mortality is markedly increased among women of color, individual risk factors alone -- such as medical comorbidities, maternal education, or income -- have not explained this disparity. Knowing that structural racism and historical segregation of neighborhoods are drivers of other poor health outcomes, such as diabetes risk, Penn Medicine researchers sought to determine whether neighborhood-level factors, like poverty, crime, and housing violations, contribute to severe maternal morbidity.

Using medical records, the research team analyzed all deliveries -- 63,334 in total -- between 2010 and 2017 at four hospitals in the University of Pennsylvania's Health System: the Hospital of the University of Pennsylvania, Penn Presbyterian Hospital, and Pennsylvania Hospital in Philadelphia, as well as Chester County Hospital, located in the Philadelphia suburbs. The health system presents an interesting case study, as it is large, and the four hospitals treat a racially- and economically-diverse patient population.

The primary outcome that the research team measured was severe maternal morbidity, defined as having at least one of the 21 indicators validated by the CDC. The team then obtained neighborhood-level information at the Census tract level from the U.S. Census Bureau and Open Data Philly, including poverty rate, violent and nonviolent crime numbers, rates of housing violations, and family income. Their study also included the percentage of those living in a given neighborhood who identified as white, Black, Asian, or Hispanic.

The researchers found that white race was the only statistically-significant, individual-level characteristic that was associated with lower odds of severe maternal morbidity. In terms of neighborhood-level factors, multiple characteristics were associated with an increased rate of severe morbidity. The most striking finding from the data was that, in the patient population studied, the rate of severe maternal morbidity increased by 2.4 percent in a given Census tract with every 10 percent increase in the percentage of individuals in the neighborhood who identified as Black or African American. Additionally, there was a 3 percent increase in the rate of severe maternal morbidity as the number of violent crimes in a given neighborhood increased.

"Since we found that neighborhood-level risk factors are independent predictors of severe maternal morbidity, this study gives further evidence that differences in race and maternal health outcomes are likely the result of historical and structural racism," said principal investigator Mary Regina Boland, PhD. "Improving our communities within the city of Philadelphia can help all individuals living in those neighborhoods, and may result in lowering rates of maternal morbidity for future generations."

Reducing maternal morbidity among Black women is a key goal of Penn Medicine. Efforts within the health system include standardizing procedures on labor and delivery, implicit bias training for physicians and staff, remote postpartum blood pressure monitoring, routine assessment of quality metrics including severe maternal morbidity stratified by race, and additional quality improvement efforts targeting disparities.

"This study gives us a blueprint for addressing racial disparities in health care at the neighborhood and population-level," said co-author Lisa Levine, MD, an assistant professor of Obstetrics and Gynecology at Penn. "Investing in neighborhoods that have been historically segregated, lacked access to government services, and subjected to racism will help to improve not only severe maternal morbidity, but also a host of other health outcomes for patients."

Evidence is growing that health care delivered by teams is superior to services delivered by a single practitioner. Published in the Journal of the American Board of Family Medicine — University of Minnesota, University of North Carolina, American Board of Family Medicine and the American Academy of Family Physicians researchers compared key elements from the practice of a pharmacist providing comprehensive medication management to the foundational components defined for primary care.
Based on a common health care team framework — the Four C’s of Primary Care (first contact, continuity, comprehensiveness, and coordination) — this team has, for the first time, articulated the impact of comprehensive medication management services delivered by pharmacists.
“We continue to see that pharmacists contribute positively to the health of patients and also to the team,” said Kylee Funk, an associate professor in the College of Pharmacy. “The results of our work demonstrate that comprehensive medication management delivered by a pharmacist both supports and aligns with the foundational elements of primary care. These are important findings as the healthcare community looks to best integrate pharmacists as key members of an interprofessional team.”
The U of M, ABFM and AAFP found in their academic commentary that:

Pharmacists support first contact by increasing provider access. When the pharmacist follows up with the provider's patients, the provider has more room in their schedule for visits with other patients;
Pharmacists improve continuity through identifying certain groups of patients who would benefit from a visit with the pharmacist. For example, patients with diabetes who are not at their blood sugar goals;
Pharmacists support primary care providers’ ability to be comprehensive in their care because pharmacists work with the patients and providers to optimize the patient’s medication regimen;
Pharmacists improve coordination by collaborating with specialists and others in the patient's healthcare team around optimization of a patient's medications.

“Comprehensive medication management is a service that can advance the mission of primary care while improving the care for patients,” added Funk. “As healthcare leaders consider ways to improve practice, increased incorporation of comprehensive medication management should be a key consideration.”

BOSTON - Medical cannabis products are not always what they seem, according to a new study led by researchers at the Massachusetts General Hospital (MGH).

In fact, the contents of these products can vary considerably from distributors' claims, according to the study, published in JAMA Network Open. This is particularly important when THC, the metabolite responsible for the "high" cannabis provides, is present in medical cannabis products labeled to be CBD only.

As more states legalize cannabis sales, demand has increased. However, there is little consistency in product regulation or labeling, unlike the strict regulation of medicines purchased through a pharmacy. As a result, labeling is often not accurately informing patients of the content of the cannabis-derived products they buy.

The psychoactive metabolite in cannabis is Δ9-tetrahydrocannabinol (THC). Cannabis products containing THC are federally banned, but states have been passing laws legalizing these products. This has in turn led to a patchwork of laws that have varied impact on guaranteeing that consumers get what they expect. Cannabidiol (CBD) does not come under FDA regulation.

In this study, researchers analyzed urine samples from nearly 100 patients enrolled in a clinical trial of the effect of medical cannabis for anxiety, depression, pain or insomnia. The purpose of the study was to see if these products were delivering the ingredients patients expected.

The results showed no CBD in about a third of the urine samples from patients who said they were using cannabis products that were CBD-dominant or had roughly equal parts CBD and THC. THC was detected in almost 80% of those samples, including among patients who thought they were only receiving CBD.

"People are buying products they think are THC-free but in fact contain a significant amount of THC," says Jodi M. Gilman, PhD, the paper's lead author and an investigator in the Center for Addiction Medicine in MGH's Department of Psychiatry. "One patient reported that she took a product she thought only contained CBD, and then when driving home that day she felt intoxicated, disoriented and very scared."

Exactly how the cannabis was consumed mattered, too. About 20% of patients who reported that they were vaping their medical cannabis had no detectable levels of THC or CBD metabolites in their urine samples. This suggests that some vaping devices may not heat cannabis products sufficiently for patients to even inhale the active ingredients.

"A lot of questions about the content of the products and their effects remain," says Gilman. "Patients need more information about what's in these products and what effects they can expect."

New York, NY - Major depressive disorder is highly prevalent, with one in five people experiencing an episode at some point in their life, and is almost twice as common in women than in men. Antidepressants are usually given as a first-line treatment, including during pregnancy, either to prevent the recurrence of depression, or as acute treatment in newly depressed patients. Antidepressant use during pregnancy is widespread and since antidepressants cross the placenta and the blood-brain barrier, concern exists about potential long-term effects of intrauterine antidepressant exposure in the unborn child.

Using the Danish National Registers to follow more than 42,000 singleton babies born during 1998-2011 for up to 18 years, researchers at the Icahn School of Medicine at Mount Sinai investigated whether exposure to antidepressants in the womb would increase the risk of developing affective disorder like depression and anxiety in the child. In a study published April 5 in Neuropsychopharmacology, the scientists found that children whose mothers continued antidepressants during pregnancy had a higher risk of affective disorders than children whose mothers stopped taking antidepressants before pregnancy. However, to understand whether the underlying disorder for which the antidepressant was given or the medication itself was linked to the child's risk of developing an affective disorder, they also studied the effect of paternal antidepressant use during pregnancy and similarly, found that children of fathers who took antidepressants throughout pregnancy had a higher risk for affective disorders. Thus, the research team speculates that rather than being an intrauterine effect, the observed link is most likely due to the parental mental illness underlying the antidepressant use.

"Approximately half of women who use antidepressants before pregnancy decide to discontinue use either before or during pregnancy due to concerns about the negative consequences for their child," said Anna-Sophie Romel, PhD, an instructor in the Department of Psychiatry at Icahn Mount Sinai and first author of the paper. "Our study does not provide evidence for a causal relationship between in-utero exposure to antidepressants and affective disorders in the child. So, while other long-term effects of intrauterine exposure to antidepressants remain to be investigated, our work supports antidepressant continuation for women with severe symptoms or a high risk of relapse because untreated psychiatric illness during pregnancy can have negative consequences on the health and development of the child. Women and their health care providers should carefully weigh all of the treatment options and jointly decide on the best course of action."