Body

September 28, 2020 - A less-invasive treatment technique called hemi-gland cryoablation (HGCryo) - destroying the areas of the prostate where cancers are located by freezing them - provides a high rate of effective prostate cancer control, according to a new study published in The Journal of Urology®, Official Journal of the American Urological Association (AUA). The journal is published in the Lippincott portfolio by Wolters Kluwer.

"Freedom from cancer, as documented by biopsy, was found in 82 percent of men who underwent HGCryo, at their 18 month follow-up," according to the research by Ryan Chuang, MD, and colleagues at the University of California, Los Angeles. The importance of utilizing modern magnetic resonance imaging (MRI)-guided prostate biopsy in monitoring the effectiveness of HGCryo is also emphasized as part of this study.

'Hemi-Gland Cryoablation' Eliminates Clinically Significant Cancer in Most Patients

In the HGCryo procedure, using an advanced ultrasound/MRI fusion system, needles are precisely placed in and around the area of the prostate where the cancer is located. Argon gas is then injected to create extremely cold temperatures, destroying the cancer and surrounding area.

According to the study, 61 men with clinically significant prostate cancer (grade 2 or higher) involving one side of the prostate gland, underwent HGCryo. Cryotherapy was performed using general anesthesia; patients were discharged on the same day as the procedure. The results were assessed through follow-up imaging procedures and MRI-guided biopsies.

Biopsies were performed at 6 months in all patients; 27 patients underwent an additional biopsy after reaching 18 months' follow-up. At both times, biopsies showed no evidence of clinically significant prostate cancer in 82 percent of patients. In men who had areas of prostate cancer detected at follow-up, repeated HGCryo or other treatments were effective.

The study assessed three different biopsy approaches for monitoring the outcomes of HGCryo therapy: tracking of prior cancer-positive sites, biopsy targeting of MRI-visible lesions, and systematic biopsy of the entire prostate using a template. "While tracking biopsy was the most sensitive, all three methods were required for maximum cancer detection," Dr. Chuang and coauthors write.

HGCryo provided notable cancer control even in six patients with more advanced prostate cancers (grade 3 or 4). None of the patients died from their cancer, and none developed metastatic prostate cancer.

Postoperative complications of HGCryo were "generally mild and short-lived." There were no serious complications, including urinary incontinence - a common complication after prostate cancer surgery. One patient developed erectile dysfunction , which was successfully treated with medication.

Cryotherapy is an FDA-approved treatment for prostate cancer and is increasingly popular as a less-invasive alternative to surgery. However, there has been limited evidence on its long-term effectiveness in controlling prostate cancer. Most studies of prostate cryoablation were performed before the availability of modern multiparametric MRI scanning of the prostate, which can provide "a targeted path to precise biopsy and focal treatment" in most men with prostate cancer.

As with other types of partial gland ablation (PGA) for treatment of prostate cancer, the findings highlight the importance of follow-up biopsy as "the most important criterion for success" in evaluating the results of HGCryo. Dr. Chuang and colleagues conclude, "As utilization of MRI-guided biopsy increases, with resulting improved accuracy of prostate tissue characterization, numbers of candidates for PGA are expected to rise."

Following two decades of research on a group of rare diseases called hypereosinophilic syndrome at Cincinnati Children's Hospital Medical Center, the U.S. Food and Drug Administration has approved the drug Nucala (mepolizumab) for use in the treatment of patients with hypereosinophilic syndrome.

Hypereosinophilic syndrome, also known as HES, is a life-threatening group of blood disorders that involve having high levels of eosinophils, a type of white blood cell that plays an important role in the immune system. Over time, these overly high levels of eosinophils enter tissues and organs and cause damage. Until now, high doses of corticosteroids were used to lower eosinophil levels to prevent damage to organs. However, disease flares still happen, and these disease flares cause dangerous damage to the body.

The FDA stated in a Sept. 25 news release that the agency had approved Nucala (mepolizumab) for patients 12 or older with HES for six months or longer without another identifiable non-blood related cause of the disease.

"We at Cincinnati Children's scored a home run in that we have been pursuing this for two decades on behalf of patients through our research," said Marc Rothenberg, MD, PhD, director of the Division of Allergy and Immunology and the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children's.

"We specialize in eosinophilic disorders, and this is a big breakthrough for the patients," added Rothenberg, who was involved in related translational research and the clinical trials of mepolizumab that preceded FDA approval. "People with rare diseases have to really fight for improved treatments and their on-label approval, and it's a long journey."

Mepolizumab, a biological antibody that blocks the eosinophil growth factor IL-5, was approved as an asthma drug in 2015.

FDA approval to treat hypereosinophilic syndrome means "that patients with HES have a treatment option that will reduce their disease flares and have improved health, without substantial side effects of this medicine," Rothenberg said.

Rothenberg focuses his lab's research on elucidating the mechanisms of allergic responses, especially in mucosal tissues such as the gastrointestinal tract and lung.

Support for Rothenberg's research has included funding from the Campaign Urging Research for Eosinophilic Diseases (CURED), which welcomed news of FDA approval for the new use of mepolizumab.

"This decision means so much to patients and their families," said Ellyn Kodroff, founder and director of the Campaign Urging Research for Eosinophilic Diseases. "Having FDA approval allows patients to afford this drug with insurance coverage, giving hope for a better and longer life. CURED is so proud to have raised and donated millions of dollars funding translational research underlying the rationale for targeting interleukins for eosinophilic conditions, like mepolizumab does. This continuing research supporting unmet needs for rare eosinophilic diseases is life changing."

Rothenberg began researching eosinophils as a doctoral student at Harvard University in the 1990s. It was at that time that he showed involvement of IL-5 in human disease and its effects on eosinophils.

At Cincinnati Children's, Rothenberg, along with other researchers around the world, provided evidence that eosinophils were pro-inflammatory cells involved in allergic diseases. Rothenberg and his colleagues contributed to the rationale of targeting eosinophils, including performing clinical studies in patients with a variety of eosinophilic disorders.

In 2008, Rothenberg led an international group of investigators to conduct a randomized clinical trial that proved the ability of mepolizumab to lower oral steroid doses in patients with HES (Rothenberg et al. New England Journal of Medicine 2008 Mar 20;358(12):1215-28. doi: 10.1056/NEJMoa070812. Epub 2008 Mar 16. PMID: 18344568).

Despite meeting the primary endpoint of the study, the FDA tightened its criteria for approval of mepolizumab, Rothenberg said. It took an additional decade of research to eventually meet the FDA's requested endpoints, focused on the clinical benefit of mepolizumab in this rare disease population.

As described in a recent publication in the Journal of Allergy and Clinical Immunology of the results of the phase 3, randomized, placebo-controlled trial in adolescent and adult patients with HES investigating the efficacy and safety of mepolizumab, mepolizumab was shown to reduce the number of HES disease flares (Roufesse et al. Journal of Allergy and Clinical Immunology 2020 Sep 18; S0091-6749(20)31276-8. doi: 10.1016/j.jaci.2020.08.037.). The 108 patients in the trial were from 39 centers and 13 countries.

A major new study has identified 2085 excess deaths in England and Wales due to heart disease and stroke during the peak of the COVID-19 pandemic. On average, that is 17 deaths each day over four months that probably could have been prevented.

Excess deaths are the number of deaths above what is normally expected - and the figure relates to the period from 2 March to 30 June, 2020.
The scientists believe the excess deaths were caused by people not seeking emergency hospital treatment for a heart attack or other acute cardiovascular illness requiring urgent medical attention, either because they were afraid of contracting COVID-19 or were not referred for treatment.

Over the same period, there was a sharp rise in the proportion of people who died at home or in a care home from acute cardiovascular diseases.
Chris Gale, Professor Cardiovascular Medicine at the University of Leeds, said: "It is entirely plausible that a number of deaths could have been prevented if people had attended hospital quickly when they began to experience their heart attack or stroke.
The sad irony is that previous research we have undertaken showed that nationwide heart attack services remained fully operational and continued to deliver high quality care during the peak of the pandemic."
The findings, based on an analysis of the information contained on death certificates, have ben published in the journal Heart.

The investigation was carried out by a team of data scientists and clinicians, led by academics at the University of Leeds. The other collaborators were from Keele University, NHS Digital, the Office for National Statistics, Barts Health NHS Trust, and University College London.
This is the third major study from academics investigating how the peak of the COVID-19 pandemic affected emergency cardiovascular services.

Dr Jianhua Wu, Associate Professor in the School of Medicine at Leeds, led the latest study. He said: "This study is the first to give a detailed and comprehensive picture of what was happening to people who were acutely ill with cardiovascular disease cross England and Wales.
"It reveals a large number of excess deaths. The findings will help Government and the NHS to develop messages that ensure people who are very ill do seek help."

Measuring excess deaths

The analysis looked at the information that is collected when a death certificate is issued. It details the cause of death and where the person died. To provide baseline data, the study looked at cardiovascular deaths from the 1 January 2014 through to 30 June 2020.

In the four months from 2 March, 2020 - when the first COVID-19 death was registered in the UK - to 30 June, there were 28,969 cardiovascular deaths. That was compared to the average number of deaths seen for the same period over each of the previous six years. It was eight percent higher, revealing 2085 excess deaths.
The excess cardiovascular deaths began to emerge in late March 2020 and peaked in early April - this was at the time the Government was promoting its 'Stay at home, Protect the NHS, Save lives' messages. That may have resulted in fewer people being prepared to go to hospital when they were becoming ill, either because they were worried about becoming infected by COVID-19 or were worried about overwhelming the NHS.

Previous studies by the researchers, published in The Lancet and European Heart Journal - Quality of Care and Clinical Outcomes, have revealed that the number of people arriving at hospital with a heart attack fell sharply, with some units seeing just over half the expected number of cases.

Changes in where people were dying

This latest analysis has revealed a shift in where people were dying. There were proportionately fewer deaths in hospital compared to the baseline data: 53.4 percent versus 63 percent. Proportionately more deaths were happening at home: 30.9 percent v 23.5 percent - and in care homes: 15.7 percent v 13.5 percent.
Excess deaths were disproportionately happening at home, up by 35 percent when compared with what would be expected, and in care homes, up by 32 percent increase.
In the paper, the scientists noted: "This 'displacement of death', most likely, signifies that the public either did not seek help or were not referred to hospital during the pandemic..."

Cause of death

For people in care homes and hospices, the most prevalent cause of death was stroke and heart failure. For those who died at home, it was heart attack or heart failure. Pulmonary embolism and cardiogenic shock, where the heart can't supply enough blood to the body, were the most frequent causes of death for those who died in hospital.

Professor Gale said: "Our study has revealed that people who died at home were most likely to have had a heart attack. This is further support for the speculation that many people were staying away from hospital even though they were very ill with an acute cardiovascular illness.
The reality of an untreated heart attack is that it will cause complications - and that will either lead to death, heart failure or life-threatening heart rhythms.
The messages that went out at the time of lockdown were important. The NHS did need protecting from a potential surge of COVID-19 cases. But some people may have taken the messaging to mean that the NHS was not able to cope if they had a medical emergency, or that hospitals were a place where they would catch the contagion. As the NHS prepares for any future wave of COVID-19, it needs to ensure people clearly understand that hospitals are open and have processes in place to minimise the risks of patients becoming infected with COVID-19."

DES PLAINES, IL -- Antacid monotherapy is more effective in relieving epigastric pain than in combination with lidocaine. That is the conclusion of a study to be published in the September 2020 issue of Academic Emergency Medicine (AEM), a journal of the Society for Academic Emergency Medicine (SAEM).

The lead author of the single-center study is Dr. Jaimee Warren, a first-year physician at the Royal Melbourne Hospital, Parkville, Victoria, Australia. The findings of the study are discussed with the author in a recent AEM podcast, We Didn't Start the Fire But Can Antacid Monotherapy Stop the Fire?

The double-blind, randomized clinical trial compared three different solutions for the treatment of adults with epigastric pain or dyspepsia presenting to the emergency department (ED): antacid monotherapy, antacid/lidocaine 2% solution, and antacid/lidocaine 2% viscous gel.

Warren, et al. concluded that all three treatments worked and there was no statistical difference in pain relief among the groups at 30 and 60 minutes; however, antacid monotherapy was found to be the most palatable solution, with statistically significant differences in taste, bitterness, and overall acceptability, and there were fewer side effects. In conclusion, the study authors recommend using antiacid monotherapy in place of lidocaine/antacid combination therapy for management of dyspepsia and epigastric pain for patients in the ED.

Commenting on the study is Robert Ehrman, MD, MS, research faculty in the department of emergency medicine at Wayne State School of Medicine in Detroit, MI:

"This study nicely demonstrates that 'more' is not always synonymous with 'better' when it comes to treating pain. Antacid alone appears to be equally efficacious to antacid-lidocaine combinations, without any of the unpleasant side effects that may discourage its use. This is important information to provide to patients as antacids are available over-the-counter, thereby allowing patients to manage their symptoms without a visit to the emergency department."

DALLAS, Sept. 28, 2020 -- A veteran's study identified more than a dozen genes associated with abdominal aortic aneurysm (AAA) that could be used to better identify people at risk for the often-deadly condition, according to new research published today in the American Heart Association's flagship journal Circulation.

Abdominal aortic aneurysm is a bulging or weakening of the aorta - the largest blood vessel in the body. Only about 20% of patients survive the rupture of an abdominal aortic aneurysm. Previous studies have detected 10 locations in the human genome associated with potential risks, however, those genes account for only a fraction of the causes for developing the condition.

"This study has doubled the number of genetic associations with abdominal aortic aneurysm, adding greatly to our understanding of the disease mechanisms," said corresponding author Philip S. Tsao, Ph.D., a professor of cardiovascular medicine at Stanford University School of Medicine and director of the VA Palo Alto Epidemiology Research and Information Center for Genomics in California. "This new information can enhance screening protocols and help identify individuals at risk for abdominal aortic aneurysm."

Researchers leveraged the world's largest genetic biobank, The Million Veteran Program,

to pinpoint several new genetic factors associated with abdominal aortic aneurysm, as well as to identify new groups of people for future therapies. The Million Veteran Program was established in 2011 to study how genes affect the health of U.S. veterans.

Using the Million Veteran Program database, researchers performed a genome-wide association study in veterans of European ancestry, testing roughly 18 million DNA sequence variants among more than 7,500 abdominal aortic aneurysm cases and 172,000 veterans without abdominal aortic aneurysms.

They then examined the effects of blood pressure on abdominal aortic aneurysms using Mendelian randomization - a technique that leverages genetic variation to study the causal relationship between traits. They also studied whether abdominal aortic aneurysms risk factors were related to aneurysms in other areas of the body.

Throughout the testing, researchers created a "polygenic risk score" to help identify subsets of the population who are more likely to develop abdominal aortic aneurysms.

The analysis found:

14 previously unidentified genetic locations associated with abdominal aortic aneurysm development - bringing the total number of known gene associations to 24.

A genetic increase of 10 mm Hg in diastolic blood pressure - the bottom number in a blood pressure reading - increased the risk of developing abdominal aortic aneurysm.

19 of the 24 risk variants for abdominal aortic aneurysm were associated with aneurysms in other parts of the body.

The polygenic risk score was strongly associated with abdominal aortic aneurysm, regardless of known risk factors, including smoking and family history.

"We were surprised that diastolic blood pressure, as opposed to systolic blood pressure, is likely of greater significance in the development of abdominal aortic aneurysm," Tsao said.

Researchers replicated the findings in an independent data set of nearly 5,000 abdominal aortic aneurysm cases and 100,000 controls (people who did not have abdominal aortic aneurysms).

Researchers say the study is somewhat limited since the database is primarily veterans of European ancestry. As the field of genetics advances, this suggests including more samples from people with diverse backgrounds to limit the possibility of ethnic disparities in precision medicine.

DALLAS, Sept. 28, 2020 -- Two newer groups of medications prescribed primarily for Type 2 diabetes treatment (SGLT2 inhibitors and GLP-1 receptor agonists) could significantly reduce risks associated with chronic kidney disease (CKD) and heart disease. Based on analyses of the clinical trials through March 2020, a group of leading experts in diabetes, heart failure, kidney disease and cardiometabolic disease believe the medicines should be considered for people with CKD and Type 2 diabetes to protect against heart and kidney disease and their serious complications, according to a new Scientific Statement from the American Heart Association, "Cardiorenal Protection With the Newer Antidiabetic Agents in Patients With Diabetes and Chronic Kidney Disease," published today in the AHA's flagship journal, Circulation.

The statement reviews evidence from multiple, large, international, randomized controlled trials of two classes of blood sugar control medications -- sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon like peptide-1 receptor agonists (GLP-1 RAs) -- in patients with Type 2 diabetes, chronic kidney disease and those who were either at risk for or already had cardiovascular disease. The composite results of the trials found that SGLT2 inhibitors and GLP-1 RAs can safely and significantly reduce the risk of cardiovascular events and death, reduce hospitalization and slow the progression of chronic to end-stage kidney disease including the risks of dialysis, transplantation or death.

"A collaborative treatment approach among primary care doctors and specialists in diabetes, cardiology and kidney disease that, when indicated, includes treatment with these two classes of medications could add more heart- and kidney disease-free years and greatly extend survival for people with Type 2 diabetes," said chair of the statement writing committee Janani Rangaswami, M.D., FACP, FAHA, associate chair of research in the department of medicine at Einstein Medical Center and associate clinical professor at the Sidney Kimmel College of Thomas Jefferson University, both in Philadelphia.

Chronic kidney disease (CKD) is a common long-term complication of Type 2 diabetes and represents a major public health problem in the U.S. The two leading causes of chronic kidney disease are Type 2 diabetes and hypertension. There are 26 million people in the U.S. diagnosed with diabetes and an additional 9.45 million are undiagnosed. In the U.S., 108 million (45%) adults have hypertension (130/80 mmHg or higher) or are taking blood pressure medications. An estimated 37 million American adults have kidney disease. Most patients with end stage kidney disease have Type 2 diabetes, and people with Type 2 diabetes are at increased risk for high blood pressure, cardiovascular disease (CVD) including heart attacks and heart failure, and stroke. Although there are established standards of care, a disproportionately high burden of kidney and cardiovascular disease exists in this population, leading to concerning levels of avoidable death, illness and health care costs, as well as poor quality of life.

The scientific statement provides detailed, practical guidance for health care professionals to recognize and treat patients who may benefit from SGLT2 inhibitor and GLP-1 RA medications.

Analysis of the clinical trials results yielded these recommendations:

Early and ongoing assessment of risks for kidney and heart disease can help identify patients who may benefit from the protective and preventive effects of these medicines.

Tailor medication choices to meet the needs of each individual patient.

Monitoring and control of high blood pressure.

Identify risks for hypoglycemia (low-blood sugar) and educate patients on the signs so they can seek treatment quickly.

Adjust all medications in tandem with these medicines and consider the burden of "polypharmacy" - meaning taking 5 or more medications daily for multiple conditions, which is common among people with Type 2 diabetes.

Patients should be counseled about the risks and symptoms of "euglycemic" diabetic ketoacidosis (DKA), when taking SGLT2 inhibitors as well as "classic" DKA (when blood sugar is very high and acidic substances called ketones build up in the body), which is serious and can be fatal.

The health care professional team should regularly screen and counsel patients about regular foot care to prevent foot ulcers or blisters that can quickly become infected and lead to amputation.

The writing group identified two additional patient subgroups who may benefit from SGLT2 inhibitors and GLP-1 RAs: people with heart failure with reduced ejection fraction (HFrEF) with or without Type 2 diabetes; and people with chronic kidney disease who do not have Type 2 diabetes. The writing group anticipates more data emerging to validate the use of SGLT2 inhibitors and GLP-1 RA medications for these at-risk patients.

GLP-1 RAs received initial FDA approval for use in glycemic control in 2005, and SGLT2 inhibitors were approved in 2013, and they were approved for treating people with Type 2 diabetes. Medications within the two classes work in different ways: SGLT2 inhibitors decrease blood sugar by causing the kidneys to remove sugar from the body through the urine. Research on medicines in this class have shown they also can reduce the risk of heart failure, slow the progression of chronic kidney disease and reduce risk of cardiovascular death. GLP-1 RAs work by simulating the functions of the body's natural incretin hormones that help lower post-meal blood sugar levels. The medicines in this group have been shown to reduce the risks of heart attack, ischemic stroke and/or cardiovascular death.

Recent studies show these newer medications are not widely prescribed, especially among patients with higher risks for cardiovascular disease and chronic kidney disease. A recent nationwide study of over one million commercially insured and Medicare Advantage adult beneficiaries showed that 7% of patients with Type 2 diabetes were treated with an SGLT2 inhibitor medication.

"Currently in the U.S., primary care professionals or endocrinologists typically initiate the use of these medications in patients with Type 2 diabetes, yet a more multi-specialty approach that includes kidney and heart specialists could help more patients benefit from treatment," noted the statement authors.

"The most important question that needs to be addressed in the future is the actual implementation of these medicines in clinical practice," said Rangaswami. "When multidisciplinary teams can identify high-risk patients and ensure targeted delivery of these therapies, as appropriate, we could greatly reduce the burden of heart and kidney disease for millions of people with Type 2 diabetes. Improving the cardiovascular and kidney health of as many people as possible - reducing morbidity, mortality and health care expenditures - are the primary goals."

It was found using observations made with the Gran Telescopio Canarias (GTC), at the Roque de los Muchachos Observatory, (Garafía, La Palma, Canary Islands), and with the ATACAMA Large Millimetre/submillimetre Array (ALMA), in Chile. The discovery was recently published in the journal Monthly Notices of the Royal Astronomical Society Letters.

The galaxy, called BOSS-EUVLG1, has a red-shift of 2.47. This is a measure of the reddening of the light coming from the galaxy, and can be used to find its distance, the further away the galaxy, the greater the value. For BOSS-EUVLG1, the value of 2.47 means that we are observing the galaxy when the universe was some 2 thousand million years old, around 20% of its present age.

The large values of redshift and luminosity of BOSS-EUVLG1 caused it to be classified previoulsy in the BOSS (Baryon Oscillation Spectroscopic Survey) project as a quasar. However, from the observations made with the OSIRIS and EMIR instruments on the GTC, and with the millimetre wave telescope ALMA, the researchers have shown that it is not a quasar but in fact a galaxy with extreme, exceptional properties.

The study revealed that the high luminosity of BOSS-EUVLG1 in the ultraviolet and in Lyman-alpha emission is due to the large number of young, massive stars in the galaxy. This high luminosity, well above the range for other galaxies, gave rise to its initial identification as a quasar. However, in quasars the high luminosity is due to the activity around the supermassive black holes in their nuclei, and not to star formation.

"BOSS-EUVLG1 seems to be dominated by a burst of formation of young, very massive stars, with hardly any dust, and with a very low metallicity, explains Rui Marques Chaves, a researcher at the CAB, formerly a doctoral student at the Instituto de Astrofísica de Canarias and the University of La Laguna (ULL), and first author of the article.

The rate of star formation in this galaxy is very high, around a thousand solar masses per year, around a thousand times higher than that in the Milky Way, although the galaxy is 30 times smaller. "This rate of star formation is comparable only to the most luminous infrared galaxies known, but the absence of dust in BOSS-EUVLG1 allows its ultraviolet and visible emission to reach us with hardly any attenuation", explains Ismael Pérez Fournon, an IAC researcher and a co-author of the article.

So, the results of the study suggest that BOSS-EUVLG1 is an example of the initial phases of the formation of massive galaxies. In spite of its high luminosity and star formation rate, its low metallicity shows that the galaxy has hardly had time to enrich its interstellar medium with dust and newly formed metals. Nevertheless, "the galaxy will evolve towards a dustier phase, similar to the infrared galaxies, -notes Camilo E. Jiménez Ángel, a doctoral student at the IAC, and a co-author of the article-. Also, its high luminosityh in the UV will last only a few hundred million years, a very short period in the evolution of a galaxy".

"This would explain why other galaxies similar to BOSS-EUVLG1 have not been discovered", finishes Claudio Dalla Vecchia, a researcher at the IAC, and a co-author of the article.

BOSS-EUVLG1 was discovered via the analysis of half a million spectra of galaxies and quasars in the BOSS project of the Sloan Digital Sky Survey (SDSS) and observations with large telescopes such as the GTC and ALMA.

CLEVELAND, Ohio (September 28, 2020)--Sleep disturbances are often reported by postmenopausal women. A new study reports just how prevalent those sleep problems are and that women who endured trauma as children or adults are more likely to suffer poor-quality sleep. Study results will be presented during the 2020 virtual Annual Meeting of The North American Menopause Society (NAMS), which opens on September 28.

This study coming out of the University of Pittsburgh used actigraphy, a noninvasive method of monitoring human rest/activity cycles, and measured sleep twice over 5 years. The study involved 166 women aged 40 to 60 years at baseline and primarily tested whether trauma exposure during childhood or adulthood resulted in persistently poor sleep quality in midlife. Although previous studies have demonstrated a similar link, they were largely based on self-reporting of sleep problems at one time point.

Of the participants in the study, 44% reported childhood trauma, and 60% reported experiencing trauma as an adult. The most common sleep-related problems documented within the group were actigraphy-measured short sleep duration (61%) and waking after the onset of sleep (WASO; 60%), as well as self-reported poor sleep quality (33%).

Researchers noted that childhood trauma was most related to persistently poor WASO, whereas adult trauma was most associated with poor sleep quality. Neither type of trauma was related to persistently poor sleep duration.

"This study provides further support that poor sleep is common in midlife women," said Dr. Karen Jakubowski, a postdoctoral scholar in the Department of Psychiatry at the University of Pittsburgh and a lead author of the study. "In addition, it highlights the adverse sleep sequelae of trauma exposure in midlife women, demonstrating that childhood and adult trauma are related to poor objective sleep continuity and subjective sleep quality, independent of sleep risk factors and depressive symptoms."

Dr. Jakubowski will be presenting the results of her study, "Trauma and sleep problems over midlife in women," during the 2020 NAMS Virtual Annual Meeting.

"Sleep quality is such an important part of a woman's overall quality of life, affecting her health as well as her cognitive functioning," says Dr. Stephanie Faubion, NAMS medical director. "That's why it's important for healthcare providers to be aware of all the factors that can affect a woman's ability to sleep, including a history of trauma."

CLEVELAND, Ohio (September 28, 2020)--Despite a common belief that women lose interest in sex as they age, a new study demonstrates that a significant percentage of women continue to rate sex as important throughout midlife. The study also identified those factors affecting which women continue to value sex most. Study results will be presented during the 2020 Virtual Annual Meeting of The North American Menopause Society (NAMS), which opens on September 28.

A number of studies have previously shown that the importance of sex is highly correlated with sexual function among midlife women. Longitudinal studies have allowed researchers to examine how the importance of sex changes as women age, giving way to the premise that women lose interest in sex as they age.

This new study included more than 3,200 women who participated in the Study of Women's Health Across the Nation. Its researchers sought to evaluate how various factors affected a woman's interest in sex throughout the menopause transition. Factors included race, education, partner status, body mass index, blood pressure, menopause status, hormones, depression symptoms, perceived stress, antidepressant use, sexual orientation, sexual satisfaction, pelvic pain, vaginal dryness, and hot flashes.

Based on this analysis, researchers identified three distinct trajectories in importance of sex with aging. For almost half of the women (45%), sex was important early in midlife and became less so over time. For roughly a quarter of the women (27%), sex remained highly important to them throughout midlife, and for another quarter (28%), sex was of low importance during midlife.

From an ethnic perspective, black women were more likely to rate sex as important for the duration of midlife, whereas Chinese and Japanese women were more likely to rate sex as not important or to see drops in importance. Other variables included women with depression symptoms, who were more likely to have low importance or see drops in importance of sex. Better sexual satisfaction was associated with maintained high levels of importance of sex over time, as was higher education.

"In contrast to prior literature reporting that the importance of sex decreases as women move through midlife, we found that, for a quarter of women, sex remains highly important to them throughout midlife," says Dr. Holly Thomas from the University of Pittsburgh, lead author of the study abstract, "How important is sex to women during midlife?"

"Studies like these provide valuable insights to healthcare providers who may otherwise dismiss a woman's waning sexual desire as a natural part of aging," says Dr. Stephanie Faubion, NAMS medical director. "Often there are other treatable reasons, such as vaginal dryness or depression, as to why a woman's interest in sex may have decreased."

Drs. Thomas and Faubion are available for interviews before and after the presentation at the virtual annual meeting.

Heart disease in young adults and teenagers may be related to exposure to diabetes in the womb, according to new research published in CMAJ (Canadian Medical Association Journal).

A study of young adults and teenagers in Manitoba, Canada, whose mothers had diabetes during their pregnancies found the offspring had a 50% to 200% higher risk of developing heart disease before age 35 than those who were not exposed in the womb.

"These observations support our hypothesis that cardiovascular disease morbidity in adolescence and early adulthood is related to exposure to maternal diabetes in utero," writes Dr. Jonathan McGavock, Children's Hospital Research Institute of Manitoba and Associate Professor at the University of Manitoba, Winnipeg, Manitoba, with coauthors.

Researchers looked at data on more than 290 000 children born to almost 190 000 mothers in Manitoba between 1979 and 2005. Of the total children, 2.8% were exposed to gestational diabetes and 1.1% to pre-existing type 2 diabetes. Exposure to both types of diabetes became more common during the study period, a trend seen elsewhere in the world.

The three most frequent diagnoses among offspring exposed to diabetes were high blood pressure (8713 people), type 2 diabetes (3568 people) and ischemic heart disease (715).

"Using data for nearly all children born in Manitoba over a period of 30 years, we found that children born to mothers with diabetes in pregnancy were 30%-80% more likely to develop a heart condition and 2.0 to 3.4 times more likely to develop a heart disease risk factor (e.g., high blood pressure, diabetes) than children born to mothers without diabetes in pregnancy," says Dr. McGavock.

Furthermore, heart conditions and risk factors were diagnosed 2 years earlier in the children exposed to diabetes in the womb.

Previous studies have documented the increased risk of type 2 diabetes, but not cardiovascular disease, from in utero exposure to diabetes.

The authors suggest these findings may be useful for preventive health practices.

"Screening children with in utero exposure to diabetes for cardiovascular disease risk factors might help to evaluate the future burden related to cardiovascular disease in the population," the authors conclude.

"Intrauterine exposure to diabetes and risk of cardiovascular disease in adolescence and early adulthood: a population-based birth cohort study" is published September 28, 2020

CLEVELAND, Ohio (September 28, 2020)--Menopause is accompanied by numerous symptoms that can interfere with a woman's quality of life, but can they also cause health problems? A new study suggests that they can, with an increased risk of cardiovascular disease in women who have two or more moderate to severe symptoms. Study results will be presented during the 2020 Virtual Annual Meeting of The North American Menopause Society (NAMS), opening on September 28.

Hot flashes are one of the most commonly reported and most bothersome symptoms of menopause. They can wreak havoc on a woman by creating fatigue and making it difficult for her to concentrate, among other issues, although in a new study out of Pennsylvania, they (by themselves) were not found to lead to any adverse health outcomes. However, it was determined that women having two or more moderate to severe menopause symptoms were at a significantly higher risk for cardiovascular disease and stroke. No association was found with other health outcomes, such as cancer risk.

Researchers also investigated whether the supplementation of calcium and vitamin D mitigated the risk, but no such evidence was found. The menopause symptoms considered as triggers for the added risk of heart disease included hot flashes, night sweats, dizziness, heart racing, tremors, restlessness, fatigue, difficulty concentrating, forgetfulness, mood swings, vaginal dryness, breast tenderness, migraines, and waking multiple times throughout the night.

"We found that even severe hot flashes were not associated with any adverse clinical health outcomes when occurring on their own, but if they or any other moderate to severe menopause symptoms were present in combination, there was an association with an increased risk of cardiovascular disease," says Dr. Matthew Nudy from Penn State Hershey Medical Center and lead author of the study, "The Severity of Vasomotor Symptoms and Number of Menopausal Symptoms in Postmenopausal Women and Silent Clinical Health Outcomes in the Women's Health Initiative Calcium and vitamin D Randomized Clinical Trial."

"With heart disease remaining the number one killer of women, studies like this are invaluable," says Dr. Stephanie Faubion, NAMS medical director. "Healthcare providers need to be aware that menopause symptoms may be more than a benign nuisance, and women suffering from these symptoms may be at increased risk for cardiovascular disease. Identifying women at high risk is important so that risk reduction strategies can be implemented."

Drs. Nudy and Faubion are available for interviews before and after the presentation at the virtual annual meeting.

CLEVELAND, Ohio (September 28, 2020)--As one of the most common treatments for effectively managing menopause symptoms, hormone therapy (HT) is also known to provide multiple health benefits, including slowing the progression of atherosclerosis. A study based on Early Versus Late Intervention Trial With Estradiol (ELITE) data evaluated the underlying mechanism of such benefit and will be presented during the 2020 Virtual Annual Meeting of The North American Menopause Society (NAMS), opening on September 28.

Atherosclerosis is a chronic inflammatory process of blood vessels that is central to most cases of cardiovascular disease. The risk of cardiovascular disease in women rapidly increases after menopause and remains the leading cause of death in US women. Data from ELITE already demonstrated the benefits of HT in reducing the progression of atherosclerosis in relatively younger, healthy postmenopausal women. In this new study, researchers specifically evaluated the effect of HT on the biomarkers of inflammation in the postmenopausal women involved in ELITE.

As part of the study, which compared oral estradiol to placebo, researchers measured the circulating concentrations of 12 inflammatory markers in 643 postmenopausal women. Through this analysis, they confirmed that HT significantly reduced the circulating concentrations of a number of key biomarkers. Women who were fewer than 6 years away from menopause showed the greatest anti-inflammatory benefits from HT compared with women more than 10 years after menopause.

"In the total sample, average on-trial levels of E-selectin, ICAM-1, IFNγ, and IL-8 were significantly lower in the hormone therapy group compared with placebo-treated women," says Dr. Roksana Karim from the University of South California Keck School of Medicine and lead author of the study "Effect of Estradiol Therapy on Markers of Inflammation: Results From the Early Versus Late Intervention Trial With Estradiol (ELITE). "Stratified by time since menopause, women within 6 years of menopause when randomized to hormone therapy showed a significant reduction in the levels of E-selectin, ICAM-1, and IL-8 compared with placebo; only E-selectin levels was significantly lower in women randomized to hormone therapy 10 or more years since menopause compared with placebo."

"This study helps us better understand the potential physiologic mechanisms that could explain why hormone therapy slows progression of heart disease early after menopause, but not in women more distant from the menopause transition," says Dr. Stephanie Faubion, NAMS medical director. "Additional research is needed to more fully understand how time since menopause alters the impact of hormone therapy on heart disease risk."

What The Study Did: This observational study examined survival rates and the use of chemotherapy before surgery among women with advanced-stage epithelial ovarian cancer in the United States from 2004 to 2016.

Authors: Alexander Melamed, M.D., M.P.H., of the NewYork-Presbyterian/Columbia University Irving Medical Center, 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.2020.17517)

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.

Peer-reviewed/Observational/People

* Nation-wide cross-sectional analysis of U.S. patients receiving dialysis finds fewer than 10% of people had COVID-19 antibodies by July 2020, and fewer than 10% of those with antibodies had been diagnosed by antigen or PCR testing.
* Researchers say this representative population is ideal for studying the general spread of COVID-19 in the U.S. because these patients undergo monthly, routine blood draws and represent other similar COVID-19 risk factors such as age, non-white race, and poverty.
* COVID-19 control efforts should prioritize minorities and people living in densely populated areas to prevent general community spread.
The first cross-sectional, nation-wide analysis of more than 28,000 patients on dialysis in the U.S. found that fewer than 10% of U.S. adults had COVID-19 antibodies as of July 2020 and fewer than 10% were diagnosed. Published today in The Lancet, the new study also shows higher COVID-19 infection rates among ethnic minorities and people living in lower-income, high density, urban areas - underling the need for COVID-19 public health efforts that prioritize these populations in order to prevent general community spread.

Researchers from Stanford University explain that patients on dialysis represent an important population to study general COVID-19 seroprevalence. These patients already undergo routine, monthly laboratory studies and represent similar risk factors to contracting COVID-19 as the general population, including age, non-white race, and poverty. Unlike community-based surveys, where a select group may show up for or agree to be tested and require a significant on-the-ground effort to launch, patients on dialysis are amenable to random sampling as part of their routine care.

The study follows previous findings from recent seroprevalence studies of highly affected countries and regions (e.g. Wuhan, China, and Spain), which have shown that despite the intense strain on resources and unprecedented excess mortality, rates of seroprevalence at the population level remain low. Other seroprevalence studies of the U.S. population have been restricted to regional hotspots, such as New York City.

"Not only is this patient population representative ethnically and socio-economically, but they are one of the few groups of people who can be repeatedly tested. Because renal disease is a Medicare-qualifying condition, they don't face many of the access-to-care barriers that limit testing among the general population," said Shuchi Anand, MD, Director of the Center for Tubulointerstitial Kidney Disease at Stanford University and lead author of the study. "We were able to determine - with a high level of precision - differences in seroprevalence among patient groups within and across regions of the United States, providing a very rich picture of the first wave of the COVID-19 outbreak that can hopefully help inform strategies to curb the epidemic moving forward by targeting vulnerable populations." [1]

The study demonstrates an urgent need for public health efforts dedicated to controlling COVID-19 to continue, with more attention paid to some of the highest risk communities the researchers identified: majority Black and Hispanic neighborhoods, low-income neighborhoods, and densely populated metropolitan areas.

Findings showed that, compared to the majority non-Hispanic white population, people living in predominantly Black and Hispanic neighborhoods experienced a two- to four-times higher likelihood of COVID-19 infection (rates of COVID-19 infection were 11.3% to 16.3% in Black and Hispanic neighborhoods, compared to 4.8% in the majority non-Hispanic white population) while poorer areas experienced a two-times higher likelihood, and the most densely populated areas showed a 10-times higher likelihood of SARS-CoV-2 seropositivity.

In the study, researchers tested the seroprevalence of SARS-CoV-2 antibodies in a randomly selected representative sample of 28,503 patients to provide a nationwide estimate of exposure to SARS-CoV-2 during the first wave of the pandemic. Of the sample population, 89% were tested in the first two weeks of July. The sampling was representative of U.S. patients on dialysis distributed by age, sex, race, ethnicity, and region - with the exception that these sampled patients were less likely to be Non-Hispanic Black compared to the general U.S. adult population. Patients in the sample lived in 46 states and 1,013 U.S. counties.

Accounting for the externally validated test sensitivity, seroprevalence ranged from 8.2% to 9.4% in the sampled population. Researchers estimated the SARS-CoV-2 standardized seroprevalence in the U.S. population to be approximately 9.3%. The authors also found significant regional variation from less than 5% in the western United States to greater than 25% in the northeast.

By comparing seroprevalence data from their study with case counts per 100,000 population from Johns Hopkins University, the authors estimate that 9.2% of seropositive patients were diagnosed.

The authors note several limitations, including that the process of undergoing in-center hemodialysis might include the use of public or non-public shared transportation to and from the facility, thus increasing the potential for exposure. Conversely, because patients on dialysis are less likely to be employed and more likely to have restricted mobility, the data might underestimate overall seroprevalence in the general population. Finally, patients receiving dialysis may have more likely died or been hospitalized due to complications of SARS-CoV-2 infection. If so, these patients would not have been present for testing in the dialysis facilities, creating a survival bias and yielding lower estimates of exposure.

Despite these limitations, this study shows that a surveillance strategy relying on monthly testing of the remainder plasma of patients receiving dialysis can produce useful estimates of SARS-CoV-2 spread inclusive of hard-to-reach, disadvantaged populations in the United States. Such surveillance can inform disease trends, resource allocation, and effectiveness of community interventions during the COVID-19 pandemic.

"This research clearly confirms that despite high rates of COVID-19 in the United States, the number of people with antibodies is still low and we haven't come close to achieving herd immunity. Until an effective vaccine is approved, we need to make sure our more vulnerable populations are reached with prevention measures," said study author Julie Parsonnet, MD, a Professor of Medicine at Stanford University. [1]

In a linked commentary, Professors Barnaby Flower and Christina Atchison from Imperial College London (UK), who were not involved in the study, note: "Although general population estimates from dialysis sampling are imperfect, they at least remain consistent across the country and from one survey to the next, permitting longitudinal surveillance. Despite the massive burden of COVID-19 in the USA, Anand and colleagues show that a small minority of the population has evidence of humoral immunity to SARS-CoV-2. Questions remain around the longevity of the immune response and correlates of protection, but high-quality longitudinal serosurveillance with accompanying clinical data can help to provide the answers. Anand and colleagues deserve credit for pioneering a scalable sampling strategy that offers a blueprint for standardised national serosurveillance in the USA and other countries with a large haemodialysing population."

It saved lives in past epidemics of lung-damaging viruses. Now, the life-support option known as ECMO appears to be doing the same for many of the critically ill COVID-19 patients who receive it, according to a new international study.

The 1,035 patients in the study faced a staggeringly high risk of death, as ventilators and other care failed to support their lungs. But after they were placed on ECMO, their actual death rate was less than 40%. That's similar to the rate for patients treated with ECMO in past outbreaks of lung-damaging viruses, and other severe forms of viral pneumonia.

The new study published in The Lancet provides strong support for the use of ECMO - short for extracorporeal membrane oxygenation -- in appropriate patients as the pandemic rages on worldwide.

It may help more hospitals that have ECMO capability understand which of their COVID-19 patients might benefit from the technique, which channels blood out of the body and into a circuit of equipment that adds oxygen directly to the blood before pumping it back into regular circulation. Small studies published early in the pandemic had cast doubt on the technique's usefulness.

Still, the international team of authors cautions that patients who show signs of needing advanced life support should receive it at hospitals with experienced ECMO teams, and that hospitals shouldn't try to add ECMO capability mid-pandemic.

Global cooperation to achieve results

The study was made possible by a rapidly created international registry that has given critical care experts near real-time data on the use of ECMO in COVID-19 patients since early in the year.

Hosted by the organization called ELSO, for Extracorporeal Life Support Organization, the registry includes data submitted by the 213 hospitals on four continents whose patients were included in the new analysis. The paper includes data on patients age 16 or older who were started on ECMO between January 16 and May 1, and follows them until death, discharge from the hospital, or August 5, whichever occurred first. The team will present the findings at the ELSO Annual Meeting on Sept. 26.

"These results from hospitals experienced in providing ECMO are similar to past reports of ECMO-supported patients, with other forms of acute respiratory distress syndrome or viral pneumonia," says co-lead author Ryan Barbaro, M.D., M.S., of Michigan Medicine, the University of Michigan's academic medical center. "These results support recommendations to consider ECMO in COVID-19 if the ventilator is failing. We hope these findings help hospitals make decisions about this resource-intensive option."

Co-lead author Graeme MacLaren, MBBS, of the National University Health System in Singapore, notes, "Most centers in this study did not need to use ECMO for COVID-19 very often. By bringing data from over 200 international centers together into the same study, ELSO has deepened our knowledge about the use of ECMO for COVID-19 in a way that would be impossible for individual centers to learn on their own."

Insights into patient outcomes

Seventy percent of the patients in the study were transferred to the hospital where they received ECMO. Half of these were actually started on ECMO - likely by the receiving hospital's team -- before they were transferred. This reinforces the importance of communication between ECMO-capable hospitals and non-ECMO hospitals that might have COVID-19 patients who could benefit from ECMO.

The new study could also help identify which patients will benefit most if they are placed on ECMO.

"Our findings also show that mortality risk rises significantly with patient age, and that those who are immunocompromised, have acute kidney injuries, worse ventilator outcomes or COVID-19-related cardiac arrests are less likely to survive," continues Barbaro, who chairs ELSO's COVID-19 registry committee and provides ECMO care as a pediatric intensive care physician at U-M's C.S. Mott Children's Hospital. "Those who need ECMO to replace cardiac function as well as lung function also did worse. All of this knowledge can help centers and families understand what patients might face if they are placed on ECMO."

"The lack of reliable information early in the pandemic hampered our ability to understand the role of ECMO for COVID-19," says co-senior author Daniel Brodie, M.D., of New York Presbyterian Hospital. "The results of this large-scale international registry study, while hardly definitive evidence, provide a real-world understanding of the potential for ECMO to save lives in a highly selected population of COVID-19 patients."
Brodie shares senior authorship with Roberto Lorusso, M.D. of the Maastricht University Medical Center in the Netherlands and Alain Combes, M.D. of Sorbonne University in Paris.

A robust statistical approach

Because the ELSO database does not track what happens to patients once they are discharged to home, other hospitals, and long-term acute care or rehabilitation facilities, the study used a statistical approach based on in-hospital mortality up to 90 days after the patient was put ECMO. This also allows the team to account for the 67 patients who were still in the hospital as of August 5, whether they were still on ECMO, in the ICU or in step-down units.

Philip Boonstra, Ph.D., of the U-M School of Public Health, helped design the study using a "competing risk" approach, based on his experience handling the statistical design and analysis of long-term data from clinical trials for cancer.

"We used 90-day in-hospital mortality because this is the highest-risk period, and because it allows us to use the information we have to the fullest, even if we don't know the final outcome for every patient," he says.

Having data through August, when only a small number of the patients in the study remained in the hospital, was important - though data are missing on a small number of patients. And even though patients who were discharged to their homes or a rehabilitation facility will likely have a long recovery ahead after the intensive level of care involved in ECMO, they are likely to survive based on past data. However, the fate of those who went to LTAC facilities, which provide long-term care at a near-ICU level, is less certain.

More about the study and next steps

More than half of the patients in the study were treated in hospitals in the United States and Canada, including Michigan Medicine's own hospitals. U-M's Robert Bartlett, M.D., emeritus professor of surgery and a co-author of the new paper, is considered a key figure in the development of ECMO, including the first use in adults in the 1980s. Bartlett led the development of the initial guidance for the use of ECMO in COVID-19.

"ECMO is the final step in the algorithm for managing life-threatening lung failure in advanced ICUs," says Bartlett. "Now we know it is effective in COVID-19."

As of August 5, 380 of the patients in the study had died in the hospital, more than 80% of them within 24 hours of a proactive decision to discontinue ECMO care because of a poor prognosis. Of the remaining patients 57% had gone home or to a rehabilitation center (311 patients); had been discharged to another hospital or a long-term acute care center (277 patients). The rest were still in the hospital but had reached 90 days after start of ECMO.

The new study adds to the information used to create the ECMO COVID-19 guidelines published by ELSO, which is in part based on past randomized controlled trials of ECMO's use in ARDS.

Barbaro and others are studying the longer-term effects of ECMO care for any patient; he leads a team that has recently received a National Institutes of Health grant for a long-term study of children who have survived after treatment with ECMO.

Meanwhile, the ELSO registry continues to track the care of patients placed on ECMO because of COVID-19. Christine Stead, the chief executive officer of ELSO, credits the rapid pivot and intense teamwork among ECMO centers and their staff for the strength of the new paper.

"We started with a WeChat dialogue with teams in China, who were able to share knowledge and help their counterparts in Japan be ready for the spread to their country," she says. "We asked all the centers that take part in ELSO to change their practice, and begin entering data about patients as soon as they were placed on ECMO, rather than waiting until they were discharged from the hospital. This has allowed us to achieve something that will help hospitals make more informed decisions, based on meaningful data, as the pandemic continues."