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A new study indicates some significant public messaging should be communicated before any COVID-19 vaccines are made available in the US. And with vaccines potentially being approved by the end of the year or early next year, the clock is ticking.

The report, published in the journal Vaccines, shows that 68% of respondents are supportive of being vaccinated for COVID-19, but concerns remain about side effects, sufficient vaccine testing and vaccine effectiveness.

"Messages promoting the COVID-19 vaccine need to alleviate the concerns of those who are already vaccine-hesitant," said senior study author Brian Poole, a professor of microbiology and molecular biology at Brigham Young University. "Vaccine hesitancy is growing and the World Health Organization has already deemed it one of the top threats to global health."

According to the study, there were two factors that most strongly predicted attitudes toward getting a COVID-19 vaccine:

How people feel about vaccines in general: If people are generally pro vaccine, they are generally pro COVID-19 vaccine.
How much of a challenge people believe the pandemic is for America: Respondents who said the pandemic was a severe problem for America were much more likely to want to be vaccinated for COVID-19.

Perhaps surprisingly in today's current climate, the researchers found no causal relationship between political ideology and attitudes toward the COVID-19 vaccine.

"Public health messaging regarding COVID-19 vaccination should be less about the individual need for vaccination and more about the country and how to get it back to where it needs to be," Poole said. "It also needs to address vaccine hesitancy head on and demonstrate how vaccines are safe."

The study also concludes that enough time should be taken to address concerns about both short- and long-term side effects before a vaccine is released.

According to previous research, roughly 10% of Americans are anti-vaccine (meaning they refuse to get vaccinated under any circumstance), but a growing number are vaccine-hesitant, roughly 10-25%. Vaccine hesitant individuals tend to want to "spread out vaccinations" and say they will get vaccinated for some diseases, but not all of them.

The current study survey was administered to respondents across the United States, with participants selected by age, race and sex to reflect national census data. Structural Equation Modeling was used to analyze the relationships of several factors with attitudes toward potential COVID-19 vaccination.

"It is critical that we understand the potential barriers to vaccine uptake prior to the release of a COVID vaccine," said study coauthor Jamie Jensen, BYU professor of biology. "By understanding these barriers, we can design publicity strategies that will speak directly to the potential issues and hopefully get out ahead of any public dissent. With a vaccine being the most powerful weapon we have to end this global pandemic, the knowledge from this study is absolutely critical."

New Rochelle, NY, October 13, 2020—Kegels are underused to treat and prevent urinary incontinence, especially during pregnancy and the postpartum period. This woman-controlled, non-invasive muscle exercise should be taught and the use of Kegels encouraged by providers. Knowledge and use of Kegels is examined in Journal of Women’s Health. Click here to read the article now.

“The current study does demonstrate the opportunity for changes in practice that improve Kegel education and performance. Approaches that emphasize the role of providers in preventing, identifying, and treating urinary incontinence (UI) may improve rates of Kegel exercise, decrease rates of UI, and improve quality of life (physical and emotional) for women,” states Susan Yount, PhD, Pelvic Floor Disorders Network, and coauthors. 

The study examined how women with UI learned about Kegels, and their experience with performing Kegels during pregnancy and up to 6 months postpartum. Only 25% of women with persistent UI postpartum sought care.

“UI risk increases during pregnancy, and Kegels are something a woman can do on her own to help prevent UI and as a treatment if UI does occur. Providers should educate pregnant women on the benefits of Kegels and how to perform them correctly,” says Journal of Women’s Health Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women’s Health, Richmond, VA. 

About the Journal
Journal of Women’s Health  published monthly, is a core multidisciplinary journal dedicated to the diseases and conditions that hold greater risk for or are more prevalent among women, as well as diseases that present differently in women. Led by Editor-in-Chief Susan G. Kornstein, MD, Executive Director of the Virginia Commonwealth University Institute for Women’s Health, Richmond, VA, the Journal covers the latest advances and clinical applications of new diagnostic procedures and therapeutic protocols for the prevention and management of women’s healthcare issues. Complete tables of content and a sample issue may be viewed on the Journal of Women’s Health website. Journal of Women’s Health is the official journal of the Society for Women’s Health Research. 

About the Publisher
Mary Ann Liebert, Inc., publishers is known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research. A complete list of the firm’s 90 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

DOI

10.1089/jwh.2019.8185

A new study summarizes over 30 years of clinical experience in the treatment and management of glutaric acidemia type 1 (GA1), a rare and potentially devastating metabolic disorder caused by variants in the GCDH gene. The study followed the clinical course of 168 individuals with GA1 who were born between 1973 and 2019 and originated from 26 states and 6 countries. Participants were divided into three cohorts based on timing of diagnosis and method of treatment. The study was a broad collaborative effort led by clinicians and researchers at the Clinic for Special Children (CSC) and will appear in Molecular Genetics and Metabolism. It establishes a safe and highly effective standard-of-care for the treatment of GA1, and should serve as a rich and valuable resource for dieticians, physicians, and GA1 families throughout the world for years to come.

Before the CSC's founding in 1989, 90% of infants and young children with GA1 suffered a catastrophic form of acute neurological degeneration. The brain injury of GA1 leaves children mute, wheelchair-dependent, and fully disabled by generalized dystonia, and often results in complications such as scoliosis, hip dislocation, pulmonary aspiration, chronic pain, and untimely death.

Today, with the benefit of early diagnosis, dietary therapy, and an effective hospital protocol, only 7% of children born with GA1 suffer brain injury. Specifically, state newborn screening coupled with strict dietary management reduces the risk of brain injury 14-fold, and uninjured children with GA1 have normal growth, motor development, and cognitive function. Overall, early diagnosis of GA1 with lysine-free, arginine-enriched metabolic formula and emergency IV infusions during the first two years of life is safe and effective - preventing over 90% of brain injuries. The need for dietary and emergency IV therapies beyond early childhood is uncertain at this time.

COVID-19 is now the third leading cause of death in the United States only behind cardiovascular disease and cancer. The U.S. accounts for more than 20 percent of COVID-19 cases (more than 7.7 million) and deaths (more than 210,000) in the world today while comprising 4.25 percent of the global population.

In a commentary published online in EClinicalMedicine by Lancet, researchers from Florida Atlantic University's Schmidt College of Medicine and collaborators state that "pandemic politics" is causing assaults on science, the U.S. Food and Drug Administration (FDA), the U.S. Centers for Disease Control and Prevention (CDC) as well as the health of the public.

As an example, the authors point out that the FDA, a world renowned regulatory authority issued an Emergency Use Authorization (EUA) for hydroxychloroquine in the absence of any reliable data from large-scale randomized trials, all of which later showed no benefit and some showed clear harm. According to the authors, what is even more disturbing is the escalation of the politicization of the CDC, formerly a role model for disease control and prevention activities worldwide. They state that during COVID-19, the CDC issued reopening guidelines after initial lockdowns that lasted only until the epidemic curve flattened, violating their own principles to continue until cases and deaths drastically fell. On Aug. 25, the CDC apparently updated guidelines excluding exposed but asymptomatic individuals from testing. Then, on Sept. 17, it was revealed that White House officials edited and published guidelines despite CDC objections.

Finally, with respect to the health of the U.S. public, the authors note that while the president of the United States publicly issued repeated denials while calling the pandemic a "hoax," he privately stated in a recorded interview that COVID-19 "was more deadly than even your strenuous flu."

"Unfortunately and tragically, the U.S. had been judged in early 2016 to have been best prepared for the existential threat of a pandemic, but turned out to be the least prepared for the actual threat in early 2020," said Scott M. Alter, M.D., M.B.A., first author, an emergency medicine physician, and an assistant professor in the Department of Integrated Medical Sciences in FAU's Schmidt College of Medicine.

The authors also state that the politicization of the FDA and CDC is producing continued losses of trust by the U.S. public as well as continued harm to their longstanding reputations of respect and admiration worldwide.

"The anticipated number of deaths from COVID-19 may become comparable to the most lethal epidemic of influenza in U.S. history, which occurred from 1918 to 1919 when approximately 675,000 Americans died," said Charles H. Hennekens, M.D., Dr.PH, senior author, first Sir Richard Doll Professor and senior academic advisor in FAU's Schmidt College of Medicine. "In stark contrast to both the current U.S. epidemic of COVID-19 and the Spanish Flu of 1918-19, the 2018-19 flu season affected about 42.9 million Americans, of which about 61,200 died."

Hennekens added, "As competent and compassionate healthcare professionals, we must redouble efforts to combat pandemic politics and promote evidence-based clinical and public health practices and discovery research."

The authors underscore that the U.S. has become and will very likely remain the epicenter of the pandemic worldwide. They say that if the past is prologue then pandemic politics concerning vaccine development will potentially lead to another premature EUA by the FDA in the absence of reliable evidence. They further state that it is more imperative than ever that the U.S. abandon pandemic politics and focus solely on effective public health strategies.

"In the U.S., there is an urgent need for a unified national approach for the implementation of effective public health mitigation strategies, predominantly social distancing, masking, avoidance of crowds, as well as frequent hand and face washing," said Alter.

Co-authors of the commentary are Suzanne LeBlang, M.D., an affiliate associate professor of integrated medical sciences, FAU's Schmidt College of Medicine; Richard D. Shih, M.D., a professor of integrated medical sciences and division director of emergency medicine, FAU's Schmidt College of Medicine; and Dennis G. Maki, M.D., a professor of medicine and an internationally renowned infectious disease clinician and epidemiologist from the University of Wisconsin School of Medicine and Public Health, who served with Hennekens for two years as lieutenant commanders in the U.S. Public Health Service as epidemic intelligence service officers with the CDC.

Training health care professionals in the skills and capacity to respond adequately to children and adults who have been exposed trauma, such as adverse childhood experiences (ACEs), is recognized as an essential need in health care. But opportunities to educate physicians and physician-trainees in the science of childhood adversity and trauma-informed care are limited.

The 2016 National Survey of Children's Health revealed that almost 50% of youth in Washington DC had experienced an ACE. Motivated by this data, a research team led by Binny Chokshi, M.D., pediatrician in the Division of Adolescent and Young Adult Medicine at Children's National Hospital, set out to create an accessible opportunity to train physicians in the science of childhood adversity, trauma-informed care, and resilience.

The study's researchers created four computer-based e-modules focused on addressing childhood adversity and implementing trauma-informed care in the pediatric primary care setting. The e-modules were designed for an individualized, self-directed experience to allow for distance learning with flexibility and provided an opportunity to train health professionals using an innovative, self-directed and low-resource mechanism. These e-modules were published Oct. 12 on MedEdPORTAL.

"Increasing the ability of health care providers to recognize and respond to childhood trauma, such as ACEs, can not only buffer the long-term negative physical and mental health impacts of traumatic exposures but also increase patient-centered care and improve patient care indicators," says Dr. Chokshi. "Given the large body of evidence that links exposure to childhood trauma with negative health outcomes, training physicians on strategies to mitigate the effects of trauma is paramount."

The e-modules were shown to be effective; findings showed that participants increased their knowledge, attitude, and confidence related to childhood adversity and trauma-informed care, after participating in the modules.

"In the era of COVID-19, employing a trauma-informed approach to care is of even graver importance because the reverberations of the overactivity of the biological stress response during this time will affect populations both in the near and distant future," says Dr. Chokshi. "Our e-modules provide an opportunity for pediatricians to take a self-directed approach to better serving their patients."

Seven months ago, the nation first heard of a surge of COVID-19 deaths in a Washington nursing home - an early warning sign of how the coronavirus could rip through such facilities. Since that time, more than 40% of the Americans killed by the pandemic have lived in nursing homes.

Now, a new study details how three Michigan nursing homes limited the spread of the coronavirus within their walls after the first cases were diagnosed in that early peak state.

The findings, published in the Journal of the American Geriatrics Society, could inform the ongoing effort to protect nursing home residents regionally and nationwide.

All three nursing homes in the study went into the pandemic with a proactive, partnership-based approach to general infection prevention, and response plans already in place that paved the way for effective COVID-19 containment.

This was made possible in part by their formal connections pre-COVID with Michigan Medicine, the academic medical center of the University of Michigan. This includes embedded U-M geriatric physicians and nurse practitioners, regular meetings among clinical and administrative team members from the institutions, and a long history of involvement in U-M research. The nursing homes also connected proactively with the county health department.

Rapid action and testing

Having these plans and connections in place meant that when coronavirus cases started popping up in Michigan in mid-March, the three facilities could immediately spring into action.

One of the linchpins in their response: COVID-19 viral DNA testing offered through Michigan Medicine's in-house diagnostic laboratory, with results available within 24 hours, or at the most two days.

Proactive testing of symptomatic and asymptomatic residents, and timely test results, played a crucial role in containing the outbreak of COVID-19 in these facilities, the authors say. The in-house laboratory prioritized samples from the nursing homes, so the results came much faster than they had with the commercial laboratories that had been used at first.

"As soon as we heard of cases in the Washington nursing homes, we teamed up to devise a point-prevalence testing effort that would test asymptomatic residents, in addition to testing those with symptoms, in an effort to mitigate transmission," says Ana Montoya, M.D., M.P.H., the medical director for sub-acute care at Michigan Medicine and first author of the new paper. "The results drove a tremendous effort by nursing home staff to prevent further spread to uninfected residents."

Such proactive testing recently became a federal requirement, with the frequency depending on the level of COVID-19 activity in the surrounding community. Nursing homes are also subject to reporting requirements and potential fines if they don't report testing results. But in recent weeks, the government has sent nursing homes rapid-testing machines that are less sensitive than the "gold standard" viral DNA tests used in the study. Further research will be needed on the impact of this approach, the researchers say.

The paper's senior author is Lona Mody, M.D., M.Sc., who has studied infection transmission and prevention in nursing homes for more than a decade and was senior author of a paper published in April about pandemic preparedness among Michigan nursing homes at the start of COVID-19. She also served as a consultant to the Center for Health and Research Transformation on its independent report about Michigan nursing homes and COVID-19.

"We were particularly happy to see various teams come together in a moment of crisis with a shared purpose," says Mody. "We knew that even a little delay would have enormous consequences. Our experience shows the incredible value of research, collaboration and connections. We hope that our work informs state-level and national actions to limit devastating consequences from COVID-19."

"While rapid-testing machines allow facilities to do their own testing, most facilities are still struggling with how to best utilize the machines," says Grace Jenq, M.D., the study's corresponding author, a geriatrics specialist and associate chief clinical officer for post-acute care at Michigan Medicine. "These rapid-testing machines most likely will be used for testing symptomatic residents and staff. Test results are available within minutes, so then they can be rapidly isolated and PPE can be deployed to staff caring for the individual. Negative tests will still need to be repeated using the more sensitive PCR tests."

Testing to stop spread

In all, 29 of the 215 residents in the three Michigan nursing homes in the study were diagnosed with COVID-19 between mid-March and late April. About half required hospitalization, and six died within 14 days of diagnosis.

Sixteen of the cases were caught by testing residents who showed symptoms between March 23 and early April.

But after a proactive testing blitz of asymptomatic residents in early April, only one case of symptomatic COVID-19 was identified through April 23 in each of the nursing homes in the study.

That blitz was important because it detected 10 residents who were infected but didn't have symptoms - which could mean they were asymptomatic or pre-symptomatic. This represents a full 4.7% of all residents.

Six of the 10 residents went on to develop symptoms within a few days of their test, which means they were likely to have spread the virus to other residents and staff if their infection hadn't been detected. None of them needed hospital care.

The "blitz" of testing was carried out in a single day at each facility in early April - a time when testing people without symptoms was very unusual. It allowed the nursing homes to move infected but asymptomatic residents away from others in designated COVID-19 sections of the facility.

More than 600 staff were also tested; 3.8% tested positive and were told to stay home until their risk of transmitting the virus had gone down.

While the new study does not include longer-term patterns of infection, the authors note that infection numbers in the three nursing homes have continued to be low. A fourth nursing home also affiliated with Michigan Medicine reported no COVID-19 cases in the peak months of March and April.

Implementing existing plans

As soon as symptoms were diagnosed or a COVID test came back positive, the nursing homes followed their plan to move COVID-19 positive residents into a dedicated wing staffed by teams that only cared for COVID-positive residents.

The creation of the COVID-19 wings took a collective effort among all nursing home staff, even those not usually involved in direct resident care and cleaning. Administrative staff helped move furniture, and more.

Montoya notes that clinical teams worked together creatively to reduce unneeded interaction between staff and patients infected with the virus.

This included changing the frequency of medication dosing, procedures that could aerosolize the virus, and temporary reduction in routine blood draws and other testing. The nursing homes implemented alternative bathing options if the resident's temporary room had no shower, and arranged to bring services to them instead of having them leave their room for therapy or meals.

Staff who worked at more than one nursing home, including those not in the Michigan Medicine-linked facilities, were asked to pick one and work there exclusively, to avoid carrying the virus between facilities.

Importantly, staff received hazard pay, meals and in one nursing home, even a dedicated space to stay overnight to avoid taking the virus home to their families. Special break areas were created in areas formerly used for communal resident activities, to allow staff a space to decompress and eat during a stressful time.

The facility's leadership communicated about testing and results with residents, healthcare professionals, and families; and embarked on intensive cleaning as well as re-education efforts for staff about personal protective equipment use. The companies that own the nursing homes also made special efforts to obtain enough PPE for staff when it was in shortage.

The Society for Obstetric Anesthesia and Perinatology (SOAP),the American Society of Anesthesiologists (ASA), the Society for Pediatric Anesthesia (SPA) the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) aim to clearly reassure pregnant women that the article "Association Between Epidural Analgesia During Labor and Risk of Autism Spectrum Disorders in Offspring," a new retrospective database study published in JAMA Pediatrics on October 12th, 2020 does not provide credible scientific evidence that labor epidurals for pain relief cause autism.

SOAP, ASA, SPA, ACOG and SMFM recognize the potential for this article to create anxiety among pregnant women who face a decision of whether or not to receive an epidural for childbirth. While this concern is certainly understandable, these five medical societies that represent more than 100,000 physicians want to assure the public that an association between a mother's use of epidural analgesia during childbirth, and her infant's risk of developing autism does not imply causation. In the scientific literature, the finding of an association between a treatment and an outcome does not prove the treatment caused the outcome.

"Neuraxial analgesia is the gold standard for labor pain relief," said Ruth Landau, Virginia Apgar Professor of Anesthesiology and president of SOAP, "We should not stop providing labor epidurals, and if anything, epidurals improve maternal and neonatal outcomes."

Millions of women worldwide benefit from epidural pain relief every year and give birth without any complications to mother or baby. There are many medical indications for analgesia and anesthesia during labor and delivery. In the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labor. Importantly, in this study many of the details about the course of these deliveries are not available. There are multiple other possible causes of autism that the study does not address.

Additionally, while the authors speculate about mechanisms (like maternal fever) that could explain a link between epidural pain relief and autism, none of these are plausible or confirmed in the analysis. Epidural analgesia involves administering small amounts of dilute local anesthetics and opioids into the mother's epidural space. Very low levels of these drugs are transferred to the infant, and there is no evidence that these very low levels of drug exposure cause any harm to an infant's brain.

We urge women to continue to choose safe ways to relieve pain, including epidurals, for a positive childbirth experience. Our organizations will continue to foster research and education in all aspects of childbirth care, including the safety of labor analgesia for mother and child.

As public interest and expanded research in human genome editing grows, many questions remain about ethical, legal and social implications of the technology. People who are seriously ill may overestimate the benefits of early clinical trials while underestimating the risks. This makes properly understanding informed consent, the full knowledge of risks and benefits of treatments, especially important.

In response to this emerging need, researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, asked patients, parents and physicians in the sickle cell disease community what they wanted and needed to know about genome editing to make informed decisions about participating in genome-editing clinical trials. Gene-editing treatments, which appear to provide a potential for sickle cell, are among the most widely publicized medical advances in recent years. The results were published this week in the journal AJOB Empirical Bioethics.

"An important goal of informed consent is to facilitate decisions that are consistent with a person's values," said Sara Hull, Ph.D., director of the Bioethics Core at NHGRI. "By talking to sickle cell disease stakeholders ahead of time, we can learn more about their values and hopefully do a better job of pinpointing what kinds of information will be most useful to potential research participants as they make very a difficult decision."

Researchers contacted adults with sickle cell disease and parents and physicians of adults and children with the disease. These participants completed a genetic literacy survey, watched an educational video about genome editing, completed a two-part survey, and took part in focus group discussions about CRISPR somatic genome editing, an experimental treatment option for sickle cell disease.

The researchers found that all participants wanted informed consent to include the treatment side effects of CRISPR somatic genome editing. Many people also wanted to know how such editing works and its impact on their quality of life. The groups reflected on the need to have flexibility in the kind of information provided since people have differing levels of knowledge of biology and genomics.

Interestingly, while some physicians were concerned about how well patients would understand concepts related to somatic genome editing, study participants demonstrated higher genetic literacy levels than estimated.

The NHGRI study suggests that the sickle cell disease community is optimistic about the promises of somatic genome editing. Responses highlight the need to begin discussing what informed consent looks like, especially when lack of information and misconceptions about the risks and benefits can influence a person's decision to participate in a clinical trial.

"Designing clinical trials for curative genetic therapies requires addressing the patient communities and their families need for accessible information about the risks and benefits," said Vence Bonham, J.D., an associate investigator in the Social and Behavioral Research Branch at NHGRI and senior author on the paper. "These first-in-human curative genome editing therapies are an opportunity to develop new consent approaches to meet the information needs of potential research study participants and their families."

By creating a standard for informed consent with respect to genome editing clinical trials, such engagement with patient communities may be replicated across biotechnology companies and research institutions.

"Participating in any clinical trial is both a matter of faith and good judgment for individuals, and the research community must build models of consent, understanding and trust as crucial pillars that promote safety and success for the patients," Bonham said.

Study shows that children with kidney disease have longer hospitalization stays, and higher hospitalization costs and mortality than children hospitalized for other chronic diseases.

Children with chronic kidney disease (CKD) often require hospitalization for various reasons. However, outcomes of this high risk population are unknown. Data were collected from US hospitals to study the potential impact of CKD on hospitalization-related outcomes. The authors found that children with CKD had longer hospital stays, incurred higher health care expenses, and were at higher risk of death than children hospitalized for other chronic illnesses. This study suggests that these associations are related to the higher degree of medical complexity among children hospitalized with CKD. Further investigation is needed to better understand the health care needs and delivery of care to hospitalized children with CKD.

Article Title: Inpatient Pediatric CKD Health Care Utilization and Mortality in the United States

Authors: Zubin J. Modi, MD, Anne Waldo, MS, David T. Selewski, MD, Jonathan P. Troost, PhD, and Debbie S. Gipson, MD, MS

Under embargo until 10 am ET on October 12, 2020. Full text of article available by email from media contact.

Depression and anxiety in mums-to-be is linked to a heightened risk of asthma and poorer lung function in their 10 year old children, finds research published online in the journal Thorax.

The findings suggest that the risk of later life respiratory disease is likely programmed in the womb, rather than necessarily influenced by as yet unmeasured genetic, social or environmental factors, say the researchers.

Psychological distress, to include anxiety and depression, during pregnancy is associated with increased risks of respiratory disease in preschoolers, but whether this association persists into later childhood isn't known.

To find out, the researchers drew on participants in the Generation R Study, a population-based prospective cohort study, which has been tracking life from early pregnancy onwards in Rotterdam, the Netherlands.

The degree of overall psychological distress, depression and anxiety experienced by each parent in the second term of pregnancy and 3 years after the birth, was assessed, using a validated 53-item questionnaire (Brief Symptom Inventory).

Depression and anxiety were assessed only in the mothers, at 2 and 6 months after the birth.

In all, 362 (nearly 9%) of the mothers and 167 (just under 4%) of the fathers were clinically depressed and/or anxious during the pregnancy.

The lung function of 3757 of the offspring was measured when they were 10 years old, and information on asthma obtained on 3640 of them. Almost 6% (213) had asthma.

Mothers' overall psychological distress and symptoms of anxiety and depression during pregnancy were all associated with a 45-92% increased risk of current asthma in their children, after adjusting for potentially influential factors, such as age, ethnicity, smoking during pregnancy, and pet keeping.

Factoring in fathers' psychological distress during pregnancy didn't change this association.

And only mothers' overall psychological distress during pregnancy was associated with one of three measures of lung power, the FVC, which was lower in their children. The children of mothers with depressive symptoms also had a lower FEV1, another measure of lung function.

Further analysis of the patterns of psychological distress showed that mostly depressive or anxiety symptoms both during and after pregnancy were associated with a heightened risk of asthma in the children.

But separating out the potentially influential factors into three different groups, including lifestyle and health-related, socioeconomic, and birth and early childhood factors, made no difference to the associations found.

Nor did fathers' psychological distress during pregnancy: this wasn't associated with poorer lung function or asthma in their children.

This is an observational study, and as such, can't establish cause. And few other studies have looked at the potential impact of a mother's distress during pregnancy on the health of her child(ren).

Nevertheless, there are plausible biological explanations for the findings, suggest the researchers. These include excess production of various hormones prompted by psychological distress: glucocorticoids, for example, are key to fetal lung development.

They conclude: "Our results may indicate an intrauterine effect of maternal psychological distress during pregnancy on fetal lung development and respiratory morbidity, rather than an effect of unmeasured genetic, social, behavioural or environmental factors."

NEW YORK, NY --Mothers with SARS-CoV-2 infection rarely transmit the virus to their newborns when basic infection-control practices are followed, according to a new study by researchers at Columbia University Irving Medical Center and NewYork-Presbyterian Morgan Stanley Children's Hospital. The findings--the most detailed data available on the risk of SARS-CoV-2 transmission between moms and their newborns--suggest that more extensive measures like separating COVID-19-positive mothers from their newborns and avoiding direct breastfeeding may not be warranted.

The study was published online today in JAMA Pediatrics.

"Our findings should reassure expectant mothers with COVID-19 that basic infection-control measures during and after childbirth--such as wearing a mask and engaging in breast and hand hygiene when holding or breastfeeding a baby--protected newborns from infection in this series," says Cynthia Gyamfi-Bannerman, MD, MSc, the Ellen Jacobson Levine and Eugene Jacobson Professor of Women's Health in Obstetrics and Gynecology at Columbia University Vagelos College of Physicians and Surgeons, a maternal-fetal medicine expert at NewYork-Presbyterian/Columbia University Irving Medical Center, and a senior author of the paper.

Basic Infection-Prevention Measures Reduced COVID-19 Risk in Newborns

The researchers examined outcomes in the first 101 newborns born to COVID-19-positive mothers at NewYork-Presbyterian Morgan Stanley Children's Hospital or NewYork-Presbyterian Allen Hospital from March 13 to April 24, 2020.

To reduce the risk of transmitting SARS-CoV-2 to newborns after delivery, hospital staff practiced social distancing, wore masks, and placed COVID-positive moms in private rooms. The hospitals provided the mothers with educational materials about COVID-19 and shortened hospital stays for all mothers without complications from delivery.

Most of the newborns roomed with their mothers, including during the first postpartum checkup. (Some were admitted to the newborn intensive care unit for non-COVID-related health reasons.) Infants who roomed with their moms were placed in protective cribs six feet away from the mothers' beds when resting. Direct breastfeeding and skin-to-skin contact with babies were strongly encouraged, provided the moms wore masks and washed hands and breasts with soap and water.

"During the pandemic, we continued to do what we normally do to promote bonding and development in healthy newborns, while taking a few extra precautions to minimize the risk of exposure to the virus," says Gyamfi-Bannerman.

Only two of the newborns tested positive for SARS-CoV-2 but had no clinical evidence of illness. (The researchers were unable to pinpoint how the babies became infected.) Physicians followed up with about half of the infants, including the two that tested positive for the virus, during the first two weeks of life, and all remained well.

Data Support Breastfeeding, Skin-to-Skin Contact with Baby Even if Mom Has COVID-19

A number of pediatric and health organizations have released interim guidelines for pregnant women with SARS-CoV-2, recommending the separation of mothers and newborns during their hospital stay, no direct breastfeeding, and bathing newborns as soon as possible. (Normally, newborns are bathed after a minimum of 24 hours of life because it interferes with bonding, breastfeeding and increases the risk of dangerously low temperatures and blood sugars.)

"These recommendations were made in the absence of data on rates of mother-to-newborn SARS-CoV-2 transmission and are based on experience with mother-newborn transmission of other infectious diseases," says lead author Dani Dumitriu, MD, PhD, assistant professor of pediatrics in psychiatry at Columbia University Vagelos College of Physicians and Surgeons and a pediatric newborn hospitalist in the Division of Child and Adolescent Health at NewYork-Presbyterian Morgan Stanley Children's Hospital. "But some of the recommendations conflict with what we know about the developmental benefits of early breastfeeding and skin-to-skin contact. Our study shows that these measures may not be necessary for healthy newborns with COVID-positive moms."

"We think it's particularly important that mothers with COVID-19 have the opportunity to directly breastfeed their newborns," Gyamfi-Bannerman says. "Breast milk is known to protect newborns against numerous pathogens, and it may help protect newborns against infection with SARS-CoV-2. Most studies have not found SARS-CoV-2 in breast milk, and breast milk has been found to contain antibodies against the virus."

HOUSTON -- Neoadjuvant, or pre-surgical, combination treatment with the immune checkpoint inhibitors tremelimumab (anti-CTLA-4) and durvalumab (anti-PD-1) was well-tolerated and showed early signs of activity in certain patients with localized bladder cancer who do not have standard treatment options available, according to a Phase I clinical trial conducted by The University of Texas MD Anderson Cancer Center.

This represents the first neoadjuvant trial of combination immunotherapy for bladder cancer patients ineligible to receive cisplatin-based chemotherapy, all of whom had tumors with high-risk features that are associated with unfavorable outcomes. The study results, published today in Nature Medicine, also shed important insight into biomarkers associated with treatment responses.

Of the 28 patients enrolled in the trial, 24 completed bladder removal surgery on the study with nine (37.5%) achieving a pathologic complete response (pCR), meaning there were no signs of cancer evident at the time of surgery. Additionally, in 12 patients with particularly large tumors (stage T3-T4), the pCR rate was 42%, and half saw their tumor size reduced to stage T1 or less.

"This study provides early evidence that neoadjuvant treatment with combination checkpoint inhibitors is feasible in a group of patients who are in need of additional treatment options," said lead author Jianjun Gao, M.D., Ph.D., associate professor of Genitourinary Medical Oncology. "In this small group of patients, the combination treatment had an acceptable safety profile with encouraging activity that supports further clinical studies in this setting."

Advancing new immunotherapy options for patients in need

For patients with localized bladder cancer, standard therapy includes cisplatin-based chemotherapy followed by surgery. However, up to half of patients are ineligible for cisplatin treatment because of conditions such as poor kidney function, heart failure or neuropathies, leaving them without standard therapy options, explained Gao.

Previous clinical trials have evaluated neoadjuvant immune checkpoint blockade in bladder cancer, but these studies included only single agents and did not focus on those with high-risk tumors.

High-risk tumors are marked by certain features, including large size, variant histology, lymphovascular invasion, hydronephrosis, and/or disease located in the upper tract of the urothelium. Patients with these tumors tend to have poor survival compared to the average patient with localized disease.

"Immune checkpoint therapy has clearly revolutionized cancer care with patients with metastatic disease in multiple tumor types, but we continue to work toward moving these therapies into earlier disease settings for patients in need," said corresponding author Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology. "By combining these therapies, we felt we could take advantage of the distinct biologic mechanisms and stimulate a more robust anti-tumor immune response for these patients."

The current trial builds on longstanding efforts by Sharma at MD Anderson to advance checkpoint inhibitors for treating patients with localized disease. In 2008, Sharma and colleagues published results from the first-ever trial of neoadjuvant checkpoint blockade (ipilimumab) in patients with localized bladder cancer in the Proceedings of the National Academy of Sciences.

Evaluating dual checkpoint blockade and biomarkers of response

The trial enrolled 28 cisplatin-ineligible patients with high-risk localized bladder cancer at MD Anderson. Each patient received two doses of durvalumab and tremelimumab in combination and 24 patients completed surgery following treatment. Trial participants were 82% Caucasian and 18% Black or other races. Median age was 71 with men accounting for 71% and women 29% of participants.

Most patients experienced immune-related side effects, the most common of which were grade 1-2 rash (29%) and asymptomatic increases in amylase (29%). Six patients (21%) experienced grade 3 or higher immune-related adverse events, including asymptomatic laboratory values, hepatitis and colitis. No treatment-related deaths occurred.

Median overall survival has not been reached, and 24 patients were still alive at one year. In addition, 82.8% of patients that had surgery were free of disease recurrence at one year.

The researchers also collected pre- and post-treatment blood and tissue samples from patients to study biomarkers associated with response in collaboration with MD Anderson's immunotherapy platform, which is co-led by Sharma. The platform is part of MD Anderson's Moon Shots Program®, a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patient's lives.

The researchers identified a higher density of specialized immune-cell clusters called tertiary lymphoid structures (TLS) in pre-treatment tumor samples from patients who responded well to combination therapy relative to those who did not respond. A higher density of TLS correlated with longer overall survival and relapse-free survival.

While these findings need to be confirmed in larger studies, the data suggests that TLS may serve as a useful predictive biomarker for those who will respond to checkpoint blockade, explained Sharma. These findings are in agreement with previously published MD Anderson research reporting that an enrichment of B cells within TLS were predictive of response to checkpoint inhibitors in patients with melanomas, soft-tissue sarcomas and renal cell carcinomas.

This research was supported by a collaboration between MD Anderson's immunotherapy platform and AstraZeneca/MedImmune, the MD Anderson Physician-Scientist Award, the Khalifa Fellows Award, which was established by the Khalifa Bin Zayed Al Nahyan Foundation, the Andrew Sabin Family Foundation Fellows Award, and Wendy and Leslie Irvin Barnhart. Sharma and co-author James P. Allison, Ph.D., are members of the Parker Institute for Cancer Immunotherapy (PICI) and co-directors of PICI at MD Anderson.

In addition to Gao and Sharma, additional collaborators on this study include: Neema Navai, M.D., Ashish Kamat, M.D., Surena Matin, M.D., John Papadopoulos, M.D., and Colin Dinney, M.D., all of Urology; Omar Alhalabi, M.D., Arlene Siefker-Radtke, M.D., Matthew Campbell, M.D., John Araujo, M.D., Ph.D., Amishi Shah, M.D., Pavlos Msaouel, M.D., Ph.D., Paul Corn, M.D., Ph.D., Jianbo Wang, M.D., Ph.D., Jianfeng Chen, Ph.D., and Sangeeta Goswami, M.D., Ph.D., all of Genitourinary Medical Oncology; Rebecca Slack Tidwell and Yu Shen, Ph.D., both of Biostatistics; Charles Guo, M.D., of Pathology; Jorge Blando, D.V.M, Fei Duan, Ph.D., Sreyashi Basu, Ph.D., Shalini Singh Yadav, Ph.D., Wenbin Liu, Yuwei Zhang, Ph.D., Marc Daniel Macaluso, Ph.D., Ying Wang, Ph.D., all of the immunotherapy platform; Jianhua Zhang, Ph.D., and Andrew Futreal, Ph.D., both of Genomic Medicine; and James P. Allison, Ph.D., of Immunology and the immunotherapy platform. A full list of authors' disclosures can be found with the paper here.

Traditionally, geneticists divide disorders into "simple," where a single gene mutation causes disease, or complex, where mutations in many genes contribute modest amounts. A new study suggests that the truth is somewhere in between.

For many years, scientists studying patient genomes have gained glimpses of genetic "burden" or additional genetic variation that contributes to the effect of disease-causing mutations and makes them more (or less) potent. In principle, this phenomenon can help explain why some people are severely affected by disease and some are not. However, the notion of genetic burden has been controversial, in large part because it has been harrowingly difficult to detect and understand its properties.

Now, scientists from the Stanley Manne Children's Research Institute at Ann & Robert H. Lurie Children's Hospital of Chicago have used a conglomerate of genetic and functional approaches to demonstrate the existence of burden in diseases thought to be caused by a single gene.

Published in Nature Genetics, their study focused on several hundred patients with Bardet-Biedl syndrome (BBS), a rare disorder affecting cognitive function, vision, renal function and body weight regulation. Critically, all of these patients had already been diagnosed genetically with BBS, in that they carried mutations in one of the 25 genes known for this disorder. In simple terms, their genetic diagnosis was finished, and they were considered "solved." However, when the authors analyzed these patients for all known BBS genes, they found that they carried three times as many additional mutations in a pattern more reminiscent of the genetic architecture of complex traits, such as Alzheimer disease or type II diabetes. Moreover, the distribution pattern of these mutations was not random, but clustered around specific subsets of genes that encode two different protein complexes. These observations intimate that the effect of these additional genetic mutations was driven not only by their number, but also their position in a "disease network."

The study also has implications about the types of genetics data can be returned to patients in the clinical setting.

"It is imperative that we broaden our search for answers beyond the single causal gene," says senior author Nico Katsanis, PhD, Director of the Advanced Center for Translational and Genetic Medicine at the Manne Research Institute at Lurie Children's. Dr. Katsanis also is Professor of Pediatrics and Cell and Molecular Biology at Northwestern University Feinberg School of Medicine. "We have always known that disease causality was not binary, but a continuum, but we lacked the proof and the tools to detect it. To me, this is not too different from the development of tools that increased the magnification of telescopes. Now we can see deeper, better, and start making predictions about diseases: why they happen, why the progress the way they do. The work also gives us multiple potential entry points for therapies: some disease-causing genes are difficult to target--but their neighbors might be amenable."

Looking forward, the research team is currently applying these concepts to a host of other related disorders, paying close attention to network mutations that both exacerbate disease severity but also attenuate. "It has taken us 20 years to get here," says Dr. Katsanis. "Now, I feel we have a new depth of resolution to understand the problem better."

SINGAPORE / MELBOURNE -- Cellular therapy is a powerful strategy to produce patient-specific, personalised cells to treat many diseases, including heart disease and neurological disorders. But a major challenge for cell therapy applications is keeping cells alive and well in the lab.

That may soon change as researchers at Duke-NUS Medical School, Singapore, and Monash University, Australia have devised an algorithm that can predict what molecules are needed to keep cells healthy in laboratory cultures. They developed a computational approach called EpiMogrify, that can predict the molecules needed to signal stem cells to change into specific tissue cells, which can help accelerate treatments that require growing patient cells in the lab.

"Computational biology is rapidly becoming a key enabler in cell therapy, providing a way to short-circuit otherwise expensive and time-consuming discovery approaches with cleverly designed algorithms," said Assistant Professor Owen Rackham, a computational biologist at Duke-NUS, and a senior and corresponding author of the study, published today in the journal Cell Systems.

In the laboratory, cells are often grown and maintained in cell cultures, formed of a substance, called a medium, which contains nutrients and other molecules. It has been an ongoing challenge to identify the necessary molecules to maintain high-quality cells in culture, as well as finding molecules that can induce stem cells to convert to other cell types.

The research team developed a computer model called EpiMogrify that successfully identified molecules to add to cell culture media to maintain healthy nerve cells, called astrocytes, and heart cells, called cardiomyocytes. They also used their model to successfully predict molecules that trigger stem cells to turn into astrocytes and cardiomyocytes.

"Research at Duke-NUS is paving the road for cell therapies and regenerative medicine to enter the clinic in Singapore and worldwide; this study leverages our expertise in computational and systems biology to facilitate the good manufacturing practice (GMP) production of high-quality cells for these much needed therapeutic applications," said Associate Professor Enrico Petretto, who leads the Systems Genetics group at Duke-NUS, and is a senior and corresponding author of the study.

The researchers added existing information into their model about genes tagged with epigenetic markers whose presence indicates that a gene is important for cell identity. The model then determines which of these genes actually code for proteins necessary for a cell's identity. Additionally, the model incorporates data about proteins that bind to cell receptors to influence their activities. Together, this information is used by the computer model to predict specific proteins that will influence different cells' identities.

"This approach facilitates the identification of the optimum cell culture conditions for converting cells and also for growing the high-quality cells required for cell therapy applications," said ARC Future Fellow Professor Jose Polo, from Monash University's Biomedicine Discovery Institute and the Australian Research Medicine Institute, who is also a senior and corresponding author of the study.

The team compared cultures using protein molecules predicted by EpiMogrify to a type of commonly used cell culture that uses a large amount of unknown or undefined complex molecules and chemicals. They found the EpiMogrify-predicted cultures worked as well or even surpassed their effectiveness.

The researchers have filed for a patent on their computational approach and the cell culture factors it predicted for maintaining and controlling cell fate. EpiMogrify's predicted molecules are available for other researchers to explore on a public database: http://epimogrify.ddnetbio.com.

"We aim to continue to develop tools and technologies that can enable cell therapies and bring them to the clinic as efficiently and safely as possible," said Asst Prof Rackham.

"The developed technology can identify cell culture conditions required to manipulate cell fate and this facilitates growing important cells in chemically-defined cultures for cell therapy applications," added Dr Uma S. Kamaraj, lead author of the study and a graduate of Duke-NUS' Integrated Biology and Medicine PhD Programme.

Cancer and its treatment can impact an individual's ability to work, and employment disruptions can lead to financial hardships. A new study indicates that women who were diagnosed with cancer as adolescents or young adults can be especially vulnerable to these effects. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society (ACS).

For the study, Clare Meernik, MPH, of the University of North Carolina at Chapel Hill, and her colleagues surveyed 1,328 young women in North Carolina and California who were diagnosed with cancer between the ages of 15 to 39 years and were employed at the time of their cancer diagnosis. Surveys were conducted a median of seven years after diagnosis, and questions in the survey assessed the impact of one's cancer diagnosis and treatment in relation to a broad range of survivorship topics.

Survey results revealed that 32 percent of the women experienced employment disruption, meaning that they stopped working or worked fewer hours following their cancer diagnosis. Twenty-seven percent of women in the study reported that they had to borrow money, go into debt, or file for bankruptcy because of their cancer treatment; and women with disrupted employment had a 17-percentage point higher prevalence of reporting this than women without disrupted employment.

Also, 50 percent of women in the study reported psychological distress about having to pay large medical bills related to their cancer treatment, and women with disrupted employment had an 8-percentage point higher prevalence of reporting this than women without disrupted employment.

"Our study addresses the burden of employment disruption and financial hardship among young women with cancer--a group who may be at particular risk for poor financial outcomes after cancer given their age and gender," said Meernik. "Our findings highlight the need for effective interventions to promote job maintenance and transition back to the workforce after cancer treatment, as well as increased workplace accommodations and benefits, to improve cancer outcomes for young women."