Body

STONY BROOK, NY, December 18, 2020 - A new study that records patient volume at Stony Brook Medicine's Bariatric and Metabolic Weight Loss Center reveals that follow-up telehealth visits are highly effective during the COVID-19 pandemic. The study, published in the December issue of the Annals of Surgery, serves as an example that surgical practices can continue to thrive with the help of telemedicine during the pandemic.

"Embracing telemedicine has been extremely effective for our practice and certainly can be for other practices during this pandemic," says Aurora D. Pryor, MD, lead author on the paper, Director of the Bariatric and Metabolic Weight Loss Center, and Professor of Surgery at the Renaissance School of Medicine at Stony Brook University. "Our patients and multiple healthcare providers involved in metabolic health and bariatric surgery services find telemedicine to be effective, because in-person care is not necessary for certain aspects of patient care and follow-up, and telemedicine saves time and reduces exposure risks for patients and providers alike."

The study, titled "The Impact of Telemedicine Adoption on a Multidisciplinary Bariatric Surgery Practice During the COVID-19 Pandemic," recorded patient volume categorized as pre-telehealth and post-telehealth - periods of a similar time range from February to April 2020. Post-telehealth is when the practice incorporated telehealth services according to pandemic guidelines.

A total of 506 patient visits were recorded in the pre-telehealth period, with 162 new patient visits and 344 follow-ups. A total of 413 patients were recorded in the post-telehealth period, with 77 new patient visits and 336 follow-ups.

After telehealth implementation, new visits for surgeons did decrease by 75 percent over the period, and follow-ups surgical visits decreased by 55 percent. However, during telehealth there was a 27 percent increase for other non-surgical practitioners involved in the Bariatric and Metabolic Weight Loss Center practice, an indication that patients have been able to continue their care to a high degree post-surgery or before elective surgery.

Dr. Pryor says this increase in patient follow-up visits for certain services because of telemedicine practices may prove to help bariatric surgery practices, and potentially other surgical practices, in their overall care of patients during the pandemic - especially since elective surgical practices have been profoundly impacted by the pandemic.

She and her coauthors conclude that although new patient visit volume decreased across the board, the increase in follow-up visits for some healthcare services provides a template for adoption of a multidisciplinary telehealth clinic in a post-pandemic world.

Why do some ferroelectric materials display bubble-shaped patterning, while others display complex, labyrinthine patterns?

A FLEET study finds the answer to the changing patterns in ferroelectric films lies in non-equilibrium dynamics, with topological defects driving subsequent evolution.

Ferroelectric materials can be considered an electrical analogy to ferromagnetic materials, with their permanent electric polarisation resembling the north and south poles of a magnet.

Understanding the physics behind their domain-pattern changes is crucial for designing advanced low-energy ferroelectric electronics, or brain-inspired neuromorphic computing.

Labyrinthine vs bubbles: what patterns reveal

The characteristic domain patterns of thin-film ferroelectric materials are strongly influenced by the type of materials, and by the film configuration (substrate, electrode, thickness, structure, etc).

“We wanted to understand what drives the emergence of one pattern rather than another,” explains Dr Qi (Peggy) Zhang (UNSW), who led experiments at UNSW.

“For example: what drives formation of mosaic-shaped domain patterning, instead of labyrinth-shaped patterning. And why would drive a subsequent change to bubble-shaped patterning.”

The research team were seeking a common framework or roadmap driving such domain arrangements.

“Is there a topological signature in these states? Is their topology evolutive? And if yes, how so? These are the types of answers we were seeking,” says lead author Dr Yousra Nahas (University of Arkansas).

“We found that self-patterning of ferroelectric polar domains can be understood by examining the non-equilibrium dynamics, and that a common framework is that of phase separation kinetics.

“We also performed topological characterization, and studied pattern evolution under an external, applied electric field, which revealed the crucial role of topological defects in mediating the pattern transformation.”

“The results of this study build a roadmap (a phase diagram of polar domain patterns) for researchers to use when wanting to ‘navigate’ through the plurality of modulated phases in low-dimensional ferroelectrics, says co-lead author Dr Sergei Prokhorenko (University of Arkansas).

This study is thus interesting in its own field (condensed matter physics, ferroelectrics) but might also be relevant for an interdisciplinary audience in regards to the universality of concepts and results.

The study

Researchers investigated domain features and domain evolutions of thin-film Pb(Zr0.4Ti0.6)O3 (or ‘PZT’) through extensive modelling and experimental study (piezoresponse force microscope).

What The Study Did: Researchers assessed the acceptability of COVID-19 vaccine mandates in the U.S. public.

Authors: Emily A. Largent, J.D., Ph.D., R.N., of the University of Pennsylvania Perelman School of Medicine in Philadelphia, 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.2020.33324)

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.

What The Study Did: Researchers used nationally representative survey data to estimate the proportion of women of reproductive age in the United States who have ever attempted to end an unwanted pregnancy on their own without medical assistance.

Authors: Lauren Ralph, Ph.D., of the University of California San Francisco, 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.2020.29245)

Editor's Note: The article includes 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.

A pioneering new eye test, developed by scientists at UCL in collaboration with the Western Eye Hospital, London, may predict wet AMD, a leading cause of severe sight loss, three years before symptoms develop.

Researchers hope their test could be used to identify the disease early enough so that treatment can effectively prevent any vision loss.

The findings of the study, funded by Wellcome, are published today in Expert Review of Molecular Diagnostics.

Wet age-related macular degeneration (AMD), also known as macular disease, is the most common cause of permanent and severe sight loss in the UK.

Currently the diagnosis of wet AMD relies on a person developing symptoms, which then leads them to seek advice from a clinician. Initially, someone with wet AMD would notice distortion in their vision, normally interfering with their reading. Very quickly, this can progress to complete central vision loss, which may be extremely troubling to elderly patients who will fear blindness and loss of independence.

Wet AMD involves abnormal growth of blood vessels, which leak fluid into the retina. The introduction of new treatments has led to much improved results for patients, for a disease that over 20 years ago was regarded as untreatable. However, patient outcomes could be even better if treatment was started in the very earliest stages of the disease.

The test, called DARC (Detection of Apoptosing Retinal Cells), involves injecting into the bloodstream (via the arm) a fluorescent dye that attaches to retinal cells, and illuminates those that are undergoing stress or in the process of apoptosis, a form of programmed cell death. The damaged cells appear bright white when viewed in eye examinations - the more damaged cells detected, the higher the DARC count.

One challenge with evaluating eye diseases is that specialists often disagree when viewing the same scans, so the researchers have incorporated an AI algorithm into their method.

Using the same technology (test) the researchers had previously found that they can detect the earliest signs of glaucoma progression. This new study, which forms part of the same ongoing clinical trial of DARC, assessed 19 of the study participants who had already shown signs of AMD, but not necessarily in both eyes. The AI was newly trained to detect the formation of leaking and new blood vessels, which corresponded with the spots that DARC picked up.

The new analysis found that DARC can uniquely highlight endothelial cells (which line our blood vessels) under stress in the retina. These stressed cells then predict future wet AMD activity with the formation of leaking and new blood vessels seen in patients three years later, using conventional eye scans with Optical Coherence Tomography (OCT).

The researchers say their test could be valuable in detecting new lesions in someone affected by AMD, often in the opposite, unaffected eye, and may eventually be useful for screening people over a certain age or with known risk factors.

Lead researcher Professor Francesca Cordeiro (UCL Institute of Ophthalmology, Imperial College London, and Western Eye Hospital Imperial College Healthcare NHS Trust) said: "Our results are very promising as they show DARC could be used as a biomarker for wet AMD when combined with the AI-aided algorithm.

"Our new test was able to predict new wet AMD lesions up to 36 months in advance of them occurring and that is huge - it means that DARC activity can guide a clinician into treating more intensively those patients who are at high risk of new lesions of wet AMD and also be used as a screening tool."

The study team hope to continue their research with a clinical trial with more participants, and hope to investigate the test in other eye diseases as well.

Chief Executive of eye research charity Fight for Sight, Sherine Krause said: "Our Time to Focus report on the social and economic impact of sight loss stressed the importance of early detection for prevention of sight loss, and so this is a very encouraging development in tackling the leading cause of blindness."

A key protein in the communication channels between cells can allow a stress response in one liver cell to spread to neighboring liver cells in mice, causing otherwise healthy cells to become dysfunctional, according to new research co-led by Harvard T.H. Chan School of Public Health and Sheba Medical Center in Israel. The findings could have implications for a range of metabolic diseases, including obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD).

The study is the first to demonstrate that the protein, Cx43, plays a role in the spread of endoplasmic reticulum (ER) stress signals among liver cells. Remarkably, the researchers noted, mice lacking Cx43 in their livers were protected from insulin resistance, glucose intolerance, and NAFLD.

The findings were published in Cell Metabolism on December 18, 2020.

"We found that when a stressed liver cell starts communicating with its neighbors, it can send stress signals to neighboring cells, causing significant problems that can lead to fatty liver disease and metabolic disease," said corresponding author Gökhan Hotam??l?gil, James Stevens Simmons Professor of Genetics and Metabolism at Harvard Chan School and director of the Sabri Ülker Center for Metabolic Research. "Here, we developed complex methods to follow molecular stress signals as they pass from one cell to another and, importantly, we showed that when these signals are stopped in the originating cell, metabolic health can be preserved even under adverse conditions such as obesity."

Previous research in the Sabri Ülker Center has shown that in obese animals and humans, liver tissue experiences stress and dysfunction of the ER. It has, however, been challenging to understand why this powerful tissue failed to launch countermeasures to mitigate this problem. The researchers found in this study that once a small group of cells in the liver experience stress, it quickly spreads to the rest of the tissue, from cell to cell, overwhelming the tissue's natural defenses.

For this new study, the researchers first screened billions of cells to find a few that naturally exhibit ER stress and others that have no sign of stress whatsoever. When they were grown next to each other, the stressed cells passed stress signals on to the healthy cells. The team then focused on liver cells isolated from mice. They experimentally induced ER stress in these cells and observed that levels and activity of Cx43 increased. As Cx43 activity increased, these cells became more capable of transmitting stress signals to nearby cells when compared with cells that were not under ER stress.

To build on these initial findings, the research team conducted a series of experiments on mice and determined that diet-induced obesity resulted in ER stress that in turn increased levels and activity of Cx43. The team then created a line of mice in which Cx43 had been deleted from the animals' liver cells. In these mice, a high-fat diet did not trigger ER stress in liver cells, and the animals were protected from insulin resistance, glucose intolerance, and NAFLD.

"Rates of obesity are rising globally, and we do not fully understand the complications associated with it, including metabolic disease and non-alcoholic fatty liver disease," said Amir Tirosh, corresponding author and director of the Division of Endocrinology, Diabetes and Metabolism at Sheba Medical Center. "This study shows that cell-to-cell communication plays an important role in spreading stress signals, and it indicates that stopping the transmissions of these stress signals could be an attractive approach to preventing and treating insulin resistance and NAFLD."

ANN ARBOR, Michigan -- While many people have listened to messaging about wearing a mask and following social distancing guidelines to limit the spread of COVID-19, resistance remains. A new study finds that appealing to people's concerns for their loved ones could overcome this resistance. And it may have implications for encouraging people to get the new vaccine.

In a recent survey, people who said social distancing and COVID-safety guidelines violated their personal freedoms responded more positively to these ideas when they felt a loved one might be at risk of severe illness for COVID-19.

"Emphasizing the benefits of being a protector for others (instead of yourself) looks to be more effective in promoting greater adherence to recommended practices," says study author Lawrence An, M.D., associate professor of general medicine at Michigan Medicine and co-director of the University of Michigan Rogel Cancer Center's Center for Health Communications Research.

As the coronavirus pandemic continues to ravage the United States, messaging focused on shaming or pressuring people to wear a mask or avoid crowds are backfiring.

"People who respond negatively to being 'told' what to do are much less likely - by more than 50% - to routinely wear a mask. However, at the same time, concern for others increases mask wearing, especially among those who report greater negativity," An says.

An and colleagues surveyed 1,074 people across the United States about their attitudes toward the coronavirus. They discovered two distinct sets of attitudes toward social distancing:

Positive beliefs that largely mirror public health messaging

Negative beliefs, including the idea that social distancing violates individual rights and freedoms

Concern about a loved one's risk of severe COVID-19 infection was tied to both higher positive attitudes and lower negative attitudes toward social distancing. When people considered their own personal risk, they had higher positive attitudes but it did not impact their negative attitudes.

"When people think about what protective behaviors to follow, negative beliefs - the perception of external control - override positive beliefs. This means that simply repeating that people should follow public health guidelines is unlikely to be effective," says study author Kenneth Resnicow, Ph.D., professor of health behavior and health education at the U-M School of Public Health and associate director of community outreach and engagement at the Rogel Cancer Center.

"However, our data show that when people consider being a protector for others, they approach risk differently. They are less likely to let their personal beliefs and politics discourage them from practicing COVID protection. Emphasizing the act of protecting others may help people who would otherwise be reluctant to practice COVID protection to feel independent and strong, rather than compliant or obedient," he says.

Recognizing that these distinct positive and negative attitudes about social distancing could help shape social distance policies and inform efforts to encourage people to follow them, An and Resnicow teamed up with CULTIQUE, an LA-based firm that advises the entertainment industry on cultural issues, to encourage messaging about protecting loved ones from the coronavirus in content, social media and news.

According to the latest data from the CDC, 40% of the population is considered at increased risk of severe illness from COVID-19. People with chronic health issues are 12 times more likely to die from COVID-19.

"For those who are caring for someone with cancer or other conditions, protecting your loved one is critical," An says.

Protectors can take responsibility for monitoring the at-risk person's COVID exposure and protecting them from the disease by limiting the person's exposure to others. This includes doing the shopping, maintaining cleaning protocols and PPE, and providing safe transportation to appointments.

"The prospect of losing someone is even more terrible knowing that we could be in the homestretch of this pandemic. With vaccines on the horizon, it's more important than ever to follow social distancing measures to help end COVID-19 sooner," Resnicow says.

Breast cancer, the second most common cancer in the United States, can result from a number of cellular misregulations, such as deficiencies in the DNA-repairing breast cancer gene, BRCA. Typically, BRCA-associated breast cancer is treated with poly ADP ribose polymerase (PARP) inhibitors and, recently, clinical trials have investigated pairing PARP inhibitor therapy with immunotherapy. Based on preclinical data, it is expected that the combination will recruit and activate T cells -- immune cells that can kill tumor cells. Despite interest in this combination, researchers are already looking ahead for ways to get even more benefit from PARP inhibitors plus checkpoint inhibitors in breast cancer patients. That is precisely what a team of Dana-Farber/Brigham and Women's Cancer Center researchers have devoted their time to: identifying ways to boost the response to PARP inhibitors. The team found macrophage-mediated immune suppression to be the weak spot of PARP inhibition treatment. Findings are published in Nature Cancer.

"The question that drove our research was: How can we overcome PARP inhibitor resistance to turn this treatment into a homerun?" said Jennifer Guerriero, PhD, senior author and member of the Brigham's Division of Breast Surgery and director of the Dana-Farber Breast Tumor Immunology Laboratory. "Our findings suggest that there's something in the tumor microenvironment limiting the ability for T cells to be activated, and that something else is likely macrophages, which we found become highly suppressive after PARP inhibitor therapy."

Initial results of the combination of a PARP inhibitor and a checkpoint inhibitor in small numbers of patients with metastatic breast cancer have shown this combination to be active. A national pre-surgical trial led by DFCI investigators has recently opened and will examine this targeted combination in patients with genetic mutations sensitive to PARP inhibitors.

Similar to BRCA proteins, PARP proteins act to repair damaged DNA; in tumors, inhibiting DNA repairs means cancer cell death, so the combined elimination of BRCA and PARP repair mechanisms induce cancer cell death. PARP inhibitors recruit T cells, which are required for the body to recognize the presence of cancerous cells.

Like T cells, macrophages are another type of immune cell, which is recruited to wounds to patch them up. With cancer, macrophages are recruited to tumor sites, which are viewed as wounds to macrophages, and repair, strengthen, and, consequentially, exacerbate the tumor state. The team found an abundance of macrophages expressing a receptor necessary for their survival, CSF-1R, to be present in cancerous tissue after PARP inhibition treatment. Therefore, they hypothesized that targeting CSF-1R-positive macrophages (a particularly suppressive macrophage type) in combination with PARP inhibition would lead to an enhanced anti-tumor response.

Since CSF-1R-positive macrophages exacerbate the tumor state, disabling these macrophages seemed an important therapeutic target for investigators. Using a triple-negative breast cancer BRCA-deficient mouse model, the team characterized these suppressive macrophages by assessing T cell and macrophage responses to different therapies and combinations of therapies.

When PARP and CSF-1R inhibition therapies were combined, there were dramatic anti-tumor responses seen with significant increase in overall survival. Furthermore, the triple combination of PARP inhibitor, CSF-1R inhibitor, and SREBP1 (a key regulator of lipid metabolism) inhibition was able to completely eliminate tumors in the aggressive triple-negative breast cancer mouse model. Researchers inferred from this therapeutic success that the PARP inhibitor directly activates macrophages to be suppressive in the tumor microenvironment.

While breast cancer tissue is often characterized before treatment, biopsies of tissue after treatment begins could provide more nuance to the characterization of these actors. Importantly, elucidating the mechanisms for PARP and macrophages will be critical in developing effective therapies and moving forward with clinical translation.

"At Dana-Farber/Brigham and Women's Cancer Center we have the opportunity to work closely with our clinical colleagues and ask these really important questions that will be critical to identify better biomarkers, so we can identify which patients will respond to which therapies," said Guerriero. "I am very optimistic about the use of PARP inhibitors -- they are a game changer for patients with BRCA-deficient cancers, and their application is not just limited to breast cancers."

BOSTON -- The growth of prenatal screening in Europe has reduced the number of babies being born per year with Down syndrome (DS) by an average of 54%, according to a new study published in the European Journal of Human Genetics by researchers from Massachusetts General Hospital (MGH) and international Down syndrome organizations. In research published in 2016, the same team found that 33% fewer babies with DS per year were born in the United States as a result of pregnancy terminations.

The researchers spent three years collecting data from multiple registries and databases in every country in Europe to estimate the number of babies being born with DS and the overall number of people with DS in the population. "People with DS were being counted sporadically, inconsistently, or not at all, depending on the country," says Brian G. Skotko, MD, MPP, a medical geneticist at MGH and senior author. "But without an accurate estimate, it's impossible for policymakers and advocacy organizations to determine how many resources and support services are needed for its Down syndrome population." The researchers applied statistical modeling to create estimates in countries where there were gaps in data. "These data are as close to accurate as possible," says Skotko. The data are laid out in both the study and an associated fact sheet.

Equally important, however, was for the study to establish a baseline of DS birth rates and pregnancy termination rates ahead of widespread adoption of new noninvasive prenatal screenings (NIPS). The new screening tests can detect the likelihood of a chromosomal condition in a fetus as early as nine weeks of gestation, after which an expectant couple can elect to pursue definitive genetic testing. As NIPS becomes widely available, fewer babies with DS are expected to be born.

NIPS was introduced in the U.S. in 2011 but has yet to be widely covered by national health care systems in European countries. "Countries that are grappling with funding decisions for NIPS should certainly be having deep discussions about its impact on the country's Down syndrome population," says Skotko, who has a 40-year-old sister with DS. Countries also must create an adequate infrastructure of support and information so that expectant couples can make informed decisions about NIPS and subsequent pregnancies.

The researchers discovered a wide variation in DS birth rates among European regions. From 2011 to 2015, Southern Europe had the highest reduction in DS births due to pregnancy terminations (71%), followed by Northern Europe (51%) and Eastern Europe (38%). There were, however, considerable differences among countries, ranging from no reduction in the percentage of babies being born with DS in Malta, where pregnancy termination is highly restricted, to an 83% reduction in Spain.

Pregnancy terminations related to DS are influenced by multiple factors. Some nations, such as Denmark, provide free access to prenatal screening, whereas there may be cost barriers for couples in other countries. A country's religious and cultural mores also play a role, as does a country's policies about the way expectant couples are counseled about prenatal screening and DS. Parents' decisions might also be influenced by the opportunities that exist for people with DS to live fulfilling, productive lives within a country. "In the U.S., people with Down syndrome have great opportunities to get an education, to fall in love, and to find satisfying jobs," says Skotko.

The modeling study also estimated the number of people with DS currently living in each country. The decreasing number of DS births is offset by people with DS living longer than ever--to an average age of around 60 in countries with resource-rich health care systems. In Europe there were 27% fewer people living with DS in the overall population in 2015 (and 21% fewer people with DS in the U.S)as a consequence of elective pregnancy termination from previous years.

Skotko and his international colleagues hope that the European and U.S. studies will pave the way for governments and DS organizations to work together and share best practices on thoughtful approaches to implementing NIPS and to supporting couples who receive a prenatal DS diagnosis. "Massachusetts, for example, has an outstanding network of parents who are willing to talk about their lived experiences of raising children with Down syndrome to expectant couples," says Skotko. "That nonprofit has trained parent groups in Brazil, Japan and elsewhere so they don't have to reinvent the wheel."

The researchers are planning a similar modeling study in Australia and New Zealand, and they will continue to update each country's data to measure the impact of different prenatal testing policies and of NIPS as it becomes more widely available. This research is unfunded; Skotko and his colleagues have volunteered their time to do these analyses. "We just feel it is so important to provide countries with accurate numbers of their citizens with Down syndrome," says Skotko.

One consequence of the COVID-19 pandemic is that more families are putting off their children's preventive care visits, causing pediatric providers to worry about missed vaccines.

In a recent study published in Pediatrics, researchers at Nationwide Children's Hospital evaluated changes in measles vaccination rates from before the pandemic to this summer, when return for clinical care was encouraged. Finding a steep and lasting decline, the researchers are making efforts to improve timely vaccination and provide safe catch-up opportunities to children in their pediatric primary care network.

"We have seen a resurgence of measles outbreaks in the U.S. and here in Ohio in recent years because fewer people have chosen to immunize," said the study's lead author Sara Bode, MD, a primary care pediatrician and medical director of Nationwide Children's Care Connection School-Based Health and Mobile Clinics. "We were concerned that with the pandemic, vaccination rates could fall further and there could be a real risk of a measles outbreak that could affect everyone in the community."

Nationwide Children's pediatric primary care network includes 12 clinic sites in Columbus, Ohio, providing care to about 100,000 patients. Dr. Bode and her colleagues examined the proportion of these children with measles/mumps/rubella (MMR) vaccination by age 16 months from March 2017 through August 2020.

They found about a 10 percent drop in the number of children who had received their first MMR vaccine. The decline began in March 2020, when the state had its first stay-at-home order. Concerningly, this pandemic-related decline in vaccination persisted through August 2020, even as clinics reopened for wellness visits.

Alex Kemper, MD, MPH, MS, division chief of primary care pediatrics at Nationwide Children's and a co-author on the study, said that a key message he and his colleagues want to get across is it is safe to come back to the clinic for preventive care.

"We are doing a lot of work to let our patients and families in the community know it is safe to come in for wellness visits," said Dr. Kemper. "We have prioritized these visits and opened up additional appointment slots throughout the day and evening."

Nationwide Children's is also working with community wellness and school health partners to offer alternative places for children to receive catch-up vaccinations, including mobile and pop-up clinics.
However, Dr. Kemper cautions that separating vaccination from the full range of preventive services is not ideal.

"We recognize that wellness visits provide important opportunities to assess growth and development, and talk to families about issues like mental health, nutrition and exercise in these challenging times," said Dr. Kemper, also a professor of pediatrics at The Ohio State University College of Medicine.

Dr. Bode agrees that reaching out to the community and assuring families that preventive visits are safe will be an important component of getting patients back to the clinics.

"Even though we are in a pandemic, child well care visits are safe and important--in fact it is unsafe miss these needed services for your child," said Dr. Bode.

LOS ANGELES -- In recent decades, the age of men who father children has increased. However some older would-be dads face a stumbling block because they have undergone vasectomies. In addition, research has shown that male fertility decreases with age.

In good news for older men, a new study from Keck Medicine of USC published in Urology shows that men over 50 who undergo a vasectomy reversal had the same rate of pregnancy with their partners as their younger counterparts. Contrary to what one might expect, the man's age was not a factor.

"These results are exciting for men looking to start families later in life who have had a vasectomy," said Mary Samplaski, MD, a male infertility specialist with Keck Medicine and the lead investigator of the study. "This research is especially timely because anecdotally, fertility doctors are seeing an increase in the number of men interested in vasectomy reversals as couples focus on family planning during the COVID-19 pandemic."

For couples wanting to pursue a pregnancy after a vasectomy, two main options exist: vasectomy reversal and sperm extraction with in vitro fertilization (IVF). "IVF can come with unique risks, such as psychological distress and multiple births, plus typically costs more than a reversal, making the reversal the best choice for some couples," said Samplaski.

Approximately 20% of American men who undergo a vasectomy will want to father children in the future, and some 6% will request a reversal, research shows. But up until now, little data has existed regarding the effect of paternal age on reversal outcomes.

In the study, Samplaski and colleagues analyzed the results of some 3,000 men over 50 and 350 men under 50 who underwent a vasectomy reversal at two separate locations, one of which was Keck Hospital of USC. The surgeries were performed by a single high-volume surgeon. The mean age for the over-50 group was 54, and for the under-50 group, 39.

Of the younger cohort, 33.4% of couples achieved pregnancy; in the older male population, 26.1%. However, the study also looked at several other factors, such as how many years ago the man received the vasectomy, the age of the female partner and if the man smoked. When the woman was under 35 and/or the man had the vasectomy less than 10 years ago, the odds of getting pregnant were higher. Smoking decreased the odds.

"When we did a statistical analysis, and examined all these other factors involved, the data showed that age had no bearing on success," said Samplaski. "Male age was not an independent factor."

For example, one reason older men were statistically less successful than younger ones in reaching pregnancy was because men with advanced age tend to have older female partners.

Looking forward, Samplaski hopes that men of a certain age will not be discouraged from having a vasectomy reversal. "The bottom line is, men over 50 can have successful outcomes in achieving pregnancy after a vasectomy reversal, and it should be considered a very viable option," she said.

Even the best-managed long-term care homes will need to step up to get through the second wave of the pandemic, suggests a new study by researchers at the UBC school of nursing.

The team, led by Professor Farinaz Havaei, evaluated the management practices of a large B.C. long-term care facility that successfully kept COVID-19 at bay at the start of the pandemic. It did not experience a single outbreak until much later in the year--when the B.C. health care system was much better prepared to fight the virus.

The study showed that a combination of good planning, strong leadership and a focus on safety above everything else contributed to this outcome.

"The facility leaders were monitoring COVID news as early as December," said Havaei, a researcher who studies workplace safety and patient care. "They created a crisis operations centre quickly so they had a plan in place when the magnitude of the crisis became clear."

Early preparation

In March, the care home started implementing many of the infection control practices that would be recommended by the BC Centre for Disease Control a few months later. These include keeping an up-to-date list of people entering the facility, enforcing staff members' hand hygiene, monitoring supplies of PPE and launching one-on-one support programs for residents.

The facility also paid full-time wages to all quarantined staff and provided them with laptops and access to fast internet so they could continue to work from home.

Like similar facilities, the care home had to restrict family visits during the pandemic but made sure that residents stayed socially connected through email and regular updates from the care home leaders.

To keep communication lines open, staff, residents and family members were also encouraged to e-mail their concerns directly to the chief executive officer and other executive leaders.

Staff stress

These practices, as well as adherence to measures mandated by the health authority, worked well to prevent outbreaks in the care home and inspire staff confidence. A UBC survey, conducted in September, saw the care staff expressing approval of the pandemic response by management.

However, the same survey also found growing levels of stress among the staff members, suggesting there is room for improvement. Thirty-eight per cent said they were dissatisfied with general staffing levels, and 48 per cent wanted more flexible sick time policies.

"The practices and policies put in place to prevent the spread of the virus also negatively affected staff workload," says Havaei. "With family visits restricted, they often had to provide the care and emotional connection that would otherwise come from the residents' families. Isolation measures were time-consuming. And despite the increased workload, staffing levels did not change--if anything they decreased as staff now couldn't work at multiple sites."

The pandemic merely exacerbated staffing issues that have long plagued Canada's long-term care sector, she said, noting that while adding staff is a goal, it's not the only answer.

"In the short term, we can look at better matching staff competencies to patient needs. We can build stronger teams through team building activities, and we can implement workplace policies and practices that better support the health and well-being of staff. Ultimately, these translate to better patient outcomes--and in the time of COVID, ensuring this is more essential than ever."

CHICAGO (December 17, 2020): The current surge in coronavirus disease 2019 (COVID-19) cases poses challenges for providers and institutions in delivering care to infected patients while also placing demands on them to keep up with timely and sometimes critical care for patients with cancer, heart disease and other serious illnesses who might experience advanced complications and/or earlier death if they have lapses in their care. Reporting on how deferred care worsened outcomes for lung cancer patients when the COVID-19 pandemic first surged in the spring of 2020, researchers from the University of Cincinnati explained that they have identified a framework that could help people with serious health conditions keep up their appointments during the current surge. The study has been selected for the 2020 Southern Surgical Association Program and published as an "article in press" on the Journal of the American College of Surgeons website in advance of print.

The researchers compared monthly visits for low-dose computed tomography (LDCT) screening for lung cancer during the three months in which COVID-19 restrictions were in place with the number of monthly visits from the three years before that. LDCT is an imaging modality known to reduce mortality from lung cancer by at least 20 percent in high-risk patients. The institution suspended LDCT on March 13 and began a phased reopening on May 5 with a full opening on June 1.

"We had 800 scans cancelled during that time and even during the resumed period, we had a decreased total volume of patients scanned and also noted a decreased number of new patients who were scanned for their lung cancer screening," said lead author Robert M. Van Haren, MD, MSPH, FACS, an assistant professor and thoracic surgeon at the University of Cincinnati College of Medicine and a member of Cincinnati Research in Outcomes and Safety in Surgery (CROSS) within the department of surgery.

The institution averaged 146 LDCT tests a month before COVID-19 compared with 39 in March to June this year (p0.01), with new patient monthly averages falling from 56 to 15 (p0.01).

"Also when we resumed our operations, we found that new patients were less likely to come back to our screening program," Dr. Van Haren added. They reported that new patient monthly LDCT rates have remained low despite resuming full operations.

"We also found that patients were more likely not to show up for their CT appointments, and this rate was again significantly increased compared with baseline," Dr. Van Haren said. The no-show rate went from 15 percent before the COVID-19 restrictions to 40 percent afterward (p0.04).

Further, when full operations resumed in June, 29 percent of patients were found to have lung nodules suspicious for malignancy compared with 8 percent in the pre-COVID-19 period (p0.01). That meant more patients were referred to a specialist for either biopsy or surgery as their suspected cancer entered a more critical phase.

These poor rates of screening probably reflect patient fears about coming into the hospital during the pandemic, although the study did not look at that concern specifically, Dr. Van Haren said.

"We've done two things to try to deal with that situation," Dr. Van Haren said. "One was that we made operational changes to ensure that screening is safe, and we made a big emphasis within our program and with our nurses and coordinators to educate patients about those changes and to really get the message out that screening is safe."

The key operational change was shifting the setting for the LDCT from the hospital to an outpatient center, but other changes included enforcing social distancing in the waiting rooms and in the scanning areas, and spacing appointments farther apart to allow for appropriate cleaning of those areas.

"Our results are important and suggest that it's critical to continue cancer screening operations, such as our lung cancer screening, during this pandemic," Dr. Van Haren said. "It's maybe more important now as we continue to undergo another surge of COVID-19 cases throughout the country."

He added, "We have to make sure as health care providers that we're taking care of patients who have COVID-19 and along with the rest of the population who don't have COVID-19, and that those two patient populations can safely co-exist and receive treatment."

In an invited commentary, William B. Weir, MD, and Andrew C. Chang, MD, FACS, of Michigan Surgery, Ann Arbor, wrote, "We must find a way to continue routine oncologic care or the true COVID-19 mortality rate will begin to include advanced stages of lung cancer."

Chemotherapy attacks all cells in our body and not just cancer cells, which is why patients undergoing the treatment often experience side effects such as physical weakness, hair loss and nausea. However, because cancer cells divide and spread faster than most normal cells, cancer cells are more sensitive to chemotherapy, which kills cells by inhibiting their ability to spread. Chemotherapy often targets and damages DNA so that cancer cells can no longer replicate their genome, which is the process of copying the genetic information, and stop the growth and die.

However, cancer cells may find ways to escape the chemotherapy. When attacked by chemotherapy, cells - including cancer cells - will try to repair or bypass the damage.

A group of researchers at the Faculty of Health and Medical Sciences, University of Copenhagen, are trying to figure out how cells repair or bypass the lesions induced by chemotherapy, in the hope to provide new methods to inhibit these repair processes and make the chemotherapy more efficient.

In a new collaborative work with different laboratories at the Center for Protein Research, Associate Professor Julien Duxin and his group have revealed a protein that seems to play a vital role in recruiting DNA key repair and signaling factors. If they are right, the discovery could be important for future chemotherapy treatment.

'We have found strong evidence that the protein RFWD3 is responsible for orchestrating the repair of different DNA lesions induced by chemotherapy. If we can inhibit this protein, we could potentially block cells from tolerating DNA lesions, which could lead to more effective chemotherapy in the future', says Julien Duxin, group leader at The Novo Nordisk Foundation Center for Protein Research.

Uncovering the knowledge gap

The findings, published in Molecular Cell, is the culmination of three years of research at the Duxin Group. The group focuses on understanding the basic principles of DNA replication and DNA repair which allow cells to repair genomic lesions like the ones induced by chemotherapy says Julien Duxin.

'Since the 1950s and the pioneer work from Sydney Farber, we have been treating cancer patients with different types of chemotherapeutic agents. These are extremely toxic agents, which have been approved in the clinic because they are effective at killing cancer cells. But the truth is that we still don't know how cells can repair the damage caused by the treatment. It is a huge knowledge gap, which we are trying to fill in with our fundamental research', he says.

Using egg extracts from African frogs, which contain the same repair factors than the ones present in our cells, the group was able to identify the protein RFWD3 as a critical coordinator of the repair events that happen when cells are replicating across from DNA lesions.

The group observed that the absence of the protein leads to a profound defect in recruitment of the components needed to repair and tolerate the damage.

'Repairing DNA lesions is a complex sequence of multiple events. Our goal is to identify the proteins at each event, which are essential to do this type of repair', says Julien Duxin.

Little is known about how repair works across different kinds of DNA damage. The group is now trying to set up simple systems so it becomes possible to molecularly study how these damages are repaired, Julien Duxin explains.

'We have very little knowledge about how most of these lesions caused by chemotherapy are repaired inside our cells. We are setting up different model systems to study this in detail and identify the key enzymes essential to this process. And by knowing those key enzymes we also get key targets that companies can aim to inhibit', he says.

Peer-reviewed / Observational / People

Study based on French national data from 89,530 patients hospitalised with COVID-19 between 1 March and 30 April 2020 and 45,819 patients hospitalised with seasonal influenza between 1 December 2018 - 28 February 2019.

Death rate among hospitalised COVID-19 patients was three times higher than seasonal influenza (15,104/89,530 [16.9%] vs influenza 2640/45,819 [5.8%]).

More patients with COVID-19 required intensive care (14,585/89,530 [16.3%] vs influenza, 4926/45,819 [10.8%]) and the average stay in ICU with COVID-19 was nearly twice as long (15 days vs 8 days)

Fewer children aged under 18 years were hospitalised with COVID-19 compared with seasonal influenza (1227/89,530 [1.4%] vs 8942/45,819 [19.5%]), but a larger proportion of those aged under 5 years required intensive care for COVID-19 (14/ 613 [2·3%] vs influenza 65/ 6973 [0·9%]). The case fatality rate in children under 5 years was similar for both groups and was very low (number of deaths COVID-19: 3/613 [0.5%] vs influenza: 13/6973 [0.2%]).

Nearly twice as many people were admitted to hospital for COVID-19 at the height of the pandemic than were for influenza at the peak of the 2018/2019 flu season, a study of French national data published today in The Lancet Respiratory Medicine journal has found (COVID-19, 89,530 patients vs influenza, 45,819 patients).

The study compared data from COVID-19 patients admitted to hospital over a two-month period in spring 2020 with influenza patients admitted over a three-month period during the seasonal flu outbreak of 2018/2019.

Researchers found that the death rate among COVID-19 patients were almost three times higher (number of deaths: COVID-19 15,104/89,530 [16.9%] vs influenza 2640/45,819 [5.8%]). In addition, a greater proportion of COVID-19 patients experienced a severe illness requiring intensive care than those with influenza (number admitted to ICU: COVID-19, 14,585/89,530 [16.3%] vs influenza, 4926/45,819 [10.8%]).

The authors note that the difference in hospitalisation rate may be partly due to existing immunity to influenza in the population, either as a result of previous infection or vaccination. In contrast, COVID-19 is a new virus where very few people would be expected to have any previous immunity. Nevertheless, they say their findings reinforce the importance of measures to prevent the spread of both diseases and are particularly relevant as several countries prepare for the COVID-19 pandemic to overlap with outbreaks of seasonal influenza.

Professor Catherine Quantin, from the University hospital of Dijon and from L'Institut National de la Santé et de la Recherche Médicale (Inserm), France, who jointly led the study, said: "Our study is the largest to date to compare the two diseases and confirms that COVID-19 is far more serious than the flu. The finding that the COVID-19 death rate was three times higher than for seasonal influenza is particularly striking when reminded that the 2018/2019 flu season had been the worst in the past five years in France in terms of number of deaths." [1]

The study is based on data from the French national administrative database (Programme de Médicalisation des Systèmes d'Information, PMSI). This database includes details for all patients admitted to either public or private hospitals in France, including information about why they were admitted and the care they received during their stay. The researchers compared hospital admissions with COVID-19 between 1 March and 30 April 2020 with seasonal flu hospital admissions between 1 December 2018 - 28 February 2019.

Overall, disease was more severe for patients with COVID-19 compared with seasonal influenza. Patients with COVID-19 were twice as likely as flu patients to require invasive mechanical ventilation during their hospital treatment (number of patients: COVID-19, 8,684/89,530 [9.7%] vs influenza, 1,833/45,819 [4.0%]). In addition, the average length of stay for COVID-19 patients in intensive care was nearly twice as long as for seasonal influenza patients (mean length of ICU stay: COVID-19, 15 days vs influenza, 8 days).

More than one in four patients with COVID-19 experienced acute respiratory failure, where the lungs are unable to get oxygen into the body, compared with less than one in five patients with influenza (number of patients: COVID-19, 24,317/89,530 [27.2%] vs influenza 7977/45,819 [17.4%]).

In line with previous reports, the most common underlying medical conditions among patients admitted with COVID-19 were high blood pressure 29,622/89,530 [33.1%], being overweight or obese (10,116/89,530 [11.3%]) and diabetes (17,050/89,530 [19.0%]).

Dr Pascale Tubert-Bitter, research director at L'Institut National de la Santé et de la Recherche Médicale (Inserm) and from the University Paris-Saclay, France, who jointly led the study, said: "Taken together, our findings clearly indicate that COVID-19 is much more serious than seasonal influenza. At a time when no treatment has been shown to be effective at preventing severe disease in COVID-19 patients, this study highlights the importance of all measures of physical prevention and underlines the importance of effective vaccines." [1]

The researchers observed that fewer children aged under 18 years were hospitalised with COVID-19, compared to flu (1227/89,530 [1.4%] vs influenza 8942/45,819 [19.5%]). However, among those aged under 5 years, a larger proportion of COVID-19 patients required intensive care support than did those with influenza (14 [2·3%] of 613 vs 65 [0·9%] of 6973). The case fatality rate in the COVID-19 group was not higher than for influenza in this age group and remained very low (number of deaths COVID-19: 3/613 [0.5%] vs influenza: 13/6973 [0.2%]).

In patients aged 11-17 years, the death rate appeared to be ten times higher in those admitted with COVID-19 compared with those admitted with flu, however the authors caution that the numbers are too small to draw meaningful conclusions (number of deaths COVID-19 5/548 [1.1%] vs 1/804 [0.1%]).

The authors note several limitations to their study. Notably, testing practices for influenza are likely to have been variable across hospitals whereas testing for COVID-19 may have been more standardised. This may account for some of the increased numbers of patients admitted to hospital with COVID-19 compared with seasonal influenza. Additionally, it is not possible to say whether the 2018/2019 flu season is representative of all seasonal influenzas, although the authors note that it was the most severe season in the past 5 years in France.

Writing in a linked Comment, Dr Eskild Petersen, who was not involved in the study, from the University of Aarhus, Denmark, said: "The large sample size is an important strength of the study and it is assumed that the indication for hospital admission in the two periods were the same and thus does not bias the results. The results clearly demonstrate that COVID-19 was more serious than seasonal influenza."