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Thursday, June 3, 2021, CLEVELAND: A Cleveland Clinic study shows that survivors of COVID-19 who have moderate or severe obesity may have a greater risk of experiencing long-term consequences of the disease, compared with patients who do not have obesity. The study was recently published online in the journal of Diabetes, Obesity and Metabolism.

Multiple studies have identified obesity as a risk factor for developing a severe form of COVID-19 that may require hospital admission, intensive care, and ventilator support in the early phase of the disease. Obesity, which is a complex disease caused by multiple factors, is associated with an increased risk for cardiovascular disease, blood clots and lung conditions. In addition, obesity weakens the immune system and creates a chronic inflammatory state. Those conditions can lead to poor outcomes after an infection with SARS-CoV-2, which is the virus that causes COVID-19.

"To our knowledge, this current study for the first time suggests that patients with moderate to severe obesity are at a greater risk of developing long-term complications of COVID-19 beyond the acute phase," said Ali Aminian, M.D., director of Cleveland Clinic's Bariatric & Metabolic Institute and principal investigator of the research.

In this observational study, researchers used a registry of patients who tested positive for SARS-CoV-2 infection within the Cleveland Clinic health system in a five-month period from March 2020 to July 2020, with follow-up until January 2021.

Researchers examined three indicators of possible long-term complications of COVID-19 - hospital admission, mortality, and need for diagnostic medical tests - that occurred 30 days or later following the first positive viral test for SARS-CoV-2. The outcomes were compared among five groups of patients based on their body mass index (BMI): 18.5-24.9 (normal), 25-29.9 (overweight), 30-34.9 (mild obesity), 35-39.9 (moderate obesity), and 40 or greater (severe obesity). Obesity is a disease classified as having a BMI of 30 or greater.

A total of 2,839 patients who did not require ICU admission and survived the acute phase of COVID-19 were included in the final results of this study. The normal BMI group was considered as a reference.

The study found that a health condition called post-acute sequelae of SARS-CoV-2 infection (PASC) is an extremely common problem in COVID-19 survivors. Specifically, during a 10-month follow-up after the acute phase of COVID-19, 44% of the study participants had required hospital admission and 1% died. Furthermore, results show that compared with patients with normal BMI, the risk of hospital admission was 28% and 30% higher in patients with moderate and severe obesity, respectively. The need for diagnostic tests to assess different medical problems, compared with patients with normal BMI, was 25% and 39% higher in patients with moderate and severe obesity, respectively.

More specifically, the need for diagnostic tests to assess cardiac, pulmonary, vascular, renal, gastrointestinal, and mental health problems was significantly higher in patients with a BMI of 35 or greater, compared with normal BMI patients.

"The observations of this study can possibly be explained by the underlying mechanisms at work in patients who have obesity, such as hyper-inflammation, immune dysfunction, and comorbidities," said Bartolome Burguera, M.D, Ph.D., chair of Cleveland Clinic's Endocrinology & Metabolism Institute and co-investigator of the study. "Those conditions can lead to poor outcomes in the acute phase of COVID-19 in patients with obesity and could possibly lead to an increased risk of long-term complications of COVID-19 in this patient population."

Future studies are planned to confirm findings of this study that obesity is a major risk factor for the development of PASC and determine the long-term and rigorous follow-up that patients with obesity need after a SARS-CoV-2 infection.

WHO: JoAnn Manson, MD, DrPH, Physician and Epidemiologist, Division of Preventive Medicine, Brigham and Women's Hospital; co-author of a new Perspective piece published in The New England Journal of Medicine (pdf attached)

WHAT: Less than 50 years ago, a U.S. Supreme Court decision paved the way for women's use of contraception irrespective of marital status, and a year later, in 1973, the Court ruled in Roe v. Wade that women have a right to legalized abortion. In recent decades, clinical researchers and policymakers alike have made important strides in promoting women's health and well-being, both within and beyond the field of reproduction. On the occasion of the 50th anniversary of the National Academy of Medicine, Manson and co-author Cynthia Stuenkel, MD, of the University of California San Diego's School of Medicine, wrote a Perspective piece for The New England Journal of Medicine chronicling major points of progress in women's health since the 1970s and expectations for the future.

"Women's health extends far beyond reproductive health. It is now recognized to encompass physical, mental, and emotional well-being, as well," writes Manson and Stuenkel. "The past half-century has been marked by important advances in reproductive health, improvement in women's well-being throughout the life course, and reductions in cardiovascular and cancer mortality in women."

In a detailed pair of timelines, the authors chart scientific advances related to women's health alongside key policy milestones that have made this progress possible. The authors also describe clinical research that has improved physicians' understanding of certain conditions that disproportionately affect women, including autoimmune disorders, diabetes, osteoporosis, and Alzheimer's disease. Sex-specific risk factors for coronary heart disease, once thought to affect only older women, have expanded standards for cardiovascular care for women of all ages, and care for diseases like breast and cervical cancer has also dramatically improved.

The authors emphasize the importance of recognizing and studying intersectional health disparities, highlighting race-based health disparities, such as maternal mortality rates that are three times higher among Black women than white women, and the need for progress in transgender health.

"The commitment to incorporating sex and gender into medical investigations and patient care considerations will transform the research and clinical agendas for the foreseeable future," the authors write. "Championing the role of science as the route to better health remains essential to spurring new discoveries to advance women's health."

Levels of antibodies in the blood of vaccinated people that are able to recognise and fight the new SARS-CoV-2 Delta variant first discovered in India (B.1.617.2) are on average lower than those against previously circulating variants in the UK, according to new laboratory data from the Francis Crick Institute and the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre, published today (Thursday) as a Research letter in The Lancet.

The results also show that levels of these antibodies are lower with increasing age and that levels decline over time, providing additional evidence in support of plans to deliver a vaccination boost to vulnerable people in the Autumn.

And, the researchers support current plans to reduce the dose gap between vaccines since they found that after just one dose of the Pfizer-BioNTech vaccine, people are less likely to develop antibody levels against the B.1.617.2 (Delta) variant as high as those seen against the previously dominant B.1.1.7 (Alpha) variant, first found in Kent.

Although laboratory results such as these are needed to provide a guide as to how the virus might be evolving to escape the first generation of vaccines, levels of antibodies alone do not predict vaccine effectiveness and prospective population studies are also needed. Lower neutralising antibody levels may still be associated with protection against COVID-19.

This is the largest study published to date investigating vaccine-induced antibody neutralising capacity against the newest variants of concern in healthy adults. Researchers have submitted their findings to the Genotype-to-Phenotype National Virology Consortium (G2P-UK), the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) and the Joint Committee on Vaccination and Immunisation (JCVI), as evidence of the level of protection people might receive against the new variants after one dose and both doses of the Pfizer COVID-19 vaccine.

As part of the SARS-CoV-2 Legacy study, led by the Crick and partners at UCL and University College London Hospitals NHS Foundation Trust (UCLH), healthcare workers and staff from the institutions have been donating regular blood and swab samples so that researchers can track changing risk of infection and response to vaccination.

Thanks to samples of the latest variants of concern being provided by NHS labs to the G2P-UK consortium, researchers have been able to quickly assess the potential risks they might pose.

Within just a few days of having enough of each variant to study, they were able to analyse antibodies in the blood of 250 healthy people who received either one or two doses of the Pfizer-BioNTech Covid-19 vaccine, up to three months after their first dose. Using a new highly accurate high throughput viral neutralisation assay developed at the Crick, they tested the ability of antibodies to block entry of the virus into cells, so called 'neutralising antibodies', against five different variants of SARS-CoV-2:

- The original strain first discovered in Wuhan, China

- The dominant strain in Europe during the first wave in April 2020 (D614G)

- B.1.1.7, the variant first discovered in Kent, UK (Alpha)

- B.1.351, the variant first discovered in South Africa (Beta)

- B.1.617.2, the newest variant of concern, first discovered in India (Delta)

They then compared concentrations of these neutralising antibodies between all variants. Data from previous clinical studies suggests that higher antibody titres (the greatest dilution level that still blocks 50% of virus infection in the lab) is a good predictor of vaccine efficacy and greater protection against COVID-19.

They found that in people who had been fully vaccinated with two doses of the Pfizer-BioNTech vaccine, levels of neutralising antibodies were more than five times lower against the B.1.617.2 variant when compared to the original strain, upon which current vaccines are based.

Importantly, this antibody response was even lower in people who had only received one dose. After a single dose of Pfizer-BioNTech, 79% of people had a quantifiable neutralising antibody response against the original strain, but this fell to 50% for B.1.1.7, 32% for B.1.617.2 and 25% for B.1.351.

While antibody levels decreased with age against all variants, no correlation was observed for sex or BMI.

The study participants analysed here had all been vaccinated with the Pfizer-BioNTech vaccine. More work is underway to test neutralising antibodies against these same variants in people who have been vaccinated with the Oxford/AstraZeneca vaccine.

Emma Wall, UCLH Infectious Diseases consultant and Senior Clinical Research Fellow for the Legacy study, said: "This virus will likely be around for some time to come, so we need to remain agile and vigilant. Our study is designed to be responsive to shifts in the pandemic so that we can quickly provide evidence on changing risk and protection.

"The most important thing is to ensure that vaccine protection remains high enough to keep as many people out of hospital as possible. And our results suggest that the best way to do this is to quickly deliver second doses and provide boosters to those whose immunity may not be high enough against these new variants."

David LV Bauer, group leader of the Crick's RNA Virus Replication Laboratory and member of the G2P-UK National Virology Consortium, said: "New variants occur naturally and those that have an advantage will spread. We now have the ability to quickly adapt our vaccination strategies to maximise protection where we know people are most vulnerable.

"Keeping track of these evolutionary changes is essential for us to retain control over the pandemic and return to normality. This work is a powerful example of effective collaborations between NHS and academic colleagues, that can help us to navigate changes in this new phase of the pandemic."

An immunotherapy drug given after surgery improved disease-free survival rates in patients with kidney cancer at high risk of relapse.

Interim results of a phase 3 trial of adjuvant therapy revealed a 32% decrease in the risk of recurrence or death with pembrolizumab compared with a placebo

This is the first positive study of immunotherapy in patients with kidney cancer at high risk of relapse.

BOSTON -- Treatment with an immunotherapy drug following kidney cancer surgery, prolonged disease-free survival rates in patients at high risk for recurrence, according to an interim report of a phase 3 clinical trial of adjuvant immunotherapy in this patient population.

Patients who were treated for nearly a year with pembrolizumab experienced a longer delay before the disease recurred, compared with those who got a placebo, said Toni K. Choueiri, MD, of Dana-Farber Cancer Institute, reporting on the KEYNOTE-564 clinical trial. This translated into a 32 percent decrease in the risk of recurrence or death in the first two years of the trial. Choueiri, the director of the Lank Center for Genitourinary Oncology at Dana-Farber, is presenting the findings in a plenary presentation to the American Society of Clinical Oncology (ASCO).

"KEYNOTE-564 is the first positive phase 3 study of an adjuvant immunotherapy in this setting and is a potential new standard of care," said Choueiri, who led the study. The report contained the first pre-specified analysis of the trial data.

Adjuvant treatment is additional therapy given after the primary treatment to lower the risk that the cancer will come back.

Reporting on the KEYNOTE-564 trial results to date, Choueiri said the estimated disease-free survival at 24 months after surgery was 77.3% with pembrolizumab treatment versus 68.1% with placebo. The trial is continuing to see if the adjuvant treatment increases overall survival. There have been too few deaths thus far to answer the question, but Choueiri said, "the early signs are quite promising." The estimated overall survival rate at 24 months was 96.6% with pembrolizumab and 93.5% with placebo.

The KEYNOTE-564 trial was designed to evaluate adjuvant immunotherapy following partial or radical nephrectomy (removal of the cancerous kidney) within 12 weeks prior to randomization. The double-blind, phase 3 study, carried out at multiple sites internationally, enrolled 994 patients who were randomized to pembrolizumab once every three weeks for about a year, or a placebo. Pembrolizumab targets a molecular pathway that cancer cells commandeer to evade recognition and killing by the body's immune system. By blocking this "checkpoint" pathway, the drug helps free the immune system - primarily with its army of T cells - to combat tumors.

For inclusion in the trial, patients were required to have a clear-cell component of their tumor and be at intermediate-high or high risk of recurrence. This risk level was defined as tumor stage 2 with nuclear grade 4 or sarcomatoid differentiation, tumor stage 3 or higher, regional lymph node metastasis, or stage M1 (metastases that had been surgically removed) with no evidence of disease.

The primary endpoint was disease-free survival, which is the time from randomization to the first documented local or distant renal-cell carcinoma recurrence or death due to any cause. Overall survival, defined as the time from randomization to death due to any cause, is a secondary end point.

The median disease-free survival was not reached in either the pembrolizumab or the placebo arm. The estimated percentage of patients who remained alive and recurrence-free at 24 months was 77.3% with pembrolizumab and 68.1% with placebo. The researchers are continuing to monitor the patients to determine if there is a difference in overall survival between the two arms of the trial, which Choueiri said may take additional follow up.

Most patients in both arms had at least one adverse event, and 32.4% of patients in the pembrolizumab arm had a grade 3-5 adverse event versus 17.7% in the placebo arm. No treatment related deaths were reported with pembrolizumab. The most common adverse events in both groups were fatigue, diarrhea, and itching, and adverse events with the greatest risk difference between the two arms were hypothyroidism, hyperthyroidism, itching and rash. In the as-treated population, 101 patients (20.7% in the pembrolizumab arm) and 10 patients (2.0% in the placebo arm) discontinued study treatment due to any-cause adverse events.

In conclusion, the study authors said, "our results support the use of pembrolizumab for patients with intermediate-high or high risk of disease recurrence in the adjuvant setting."

Choueiri said researchers will look for biomarkers to help determine which patients need adjuvant therapy. "There are patients in our study who were very likely cured only with surgery and didn't need any adjuvant therapy, and there are patients who received pembrolizumab and still their disease progressed."

While early detection of breast cancer is critical, early prediction of how well the neoadjuvant chemotherapy treatment before surgery is working also may provide a window of opportunity when treatment could be altered and have a big impact on the patient's quality of life.

An interdisciplinary team of researchers at Washington University in St. Louis has found that combining data from tumor biomarkers, ultrasound, and ultrasound-guided diffuse optical tomography (DOT) after a patient's first cycle of pre-surgical neoadjuvant chemotherapy provided a highly accurate prediction of how the tumor was responding to the treatment. The results from a clinical trial at Washington University School of Medicine and Barnes-Jewish Hospital were published online in Breast Cancer Research and Treatment May 10, 2021.

Quing Zhu, professor of biomedical engineering in the McKelvey School of Engineering and of radiology at the School of Medicine, led a team of engineers and radiologists in the three-year clinical trial involving patients with various types of breast cancer, including triple-negative breast cancer, human epidermal growth factor receptor 2 (HER2+), and estrogen receptor-positive/human epidermal growth factor 2 negative (ER+/HER2-). By conducting imaging after the first cycle of neoadjuvant chemotherapy, which ranges from two to three weeks depending on the type of treatment regimen used, Zhu said. The prediction model based on tumor biomarkers and imaging parameters can predict how well the cancer is responding.

"We found that the tumor biomarkers and near-infrared and ultrasound imaging parameters together would be the best earlier predictors to give us an area under the receiving operating curve, or AUC, of 0.94," said Zhu, a pioneer of combining ultrasound and near-infrared imaging modalities for cancer diagnosis and treatment assessment. "If we extended the imaging to the end of cycle 3 of neoadjuvant treatment, 1 1/2 to two months into the six-month treatment period, the prediction can reach AUC 0.97, the best in the literature regarding monitoring neoadjuvant chemotherapy treatment response."

In the study, 38 women patients with breast cancer underwent ultrasound and ultrasound-guided DOT prior to beginning neoadjuvant chemotherapy, at the end of each of the first three treatment cycles and prior to surgery. The DOT system consists of a 10-centimeter handheld probe and a near-infrared system developed in Zhu's lab that takes data noninvasively from the breast from nine sources and 14 detectors in less than 4 seconds.

"In this technology, the near-infrared light is delivered to the breast tissue and gets absorbed by the tumor," Zhu said. "If there is no tumor, there will be a stronger reflection of the light back to the breast tissue surface. Using a tomography image reconstruction algorithm, the tumor absorption map can be reconstructed, and the total hemoglobin concentration can be computed from absorption maps of multiple optical wavelengths. Total hemoglobin concentration is directly related to tumor vasculature. This technology is very sensitive, and light penetration depth can reach 4 centimeters to 5 centimeters, but the resolution is low, so we couple it with the ultrasound to improve the resolution."

Through this dual-modality combination, the researchers can determine if the vasculature, or blood vessel network, of the tumor is reducing and the tumor size is shrinking, which predicts a good treatment response, Zhu said. Otherwise, the tumor may not respond to treatment, and physicians may consider either early surgery or change to a different treatment regimen to improve patient treatment outcomes.

Going forward, Zhu would like to make the DOT system smaller so that it can be used at the patient's bedside in the infusion clinics. Eventually, she would like to integrate it with an existing ultrasound machine, which is compact and low-cost, to provide a dual-modality imaging assessment. She is working with the university's Office of Technology Management to commercialize the technology, which has US Patents pending.

"We could image the patient right before treatment and at early treatment cycles to help physicians decide who is responding and who is not responding," she said. "If we can decide this early on, we don't have to continue to give the patient the toxic chemotherapy drugs and find out at the end of treatment that tumors do not respond to the drugs."

A new method to monitor epidemics like COVID-19 gives an accurate real-time estimate of the growth rate of an epidemic by carefully evaluating the relationship between the amount of viruses in infected people's bodies, called the viral load, and how fast the number of cases is increasing or decreasing.

"This new method, which effectively links what we know about how the virus grows within the body to the dynamics of how the virus spreads across a population, provides a brand new metric that public health officials, policy makers, and epidemiologists will be able to use to get up-to-date real-time information on the epidemic," said Michael Mina, assistant professor of epidemiology at Harvard T.H. Chan School of Public Health and a core member of the Center for Communicable Disease Dynamics.

Mina is the senior author of a paper that describes the method, published June 3, 2021 in the journal Science.

Monitoring epidemics is essential for public health response to understand how well interventions like masks, lockdowns, or vaccines are working, and to know where to distribute extra resources when cases are rising.

The current approaches to monitoring epidemics rely almost entirely on following case counts or hospitalization rates over time, and looking at test positivity rates and deaths. Throughout the COVID-19 pandemic, for example, daily case data like that published by the New York Times has been crucial for public health officials and researchers to evaluate how well states and countries are controlling the spread of the SARS-CoV-2 virus that causes COVID-19. However, these types of data can often be of only limited use because of variable testing practices or poor reporting. For example, a growing epidemic might look like it is leveling off if testing capacity is maxed out or if reporting is delayed because resources are being focused elsewhere. These pitfalls of monitoring case reports over time can adversely impact appropriate public health responses.

Because outbreaks grow or fall exponentially, when cases are growing, most people who are positive at any moment in time will have been recently infected and will thus have higher viral loads--as measured in PCR (polymerase chain reaction) tests--at the time that they are tested. This is because the virus is at its peak amount in the body early after infection and then falls to very low but still detectable levels in PCR tests over weeks or even months after infection. When the outbreak is slowing down and cases are falling, the average person who is detected as positive in surveillance testing will have been infected potentially weeks before testing and thus will have lower viral loads at the time of testing.

To better track pandemic hotspots, researchers at Harvard Chan School developed a mathematical tool that carefully evaluates the relationship between viral load--measured from the PCR test in a value called the cycle threshold (Ct value)--and how fast cases are increasing or decreasing. Using even the relatively small number of 30 SARS-CoV-2 positive samples taken from surveillance testing on a single day can give an accurate real-time estimate of the growth rate of the epidemic. When Ct values are available from multiple time points, the researchers discovered that they can use even a very limited amount of positive results to reconstruct the epidemic curve and estimate how many people have been infected over time.

Even viral amounts detected in positive PCR test samples collected from one location at just a single point in time can help estimate the growth or decay rate of an outbreak across a population, the researchers found.

In the U.S. and in much of the world, the PCR Ct values--the values that show how much virus is collected on the swab from someone's nose--are often discarded and the results of the PCR test returned with a simple "positive" or "negative" result.

"Our work demonstrates just how valuable the Ct values are and why we should not only stop our current practice of throwing them away, but why we should instead make them a key piece of data to collect for our pandemic response," said Mina, who has previously published on the use of PCR Ct values to aid in clinical decision making and who has been a leader in developing new approaches for using COVID-19 tests to limit the disease's spread.

James Hay, who co-led the research as a postdoctoral researcher in Mina's lab, stressed that the new technique is not COVID-19-specific but is a method that will be valuable for monitoring outbreaks and epidemics of other viruses in the future. "This tool is not just for COVID, but rather provides a new approach to estimating epidemic trajectories of many types of viruses, and is an approach that does not rely on potentially biased approaches like counting cases over time and will not be reliant on accurate reporting of cases or hospitalization," he said.

PORTLAND, OR - Patients with high-risk melanoma who had a course of pembrolizumab after their surgery had a longer time before their disease recurred than patients who got either ipilimumab or high-dose interferon after surgery. These findings of a large SWOG Cancer Research Network clinical trial, S1404, will be presented at the ASCO annual meeting June 6, 2021.

Researchers also measured overall survival and found no statistically significant difference in overall survival rates between the two groups of patients three and one-half years after the last patient enrolled to the trial. They did find, however, that patients taking pembrolizumab had fewer serious side effects than those treated with either high-dose interferon or ipilimumab.

The S1404 trial is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), designed and led by the SWOG Cancer Research Network, and conducted by the NIH-funded National Clinical Trials Network (NCTN).

Kenneth F. Grossmann, MD, PhD, of the Huntsman Cancer Institute at the University of Utah Medical Center and chair of SWOG's Melanoma Committee was lead investigator on the study. He spoke about the pembrolizumab treatment that was tested: "The recurrence-free survival advantage and improved safety profile over the previous standard of care make this therapy a continued standard for treating patients with high-risk resected melanoma."

Noting that overall survival measures were not significantly different between the two arms, Grossmann said, "The overall survival analysis was performed at a pre-defined time point with only approximately 50% of events needed for a fully powered analysis. We suspect that effective use of PD-1 blockade and other improved therapies for stage IV disease improved outcomes of relapsing patients on the control arm such that overall survival was not different between the two groups."

Grossmann added that further data to come from this trial will include studies to evaluate pre-treatment predictors of whether patients are likely to benefit from treatment and quality of life studies to better understand the impact of relapse in patients with high-risk resectable melanoma.

The study randomized 1,345 adult patients with stage III or IV melanoma who had undergone surgery to remove their tumors. Patients were assigned at random to either the pembrolizumab arm or the control arm. Those on the control arm decided with their physicians whether to follow a course of high-dose interferon or a course of ipilimumab, both of which are approved by the FDA for use in treating these patients.

Pembrolizumab, an immunotherapy drug known as a PD-1 inhibitor, was chosen for the trial because of its comparatively low toxicity and its activity in metastatic disease. Another trial has also since shown a recurrence-free survival benefit for the drug when compared to a placebo. High-dose interferon and ipilimumab, which were standard of care treatments for these patients at the start of the study, often come with serious side effects. As the S1404 researchers had expected, toxicity was lower in patients on the pembrolizumab arm. Among patients taking high-dose interferon, roughly 72% had severe side effects (grade 3 or higher adverse events). The rate of such side effects was about 58% for those on ipilimumab, but it was only about 32% for patients on pembrolizumab.

ANN ARBOR, Mich. -- A different type of surge may be on the way more than a year into the pandemic - a baby surge.

The COVID-19 shutdown initially seemed to hit pause on pregnancy and birth rates, new research from one major hospital system suggests, but that trend is quickly reversing.

"Birth rates declined early on in the pandemic, but we expect a dramatic rebound soon," says lead author Molly Stout, M.D., MSci, maternal fetal medicine director at Michigan Medicine Von Voigtlander Women's Hospital.

"We're already seeing signs of a summer baby surge."

While infectious disease experts have been modelling COVID cases to project surge trends, Stout and her team have been doing the same for pregnancy trends.

Using electronic health records for a cohort of pregnancies at Michigan Medicine, researchers were able to model pregnancy episodes and accurately project anticipated changes in pregnancy volumes over the last year during pandemic societal changes.

Pregnancies at U-M gradually increased between 2017 and 2020, up from 4,100 pregnancies to 4,620 annually, according to the study in JAMA Network Open. But pregnancy volumes diverged from that pattern, decreasing by about 14 % between November, 2020 and spring of 2021 which the researchers associate with a conception window starting during the U.S. COVID shutdown in March, 2020.

Experts point to multiple potential factors for the decline, including economic uncertainty, lack of child care or usual support systems, the impact on women in the workforce and postponement of reproductive and fertility care.

Based on the same modelling system, authors now anticipate a birth surge. The hospital is planning for a 10-15 % increase in births over what would normally be expected in the summer and fall of 2021.

While speculations of a COVID baby boom have previously been reported in the media, they were mostly speculative and not based on data, Stout says.

"What we have shown here is that through modeling of pregnancies within a healthcare system we can project birth rate increases and decreases associated with major societal shifts," she says.

"Major societal changes certainly seem to influence reproductive choices, population growth and fertility rates. Usually, we see the effects by modeling birth and death rates, only as the changes are occurring. With this methodology we can accurately project anticipated birth rates ahead of the actual changes."

This has also been noted during other times in history, such as the 1918 H1N1 influenza pandemic, the Great Depression in 1929 and recession of 2008.

Stout says the ability to predict upcoming birth trends through the Michigan team's modeling system can hopefully help health systems better plan for labor and delivery needs to provide the safest care for patients and their babies.

"These projection techniques can inform planning for capacity, staffing needs and other downstream effects on the hospital system," she says.

"But it can also be used in partnerships between hospitals and governmental groups to better understand population dynamics and help minimize the negative effects of a pandemic or any other major event on society."

After a 2020 Vanderbilt University Medical Center study showed women have a difficult time accessing treatment for opioid use disorder (OUD), investigators analyzed comments received from the study's participants to further shed light on barriers to care, which included everything from long on-hold times to difficult interactions with clinic receptionists during phone calls seeking appointments.

A "secret shopper" study published in JAMA Network Open in 2020 used trained actors trying to get into treatment for opioid use disorder in 10 U.S. states. More than 10,000 unique "patients" were randomly assigned to be pregnant or non-pregnant and have private or Medicaid-based insurance to assess differences in the experiences of access.

The results revealed many challenges in scheduling a first-time appointment to receive medications for OUD, including finding a provider who takes insurance rather than cash. Access to treatment was even more difficult for women who are pregnant and have OUD, with pregnant women about 20% less likely to be accepted for treatment than nonpregnant women.

The trained actors provided nearly 18,000 comments describing what happened during calls, and pregnant callers and those with Medicaid documented the most barriers in obtaining an appointment. The qualitative study is published in Women's Health Issues.

"Even though these trained callers didn't actually have opioid use disorder, and even though they weren't desperately trying to get help for themselves and their baby, they still felt stigmatized during these calls," said lead author Julia Phillippi, PhD, CNM, assistant professor and academic director of the Nurse-Midwifery program at Vanderbilt University School of Nursing. "They often felt overwhelmed by emotion because of how they were treated, both good and bad. That really says something."

Many callers experienced less than welcoming, and often stigmatizing, responses from the person answering the phone. One secret shopper reported the receptionist said, "People usually don't show up to appointments because they decide they want to have one last hoorah on dope before coming."

Callers were often placed on hold or transferred repeatedly. One caller commented, "The wait time to speak with someone is crazy," while another said, "I told them I was seeking addiction treatment and four months pregnant; they put me on the classic immediate hold."

Not all interactions were negative. One caller reported, "I would like to note that everyone I spoke with throughout the call, including the receptionist, was deeply empathetic, knowledgeable and helpful."

As the U.S. opioid crisis has grown, women have been increasingly affected. According to the National Center for Health Statistics, from 1999-2016 the rate of drug-related deaths among women jumped from 3.9 to 13.4 per thousand.

Treatment involving medications for opioid use disorder (MOUD) is highly effective in reducing overdose death and improving quality of life. For pregnant women, MOUD improve pregnancy outcomes, including preterm birth.

"We're setting record levels of overdose deaths in the U.S., very likely worsened by the COVID-19 pandemic," said Stephen Patrick, MD, director of the Center for Child Health Policy at Vanderbilt University School of Medicine, associate professor of Pediatrics and Health Policy and Vanderbilt University Medical Center neonatologist. "We know medications to treat opioid use disorder reduce the risk of overdose deaths for mom and increase the likelihood that the birth is going to go to term with a higher birth weight. We should make access to treatment easy, and certainly not harder."

The authors recommend interventions to improve access to OUD care for reproductive-age women, including increasing the number of clinics in the U.S. that provide MOUD regardless of pregnancy and insurance status; more training for clinic call-takers; and addressing the issue nationally through policy reform.

June 3, 2021 - LA JOLLA, CA--Mining the world's most comprehensive drug repurposing collection for COVID-19 therapies, scientists have identified 90 existing drugs or drug candidates with antiviral activity against the coronavirus that's driving the ongoing global pandemic.

Among those compounds, the Scripps Research study identified four clinically approved drugs and nine compounds in other stages of development with strong potential to be repurposed as oral drugs for COVID-19, according to results published June 3 in the journal Nature Communications.

Of the drugs that prevented the coronavirus from replicating in human cells, 19 were found to work in concert with or boost the activity of remdesivir, an antiviral therapy approved for treatment of COVID-19.

"While we now have effective vaccines against COVID-19, we still lack highly effective antiviral drugs that can prevent COVID-19 infections or stop them from worsening," says Peter Schultz, PhD, president and CEO of Scripps Research.

"Our results raise the possibility of a number of promising avenues for repurposing existing oral medications with efficacy against SARS-CoV-2," he adds. "We have identified promising existing drugs and are also leveraging our findings to develop optimized antivirals that will be more effective against SARS-CoV-2, including variants and drug resistant strains, as well as against other coronaviruses that currently exist or might emerge in future."

In a collaboration between Calibr, the drug discovery division of Scripps Research, and a team of researchers in the institute's Department of Immunology and Microbiology, the study tested more than 12,000 drugs in two different types of human cells infected with SARS-CoV-2.

The drugs used in the study came from the ReFRAME drug repurposing library, which was established by Calibr in 2018 with support from the Bill & Melinda Gates Foundation to tackle areas of urgent unmet medical need, especially neglected tropical diseases. The collection contains FDA-approved drugs and other experimental compounds that have been tested for safety in humans.

"Early in the COVID-19 pandemic, we saw that ReFRAME could be leveraged to screen for hits against SARS-CoV-2," says Arnab Chatterjee, PhD, vice president of medicinal chemistry at Calibr. "In the months that followed, we launched many scientific collaborations to speed drug discovery, both internally at Scripps Research and with partners nationally and internationally."

In the Scripps Research study, the scientists treated two different types of laboratory-cultured SARS-CoV-2-infected human cells with each of the 12,000 drugs from ReFRAME. After 24 or 48 hours, they measured the level of viral infection in the cells to determine if the drugs prevented the virus from replicating. In some cases, they applied two drugs at a time to see if the compounds would work together against the virus.

"Some of the most effective antiviral strategies are 'cocktails' in which patients are given several different drugs to combat the infection, such as those used to treat HIV infections," says the study's corresponding author Thomas Rogers, MD, PhD, an adjunct assistant professor in the Department of Immunology and Microbiology at Scripps Research and assistant professor of Medicine at UC San Diego.

From the thousands of drugs screened, the researchers identified a total of 90 compounds that prevented SARS-CoV-2 from replicating in at least one of the human cell lines. Of those, 13 had the highest potential to be repurposed as COVID-19 therapies, based on their potency, cell line-independent activity or a likely mechanism of action, pharmacokinetic properties and human safety profiles.

Four of the drugs--halofantrine, nelfinavir, simeprevir and manidipine--are already FDA approved and nine others are in various stages of the drug development process.

From the drug combination screens, the researchers found 19 drugs that had an additive effect when administered with remdesivir, the antiviral produced by the pharmaceutical company Gilead that is FDA approved for use in patients diagnosed with COVID-19. An additive effect means that the drugs were both active against the virus when applied together.

"The potential advantage of a therapeutic strategy that uses a combination of drugs is that taking a lower dose of any one drug could reduce the risk of side effects of that drug," says Malina Bakowski, PhD, the lead author on the Nature Communications paper and principal investigator at Calibr.

Two additional drugs went a step further to have a synergistic effect on remdesivir, meaning the drugs heightened remdesivir's ability to suppress the virus. These two drugs were riboprine, a compound that's been tested as a preventative for nausea and surgical infection, and 10-deazaaminopterin, a derivative of the vitamin folic acid.

Based on the results of cell culture screens, the researchers tested the best-performing drug candidates in human tissue cells and an animal model to determine which are most likely to work in human patients. Building on their success in identifying potential COVID-19 therapies, the Scripps Research team is continuing to advance other promising candidates through their drug discovery pipeline.

"The results from the cellular assays and animal models are very promising and the need for medical remedies to address COVID-19 remains urgent," says Schultz. "It is critical we proceed with the utmost rigor to determine what is safe and effective, as diligence is the most expedient path to finding new therapies that will make a difference for patients."

Results from the screen of the ReFRAME library are available at the reframedb.org data portal.

The number of people engaging with life-enhancing cardiac rehabilitation clinics has declined during the pandemic, according to a BMJ clinical update which makes the case for more home-based and virtual alternatives.

Before the covid-19 pandemic, 100?000 people were admitted to hospital with heart attacks and approximately 200?000 were diagnosed with heart failure annually in the UK. There was a 40% decline in the number of patients admitted with heart attacks (acute coronary syndromes ) in 2020.

Cardiac rehabilitation is crucial to helping people who have encountered a heart attack or heart failure have a better quality of life. Now, a new review, undertaken by cardiac rehabilitation experts based at the Universities of Exeter, Glasgow and York and published in the BMJ, reports that the number of people with heart failure attending UK clinics dropped from an already low ten per cent (4,969 patients) of those eligible pre-pandemic, to just five per cent (1,474). The review attributes the drop to many vulnerable people shielding, and many rehabilitation clinics closing during this period because of staff redeployment to respond to the pandemic.

A British Heart Foundation (BHF) National Audit of Cardiac Rehabilitation COVID-19 analysis published in 2020 mirrored other cardiac audits, showing a 30-40 per cent decrease in use of cardiology and rehabilitation services due to the pandemic compared with a similar period in 2019.

However, the number of people taking up home-based rehabilitation options has more than trebled over the same time period, rising from 22 to 74 per cent - strengthening the case for the use of more evidence-based programmes in this field to be rolled out.

Dr Hasnain Dalal, of the University of Exeter, co-authored the review. He said: "Cardiac rehabilitation can enhance quality of life and reduce unplanned hospital admissions, yet uptake has been low, and has plummeted throughout the pandemic, creating a backlog. We know that home-based cardiac rehabilitation can work well for patients, and COVID-19 has provided an opportunity to reimagine how we delivery rehabilitation. Offering patients a choice of rehabilitation in clinics or at home - or a combination of both could help improve the numbers who can participate in the future".

ROCHESTER, Minn. -- A study by Mayo Clinic researchers provides some clarity in the use of direct oral anticoagulants (DOAC), such as apixaban and rivaroxaban, to treat acute venous thromboembolism (VTE) in patients with gastrointestinal cancers. The findings were published Wednesday, June 2, in Mayo Clinic Proceedings.

Among the study's findings:

Rivaroxaban showed no higher risk of bleeding in luminal gastrointestinal cancer and should not be considered contraindicated in this group of patients.

Apixaban showed a higher risk of bleeding in patients with luminal gastrointestinal cancer, and it should be used with great caution to treat this type of cancer until more studies are available to establish its safety.

Direct oral anticoagulants can be used in patients with venous thromboembolism and nonluminal gastrointestinal cancers, such as pancreatic cancer and hepatobiliary cancer. This is similar to the way patients with nongastrointestinal cancers are treated for venous thromboembolism.

"It is well known that nearly 1 in 5 patients with cancer will develop a clot in the veins, referred to as either a deep vein thrombosis or pulmonary embolism," says Waldemar Wysokinski, M.D., Ph.D., a Mayo Clinic cardiologist. "Clotting events can be deadly, with pulmonary embolism being the second most common cause of death in cancer patients."

Dr. Wysokinski says patients with cancer who are treated with anticoagulants for venous thromboembolism have a higher risk of a new clot formation and bleeding, and every anticoagulant should be specifically checked for its effectiveness and safety in this group of patients.

"In the past, the front-line treatment for VTE in patients with cancer was low molecular weight heparin, or LMWH, injected via syringe," says Dr. Wysokinski. "However, between 2018 and 2020, three new anticoagulants ? edoxaban, rivaroxaban and apixaban ? previously approved by the FDA (Food and Drug Administration) for VTE treatment were specifically evaluated in patients with cancer-associated VTE and found to be noninferior to LMWH, specifically dalteparin."

Dr. Wysokinski says that in the randomized clinical trial with rivaroxaban, a safety analysis of patients treated with this blood thinner identified four major bleeding events that occurred among 11 patients, or 36% of patients, whose cancers were located in the upper portion of the gastrointestinal tract ? esophagus or esophagus-stomach junction ? compared to one major bleeding event in 19 patients, or 11% of patients, treated with low molecular weight heparin. This observation resulted in excluding patients with this type of cancer from further enrollment in this trial.

Dr. Wysokinski says that a retrospective analysis of patients with gastrointestinal cancer enrolled in a study comparing efficacy and safety of another direct oral anticoagulant ? edoxaban ? to low molecular weight heparin showed a nearly fourfold higher risk of major bleeding in patients treated with this blood thinner, compared to patients treated with low molecular weight heparin.

"These two observations prompted changes in medical guidelines recommending against using DOACs such as rivaroxaban or edoxaban in patients with GI cancer in favor of LMWH," says Dr. Wysokinski. "We felt that these recommendations were based on a very small number of patients and that the findings would require further evaluation to define if restrictions on the use of DOACs applied to all blood thinner of this category ? and to the whole group of patients with GI cancers or only to patients with luminal GI cancers."

Dr. Wysokinski says at the time his team completed its analysis and submitted their study for publication, there were no studies of patients with cancer-associated venous thromboembolism that compared apixaban to low molecular weight heparin in a subgroup of patients with gastrointestinal cancer. He says that while the current study showed no higher risk of bleeding in patients with luminal gastrointestinal cancer treated with rivaroxaban, there was a higher risk of bleeding in patients treated with apixaban.

"Our study does not support the observations of previous clinical trials of rivaroxaban, but it does raise concerns regarding the use of apixaban in this type of cancer and indicates the need for further studies to establish its safety," says Dr. Wysokinski.

Cancer researchers say they have established a new, life-extending treatment option for men with prostate cancer that has spread and become resistant to hormone therapy. The injected treatment combines a targeting compound with a radioactive isotope to irradiate and kill cancer cells.

An international clinical trial sponsored by Endocyte, Inc., a Novartis company tested the targeted radioligand therapy in study participants with advanced prostate cancer. All subjects had cancers that had spread to other organs and continued to progress after previous treatment with two kinds of drugs, androgen axis inhibitors and taxanes. The experimental treatment significantly extended survival, delayed progression and was generally well tolerated by study subjects, researchers said.

"This is a completely new treatment option that extends life and disease control in metastatic castration-resistant prostate cancer - the most aggressive and deadly type," said Tom Beer, M.D., one of the study leaders and deputy director of the Oregon Health & Science University Knight Cancer Institute.

The added option is particularly important, Beer said, because the existing most effective treatments developed for metastatic castration resistant prostate cancer are now being used to treat early-stage disease.

"Some of our best treatments are being used earlier, so by the time you get to metastatic castration resistant disease, you have fewer options," he said.

Beer is a co-author of the presentation of the results at the American Society of Clinical Oncology Annual Meeting on Sunday. The OHSU Knight Cancer Institute was among the top sites for enrolling subjects.

The experimental therapy is called Lutetium-177-PSMA-617. It carries the radioactive isotope Lutetium-177 and targets prostate-specific membrane antigen, or PSMA, a protein that appears on the surface of most prostate cancer cells. After injection into the bloodstream, the drug binds to prostate cancer cells bearing PSMA, and thus delivers radiation selectively to the cancer. The emitted beta particle radiation works over short distances to limit damage to surrounding tissues.

More than 80 percent of advanced prostate cancers bear the PSMA protein, and patients with PSMA-bearing tumors can be identified with a PET scan.

The randomized, phase 3 clinical trial enrolled more than 800 subjects at 84 sites. They were randomly assigned to receive Lutetium-177-PSMA-617 in addition to standard of care, or to receive standard of care alone. Those in the experimental therapy group received intravenous infusions of the radioligand therapy once every six weeks for up to six cycles.

Overall survival was significantly longer in those treated with the targeted radioligand: a median of 15.3 months versus 11.3 months. Survival without tumor progression also was significantly longer in the radioligand group: a median of 8.7 months versus 3.4 months.

Researchers said the effect of Lutetium-177-PSMA-617 treatment on overall survival was substantial especially given that all of the subjects enrolled had disease progressing despite treatment with modern androgen axis inhibitors and taxane chemotherapy. They said ongoing trials will address the question of whether the targeted radioligand therapy can provide therapeutic benefit earlier in the treatment sequence than was the case in the present clinical study.

The incidence of treatment-emergent adverse events of grade 3 or above was higher in the group given the targeted radioligand than in group given the standard of care only. Fatigue, dry mouth and nausea were the most commonly reported adverse events in the radioligand group.

"It's pretty well tolerated," Beer said. "I think it's going to be an asset in treating cancer without taking a big toll on patients."

WHAT TO EXPECT AND PREPARE FOR AS YOU RETURN TO REGULAR HEALTH CARE APPOINTMENTS

Media Contact: Maura Kinney, mkinney4@jhmi.edu

Over the past year-plus of quarantining, many people have avoided leaving their homes as much as possible, not even to see their health care provider for regular checkups and other preventive care. As COVID-19 cases in the U.S. drop, some are wondering how to prepare for non-COVID-related doctor's visits. Paul O'Rourke, M.D., M.P.H., an assistant professor of medicine at the Johns Hopkins University School of Medicine and the associate program director of the Johns Hopkins Bayview Internal Medicine Residency Program, has some suggestions.

Reflect on your major health questions and concerns before the appointment. "Write them down so you can review them during your visit," O'Rourke says. "After a long time away, it's helpful to come prepared and ensure you address the issues important to you."

Bring a list of your current medications and supplements, as well as documentation of any vaccines (including the COVID-19 vaccine) that you may have received elsewhere. "This enables your physician to update your records and ensure you are current with recommendations," says O'Rourke.

Prepare for certain aspects of your appointment to be different. "For example, waiting rooms have been rearranged to maintain physical distancing," O'Rourke says. "Nurses and doctors wear facial coverings now. And some clinics will ask to conduct a COVID-19 screening prior to your appointment."

"Hesitancy is understandable," O'Rourke adds. "This has been a very stressful time for everyone. But, it is important for patients to return to medical and preventive care services -- and to know that all medical clinics have precautions in place to minimize the risk of acquiring COVID-19."

O'Rourke cites three primary reasons for patients to return to their doctors: to address any current health concerns; to address any chronic medical conditions, such as diabetes or chronic obstructive pulmonary disease; and to receive preventive health screenings.

For those still concerned about returning to their doctor, O'Rourke encourages them to contact their physician's office.

"Your health care providers want you to be safe," he says. "Reach out to them and ask for information about their COVID-19 safety procedures if you need reassurance about coming back."

O'Rourke is available for interviews to discuss returning to care.

STUDY SUGGESTS SUDDEN HEARING LOSS NOT ASSOCIATED WITH COVID-19 VACCINATION

Media Contact: Waun'Shae Blount, wblount1@jhmi.edu

In a new study, Johns Hopkins Medicine researchers have tried to address recent reports that sudden sensorineural hearing loss -- a condition that occurs as a result of damage to the inner ear -- has been suspected of being a potential side effect of vaccination against SARS-CoV-2, the virus that causes COVID-19. Their conclusion so far: Vaccination does NOT increase one's risk for sudden hearing loss.

A research letter detailing the team's findings appeared May 20 in JAMA Otolaryngology-Head and Neck Surgery.

Researchers at Johns Hopkins and across the country experienced an increase in patients presenting with sensorineural hearing loss after COVID-19 vaccination.

"Sudden hearing loss can occur naturally, so it hasn't yet been confirmed whether sudden hearing loss occurring after COVID-19 vaccination is coincidental or related to the vaccine," says study co-author Daniel Sun, M.D., assistant professor of otolaryngology-head and neck surgery at the Johns Hopkins University School of Medicine.

Though current data do not provide clues as to whether the hearing loss is temporary or permanent, doctors have been treating the hearing loss like other cases of idiopathic sudden sensorineural hearing loss, with either steroids by mouth or steroids injected through the ear drum into the middle ear.

For their study, Sun and colleagues used data related to sudden hearing loss after COVID vaccination from the U.S. Centers for Disease Control and Prevention's Vaccine Adverse Events Reporting System (VAERS), a national repository of reports tracking medical problems following vaccinations in the country. For the period Dec. 14, 2020, to March 2, 2021, the researchers found 40 reports of sudden hearing loss in 86,553,330 people who received one dose of either the Pfizer or Moderna mRNA vaccines (0.3 cases per 100,000 per year) and 147 reports in 43,276,665 patients who received two doses during the same time span (4.1 cases per 100,000 per year). The investigators narrowed the reports to only those describing hearing loss diagnosed by a clinician within three weeks of receiving the vaccine. Researchers chose data for people experiencing hearing loss in this time frame since vaccines doses are spaced between three and four weeks and hearing loss examined after four weeks may not be correlated to the vaccine.

"Based on the rate of hearing loss reported in VAERS, so far there is no evidence that people receiving a COVID-19 vaccination are at higher risk of developing sudden hearing loss than those who have not been vaccinated," says Sun.

Individuals should continue to receive COVID-19 vaccinations as recommended by the CDC, Sun says, and clinicians should report any suspected adverse effects, including sudden hearing loss, to the CDC via VAERS. He adds that anyone who experiences sudden hearing loss at any time should immediately seek the care of an otolaryngologist. "The sooner it is treated, the more likely the hearing can be restored," says Sun.

"Although this preliminary analysis suggests that the COVID-19 vaccine is not associated with sudden hearing loss, more research is needed to address this question," says study lead author Eric Formeister, M.D., a neurotology fellow at the Johns Hopkins University School of Medicine. "Our study depended on data produced by voluntary submission of reports to a database, so there is a possibility that there was underreporting, meaning that some cases of post-vaccine hearing loss were undocumented."

To validate the preliminary results of their latest study, the researchers would like to conduct comprehensive investigations that can more accurately define the risk of hearing loss following COVID-19 vaccination. They also plan to look for any specific medical risk factors that may increase the risk of developing sudden hearing loss after COVID vaccination in certain individuals.

Sun and Formeister are available for interviews.

VACCINATION MAY NOT RID COVID-19 RISK FOR THOSE WITH RHEUMATIC, MUSCULOSKELETAL DISEASES

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

Johns Hopkins Medicine researchers recently reported that while two doses of a vaccine against SARS-CoV-2 -- the virus that causes COVID-19 -- confers some protection for people who have received solid organ transplants, it isn't sufficient to enable them to dispense with masks, physical distancing and other safety measures.

Now, the researchers have shown a similar lower-than-normal immune response to the messenger RNA (mRNA) COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases (RMDs), conditions that often call for treatment with medications that suppress the immune system.

The study was detailed in a research letter published May 25 in the Annals of Internal Medicine.

"Our findings suggest that patients with RMDs who are on immunosuppressive therapies have less-than-optimal responses to vaccination, and therefore, are still at risk for SARS-CoV-2 infection," says study lead author Caoilfhionn Connolly, M.D., a postdoctoral fellow in rheumatology at the Johns Hopkins University School of Medicine.

According to the American College of Rheumatology, RMDs are a diverse group of autoimmune diseases that affect children and adults, and can impact any organ of the body, often the joints. Most RMDs are due to problems of the immune system, which can result in inflammation and gradual deterioration of joints, muscles and bones. Over 46 million people in the United States are living with some type of RMD, including rheumatoid arthritis, systemic lupus erythematosus, scleroderma, vasculitis and Sjögren's syndrome.

Between Dec. 7, 2020, and March 11, 2021, the Johns Hopkins Medicine researchers recruited patients age 18 and older with RMDs for the immune response study. One month after the participants received their second dose of either the Pfizer-BioNTech or Moderna mRNA COVID-19 vaccine, blood samples were analyzed for neutralizing antibodies against the target of both vaccines, the SARS-CoV-2 spike protein.

Twenty patients did not have detectable antibodies. The majority were women (95%), white (90%), diagnosed with lupus (50%) and receiving multiple immunosuppressive agents (80%) -- of which the most common medications were rituximab (55%), a biologic used to treat autoimmune disorders such as rheumatoid arthritis and vasculitis, and mycophenolate (50%), a drug commonly used as a first-line therapy for scleroderma lung disease and lupus nephritis (kidney inflammation). Both immune suppressants work by depleting B-lymphocytes (also known as B-cells), immune cells that produce antibodies in response to foreign invaders such as bacteria and viruses.

"Based on our findings, we urge patients with autoimmune diseases who are taking these particular immunosuppressive agents to continue practicing recommended COVID-19 safety measures, even after vaccination," says study co-author Brian Boyarsky, M.D., Ph.D., a research fellow at the Johns Hopkins University School of Medicine.

Connolly and Boyarsky say additional research is needed to better understand the immune response to COVID-19 vaccination in patients with RMDs to find potential methods for raising the vaccine effectiveness in this population -- including adjusting the dosage and timing of immunosuppressive agents prior to vaccination.

Connolly and Boyarsky are available for interviews.

HOUSTON-(June 3, 2021) - Results were released this week on a new treatment with the potential to improve the outcomes for patients with hereditary BRCA mutations and high-risk, early-stage breast cancer. These results represent the first time a drug that blocks cancer cells from repairing their DNA (called a PARP inhibitor) has been shown to significantly reduce the risk of breast cancer returning in high-risk patients following completion of standard chemotherapy, surgery and radiation therapy.

Titled "Adjuvant Olaparib for Patients with BRCA1 or BRCA2 Mutated Breast Cancer," the paper appears in the June 3 issue of the New England Journal of Medicine and will be presented June 6 as the first abstract during the plenary session at the 2021 American Association of Clinical Oncology (ASCO) Annual Meeting. Lead author and the OlympiA trial steering committee chair Andrew Tutt, M.D., Ph.D., of The Institute of Cancer Research and King's College London was principal investigator on the portion of study conducted in patients outside the U.S. and will present the results at ASCO.

Led by top experts in BRCA-associated breast cancer from around the world, the OlympiA trial's co-chairs were Charles E. Geyer, Jr., M.D., a breast medical oncologist and deputy director of the Houston Methodist Cancer Center, Judy E. Garber, M.D., M.P.H., of the Dana-Farber Cancer Institute, and Bella Kaufman, M.D., of the Sheba Medical Center in Israel. Geyer was the principal investigator on the NCI-sponsored portion of the study conducted in the U.S.

"OlympiA represents a successful global collaboration among leading international academic breast cancer research groups, cancer genetics experts, the National Cancer Institute and pharmaceutical industry partners to evaluate the efficacy and safety of olaparib to address the unmet need for improved therapy for individuals with high-risk, BRCA mutation-associated early breast cancer," said Geyer, who also is a professor of medicine in oncology with the Houston Methodist Research Institute and has provided scientific leadership on the trial since 2013.

The OlympiA trial was a tremendous effort recruiting 1,836 patients from 420 centers across 23 countries. A randomized double-blind phase 3 trial, OlympiA was designed to test the efficacy of the Poly(ADP-ribose)-polymerase (PARP) inhibitor drug olaparib and showed that it significantly improved invasive and distant disease-free survival when given for 52 weeks following the completion of such standard therapies as chemotherapy, surgery and radiation.

Patients were recruited from June 2014 through May 2019, and patients who consented to participate were randomly assigned to receive olaparib or a placebo. After three years following initiation of treatment with olaparib, 85.9% of patients were alive and free of recurrent, invasive breast cancer and new second cancers, compared with 77.1% of patients who received a placebo. During this same timeframe, 87.5% of patients receiving olaparib were alive and free of distant metastatic disease, compared to 80.4% on the placebo.

While olaparib was also associated with 27 fewer deaths than those on placebo, researchers say longer blinded follow up is required to assess the impact of this therapy on overall survival. What is certain, say researchers, is that germline BRCA1 and BRCA2 sequencing is becoming an important biomarker for the selection of systemic therapy in early breast cancer.