Body

With the COVID-19 pandemic taking a disproportionate toll on low-income people of color, a research team headed by Marya Gwadz of the Silver School of Social Work at New York University set out to understand the ways the pandemic may put individuals at risk for adverse outcomes, and the ways they successfully adapted to and coped with the emerging pandemic, focused on those from low-socioeconomic status backgrounds who have lived with HIV for a decade or longer.

The team's newly published study explores the effects of COVID-19 on engagement in HIV care, HIV medication use and overall wellbeing during the early stages of the pandemic through a structured assessment of 100 low-income Black and Latino individuals who have lived with HIV for 17 years on average. In-depth interviews were conducted with 26 of these long-term HIV survivors.

The lead author, Marya Gwadz, is professor and associate dean for research at the Silver School of Social Work and head of the Intervention Innovations Team Lab (ITT-Lab), which carried out this research She is also an associate director in the Transdisciplinary Research Methods Core in the Center for Drug Use and HIV Research (CDUHR) at the NYU School of Global Public Health.

The study was published online by Springer Nature.

"We were interested in risks but also in identifying 'indigenous coping strategies' and gaps that could be addressed for better future preparedness in times of crisis," Gwadz explained. "We define these as effective ways of managing health and wellbeing in the time of COVID-19 that emerge from the community, but are not necessarily strategies that researchers or experts would have come up with."

Among the findings:

Participants were early adopters of COVID-related public health recommendations such as social distancing, and also sophisticated in their approach to gathering and interpreting public health information from various sources. Trust in local sources of information was higher than trust in various federal sources.

Their experiences with and knowledge gleaned from the HIV pandemic and living in poverty were often applied to managing COVID-19. For example, participants knew how to "hustle" for food and other resources, and they frequently shared these resources with others in their community. However, the need to hustle, rather than being able to remain at home, placed them at heightened risk of exposure to COVID-19.

HIV care visits were commonly canceled as a result of the risk factors occasioned by the COVID-19 pandemic, such as inadequate access to some forms of telehealth, and food insecurity -- "but, overall, engagement in HIV care and antiretroviral therapy use were not seriously disrupted." Similarly, substance use treatment appointments and supports including 12-step meetings were initially cancelled and eventually switched to a virtual platform, although not all participants could access these services.

Most had cell phone or internet service (but not both) through the "Obama Phone" program (that is, the Federal Lifeline Assistance program), and generally did not have the equipment, access or technical skills to attend telehealth appointments. Enhancing the Federal Lifeline Assistance program and providing technical training and support are needed to prevent this same problem from arising in future crises.

The early stages of the COVID-19 pandemic coincided with the re-emergence of the racial justice movement. Participants drew a direct line between structural racism and the disproportional adverse effects of COVID-19 on communities of color, to similar racial/ethnic disparities in HIV prevalence and morbidity and mortality associated with the HIV pandemic.

The study also examines implications for future crisis preparedness, including how the National AIDS/AIDS Strategy can serve as a model to prevent COVID-19 from becoming "another pandemic of the poor."

Philadelphia, February 22, 2021 - Runt-related transcription factor 1 (RUNX1) has been linked to retinal neovascularization and the development of abnormal blood vessels, which result in vision loss in diabetic retinopathy. Now, scientists have found that RUNX1 inhibition presents a new therapeutic approach in the treatment of age-related macular degeneration (AMD), which is the leading cause of blindness in the elderly worldwide. Their results are reported in The American Journal of Pathology, published by Elsevier.

Abnormal growth of blood vessels, or aberrant angiogenesis, arises from the choroid, a part of the eye located behind the retina. This condition, known as choroidal neovascularization (CNV), is present in several ocular diseases that lead to blindness such as AMD. This study is the first to implicate RUNX1 in CNV and to test RUNX1 inhibition therapy for treating CNV. Researchers found that application of a RUNX1 inhibitor, alone or in combination with a standard treatment for AMD, may represent an important therapeutic advance.

"Incomplete response to anti-vascular endothelial growth factor (VEGF) drugs is a critical problem that hinders visual outcomes in CNV. RUNX1 represents a promising therapeutic target that may help address current limitations of anti-VEGF therapy," explains first author Lucia Gonzalez-Buendia, MD, a retina specialist at Puerta de Hierro-Majadahonda University Hospital (Spain), former postdoctoral fellow at the Schepens Eye Research Institute of Mass Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.

Researchers induced CNV lesions in mice. Immediately thereafter the mice received a single intravitreal injection of saline, aflibercept (a Food and Drug Administration-approved treatment for VEGF), the RUNX1 inhibitor Ro5-3335, or a combination of Ro5-3335 and aflibercept. A single intravitreal injection of Ro5-3335 alone significantly decreased the CNV lesion size seven days after induction of the CNV lesions. The combination of Ro5-3335 and aflibercept reduced vascular leakage more effectively than aflibercept alone.

"RUNX1 inhibitors hold significant promise to complement or replace anti-VEGF therapies for patients in which anti-VEGF therapy is no longer effective, and with the potential to be administered topically it could be transformative in the field," suggests co-lead investigator Joseph F. Arboleda-Velasquez, MD, PhD, Assistant Scientist, Schepens Eye Research Institute of Mass Eye and Ear, and Assistant Professor of Ophthalmology, Harvard Medical School, Boston, MA, USA.

RUNX1 was detected in all cell types studied that are known to be involved in CNV pathogenesis, suggesting that RUNX1 inhibition may target not only angiogenesis, but also other processes important in CNV pathogenesis such as inflammation and fibrosis. It has the potential to impact a wide variety of ocular diseases including AMD, diabetic retinopathy, retinopathy of prematurity, retinal vein occlusions, and other angiogenic diseases of the eye.

"Demonstrating the potential of RUNX1 inhibition for the treatment of CNV beyond anti-VEGF therapy presents a unique approach for the treatment of exudative age-related macular degeneration and suggests the importance of future studies to test its efficacy in patients," concludes co-lead investigator Leo A. Kim, MD, PhD, Assistant Scientist, Schepens Eye Research Institute of Mass Eye and Ear, and Assistant Professor of Ophthalmology, Harvard Medical School, Boston, MA, USA.

Current treatment for AMD is invasive and loses efficacy over time. Patients are given multiple injections of anti-VEGF drugs into the eye. Around half of all patients report persistent retinal fluid arising from leaky blood vessels despite chronic treatment, which carries a substantial burden for these patients as well as the health system.

Understanding how the immune system responds to acute brain hemorrhage could open doors to identifying treatments for this devastating disease. However, up until now, there has been limited information on inflammation in the brain from human patients, especially during the first days after a hemorrhagic stroke.

This led a team of researchers to partner with a large clinical trial of minimally-invasive surgery to tackle defining the human neuroinflammatory response in living patients.

"Our goal was to find out, for the first time, how certain key cells of the immune system are activated when they enter the brain after a hemorrhage and how this may shift over the first week. This is a critical time for our patients," said Lauren Sansing, MD, Academic Chief of Stroke and Vascular Neurology and Associate Professor of Neurology and Immunobiology at Yale.

The study, published in Science Immunology, was led by an interdisciplinary team of researchers including Sansing and Michael Askenase, PhD, Associate Research Scientist (both of Yale), and MIT scientists Alex Shalek, PhD, J. Christopher Love, PhD, and Brittany Goods, PhD. Using RNA-sequencing, they found that CD14+ macrophages and neutrophils change rapidly in the brain over the first few days after the hemorrhage. They were also able to find signatures in the macrophages that were consistent in patients with good recovery.

According to the American Heart Association, intracerebral hemorrhage (ICH) makes up approximately 13% of all stroke cases. It occurs when a blood vessel bursts and releases blood into the brain, damaging the surrounding brain tissue. The mortality rate is up to 40%, most survivors are left with some disability, and there is no cure.

ICH generates an acute local immune response within and around the hematoma. Researchers have predicted that inhibiting this inflammation may improve patient outcomes, but so far haven't identified cellular and molecular targets that have been effective therapies in patients.

The study's research team partnered with the MISTIE III surgical trial, which implemented a minimally invasive surgery wherein tissue plasminogen activator (tPA) was administered via a small catheter to liquify the clot and allow drainage of blood from the brain over several days. The blood clots were shipped daily from hospitals around the nation to the Sansing Lab.

According to Dr. Askenase, "We used the detailed patient outcome measures collected by MISTIE III to identify key molecular circuits within CD14 monocytes/macrophages that correlated with good neurological outcomes, thereby uncovering potential mechanisms by which these cells may help contribute to patient recovery. In particular, we found that these cells preferentially use glycolytic metabolism to generate a key anti-inflammatory lipid known as prostaglandin E2 that, if it activates the right receptor, may have broad pro-recovery effects not only on neighboring immune cells, but also on brain-resident neurons and glia."

This could allow physicians to target the brain's immune response to ICH and unlock new treatment options for an otherwise deadly form of stroke, although further research is needed to study these pathways.

A study of this breadth demanded collaboration and coordination.

"This project could only be done with great team work across many institutions," said Dr. Sansing.

Dan Hanley, MD and the MISTIE III trial leadership, the coordination with the trial substudies through MTI:M3, the trial investigators and clinical coordinators nationwide who collected the samples and all the scientific collaborators were key to the study success. The investigators thank the patients and families who took part in the study.

"I'm proud to be a part of one of the leading ICH research teams in the country. The ability to learn deeply from surgical samples opens the door for exciting new avenues in ICH research," said Charles Matouk, MD, Chief of Neurovascular Surgery at Yale and the MISTIE III co-site PI and collaborator on the research.

The study serves as a model for future studies to leverage a brain hemorrhage clinical trial to gain significant insight into the fundamental mechanisms of the disease and provide a more targeted approach to treating ICH.

February 22, 2021 - Widely used medications for benign prostatic hyperplasia (BPH) - also known as enlarged prostate - may be associated with a small, but significant increase in the probability of developing heart failure, suggests a study in The Journal of Urology®, Official Journal of the American Urological Association (AUA). The journal is pub lished in the Lippincott portfolio by Wolters Kluwer.

The risk is highest in men taking a type of BPH medication called alpha-blockers (ABs), rather than a different type called 5-alpha reductase inhibitors (5-ARIs), according to the new research by D. Robert Siemens, MD, and colleagues of Queen's University, Kingston, Ont., Canada. "While no one should stop taking their BPH medications based on these results, our study contributes new evidence for understanding the complex interaction of factors affecting heart disease risk in men with BPH," Dr. Siemens comments.

Do BPH drugs affect heart failure risk? New long-term, follow-up data

Benign prostatic hyperplasia is a very common condition in men, especially at older ages. It occurs when the prostate gland becomes enlarged, causing urinary symptoms (such as frequent and difficult urination). Millions of men take medications to reduce BPH symptoms - most commonly ABs, 5-ARIs, or a combination of the two.

Both BPH and cardiovascular disease are common in older men, which may reflect shared risk factors or causes. Clinical trials have suggested that men taking ABs or 5-ARIs might be more likely to develop heart failure: a chronic condition where the heart can't pump enough blood to keep up with demand. However, other studies have found no such link.

To clarify the association between BPH medications and heart failure, Dr. Siemens and colleagues used Ontario health data to identify more than 175,000 men diagnosed with BPH. About 55,000 patients were being treated with ABs alone, 8,000 with 5-ARIs alone, and 41,000 with a combination of ABs and 5-ARIs. The rest were not taking either type of BPH medication.

On analysis of follow-up data, men treated with ABs and/or 5-ARIs were more likely to be diagnosed with heart failure. The risk of developing heart failure were increased by 22 percent in men taking ABs alone, 16 percent for those taking combination therapy, and 9 percent for those taking 5-ARIs alone, compared to the control group of men not taking BPH medications. The associations were significant after adjusting for other characteristics, including heart disease risk factors.

Heart failure risk was higher with older "nonselective" ABs compared to newer "selective" ABs. Risk was higher in men taking ABs for a prolonged time: 14 months or longer.

Dr. Siemens and coauthors emphasize that while the increased probability of developing heart failure was statistically high, the absolute risk was relatively low. Risk factors such as previous heart disease, high blood pressure and diabetes had a much greater impact on heart failure risk compared to BPH medications. The researchers also note the control group of patients not taking 5-ARIs or ABs may have had less severe BPH symptoms, with possible differences in heart disease risk factors.

"Our study suggests men taking ABs and/or 5-ARIs are more likely to be diagnosed with heart failure," Dr. Siemens comments. "This is an important finding, given that BPH is so common among older men, and that these medications are so widely used."

Dr. Siemens adds: "Since men with BPH may continue these medications for several years, it is important physicians be aware of this risk, including both primary care physicians and urologists, perhaps especially in patients with previous heart disease or cardiovascular risk factors."

Long before COVID-19 entered the picture, West Virginia had been battling two other major public health crises: opioids and HIV.

Dr. Sally Hodder, a leading infectious disease expert at West Virginia University, believes that despite the threat of COVID-19, the opioid and HIV epidemics should not be ignored. The two have become so intertwined in the Mountain State, that they must be treated together, she said.

"We cannot try to solve the opioid epidemic or our emerging HIV epidemic by combating them separately," said Hodder, who serves as director of the West Virginia Clinical and Translational Science Institute and associate vice president for clinical and translational research at WVU. "Since they are both so interconnected, we have to look at this as one larger issue, and treat it as such."

Hodder was recently published, along with WVU colleague and professor Judith Feinberg, in a Lancet series focused on the ongoing challenges to ending HIV. These challenges include racial, sexual and gender disparities; gaps in domestic HIV program funding; and a lack of access to treatment and prevention services. The Lancet is the world's oldest peer-reviewed general medical journal.

Hodder and Feinberg noted that while West Virginia has a variety of barriers (economic hardships, limited access to healthcare and treatment services) to combating these intertwined epidemics, one of the biggest obstacles that must be addressed is stigma.

"We won't be able to end the co-epidemics of HIV and opioids until we reduce the stigma associated with both substance abuse and HIV, especially in rural areas that may be suboptimally equipped to deal with these issues in the first place," Hodder said. "In places such as West Virginia, where the collapse of the coal mining industry and extreme poverty have exacerbated the opioid epidemic, decriminalizing substance abuse, providing clean, safe places for syringe service programs and other interventions, and offering comprehensive HIV prevention, care and treatment services are all essential to ending these intertwined epidemics."

West Virginia continues to lead the nation in drug overdose death rates at 51.5 per 100,000, according to the most recent Centers for Disease Control and Prevention data.

While West Virginia and Appalachia have historically seen very low HIV rates, the number of individuals who inject drugs has skyrocketed. This opioid epidemic-related transmission has led to multiple HIV clusters that have not been seen in the past.

"West Virginia has had HIV outbreaks across the southern coalfields, then in Cabell County, and most recently, in Kanawha County," said Dr. Feinberg, vice chair of research and professor, WVU School of Medicine. "In 2020, there were 37 new HIV diagnoses in Kanawha County compared to 38 in 2019 in all of New York City, leading the Centers for Disease Control and Prevention to say that this outbreak was currently their highest concern."

"What we saw in previous HIV outbreaks was that people lived in more urban areas," Hodder said. "This afforded them greater access to medical care and harm reduction services. These are things that are huge challenges in Appalachia. Geographical barriers may make finding and traveling to medical care and syringe services more difficult."

This is not the first time Hodder has fought HIV. After completing her medical training, she worked in Kenya and witnessed the emergence of AIDS in Africa. Hodder also spent 9 years running an HIV program in Newark, New Jersey, an area that at the time had an almost 3% HIV positive rate.

While there is still a lot of work to be done to combat these issues, Hodder remains hopeful.

"I have seen firsthand what communities can do together when people from multiple constituencies are part of the conversation," Hodder said. "Let's continue the great work that is ongoing in many West Virginia communities to provide necessary care, treatment and access to harm reduction that are all necessary to tackle HIV."

DALLAS - Feb. 22, 2021 - Three decades-old antibiotics administered together can block a type of pain triggered by nerve damage in an animal model, UT Southwestern researchers report. The finding, published online today in PNAS, could offer an alternative to opioid-based painkillers, addictive prescription medications that are responsible for an epidemic of abuse in the U.S.

Over 100 million Americans are affected by chronic pain, and a quarter of these experience pain on a daily basis, a burden that costs an estimated $600 billion in lost wages and medical expenses each year. For many of these patients - those with cancer, diabetes, or trauma, for example - their pain is neuropathic, meaning it's caused by damage to pain-sensing nerves.

To treat chronic pain, prescriptions for opioid painkillers have increased exponentially since the late 1990s, leading to a rise in abuse and overdoses. Despite the desperate need for safer pain medications, development of a new prescription drug typically takes over a decade and more than $2 billion according to a study by the Tufts Center for the Study of Drug Development, explains study leader Enas S. Kandil, M.D., associate professor of anesthesiology and pain management at UTSW.

Seeking an alternative to opioids, Kandil and her UT Southwestern colleagues - including Hesham A. Sadek, M.D., Ph.D., professor of internal medicine, molecular biology, and biophysics; Mark Henkemeyer, Ph.D., professor of neuroscience; Mahmoud S. Ahmed, Ph.D., instructor of internal medicine; and Ping Wang, Ph.D., a postdoctoral researcher - explored the potential of drugs already approved by the Food and Drug Administration (FDA).

The team focused on EphB1, a protein found on the surface of nerve cells, which Henkemeyer and his colleagues discovered during his postdoctoral training nearly three decades ago. Research has shown that this protein is key for producing neuropathic pain. Mice genetically altered to remove all EphB1 don't feel neuropathic pain, he explains. Even mice with half the usual amount of this protein are resistant to neuropathic pain, suggesting EphB1's promise as a target for pain-relieving drugs. Unfortunately, no known drugs inactivate EphB1.

Exploring this angle further, Ahmed used computer modeling to scan a library of FDA-approved drugs, testing if their molecular structures had the right shape and chemistry to bind to EphB1. Their search turned up three tetracyclines, members of a family of antibiotics used since the 1970s. These drugs - demeclocycline, chlortetracycline, and minocycline - have a long history of safe use and minimal side effects, Ahmed says.

To investigate whether these drugs could bind to and inactivate EphB1, the team combined the protein and these drugs in petri dishes and measured EphB1's activity. Sure enough, each of these drugs inhibited the protein at relatively low doses. Using X-ray crystallography, Wang imaged the structure of EphB1 with chlortetracycline, showing that the drug fits neatly into a pocket in the protein's catalytic domain, a key portion necessary for EphB1 to function.

In three different mouse models of neuropathic pain, injections of these three drugs in combination significantly blunted reactions to painful stimuli such as heat or pressure, with the triplet achieving a greater effect at lower doses than each drug individually. When the researchers examined the brains and spinal cords of these animals, they confirmed that EphB1 on the cells of these tissues had been inactivated, the probable cause for their pain resistance. A combination of these drugs might be able to blunt pain in humans too, the next stage for this research, says Kandil.

"Unless we find alternatives to opioids for chronic pain, we will continue to see a spiral in the opioid epidemic," she says. "This study shows what can happen if you bring together scientists and physicians with different experience from different backgrounds. We're opening the window to something new."

Eating a low quality diet, high in foods and food components associated with chronic inflammation, during pregnancy may be associated with an increased risk of obesity and excess body fat in children, especially during late-childhood. The findings are published the open access journal BMC Medicine.

Researchers from University College Dublin, Ireland found that children of mothers who ate a higher quality diet, low in inflammation-associated foods, during pregnancy had a lower risk of obesity and lower body fat levels in late-childhood than children whose mothers ate a lower quality diet, high in inflammation-associated foods, while pregnant. This association was not observed in early or mid-childhood.

Ling-Wei Chen, the corresponding author said: "Obesity in childhood often carries on into adulthood and is associated with a higher risk of chronic diseases, including type 2 diabetes. Mounting evidence suggests that maternal diet influences pregnancy and birth outcomes and points to the first one thousand days of a child's life, from conception to two years old, as a critical period for preventing childhood obesity. Our research indicates that children born to mothers who eat a low-quality diet, high in inflammation-associated foods, during pregnancy may be more likely to have obesity or excess body fat in late childhood than those born to mothers who eat a high-quality diet low in inflammation-associated foods."

To examine the effects of maternal diet on the likelihood of childhood obesity and excess body fat, the authors analysed data collected from 16,295 mother-child pairs in seven European birth cohort studies, from Ireland, France, United Kingdom, Netherlands and Poland, which are involved in the ALPHABET consortium. On average, mothers were 30 years old and had a healthy BMI. Mothers reported the food they ate before and during pregnancy. The researchers assessed dietary quality and whether diets were high in foods and food components associated with chronic inflammation, such as saturated fat, refined carbohydrates and red and processed meat. Children's BMI was calculated in early, mid and late childhood. Additional data on children's body composition during mid or late childhood was collected in five of the cohorts included in the study.

The researchers found that children born to mothers who ate diets high in foods associated with inflammation throughout pregnancy tended to have lower levels of fat-free body mass, indicating lower levels of muscle mass, in late-childhood than those whose mothers ate diets low in inflammation-associated foods. Previous research has found that low levels of muscle mass may be associated with a higher risk of combined diabetes, high blood pressure and obesity

An association between a lower quality maternal diet, high in inflammation-associated foods, and lower levels of fat-free body mass in late-childhood was found to be stronger in boys than in girls. An association between lower quality maternal diet, high in inflammation-associated foods, and higher body fat levels in mid-childhood was stronger in girls than in boys.

Catherine Phillips, the principal investigator and coordinator of the ALPHABET project said: "Previous research has suggested that lower maternal carbohydrate intake in early pregnancy can induce epigenetic changes - that is changes which alter gene expression - in children that may be associated with an increased risk of obesity. We propose that a lower quality maternal diet, high in inflammation-associated foods, may similarly induce epigenetic changes and that this may increase the risk of children having obesity or excess body fat in later childhood. Our findings suggest that promoting an overall healthy diet, high in fruit and vegetables and low in refined carbohydrates and red and processed meats, throughout pregnancy may help prevent childhood obesity."

The authors caution that the observational nature of the study does not allow for conclusions about a causal relationship between maternal diet and childhood obesity and excess body fat. Future research should account in more detail for other factors that could influence the risk of obesity in childhood, such as childhood physical activity and diet, according to the authors.

Scientific strides in HIV treatment and prevention have reduced transmissions and HIV-related deaths significantly in the United States in the past two decades. However, despite coordinated national efforts to implement HIV services, the epidemic persists, especially in the South. It also disproportionately impacts marginalized groups, such as Black/African-American and Latinx communities, women, people who use drugs, men who have sex with men, and other sexual and gender minorities. Following the release of the HIV National Strategic Plan and marking two years since the launch of the Ending the HIV Epidemic: A Plan for America (EHE)--a U.S. Department of Health and Human Services initiative to reduce new HIV transmissions by at least 90% by 2030--researchers, advocates, and other stakeholders reported on the HIV epidemic response in The Lancet HIV in the USA Series, published online today.

Literature reviews, commentaries, and data analyses in the series outline recommendations to overcome barriers to implementing HIV services, such as counseling, testing, treatment, pre-exposure prophylaxis (PrEP), and syringe services programs. These services are critical to preventing new HIV transmissions and helping people living with HIV achieve and maintain a "durably undetectable" viral load (the amount of HIV in the blood). Maintaining an undetectable viral load both preserves individual health and eliminates the risk of sexually transmitting the virus to others, a concept known as Undetectable = Untransmittable (U=U). By leveraging these services and addressing structural barriers, the experts argued, the EHE goals remain attainable and important, even as the COVID-19 pandemic presents new challenges and exacerbates existing health disparities.

The series was funded in part by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health within HHS. The authors received additional support from the NIH-funded Centers for AIDS Research and NIH's National Institute of Allergy and Infectious Diseases (NIAID).

"Scientific advances have transformed the course of HIV in individuals. To transform the course of the epidemic, we need to expand care and prevention strategically to those who need it most," said NIDA Director Nora D. Volkow, M.D. "That means taking a hard look at who has been excluded from services and take immediate steps to overcome systemic barriers like stigma, structural racism, and other forms of discrimination to connect hardly reached people--such as individuals with substance use disorders--with HIV testing, prevention, and treatment."

The series' authors recommend allocating resources to the areas and populations most hard-hit by the HIV epidemic, especially the U.S. South, where 52% of new HIV transmissions occurred in 2018 despite being home to only 37% of the U.S. population. The recommendation echoes a key EHE strategy to prioritize the 57 counties, U.S. territories, and states in which more than half of U.S. HIV transmissions occurred in 2016 and 2017 for targeted interventions.

"To end the HIV epidemic, we must continue to develop and deploy novel HIV treatment and prevention strategies suited to the different needs and preferences of diverse populations disproportionately affected by HIV," says NIAID Director Anthony S. Fauci, M.D. "It is also essential that HIV health services continue during the COVID-19 pandemic."

The authors explained that stark disparities in HIV outcomes also exist between certain age, racial, and ethnic groups, as well as between sexual and gender identities. While HIV diagnoses decreased overall and among white men who have sex with men between 2009 and 2018, new cases remained stable among Black/African-American men who have sex with men and increased among young people aged 25-34 and Latino men who have sex with men. While Blacks/African Americans make up only about 13% of the U.S. population, they accounted for 43% of HIV-related deaths in 2018. Researchers suggested that culturally appropriate, tailored interventions may help communities respond to the unique needs of people in--or at the intersections of--these groups.

Such interventions to promote HIV prevention and treatment adherence, the authors suggested, should take a multi-faceted approach and address the whole individual.

"We have incredible tools to prevent and treat HIV, but people may not fully utilize them if they are facing personal or structural issues that pose more immediate hardship like substance use and mental health disorders," said Chris Beyrer, M.D., M.P.H., investigator at the Johns Hopkins Bloomberg School of Public Health, Baltimore, and a lead author on the series. "You may struggle to take a daily medication if you are facing food insecurity or cannot find affordable treatment for your substance use disorder."

The authors detailed additional economic barriers to accessing HIV health services in the United States. These included unequal access to Medicaid, on which 40% of people living with HIV rely, depending on one's state of residence. The series' authors recommended implementing universal healthcare coverage and expanding safety net programs for the uninsured or underinsured, such as the Ryan White HIV/AIDS Program, on which 82% of uninsured people living with HIV rely for medical care.

Stigma, discrimination, and bias by healthcare providers were among major barriers to care identified by the series authors and disproportionately affected marginalized racial groups, people who use drugs, and sexual and gender minorities. Healthcare professionals may help address these concerns by cultivating informed, supportive care practices that integrate mental health care and substance counselling. Because internalized HIV stigma can also negatively affect a person's mental health and adherence to medication, the authors recommended promoting awareness of U=U through a national campaign.

While the series' authors cite a large body of HIV research in making these recommendations, they also highlighted opportunities for additional research that could help end the HIV epidemic. Women make up one out of every four people living with HIV in the United States, and rates of HIV transmission are high among transgender people, demonstrating the need for continued efforts to ensure the needs of these populations are taken into account at all stages of clinical research. The authors also supported continued investment in efforts to develop a preventive HIV vaccine and HIV cure, both of which would accelerate an end to the HIV epidemic in the U.S. and around the globe.

People who are racial, sexual, and gender minorities continue to be affected by HIV at significantly higher rates than white people, a disparity also reflected in the COVID-19 pandemic.

The US HIV epidemic has shifted from coastal, urban settings to the South and rural areas.

Despite its role as the largest funder for HIV research and global AIDS programs worldwide, the USA has higher rates of new HIV infections and a more severe HIV epidemic than any other G-7 nation.

Series authors call for a unified effort to curb the HIV epidemic in the USA, including universal health coverage, programs to address disparities in HIV services, and actions to end discrimination and racism in health care.

`The USA continues to lag behind other G-7 nations when it comes to controlling its HIV epidemic and is the only high-income country among the top 10 most HIV-affected countries worldwide. The majority of HIV infections are now concentrated in the South and rural areas, where women and minorities are disproportionately affected; a disparity that has also been seen in the COVID-19 pandemic which has disproportionately affected African Americans, Latinx Americans, Native Americans, and prisoners and detainees.

The USA's inability to control its own epidemic is in stark contrast to its role as the largest global funder of HIV research and AIDS programs worldwide.

In a new six-paper Series published today in The Lancet, authors highlight the ongoing challenges to ending the HIV epidemic in the USA, including racial, sexual, and gender disparities; significant gaps in domestic program funding; and a lack of access to HIV treatment and prevention services due to geography and a patchwork health care system.

The USA failed to meet the ambitious 2020 targets set by the Obama administration's National AIDS Strategy in 2010 [1], and public health efforts have been drastically slowed due to the COVID-19 pandemic, especially for women and minorities. The authors call for significant and sustained public health actions, including continuing to support the Ending the HIV Epidemic (EHE) initiative, which aims to decrease the number of new HIV infections in the USA by 90% within the next 10 years [2].

"The profound racial and gender health disparities brought to light by the COVID-19 pandemic, while alarming, are sadly nothing new, as the HIV epidemic has shown us for more than 40 years," says Dr Chris Beyrer a professor of Public Health and Human Rights in the Johns Hopkins Bloomberg School of Public Health, who led the series.

He continues, "Since the early days of HIV we've seen sexual and gender minorities along with people of color bear the brunt of the epidemic. While the papers in our Series point out the significant advances we've made in developing treatment and prevention measures and highlight how the face of the epidemic has changed demographically and geographically, the one thing that sadly hasn't changed is that the people who need interventions the most are often the ones left out." [3]

Although overall HIV infections in the USA declined by 16% during the past decade, from 44,716 in 2009 to 37,428 in 2018, significant disparities in race, gender, ethnicity, and sexual minorities remain. The risk of HIV infection has increased for Black people, Hispanic people, and men who have sex with men (MSM). And these unequal risks of infection are even greater for populations living in the South and rural areas across the country.

A shifting HIV landscape

The geography of the US epidemic has shifted dramatically and is now most intense in the South, which represents 37% of the US population but 51% of people living with HIV and 47% of new HIV diagnoses in 2018.

People living with HIV in the South are more likely to live in rural areas, creating more challenges in reaching HIV care and prevention services, including pre-exposure prophylaxis (PrEP) services, than people who live in urban or periurban areas. For example, the South has the lowest number of PrEP users per new HIV diagnosis (i.e., PrEP-to-need ratio), at 1.0 compared with 1.8 nationally and more than half of MSM who live at least 60 minutes' drive from PrEP services live in the South. In addition, more than half of the 12 states that have not yet expanded Medicaid, restricting access to both general health care and HIV treatment services, are in the South (Texas, Tennessee, Mississippi, Alabama, Florida, Georgia, South Carolina, and North Carolina).

HIV-related, anti-gay stigma, and suboptimal rates of health literacy in the South also play essential roles in lower access to HIV prevention and treatment services in this area than in other areas of the country.

Disproportionate burden among Black people in the South occurs in both men and women: in 2018, 38% of all new HIV diagnoses among MSM were in the Black population, and 63% of those diagnoses occurred in the South. Similarly, 58% of new HIV diagnoses among women were in the Black population, and 65% of those diagnoses occurred in the South.

"What first started as an epidemic concentrated in large, coastal cities has transformed--becoming increasingly Southern and increasingly rural. As the geography shifts so do other demographics, which accounts for the rise in infections among people of color and other sexual and gender minorities," says series author Dr Patrick Sullivan, a professor of epidemiology in Emory University's Rollins School of Public Health. "It's incredibly important to understand where the epidemic is surging and why so that we can reach these populations with essential HIV services to help keep them healthy and virally suppressed and prevent them from spreading HIV to others." [3]

When race, gender, and place intersect

Geographic disparities are driven by race and ethnicity, with a higher burden of HIV infection among Black people than among individuals of other races or ethnicities. Black people, who represent 13% of the US population have accounted for 41% of the 700,000 total AIDS-related deaths in the USA since the epidemic began. In 2018, Black people accounted for 43% of HIV diagnoses, while Hispanic or Latinx people accounted for 26% of diagnoses (and 18% of the population) and white people for 26% of diagnoses (and 77% of the population).

The Black-white disparity is even more pronounced among women. Although new diagnoses of HIV infections have decreased among women in the USA overall, in 2018 Black women accounted for 58% of HIV diagnoses among women despite being 14% of the US female population.

Women living with HIV include women of reproductive age, older women, and transgender women, who all require unique health interventions, including access to reproductive health services, and access to care for chronic co-morbidities, including obesity, cardiovascular disease, and neurocognitive impairment

Transwomen, especially transwomen of color, report some of the highest HIV burdens, with HIV prevalence substantially higher among transwomen (14%) than among cis women (less than 1%) in the USA. However, many transwomen are unaware of their infection and more than half (51.4%) of seropositive Black transwomen in a study in six US cities had not been diagnosed.

"Women living with HIV are often left out of research and clinical trials, making it that much more challenging to reach them with care and treatment innovations," says series author Dr Adaora Adimora, a professor of Medicine and Epidemiology at the University of North Carolina at Chapel Hill. "We need robust public health reforms to ensure that women not only have access to HIV services but can also access additional crucial support systems such as safe housing, resources to prevent gender-based violence, and the elimination of structural and system racism." [3]

Race, place, and ethnicity also play a key role in new infections among MSM. In 2018, 38% of all new HIV diagnoses among MSM were in the Black MSM population, and 63% of those diagnoses occurred in the South. Although HIV diagnoses among MSM were stable from 2009 to 2018, that stability belies underlying inequities: during that decade, diagnoses among non-Hispanic white MSM decreased by 25%, remained stable among Black MSM, and increased by 20% among Hispanic MSM.

"While MSM have been the face of the AIDS epidemic since the 1980s, the demographics are clearly shifting and as MSM living with HIV are more likely to be Black or Hispanic and live outside of urban centers, and we must find culturally appropriate and nuanced solutions that will reach these populations, no matter where they live," says series author Dr Kenneth Mayer, Medical Research Director of Fenway Health and a professor at Harvard Medical School and Harvard TC Chan School of Public Health. [3]

Intertwined epidemics

The opioid epidemic, especially in the rural area areas such as Appalachia, has become intertwined with the HIV epidemic among people who inject drugs (PWID) and has been associated with large transmission clusters, many in counties with historically low HIV prevalence from sexual contact.

In serial surveys of PWID in 22 metropolitan cities from 2005-15, the racial composition of new PWID changed; the percentage of new Black PWID decreased from 38% to 19%, while new white PWID increased from 38% to 54%. These findings were echoed both in new HIV diagnoses during 2010-16 when HIV diagnoses decreased by 52% among Black PWID and 30% among Hispanic PWID. By 2015, new HIV diagnoses in PWID shifted to people who were predominantly white, were younger than 35 years of age, and who resided in non-urban settings.

Rural communities are especially vulnerable to the opioid and HIV co- epidemics due to reduced access to health care, fewer providers to treat opioid use disorder and HIV, very few harm-reduction programs such as syringe exchanges, overdose education, naloxone distribution, and addiction treatment programs.

Gender differences in PWID are common. Women who inject drugs are 1.2 times more likely to acquire HIV than their male counterparts, often being second to use the needle after their male injection partner. In 2017, women accounted for 28% of new HIV diagnoses among PWID.

"We won't be able to end the co-epidemic of HIV and opioids until we reduce the stigma associated with both substance abuse and HIV, especially in rural areas that are poorly equipped to deal with these issues in the first place," says series author Dr Sally Hodder, rofessor of Medicine and director, West Virginia Clinical and Translational Science Institute, West Virginia University. "In places such as West Virginia, where the collapse of the coal mining industry and extreme poverty have exacerbated the opioid epidemic, this includes decriminalizing substance abuse, providing clean, safe places for syringe exchanges and other interventions, and offering comprehensive HIV prevention, care, and treatment services." [3]

From patchwork coverage to progress

People living with and at risk for HIV seek health services via a patchwork network of payers, providers, and financing mechanisms. People living with HIV are primarily covered by Medicaid (40%), followed by private insurance (35%), with smaller shares covered by Medicare (8%) and other sources (7%), and with 11% uninsured. Many also get care through other programs, particularly the Ryan White HIV/AIDS Program, which serves as the nation's safety net for people with HIV who remain uninsured or underinsured but offers modest or no support for prevention services.

While uninsurance has drastically declined over the past decade thanks to the Affordable Care Act (ACA), the USA trails other high-income countries in key HIV-specific metrics, including rates of viral suppression [4]. And the system remains complex with coverage opportunities varying substantially across the country, leaving many people outside the system.

"Despite the ACA's major expansions, coverage remains uneven across the country, leaving some people with and at risk for HIV outside the system, particularly in the South," says series author Jennifer Kates, Senior Vice President of Global Health and HIV Policy at the Kaiser Family Foundation. "The Obama and Trump administrations developed key targets to curb the epidemic, but the fractured nature of the US health system could make it hard to reach them, particularly for the most vulnerable."
[3]

Series authors conclude that ending the HIV epidemic in the USA will require a unified, national approach that includes universal access to healthcare; reduces geographical, racial, and ethnic disparities in HIV services; and addresses discrimination and racism in health care.

"The USA has shown tremendous leadership in fighting the AIDS epidemic on a global scale, now we must also show that same leadership here at home. We have the innovations and expertise to make it possible, we just need the political will to do it," Beyrer says.

Writing in a linked comment, Dr Errol Fields of the Johns Hopkins University School of Medicine notes, "Policy, public health, clinician, and community stakeholders must prioritise strategies that attend to the social inequities at the intersection of race, gender, class, age, and sexuality that compound the impacts of HIV and COVID-19 in Black communities. The racial disparities that so rapidly emerged with COVID-19 are a reminder that until these inequities are addressed, disparities in HIV and COVID-19 outcomes will persist and ending the HIV epidemic will remain elusive."

SEATTLE -- February 19, 2021 -- A team of scientific experts from across the U.S. and Puerto Rico are advocating for increased diversity in vaccine trials after publishing a new report that highlights a decade's worth of disparities. The new study, published in JAMA Network Open, found that among U.S.-based vaccine clinical trials, people who are Black/African American, American Indian/Alaska Native, Hispanic/Latino and age 65 and older were the most underrepresented groups. Conversely, adult women were overrepresented.

The research team examined 230 U.S.-based vaccine trials of all phases, with nearly 220,000 participants from July 2011 through June 2020. The researchers found that many trials did not fully report demographic information, and for the studies that did, racial and ethnic minorities were frequently underrepresented as were older adults. Top findings from their analysis of the studies that reported demographic information include the following:

White people accounted for 78% of all participants

Women accounted for 56%

Black/African Americans accounted for 11%

American Indians/Alaska Natives accounted for 0.4%

Hispanics/Latinos accounted for 12%

People 65 and older accounted for 12%

Asian and Native Hawaiian/Pacific Islander participants were equitably represented in vaccine trials compared to the U.S. population.

"The COVID-19 pandemic and its devastating impact, particularly on BIPOC (Black, Indigenous and people of color) communities and older adults, is a painful reminder of the health disparities in our country," said Dr. Steve Pergam, an associate professor in the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Research Center and one of the corresponding authors of the study). "This collaborative work highlights a problem that's plagued the scientific community for too long -- inadequate representation in clinical trials. The diversity seen in COVID-19 vaccine trials demonstrate we can do this, but we need to assure future studies focus not just on rapid enrollment but also on inclusion."

The research team also discovered that problems with capturing and underreporting participant demographics remain, despite efforts from the National Institutes of Health and Food and Drug Administration to implement policies and guidelines.

"Going forward, we need to ensure all vaccine studies report demographic information," said Dr. Julie Silver, one of the senior authors on the study and an associate professor at Harvard Medical School in the Department of Physical Medicine and Rehabilitation. "Although we have some missing data, it is clear from the large number of studies which did report this information, that racial and ethnic minorities as well as older individuals are frequently not being equitably represented."

The authors insist improving racial and ethnic diversity in clinical trials is important because enrollment may impact vaccination rates among minorities.

"Vaccine hesitancy and a lack of understanding about safety is a major challenge we're facing with COVID-19," said Dr. Michele Andrasik, a senior staff scientist at Fred Hutch and study co-author who also leads engagement efforts for the COVID-19 Prevention Network. "By improving enrollment diversity, we can better engage these underrepresented groups early in the trials stage and address the education and trust issues."

To address this problem, the National Academies of Sciences, Engineering, and Medicine recently set up a committee dedicated to improving the representation of women and underrepresented minorities in clinical trials and research. Dr. Carlos del Rio, distinguished professor of medicine at Emory University School of Medicine and co-author of the study, is a member of the committee.

The authors also suggest future trials emphasize the inclusion of older men and women. The aging of the population in the US and many other countries requires testing vaccines in older adults. As the current pandemic has shown, diseases like COVID-19 disproportionately impact older adults, especially those in long-term care facilities.

Women of minority races and ethnicities and with less education and income have had relatively lower access to 3D mammography, a technology that can improve breast cancer detection and decrease false alarms, according to research published today.

"This study was about whether adoption of this technology is equitable. We're showing that it has not been, even though it has been FDA-approved for a decade now," said Dr. Christoph Lee, professor of radiology at the University of Washington School of Medicine. "Black and Hispanic women, and less-educated and lower-income women have not been able to obtain 3D mammography as easily as white, well-educated, and higher-income women."

Lee was lead author of the paper, published in JAMA Network Open.

The research team reviewed 2.3 million breast-screening exams collected by the national Breast Cancer Surveillance Consortium, making it the largest-ever study of U.S. access to digital breast tomosynthesis (DBT), commonly called 3D mammography. In February 2011, the Food and Drug Administration approved DBT as an alternative to digital mammography, then the standard of care. Subsequent observational studies have shown that DBT is more accurate than digital mammography by detecting more cancers and yielding fewer false-positive readings.

This study included patients' screening exams from 92 imaging facilities across five states, and spanned January 2011 through December 2017. The researchers analyzed whether the facilities offered DBT onsite at the time of a screening exam, and compared the use of DBT and digital mammography across patient populations at those facilities.

"Given the large research sample and our longitudinal data collection, we were able to evaluate use by minority and traditionally underserved populations," said Diana Miglioretti, Ph.D., professor and division chief of biostatistics at the University of California Davis and senior author on the study. "Unfortunately we were not surprised to find that these traditionally underserved populations were less likely to attend facilities that offered 3D mammography, and even when they did, they were less likely to receive a 3D mammogram."

In 2011, only 3% of women in the study could access DBT at the time of their screening; by 2017, that figure had grown to 82%. Despite facilities' adoption of 3D technology over those seven years, the improved availability was not experienced equally.

When both 2D and 3D mammograms were available onsite at time of screening, DBT was obtained by:

37% of Black women vs. 43% of Asian-American women, 44% of Hispanic women, and 53% of white women

41% of women with less than a high school education vs. 50% of women with a college degree

44% of women living in zip codes with the lowest quartile of median household income vs. 51% of women living in zip codes with the highest quartile of median household income

"These subpopulations of women with poorer access to 3D are already traditionally underserved and more at risk for greater morbidity and mortality from breast cancer," Lee said.

The study did not address whether structural racism in healthcare environments or out-of-pocket costs might contribute to the lower access and use of new technologies among women of minority race/ethnicity. However, these may be real barriers, the researchers said.

"DBT costs more than 2D because it generates digital 'slices' of breast tissue, which take more time to acquire and to interpret," Lee said. "In 2018, Washington state enacted a law requiring facilities not to charge more for 3D screening images and interpretation. So, even if a patient's insurance doesn't cover 3D, they can still get it for the same cost as 2D screening, which is free. But most other states don't have such a law and, depending on a patient's insurance, they may be told that they will have to pay out-of-pocket for the difference."

In assessing education's potential effect, Lee said women with higher achievement might have more opportunity to explore healthcare options and to know about 3D mammography's benefits. They might seek facilities where 3D mammography is available and perhaps even ask for it directly, he suggested.

According to the FDA, more than two-thirds of U.S. screening facilities now offer DBT on at least one of their mammography units, but fewer than half of all certified units are actually DBT-capable.

Perhaps surprisingly, facility location - urban vs. rural - was not found to be a major factor of 3D mammography availability. Lee offered context.

"If there is a rural site that has one digital mammography machine, and they switch to DBT, automatically their entire patient population has DBT access - whereas large, urban facilities may have several mammography units but can only afford to replace one at a time (at a cost of about $750,000 per) to become 3D-capable. More of those patients will still be directed to the 2D technology."

He expressed concern that subpopulations of women are not receiving 3D mammography even when they have that option at their facility at the time of screening.

"We're going in the wrong direction. You have a lot more women in certain subpopulations benefiting from new technologies and other subpopulations not. Existing disparities in breast cancer screening outcomes could widen unless these factors are addressed," he said.

Health insurers that have so far taken "stalwart" positions toward covering 3D mammography have an opportunity to make a meaningful difference to underserved women, he added.

When can tuberculosis therapy be stopped without risk of relapse? Doctors are faced with this question time and again, because the lack of detection of the tuberculosis pathogen Mycobacterium tuberculosis is no guarantee for a permanent cure of the lung infection. Patients who respond to the standard therapy may be out of treatment after six months. But for resistant cases, more than 18 months of treatment duration is currently advised. "This is a very long time for those affected, who often have to take more than four antibiotics every day and suffer from side effects", explains Prof. Dr. Christoph Lange, Clinical Director at the Research Center Borstel and director of the study, conducted at the German Center for Infection Research (DZIF) in cooperation with the German Center for Lung Research (DZL). "We urgently need a biomarker that enables the implementation of an individualised treatment duration," he emphasises. After all, not every patient needs so long to recover.

Since the absence of bacteria in the sputum does not justify a safe stop in therapy, the team around Christoph Lange set out to find alternative biomarkers in the patient. In collaboration with international tuberculosis centres, on the basis of patient cohorts a model for the end of therapy could be developed that is based on an RNA determination in the blood. From many thousands of genes, 22 have been identified whose activity correlates with the course of the disease. "The production of RNA of these 22 genes in human blood can tell us whether the patient is cured," PD Dr Jan Heyckendorf from the FZ Borstel sums it up. Together with Maja Reimann and Dr Sebastian Marwitz, he is the lead author of the study. "It is an RNA signature from 22 genes identified on two cohorts and validated on another three cohorts," adds the scientist. "No other published transcriptom marker shows comparable properties so far."

To identify this individual biomarker, the scientists within the DZIF have established five different patient cohorts. In all cases, these were adults who had contracted pulmonary TB, partly from non-resistant, partly from resistant forms. In addition to cohorts in Germany, patients in Bucharest (Romania) were also included, where the DZIF supports a study centre.

"The individualisation of the treatment duration is an important milestone on the road to precision medicine for tuberculosis," affirms Christoph Lange. Even without progression values, one could risk to end a patient's treatment on the basis of this RNA determination. As a next step, the researchers are planning a prospective study at the DZIF. The aim is for patients in one study arm to receive treatment for as long as the biomarker suggests, while patients in the other arm receive treatment for as long as the national tuberculosis programme recommends. The scientists then want to see whether the biomarker makes a shorter treatment duration possible. The team around Christoph Lange is confident.

"Hopefully, it will then be possible for patients with multidrug-resistant tuberculosis to save about one-third of treatment on average," says Lange.

Parent education programs and interventions that begin shortly after the birth of a child have shown to significantly impact parenting behaviors that support social and academic engagement for children growing up in poverty, according to a study led by pediatricians and psychologists across the country, including NYU Grossman School of Medicine, NYU Steinhardt, and the University of Pittsburgh.

The study, published today in the journal Pediatrics, examines the Smart Beginnings Project, a first-of-its-kind comprehensive approach to the promotion of school readiness in low-income families. This model addresses one of the most important causes of inequity - that many children from low-income families start school behind and may never catch up.

"Lack of opportunities for pretend play and children's book reading leaves children, particularly those in poverty, less prepared for learning, less healthy, and is even linked with lower income throughout their lives," said Alan Mendelsohn, MD, professor in the departments of Pediatrics, Population Health, and the division of Developmental-Behavioral Pediatrics at NYU Grossman School of Medicine, and one of the study's principal investigators. "Smart Beginnings provides a practical approach for helping all children have an equal start in school and in life."

Smart Beginnings addresses these longstanding challenges by integrating the Video Interaction Project (VIP), reaching families during routine pediatric check-ups, with a second targeted program, Family Check-Up (FCU) during at-home visits for families identified as having additional risks and challenges.

The VIP is provided to families at the child's well visit early in infancy. During the session, a trained parenting coach meets with the family, provides a children's book or toy, and records a brief video of the parent and child reading or playing. The video is watched together in real-time to support family strengths and goals. This process strengthens relationships between parents and children during this critical period for brain development in children from birth to three years of age.

The second, targeted program, FCU, is home-based and family-centered for those found to have added risks and challenges. FCU helps families see their strengths and think about their challenges. The program uses clinical-level guidance tailored to the family's needs and goals to provide additional support to families who need it.

What the Study Showed

The two-site study replicates and extends prior VIP findings across racially and ethnically diverse families in New York City and Pittsburgh.

The results of the study showed large increases in parents' engaging their children in reading, playing and talking, measured by surveys and observing parents reading and playing with their children. Comparable impacts across the two sites supports the feasibility for parents from diverse geographic locations and racial/ethnic background to improve parent-child interactions. The study also supports bringing this model "to scale" as an inexpensive solution for reaching families in need.

"One clear advantage of providing parents with a program like the Smart Beginnings project is that it can be delivered at about one-tenth of the cost of other programs with comparable impacts," said lead author Erin Roby, PhD, developmental psychologist and research scientist at NYU Grossman School of Medicine. "Smart Beginnings' had large impacts, demonstrating that this model has the potential to address some of the most important equity issues of our time."

Researchers conducted a randomized controlled trial at two sites: NYC Health + Hospitals/Bellevue, affiliated with NYU Langone Health, and UPMC Children's Hospital of Pittsburgh. The study enrolled 403 pairs of mothers and children in two phases starting in the postpartum units of NYC Health + Hospitals/Bellevue from June 2015-January 2017 and at UPMC Children's Hospital of Pittsburgh from June 2016-October 2017. Families were then randomly assigned to either the Smart Beginnings project or a control group, which received standard pediatric care.

The study will continue to follow families over time to determine the overall impact of the full Smart Beginnings model, including potential additive impacts of the FCU for families at elevated risk.

Growing Up in a Pandemic: How COVID-19 is Affecting Children's Development

With childcare programs closed and social distancing measures in place, many children are missing out on opportunities for development. Pediatricians have noted delays in speech and language as well as trouble sharing and being in groups.

"Children are not getting the cognitive and social experiences that they would normally get outside their home," said Mendelsohn. "Numerous studies suggest that COVID-19 is causing challenges and stressors for families that will affect children throughout their lives, yet there has been little attention to the effects of the pandemic on families with very young children."

Over the last year, Mendelsohn and the team have adapted the Smart Beginnings model to be delivered fully remote to continue to provide support to families in isolation during the pandemic.

Most recently, VIP has expanded to Flint, Michigan, a community deeply affected by a major crisis when its drinking water was contaminated by lead. The team is prepared for a large-scale implementation of the program nationwide. "Expanding our programs will make a tremendous difference for families facing large challenges that will continue long after the pandemic ends," said Mendelsohn.

A combination of robust vaccination programmes and strict physical distancing rules could avoid recurring peaks of COVID-19 without the need to rely on stay-at-home restrictions, according to a new study by epidemiologists and demographers from WorldPop at the University of Southampton, in collaboration with The Chinese University of Hong Kong.

This research used anonymised mobile phone geolocation data with epidemiological and coronavirus case data from China to model the potential impact of vaccination and physical distancing on virus transmission. They predicted the effect of different combinations of interventions on low, medium and high density cities in the country.

The impact of physical distancing in containing future resurgences of COVID-19 depends greatly on the intensity of measures, population density, and the availability of vaccines across geographical areas and time. The researchers set out to gain a greater understanding of the relationship between these factors.

The findings are published in the journal Nature Human Behaviour.

The team predicts that in most cities, vaccination programmes and physical distancing combined will be enough to contain virus resurgence without the need to greatly restrict population mobility. Containment in this study was defined as maintaining a low transmission rate, or 'R' below one.

The researchers report cities with medium and high density populations will need both vaccination and distancing to prevent future intense waves of COVID-19, until herd immunity is reached. However, they suggest cities with low populations and effective vaccination could fully interrupt transmission without the need for physical distancing. In all cities, full 'stay-at-home' lockdowns would no longer be necessary.

The team's results also suggest strong physical distancing interventions implemented for short periods of time may be more effective than mild, longer term ones.

The author and spatial epidemiologist, Dr Shengjie Lai, Senior Research Fellow in Geography and Environmental Sciences at the University of Southampton comments: "Our research provides a framework and set of outputs that can be used by policy-makers and public health authorities to identify appropriate levels of intervention to keep COVID-19 outbreaks in check over time. Although our study was based on data from China, our methods and findings are applicable to cities worldwide with similar levels of population density and social contact patterns."

Director of WorldPop, Professor Andy Tatem, added: "Previous studies have assumed that when people reduce mobility, they proportionately reduce their social contacts, but this isn't necessarily the case and as more SARS-CoV-2 vaccines come online, there is an urgent need to understand the relationship between these factors, so we can adjust and tailor interventions and open up sections of society in a safer way."

The researchers recognise some limitations to their study, for example, the absence of data on the contribution of handwashing and face masks and challenges of vaccine supply, but emphasise that their approach can be quickly adapted to provide near real-time data to address emerging, time critical needs.

Over 20.5 million years of life may have been lost due to COVID-19 globally, with an average of 16 years lost per death, according to a study published in Scientific Reports. Years of life lost (YLL) - the difference between an individual's age at death and their life expectancy - due to COVID-19 in heavily affected countries may be two to nine times higher than YLL due to average seasonal influenza.

Héctor Pifarré i Arolas, Mikko Mÿrskyla and colleagues estimated YLL due to COVID-19 using data on over 1,279,866 deaths in 81 countries, as well as life expectancy data and projections for total deaths of COVID-19 by country.

The authors estimate that in total, 20,507,518 years of life may have been lost due to COVID-19 in the 81 countries included in this study - 16 years per individual death. Of the total YLL, 44.9% seems to have occurred in individuals between 55 and 75 years of age, 30.2% in individuals younger than 55, and 25% in those older than 75. In countries for which death counts by gender were available, YLL was 44% higher in men than in women. Compared with other global common causes of death, YLL associated with COVID-19 is two to nine times greater than YLL associated with seasonal flu, and between a quarter and a half as much as the YLL attributable to heart conditions.

The authors caution that the results need to be understood in the context of an ongoing pandemic: they provide a snapshot of the possible impacts of COVID-19 on YLL as of 6 January, 2021. Estimates of YLL may be over- or under-estimates due to the difficulty of accurately recording COVID-19-related deaths.