Jared Kaltwasser

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ISIIResults from an early-stage animal study using the CRISPR technique suggest that the gene-editing technology might be useful in eventually developing a cure for HIV.

(clustered regularly interspaced short palindromic repeats) gene-editing platform can be used to disable viruses in animal models. If replicated in humans, it could might move HIV/AIDS from being a “chronic” disease, managed through antiretroviral therapy (ART), to one that could be deemed as cured.

The experiment tested CRISPR as strategy to deal with simian immunodeficiency virus (SIV) in rhesus macaque monkeys. SIV is a frequently used as a model for HIV, although success in animal models by no means is a guarantee that the same approach will work in humans. The investigators first designed an SIV gene-editing construct using the CRISPR-Cas9 tool, and then packaged it into an adeno-associated virus 9 (AAV9) carrier. The construct was programmed to eliminate proviral SIV DNA by distributing editing molecules to cleave and remove fragments of integrated proviral DNA from the genome of infected blood and tissue cells where SIV can hide. It was administered intravenously into the animal subjects.

“We show for the first time that a single inoculation of our CRISPR gene-editing construct,carried by an adeno-associated virus, can edit out the SIV genome from infected cells in rhesus macaque monkeys,” said co-senior investigator Kamel Khalili, Ph.D., of the Lewis Katz School of Medicine at Temple University in Philadelphia, in a press release.

Such viral reservoirs are one of the key barriers to curing HIV, and the construct’s apparent ability to reach those reservoirs is particularly notable, Khalili investigators said.

In the study, Khalili and colleagues explained that while ART can suppress viral replication by essentially stopping the life cycle of the virus, it cannot affect the virus’s integrated proviral DNA. That’s why patients with HIV must remain vigilant against a rebound of HIV by continually taking ART.

“As such, a permanent cure for HIV-1 disease requires, in addition to a pharmacologic approach for prevention of viral propagation and its spread, a genetic strategy to eradicate the silent proviral DNA to the extent that even in the absence of the ART no viremia is detected,” the authors wrote.

The investigators have already shown that a similar CRISPR-based strategy can eliminate HIV DNA from cells and tissues in small animal models infected with HIV.

, Ph.D., of the Tulane University School of Medicine, said the next step in the group’s research is to evaluate the treatment over a longer period of time to see if complete elimination of the virus is possible. If so, it could mean patients could eventually be taken off of ART medication once the CRISPR construct has finished its work. But even if the CRISPR construct does not completely eliminate HIV, it might be slow any kind of rebound of the virus after ART.

Larger studies are in the works. Those studies will be funded in part by Excision BioTherapeutics, a biotech company that Khalili is the scientific founder of.Khalili said the investigators hope to move to clinical studies in humans soon.

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New research by shows how one of the major scientific breakthroughs of recent years might be used to eliminate HIV infection.

CRISPR Gene-Editing Shows Promise Against HIV

As the United States begins what is expected to be the largest mass-vaccination campaign in the country’s history, American optometrists say they are well positioned to play an important role in the effort.

Earlier this month, the American Optometric Association sent a letter 

 urging him not to set federal restrictions on which types of providers can administer the COVID-19 vaccines. Instead, they said, HHS should continue to encourage states to think broadly about who should be included in vaccine administration plans.

, O.D., the association’s president, noted in the letter that optometrists have a wide geographical footprint and are already given the authority to administer vaccines in many states.

“Overall more than 90% of the U.S. Medicare beneficiary population lives within 15 minutes of a doctor of optometry,” Reynolds said. “Doctors of optometry in some states are eligible by their scope of practice to provide vaccinations. Additionally, doctors of optometry in 19 states are already authorized to administer injections.”

In 22 additional states, Reynolds said, doctors of optometry are authorized to provide anaphylaxis through injection.

There are more than 46,000 optometrists in the United States, according to AOA.

However, administrative and other hurdles remain even in states where regulations allow optometrists to administer the vaccine. For instance, although California in passed a law allowing optometrists to administer flu, shingles, and pneumonia vaccines, the state has been slow to process some vaccination administration applications submitted by providers.

, California optometrist Frank Giordana, O.D., noted that he took and passed a 20-hour vaccination administration course two years ago. The state has yet to process his application, he said.

Similarly, Ohio passed legislation letting optometrists and other types of medical professionals administer drugs or vaccines in declared emergencies five year, even if such treatment is normally outside of their scopes of practice. The AOA said it is currently “in the process of reminding state health officials” of this provision, in hopes that they will promote optometrist administration of vaccines as part of their rollouts.

The push for a role in vaccine distribution also comes at a time of upheaval in the optometry industry. At the start of the pandemic, some chains and independent practices 

 or were forced to stop routine care due to local regulations. Even when clinics were open, some patients chose to forego routine exams out of fear of infection.

In its statement, AOA noted that an estimated 60% of patients they treated in the early stages of the pandemic would otherwise have sought care at an emergency department or urgent care clinic. That’s why the association is urging HHS and the CDC to consider optometrists to be front-line healthcare workers. In addition to asking for a role in vaccine administration, the association is asking state and federal public health agencies to prioritize optometrists as they make decisions about who should get the vaccine first.

“While our doctors and their staff will continue to do all they can to address eye and vision care needs in our communities, we believe that ensuring health care workers, including doctors of optometry and their staff, are prioritized for vaccinations in phase 1a is critical to the overall health of our country,” Reynolds wrote.

In its December 3 guidance for states, the CDC says “healthcare personnel” and residents of long-term care facilities should be prioritized in phase 1a. The guidelines do not specifically mention optometrists, but the website’s definition of healthcare personnel is broad, including everyone from doctors and nurses to pharmacists and nonmedical hospital staff.

Optometrists say their wide distribution and medical expertise make them ideal candidates to administer the COVID-19 vaccine. As healthcare workers they also want to be prioritized to receive the vaccine.

Optometrists Push to Help Administer, Receive COVID-19 Vaccine

Social determinants of health (SDOH) have long been a concern of the public health community, but a new study suggests the number, not just the type, of social determinants can be an important risk factor for coronary heart disease (CHD).

, M.D., of Weill Cornell Medicine, and colleagues noted that investigators have developed indices of social deprivation that can be used by physicians to better understand SDOH-based risk.

“However, indices often include characteristics of small geographic areas and may be difficult for clinicians to construct and interpret for their patients during a clinical encounter,” Safford and colleagues wrote.

In light of this difficulty, Safford and colleagues sought to investigate a simpler way of quantifying SDOH risk, focusing not on individual types of determinants, but rather on the total number of them.

The investigators looked at data from the prospective longitudinal Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national study that from 2003-2007 enrolled 30,000 Americans initially with the goal of tracking stroke risk. The study included SDOH data, making it a valuable dataset for Safford and colleagues’ investigation.

The team focused on social factors which have been associated with CHD outcomes and which can easily be ascertained by physicians.

“Education, where they live, whether the area is in a physician shortage area, which state you’re in, how isolated they are socially, their race/ethnicity, their health insurance—all these are recommended parts of the social history,” Safford told 

 “So, in a nutshell, the information we included in the study should be routinely collected as part of high-quality healthcare, albeit indirectly for annual household income.”

The investigators’ analysis cohort yielded 22,152 patients in the REGARDS dataset who did not have CHD at baseline. A majority (58.8%) were women, and 42.0% were black. The cohort was fairly evenly spread in terms of number of SDOH: 20.6% had no SDOH, 30.6% had a single SDOH, 23% had two, and 25.8% had at least three.

At a median follow-up of 10.7 years, 463 fatal incident CHD events were reported, and 932 nonfatal myocardial infarction events were reported.

Adjusted for age, the data showed a clear increase in risk as the number of social determinants increased. For instance, the incidence of fatal CHD per 1,000 person-years was 1.3 for people with 0 SDOH, but 2.86 for people with three or more SDOH. For nonfatal MI, the rate per 1,000 person-years was 3.91 among people with no SDOH, but 5.44 among people with at least two SDOH.

A person with three or more SDOH had a 3 crude HR and a 1.67 fully adjusted HR for fatal incident CHD. For nonfatal MI, the crude HR of a person with two or more SDOH was 1.57 and the adjusted HR was 1.14.

Safford and colleagues concluded that targeted interventions could make a meaningful difference for many patients with SDOH and suggested that population health managers could play a crucial role in these cases.

“In conclusion, a simple count of widely available SDOH may be a novel approach to identify individuals at high risk of incident CHD events that could be used in the course of clinical care,” they said.

The idea that social factors affect health outcomes is not new, but new research suggests total number of social determinants of health is a valuable proxy for coronary heart disease risk.

Number, Not Just Type, of Social Determinants Impacts Cardiovascular Health

A year ago, if you asked anyone outside the healthcare and manufacturing industries what “PPE” was, chances are they wouldn’t have been able to even venture a guess. Now the initialism for “personal protective equipment” has entered the vernacular along with other COVID-19-related terms like “social distancing” and “face mask.”

Common understanding of PPE may have evolved, but the equipment itself —gloves, masks, respirators, gowns — hasn’t changed all that much amid the pandemic. The innovation has occurred mainly in logistics, supply lines and massive increases in production to meet a demand that was beyond imagination not many months ago.

For many manufacturers, keeping up with the demand for PPE has been challenge enough. Tim Post, a spokesperson for 3M, the largest maker of N95 respirator masks, says that at the beginning of this year, most of the orders for the St. Paul, Minnesota, company’s masks came from industrial clients. When the pandemic hit the U.S. in March, the demand from the healthcare sector jumped 20- to 40-fold seemingly overnight. He says that previously, healthcare sector orders for N95s came primarily from hospitals treating patients with highly infectious illnesses such as influenza A and tuberculosis.

To meet that demand, the company dramatically increased production. Post says that globally, 3M has doubled N95 respirator production since January and is on pace to produce 2 billion respirators by the end of the year. In the U.S., 3M was on pace to produce 95 million masks a month by October. That’s triple the production in April, but Post says it still won’t be enough: “The reality is that even with 3M’s accelerated production, combined with capacity from other manufacturers, the demand for N95 and other respirators continues to exceed supply for the entire industry and will for the foreseeable future.”

Charles Johnson, M.A., president of the International Safety Equipment Association, a trade group, says PPE manufacturers are working around the clock to produce the most essential equipment. The pandemic, he says, “has likely forever changed PPE demand within the health and safety landscape.”

All areas of the safety equipment industry, including importers and distributors, have adjusted to meet spiking demand, according to Johnson. Some PPE producers who specialize primarily in sectors such as industrial or construction protection have begun partnering with medical device makers to begin making products for medical settings.

Meanwhile, manufacturers in completely different industries have jumped into the fray. For example, Ford Motor Company shipped out its first powered air-purifying respirators in May, made in partnership with 3M, which provided technical and regulatory know-how. Ford also started making reusable gowns for healthcare workers, sparked by a 500,000-unit order from the state of New Jersey.

A few experts say this rush to deploy PPE is happening in the absence of solid evidence about how protective PPE really is. Jos H. Verbeek, M.D., Ph.D., an occupational health physician at the University of Amsterdam, has long advocated for evidence-based improvement of PPE. He has written about the lack of randomized trials to back up the efficacy claims of common PPE items and argues that the industry needs uniform, high standards, which, in his view, are sorely lacking. He told 

® that although the COVID-19 pandemic has centered attention on PPE, that awareness has not translated into systematic improvement: “Everything has been focused on dealing with the crisis, and there hasn’t been any concerted effort in improving the situation: no trials, no comparative studies, no standardized naming.”

In April, Verbeek and colleagues published a Cochrane Library review of PPE studies that also included research into the risk of contamination associated with donning and doffing the equipment. They found that the results of two dozen relevant studies suggested that covering more parts of the body, such as the neck and the head, could improve protection and that modifications like pull tabs to ease removal of the equipment could cut down on inadvertent contamination. In an opinion piece in The 

 in June, Verbeek said a key takeaway from the review is that there is a frustrating lack of evidence to instruct healthcare workers and manufacturers on which types of PPE work best and how best to handle the equipment in the real world. “All evidence was rated as low to very low quality,” he wrote.

Although much attention has been paid to face coverings and respirators, Verbeek argued that PPE ought to be evaluated holistically because face masks are generally just one of many pieces of equipment used by healthcare workers in high-risk environments. Moreover, he said, the use or misuse of equipment can have a significant impact on effectiveness. Improperly used PPE will not be protective, and Verbeek emphasized the need to address the practical aspects of the gear. “PPE needs to be feasible in healthcare settings because protection depends not only on the technical qualities of the garment but also on the composition of PPE items, interfaces between pieces of PPE, and the ways in which they are put on and taken off,” he wrote.

COVID-19 has pumped billions into the buying and selling of PPE, and, notwithstanding Verbeek’s concerns about the lack of standards, companies leaped at the chance and are out there, selling their PPE ware. For instance, Aegle Gear, which makes scrubs, now sells products treated with Protx2, a proprietary spray created by Intelligent Fabric Technologies (North America) to protect fabric from odor-causing bacteria and fungi. Aegle’s website says the garments have been tested against various pathogens but also carries a disclaimer noting that the Protx2 finish is used “solely to protect the finished product itself,” and the company makes no claims about its health benefits. Intelligent Fabric Technologies says its recently developed follow-on product, Protx2 AV, can effectively protect against SARS-CoV-2, the virus that causes COVID-19.

PPE makers are also busy tweaking products to make them more comfortable. Working with Nissha Medical Technologies, 3M put a hydrophilic film on face shields that wicks away fluid and prevents them from fogging up.

A number of manufacturers, including 3M, are working with the FDA to find and evaluate ways to safely decontaminate and reuse N95 masks. Johnson says developing reusable PPE is now seen as important because it would help alleviate the supply problem.

“Elastomeric respirators (reusable-filter-style respirators) and powered air-purifying respirators provide greater protection and can help to prevent shortages of disposable alternatives,” he says, “so we expect to see them used more often as healthcare facilities continue to battle this and future health emergencies.“

Verbeek acknowledges that new products could improve PPE but says he still sees a problem of science and rigorous evaluation lagging.

The wide array of face coverings designed for source control — protecting people from asymptomatic carriers — is a new product segment, according to Johnson. He says his association and its members are working to establish standards and guidance to ensure that such products are safe and effective. There certainly seems to be a strong appetite for scientific evidence about the effectiveness of face masks: Duke University researchers were in broke-the-internet territory in August when they reported results about how well different face masks hindered exhalation of droplets.

Verbeek concedes that it might be asking too much to conduct rigorous comparative research in the middle of a pandemic, but that doesn’t mean there is no opportunity for progress: “A realistic alternative is to conduct observational studies in which the PPE of healthcare workers is registered prospectively, and the healthcare workers are followed for their risk of infection.”

Jared Kaltwasser is a healthcare reporter based in Iowa.

Suppliers of personal protective equipment have come up with innovative ways to meet the demand, but one expert notes the lack of rigorous research into its efficacy.

Jared Kaltwasser

Articles

CRISPR Gene-Editing Shows Promise Against HIV

Optometrists Push to Help Administer, Receive COVID-19 Vaccine

Number, Not Just Type, of Social Determinants Impacts Cardiovascular Health

The PPE Scramble