Jared Kaltwasser

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A new study is helping to clarify the links between genetic factors and the risk of lung cancer, identifying 25 new variants that appear to correlate with an increased susceptibility to the disease.

, M.S., Ph.D., of the Institute for Clinical and Translational Research at Baylor University, explained what his team found when they performed whole exome and targeted sequencing of germline DNA on 1,045 samples from patients with lung cancer who risk for the disease seemed likely to be genetic rather from environmental exposure such as smoking. The patients included those with a family history and with ealy onset forms of the disease. Amos and his colleages compared those cases with 885 controls.

"We were looking for variants that have a relatively high impact on risk but occur at relatively low frequency," Amos said, in a press release.

Researchers have, of course, been investigating genetic susceptibility to lung cancer for some time now, Amos and his co-authors noted. Sometimes the connections are not direct; for instance, certain genetic variants appear to be correlated with a greater difficulty quitting smoking, which in turn can increase a patient’s risk of lung cancer.

Overall, lung cancer heritability is believed to be about 18%, and Amos and colleagues said rare variants are likely to account for a significant portion of those cases.

The sequencing analysis found 25 new pathogenic variants linked with lung cancer susceptibility, of which the investigators validated 5 variants. Two of the validated variants, ATM and MPZL2, were related to genes previously linked with lung cancer risk, ATM and MPZL2. The remaining 3 involved novel links to lung cancer risk: POMC, STAU2, and MLNR.

Yanhong Liu, Ph.D., a co-author on the study and member of the Dan L. Duncan Comprehensive Cancer Center at Baylor, said in the press release that one notable finding of the study was the impacts of insertions and deletions of DNA sections.

"Mutations of DNA where sections are either inserted or deleted have been understudied compared to single nucleotide variants, but they are also very important because they can result in truncated proteins," Liu said. Two-thirds of the candidate variants in the study were insertions or deletions, according to Liu.

The investigators next applied endogenous DNA damage assays in hopes of better understanding how the variants affect cancer risk. They wondered whether an increased level of endogenous DNA damage leads to genomic instability and ultimately cancer. They found that POMC, MLNR, and ATM variants were associated with increased levels of DNA damage. Amos and colleagues noted that ATM is believed to be a “first responder” to DNA damage, and variants in ATM have been linked with increased risk of multiple cancers.

® that, as with other cancers, a particular person’s cancer risk is based on a variety of factors, including lifestyle, environmental, and genetic factors. With lung cancer in particular, 85% of cancers occur in people who have smoked or currently smoked. However, Amos said that still leaves a significant number of people for whom genetic variants might be a key contributing factor.

“[G]enetic factors do contribute and can also be a very important factor for some individuals,” he said. “...These factors may have relevance at an individual level and also become relevant for screening as genetic sequencing becomes more commonly applied.”

Articles

Although smoking is the predominate risk factor for lung cancer, about 1 in 5 cases cases are believed to be linked to genetic factors.

Study Identified 25 Genetic Variants Linked with Lung Cancer Risk

Perhaps no industry better straddles the dichotomy between cutting-edge technology and inefficient obsolete devices than the healthcare industry.

In one corner of a hospital, a physician in another room (or another state) can perform precision surgery using state-of-the-art robotics, while just down the hall a nurse receives the patient’s medical records via fax machine and the patient’s spouse uses a pen to fill out paperwork.

Those throwbacks exist for many reasons, but perhaps the most important is the Health Insurance Portability and Accountability Act of 1996 (HIPAA), which requires providers and health plans to protect a patient’s health data. Say what you will about fax machines, but they are sturdily HIPAA-compliant.

But if government regulation to protect patient privacy is the root cause of the vestigial methods for transferring healthcare data, then new regulations might pull them into the 21st century.

The agents of change are new healthcare data interoperability rules from HHS Office of the National Coordinator for Health Information Technology (ONC) and CMS. Enforcement of some parts of the ONC rule is scheduled to begin in April after HHS delayed enforcement last year because of the COVID-19 pandemic. Other parts will go into effect in 2022 and 2023. The CMS rule will be enforced starting in July.

The intent of the ONC rule is to make it easier for patients to access their own health information and for patient healthcare information to circulate easily among providers and provider organizations. It is also supposed to ease the way for design and use of healthcare-oriented computer and smartphone applications.

Nilesh Chandra, MBA, a partner in healthcare strategy at PA Consulting, an international consulting firm, says the changes could have life-or-death implications. He paints the scenario of someone coming to the emergency department with a rapidly worsening case of COVID-19. Because of the interoperability rules, the patient’s records will be readily accessible. “The attending physician cannot speak to the sedated, intubated patient but can pull medical history to understand underlying health conditions and risk factors while administering care,” he says. In the past, providers of health-related services have used “information blocking” to keep data in-house in hopes of creating some kind of competitive advantage. Under the new rule, that will be illegal, with a limited number of exceptions, such as when requests are infeasible or pose privacy concerns.

The ONC rule also requires covered entities to adopt the Health Level 7 Fast Healthcare Interoperability Resources (FHIR) standard for application program interfaces (APIs). This change will make data sharing easier by standardizing the way data are stored and transmitted between payers, providers and other healthcare entities.

John D’Amore, M.S., co-founder and president of Diameter Health, a health information company, explained in an interview with 

® that once the FHIR — pronounced “fire” — standards are universal, healthcare records won’t function like a single document but, rather, as separate pieces of information. That will make information about, say, a patient’s allergies or current medications more easily extracted from those records.

“It’s really going to bring us a lot more into the 21st century for how data exchange occurs,” D’Amore says noting that easily shareable data have made other industries fertile grounds for innovation. He points to the financial industry and its ability to access and aggregate a user’s financial data to provide financial tracking and insights.

The new CMS rule leverages the new API requirements to force payers and plans to share claims and other health information securely with patients in a secure, user-friendly, electronic format. The rule applies only to clinical information already made available to payers and does not create a requirement for payers to access additional data from providers.

The CMS rule also requires participating hospitals to send electronic notifications to other providers anytime a patient is admitted, discharged or transferred from the hospital. The goal is to spark better care coordination and, ultimately, better patient outcomes. Starting in April 2022, states must begin sending daily data reports on Medicare and Medicaid beneficiaries, a requirement that is also supposed to lead to better coordination and more accurate billing.

These new requirements technically apply only to payers and plans that participate in Medicare, Medicaid or other federally facilitated exchanges. D’Amore says they’re likely to carry over into the private market — even the self-insured one — because the insurance industry’s major players are all so deeply involved in the public payer programs. Although proponents of the new regulations say that they merely bring healthcare in line with patient expectations for data access and functionality, the insurance and hospital industries have pushed back on them. Matt Eyles, M.S., president and CEO of America’s Health Insurance Plans, the industry’s main trade group, is on record as saying the new rules could threaten patient privacy. “We are seriously concerned that patient privacy will still be at risk when healthcare information is transferred outside the protections of federal patient privacy laws,” he said in a press release last year.

Although providers, insurers and their business partners are covered by HIPAA, HHS acknowledged that the new rules raise the potential for health information to be sent to third parties that may or may not have sufficient data security protections. Eyles noted in the statement that even de-identified health information could easily be traced to individuals by combining it with other available personal and health information.

The American Hospital Association has voiced similar concerns. In March 2020, Rick Pollack, the association’s president and CEO, said in a prepared statement that the rules lack “the necessary guardrails to protect consumers.” HHS partially addressed this concern by publishing a guidance indicating that covered entities would not be held responsible for leaks related to the transfer of patient health data to noncovered entities, such as third-party applications. Chandra concedes that there is risk associated with the transfer of data, particularly if the third-party applications don’t have secure data-transfer channels. But he believes the primary risk to patient privacy is the intentional theft of data, using ransomware or malware, not the incidental leakage of it. “I think those risks are substantially greater and pose a much greater risk to patient data than the accidental exposure through a poorly configured data interface between two HIPAA-covered entities,” he says.

As for the timing of enforcement, most agree that the delays were wise. The healthcare industry had more than enough to deal with last year with the COVID-19 pandemic. But the reality is that the covered entities have been preparing for the change for years. After all, the legislation authorizing the new rules, the 21st Century Cures Act, was passed in 2016.

Chandra says the time has come for meaningful interoperability: “The pandemic has further exacerbated the need for data sharing with public health officials and also to coordinate care for patients affected by COVID-19.”

Jared Kaltwasser is a healthcare reporter in Iowa.

Enforcement of rules to encourage the freer flow of healthcare data were delayed because of the COVID-19 pandemic. They are now scheduled to go into effect this year. 

Interoperability is Coming — at Last

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.

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.

Jared Kaltwasser

Articles

Study Identified 25 Genetic Variants Linked with Lung Cancer Risk

Interoperability is Coming — at Last

CRISPR Gene-Editing Shows Promise Against HIV

Optometrists Push to Help Administer, Receive COVID-19 Vaccine