Renuka Tipirneni, MD, of the University of Michigan, was named the recipient of the 2020 Seema S. Sonnad Emerging Leader in Managed Care Research Award.

Congratulations to the 2020 Recipient of the Emerging Leader in Managed Care Research Award!

The Mediterranean diet, which is known to have health benefits, may help prevent rheumatoid arthritis in current or previous smoker.

Mediterranean Diet May Prevent RA in Current or Previous Smokers

Higher levels of the omega-3 fatty acid eicosapentaenoic acid (EPA) found in the blood appear to explain why icosapent ethyl drives down the risk of a cardiovascular (CV) event.

REDUCE-IT: Serum EPA Levels Hold Key to Vascepa's Dramatic CV Benefits

Through a collaborative effort by Catalyst for Payment Reform (CPR), the American Benefits Council, and Mercer, 4 key telemedicine considerations were issued for policymakers seeking to capitalize on the substantial growth in telemedicine and virtual care use, said Andréa Caballero, MPA, program director for CPR.

: Hello, I'm Matthew Gavidia. Today on the MJH Life Sciences’ Medical World News, 

® is pleased to welcome Andréa Caballero, program director for CPR.

Andréa, great to have you on. Can you just introduce yourself and tell us a little bit more about your work?


: Sure. Thank you, Matthew! Thanks for having me. My name is Andréa Caballero, and I am the program director for Catalyst for Payment Reform. In my role, I do a variety of things. Measuring payment reform at the state and national level is sort of my primary role. I also follow health policy issues, state and federally. About CPR, we're a national nonprofit 501(c)(3) independent organization that represents public purchasers [and] private purchasers, about 32 organizations that represent about 16 million plus covered lives and about $84 billion in health care spending.

: Amid the COVID-19 pandemic, use of telemedicine and virtual health care have risen substantially as more patients seek care without the threat of infection. Can you speak on the current state of telehealth in the health care ecosystem?

: Sure, I guess it might be the understatement of the year if I were to say that the use of telemedicine has increased substantially. It's not just because this is the first time telehealth is being offered to employees. I think the most current statistic is from FAIR Health; t has a monthly health regional tracker on telehealth, and it's said that telehealth visits have increased 8336% year-over-year since April. So, that is a tremendous growth.

With that growth comes some challenges, so changes in the ecosystem. On the provider side, they're having to adjust to new technology, to relating to patients in a virtual way and not in a physical way. Payers are adjusting to new payment methods for telemedicine and they're having to adjust their benefit adjudication because they have rules now where they might have to waive copays or coinsurance. Regulators are responding very rapidly or trying to respond rapidly and implementing emergency rules. And of course, purchasers are looking just to make sure that their employees are getting the care that they need.

In the background, you have vendors who are offering telehealth services that are rapidly changing their business models and trying to keep up with the demand. And so you have all of these moving parts that really require fast adjustment during the pandemic, and it's within a system that historically just does not move very rapidly.

: Beyond the social distancing attributes present during the pandemic, what are some other notable benefits of telehealth and ways it can surpass even that of normal in-patient care?

: I think if you talk to a normal patient—I myself have had a telehealth visit—I think people would probably say a benefit is convenience. Last year, about 77% of people said they would try telemedicine, but only 9% were actually using it–this was in 2019. But now you have massive use, as I stated before, of telemedicine. So, the convenience, people are working from home; the travel they don't have to account for. So there's convenience. But I also think that access is a tremendous benefit for this. You've got access to perhaps primary care specialists or mental health specialists or things that you might not have been able to get in a timely way before, so you got the benefit of access.

You also have, I guess I would say, benefits related to short-term cost savings. As I mentioned, health plans and self-funded 

 are waiving copayments for telehealth visits, and they're doing this temporarily, but that's a benefit to employees because that lowers their out-of-pocket spending. You also have new rules. The CARES Act enacted by Congress allows for telehealth visits to be covered on a predeductable basis. So, this means that patients don't have to meet their deductible before they can get a telehealth visit. So, that too, provides a cost savings.

I think just the access to care in underserved communities. You have these underserved communities, rural communities, [that] may not have a lot of providers with timely access. It's all just kind of being accommodated, and it's a benefit to telemedicine. I also think we've all probably been talking about mental health these days, and there were challenges to access to mental health services prior to the pandemic. But at least during the pandemic, if there's a sort of a bright spot here, it's that people who are needing mental health services now more than ever, with the anxiety of the economy or losing a job or having children at home and teaching them at home—we have unprecedented reports of anxiety and depression, and so people who might otherwise not get that care might need to travel and have an hour in-person visit with someone–they might not have done that, but now they're able to do that. So, that's another added benefit.


: To build on that, what are some current challenges that employers and health care purchasers face when seeking to better leverage telemedicine and virtual health services?

: Well, there are some really well-intended, temporary policy decisions that were made in the early days of the pandemic. Things like waiving the copays or relaxing the rules on who can deliver care to patients, who didn't have to have had a preexisting relationship. Even the technology platform. They're allowing it to be Zoom or it could be FaceTime. Those are all things that weren't allowed before. So, those were really well-intended, necessary things. But there are a few things. So, traditional telemedicine was offered through vendors like Teladoc, Doctor on Demand—things we understood and you had them on your smartphone or something like that. Utilization was low, but it was really for urgent care, episodic care. zit was not intended to have a long term relationship with your doctor. And those visits cost about $40 to $50. But now we're transitioning from  traditional telemedicine to virtual care and that's really different.

Virtual care is where you have an established relationship with your provider, not someone you might just see on an urgent basis. And they're offering more complex care, because they have an established patient–provider relationship. So, vendors are now changing their business models, and they're marketing themselves as virtual care, virtual primary care, and what used to be $40 to $50 per visit, they're now increasing their prices.

So, you have the challenge of rising costs just on your traditional telemedicine. But then you also have the issue of how do purchasers pay for care and how are their benefits changing. And we're CPR so we care deeply about how care is paid and want to make sure that it's value-based. We want to make sure that any rules that go into place permanently aren't restrictive in the way employers can design their benefits. So, I'll just give you an example of that. Payment parity, meaning that payers, including self-funded purchasers, have to pay a virtual visit the same as they would an in-person visit, these are temporary rules. But if you look long term, virtual care just doesn't require the same brick and mortar, doesn't require the same time. And so virtual doesn't always justify equal payment.

It also could result in purchasers find challenges in the possibility of upcoding. So, our current coding system under fee-for-service doesn't really allow for the adjustment in time or intensity that is required for in-person visits. In other words, the payments might not match the level of intensity and you end up paying more for something then you might for an in-person visit. I guess if you think about this, and purchasers think about this a little bit more long term, virtual visits are not ultimately going to replace in-person visits on a 1-to-1 basis. So you're not offsetting one with the other.

Eventually, there's going to be the combination of both virtual care and in-person care. And so since you're not going to have an offset here, you're going to have a combination, you actually increase utilization and then total cost of care will increase. So, purchasers are concerned about total cost of care, and if you can't adjust the payment to accommodate what kind of care virtual care is really delivering and paying it not on a fee-for-service basis, but paying for it in a way that makes sense, then purchasers can really see challenges to being able to deliver those value-added benefits.

: In looking at a post–COVID-19 world, the American Benefits Council, Catalyst for Payment Reform, and Mercer provided 

 for policymakers to capitalize on the current momentum behind telemedicine and virtual health care. Can you speak further on each of these considerations?

: Sure. So, there are 4 recommendations that all 3 of our organizations are educating people about and advocating for, which is, first we’d like Congress to make permanent the provision in the CARES Act that allows telehealth visits to be paid for on a predeductible basis. So, for HSA [health spending account]-eligible plans, we'd like them to make that provision permanent where telehealth visits can be made before the deductible is met. So, that's the first one, and it's in the CARES Act and to make that permanent is perhaps not that challenging.


The second is that purchasers and purchasers that we work with would like to offer telehealth and telemedicine benefits as a stand-alone benefit, but right now, they have to be part of the medical benefits and they have to be equal. So, it's a little bit of a wonky situation, but we would like to continue to be able to offer telehealth benefits on a stand-alone basis. And if we do that, we would like it to be what's called an accepted benefit under the Affordable Care Act (ACA) and therefore that standalone benefit is not in violation of the ACA.


The third is one that involves states, but if Congress was able to send the signal to states to remove the barriers to telemedicine, I think that would be very beneficial. States have already tried to do this on an individual basis, but Congress sending that message could be very helpful. So, some of these barriers are requirements that providers and patients have preexisting relationships. So, removing that barrier. Allowing patients and providers to be in different states and not having to reside in the same state or having the same state licensure, that's another barrier that we would like to have removed.


Then, finally, the fourth thing that we are advocating, or educating I should say at least as a 501(c)(3) educating on, is that we really urge anyone to oppose mandates that will limit an employer or a purchaser’s ability to create value-based benefit designs and value-based payment. These mandates are things, as I mentioned, like payment parity, paying for virtual care at the same level as in-person visit, that's a mandate. And so we would urge people to not have that mandate. It also includes covering telemedicine services at the same level of medical services or in-person service, any in person service, and that just really isn't feasible. So, opposing those types of mandates is the fourth item that we're recommending.

: Lastly, do you have any other concluding thoughts?

: Well, I guess I would say that if there was a bright spot in the pandemic, it's that there has been such a tremendous use of telehealth. Patients are embracing it, and providers are embracing it. And so that's a real bright spot. I think the last thing is that we're Catalyst for Payment Reform, and we've been measuring payment reform over the past 10 years. We've been trying, the industry has made progress, but we've been building off an old fee-for-service system. And we have an opportunity here to take a look at telemedicine and how we pay for telehealth services versus in-person visits and really create a new payment model that works under the system. One that doesn't try to fit a square peg into a round hole, and putting fee-for-service and applying it to telehealth when it wasn't intended to.


So, we really think there's an opportunity to address payment and ensure that access is preserved and people can continue to use these services, which there's no question that people will continue to want to. So, I think those are the bright spots and opportunities.

: To learn more, visit our website at AJMC.com. I’m Matthew Gavidia, thanks for joining us!

Videos

Through a collaborative effort by Catalyst for Payment Reform, the American Benefits Council, and Mercer, 4 key telemedicine considerations were issued for policymakers seeking to capitalize on the substantial growth in telemedicine and virtual care.

Considerations for Policymakers Wanting to Optimize Telemedicine, Virtual Care

Incidence prevalence rates of narcolepsy were assessed in a meta-review of 30 countries, with a trend of underreporting found in ethnic/race and gender minorities, childhood narcolepsy type 2 (NT2), and among patients with comorbid conditions, according to 

Characterized by excessive daytime sleepiness with or without cataplexy, narcolepsy type 1 (NT1) and NT2 are diagnosed by clinical, electrophysiological, and biological evaluations, which often leads to a delayed diagnosis ranging from 8.7–22.1 years and risk of misdiagnosis, noted author Karen Spruyt, PhD, clinical psychologist and child psychologist at the Free University of Brussels and at the University of Chicago.


“In an era of increased sleepiness complaints at societal level; a new pandemic, coronavirus disease 2019; and personalized medicine, we aim to systematically review the literature concerning the presentation of narcolepsy in diverse populations,” wrote Spruyt.


Performing a systematic literature search in PubMed, Scopus, and Web of Science, Spruyt divided population-based data of 30 countries (209 data sets) into continents and ethnicity/race groups based on definitions set by the National Insitute of Health Diversity Programs. Spruyt categorized the study cohort by age, in which children were classified as being < 19 years and adults > 19 years.

Addressing another pandemic of the past, H1N1, Spruyt additionally sought to examine associated adverse events of rising narcolepsy incidence reported by Sweden and Finland after vaccination. She categorized data based on reports before the pandemic (< 2009), during/after (≥ 2009), and a mixture of both.

In the meta-review, there was a narcolepsy rate of 0.87–1.21 worldwide, with NT1 research noted to be prioritized in studies. Among those who were vaccinated during and after the H1N1 pandemic, the pooled incidence rate was shown to be 1.58.

“Caution is needed in interpreting these pooled rates, because the year 2009 (or H1N1 pandemic circulation) is a crude time point applied in different ways throughout the literature, particularly in combination with the recollection of the onset of symptoms of narcolepsy,” wrote Spruyt.

Spruyt additionally indicated a “striking” gap in epidemiological data involving minorities and gender disparities, with data representing mainly European and Caucasian samples.

“The reviews published since 2017 moreover highlight the gap in knowledge regarding co-occurrence of disorders that may mask symptomatology of narcolepsy,” wrote Spruyt. “Especially given the associated features of narcolepsy, such as hypnagogic or hypnopompic hallucinations, 

 paralysis, and obesity, misdiagnosis might be common.”

Spruyt K. Narcolepsy presentation in diverse populations: an update. 

. Published online November 25, 2020. doi:10.1007/s40675-020-00195-7

Articles

Incidence and prevalence rates of narcolepsy were assessed in a meta-review of 30 countries, with a trend of underreporting found in ethnic/race and gender minorities, childhood narcolepsy type 2, and among patients with comorbid conditions.

Assessing Presentation of Narcolepsy Worldwide

Certain antiretroviral therapies can decrease contraception’s effectiveness, so it's important to have family-planning conversations, said Milena Murray, PharmD, MSc, BCIDP, AAHIVP, associate professor at Midwestern University College of Pharmacy, who practices at Northwestern Medicine's Infectious Disease Center in Chicago.

How might hormonal contraceptives and antiretroviral therapies interact in ways that could counteract their effects in female patients living with HIV?

Family planning conversations are so important to have with every patient at each clinic visit, and there are drug interactions that decrease the effectiveness of the hormonal contraceptives. And we know that most medications or antiretroviral medications are not affected by the hormones themselves. So it’s really important to not prescribe antiretrovirals that are going to decrease the effectiveness of the hormones, because that may lead to unintended pregnancies. However, it has to be a conversation with the patient about what do they prefer. Do they want an injectable hormonal contraceptive? Do they want an intrauterine device?

Some of these obviously have less drug interactions than oral hormonal contraceptives. And there are many antiretrovirals that now do not interact. So it shouldn’t be a, “Oh, we can’t use these at all,” because there’s no options for the patients. It’s really about the preference of the patients, the effectiveness, having that conversation just as you would with a patient not living with HIV and making sure that if they don’t want children at this point, that we’re doing the best to help them with that. And if they do want children, that we’re prescribing antiretrovirals that are preferred in pregnancy, as well as looking at the rest of their comedications to make sure they’re not on anything that might be 

Certain antiretroviral therapy (ART) drugs can decrease contraception’s effectiveness, said Milena Murray, PharmD, MSc, BCIDP, AAHIVP, associate professor, Midwestern University College of Pharmacy.

Dr Milena Murray: Be Careful When Prescribing ART for Patients on Hormonal Contraception

Fauci Warns of Uptick in COVID-19 Cases After Holiday Travel

Yesterday, the nation’s top infectious disease expert Anthony Fauci, MD, warned of potential upticks in cases of coronavirus disease 2019 (COVID-19) after many Americans refused to adhere to warnings by public health officials against traveling this past holiday week. Reported by 

, Fauci urged travelers to be safe when returning home and encouraged them to quarantine if possible and get tested. This past Wednesday, the travel rate reached its highest level since March, with approximately 1.1 million passengers going through airport security.

UK Set to Be First to Clear Pfizer, BioNTech Vaccine

, the United Kingdom (UK) could give the first approval to Pfizer Inc. and BioNTech’s COVID-19 vaccine candidate, BNT162b2, as early as this week. The UK has ordered doses of the 2-shot vaccine to immunize approximately 20 million people, although it is noted that it will not be available right away. The first injections are said to potentially take place starting December 7.

Free HIV Testing Available Across South Carolina

As part of World Aids Day on December 1, health officials from South Carolina are offering free 

 testing, as well as testing for other sexually transmitted diseases and Hepatitis C at local health clinics statewide. Reported by 

, health officials estimate that over 20,000 people in South Carolina are living with HIV, with 1 in 6 noted to be unaware of their status. The South Carolina Department of Health and Environmental Control additionally plans to hold a panel discussion tomorrow, called "Ending the Epidemics" that will include information on preventing the spread of HIV and how those infected live with the virus.

Anthony Fauci, MD, warns of potential upticks in cases of coronavirus disease 2019 (COVID-19) after holiday travel; the United Kingdom is set to give the first approval to Pfizer, BioNTech’s COVID-19 vaccine candidate; health officials from South Carolina to offer free HIV testing.

What We're Reading: Fauci Warns of Holiday Travel Uptick; UK to Clear Vaccine Candidate; SC Offering Free HIV Testing 

The 5-year risk of women dying or developing 

 following a first severe heart attack is 20% higher compared with men, according to 

“Identifying when and how women may be at higher risk for heart failure after a heart attack can help providers develop more effective approaches for prevention,” said lead study author Justin A. Ezekowitz, MBBCh, MSc, a cardiologist and codirector of the Canadian VIGOUR Centre at the University of Alberta in Edmonton, Alberta, Canada, 

Ezekowitz and his fellow authors conducted their population-based cohort study on 45,064 patients admitted to an Alberta hospital between April 1, 2002, and March 31, 2016, who had a first heart attack of 1 of 2 types that required hospitalization:

ST-segment elevation myocardial infarction (STEMI), a life-threatening heart attack (45.1%)

Non–STEMI (NSTEMI), a less severe and more common heart attack (54.9%)

A second hospitalization within 24 hours of the first was “considered to be part of the same episode,” noted the authors.

The female study population was older, and despite the women having more comorbidities, the results show that 74% of them vs 87% of men had a diagnostic angiography. Following this test, however, higher rates of 1-vessel disease or nonobstructive coronary artery disease were seen in the women: 39.6% vs 29.1% (

STEMIs and NSTEMIs resulted in higher unadjusted rates of death in women vs men: 9.4% vs 4.5% and 4.7% vs 2.9%, respectively. Adjusting for confounders did not alter the finding that these types of heart attacks were more likely to lead to the death of female patients:

STEMI: adjusted odds ratio (aOR), 1.42 (95% CI, 1.24-1.64)

Fewer women than men had an NSTEMI: 34.3% vs 65.7%. An overall 55% (n = 24,737) of patients in the study experienced this type of heart attack.

Fewer women than men had a STEMI: 26.5% vs 73.5%. An overall 45% (n = 20,327) experienced this type of heart attack.

 were more common risk factors among women when they had a heart attack.

Women were seen 15.4% less often by a cardiovascular specialist compared with men: 72.8% vs 84%.

Beta-blockers and cholesterol-lowering drugs were prescribed less often for women.

Fewer surgeries were performed among women to restore blood flow.

Overall, in the aftermath of a hospital discharge, heart failure was the more likely ultimate outcome in women compared with men after both a STEMI and an NSTEMI: 22.5% vs 14.9% and 23.2% vs 15.7%, respectively.

Clinicians need to recognize that there are gaps in care between women and men, be aware of possible biases, and be more attuned to their highest-risk patients to provide better care, 

 Padma Kaul, PhD, one of the study’s coauthors. Future studies also should investigate the levels of care that all patients with heart issues are receiving, as well as identify possible oversights and how to surmount them, the authors stated.

“The development of HF either in-hospital or after discharge remained higher for women compared with men, even after adjustment,” they concluded. “Given its frequency, further attention should be paid to all patients with acute coronary syndromes for the prevention of future HF outcomes.”

Ezekowitz JA, Savu A, Welsh RC, McAlister FA, Goodman SG, Kaul P. Is there a gap in surviving an acute coronary syndrome or subsequent development of heart failure? 

Published online November 30, 2020. doi:10.1161/CIRCULATIONAHA.120.048015

The 5-year risk of women dying or developing heart failure following a first severe heart attack is 20% higher compared with men, according to the findings in Circulation.

Risk for Heart Failure Higher in Women vs Men After a Heart Attack 

The wonders of chimeric antigen receptor (CAR) T-cell therapy, which harness the immune system in the fight against cancer, have thus far proved successful in blood cancers such as leukemias and lymphomas. Solid tumors have proved more challenging, and glioblastoma—the deadly form of brain cancer—has been most difficult of all.

But a group of researchers at Penn Medicine has potentially unlocked the secret to letting CAR T-cell therapy do its job in glioblastoma. The solution calls for pretreating the cells that line the blood vessel walls that prevent CAR T-cells from reaching the tumor, thus allowing the immunotherapy to reach the cancer and do its job.

, authors walk through the painstaking steps of screening more than 500 different kinases that might hold to the key to their puzzle—which enzyme regulated blood vessel activation in endothelial cells? Once they settled PAK4, a known instigator of solid tumor growth, they developed a PAK4-knockout mouse model for one type of experiment.

They implanted glioblastoma tumor cells in these mice, and found that by limiting PAK4, they reduced vascular abnormalities and appeared to allow T cells to penetrate the tumor. “Interestingly, PAK4 knockout robustly stimulated T cell infiltration into the tumors, probably contributing to the inhibition of tumor growth,” the authors wrote.

Approximately 80% of the PAK-knockout mice survived for at least 60 days after the experiment ended; by contrast, all the wild-type mice died within 40 days of having the tumor cells implanted, despite having a T-cell infusion.

“We suggest that the therapeutic efficacy associated with enhanced T cell delivery and homing by PAK4 inhibition can be further improved when combined with other immunotherapy approaches capable of increasing T cell persistence by inhibiting T cell exhaustion and/or by stimulating T cell activation in the tumor microenvironment.,” the authors wrote. Thus, they write, targeting PAK4 makes the tumor microenvironment more receptive for T cells to do their job, and may have implications beyond glioblastoma and even immunotherapy.

Returning blood vessels to their normal state by reducing oxygen deprivation, known as hypoxia, could improve results across a range of cancer treatments, from targeted therapy, to radiation, to chemotherapy.

"To our knowledge, we are the first to show how we can reprogram the whole vascular microenvironment with a PAK4 inhibitor and promote cellular therapy," said senior author Yi Fan, PhD, an associate professor of Radiation Oncology in the Perelman School of Medicine at the University of Pennsylvania. "Importantly, this may not only be limited to brain tumors; it could potentially be used for all types, including breast, pancreatic, and others, because vascular abnormality is a common feature for almost every solid tumor."

Ma W, Wang Y, Zhang R, et al. Targeting PAK4 to reprogram the vascular microenvironment and improve CAR-T immunotherapy for glioblastoma. 

. Published online November 30, 2020. er at https://doi.org/10.1038/s43018-020-00147-8.

Penn Medicine researchers use mice experiments to find a potential solution to the challenge of delivering CAR T cell treatments to solid tumors in glioblastoma.

Pretreating Cells With PAK4 Inhibitor Lets CAR T-Cell Treatment Work in Solid Tumors

There are certain diseases, like lung cancer, that are leading the way in precision medicine and where broad molecular testing is recommended, said W. Michael Korn, MD, professor of medicine in the Division of Hematology/Oncology at the University of California, San Francisco, and chief medical officer of Caris Life Sciences.

Are there certain cancers where we've made more progress using precision medicine to make treatment decisions compared with other cancers?

Absolutely. I think what has turned out is there are certain clinical scenarios and diseases where there is lots of opportunity, lots of already existing data and those areas pave the road, I think for, you know, other disease settings that are following. And the best example is really lung cancer, where—first of all, it is one of the most frequent cancer types, affecting over 200,000 people in the United States every year—but we have learned a lot about the molecular features of this disease. And so, we're not looking at lung cancer as one disease anymore. We're looking at segments of the disease that have all the different types of treatments associated with them. And this has become standard now. The NCCN [National Comprehensive Cancer Network] guidelines recommend broad molecular testing for lung cancer, because of that complexity, and we know that this improves outcomes.

Other diseases are following. Like, I’ll give you an example: breast cancer, colorectal cancer are other big disease groups where this is following. So, we will see a kind of steady development until, in my opinion, it becomes standard to test every cancer being diagnosed right up front when the patient presents himself, at least in the advanced disease setting, to the oncologist.

Have we made more progress in solid tumors compared with liquid tumors?

These are kind of somewhat different worlds. There has been clearly tremendous progress on the side of solid tumor, kind of molecularly guided therapy. I think the hematologic world is following, but it depends very much on what aspect of hematology you're looking at. So, certainly, in diseases like AML [acute myeloid leukemia], recurrent AML, we are still looking for a similar approach. Whereas in others, in lymphomas and so on, there might be already very established linkage between certain molecular findings and treatments.

There are certain diseases, like lung cancer, that are leading the way in precision medicine and where broad molecular testing is recommended, said W. Michael Korn, MD, of University of California, San Francisco, and Caris Life Sciences.

Dr Michael Korn Discusses Precision Medicine Progress in Various Cancers

Updating guidelines requires having sufficient information on the elements that are your focus. The new European Respiratory Society (ERS)/American Thoracic Society (ATS) guidelines, for example, include recently developed biologic agents, noted Dan Ouellette, MD, MS, FCCP, senior staff physician and director of the Respiratory Ward at Henry Ford Hospital and associate professor of medicine at Wayne State University School of Medicine.

What guidelines are most important among the new ones from the European Respiratory Society and the American Thoracic Society?

I think that there are elements in the new European Respiratory Society/American Thoracic Society [ATS] guideline that will be of great interest. When a society, when a group develops a guideline, the process takes a while. And when you pick the elements that you're focusing your guideline upon, we choose elements for which we have sufficient information to be able to address a question.

And both the GINA [Global Initiative for Asthma] guidelines and the guidelines that are being developed by the National Institutes of Health in the United States, which should be published later this year, answer questions that are very common and important. But there are new technologies, new treatments that are developing, which neither of those guidelines has really been able to address just because of the novelty of the information and the fact that this is emerging research.

And the gap that the European Respiratory Society guideline and the ATS guideline—the combined society guideline—the gap that that fills is providing information about these biologic agents that have been recently developed and are emerging. And in this guideline, contrary to the others, they're actually recommendations about use.

So, I think this will be an exciting guideline, because it fills a gap and it gives clinicians guidance about how to use these new agents that are being developed.

Updating guidelines requires having sufficient information on the elements that are your focus, noted Dan Ouellette, MD, MS, FCCP, senior staff physician and director of the Respiratory Ward at Henry Ford Hospital.


Dr Dan Ouellette: The New ERS/ATS Guidelines Provide Information on Biologic Agents

What are some of the considerations that clinicians should take into account when choosing a disease-modifying therapy?

Well, I think there are multiple factors in shared-decision making. I think the principle of early treatment is very key. The principle of shared decision making is very key—you want the patient to be a partner. So you want them to be informed and educated to have a true understanding about MS. And then I think principal factors are, what are individual goals and this would also account for, do they have comorbid conditions, what are their lifestyle expectations? Are they looking at pregnancy as something down the line that is important? So there are individual subject goals. There are MS disease goals. How active is their MS? What sort of prognostic profile does the patient have? Someone who has very active disease, somebody that you're very worried about, [they] look like they're fitting into a poor prognosis. Efficacy of your DMT choice now becomes very important, critically important. And then I think finally, the DMT. And this is the mode of delivery, the safety, the tolerability, the adverse events, the efficacy of the drug, the monitoring that is required. These are kind of the principal factors that are calculated into coming up with the best disease-modifying therapy choice for the individual patient.

Multiple factors come into play when providers and patients discuss a disease-modifying therapy for multiple sclerosis (MS), explains Patricia K. Coyle, MD, of Stony Brook University Neurosciences Institute.

Dr Patricia Coyle on Considerations in Choosing a DMT for MS

 since 2019 and has a BA in philosophy and journalism & professional writing from The College of New Jersey. 

Large telemedicine diabetic retinopathy (DR) screening (TDRS) networks based in federally designated safety-net clinics (FDSCs) may be able to increase screening access and compliance among otherwise underscreened populations, according to study 

. However, outcomes can vary greatly among clinics and further work to optimize program implementation is needed to maximize the model’s impact, the researchers wrote.

DR is a common microvascular complication resulting from 

 among adults. Although annual DR screening with early intervention has been proven to reduce the risk of severe DR-related vision loss and is recommended by the American Academy of Ophthalmology for all patients with diabetes, current screening rates in the United States remain low. Reduced screening rates are especially prevalent in vulnerable populations.

Effective treatments for DR are available, but missed opportunities for secondary prevention lead to overall decreased productivity, increased morbidity, and increased health care expenditures. Common barriers to conventional DR exams include geographic and logistic obstacles, lack of motivation, and specialist availability.

To help overcome these barriers and improve screening rates, the researchers of the present study began building a statewide TDRS network in 2013. “The partnership connected FDSCs across Kentucky to an academic medical center providing low-cost telemedicine services (image interpretation, reporting, and referral),” the authors said.

They analyzed results from the first 5 years of the program, called the Appalachia Diabetic Eye Network (ADEN), and assessed pre- and postimplementation screening rates from a subset of clinic sites.

Participating clinics were offered nonmydriatic fundus photography (nFP) cameras, interpretation and reporting resources, staff training, and ongoing technical support without charge for 3 years. After, a nominal charge was applied per screening for interpretation. However, during the study period all FDSCs provided TDRS to patients as a free service (not billed to insurance, no out-of-pocket cost), as cost of care is a significant patient-perceived barrier to TDRS utilization.

The current analysis includes data from an electronic chart review of all patients who participated in ADEN between February 2014 and January 2019. Twenty-two clinics remained in the network throughout the period, and “in many clinics, costs were offset by gains in performance-based bundled-care bonuses.”

The 22-FDSC network comprised 6 federally qualified health center and 1 rural health clinic multisite systems. Clinics averaged 5.9 providers per site while all but the 5 urban sites served rural populations. 

Throughout the first 5 years, 13,923 TDRS exams were completed on 10,056 unique patients. Gender was evenly balanced, and the mean patient age was around 55. Patient surveys were also completed to assess intervention acceptability.

A total of 10,540 individual telescreening encounters were of sufficient quality to either rule out DR or identify a life- or sight-threatening pathology requiring referral. Of these, 3532 (33.5%) patients with ocular pathology were identified, 2319 (22.0%) patients had some level of DR with 1604 (15.2%) requiring specialist referral, and 808 (7.7%) patients required referral for other ocular pathologies.

The mean screening rate for audited clinics in the year prior to program implementation was 29.9% (641/2147) and increased to 47.7% (1012/2124) in the program’s first year, doubling patients’ odds of being screened (odds ratio [OR] 2.2; 95% CI, 1.3-3.7; 

A total of 5709 patients were recommended for follow-up or specialist referral, and the overall rate of referral was 41.0% (5709/13,923 exams)

Diabetic pathology was found in 22% of adequate screenings

Gains in screening rates were sustained over 4 years following implementation (OR, 1.9; 95% CI, 1.1-3.1; 

 = .018) despite varied clinic screening performance (4-year averaged range, 22.9%-55.1%)

Odds of early detection of DR doubled for patients with consecutive screenings (OR, 2.2; 95% CI, 2.0-2.4; 

Surveyed patients preferred TDRS to specialist exams (82.5%; 776/941) and would recommend the service to friends (92.7%; 868/936)

In total, “The need for over 8000 specialist exams was eliminated; more than 2000 referable pathologies were detected; odds of patients’ being screened doubled, and gains were sustained over years; care continuity doubled the odds of early detection of referable pathology and increased odds of future screening compliance; and most patients preferred and endorsed the intervention over traditional specialist exams,” the researchers wrote.

Over 95% of screenings that indicated DR presence were for nonproliferative DR, presenting an opportunity for providers to forestall disease progression in susceptible patients.

TDRS had a gradability rate of over 75%, which is just below the range observed in similar studies of nFP screenings. However, the authors note inconsistent image quality is at least partly due to multilevel barriers and inadequate implementation.

In addition, varied increases in screening rates across clinics point to implementation challenges across different contexts and practices. These discrepancies also imply unidentified upstream, multilevel variables affecting the program’s success.

Lack of demographic and clinical data precluded regression analyses from identifying patient-level predictors of screening outcomes, marking a study limitation.

“Combined, our findings provide a useful framework for other stakeholders to implement sustainable large-scale TDRS programs compatible with social distancing, appropriate for vulnerable populations, and synergistic with care continuity,” the researchers concluded.

“Despite high patient acceptability, screening rates across our clinics were variable and aggregate performance lagged the national DR screening rate, suggesting that to achieve full intervention potential, optimal implementation is essential. Future studies should address poorly understood barriers to TDRS implementation at the level of professionals, health care institutions, and payer systems.”

de Carvalho AB, Ware SL, Lei F, Bush HM, Sprang R, Higgins EB. Implementation and sustainment of a statewide telemedicine diabetic retinopathy screening network for federally designated safety-net clinics. 

. Published online November 4, 2020. doi:10.1371/journal.pone.0241767

Large telemedicine diabetic retinopathy screening networks based in federally designated safety-net clinics may be able to increase screening access and compliance among otherwise underscreened populations. 

Kentucky Telemedicine Program Increases Diabetic Retinopathy Screening Rates

Among children and adolescents suffering from 

, results from a prospective study show being overweight is associated with a higher frequency of migraine attacks and separation anxiety symptoms. The 

Migraine and obesity are common conditions among pediatric populations as epidemiological studies have found prevalence of migraine ranges from 3% in preschool age children to 8% to 23% in adolescents. Obesity and migraine are multifactorial diseases influenced by genetic, environmental, and psychological factors, and are associated with a poor quality of life, high health care costs, and increased risk of psychological disorders, researchers wrote.

Previous evidence has shown a beneficial effect of weight loss on headache severity while additional studies have documented the association of being overweight and the transformation of episodic migraine to chronic migraine. However, literature on the associations is inconclusive.

“Little is known about the psychological profile of headache patients who suffer from being overweight,” authors explained. “Data concerning the possible association between body weight, psychological factors, and headache are sparse, and involves only adult patients.”

In the current study, researchers set out to explore the role of weight and psychological symptoms on pediatric migraine by investigating the association between the 2 conditions, possible differences in anxiety and depression symptoms, and the potential mediating role of anxiety and depression in the association between bodyweight and frequency of migraine attacks. It is the first to investigate the association between body weight and anxiety depression in children migraineurs.

A total of 111 patients who presented to a headache center in Rome between January 2015 and April 2017 were included in the study. Mean (SD) patient age was 11.7 (2.4) years while the majority of patients (n = 64) were female. At the first clinic visit, all participants underwent a neurological examination and general physical exam. All patients were diagnosed with migraine without aura based on criteria of the International Classification of Headache Disorders, 3rd edition.

Participants also completed a headache diary between the 1st and 2nd visits to the clinic, documenting attack frequency. Patients were divided into 2 groups: high frequency (HF) patients with weekly to daily attacks, and low frequency (LF) patients with 3 or less episodes documented per month.

Researchers used the Italian Self-Administered Psychiatric Scales for Children and Adolescents (SAFA) battery of tests to assess psychiatric symptoms and psychological conditions. These include anxiety-related areas (SAFA-A), depression-related areas (SAFA-D), somatic concerns (SAFA-S), obsessive-compulsive symptoms (SAFA-O), psychogenic eating disorders (SAFA-P), and phobias (SAFA-F).

Of the 111 participants, 55 (49.6%) were normal weight (NW) and 56 (50.4%) were classified as overweight (OW; overweight/obese) based on body mass index (BMI) measurements. Mean BMI among this cohort was 29.5 (5.2). In addition, 60 children (54%) reported LF of attacks and 51 (45.9) reported HF.

HF patients were more common in the OW group (64.7%) than among the NW patients (35.3%; OR 2.5; CI 1.1–6.3; 

61.7% of the LF patients had normal body weight, while 38.3% were overweight

No gender or age differences were found between the HF and LF patients nor between the NW and OW patients

HF children showed higher levels of total anxiety as compared with the LF patients (SAFA-A Total: 

HF patients reported higher scores in all the SAFA-A subscales (

 < .025), suggesting that the HF patients were more anxious in several fields, such as school (

OW patients showed significantly higher scores in the “Separation anxiety” subscale (

Sobel’s test showed a mediating role between being overweight and HF of attacks for social anxiety (

Overall, results confirm the possible interaction between weight and migraine severity and may have clinical implications for the management and treatment of pediatric migraine.

As most drugs used for migraine prophylaxis can lead to body weight increase and because BMI increase can worsen migraine, researchers argue this factor should be taken into account when prescribing these medications to children and adolescents, especially when the treatment is associated with a paradoxical increase in attack frequency.

“In our study, the association between migraine, overweight, and separation anxiety symptoms may be due to the common psychological vulnerability factors,” researchers wrote. “Migraine and obesity may share an increased risk for internalizing disorders, difficulties in emotional regulation, and dysfunctional mother-child interaction.”

Obese children often exhibit low self-esteem, social anxiety, and social isolation, characteristics which have also been described in children with migraine. Authors hypothesize social anxiety may be amplified by being overweight, causing children to be less able to meet social expectations and potentially promoting migraine onset or aggravate attacks.

To prevent the cycle between weight, anxiety, and migraine, researchers suggest detecting anxiety symptoms, in particular social anxiety, could mitigate the effect of weight on migraine severity and may reduce the risk of migraine chronification. “A psychological intervention, such as cognitive-behavioral, may help children with migraine to identify and modify their negative thoughts about self, and may improve children’s self-esteem and coping ability.”

As the study only included children referred to a single center, results may not be representative of the entire pediatric migraine population, marking a limitation to the study. Psychological tools were based on self-reported questionnaires and are not diagnostic for anxiety or depression. Future studies ought to also differentiate between overweight and obsess patents.

“Because of the potential impact that the psychological symptoms and body weight can have on the migraine outcome, a systematic evaluation of children and adolescents with migraine should include both a psychological screening and a particular concern about body weight,” researchers concluded.

Tarantino S, Papetti L, Di Stefano A, et al. Anxiety, depression, and body weight in children and adolescents with migraine. 

 Published online October 28, 2020. doi:10.3389/fpsyg.2020.530911

Among children and adolescents suffering from migraine, results from a prospective study show being overweight is associated with a higher frequency of migraine attacks and separation anxiety symptoms.

Obesity Associated With More Attacks, Separation Anxiety in Pediatric Migraineurs

Researchers have published their postmortem report on a case of spinal muscular atrophy type 3 complicated by spinal superficial siderosis, 

 on their neuropathological and molecular findings.

The subject of the case report, a 55-year-old woman, had SMA type 3 and presented with lower extremity sensory symptoms characterized by pain and consistent with a myelo-radiculo-neuropathy. The woman, who began experiencing these symptoms at age 35, was diagnosed with SMA type 3—also known as the Kugelberg-Welander form of SMA—at 5 or 6 years. She was never fully ambulatory and had a surgical rod inserted at the age of 19 years for her severe scoliosis.

Prior to this case report, there was just 1 autopsy report of a patient with SMA type 3 genetically documented. According to the researchers, the neuropathological findings of the current case are in line with that first report, with classic changes of lower motor neuron neurodegeneration. Although, they noted the significant finding of a severe superficial siderosis involving predominantly the lower thoracic and lumbar-sacral spinal cord and nerve roots.

According to the researchers, the pathology of superficial siderosis in the central nervous system has previously been analyzed in an analysis of tissue from 9 patients, which found extensive deposits of iron and ferritin in siderotic tissues, severe loss of axons but better preservation of axons where the accumulation of iron is less severe, and anuclear foamy structures that were through to be to be axonal swellings. The researchers of the analysis concluded that the iron-induced neuronal injury was likely nor reversible.

In the current case study, the researchers saw similar findings, observing that axonal damage resulting from the superficial siderosis was present and severe. They also documented some axonal swellings in the affected tissue.

“In the sensory pathways specifically, the unbalanced demyelination of the gracile fasciculi (superficial regions as opposed to the inner regions) empasises the loss of axons within the siderotic regions. In the sensory nerve roots, the axonal loss was subtle, but the deposition of hemosiderin was significant,” noted the researchers. “We propose that the nerve root involvement, that is axonal loss or chemical irritation, best explain the sensory symptoms our patient presented in the evolution of her SMA type III with the understanding that mechanical factors cannot be totally excluded.”

Other neuropathologic observations included:

The anterior gray horns in the spinal cord were significantly decreased in volume

A severe circumferential hemosiderosis as shown by spinal lower thoracic and lumbo-sacral levels

Very thin anterior nerve roots with severe loss of myelinated axons and fibrosis

A very mild subacute leptomeningitis with Gram positive cocci

Pringle C, Nelson R, Miller W, Kothary, Michaud J. Spinal muscular atrophy type III complicated by spinal superficial siderosis: a case report with molecular and neuropathological findings. 

 Published online November 9, 2020. doi:10.1186/s40478-020-01063-9

Researchers have published their postmortem report on a case of spinal muscular atrophy type 3 complicated by superficial siderosis, offering details on their neuropathological and molecular findings.