Almost Half of Young Asthma Patients Misuse Inhalers

Many children with asthma don’t use their inhalers properly and don’t get a full dose of medicine, researchers report.

They evaluated inhaler use among 113 children between the ages of 2 and 16 who were hospitalized for asthma. Such patients are at highest risk for complications and death from asthma.

At least one crucial step in inhaler technique was missed by 42% of the children. About 18% did not use a spacer device with their inhaler. A spacer is a device that’s recommended for use with an inhaler to help the right amount of asthma medication reach the lungs.

Teens were the most likely to make mistakes in inhaler technique and to skip use of a spacer, according to the study published April 17 in the Journal of Hospital Medicine.

“We know that asthma can be well-managed in the majority of patients and using your inhaler correctly is key factor to managing asthma,” said lead author Dr. Waheeda Samady, a hospitalist at Ann & Robert H. Lurie Children’s Hospital of Chicago.

“Improper inhaler technique can contribute to children having uncontrolled asthma and needing to come to the hospital for their asthma,” Samady said in a hospital news release.

“Our study suggests that as health care providers we can do a better job showing patients and families the correct inhaler and spacer technique, and checking it frequently to ensure they master it,” she added.

“We see that our adolescent patients, who are transitioning to independent medication management, still need close monitoring to make sure they use their inhaler and spacer appropriately to achieve optimal asthma control,” Samady said.

She pointed out that teens may feel that using a spacer is only for younger children, but “using a spacer is recommended for adults as well,” Samady explained.

Previous research shows that adding a spacer to an inhaler boosts the amount of asthma medication a person takes in from 34% to 83%.

“Children with asthma can lead full lives if they receive the right medication at the appropriate dose, which is why correct inhaler technique is so crucial,” Samady concluded.

More information

The American Academy of Pediatrics has more on asthma inhalers.

SOURCE: Ann & Robert H. Lurie Children’s Hospital of Chicago, news release, April 17, 2019

https://consumer.healthday.com/respiratory-and-allergy-information-2/asthma-news-47/almost-half-of-young-asthma-patients-misuse-inhalers-745270.html

Pig brain tech could spur stroke therapies, drug and target validation

While Wednesday’s announcement that Yale researchers restored cell function in postmortem pig brains sheds no light on the feasibility of reviving consciousness, it does suggest new opportunities for stroke treatments, disease models and validation of findings from banked brain tissues.

In a study published in Nature, a team from Yale School of Medicine showed a perfusion system delivering a cell-protective cocktail, dubbed BrainEx, preserved tissue architecture and restored cellular function and metabolism in pig brains four hours postmortem.

The cocktail contained agents that suppressed neuronal firing in the brains, and the group did not detect activity patterns indicative of cognitive function. The researchers did show in separate experiments, however, that individual neurons in these brains were capable of firing action potentials, demonstrating that at least some of their electrophysiological function had been preserved.

The results contradict the assumption that irreversible loss of brain function occurs within minutes of blood flow interruption, and suggest therapies with multipronged effects similar to the BrainEx cocktail could help recover some brain cell functions after stroke. Yale has filed a patent covering broad use of the technology.

The cocktail consisted of Hemopure, a hemoglobin-containing blood substitute from HbO2 Therapeutics LLC, spiked with sugars, antibiotics, a free radical trapping agent, a vasodilator, the anti-convulsant lamotrigine, and inhibitors of caspase activity, necroptosis and reactive oxygen species formation, as well as a detection agent.

HbO2 Therapeutics markets Hemopure in South Africa to treat adult surgical patients with anemia, and in the Russian Federation for acute anemia. The company, which did not participate in the Nature study beyond a material transfer agreement, did not return requests for comment.

The authors think the BrainEx technology could also be used to characterize drug effects. They showed the treated brains responded as expected to the antihypertensive drug nimodipine and the immunostimulant lipopolysaccharide.

The technology could also help bridge the gap between molecular studies in banked brain tissues and functional studies in live subjects, providing a platform for functional target validation through experiments gauging cell- or tissue-level activity. Researchers in search of molecular targets and biomarkers for neurological diseases have been ramping up transcriptomic studies of postmortem human brain samples (see “Molecular Mentality“).

“This platform could offer investigators the opportunity to conduct prospective, functional ex vivo studies in intact brains that would otherwise be limited to static histological, biochemical or structural investigation,” the authors wrote.

Andrea Beckel-Mitchener, team lead for the BRAIN Initiative at NIH’s National Institute of Mental Health (NIMH), said several hurdles would have to be cleared before the technology could move from animal to human brains, including optimizing the BrainEx system for human biology, and adapting donor informed consent procedures.

NIMH’s Brain Initiative co-funded the study.

https://www.biocentury.com/bc-extra/preclinical-news/2019-04-18/pig-brain-tech-could-spur-stroke-therapies-drug-and-target-

Syringe ‘watch’ puts a life-saving allergy shot on your wrist

Brandon Martin/Rice University

If you’re prone to serious allergic reactions, carrying an epinephrine shot (such as an EpiPen) could be vital. Those shots are often bulky, though, and there’s a real chance you could lose yours right before you need it. Students at Rice University have a (relatively) simple solution: put the shot on your wrist. They’ve developed a wearable, the EpiWear, that hides a foldable epinephrine syringe in a device not much larger than a watch. If you’re in an emergency, you just need to unfold it, flick a safety lever and push a button when you’re ready to inject the medicine into your thigh.

The team is keenly aware of safety concerns. The three-piece folding design makes it effectively impossible to trigger the needle by accident, and there are plans for a case that would prevent the button from touching anything until the shot is necessary.

EpiWear is still very young, to the point where it’s made of 3D-printed parts. The students plan to refine it, however, including a smaller, more refined look that would be more acceptable on a night out. They’re even considering adding watch functionality so that it does more than sit on your wrist in ordinary situations. Should it become a practical reality, you might not have to feel awkward about carrying a life-saving injection with you — and you’d never have to worry about leaving it behind.

Source: Rice University

https://www.engadget.com/2019/04/19/rice-epinephrine-wearable/

CMS to block use of drugmaker coupons on ObamaCare plans’ out-of-pocket costs

CMS is taking aim at increasing the use of generic drugs in ACA plans in a new rule filed Thursday evening.

In the rule (PDF), the Centers for Medicare & Medicaid Services included a provision to allow insurers in the 2020 plan year to implement copay accumulator programs that would block the use of manufacturer coupons to lower annual out-of-pocket costs on certain brand name drugs when there’s a generic available.

Virginia and West Virginia have banned these programs in their individual markets, and several additional states are considering similar moves.

CMS, however, argues that the practce would decrease drug spending and encourage people to use generics.

“At CMS, we have improved the operations of the exchange to deliver a better consumer experience at a lower cost,” CMS Administrator Seema Verma said in an announcement.

Here’s a look at the collection of notes and changes CMS included in the new rule:

• CMS reiterated its support for a legislative fix to end ACA plan “silver-loading,” including the potential for cost-sharing reduction payments to be reinstated. It noted that all the comments it received in response to a request for more information in the proposed rule supported allowing silver loading to continue.

Insurers offering plans on the Affordable Care Act exchanges responded to the Trump administration’s 2017 decision to end CSRs by stacking most premium increases on silver plans, which are used to determine federal subsidies. This offered an alternative way to lower cost-sharing.

“The administration supports a legislative solution that would appropriate CSR payments and end silver loading,” CMS said in the rule. “In the absence of congressional action, we sought comment on ways in which HHS might address silver loading.”

It did not take any action to change the practice. The earliest it might act would be for the 2021 plan year, CMS said.

• CMS is also considering changes for automatic re-enrollment in 2021, according to the rule. The agency requested feedback on changes in this area as well in the proposed rule. CMS expressed concern that the current form of re-enrollment may prevent plan members from updating their information in a timely manner, which could lead to wasteful spending on tax credits.

All commenters that weighed-in on the issue called for CMS to leave the current re-enrollment policy in place, as it eases administrative burden and can prevent lapses in coverage.

CMS said it will consider those responses as “we continue to explore options to improve exchange program integrity.”

• The rule also finalizes several policy adjustments for the 2020 plan year in the individual, small group and large group markets. The agency reduced user fees borne by insurers that funds operation of state exchanges and Healthcare.gov from 3% to 2.5%.

This decrease will go toward further decreasing premiums, CMS said.

• CMS also aimed to improve transparency in its enhanced direct enrollment program, which allows people to sign up for ACA plans directly through an approved payer or broker without the need to visit Healthcare.gov. Web brokers will be required to provide the agency will a list of brokers and agents that use their platforms.

https://www.fiercehealthcare.com/payer/cms-rule-aims-to-block-use-drugmaker-coupons-aca-plan-members-out-pocket-costs

Discovery may explain why women get autoimmune diseases more than men

It’s one of the great mysteries of medicine, and one that affects the lives of millions of people: Why do women’s immune systems gang up on them far more than men’s do, causing nine times more women to develop autoimmune diseases such as lupus?

Part of the answer, it turns out, may lie in the skin.

New evidence points to a key role for a molecular switch called VGLL3. Three years ago, a team of University of Michigan researchers showed that women have more VGLL3 in their skin cells than men.

Now, working in mice, they’ve discovered that having too much VGLL3 in skin cells pushes the immune system into overdrive, leading to a “self-attacking” autoimmune response. Surprisingly, this response extends beyond the skin, attacking internal organs too.

Writing in JCI Insight, the team describes how VGLL3 appears to set off a series of events in skin that trigger the immune system to come running—even when there’s nothing to defend against.

“VGLL3 appears to regulate immune response genes that have been implicated as important to autoimmune diseases that are more common in women, but that don’t appear to be regulated by sex hormones,” says Johann Gudjonsson, M.D., Ph.D., who led the research team and is a professor of dermatology at the U-M Medical School. “Now, we have shown that over-expression of VGLL3 in the skin of transgenic mice is by itself sufficient to drive a phenotype that has striking similarities to systemic lupus erythematosus, including skin rash, and kidney injury.”

Effects of excess VGLL3

Gudjonsson worked with co-first authors Allison Billi, M.D., Ph.D., and Mehrnaz Gharaee-Kermani, Ph.D., and colleagues from several U-M departments, to trace VGLL3’s effects.

They found that extra VGLL3 in skin cells changed expression levels of a number of genes important to the immune system. Expression of many of the same genes is altered in autoimmune diseases like lupus.

The gene expression changes caused by excess VGLL3 wreaked havoc in the mice. Their skin becomes scaly and raw. Immune cells abound, filling the skin and lymph nodes. The mice also produce antibodies against their own tissues, including the same antibodies that can destroy the kidneys of lupus patients.

The researchers don’t yet know what causes female skin cells to have more VGLL3 to begin with. It may be that over evolutionary time females have developed stronger immune systems to fight off infections—but at the cost of increased risk for autoimmune disease if the body mistakes itself for an invader.

The researchers also don’t know what triggers might set off extra VGLL3 activity. But they do know that in men with lupus, the same VGLL3 pathway seen in women with lupus is activated.

Many of the current therapies for lupus, like steroids, come with unwanted side effects, from increased infection risk to cancer. Finding the key factors downstream of VGLL3 may identify targets for new, and potentially safer, therapies that could benefit patients of both sexes.

Lupus, which affects 1.5 million Americans, can cause debilitating symptoms, and current broad-based treatment with steroids can make patients far more vulnerable to infections and cancer.

Patients’ role in future research

Their colleague and senior coauthor Michelle Kahlenberg, M.D., of the U-M Division of Rheumatology, is now recruiting patients with lupus for a study sponsored by U-M’s A. Alfred Taubman Medical Research Institute that could provide answers to these questions and more.

Billi, a resident in dermatology, notes that when she speaks with patients who come to Michigan Medicine’s dermatology clinics for treatment of the skin problems lupus can cause, she has to acknowledge the limits of current treatment. Even so, she says, patients are eager to take part in studies by contributing skin and DNA samples that could lead to new discoveries about their condition.

“Many patients are frustrated that they’ve had to try multiple therapies, and still nothing is working well,” she says. “To be able to tell them that we’re working on a mouse that has the same disease as them, and that we need their help, brings out their motivation and interest in research. They know that it’s a long game, and they’re in for it.”

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Explore further

‘Master regulator’ in genes may make women more susceptible to autoimmune diseases

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More information: Allison C. Billi et al, The female-biased factor VGLL3 drives cutaneous and systemic autoimmunity, JCI Insight (2019). DOI: 10.1172/jci.insight.127291

https://medicalxpress.com/news/2019-04-discovery-women-autoimmune-diseases-men.html

New Antibody May Suppress HIV for Up to 16 Weeks Without Antiretroviral

Monotherapy with UB-421 may suppress human immunodeficiency virus (HIV) for up to 4 months in infected patients undergoing a short-term antiretroviral therapy (ART) pause, according to a study published online today in the New England Journal of Medicine.

“UB-421 monotherapy maintained suppression of plasma viremia (< 20 copies per milliliter) in the absence of ART for up to 8 weeks in participants receiving 10 mg per kilogram every week, and for up to 16 weeks in participants receiving 25 mg per kilogram every 2 weeks,” write Chang-Yi Wang, PhD, from United Biomedical, Hauppauge, New York, and colleagues.

ART has changed HIV infection from a fatal condition to a manageable, chronic illness. However, there is growing interest in identifying new approaches to suppressing HIV.

In an interview with Medscape Medical News, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, Rockville, Maryland, highlighted three potential reasons why an individual might want to move away from taking daily ART.

First, pill fatigue is not uncommon, he explained, because some individuals do not like the idea of taking a pill every day for life — often because of the associated stigma.

Second, some individuals have virus that is resistant to the combination of drugs in their ART regimen.

And, third, some experience ART-related toxicities that they find unacceptable, said Fauci.

Although broadly neutralizing HIV-specific monoclonal antibodies have been investigated as a treatment option, emergence of antibody-resistant HIV, leading to viral rebound when ART is discontinued, remains a problem.

In contrast, UB-421 is a novel investigative broadly neutralizing monoclonal antibody.

“The unique thing about this antibody,” said Fauci, “is that it is directed against the host’s CD4 cell surface receptor” and thus blocks HIV entry into cells.

The antiviral activity of UB-421 has already been demonstrated in a phase 1 study and a phase 2a study in HIV-infected people who had not previously received treatment.

With this in mind, Wang and colleagues conducted a phase 2, open-label, nonrandomized study to examine whether UB-421 monotherapy can prevent plasma viremia and reversibly reduce the population of regulatory T cells, while maintaining CD4+ T-cell counts in ART-stabilized HIV-infected patients.

They enrolled 29 patients with well-controlled HIV infection who stopped their oral ART, either at the time of their first infusion or 1 week later, depending on their ART regimen. Patients entered one of two study cohorts, each of which received eight intravenous infusions of UB-421.

Cohort 1 (14 patients) received weekly infusions at a dose of 10 mg/kg, whereas Cohort 2 received infusions every other week at a dose of 25 mg/kg.

The study’s primary outcome was the time to viral rebound (≥ 400 copies per milliliter) after the first UB-421 infusion.

At the end of the 8- or 16-week treatment phase, patients in both cohorts restarted their ART regimens and were followed for 8 more weeks.

No patients in either cohort experienced plasma viral rebound to more than 400 copies per milliliter.

In addition, UB-421 infusion maintained HIV suppression (< 20 copies per milliliter) in all patients (94.5% of measurements at study visits 2 through 9) during ART interruption. Although low-level viral blips occurred in eight patients (28%) across both cohorts, they did not require specific treatment.

Throughout the study, CD4+ T-cell counts remained stable, while the percentage of CD4+ regulatory T-cells dropped significantly (mean reduction, 31% to 56% from baseline), but returned to baseline levels after the treatment phase. CD8+ T-cell counts increased (P < .001) in both cohorts.

UB-421 was also generally well tolerated and safe. Of the 29 enrolled patients, two in Cohort 2 did not complete all eight infusions of UB-421 (one was lost to follow-up, and one withdrew as a result of a grade 2 skin rash).

Three patients in Cohort 1 (21%) and five (33%) in Cohort 2 experienced adverse events (AEs) of grade 2 or higher.

The most common AE that was considered drug related was rash, which was typically mild and transient. Twelve patients (41%) had a rash of grade 1, and three (10%) had a rash of grade 2.

Only 1 serious AE (a grade 1 inguinal hernia in a patient in Cohort 1) was reported.

The researchers found no evidence of HIV resistance to UB-421 but acknowledge that a study so small and of such short duration is limited in its ability to identify this.

“Future clinical studies with continued monitoring for drug-resistant strains during long-term administration of UB-421 are needed to properly assess this concern,” they emphasize.

Overall, “this is an interesting study that provides successful proof of concept,” concluded Fauci.

This study was supported by United Biomedical; United Biomedical Asia; United BioPharma; the Ministry of Economic Administration, Taiwan; the National Institute of Allergy and Infectious Diseases, National Institutes of Health. Several authors have disclosed receiving personal fees from United Biomedical Inc or United BioPharma; being a cofounder of and/or salaried employers and/or shareholders at United Biomedical Inc; and holding several patents. Fauci has reported that one of the authors, Tae-Wook Chun, PhD, is an independent investigator in his laboratory; however, Fauci reports having no involvement in this study and no input into the paper. The remaining authors have disclosed no relevant financial relationships.

New Engl J Med. Published online April 17, 2019. Abstract

https://www.medscape.com/viewarticle/911942#vp_1

Washington University Med School Latest to Offer Free Tuition

The Washington University School of Medicine in St. Louis on Wednesday became the seventh US medical school to offer its students free tuition, as the national trend starts to build momentum, according to a school news release.

The St. Louis medical school said it has committed $100 million over the next decade to allow up to half of future medical students to attend its classes for free. Many other students will receive partial tuition support, the announcement said.

Unlike the tuition-free programs at some other schools, which are funded by wealthy donors, the one at Washington University will come “primarily” from the school of medicine via its departments and its affiliated training hospitals, Barnes-Jewish Hospital and St. Louis Children’s Hospital, according to the news release.

The tuition grants will start with the incoming class of 2019-2020. Scholarships will be awarded on the basis of need, merit, or some combination of the two.

A portion of the $100 million will be spent on improving the medical school’s curriculum. Among the goals of the revamp, the university wants to encourage more young doctors to become academic physicians.

Before announcing the scholarships, Washington University School of Medicine was already helping students graduate with as little debt as possible. The school’s policy is to freeze the tuition of incoming students so that they pay the same amount each year for the 4 years of medical education.

Of the 120 students in each class, 20 already receive full scholarships, and 40 receive partial tuition. The annual cost of tuition for the 2018-2019 first-year class is about $65,000.

Partly as a result of these policies, the average debt of Washington University medical students when they graduate is $99,088, 40% less than the national average of $166,239. In 4 of the past 5 years, the institution has been ranked as the second lowest nationally in average medical school debt, according to the school.

“For most medical students, debt is a significant factor in selecting a school and a career path,” Eva Aagaard, MD, senior associate dean for education and the Carol B. and Jerome T. Loeb Professor of Medical Education, said in the release. “We want to help alleviate that financial burden and instead focus on training the best and brightest students to become talented and compassionate physicians and future leaders in academic medicine.”

Rapidly Growing Trend

The best-known free tuition program is the one at New York University School of Medicine, thanks to a recent segment on the television program, 60 Minutes. NYU announced last August that it would offer free medical school tuition to all current and future students, regardless of need or merit.

The cost of a year’s tuition there is $55,000, but students have to cover their university-subsidized living costs and insurance, which amounts to about $28,000 a year. NYU is paying for the students’ education through an endowment that is currently worth $450 million.

Although NYU is the largest and most highly ranked medical school to make this commitment, it was not the first. In December 2017, the Columbia University College of Physicians and Surgeons, in New York City, announced it would cover tuition for all students who qualified for financial aid and who received student loans. The scholarship, made possible by a gift from Columbia alumnus and former Merck CEO Roy Vagelos, replaces the student loan.

The David Geffen School of Medicine at the University of California, Los Angeles, also offers full, merit-based free tuition, room and board, books, and supplies to about 20% of each class. The program is funded from the endowment that entertainment mogul Geffen bestowed on the university in 2012.

The Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, in Ohio, has offered free tuition since 2008. Each year, about 2000 applicants vie for the 32 tuition-free slots in the medical school.

Two new medical schools are offering free tuition as well. In July 2018, the University of Houston’s new College of Medicine announced that all 30 students in its inaugural class will receive their education gratis when the school opens in 2020.

Kaiser Permanente’s School of Medicine, in Pasadena, California, which opens in summer 2020, will waive tuition for 4 years for its first five classes of students, it was recently announced.

https://www.medscape.com/viewarticle/912009