Migraine treated without medicine in pilot study

By slightly changing the body’s own molecules using a small inhaler, certain migraine patients can either cut down on medication or do without it completely. This is shown by a pilot study which has been published in the scientific journal Cephalalgia.

Patients who suffer from migraine with aura, which is where they experience either sensory or visual disturbances before the painful headaches begin, have been examined in the study. Eleven patients participated in the pilot study, which will now be followed by a large clinical trial.

One of the authors is MSc in Engineering and PhD Troels Johansen, who carried out the study as part of his PhD at the Department of Clinical Medicine at Aarhus University and the Headache Clinic at Aarhus University Hospital, Denmark.

He explains that migraines occur as part of a chain reaction during which the veins in the brain contract and the blood cannot therefore supply the brain with sufficient oxygen.

“We utilise CO2 and oxygen, which are the body’s natural molecules for mobilising its own defence against migraine attacks. The inhaler expands the blood vessels that supply the brain with oxygen by up to seventy per cent and thereby stops the destructive chain reaction,” says Troels Johansen, adding that the effect of the treatment starts after a few seconds.

The pilot study was carried out from 2016-2017 with eleven patients with migraine with aura. One of the results was that the effect of the pain relief increased significantly with each use of the inhaler. Forty-five per cent experienced an effect the first time, and that number rose to 78 per cent the second time.

“The study shows some very significant physiological effects in the body,” says Troels Johansen, who currently teaches at the Aarhus University School of Engineering. Together with a team of employees, he has put the inhaler into production through the company BalancAir.

Since the pilot project is limited to migraine with aura and only comprised eleven patients, Troels Johansen is now planning to conduct a large clinical trial that will also include migraine without aura and chronic migraine.

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Story Source:

Materials provided by Aarhus University. Note: Content may be edited for style and length.

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Journal Reference:

1. Cecilia H Fuglsang, Troels Johansen, Kai Kaila, Helge Kasch, Flemming W Bach. Treatment of acute migraine by a partial rebreathing device: A randomized controlled pilot study. Cephalalgia, 2018; 38 (10): 1632 DOI: 10.1177/0333102418797285

https://www.sciencedaily.com/releases/2018/10/181004110050.htm

DNA-encoded checkpoint inhibitor antibodies advance immunotherapy

Wistar scientists and collaborators demonstrate for the first time that through engineering constructs, they can express DNA-encoded monoclonal antibodies (DMAbs) targeting CTLA-4, an important cancer checkpoint molecule that blocks anti-cancer immunity. Using a synthetic DNA platform, they built versions of the anti-CTLA-4 molecule and were able to then deliver the DMAbs and have them generate fully functional anti-CTLA4 molecules in vivo. This proof-of-principle study opens new avenues for the design and delivery of therapeutic checkpoint inhibitors and suggests potentially novel applications of this technology in cancer treatment. Study results were published online in Cancer Research.

Treatment of cancer with checkpoint inhibitors has recently revolutionized cancer immunotherapy. Since the discovery of immune checkpoints, which was recognized as a groundbreaking development for cancer therapy and awarded the Nobel Prize in physiology or medicine this week, checkpoint inhibitors are becoming standard of care for various malignancies, showing unprecedented impact for patients.

Despite the tremendous advancement in cancer therapy brought by monoclonal antibodies targeting checkpoint molecules, manufacturing complexity and repeated dosing may limit a broader use of this technology.

“Our work provides the first demonstration that we can use synthetic DNA technology to produce checkpoint inhibitor molecules in vivo to impact tumor growth in a preclinical setting,” said lead researcher David B. Weiner, Ph.D., executive vice president and director of the Vaccine & Immunotherapy Center at The Wistar Institute, and W.W. Smith Charitable Trust Professor in Cancer Research. “We showed that DMAbs may represent a valuable addition to the cancer immunotherapy toolbox: In our preclinical studies, DMAbs achieved antitumor activity comparable to that of traditional monoclonal antibodies, while being delivered through a simpler formulation that may provide a bridge to expand target populations for checkpoint inhibitors.”

The team developed a synthetic, sequence-optimized DNA plasmid designed to encode anti-mouse CTLA-4 monoclonal antibodies. When injected in the muscle of mice with the aid of an electroporation device to enhance uptake, the anti-CTLA-4 DMAbs resulted in significant and prolonged antibody expression with even a single dose. Importantly, this approach stimulated robust CD8+ T-cell infiltration, achieving tumor clearance across multiple mouse tumor models. The researchers then went on to develop human checkpoint inhibitor molecules and demonstrated their production in mice and their ability to stimulate human T-cell responses associated with antitumor activity.

“Our results open the door for further applications of DMAbs in cancer immunotherapy,” said Elizabeth K. Duperret, Ph.D., postdoctoral fellow in the Weiner Lab and first author on the study. “This platform is rapid and flexible, allowing for further optimization of antibody sequences, including development of novel therapeutic approaches for which conventional monoclonal antibodies are not suitable.”

This work was supported by National Institutes of Health grants F32 CA213795 and SPORE P50CA174523, and funding from the W.W. Smith Family Trust and the Basser Foundation. Core support for The Wistar Institute was provided by the Cancer Center Support Grant P30 CA010815. Additional funding was provided by Inovio Pharmaceuticals.

Co-authors of this study from The Wistar Institute include Aspen Trautz, Regina Stoltz, Ami Patel, Alfredo Perales-Puchalt, and Kar Muthumani. Other co-authors include Megan C. Wise, Trevor Smith, Kate Broderick, Emma Masteller, J. Joseph Kim, and Laurent Humeau from Inovio Pharmaceuticals.

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Story Source:

Materials provided by The Wistar Institute. Note: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2018/10/181004112544.htm

Rigel Pharma Analyst Day saw 85% tavalisse refill rate, says Piper Jaffray

Piper Jaffray analyst Christopher Raymond kept his Overweight rating and $8 price target on Righer Pharmaceuticals after the company’s Analyst Day. He says the presentation indicated utilization of Tavalisse across all lines and a 85% refill rate, suggesting that the drug had higher demand than anticipated. Raymond contends that the launch so far has been successful while also pointing to the company’s “positive progress for fostamatinib in AIHA and other pipeline products”.
https://thefly.com/landingPageNews.php?id=2800113

‘Swatting’ and other cyberthreats a growing problem for 911 call centers

In a northern Virginia suburb of Washington, D.C., several months ago, police from two departments rushed to a school full of students after receiving a 911 call from a person who said they were feeling “homicidal.”

The call was a false alarm. But there was little they could do, officials said.

The call was ultimately traced to an IP address located outside the country, said Eddie L. Reyes, director of Public Safety Communications for Prince William County, as he addressed lawmakers on Capitol Hill.

“In Prince William County, it’s difficult to find legitimate callers—people who are calling 911 because they can’t breathe or they’re having a robbery in progress—let alone, the swatters,” Reyes said, referring to the harassment tactic of deceiving an emergency service into sending a police and emergency service response team to another person’s address.

He was testifying in support of an anti-swatting act which would create stiffer criminal penalties against those who purposely transmit false caller ID information in order to trigger an emergency response to a false location.

Swatting has become a growing issue around the country—including an attack against Parkland High School shooting survivor turned anti-gun activist David Hogg, when police knocked down the door of his family’s home after receiving a “swatting call” to his address—experts testified during a hearing on possible legislation to improve public safety communications.

In some cases, swatting incidents have turned deadly, as with the ongoing case against a California man charged with making a fake emergency call that turned deadly for a Kansas man in December.

“Most states and municipalities do not have laws that address these types of incidents, so at best, those who are identified and arrested often only face misdemeanor charges,” Reyes said in testimony submitted to the House Energy and Commerce Committee. “Swatting has proven not only costly for 9-1-1 centers and field responders, but also extremely difficult to combat. Thus, enhancing the penalties for swatting and providing reimbursement to public safety agencies will be very helpful.”

Lawmakers were also considering legislation that would block state and local government from diverting funds designated for emergency communications for other purposes. Reyes and other experts testifying before lawmakers said that funding putting additional resources into fending off cyber attacks. “Our networks are constantly being attacked, the threats are growing stronger on a regular basis but, unfortunately at the local municipal level, we don’t have the resources in both funding and personnel to address or tackle those types of constant threats. We’re not in a proactive mode. We’re more in a reactive mode,” Reyes said referring to the additional threat of denial of service attacks.

James Curry, the communications division head in Hunterdon County, which is part of the New Jersey Department of Public Safety, testified in support of the fee integrity act after New Jersey officials reportedly diverted 911 funding for other parts of the state’s budget. He said having the funding available to update to next-generation 911 technology could help fight threats to the 911 system.

Curry was referring to internet protocol (IP)-based 911 systems which allow 911 to collect digital messages including voice, photos, videos, text messages.

While NPR reported earlier this year that it further raises concerns about swatting threats, Curry said the technology would help his department more easily track down callers.

https://www.fiercehealthcare.com/hospitals-health-systems/emergency-911-centers-need-more-funding-to-fight-back-against-cyber

Regular Aspirin Use Curbs Risk of Liver and Ovarian Cancer

Two new studies have found that regular long-term aspirin use may lower the risk of certain cancers, adding to the growing evidence that aspirin may play a role as a chemopreventive agent.

In the first study, a pooled analysis of two prospective US cohort studies, found that aspirin use was associated with a dose-dependent reduction in the risk of epatocellular cancer (HCC), an effect that was not observed with nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs).

The second study analyzed NSAID use and ovarian cancer diagnosis using data from two large prospective cohorts and found that regular aspirin users had a lower risk of ovarian cancer. Conversely, an increased risk of ovarian cancer was observed with long-term high-quantity use of other analgesics, particularly nonaspirin NSAIDs.

In an accompanying editorial, Victoria L. Seewaldt, MD, from the City of Hope Comprehensive Cancer Center, Duarte, California, states that these two studies “have the power to start to change clinical practice.”

“Both ovarian cancer and HCC are deadly cancers in need of new prevention strategies,” she writes. “The findings from these two studies provide important information that can guide chemoprevention.”

The two articles and editorial were published online October 4 in JAMA Oncology.

Finding the Connection

A growing number of studies have attempted to tease out the relationship between aspirin use and its possible use for chemoprevention.

Last year, for example, a large observational study found that regular aspirin use was associated with both a reduced relative risk for death from any cause and also death from cancer.

Also in 2017, a study showed that regular use of NSAIDs in long-term survivors of colorectal cancer was significantly associated with improved overall survival, although this benefit was limited to patients with KRAS wild-type tumors.

A third recent study also found that regular aspirin use was associated with a 46% reduced relative risk for pancreatic cancer.

“Several decades of research provide strong evidence that the anti-inflammatory properties of aspirin may reduce cancer risk, particularly for colorectal cancer,” writes Seewaldt in her editorial. “In 2015, given the strength of the association between aspirin use and colorectal cancer risk reduction, the US Preventive Services Task Force (USPSTF) recommended that in individuals aged between 50 and 69 years with specific cardiovascular risk profiles, colorectal cancer prevention be included in the rationale for regular aspirin prophylaxis.”

However, she emphasized that despite the USPSTF recommendations, there are still many unanswered questions regarding the use of aspirin as a means of lowering the risk of colorectal cancer. These include the dose and timing of aspirin chemoprevention and the molecular mechanisms underlying aspirin’s chemoprevention effects.

Seewaldt says the most important unanswered question is “the ability of aspirin to prevent other malignant neoplasms.”

The findings of these two new studies may help answer that last question. The articles provide “key evidence that supports the ability of regular aspirin use to prevent ovarian cancer and HCC, respectively,” she says. “The findings from these two studies provide important information that can guide chemoprevention.”

Reducing HCC Risk

In the first study, Tracey G. Simon, MD, from Massachusetts General Hospital in Boston, and colleagues, assessed the potential benefits of aspirin use for the primary prevention of HCC using data from the Nurses’ Health Study and Health Professionals Follow-up Study, with a total cohort of 133,371 healthcare professionals (87,507 women and 45,864 men). Regular use was defined as standard dose (325 mg) aspirin tablets taken at least two or more times per week.

After more than 26 years of follow-up, the authors found that regular aspirin use was associated with a significant 49% reduced risk of developing HCC.

The HCC incidence rate among regular aspirin users was 2.1 cases/100,000 person-years, while it was 5.2 cases/100,000 person-years for non-users (P < .001). This benefit appeared to be both dose- and duration-dependent and was evident with aspirin use of 5 years or more, at a dose of 1.5 or more standard tablets per week.

Adjusting for regular use of nonaspirin NSAIDs (≥ 2 tablets/week) had no effects on the results, and the benefit from aspirin in relation to HCC was consistent across all prespecified groups (all P > .05).

As for nonaspirin NSAIDs, a reduction in HCC risk was not observed with regular versus nonregular use, and there was also no association between increasing duration of NSAID use and HCC risk (HR for ≥ 10 years of use vs nonuse, 1.06; P for linear trend = .20 among users).

“Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer,” the authors conclude.

Risk Reduction in Ovarian Cancer

The second study evaluated whether regular aspirin or nonaspirin NSAID use could lower the risk of  ovarian cancer. Led by Mollie E. Barnard, ScD, from the Chan School of Public Health at Harvard University, Boston, Massachusetts, the authors evaluated the use of aspirin or nonaspirin NSAIDS with the risk of ovarian cancer.

Their data came from two prospective cohorts: 93,664 women in the Nurses’ Health Study followed from 1980 to 2014 and 111,834 women in the Nurses’ Health Study II followed from 1989 to 2015.

The timing, duration, frequency, and number of tablets used were evaluated for each type of analgesic (aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen) and data were updated every 2 to 4 years. A total of 1054 cases of incident epithelial ovarian cancer occurred in the total combined cohort.

There were no significant associations observed between aspirin use and ovarian cancer risk when current versus nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83 – 1.19). But when the authors evaluated low dose and standard dose separately, there was an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61 – 0.96), but none for standard-dose aspirin (HR, 1.17; 95% CI, 0.92 – 1.49).

Overall, this extrapolated to a 23% lower risk of ovarian cancer among current low-dose aspirin users compared with nonusers.

There was a positive association for longer duration of use with standard-dose aspirin (≥ 5 years vs < 1 year) (HR, 1.77; 95% CI, 1.13 – 2.77; P = .004 for trend) and for 2500 or more tablet-days of standard-dose aspirin compared with no regular use (HR, 1.58; 95% CI, 1.00 – 2.48; P = .02 for trend).

In contrast, current use of nonaspirin NSAIDs was positively associated with an increased risk of ovarian cancer compared with nonuse (HR, 1.19; 95% CI, 1.00 – 1.41), with significant positive trends for duration of use (P = .02 for trend) and cumulative average tablets per week (P = .03 for trend).

These data translated into a 19% higher relative risk of ovarian cancer among regular NSAID uses compared with nonusers.

The HCC study was supported by grants from the Nurses’ Health Study, Health Professionals Follow-up Study, and National Institutes of Health. The ovarian cancer study was supported by the National Institutes of Health. A co-author of the HCC study previously served as a consultant for Bayer Pharma AG on work unrelated to the study. No other disclosures were reported. Seewaldt is supported by grants from the National Cancer Institute and Prevent Cancer Foundation.

JAMA Oncol. Published online October 4, 2018. Study 1, Study 2, Editorial

https://www.medscape.com/viewarticle/902974#vp_1

MediciNova Gets Orphan Drug Tag for Glioblastoma Med

MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number:4875), today announced that the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation to MN-166 (ibudilast) as adjunctive therapy to temozolomide  for the treatment of glioblastoma (GBM).

Yuichi Iwaki, MD, PhD, President and Chief Executive Officer of MediciNova, Inc., commented, “We are very pleased that the FDA has granted orphan-drug designation for MN-166 as adjunctive therapy to temozolomide for the treatment of GBM, a rare cancer with a high recurrence rate and poor prognosis.”

https://globenewswire.com/news-release/2018/10/04/1617208/0/en/MediciNova-Announces-FDA-Grants-Orphan-Drug-Designation-to-MN-166-ibudilast-for-Glioblastoma.html

In Philly building trades, construction workers help colleagues battle addiction

Last year, as a construction apprentice learning to install insulation and remove asbestos, Michael Rossi injured his knee. After telling his coworkers he would be out for a few weeks for surgery, one man pulled him aside.

“He said, ‘You’re an apprentice, you need the money, why not go to a doctor and get something and mask the pain,’” Rossi recalled. “And I had to tell him, that’s not really an option for me. I was coming up on five years of sobriety. I’d struggled with painkillers. The last thing I wanted to do was get a script for them.”

Rossi had just gotten a lesson in a hidden reality of the construction industry: In these physically demanding workplaces, painkillers are still a common way to get through the day, even as the opioid crisis has spiraled and workers have attended funeral after funeral. Workplace data on addiction is sparse, but recent research has indicated that construction workers are at higher risk for fatal overdoses — particularly heroin overdoses.

Rossi couldn’t stop thinking about the conversation. At home, recovering from surgery, he called the president of his union. “I’d already seen a lot of guys in the trades who ended up dying or getting thrown out of the apprenticeship program,” he said. “And so I asked him what we were doing about the opioids.”

These days, Rossi is a peer advocate, one of a few dozen construction workers in Philadelphia’s building trades who double as recovery aides on job sites around the city. They watch for coworkers who might be showing the signs of a substance use disorder and encourage them to seek treatment. Or they help colleagues in recovery stay sober on the job site.

“I never thought I’d be breaking my anonymity,” said Rossi, who participates in a 12-step recovery program. “But I feel compelled to now.”

The peer advocates are all volunteers, trained by the Allied Trades Assistance Program, the building trades’ program that refers members and their families to substance-use treatment. ATAP has been around for 30 years, but its peer advocates program is just a year old, spearheaded by executive director Ken Serviss.

Advocates say they work to dispel the stigma against addiction on the job site by being as open as they can about their lives, hoping that coworkers will come forward.

“If you’re working in the room with me, you know what I had for breakfast, I’m going to tell you about my kids, and I’m going to tell you about my peer advocacy,” said Ed O’Toole, a plumber. “I tell the general contractor on the job, if there’s anyone struggling, let me know, before they lose their job.”

JESSICA GRIFFIN / STAFF PHOTOGRAPHER

Ed O’Toole on a job site: “I tell the general contractor on the job, if there’s anyone struggling, let me know, before they lose their job.”

Serviss is hoping to expand the peer advocate program by applying for federal grants, recruiting more members and training advocates to dispense Narcan, the overdose-reversing spray, on job sites.

Advocates, who meet every month at ATAP’s headquarters in the Far Northeast, are split between older union members, who largely have dealt with alcoholism, and a younger group more familiar with painkillers and heroin addiction.

One advocate was homeless for 15 years before entering recovery and getting a job as a laborer; another, sober for decades, is now trying to help his son through an opioid addiction as he counsels coworkers on job sites.

Others came to the program after losing coworkers to overdoses: “We had a young man on one job, and he was messing with heroin, and they fired him, and within a year he was dead,” said John “Mac” McFadden, a painter. “I’m just not quiet about being sober anymore. Now that I’m a peer I make sure everyone knows who I was and what I’m about. We’ve got ATAP stickers on the damn hard hats now.”

The nature of the industry, Serviss said, presents unique challenges for construction workers entering recovery. A tradition of drinking and substance use among some in the trades can make it difficult for newly sober workers to feel comfortable with people they used to party with after work. “Work hard, play hard,” said Michael Pollack, a laborer in recovery from heroin addiction, “except then you start playing at work.”

Stigma against medication-assisted treatment, considered the gold standard for treating opioid addiction, is even stronger in an industry where drug testing is frequent and employers are worried about liability.

The treatment medications methadone and suboxone, both shown to help produce far more lasting recovery than abstinence alone, are themselves opioids, but used at doses that stave off cravings without producing a high. Still, Serviss said, if they are found on a drug test, it’s grounds for getting kicked off a job site. Some of his advocates who got sober in abstinence-only programs are wary of opioid-based treatments, thinking they could be misused. “When I’m up on a swing,” a painter said at a recent meeting, “I don’t want no one on suboxone next to me.”

“Do we work on changing some of those policies to help people, or do we continue down the same road?” Serviss asked. “The stigma around [medication-assisted treatment] is the most difficult component. To change that mindset is very difficult.”

Still, he said, as the opioid crisis has deepened, he sees union leadership paying closer attention. At union meetings, he said, leaders are pointing out peer advocates, encouraging their workers to reach out to them, speaking about the building trades’ options for substance abuse treatments.

“I think we’re having a lot more success in penetrating our leadership,” he said, “because everyone’s going to a funeral.”

http://www2.philly.com/philly/health/addiction/in-philadelphias-building-trades-construction-workers-are-helping-their-colleagues-battle-addiction-20181003.html