Potential cause of elevated nighttime blood pressure with apnea identified

Obstructive Sleep Apnea (OSA) affects an estimated 22 million Americans. In addition to sleep problems, the condition can cause other health issues, including high blood pressure, chronic heart failure and stroke. Some patients with OSA are at an even higher risk of cardiovascular problems because of a phenomenon called “reverse dipping” that causes blood pressure to rise rather than lower during sleep. Most people experience lower blood pressure at night. Now, University of Missouri School of Medicine researchers have found a potential cause for reverse dipping that may help patients with OSA get the help they need before cardiovascular disease develops.

“We can now identify those with OSA at the highest risk of cardiovascular problems in order to prevent them from developing additional complications,” said David Gozal, MD, the Marie M. and Harry L. Smith Endowed Chair of Child Health at the MU School of Medicine. “We can treat those patients more aggressively to ensure they adhere to therapy and use their continuous positive airway pressure device (CPAP) properly.”

Gozal and fellow MU collaborator Abdelnaby Khalyfa, PhD, studied 46 patients diagnosed with OSA. They ranged in age from 18 to 70. Fifteen participants were identified to have a rise in blood pressure during sleep, while the remaining 31 participants had blood pressure readings that either remained the same or declined at night. The researchers collected blood from each participant to study the messages cells produce and send to each other through microscopic packages called exosomes.

“We found that the cell messages coming from participants with night-time elevated blood pressure were different than those transmitted in subjects with normal blood pressure,” Gozal said. “The altered messages caused the cells that line the blood vessels to become dysfunctional. Those disturbed vessels allowed inflammatory cells to enter the vessels’ walls, causing hardening of those vessels and leading to cardiovascular disease.”

Gozal said the cell message discovery will help clinicians personalize treatment for each patient diagnosed with OSA. A simple blood test administered at the beginning of a sleep study could indicate each patient’s cardiovascular risk.

Gozal said additional research is needed to study the patients at highest risk of cardiovascular complications from OSA to see if CPAP compliance can actually reduce blood pressure or normalize the cell messages used to determine a patient’s risk.

###

In addition to Gozal and Khalyfa, the study authors include Bharati Prasad, MD, University of Illinois Hospital and Health Sciences System; and Wen-Ching Chan, PhD, and Jorge Andrade, PhD, of the University of Chicago’s Center for Research Informatics.

The study, “Circulating Plasma Exosomes in Obstructive Sleep Apnea and Reverse-Dipping Blood Pressure,” was recently published in the European Respiratory Journal. Research reported in this publication was supported by the U.S. Department of Veterans Affairs. The authors of the study declare that they have no conflicts of interest related to this study. The content is solely the responsibility of the authors and does not necessarily represent the views of the funding agencies.

https://www.eurekalert.org/pub_releases/2019-12/uom-pco120419.php

Lymphoma patients may have new path to remission, even if CAR T therapy fails

A new, experimental immunotherapy can put patients with B-cell non-Hodgkin lymphoma (NHL) that is resistant to or has come back after multiple other therapies, including CAR T therapy, into remission. A global, multi-center trial found almost half of patients with slow growing lymphomas had complete responses to the antibody called mosunetuzumab. Among patients on the study whose lymphoma progressed after CAR T therapy, 22 percent went into complete remission when treated with the drug. Stephen J. Schuster, MD, director of the Lymphoma Program at the Abramson Cancer Center of the University of Pennsylvania, will present the findings in a plenary session as well as during the press program at the 61st American Society of Hematology Annual Meeting and Exposition in Orlando (Abstract #6).

Non-Hodgkin lymphoma is a cancer that affects the lymphatic system, which is the body’s way of clearing toxins and waste. About 85 percent of NHL cases are B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. While many of these patients respond to frontline chemo-immunotherapy, those who do not frequently do not respond to second line therapies as well. About 40 percent of these non-responders with DLBCL can benefit from CAR T therapy, which is approved for use after two prior lines of treatment. CAR T is not approved for follicular lymphoma, though clinical trials have shown it holds promise.

“There is still a large need for new treatments in relapsed or refractory cases, since some patients fail CAR T and others are too sick to wait for cell manufacturing,” Schuster said. “One of the benefits of this treatment is that it’s ‘off-the-shelf,’ meaning it does not need to be manufactured for each patient.” Mosunetuzumab is an antibody designed to bind to two specific receptors on tumors cells. Just as CAR T therapies in lymphoma target a receptor called CD19, mosunetuzumab binds to CD20 as well as a natural receptor on T cells, one type of immune cell. Patients receive the therapy infusion over several months.

To date, more than 270 patients in seven countries in North America, Europe, Asia, and Australia have received the experimental therapy. All patients had B-cell lymphomas that had relapsed or had not responded to prior therapies. Of that group, 193 patients were evaluable. This included 124 (65 percent) with aggressive lymphomas and 67 (35 percent) whose cancers were slow-growing. The overall cohort included patients whose disease had progressed after stem cell transplant, as well as those whose disease did not respond to or relapsed after CAR T.

Among the group with aggressive lymphomas, 46 (37 percent) saw the amount of cancer in their body decrease, while 24 (19 percent) achieved complete remission. Among patients with slower growing lymphomas, 42 (63 percent) saw a decrease in cancer, and 29 (43 percent) achieved complete remission. The data also suggest that higher doses of the drug correlate with patient responses, but this still needs to be confirmed with additional analyses and longer follow up.

For the patients who saw their disease disappear entirely, the remissions appear to be long-lasting. At a median follow up of six months, 24 of the 29 (83 percent) slow-growing lymphoma patients and 17 of the 24 (71 percent) aggressive lymphoma patients were still disease free. In four patients whose disease came back after remission, three saw a response when they started treatment again.

This includes one patient who went back into a remission that has now been ongoing for 13 months. Further, in some of the patients who had previously received CAR T therapy, molecular testing showed the CAR T cells in their bodies increased in number in their blood after treatment with mosunetuzumab.

“This could mean that not only does mosunetuzumab have the ability to kill cancer, but also that it may help re-engage CAR T cells and boost the effect of the prior CAR treatment,” Schuster said. He notes further study is needed to confirm this and to determine when in the course of treatment mosunetuzumab may be most effective. Cytokine-release syndrome (CRS), a toxicity known to be associated with cellular therapies, was reported in 29 percent of patients on this study. Only three percent required treatment with tocilizumab. Four percent of patients also reported moderately severe neurologic side effects.

Schuster said that while these findings are encouraging, they need to be confirmed by larger, randomized trials. He also notes that longer follow-up of patients on the current trial will ultimately provide more information on the durability of responses.

###

The press briefing for this study will begin at 7:30 a.m. on Saturday, December 7th, in room W221DE, Orange County Convention Center, West Building, Level 1. 9. The plenary session will begin at 2:00 p.m. on Sunday, December 8th in Hall D.

The study was supported by Genentech, which manufactures mosunetuzumab.

https://www.eurekalert.org/pub_releases/2019-12/uops-lpm120219.php

Most behavioral health apps not backed by sufficient evidence

Though many mobile apps designed to target depression and smoking habits have been linked to positive outcomes, those claiming to treat anxiety, alcohol use and other mental health issues should not be used as standalone interventions, a new analysis found.

In the study, researchers examined the results of 19 randomized controlled trials comprising a total of 3,681 participants, as detailed in 5,945 records and 165 full-text articles. The apps included in the trials were used as standalone interventions for behavioral health issues including depression, anxiety, substance use, self-harm, PTSD and sleep problems.

Across the studies examined in the analysis, behavioral health mobile apps were found to have “significant” effects on depression and smoking behavior, but had no significant pooled effects on anxiety, suicidal ideation, self-injury or alcohol use. Additionally, the apps’ effects on PTSD and insomnia varied too widely to be considered successful.

As a result, the authors of the analysis wrote, “Although some trials showed potential of apps targeting mental health symptoms, using smartphone apps as standalone psychological interventions cannot be recommended based on the current level of evidence.”

Still, they added, behavioral health apps could be beneficial when used in tandem with more traditional evidence-based treatment methods such as in-person or online therapy sessions. “One possibility to benefit from apps that already show small effects such as for depression, smoking, and sleep problems could be to have them integrated into a clinical setting in which a professional can monitor progress and provide additional support,” they wrote.

https://www.beckershospitalreview.com/healthcare-information-technology/most-behavioral-health-apps-not-backed-by-sufficient-evidence-study-finds.html

Counterterrorism devices repurposed to test for fentanyl

The MX908 mass spectrometer device, which was originally marketed by portable chemical analysis startup 908 Devices as a counterterrorism tool, is now being used by the Boston Public Health Commission to combat the opioid crisis, NPR reports.

Members of the commission’s harm reduction services team are field-testing the new use for the devices, which were designed predominantly to help groups such as the military and hazardous material specialists detect biological weapons and identify chemicals present in spills and explosions.

The Boston group, however, uses the MX908 to detect the presence of fentanyl in even miniscule samples of illicit drugs, as the incredibly potent synthetic opioid is increasingly used to augment drugs such as heroin and cocaine and is a common contributor to fatal drug overdoses in the U.S. This new use for the device is not widespread, largely due to its prohibitive price tag of $65,000; the only other group known to be using the MX908 for a similar purpose is the Chicago Recovery Alliance.

Though it is too early to know the impact of using the device for drug testing on the nation’s opioid crisis, advocates believe that having a better understanding of the makeup of the nation’s drug supply will help public health officials, authorities and drug users be more prepared to address the associated risks, according to the NPR report.

“This improvement in consumer knowledge and confidence in what they’re getting, and how to use it, can improve the safety of the larger supply,” said Traci Green, PhD, a researcher in emergency medicine at Rhode Island Hospital and Brown University, who is evaluating the Boston commission’s trial run of the MX908.

https://www.beckershospitalreview.com/opioids/counterterrorism-devices-repurposed-to-test-for-fentanyl.html

Origins of the Opioid Crisis and Its Enduring Impacts

Abby E. Alpert, William N. Evans, Ethan M.J. Lieber, David Powell

NBER Working Paper No. 26500
Issued in November 2019
NBER Program(s):Health Care Program, Health Economics Program

Overdose deaths involving opioids have increased dramatically since the mid-1990s, leading to the worst drug overdose epidemic in U.S. history, but there is limited empirical evidence on the initial causes. In this paper, we examine the role of the 1996 introduction and marketing of OxyContin as a potential leading cause of the opioid crisis. We leverage cross-state variation in exposure to OxyContin’s introduction due to a state policy that substantially limited OxyContin’s early entry and marketing in select states. Recently-unsealed court documents involving Purdue Pharma show that state-based triplicate prescription programs posed a major obstacle to sales of OxyContin and suggest that less marketing was targeted to states with these programs. We find that OxyContin distribution was about 50% lower in “triplicate states” in the years after the launch. While triplicate states had higher rates of overdose deaths prior to 1996, this relationship flipped shortly after the launch and triplicate states saw substantially slower growth in overdose deaths, continuing even twenty years after OxyContin’s introduction. Our results show that the introduction and marketing of OxyContin explain a substantial share of overdose deaths over the last two decades.

https://www.nber.org/papers/w26500#fromrss

U of Arizona Offers Free Med School Tuition for Primary Care

The University of Arizona (UA) Colleges of Medicine in Tucson and Phoenix will offer free tuition starting in the spring semester for qualifying medical students to boost the primary care workforce in underserved communities in the state.

Students must agree to practice primary care in a federally designated underserved community in Arizona for at least 2 years after their residency.

Arizona currently meets only 40% of its primary care physician (PCP) need, according to the Health Resources and Services Administration. Arizona ranks 42nd among states for total active PCPs at 77.9 per 100,000 (the US average is 91.7) according to the university’s physician workforce report published in October.

“Arizona needs nearly 600 primary care physicians today, and the number is expected to grow to more than 1900 by 2030,” Michael D. Dake, MD, senior vice president for UA Health Sciences, said in a press release.

The two colleges are the only two designated medical schools in the state.

To be considered for free tuition, applicants must be an Arizona resident and current full-time medical student enrolled in one of the UA Colleges of Medicine.

The minimum commitment of 2 years practicing in an underserved Arizona community must be started within 6 years of graduation from medical school and completed within 10 years of graduation.

The money will come from part of the $8 million annual funding approved by the Arizona Legislature in May. According to the press release, nearly 100 students or about 10% of the student body could get free tuition at the two medical schools.

In addition to building up the state’s primary care workforce, the waived tuition is meant to reduce financial barriers to even applying to medical school with the looming promise of student debt.

Nearly half of medical school graduates owe more than $200,000 in medical school loans, according to the latest Medscape Residents Salary and Debt Report.

Medscape Medical News has reported on several other medical schools that are waiving tuition, including New York University, which is offering free tuition to all current and future medical students; the University of Houston’s new College of Medicine, where all 30 medical students in the inaugural class will receive free tuition when the school opens in the fall of 2020; Kaiser Permanente School of Medicine in Pasadena, California, which announced in February that it will waive tuition for all 4 years for the school’s first five classes starting in summer of 2020; and Weill Cornell Medicine in New York City, which is waiving tuition for all students who qualify for financial aid beginning as of the current 2019-2020 academic year.

https://www.medscape.com/viewarticle/922275

12 Biotech Stocks Primed For A Short Squeeze

Biotech investment is risk fraught. Most biotech stocks are at the mercy of binary events, which serve as make-or-break catalysts. These binary events, however, provide an opportunity for making huge profits for those investors placing the right bets.

Even if the outcome is expected to be negative, one can still make money by adopting a strategy called shorting, which is a bet placed on the price of the security falling in the near future.

Pros And Perils Of Shorting

The mechanism of shorting works like this: borrow a stock and sell it at the prevailing market price, hoping to buy it back later at a less price in order to square up the position. Since the short bet is placed on the premise the security will decline in value, one can make a neat profit out of the price differential between the purchase and sale transactions.

Contrary to expectation, if the stock price begins to move up, a short seller would be left staring at a loss. The situation gets worse when several short sellers, in a bid to cut their losses, scramble to buy the stock, pushing the stock price up further. This is known as a short squeeze.

Why Biotech Stocks Are Ideal Candidates For Short Selling

Most binary events have prescheduled deadlines, giving a clear idea on the investment timeframe.

For instance, Lexicon Pharmaceuticals, Inc.’s (NASDAQ: LXRX) sotagliflozin faced a FDA panel review in mid-January, with the reviewers handing out a split verdict. The investigational asset had a PDUFA action date of March 22. With the writing on the wall fairly clear, a short seller could have got away with a bet against the stock.

The stock slumped about 23% post the Adcom decision, and plunged an incremental 29% over two sessions after the FDA refused to approve the diabetes drug candidate.

That said, the inherent volatility and low float characterizing biotech stocks make shorting a risky proposition. One can end up losing money if the bet goes awry. A short seller trying to cover up his short position in the event of a short squeeze may not be able to buy the stock, especially when it is of a low float.

Metrics Associated With Shorting

The short interest is denoted in absolute number of shares shorted. This apart, short interest is expressed as a percentage of float. Another metric called short ratio refers to the number of days it would take to cover the short positions. Mathematically, it is the number of shorted shares divided by the average daily trading volume, expressed in percentage terms.

Here are the some of the heavily shorted stocks in the biotech stocks (based on data from shortsqueeze.com):

• Intrexon Corp (NASDAQ: XON): short interest 52.79%, short ratio 34.9
• AMAG Pharmaceuticals, Inc. (NASDAQ: AMAG) short interest 48.46%, short ratio 16.4
• Ligand Pharmaceuticals Inc. (NASDAQ: LGND) short interest 44.95%, short ratio 19.5
• Polarityte Inc (NASDAQ: PTE) short interest 38.02%, short ratio 17.4
• Paratek Pharmaceuticals Inc (NASDAQ: PRTK) short interest 37.60%, short ratio 17.2
• Eidos Therapeutics Inc (NASDAQ: EIDX) short interest 36.47%, short ratio 15.5
• Axsome Therapeutics Inc (NASDAQ: AXSM) short interest 36.25%, short ratio 11.5
• Heron Therapeutics Inc (NASDAQ: HRTX) short interest 34.02%, short ratio 18.2
• ZIOPHARM Oncology Inc. (NASDAQ: ZIOP) short interest 33%, short ratio 35.7
• Cronos Group Inc (NASDAQ: CRON) short interest 30.23%, short ratio 8
• Akcea Therapeutics Inc (NASDAQ: AKCA) short interest 30.19%, short ratio 16.5
• Viking Therapeutics Inc (NASDAQ: VKTX) short interest 29.57%, short ratio 13.6

https://www.benzinga.com/general/biotech/19/12/14931993/12-biotech-stocks-primed-for-a-short-squeeze