Penn takes on Philadelphia’s opioid epidemic

Penn takes on Philadelphia’s opioid epidemic

The University is leveraging its expertise to fight the city’s opioid crisis on multiple fronts.

1,200.

That’s how many lives are expected to be claimed from drug overdoses, mainly involving opioids, this year in Philadelphia.

In 2016, there were 907.

Far too high of a number for one city, and ever-increasing throughout each town in the country, “the opioid crisis is going to be a defining public health issue of my generation,” says Mara Gordon, a resident in family medicine at Penn, who graduated from the Perelman School of Medicine in 2015.

An epidemic in every form of the word, 91 Americans die every day from an opioid overdose. A tough challenge with a lot of unanswered questions, addressing this crisis is something Penn is taking head-on, not just behind-the-scenes with research, but on the ground, too.

“We’re on our way, and the potential exists, for Penn to be a big, national leader in fighting this,” says Brian Work, an assistant professor of clinical medicine.

Zachary Meisel, an associate professor of emergency medicine, agrees.

“Penn is leveraging what it does best, which is science, the delivery of unparalleled care, and through education,” he says. “Penn tends to lead the way during major health crises … so why shouldn’t we be the leader now?”

Penn Opioids

Penn Medicine’s Brian Work, board chair of Prevention Point, leads a health clinic at the Kensington site with students and residents from Penn and other area universities. Photo by Eric Sucar

Empathetic care in a safe space
Work, also a clinical site director at Prevention Point for Penn’s Bridging the Gaps program, steps off the subway at SEPTA’s Somerset Station, clad in his khakis, white button-down, and a bowtie. He walks two blocks to Prevention Point, a multiservice public health organization, which first garnered attention in the 1990s for its syringe exchange program. Today, it’s widely known for its trainings that teach individuals how to use naloxone, a medication that reverses an opioid overdose.

A volunteer at Prevention Point since 2002, Work has served as its board chair for the past two years. Every Wednesday afternoon at the Kensington clinic, which is in an old church refurbished with the help of the city, he sees patients from the community, often who are homeless, lacking insurance, and struggling with health issues, many times including addiction to opioids—specifically heroin.

“These are not so-called ‘junkies,’” says Work, also a senior fellow at the Penn Center for Public Health Initiatives (CPHI). “These are people’s moms, dads, brothers, and sisters.”

Penn Opioids

Prevention Point, a multi-service public health organization in Kensington, is widely known for its trainings that teach people how to use naloxone, a medication that reverses an opioid overdose. Photo by Eric Sucar

Work hugs a former client who’s in the busy “drop-in room,” where people can take shelter from the cold or heat, grab some coffee, eat lunch, and take a snooze or watch TV on a comfortable couch.

Affectionately known simply as “Doc” at Prevention Point, Work says later that the patient was “recovering nicely” after treatment of some severe wounds on his arms that were infected from injecting heroin.

There are eight exam rooms, where Work tends to patients privately, along with Penn, Drexel, Temple, and Jefferson medical residents and students. Nursing, social work, and undergraduate students from various schools at Penn are also often seen working at Prevention Point.

Gordon, who volunteered at Prevention Point as a medical student, and is still involved as a medical resident, says the experience has been one she’ll never forget.

“It’s really powerful for me to see how I can start to gain the skills to be the type of doctor to meet people where they are, and take care of them in a way that makes them feel safe,” she says. “It’s been great exposure to learning how to practice compassionate and non-judgmental medicine, and 100 percent influenced what I want to do in the future.”

Another room at Prevention Point is bustling with social workers. Downstairs, there’s a homeless shelter.

While peering into the basement, where cots are set up with blankets and pillows, Work says they’ll accept anyone who needs a place to stay, whether or not they have an addiction.

The goal of Prevention Point, he says, is harm reduction and education.

“We’re not going to stop everyone from using today,” Work says. “So let’s get them some clean needles, let’s give them Narcan, teach people to not use alone, so they don’t die before they get a chance to recover.”

Penn Opioids

Penn professors M. Kit Delgado, left, and Jeanmarie Perrone are researching the best ways to address the city’s opioid crisis. Photo by Tommy Leonardi

The rise and fall of prescription opioids
The devastating number of opioid deaths in the United States, which have quadrupled since 1999, has been fueled in large part by prescribing practices of health care providers, due to persuasive drug company ad campaigns and poor studies that ignored opioids’ highly addictive properties.

“It taught an entire generation of medical students to be liberal when prescribing opioids,” explains Jeanmarie Perrone, a professor of emergency medicine, director of Penn Medicine’s Division of Medical Toxicology, and a CPHI fellow. “Now we’re trying to step back and get the horse back into the barn.”

Treating pain in such an expanded way was a noble effort, says Meisel, also a physician in the Hospital of the University of Pennsylvaniaemergency department, “because pain is terrible and it also undermines your health.”

But, unfortunately, he continues, “It may have led to some of these unintended consequences, with patients becoming addicted, and opioids just flooding the market.”

Also, until relatively recently, there wasn’t a way for health care providers to monitor if patients were “doctor shopping,” or going from emergency room to emergency room asking for prescriptions.

Opioids Penn

In a recent report by the Philadelphia Department of Public Health, it was estimated that 1 in 3 adults in the city—or about 469,000 people—used a prescription opioid in the past year.

Although an issue for the entire nation, the numbers are drastic when it comes to prescription opioids in Philadelphia, says Thomas Farley, the city’s health commissioner. In a recent report by the Department of Public Health, it was estimated that 1 in 3 Philadelphia adults—or about 469,000 people—used a prescription opioid in the past year.

“Many people with pain receive more opioids than they need or use, which increases the risk of addiction,” Farley says.

One of the major related efforts that Meisel, along with M. Kit Delgado, an assistant professor of emergency medicine, are trying to push is changing the default settings on the electronic medical record, which doctors use to prescribe opioids.

“The first thing that pops up when you prescribe something like Percocet might be 20 tabs,” says Delgado, also a senior fellow at the Leonard Davis Institute of Health Economics(LDI). “For almost every prescription, people just pick the first thing that pops up, so if we change the default from, say, 20 to 10 tabs, it might actually make a difference.”

Providing opioid alternatives for minor injuries is ideal, but if opioids must be prescribed, Delgado wants to find clear evidence on the granular: What’s the science behind how many tablets people need to manage pain? For Meisel, also an LDI senior fellow, he’s studying the best communication strategies for physicians to use with patients who might need opioids.

Other researchers navigating the opioid epidemic in a similar capacity run the gamut at Penn, including faculty members such as Peggy Compton, from NursingElliot Hersh, from DentalMary Robinson, from Vet; and Jeffery Saven, from the School of Arts & Sciences’ Department of Chemistry. From 2014 to 2016, the CPHI implemented a cutting-edge, evidence-based public health education program about the epidemic of opioid misuse and overdose in Philadelphia.

And, although it’s important to focus on turning the faucet off for people entering into physical dependence, we must also face “the huge ocean of people who already have some dependence,” says Delgado.

Chatting in his office in Blockley Hall, Delgado recalls a story of a recent patient he tended to in Penn Presbyterian Medical Center’s emergency department after she overdosed from heroin—and was revived with naloxone.

“She had back surgery and was being treated with prescription opioids, and it got to a point where her surgeon and primary care doctor said they would no longer continue to prescribe her opioids, appropriately,” he says. “Basically, she was cut off cold turkey and was referred to pain management, but there was a wait. She came to Philadelphia to sightsee, was in a lot of pain and felt a craving, and found someone on the street and snorted heroin and overdosed. It was her first time.”

Indicative of the opioid epidemic right now, this is a story far too common for Philadelphia—a city known for its pure and cheap heroin, which gives a similar but more potent mind-altering experience as a prescription opioid.

Penn Opioids

Work, who has volunteered at Prevention Point since 2002, says people who are addicted to opioids are not so-called “junkies.” “These are people’s moms, dads, brothers, and sisters,” he says. Photo by Eric Sucar

Treatable moments in the ER
A lot of times, Meisel says, when a person who overdosed from heroin is saved with naloxone, “they wake up, and they want treatment because they almost died, or they’re with a loved one that’s pushing for them to get their stuff together.”

Having options for these particular patients during these “treatable moments,” as Perrone calls them, is critical.

Often, says Delgado, “these patients have been put into acute withdrawal and are at even higher risk for re-using as soon as they walk out of the ER.”

One of Perrone’s biggest efforts throughout the past year has been advocating for medication-assisted treatments, such as Suboxone, an opioid agonist-antagonist, in Penn’s emergency departments and primary care clinics, as well as the appropriate trainings for doctors who would be able to administer them.

“If we are able to start them immediately on an opioid replacement treatment, they can have a chance at feeling what treatment is like, that they can do it, and they won’t have withdrawal symptoms all the time,” Perrone says.

Perrone, an LDI senior fellow as well, is also helping Penn Presbyterian establish a “Center of Excellence,” which will use state funding for specific space in the hospital for people with opioid addictions, ensuring they stay in treatment, and receive follow-up care and support.

Philadelphia Opioids

 

A city-wide effort
Perrone and Meisel brought their ER knowledge and opioid research experience to the table when they served on Philadelphia Mayor Jim Kenney’s Opioid Task Force earlier this year.

The Task Force enlisted several members of the interdisciplinary Penn community, who worked with experts from other academic institutions, city agencies, businesses, community organizations, and health care systems to create a report full of recommendations to address the opioid epidemic in Philadelphia.

Perrone and Meisel, as well as Michael Ashburn, a professor of anesthesiology and critical care, and director of the Penn Pain Medicine Center, served together on the Public Education and Prevention Strategies subcommittee.

An important aspect that the subcommittee discussed was the necessity of the city establishing a one-stop shop—either a phone number, website, or app—that would provide people in need with the available treatment facilities, in real time.

Robert Ashford, who recently graduated with his master’s degree in social work from the School of Social Policy & Practice at Penn, and also a person in long-term recovery, emphasizes the importance of this centralized hub for information.

Robert Ashford

Robert Ashford, a recent graduate of the School of Social Policy & Practice and founder of Quaker Peer Recovery. Photo by Mark Stehle

“Before I went into treatment, I couldn’t imagine being in that frame of mind, dealing with the disease, and trying to find my own care,” he says. “We have to effectively reduce any barriers that exist because the window of opportunity for somebody dealing with a substance use disorder is small. If they are willing to ask for help, we have to get them help right now.”

Ashford, who started the collegiate recovery community, Quaker Peer Recovery, on campus last year, and still conducts research with Brenda Curtis at the Center on the Continuum of Care in the Addictions, served on the Data Analysis and Sharing subcommittee of the Task Force, with David Metzger, a research professor of social policy in psychiatry at Penn Medicine, and Matt Miclette, a master of public health student at Penn.

The subcommittee came up with a variety of recommendations for the city to collect and analyze data around key opioid use and overdose trends, establishing an efficient surveillance program that would, for instance, better monitor the epidemic and establish a rapid response plan.

“The experience was something that was positive overall,” says Ashford. “And the report that was produced in May is a testament to the commitment that Philadelphia has in addressing the overdose crisis and the opioid use disorder problem that exists across the city.”

This summer, Miclette, who co-founded the award-winning prescription take back initiative “Take Back Our City,” worked as a policy associate with LDI and CHERISH, the Center for Health Economics of Treatment Interventions for Substance Use Disorder, HCV, and HIV. In addition, he’s been working to make Narcan distribution more efficient, while serving as the policy director of Action Tank, a separate think tank and community service organization he started with fellow military veterans across Philadelphia. This year, Action Tank focused on the opioid crisis by pushing for policies that are evidence based and make large, positive impacts.

First, Miclette says, one of the biggest challenges—for the city and the country—is overcoming stigma, whether it be for the opioid use disorder itself or its treatment.

“I think once the community realizes this isn’t something we can be hush-hush about, that this is something affecting everyone, we’ll see more people working full force toward solving this,” Miclette says. “It’s an epidemic, and that’s not a word that’s used loosely. It’s only going to get worse before it gets better.”

Nobody can hide from the opioid epidemic, says Ashford, and that’s including on Penn’s campus.

“A certain segment of the population, everywhere, is facing this issue,” he says.

In agreement, Ashford and Miclette take comfort knowing the University, and the city, are actively working to bring the brightest minds together to aid the opioid crisis.

“Penn absolutely can be a leader, with its centers and faculty members already leading in the field,” says Ashford. “We’ve got to take a stance that this is something that needs to be talked about, and put our full weight and support behind it as a University.”

Originally published on .

Immunotherapy Arms Canines to Fight Cancer

Immunotherapy Arms Canines to Fight Cancer

By: Sacha Adorno
Published: Sep 1, 2017

Mrs. Kasey

When Kasey bounded on the bed, her owner Dave Sabey knew something was wrong. The precocious, playful two-year-old pup, who performed this routine every night with great joy, jumped around nervously, heart racing. Assuming a torn ligament, Sabey brought her to their veterinarian, who took a radiograph of the Labrador’s rear left leg. It revealed a lesion on Kasey’s left distal tibia consistent with a diagnosis of osteosarcoma, the most common bone tumor found in dogs. This vet visit began a journey that ended at Penn Vet.

“Kasey wasn’t expected to live beyond a year at most,” said Sabey, who with his wife and Kasey splits time between Seattle and Montana. “We went ahead with the recommended course of standard treatment, which was amputation and chemotherapy, but wanted to do more. I learned about an osteosarcoma clinical trial at Penn Vet led by Dr. Mason and called immediately.”

Dr. Nicola Mason, Associate Professor of Medicine and Pathobiology at Penn Vet, runs a translational research lab that focuses on harnessing a dog’s immune system to kill cancer. The approach—immunotherapy—is among the most promising new developments in cancer research in many decades.

From her desk in Philadelphia, Mason took Sabey’s call. After discussion and testing, she determined that Kasey qualified for an osteosarcoma trial open at the time. And, in 2013, the indefatigable dog started making regular trips across the country to participate in research that is catching national and international attention for the promise it holds for dogs and humans.

 

Arming the Immune System With Vaccine

The study that Kasey enrolled in uses a vaccine to jump start the immune system to recognize and eliminate metastatic cancer cells. It aims to prevent recurrence of the disease in dogs that have already received standard care for osteosarcoma and are in remission.

This photo shows Listeria bacteria cells genetically modified by the Mason laboratory to express the tumor protein HER2/neu, as well as reduce its virulence.Participating dogs received three doses of a vaccine that is based on Listeria monocytogenes, a bacteria that in its original form can cause food poisoning. For the vaccine, the Listeria has been genetically modified to reduce its virulence so it won’t cause disease in the patient. It has also been modified to express the tumor protein HER2/neu, which is over-expressed in some solid cancers, including osteosarcoma, so that it will trigger an immune response to fight HER2/neu expressing cells.

Mason’s close ties to Penn Medicine, where similar research focuses feverishly on advancing treatments and cures for human cancers, sparked this specific trial in dogs.

“It’s a great story,” Mason explained. “In 1999, when I was a PhD student in the Immunology Graduate Group at Penn, I performed a laboratory rotation with Dr. Yvonne Paterson, a Penn microbiologist who pioneered the use of Listeria to fight different HER-2/neu positive cancers. Years later, Yvonne invited me to talk to her students about my immunotherapy work with dogs. I told them about the high number of dogs we were seeing with osteosarcoma and that this tumor expresses HER-2/neu. Yvonne said, ‘I’ve got a vaccine for that’!”

Paterson had been testing the ADXSHER2 vaccine in mice, and it was working. But she and Mason understood an even better test of the immunotherapy’s safety and effectiveness would be with dogs. Dogs develop cancer spontaneously, and many of the cancers have similar genetics, biology, clinical presentation, and therapeutic responses as their human counterparts. In most cases, researchers use mouse models to assess the effectiveness of cancer therapies. But mouse models are increasingly recognized as poor predictors of safety and therapeutic response to new treatments. To advance translational cancer research, researchers need better models that more accurately recapitulate the human disease—so that what Mason and Paterson would learn about the vaccine in dogs would be much more translatable to human cancer research.

The study launched in 2012 with Sasha, an American Bulldog. “After administering the vaccine, I kept a very close eye on Sasha for 72 hours, spending a lot of time with her in her run,” said Mason. But Sasha responded well—surviving another 738 days before succumbing to her disease.

Dr. Mason assists Radiology staff in positioning a clinical trial participant for x-rays.

Since then, 18 dogs have received the vaccine, and the median survival time of vaccinated dogs is 956 days. “For 20 to 30 years, the average survival for dogs with osteosarcoma post-amputation and chemo has been around 320 days,” said Mason. “This approach has tripled that time, and it’s very exciting to think we may be working on something really big here.”

This trial closed in 2016. Mason recently received a $1 million grant from the Morris Animal Foundation to extend her studies and  perform a clinical trial to test this vaccine approach in 80 dogs with osteosarcoma. The National Cancer Institute’s Comparative Oncology Program will run the trial, which will include testing the vaccine in patients who develop metastatic disease during chemotherapy.

One Health Connections

The collaboration between Mason and Paterson, Professor of Microbiology at Penn and former Associate Dean for Research at Penn’s School of Nursing, earned them the University of Pennsylvania One Health Award in 2013. The award recognizes exemplary contributions toward expanding interdisciplinary education and improving health care for the benefit of humans, animals, and the environment.

Since then, the promising results of Mason’s dog studies have paved the way for similar clinical trials in humans. “Our dog data were pivotal in supporting an Investigational New Drug application for this vaccine in human clinical trials for adults with HER-2/neu positive tumors,” said Mason.

Osteosarcoma in humans is rare. In the United States, around 800 cases are diagnosed a year, mostly in children and teenagers. Mason is currently working on a similar trial for children in collaboration with the Children’s Oncology Group, a National Cancer Institute supported clinical trials group and the largest organization in the world devoted exclusively to childhood and adolescent cancer research.

“Dr. Mason’s results with vaccine therapy in dogs with osteosarcoma are the most exciting data I’ve seen for treatment of this disease,” said Dr. Kristy Weber, Chief of Orthopedic Oncology and Director of the Sarcoma Program at Penn Medicine’s Abramson Cancer Center. “We have seen no substantial improvement in the survival of children with this malignant bone tumor in more than three decades, and her work gives me hope that this success in dogs can be translated to children.”

Putting Cells to Work

Vaccination is only one of the groundbreaking immunotherapies Mason’s lab is investigating. Another is chimeric antigen receptor (CAR) T cell therapy, an approach that has shown promising results for humans, especially in liquid tumors like lymphoma and leukemia. Further amplifying the interconnection between animal and human health, this research stems from Mason’s association with Dr. Carl June, Richard W. Vague Professor in Immunotherapy at Abramson Cancer Center, who is at the forefront of CAR T cell research.

Dr. NIcola Mason, Associate Professor of Medicine and Pathobiology

Mason is currently conducting a CAR T cell trial for dogs with B cell malignancies, including B cell lymphoma or leukemia. The study uses T cells genetically modified to express a chimeric receptor that recognizes B cells. Upon recognition of a B cell, the genetically modified T cell activates and kills the B cell target.

“This is such an exciting approach,” said Mason. “It’s a living treatment. We collect T cells from an individual patient’s blood and genetically modify them to re-direct their specificity. In the lab, we expand these modified cells until there are many billions of them, capable of recognizing and killing malignant B cells. Then we put this great army of genetically modified T cells, known as CAR T cells, back into the patient’s body. Ideally, they’ll engraft, recognize the cancer cells they’re trained to target, proliferate, and kill the target cells.”

The Long Game

“In the short term, it’s likely that the use of immunotherapy will change cancer from a terminal disease to a chronic disease and patients will enjoy longer survival times. Long term, my hope is that immunotherapies are ultimately going to enable us to move toward a cure,” Mason said.

Sabey has both the short and long term in sight. He wants more quality time with his beloved Kasey. At the same time, he wants to contribute to an ultimate eradication of cancer. “We had nothing to lose with Kasey,” said Sabey. “We knew the statistics. This trial was our last hope. Without it our girl would be dead, but she’s still a vibrant, almost six-year-old dog.”

Among the Sabeys’ family and friends, Kasey is now known as Mrs. Kasey—the added prefix a moniker from her cancer journey. “We call her Mrs. Kasey, like a teacher, because she has taught us about spirit, resilience, and strength in the face of disease,” Sabey explained, adding, “She is teaching science so much about cancer. It’s the greatest role she could have.”

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