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Arts and Health as Prescriptions for the Future

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Great to join world-renowned soprano Renée Fleming for a session at the virtual 2021 Lake Nona Impact Forum. This session, held on April 22, was titled the “Arts and Health as Prescriptions for the Future.” The session gave us some time to reflect on the successful launch of the Sound Health initiative, a partnership between NIH, the Kennedy Center, and the National Endowment for the Arts. We also discussed how Sound Health has fostered growing research interest in music and the arts and its impact on health. Best of all, I got to join a world-class artist to conclude with a song. It’s a number that she and I pre-recorded and which should resonate with everyone as we work our way closer to the pandemic’s end: “Hard Times Come Again No More.”

Risky Business: Prescription Drug Abuse Among Teens

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First-term finals are nearly upon us and sadly a disturbing percentage of high school seniors are abusing stimulants Adderall (dextroamphetamine) and Ritalin (methylphenidate), which are prescribed for Attention Deficit Hyperactivity Disorder (ADHD). These drugs increase alertness, attention, and energy the same way cocaine does—by boosting the amount of the neurotransmitter dopamine.

Even though these drugs are legal, they’re quite dangerous if not used properly. Taking high doses can cause irregular heartbeat, heart failure, or seizures. High doses of these stimulants can lead to hostility or feelings of paranoia. So, rather than popping pills, it’s a lot safer—and smarter—to boost your grades the old-school way: by studying.


U.S. Surgeon General on Emotional Well-Being and Fighting the Opioid Epidemic

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From September 2019 to September 2020, the Centers for Disease Control and Prevention reported nearly 90,000 overdose deaths in the United States. These latest data on the nation’s opioid crisis offer another stark reminder that help is desperately needed in communities across the land. NIH’s research efforts to address the opioid crisis have been stressed during the pandemic, but creative investigators have come up with workarounds like wider use of telemedicine to fill the gap.

Much of NIH’s work on the opioid crisis is supported by the Helping to End Addiction Long-term (HEAL) Initiative. Recently, the more-than 500 investigators supported by HEAL came together virtually for their second annual meeting to discuss the initiative’s latest research progress and challenges.

As part of the meeting, I had a conversation with Dr. Vivek Murthy, the U.S. Surgeon General. Dr. Murthy served as the 19th U.S. Surgeon General under the Obama Administration and was recently confirmed as the 21st Surgeon General under the Biden Administration. In his first term as America’s Doctor, in which I had the privilege of working with him, Dr. Murthy created initiatives to tackle our country’s most urgent public health issues, including addiction and the opioid crisis. He also issued the nation’s first Surgeon General’s Report on addiction, presenting the latest scientific data and issuing a call to action to recognize addiction as a chronic illness—and not a moral failing.

In 2016, Dr. Murthy sent a letter to 2.3 million healthcare professionals urging them to join a movement to tackle the opioid epidemic. This was the first time in the history of the office that a Surgeon General had issued a letter calling the medical profession to action on this issue. In 2017, Dr. Murthy focused his attention on chronic stress and isolation as prevalent problems with profound implications for health, productivity, and happiness.

Our conversation during the HEAL meeting took place via videoconference, with the Surgeon General connecting from Washington, D.C., and me linking in from my home in Maryland. Here’s a condensed transcript of our chat:


Collins: Welcome, Dr. Murthy. We’ve known each other for a few years, and I know that you’ve talked extensively about the national epidemic of loneliness. What have you learned about loneliness and how it affects our emotional wellbeing?

Murthy: Thanks, Francis. Loneliness and perceived social isolation are profound challenges for communities struggling with addiction, including opioid use disorders. I had no real background in these issues when I started as Surgeon General in 2014. I was educated by people I met all across the country, who in their own way would tell me their stories of isolation and loneliness. It’s a common stressor, especially for those who struggle with opioid use disorders. Stress can be a trigger for relapse. It’s also connected with overdose attempts and overdose deaths.

But loneliness is bigger than addiction. It is not just a bad feeling. Loneliness increases our risk of anxiety and depression, dementia, cardiac disease, and a host of other conditions. However you cut it, addressing social isolation and loneliness is an important public-health issue if we care about addiction, if we care about mental health—if we care about the physical wellbeing of people in our country.

Collins: Vivek, you made the diagnosis of an epidemic of American loneliness back before COVID-19 came along. With the emergence of COVID-19 a little more than a year ago, it caused us to isolate ourselves even more. Now that you’re back as Surgeon General and seeing the consequences of the worst pandemic in 103 years, is loneliness even worse now than before the pandemic?

Murthy: I think there are many people for whom that sense of isolation and loneliness has increased during the pandemic. But the pandemic has been a very heterogenous experience. There are some people who have found themselves more surrounded by their extended family or a close set of friends. That has been, in many ways, a luxury. For many people who are on the frontlines as essential workers, whose jobs don’t permit them to just pick up and leave and visit extended family, these have been very stressful and isolating times.

So, I am worried. And I’m particularly worried about young people—adolescents and young adults. They already had high rates of depression, anxiety, and suicide before the pandemic, and they’re now struggling with loneliness. I mention this because young people are so hyperconnected by technology, they seem to be on TikTok and Instagram all the time. They seem to be chatting with their friends constantly, texting all the time. How could they feel isolated or lonely?

But one of the things that has become increasingly clear is what matters when it comes to loneliness is the quality of your human connections, not the quantity. For many young people that I spoke to while traveling across the country, they would say that, yes, we’re connected to people all the time. But we don’t necessarily feel like we can always be ourselves in our social media environment. That’s where comparison culture is at its height. That’s where we feel like our lives are always falling short, whether it’s not having a fancy enough job, not having as many friends, or not having the right clothing or other accessories.

We talk a lot about resilience in our country. But how do we develop more resilient people? One of the keys is to recognize that social connections are an important source of resilience. They are our natural buffers for stress. When hard things happen in our lives, so many of us just instinctively will pick up the phone to call a friend. Or we’ll get into the car and go visit a member of our family or church. The truth is, if we want to build a society that’s healthier mentally and physically, that is more resilient, and that is also more happy and fulfilled, we have to think about how we build a society that is more centered around human connection and around relationships.

My hope is that one of the things we will reevaluate is building a people-centered society. That means designing workplaces that allow people to prioritize relationships. It means designing schools that equip our children with social and emotional learning tools to build healthy relationships from the earliest ages. It means thinking about public policy, not from just the standpoint of financial impact but in terms of how it impacts communities and how it can fracture communities.

We have an opportunity to do that now, but it won’t happen by default. We have to think through this very proactively, and it starts with our own lives. What does it mean for each of us to live a truly people-centered life? What decisions would we make differently about work, about how we spend time, about where we put our attention and energy?

Collins: Those are profound and very personal words that I think we can all relate to. Let me ask you about another vulnerable population that we care deeply about. There are 50 million Americans who are living with chronic pain, invisible to many, especially during the pandemic, for whom being even more isolated has been particularly rough—and who are perhaps in a circumstance where getting access to medical care has been challenging. As Surgeon General, are you also looking closely at the folks with chronic pain?

Murthy: You’re right, the populations that were more vulnerable pre-pandemic have really struggled during this pandemic—whether that’s getting medications for treatment, needed counseling services, or taking part in social support groups, which are an essential part of the overall treatment approach and staying in recovery. It’s a reminder of how urgent it is for us, number one, to improve access to healthcare in our country. We’ve made huge strides in this area, but millions are still out of reach of the healthcare system.

A potential silver lining of this pandemic is telemedicine, which has extraordinary potential to improve and extend access to services for people living with substance use disorders. In 2016, I remember visiting a small Alaskan fishing village that you can only get to by boat or plane. In that tiny village of 150 people, I walked into the small cabin where they had first-aid supplies and provided some basic medical care. There I saw a small monitor mounted on the wall and a chair. They told me that the monitor is where people, if they’re dealing with a substance use disorder, come and sit to get counseling services from people in the lower 48 states. I was so struck by that. To know that telemedicine could reach this remote Alaskan village was really extraordinary.

I think the pandemic has accelerated our adoption of telemedicine by perhaps five years or more. But we must sustain this momentum not only with investment in broadband infrastructure, but with other things that seem mundane, like the reimbursement structure around telemedicine. I talk to clinicians now who say they are seeing some private insurers go back on reimbursement for telemedicine because the pandemic is starting to get better. But the lesson learned is not that telemedicine should go away; it’s that we should be integrating it even more deeply into the practice of medicine.

The future of care, I believe, is bringing care closer to where people are, integrating it into their workflow, bringing it to their homes and their neighborhoods. I saw this so clearly for many of the patients I cared for who fell into that category of being in vulnerable populations. They were working two, three jobs, trying to take care of their children at the same time. Having a conversation with them about how they could find time to go to the gym was almost a laughable matter because they were literally dealing with issues of survival and putting food on the table for their kids. As a society we have to do more to understand the lives of people who fall into those categories and provide services that bring what they need to them, as opposed to expecting them to come to us.

If we continue in a purely fee-for-service-based environment where people must go multiple places to get their care, we will not ultimately get care to the vulnerable populations that have struggled the most and that are hoping that we will do better this time around. I think we can. I think we must. And I think COVID may just be, in part, the impetus to move forward in a different way that we need.

Collins: Let’s talk a minute about the specifics of the opioid crisis. If we’re going to move this crisis in the right direction, are there particular areas that you would say we really need more rigorous data in order to convince the medical care system—both the practitioners and the people deciding about reimbursement—that these are things we must do?

Murthy: There are a few areas that come to mind, and I’ve jotted them down. It is so important for us to do research with vulnerable populations, recognizing they often get left out. It’s essential that we conduct studies specifically for these populations so that we can better target interventions to them.

The second area is prevention programs. People want to prevent illnesses. I have not met anybody anywhere in the United States who has said, “I’d rather get diabetes first and treat it versus prevent it in the first place.” As silly as that might sound, it is the exact opposite of how we finance health interventions in our country. We put the lion’s share of our dollars in treatment. We do very little in prevention.

The third piece is the barriers faced by primary-care clinicians, who we want to be at the heart of providing a lot of these treatment services. I’ll tell you, just from my conversations with primary-care docs around the country, they worry about not having enough for their patients in the way of social work and social support services in their offices.
Finally, it has become extraordinarily clear to me that social support is one of the critical elements of treatment for substance use disorders. That it is what helps keep people in recovery. I think about the fact that many people I met who struggle with opioid use disorders had family members who were wondering how they could be helpful. They weren’t sure. They said, “Should I just keep badgering my relative to go to treatment? Should I take a tough love approach? What should I do to be helpful?”

This actually is one of the most pressing issues: social support is most often going to come from family, from friends, and from other community members. So, being able to guide them in an evidence-based way about what measures, what forms actually can be helpful to people struggling with opioid use disorders could also be immensely helpful to a group that is looking to provide assistance and support, but often is struggling to figure out how best to do that.

Collins: Vivek, you were focused as Surgeon General in the Obama Administration on the importance of changing how America thinks about addiction—that it is not a moral failing but a chronic illness that has to be treated with compassion, urgency, skill, and medical intervention. Are we getting anywhere with making that case?

Murthy: Sometimes people shy away from addressing the stigma around addiction because it feels too hard to address. But it is one of the most important issues to address. If people are still feeling judged for their disorders, they are not going to feel comfortable coming forward and getting treatment. And others will hesitate to step up and provide support.

I will always remember the young couple I met in Oklahoma who had lost their son to an opioid overdose. They told me that previously in their life whenever they had a struggle—a job loss or other health issue in the family—neighbors would come over, they would drop off food, they would visit and sit with them in their living room and hold their hands to see if they were okay. When their son died after opioid use disorder, it was silent. Nobody came over. It’s a very common story of how people feel ashamed, they feel uncomfortable, they don’t know quite what to say. So they stay away, which is the worst thing possible during these times of great pain and distress.

I do think we have made progress in the last few years. There are more people stepping forward to tell their stories. There are more people and practitioners who are embracing the importance of talking to their patients about substance use disorders and getting involved in treating them. But the truth is, we still have many people in the country who feel ashamed of what they’re dealing with. We still have many family members who feel that this is a source of shame to have a loved one struggling with a substance use disorder.

To me, this is much bigger than substance use disorders. This is a broader cultural issue of how we think about strength and vulnerability. We have defined strength in modern society as the loudest voice in the room or the person with the most physical prowess, the person who’s aggressive in negotiations, and the person who’s famous.
But I don’t think that’s what strength really is. Strength is so often displayed in moments of vulnerability when people have the courage to open up and be themselves. Strength is defined by the people who have the courage to display love, patience, and compassion, especially when it’s difficult. That’s what real strength is.

One of my hopes is that, as a society, we can ultimately redefine strength. As we think about our children and what we want them to be, we cannot aspire for them to be the loudest voice in the room. We can aspire for them to be the most-thoughtful, the most-welcoming, the most-inviting, the most-compassionate voice in the room.

If we truly want to be a society that’s grounded in love, compassion, and kindness, if we truly recognize those as the sources of strength and healing, we have to value those in our workplaces. They have to be reflected in our promotion systems. We have to value them in the classroom. Ultimately, we’ve got to build our lives around them.

That is a broader lesson that I took from all of the conversations I’ve had with people who struggle with opioid use disorders. What I took was, yes, we need medication and assisted treatment; yes, we need counseling services; yes, we need social services and wraparound services and recovery services. But the engine that will drive our healing is fundamentally the love and compassion that come from human relationships.

We all have the ability to heal because we all have the ability to be kind and to love one another. That’s the lesson that it took me more than two decades to learn in medicine. More important than any prescription that I could write is the compassion that I could extend to patients simply by listening, by showing up, by being present in their lives. We all have that ability, regardless of what degrees follow our name.

Collins: Vivek, this has been a wonderful conversation. We are fortunate to have you as our Surgeon General at this time, when we need lots of love and compassion.

Murthy: Thank you so much, Francis.


Links:

Opioids (National Institute on Drug Abuse/NIH)

Opioid Overdose Crisis (NIDA)

Vice Admiral Vivek H. Murthy (U.S. Department of Health and Human Services, Washington, D.C.)

Helping to End Addiction Long-term (HEAL) Initiative (NIH)

Video: Emotional Well Being and the Power of Connections to Fight the Opioid Epidemic (HEAL/NIH)


Could CRISPR Gene-Editing Technology Be an Answer to Chronic Pain?

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Active Neurons
Credit: iStock/Firstsignal

Gene editing has shown great promise as a non-heritable way to treat a wide range of conditions, including many genetic diseases and more recently, even COVID-19. But could a version of the CRISPR gene-editing tool also help deliver long-lasting pain relief without the risk of addiction associated with prescription opioid drugs?

In work recently published in the journal Science Translational Medicine, researchers demonstrated in mice that a modified version of the CRISPR system can be used to “turn off” a gene in critical neurons to block the transmission of pain signals [1]. While much more study is needed and the approach is still far from being tested in people, the findings suggest that this new CRISPR-based strategy could form the basis for a whole new way to manage chronic pain.

This novel approach to treating chronic pain occurred to Ana Moreno, the study’s first author, when she was a Ph.D. student in the NIH-supported lab of Prashant Mali, University of California, San Diego. Mali had been studying a wide range of novel gene- and cell-based therapeutics. While reading up on both, Moreno landed on a paper about a mutation in a gene that encodes a pain-enhancing protein in spinal neurons called NaV1.7.

Moreno read that kids born with a loss-of-function mutation in this gene have a rare condition known as congenital insensitivity to pain (CIP). They literally don’t sense and respond to pain. Although these children often fail to recognize serious injuries because of the absence of pain to alert them, they have no other noticeable physical effects of the condition.

For Moreno, something clicked. What if it were possible to engineer a new kind of treatment—one designed to turn this gene down or fully off and stop people from feeling chronic pain?

Moreno also had an idea about how to do it. She’d been working on repressing or “turning off” genes using a version of CRISPR known as “dead” Cas9 [2]. In CRISPR systems designed to edit DNA, the Cas9 enzyme is often likened to a pair of scissors. Its job is to cut DNA in just the right spot with the help of an RNA guide. However, CRISPR-dead Cas9 no longer has any ability to cut DNA. It simply sticks to its gene target and blocks its expression. Another advantage is that the system won’t lead to any permanent DNA changes, since any treatment based on CRISPR-dead Cas9 might be safely reversed.

After establishing that the technique worked in cells, Moreno and colleagues moved to studies of laboratory mice. They injected viral vectors carrying the CRISPR treatment into mice with different types of chronic pain, including inflammatory and chemotherapy-induced pain.

Moreno and colleagues determined that all the mice showed evidence of durable pain relief. Remarkably, the treatment also lasted for three months or more and, importantly, without any signs of side effects. The researchers are also exploring another approach to do the same thing using a different set of editing tools called zinc finger nucleases (ZFNs).

The researchers say that one of these approaches might one day work for people with a large number of chronic pain conditions that involve transmission of the pain signal through NaV1.7. That includes diabetic polyneuropathy, sciatica, and osteoarthritis. It also could provide relief for patients undergoing chemotherapy, along with those suffering from many other conditions. Moreno and Mali have co-founded the spinoff company Navega Therapeutics, San Diego, CA, to work on the preclinical steps necessary to help move their approach closer to the clinic.

Chronic pain is a devastating public health problem. While opioids are effective for acute pain, they can do more harm than good for many chronic pain conditions, and they are responsible for a nationwide crisis of addiction and drug overdose deaths [3]. We cannot solve any of these problems without finding new ways to treat chronic pain. As we look to the future, it’s hopeful that innovative new therapeutics such as this gene-editing system could one day help to bring much needed relief.

References:

[1] Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice. Moreno AM, Alemán F, Catroli GF, Hunt M, Hu M, Dailamy A, Pla A, Woller SA, Palmer N, Parekh U, McDonald D, Roberts AJ, Goodwill V, Dryden I, Hevner RF, Delay L, Gonçalves Dos Santos G, Yaksh TL, Mali P. Sci Transl Med. 2021 Mar 10;13(584):eaay9056.

[2] Nuclease dead Cas9 is a programmable roadblock for DNA replication. Whinn KS, Kaur G, Lewis JS, Schauer GD, Mueller SH, Jergic S, Maynard H, Gan ZY, Naganbabu M, Bruchez MP, O’Donnell ME, Dixon NE, van Oijen AM, Ghodke H. Sci Rep. 2019 Sep 16;9(1):13292.

[3] Drug Overdose Deaths. Centers for Disease Control and Prevention.

Links:

Congenital insensitivity to pain (National Center for Advancing Translational Sciences/NIH)

Opioids (National Institute on Drug Abuse/NIH)

Mali Lab (University of California, San Diego)

Navega Therapeutics (San Diego, CA)

NIH Support: National Human Genome Research Institute; National Cancer Institute; National Institute of General Medical Sciences; National Institute of Neurological Disorders and Stroke


Study Highlights Need for Continued Care of COVID-19 Survivors

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Collage of people being cared for after contracting COVID-19
Credit: Composed of images from Getty

The past several months have shown that most people hospitalized with COVID-19 will get better. As inspiring as it is to see these patients breathe on their own and converse with their loved ones again, we are learning that many will leave the hospital still quite ill and in need of further care. But little has been published to offer a detailed demographic picture of those being discharged from our nation’s hospitals and the types of community-based care and monitoring that will be needed to keep them on the road to recovery.

A recent study in the journal EClinicalMedicine helps to fill in those gaps by chronicling the early COVID-19 experience of three prominent hospitals in the Boston area: Massachusetts General Hospital, Brigham and Women’s Hospital, and Newton-Wellesley Hospital. These data were reported from a patient registry of 247 middle-aged and older COVID-19 patients. The patients were admitted over three weeks last March into one of these hospitals, which are part of New England’s largest integrated health network.

The data confirm numerous previous reports that COVID-19 disproportionately affects people of color. The researchers, led by Jason H. Wasfy and Cian P. McCarthy, Massachusetts General Hospital and Harvard Medical School, Boston, found a large number of their patients were Hispanic (30 percent) or Black (10 percent). Wasfy said these numbers could be driven by many factors, including a low income, more family members living in one home, greater difficulty accessing healthcare, presence of chronic illness (health disparities), and serving as essential workers during the pandemic.

The researchers also tracked the patients after discharge for about 80 days. About a third of patients left the hospital for a post-acute care facility to continue their rehabilitation. After discharge, many required supplemental oxygen (15 percent), tube feeding (9 percent), or treatment with medications including antipsychotics and prescription painkillers (16 percent). About 10 percent were readmitted to the hospital within weeks or months of their initial discharge.

Wasfy and colleagues also found:

· Many patients undergoing treatment were enrolled in Medicaid (20 percent) or both Medicaid and Medicare (12 percent).

· A substantial number also were retired (36 percent) or unemployed (8.5 percent), highlighting the role of non-occupational spread. Many others worked in the hospitality industry, healthcare, or public transportation.

· A large proportion (42 percent) of hospitalized patients required intensive care. The good news is that most of them (86 percent) ultimately recovered enough to be discharged from the hospital. Tragically, 14 percent—34 of 247 people—died in the hospital.

These findings represent hospitals in just one notable American city hard hit early in the pandemic. But they spotlight the importance of public health efforts to prevent COVID-19 among the most vulnerable and reduce its most devastating social impacts. These are critical points, and NIH has recently begun supporting community engagement research efforts in areas hardest hit by COVID-19. With this support and access to needed post-discharge care, we aim to help more COVID survivors stay on the road to a full recovery.

Reference:

[1] Early clinical and sociodemographic experience with patients hospitalized with COVID-19 at a large American healthcare system. McCarthy CP et al. EClinicalMedicine. August 19, 2020.

Links:

Coronavirus (COVID-19) (NIH)

Massachusetts General Hospital (Boston)

Brigham and Women’s Hospital (Boston)

Newton-Wellesley Hospital (Newton, MA)

Jason Wasfy (Massachusetts General Hospital)


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