Opioid Guidelines Leave Some Surgery Patients in Pain

By Pat Anson, PNN Editor

In recent years, many U.S. hospitals have adopted policies that reduce or eliminate the use of opioids during and after surgery.

Patients at Houston Methodist Hospital, for example, are getting acetaminophen (Tylenol) for post-operative pain after hernia repairs and other minimally invasive surgeries. And dozens of hospitals in Michigan have adopted guidelines for post-operative pain that have significantly reduced the use of opioids.

But a new study presented at the annual meeting of the American College of Surgeons suggests that policies that discourage the use of opioids for post-operative pain may be neglecting patients that need opioids for better pain control.

“The key findings of our study are that we were able to successfully reduce how many opioids we were prescribing for patients after operations using evidence-based guidelines,” said lead author Cornelius Thiels, DO, a surgical oncology fellow at Memorial Sloan Kettering Cancer Center and a researcher at the Mayo Clinic.

“However, the other finding of our research is that there’s still additional room to improve in terms of making sure all patients after surgery have their pain well controlled.”

The researchers evaluated 138 patients who had one of 12 elective surgeries after the Mayo Clinic adopted guidelines in 2018 that call for “multimodal pain control,” a combination of opioids with non-opioid pain relievers such as ibuprofen, naproxen and acetaminophen. Those patients were compared with 603 patients who had the same procedures before the guidelines, when opioids were used more widely.

While most patients in the post-guideline group were satisfied with their pain control after discharge, a significant number were not.

In telephone surveys conducted about four weeks after discharge, the percentage of patients in the post-guideline group who were dissatisfied with their pain control was more than double that of the pre-guideline group (9.4% vs. 4.2%). The percentage who said they were not prescribed enough pain medication was also higher (12.5% vs. 4.9%).

“There is a small subset of patients who we’re not optimally managing yet, and this study confirmed that this is a small number,” Thiels said. “However, I think that’s a critically important subset of patients.”

Thiel says about half of patients need opioid medication after major surgeries, and doctors need to do a better job identifying who they are.

“Our goal is to give them the exact right amount so that we limit the number of un-used opioids in our community while also making sure we don’t reduce it down too far and then leave them in pain,” he said. “The right answer may be more non-opioid based pain medications, better patient education and setting of expectations, or in some cases patients may actually require slightly more opioid medications, and that is OK.”  

Opioid addiction is actually rare after surgery.  A large 2016 Canadian study found only 0.4% of older adults were still taking opioids a year after major elective surgery.  Another large study in the British Medical Journal found only 0.2% of patients who were prescribed opioids for post-surgical pain were later diagnosed with opioid dependence, abuse or had a non-fatal overdose.

President Trump Should Consider Stem Cell Therapy for His COVID-19

By A. Rahman Ford, PNN Columnist

President Trump remains hospitalized at Walter Reed Medical Center after being diagnosed with COVID-19 last week, along with First Lady Melania Trump. The president suffered from fever, congestion and fatigue, and received supplemental oxygen therapy before being admitted Friday.

Details about his current condition and treatment are scant, but Trump has reportedly received an experimental antibody drug and started a course of the antiviral drug remdesivir. In a video posted on Twitter Saturday night, the president said he was “starting to feel good” but the next few days would be “the real test.”

With few effective treatments available for coronavirus, the president and his doctors should seriously consider stem cell therapy, which is being investigated in dozens of clinical trials as a treatment for coronavirus. Other experimental therapies like hydroxychloroquine, remdesivir and blood plasma are not effective for all patients.

Coincidentally, President Trump has long been an advocate for stem cell therapy. In his 2017 State of the Union Address, he acknowledged the medical plight of a woman who was forced to travel to Mexico to use her own stem cells to treat her systemic idiopathic juvenile arthritis. Trump said seriously ill patients “should have access to experimental treatments” without traveling overseas and urged Congress to pass the Right to Try Act so that Americans can get help “right here at home.”

Stem cell therapy may be the safest and most effective treatment for the most life-threatening symptom of COVID-19, acute respiratory distress syndrome (ARDS), an inflammatory “cytokine storm” in the lungs that makes breathing difficult. The conventional intervention for ARDS – mechanical ventilation – is invasive, overused and can increase the likelihood of bacterial infections.

Stem cells have intrinsic immune supporting properties that can ease the deleterious effects of ARDS. They could also potentially heal any tissue damage that ARDS may cause to lungs.

Research Supports Stem Cells for COVID-19

Even if President Trump’s symptoms are mild, the prophylactic use of stem cells to prevent disease spread is worthy of investigation. Celltex Therapeutics is currently conducting a Phase 2 multi-center, double-blind, randomized, placebo-controlled trial to evaluate the prophylactic effectiveness of autologous, adipose-derived mesenchymal stromal cells (MSC).

A recent review of the scientific literature on MSC therapy concluded that “Cellular based therapies hold great promise for the treatment of COVID-19.” Another study echoed that finding, saying “MSCs possess both regenerative and immunomodulatory properties, the latter of which can be harnessed to reduce the severity and longevity of ARDS in patients under intensive care due to SARS-CoV-2 infection.”

Researchers in China have called MSC therapy a “promising strategy” for COVID-19, but cautioned that “there is not enough clinical evidence to prove the effectiveness of MSCs in the treatment of ARDS.”  They called for large-scale, multicenter trials to further explore the safety and efficacy of MSCs.  

Other recent studies have concluded that stem cells “may possibly be one of the most ideal therapeutics” for COVID-19 and “might be considered for compassionate use in critically ill patients.”

FDA Approved Trials

Early in the pandemic, the FDA approved several clinical trials of stem cells for treating COVID-19. These trials are now at various stages of progress, ranging from investigational new drug (IND) applications, to active recruitment of patients, to late stage clinical studies. Trial sponsors include: VetStem, M.D. Anderson Cancer Center, Personalized Stem Cells, Hope Biosciences, Thomas Advanced Medical, Restem, University of Miami, Mesoblast, NantKwest, Baylor College of Medicine, Athersys, Masonic Cancer Center, Celltex and Pluristem Therapeutics.

More recently, Baylx had its IND application approved for umbilical cord-derived MSC cells and Stemedica Cell Technologies’ IND application for intravenous allogeneic MSCs. The FDA has even cleared Pluristem Therapeutics’ existing stem cell product for treating ARDS, allowing the company to treat up to 100 severely affected COVID-19 patients outside of a clinical trial.

There are also several ongoing international trials of stem cells, including studies in Jordan, United Arab Emirates, Pakistan, Mexico and Brazil.

President Trump and First Lady Melania owe it to themselves – and to us – to consider every possible treatment for COVID-19. The administration should also ensure that all Americans have access to stem cell therapy for COVID-19, by expediting clinical trials, expanding compassionate use, and granting emergency use authorization for advanced stem cell products, as was done for convalescent plasma. Ultimately, the president and FDA should relax restrictions on the use of our own stem cells for indications beyond COVID-19.

We all wish the President and First Lady a full and speedy recovery.

A. Rahman Ford, PhD, is a lawyer and research professional. He is a graduate of Rutgers University and the Howard University School of Law, where he served as Editor-in-Chief of the Howard Law Journal. Rahman lives with chronic inflammation in his digestive tract and is unable to eat solid food. He has received stem cell treatment in China. 

Pre-Existing Conditions Deserve Affordable Treatment

By Dr. Lynn Webster, PNN Columnist

The National Institutes of Health reports that about 10 percent of Americans experience a substance use disorder (SUD) at some point in their lives. Most of those who suffer from an SUD receive no treatment.

About twice as many Americans – 20 percent -- have chronic pain. Many of them also cannot find adequate treatment or even a provider willing to treat them. 

Making treatment accessible for both of these conditions -- which are defined as pre-existing for insurance purposes -- is always a topic of concern. These days, it is of paramount concern that access to treatment is available. And it requires us to take action.

We’re All at Risk for Pain and Drug Abuse

Poverty and hopelessness are risk factors for drug abuse, even though not everyone who is economically challenged develops an SUD. Unfortunately, prevention and treatment programs for SUDs are less available to those who cannot pay for them and who most need them.

Anyone can suffer from chronic pain, but even those with resources may not have access to adequate pain management.

My concern is more than theoretical. It is personal. I have friends, former patients and family members who suffer from SUDs. If the Affordable Care Act (ACA) — widely known as Obamacare — ends and we lose coverage of pre-existing conditions, I fear they will be abandoned in exactly the same way as people in pain have been abandoned ever since the CDC issued its 2016 opioid prescribing guideline.

In recent years, I have received hundreds of emails and calls from people in pain. Their medications have been tapered and they don't know where to turn for help. Untreated chronic pain, as well as untreated SUDs, can result in ruinous consequences: disability, destitution, isolation, poverty and suicide.

We need to help healthcare providers find more effective ways to treat their patients. The Centers of Excellence in Pain Education (CoEPEs) program was created to teach healthcare professionals about pain and its treatment. Since this is something most doctors do not study adequately during medical school, it's important to have continuing medical education opportunities to learn about the stigma associated with pain treatment and substance abuse disorders.

Abolishing ACA Could Have Devastating Consequences

The current administration has appealed to the Supreme Court to abolish the ACA. President Trump has said that Obamacare "must fall." Given the fact that we're in the middle of a pandemic and millions of people are unemployed and may have lost access to employer-sponsored healthcare, the timing seems terrible.  

But even without a pandemic, reversing the ACA would be devastating for millions of Americans who have an SUD or chronic pain. President Trump signed an executive order on September 24 that claims to protect people with pre-existing conditions. However, experts dispute whether his executive order can actually do what it promises.

Regardless, eliminating the ACA will likely allow insurance companies to charge higher rates for people with pre-existing conditions. This would essentially render treatment for chronic pain and SUD unaffordable for many people, leading to an increase of the terrible consequences mentioned above. And, of course, SUDs and chronic pain are only two of the pre-existing conditions that would no longer be protected. 

It is time for everyone to understand the consequences that losing the ACA may have for their community, family, friends and themselves. There is still time to be heard, but you have to act quickly. Click here to find your federal, state, and local elected officials and express your views.  

Let us also send healing thoughts and prayers to President Trump, the First Lady and everyone else infected with COVID-19.

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book The Painful Truth, and co-producer of the documentary It Hurts Until You Die. Opinions expressed here are those of the author alone and do not reflect the views or policy of PRA Health Sciences. You can find Lynn on Twitter: @LynnRWebsterMD. 

COVID-19 Research Could Lead to New Painkillers

By Pat Anson, PNN Editor

A loss of taste or smell is one of the early signs of being infected with COVID-19. Scientists say the virus appears to bind itself to nerves in the nasal cavity, causing inflammation that blocks sensory signals associated with smell and taste from reaching the brain.

Researchers at the University of Arizona believe SARS-CoV-2 may have a similar effect on pain signals and essentially acting as an analgesic. That may explain why nearly half the people infected with COVID-19 experience few or no symptoms, even though they are still able to spread the disease.

"It made a lot of sense to me that perhaps the reason for the unrelenting spread of COVID-19 is that in the early stages, you're walking around all fine as if nothing is wrong because your pain has been suppressed," says Rajesh Khanna, PhD, a pharmacology professor at UArizona Health Sciences College of Medicine Tucson.

"You have the virus, but you don't feel bad because your pain is gone. If we can prove that this pain relief is what is causing COVID-19 to spread further, that's of enormous value."

Viruses cause infections by attaching themselves to protein receptors on cell membranes. Early in the pandemic, scientists established that SARS-CoV-2 enters the body via the ACE2 protein on the surface of many cells. Recent preliminary studies suggest there is another route to infection, in which the virus attaches itself to a receptor called neuropilin-1.

"That caught our eye because for the last 15 years my lab has been studying a complex of proteins and pathways that relate to pain processing that are downstream of neuropilin," said Khanna. "So we stepped back and realized this could mean that maybe the spike protein is involved in some sort of pain processing."

How COVID-19 Blocks Pain Signals

Many biological pathways send pain signals to the brain. One is through a protein called vascular endothelial growth factor-A (VEGF-A), which plays an essential role in blood vessel growth but also has been linked to inflammatory diseases such as rheumatoid arthritis and osteoarthritis. VEGF-A binds to neuropilin in a way that triggers a cascade of pain signals.

In research on rodents, Khanna says his team found that the SARS-CoV-2 binds to neuropilin in exactly the same location as VEGF-A, which “completely reversed the VEGF-induced pain signaling." The virus had an analgesic effect at both high and low doses.

Khanna and his colleagues’ groundbreaking research has been published in the journal PAIN. He also authored a blog post in the Daily Beast to explain the findings in layman’s terms. He says the discovery could not only lead to new treatments for COVID-19, but new ways to block pain signals.

“Sneaky virus, fooling people into believing that they do not have COVID-19. But, ironically, it may be gifting us with the knowledge of a new protein, critical for pain. Two roads emerge in the forest ahead: (1) block neuropilin-1 to limit SARS-CoV-2 entry, and (2) block neuropilin-1 to block pain,” Khanna wrote in the Daily Beast.

In future studies, Khanna say his research team will be examining neuropilin as a new target for non-opioid pain relief. They have already tested existing neuropilin inhibitors developed to suppress tumor growth in cancers and found they provided the same pain relief as SARS-CoV-2 when it binds to neuropilin.

"We are moving forward with designing small molecules against neuropilin, particularly natural compounds, that could be important for pain relief," Khanna said. "We have a pandemic, and we have an opioid epidemic. They're colliding. Our findings have massive implications for both. SARS-CoV-2 is teaching us about viral spread, but COVID-19 has us also looking at neuropilin as a new non-opioid method to fight the opioid epidemic."

A Different Perspective on Disbelief

By Carol Levy, PNN Columnist

I was watching a 2009 episode of Law and Order. The plot line revolved around a fetus who had Ehlers-Danlos syndrome (EDS). They talked about the trials the fetus would face if born, because he would have “fragile” skin that could tear at the slightest touch.

Never once was chronic pain, a major aspect of the disorder, even mentioned. I wondered why they ignored such an essential part of living with EDS. Could it be that the idea of chronic pain is foreign to most people, including scriptwriters? Not a novel thought by any means, but then I took the idea further.

Most of us know what a sprained ankle, aching tooth or thumb hit with a hammer feels like. It hurts like heck, but we know it will go away. We do as much as we can to make it stop as quickly as possible. Pain is something our bodies and minds abhor. And rightfully so.

For most people, acute pain is short lived. It does not disable us, at least not for more than a few hours or days. It is not debilitating. It does not take over our lives.

But for some of us, the pain lingers and becomes chronic. It changes our lives irretrievably. Our experience is antithetical to what most people know and how they experience pain. We still expect them to understand, but way too often they don't. And it is upsetting, even maddening, when they don’t.

But maybe it is not merely that they don’t “get it.” Our minds and bodies are created in such a way that we are meant to turn away from pain. Maybe that also means to turn away from the horrible idea that there can be pain that does not heal and does not go away.

It is easy to think – and hope -- that if I explain my chronic pain to those who deny it, who call me a hypochondriac or malingerer, that they will ultimately come around and understand.

Not understanding, or being unwilling to understand, always seemed to me as a failing in the other person; a lack of empathy or compassion. But maybe it is more than that. Maybe it is a biological and psychological imperative. To accept that pain can be chronic is anathema to the way our minds and bodies are programmed to respond to pain.

Not an excuse, but maybe a way to understand when someone says, “I don’t believe you.”

Carol Jay Levy has lived with trigeminal neuralgia, a chronic facial pain disorder, for over 30 years. She is the author of “A Pained Life, A Chronic Pain Journey.”  Carol is the moderator of the Facebook support group “Women in Pain Awareness.”



Cannabis-Based Drugs Risky for Older Patients with COPD

By Pat Anson, PNN Editor

While many senior citizens are discovering the benefits of medical cannabis in relieving pain and other health problems, a large new study suggests caution is warranted for those with chronic obstructive pulmonary disease (COPD).

Researchers at St. Michael's Hospital in Toronto say older adults with COPD who take prescription drugs made with synthetic cannabinoids were 64% more likely to die. The odds are even worse for elderly patients with COPD who take high-dose cannabinoids for the first time. New users had a 178% higher risk of being hospitalized for COPD or pneumonia and a 231% increased risk of death.

"Cannabinoid drugs are being increasingly used by older adults with COPD, so it is important for patients and physicians to have a clear understanding of the side-effect profile of these drugs," says lead author Nicholas Vozoris, MD, a respiratory specialist at St. Michael's and assistant professor at the University of Toronto.

"Our study results do not mean that cannabinoid drugs should be never used among older adults with COPD. Rather, our findings should be incorporated by patients and physicians into prescribing decision-making. Our results also highlight the importance of favouring lower over higher cannabinoid doses, when these drugs actually do need to be used."

The study analyzed the health data of over 4,000 older adults diagnosed with COPD who took either nabilone or dronabinol, two medications made with synthetic cannabinoids that are used to treat nausea, vomiting and loss of appetite.

The findings, published in the journal Thorax, suggest that nabilone and dronabinol may cause sedation and suppress breathing in patients whose health is already compromised by COPD, a progressive lung disease that causes difficulty breathing and chronic coughing.

"Older adults with COPD represent a group that would likely be more susceptible to cannabinoid-related respiratory side-effects, since older adults less efficiently break down drugs and hence, drug effects can linger in the body for longer,” said Vozoris.

“Cannabinoids may not be any safer to use among older adults with COPD than opioids, which are also associated with a heightened risk of respiratory- related morbidity and mortality. While further research is needed to confirm the safety profile of cannabinoid drugs among older adults with COPD, our findings should be taken into consideration in prescribing decision making in this population.”

Cannabis and Menopause

While high doses of cannabinoids may not be appropriate for older patients with COPD, many middle-aged women are using cannabis to treat symptoms of menopause.

According to a small study being presented at the annual meeting of The North American Menopause Society, over one in four women have either used or are currently using cannabis to manage menopause symptoms.

The study involved 232 female military veterans (average age of 56) living in Northern California. Over half reported hot flashes and night sweats regularly. Twenty-seven percent said they had used marijuana to help battle menopause symptoms, while another 10% said they were interested in trying cannabis.

“While the therapeutic use of cannabis by veterans is not altogether uncommon, this study is among the first to highlight veterans’ use of marijuana for this particular condition. Given cannabis’ relatively high rate of use among the women in this cohort, scientists and others would be well-advised to further explore its safety, efficacy, and prevalence among women experiencing menopause,” said Paul Armentano, Deputy Director of NORML, a marijuana advocacy group.

A 2018 survey of over 2,700 elderly patients in Israel found that medical marijuana significantly reduced their chronic pain without adverse effects. Nearly one in five patients stopped using opioid medication or reduced their dose.

Lesbian, Gay and Bisexual Americans More Likely to Have Migraines

By Pat Anson, PNN Editor

A groundbreaking survey has found that lesbian, gay and bisexual (LGB) Americans are significantly more likely than straight people to suffer from migraines, according to a research letter published online in JAMA Neurology.

Researchers at University of California-San Francisco surveyed a nationally representative sample of nearly 10,000 adults aged 31 to 42, asking about their sexual orientation and whether they experienced migraine headaches.  

Nearly one third — 30.7 percent — of those who identified as lesbian, gay or bisexual reported having migraines, compared to 19.4 percent of those who said they were exclusively heterosexual.

Interestingly, participants who said they were mostly heterosexual but somewhat attracted to people of the same sex had nearly the same likelihood of migraine (30.3%) as those who identified as lesbian, gay or bisexual.

The researchers did not identify why LGB Americans are more likely to have migraines, but one possibility is the stress of living in families or communities that are not always tolerant of sexual minorities.

“Many members of sexual minority groups experience prejudice, stigma, and discrimination termed sexual minority stress, which could trigger or exacerbate migraine. Furthermore, members of sexual minority groups may encounter barriers to health care and experience greater physical and mental health problems, which could contribute to migraine,” wrote lead author Jason Nagata, MD, an assistant professor of pediatrics at UCSF.

“It is notable that even people identifying as mostly heterosexual had higher odds of migraine compared with those who identified as exclusively heterosexual, in accordance with other physical health disparities noted among nonexclusively heterosexual populations.”

The research is believed to be the first national study to show disparities in migraine based on sexual orientation. Previous studies found a high prevalence of migraine in sexual minorities in California and higher rates of health problems among LGBs who experienced prejudice.    

Migraine affects more than 37 million people in the United States, according to the American Migraine Foundation. In addition to headache pain, migraine can cause nausea, blurriness or visual disturbances, and sensitivity to light and sound. Women are three times more likely to suffer from migraines than men.

COVID-19 Lockdown Made Symptoms Worse for Pain Patients

By Pat Anson, PNN Editor

A new survey is providing some insight into how patients suffering from arthritis, fibromyalgia and other types of joint and muscle pain fared during the early stages of the coronavirus pandemic.

In late April, researchers at the University of East Anglia (UEA) surveyed 678 patients in the UK with musculoskeletal pain, asking how the pandemic impacted their well-being and access to healthcare. The online survey was conducted five weeks after the start of a nationwide lockdown in which at-risk patients were told to “shield” at home, avoid all social contact, and postpone or cancel non-urgent healthcare appointments.  

"When lockdown happened, we were worried that this may become a much greater problem - particularly for those with bone, joint and muscle pain,” said co-author Toby Smith, PhD, a professor at UEA's School of Health Sciences. “We wanted to know how the new restrictions might affect pain, and better understand who is most at risk of experiencing flare-ups, or reduced well-being due to social isolation and loneliness.

"Our results show that the coronavirus pandemic is a major challenge to people's health and well-being, both to young and older people.”

Over half the patients (53%) reported that their musculoskeletal symptoms had worsened since the start of lockdown. About a third said they had seen a general practitioner or hospital rheumatologist because their pain, stiffness and overall health had significantly worsened. Those who reported greater social isolation and loneliness were less likely to access healthcare.

The vast majority of respondents, over 88 percent, reported little difficulty getting medication during the lockdown, but nearly half (44%) needed the assistance of others to do it.

"Should further isolation measures need to be enforced as we have seen in some part of the UK as the pandemic continues, particular efforts should be made to protect and support the socially isolated as a vulnerable group,” said co-author Alex MacGregor, PhD, a professor at UEA's Norwich Medical School. "Healthcare providers should reach out to individual patients who do not come forward for advice, and who might be silently struggling with their disease.”

Due to a recent surge in coronavirus infections, British Prime Minister Boris Johnson recently tightened nationwide restrictions, ordering bars and restaurants to close by 10pm. More people are also being required to wear masks. Asked about reports the government was planning a “total social lockdown” in northern England and London, Johnson’s health minister told the BBC she wouldn’t rule it out.

The UK survey findings, published in the journal Rheumatology: Advances in Practice, are similar to those found in a PNN survey of over 2,200 patients in April. About 70% said they were worried about going to a hospital or doctor’s office and had postponed or cancelled a medical appointment. A little over half said social isolation made them feel lonely.

6 Reasons to Participate in Clinical Trials

By Dr. Lynn Webster, PNN Columnist

The COVID-19 pandemic has left many people feeling helpless -- yet you can help defeat the virus. You may not be a medical researcher, but you can still be part of developing a vaccine. There are three COVID-19 late-phase vaccine trials currently underway in the United States, and they will involve more than 100,000 individuals. 

All stages of research  require volunteer subjects. Early-phase trials require healthy volunteers, who may not directly benefit from a vaccine or medication but participate for other reasons. The current COVID-19 vaccine trials, for example, involve people who do not have the infection. Some will receive the new vaccine and others will get a placebo.

Only after volunteers are exposed to the virus can scientists determine if the vaccine is safe and effective when compared to a placebo. If a participant becomes ill because of exposure during the trial, the sponsor of the study generally pays for their medical expenses.

Not all clinical trials involve a placebo, but most do. Later-phase trials may offer benefits to the volunteers who have the disease or condition that the drug targets.

There are various ways to get involved in a trial. You may be invited to join one of these trials. Your physician may be part of network of providers participating in a study. If so, they can offer you an opportunity for enrollment. Or, if you are looking for a specific treatment, you can go online to find a study that may be of interest to you.

Here are six reasons to consider participating in a clinical trial:

1) Clinical trials provide safer and more effective therapies

Without clinical trials, development of new and more effective treatments would not be possible. Medical advances depend upon people who are willing to participate in trials. Every drug, from vaccines to pain treatments, approved by the FDA has been studied in clinical trials.

2) Clinical trials provide you with free access to a new treatment

When I started to treat people in pain, I conducted clinical trials to provide my patients with cutting-edge technology that was not yet publicly available. I wanted my patients to have access to the best and newest therapies in the pipeline.

Of course, there was no guarantee that the experimental therapies would be effective. However, the treatments were free to participants in the trial. If the risks were perceived as acceptable, it could be worth it for patients to take the chance.

3) Clinical trials can save your life

Late-phase clinical trials, such as the three currently underway for COVID-19, may provide immunization that could save the life of the participant. Through other clinical trials, we have provided lifesaving therapies to subjects who otherwise could not have obtained them because they couldn’t afford the treatments, or the treatments simply were not available to consumers.

4) Clinical trials can save a loved one’s life

Clinical trials provide researchers with more knowledge and potential therapeutic options. Participating in vaccine trials can lead to the approval of a treatment. This could save the life of a family member who may one day need a vaccination or drug treatment.

5) Clinical trials are regulated by FDA

Clinical trials are highly regulated and generally regarded as safe. Most clinical trials sponsored by industry are required to have their protocols reviewed and accepted by the U.S. Food and Drug Administration, which assesses the safety of every trial. The agency will not allow a company to begin a trial that has not been fully vetted by several FDA departments.

In addition, all protocols must be submitted to an institutional review board (IRB) for approval. This is an independent body charged by the FDA to evaluate and monitor trials. The IRBs and principal investigators contract with the FDA to follow guidance from the Federal Office for Human Research Protections. Both IRBs and principal investigators can be criminally charged if they fail to adequately monitor and accurately report results of a trial.

When the FDA grants permission to fast-track a particular therapy because of an emergency situation, protocols may be loosened. The potential benefits, in that case, have been determined to outweigh the risks. We have to hope that the accelerated approval process for a COVID-19 vaccine will not cause adverse events.

Prior to enrolling in a trial, participants are provided with an informed consent form that describes the trial in layman's terms and explicitly states all of the potential risks. Participation in clinical trials is always voluntary, and a person can withdraw from a trial at any time.

6) Clinical trials may compensate participants

Some trials compensate participants for their time and travel. This occurs more often in early-phase trials for which there is no clear clinical benefit to the individuals. Most trials requiring participants to stay overnight in a research facility compensate volunteers. Participants' compensation depends on the amount of time the testing takes and the types of tests that are performed.

Compensation must be reasonable, yet not excessive. Compensation ranges from $50 or less for a simple saliva sample to $10,000 or more for studies that require staying in a facility for 30 days or so. 

You can learn more about clinical trials at the National Institutes of Health website or by visiting the Clinical Trials website. The National Institute of Allergy and Infectious Diseases also has a website to connect volunteers to coronavirus vaccine trials. And COVID Dash has a portal where people can volunteer for dozens of coronavirus studies around the world.

One clinical trial may create the breakthrough that helps us get the pandemic under control. But that can only happen if enough people from a variety of demographics are willing to volunteer to be a part of the effort.

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book The Painful Truth, and co-producer of the documentary It Hurts Until You Die. Opinions expressed here are those of the author alone and do not reflect the views or policy of PRA Health Sciences. You can find Lynn on Twitter: @LynnRWebsterMD. 

My Undiagnosed ‘Growing Pains’ Nearly Killed Me

By Mikki Ingram, Guest Columnist

When I was a little girl growing up in Oklahoma, I was a tomboy. I played outside constantly no matter the season and was excited to be so close to nature. I did this in spite of frequent sprains, joint dislocations and abnormally bad “growing pains” starting at age three.

To me, those things were normal. I never thought to ask anyone about their own experiences, because my parents never made any fuss. Why should I?

As I grew up, the growing pains never stopped. I remember multiple times, as I was in the throes of puberty and even after, waking up in the middle of the night, crying and rubbing my joints. I had menstrual cramps so bad that I had to miss school. No Tylenol or ibuprofen combination would touch those pains. My dad thought I was being overly sensitive.

MIKKI INGRAM

After my daughter was born in 2003, I became extremely ill. The growing pains that I had come to regard as normal were more extreme than ever. Fatigue also swept over me. I missed the first 6 months of my daughter’s life because I was asleep for most of it.

The pain was consistent, the fatigue more so, and every doctor I went to said the same thing: “You look fine. You’re too young for this.”

I was diagnosed that year with fibromyalgia by a rheumatologist who called it a “diagnosis of convenience.” I was also advised to lose weight, eat better food and that the pain was all in my head. My primary care provider even said I should put my child up for adoption.

After months of plying me with random medications, none of which worked for this pain, I went to a hospital emergency room. The nurse that I saw is a woman I’ll never forget.

She ran an ultrasound on my gallbladder and came back saying, “You have gallstones. There are four of them and one of them is almost one and a half inches wide. You need your gallbladder out. Take these slides to your doctor and get a surgery scheduled.”

I was grateful beyond measure to her. My doctor, however, wasn’t. He didn’t see the need for urgency, so he scheduled my surgery for several months later. Meanwhile, the pain refused to stop. My fat-free diet did nothing and I was in trouble. In the ER of that same hospital, they told me that if I didn’t have the gall bladder out within two days, I’d be dead.

I filed a complaint about the doctor later. Nothing was done and he continued to practice until retirement.

That same provider sent me to a spine doctor. They were trying to figure out if the pain was coming from my back. The doctor said I needed to exercise more and do yoga, and insisted I get corticosteroid injections into my spine. I dutifully obliged the doc, getting multiple injections with no positive result. They only made the pain worse, so much so that we had to beg the doctor to stop scheduling me for them.

In 2018, at the age of 35, I was finally diagnosed with hypermobile-type Ehlers-Danlos Syndrome (EDS), a connective tissue disorder that explained my lifetime of sprains, dislocations and growing pains. I also found out that those “miracle” epidural and corticosteroid injections had further damaged my connective tissues.

That damage occurred when, prior to my EDS diagnosis, I had been given both ciprofloxacin and levaquin antibiotics to treat my chronic sinus infections. Both of those medications weakened my body’s tendons and, four years later, still give me pain. The warning labels on those antibiotics specifically say they are not for people with connective tissue disorders like EDS.

People have looked at me throughout my life and accused me of everything from faking, to lying,to being a hypochondriac. I’ve been told that it’s my weight, accused of taking methamphetamine (due to my near-scurvy levels of vitamin D and having to have all of my teeth removed) and much more, all while being told, in spite of the evidence on my chart, that I am “fine” because I somehow look fine.

When I look at me, I don’t see “fine.” I see a woman who barely sleeps because of excess adrenaline due to EDS. I see a woman who has nearly died due to medical negligence. I see a woman who has permanent nerve damage due to that same negligence. I see a woman who was used by many providers as a guinea pig for their pet projects to prove that I really was “fine.”

I see a woman who now suffers from severe post-traumatic stress syndrome, as well as Impostor syndrome, due to all the times she was called a liar in spite of mountains of evidence to the contrary. I see a woman who survived in spite of it all.

Most of all, I see a woman who fights to be treated like a person with a chronic condition, multiple comorbidities and intractable pain, instead of a person who is actually “fine.” But, maybe that’s just me. 

Mikki Ingram lives in New Mexico. Mikki is a proud supporter of the Ehlers- Danlos Society.

Pain News Network invites other readers to share their stories with us. Send them to editor@painnewsnetwork.org.

FDA Requires Stronger Warning Labels for Benzodiazepines

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration is ordering drug manufacturers to update warning labels for benzodiazepines to strongly caution patients and providers about the risk of abuse, addiction, dependence and withdrawal. The agency said current warning labels are inadequate about the risks associated with anti-anxiety medications such as Xanax and Valium, even when they are taken as prescribed.

Benzodiazepines are generally used to treat anxiety, insomnia, seizures and social phobia, and they were once commonly prescribed to chronic pain patients to reduce anxiety and help them sleep. In recent years, many pain patients were taken off the drugs because they are considered risky when taken with opioid medication.

“While benzodiazepines are important therapies for many Americans, they are also commonly abused and misused, often together with opioid pain relievers and other medicines, alcohol and illicit drugs,” said FDA Commissioner Stephen Hahn, MD. “We are taking measures and requiring new labeling information to help health care professionals and patients better understand that while benzodiazepines have many treatment benefits, they also carry with them an increased risk of abuse, misuse, addiction and dependence.”

In 2019, an estimated 92 million benzodiazepine prescriptions were dispensed by U.S. pharmacies, with alprazolam (Xanax) being the most common, followed by clonazepam (Klonopin) and lorazepam (Ativan).

The FDA said it reviewed post-marketing databases and its Adverse Events Reporting System, and found that benzodiazepines were often prescribed for long periods. In 2018, about half of patients prescribed the drugs received them for two months or more, even though most benzodiazepines are only recommended for short-term use. Physical dependence can occur after taking benzodiazepines for several days or weeks, according to the FDA.

“They are also widely abused and misused, often together with alcohol, prescription opioids, and illicit drugs, which worsen the risks of serious problems. We also found that some patients have had serious withdrawal reactions after benzodiazepines were stopped suddenly or the dose was reduced too quickly. Some patients experienced withdrawal symptoms lasting many months,” the agency said.

The FDA previously warned about the risks of combining benzodiazepines with opioids in 2016. Opioids and benzodiazepines are both central nervous system depressants that can cause sleepiness, respiratory depression, coma and death. In 2016, the number of emergency department visits due to non-medical use of benzodiazepines was higher than the number of ER visits for non-medical use of prescription opioids.

Fatal overdoses involving benzodiazepines increased from 1,298 deaths in 2010 to 11,537 deaths in 2017. The vast majority of those overdoses also involved other substances.

Study Finds Cannabis Effective for 82% of Migraine Patients

By Pat Anson, PNN Editor

Nearly a third of migraine patients have tried medical marijuana or cannabinoids to relieve their pain and other symptoms, according to a large new study that found 82 percent of those who used cannabis found it effective in providing pain relief.

The study gathered data from nearly 10,000 migraine sufferers in the U.S. and Canada who use Migraine Buddy, a migraine tracking app made by Healint, a healthcare technology company based in Singapore. Participants ingested cannabis by a variety of different methods, such as smoking, vaping, tinctures, oils and edibles. No form of ingestion was signficantly more effective than another.

"Cannabis is becoming a prominent treatment option for chronic pain patients, especially for migraineurs," Healint CEO and co-founder Francois Cadiou said in a press release.

"With more and more states across the United States legalizing medical marijuana, migraine patients are becoming acquainted with cannabis as a natural remedy that can help alleviate migraines and even prevent them. Research about the benefits of cannabis use among migraine patients is slowly emerging, but more must be done to properly inform individuals about the use and dosage of medical marijuana to treat migraines."

The findings are similar to a 2019 study, published in The Journal of Pain, that found inhaled cannabis cut headache and migraine severity in half. The effectiveness of cannabis diminished over time, however, as migraine patients appeared to develop a tolerance for the drug and used larger doses for pain relief.

Another recent study, published in the Journal of Integrative Medicine, reported that 94 percent of migraine sufferers who inhaled cannabis experienced symptom relief within two hours.

A major weakness of all three studies is that there was no control group or use of a placebo, and the data was self-reported by patients on mobile software apps. The Migraine Buddy app allows users to report the duration, frequency and intensity of their migraines and medication use, as well as information about sleep, diet and weather-related triggers.

“Migraines have a debilitating impact on tens of millions of Americans and, in many cases, are poorly addressed by conventional therapies. Therefore, it is not surprising to see a significant percentage of migraine sufferers turning to cannabis as a therapeutic option. Those that do so are consistently reporting it to be safe and effective at reducing both migraine symptoms and migraine frequency,” said Paul Armentano, Deputy Director of NORML, a marijuana advocacy group.

About a billion people worldwide suffer from headaches caused by migraines, which affect three times as many women as men. Over 37 million people in the United States live with migraines, according to the American Migraine Foundation.

American Mystery: Why Do Middle-Aged Adults Have More Pain?

By Pat Anson, PNN Editor

A provocative new study is warning that middle-aged Americans are experiencing more acute and chronic pain than the elderly, a dramatic shift in pain demographics that is putting further strain on the U.S. healthcare system.

Researchers at Princeton University and the University of Southern California (USC) analyzed survey responses from more than 2.5 million people in the U.S. and European Union. They found a unique pattern in the United States: Physical pain is rising in working class and less-educated Americans under the age of 60.

The findings run counter to long held assumptions that the elderly are more likely to feel pain due to arthritis and other chronic illnesses associated with old age.

“This is the mystery of American pain. Using multiple datasets and definitions of pain, we show today’s midlife Americans have had more pain throughout adulthood than did today’s elderly,” researchers reported in the Proceedings of the National Academy of Sciences (PNAS). “If these patterns continue, pain prevalence will continue to increase for adults; importantly, tomorrow’s elderly will be sicker than today’s elderly, with potentially serious implications for healthcare.”

Researchers Anne Case, PhD, and Sir Angus Deaton of Princeton University and Arthur Stone, PhD, a psychology professor at USC, have studied morbidity and mortality rates around the world. It was the husband-and-wife team of Case and Deaton who first reported on the so-called “deaths of despair” in 2015, an unusual spike in deaths of nearly half a million middle-aged, mostly white Americans.

To build on that groundbreaking research, Case, Deaton and Stone looked at different generations born between 1930-90. They found that men and women of all races usually reported more pain as they aged. But that finding did not hold true for less educated Americans who do not have a college bachelor’s degree – about two-thirds of the adult U.S. population.

"Our expectation was that pain would increase as one's age increases, due to physical deterioration and higher probability of chronic illnesses," said Stone. "But our research found middle-aged Americans had higher levels of pain than the elderly, which is especially pronounced for people without a college degree, and the question was, why?"

Researchers say their findings have major policy implications. As less educated, middle-aged Americans become elderly, they are likely to experience more pain, adding further strain on pain management practices and the healthcare system in general.

Many patients already feel their pain care is inadequate, due to lack of access to opioid pain medication and alternative treatments that are either ineffective or not covered by insurance.

“Pain is getting worse for less-educated Americans. This not only makes their lives worse, but will pose long-term problems for a dysfunctional healthcare system that is not good at treating pain.”

— Sir Angus Deaton, Princeton University

Researchers believe the rise in pain in the working class was caused by the deterioration of their social and economic conditions. Less-educated Americans born after 1950 are more likely to experience social isolation, more fragile home lives, less marriage and more divorce, as well as stagnant wages and job loss. This “epidemic of despair” has barely touched more-educated Americans.

Another explanation for the increase in pain is that people could be more likely to report minor pain than in the past. The growing number of Americans who are obese could also be contributing to the problem, because more weight increases the risk of health problems like arthritis, diabetes and cardiovascular disease.

Whatever the cause, researchers say their findings should signal to policymakers that less-educated Americans are experiencing more distress, and that tomorrow's elderly will feel more pain than today's elderly.

"Pain undermines quality of life, and pain is getting worse for less-educated Americans," Deaton said. "This not only makes their lives worse, but will pose long-term problems for a dysfunctional healthcare system that is not good at treating pain."

My Pain Doctor Abandoned Me, But I'm Not Going Away Quietly

By CindyLee Calaluca, Guest Columnist

Recently I was terminated by my pain management physician without notice and with no plan for continued care. Why? I complained to the physician that I did not appreciate getting no call back when I repeatedly contacted his practice — over an 8-day period — to report that my chronic pain now had a severe acute component to it.

The acute problem is caused by a severe deep vein thrombosis, extending from the groin to the toes in my left leg – the result of a surgical wound from a toe amputation tearing open from severe swelling. Additionally, an old pressure ulcer had abscessed. The acute pain I am experiencing is because of an overlap with my poorly controlled chronic pain, thanks to the CDC guideline for prescribing opioid medication.

All I can do now, because of the pain, is lay in bed and force myself to sleep to cope with the pain. I am totally incapacitated and unable to do daily activities independently. I am 70 years old, a widow, and my only living relative is a 69-year-old brother who lives 2,000 miles from me.

The physician responded to me inappropriately. He told me he gets 3,000 phone calls a day and saw no reason to respond me, because there was nothing he was going to do about my pain. Furthermore, he had an arrogant demeanor and feels he isn't required to call me. I get an appointment once a month with him and that's where his responsibility for my care ends, he said.

Naturally, that opened the door wide open to abandonment and neglect of a patient. His practice has no after-hour or weekend coverage beyond an answering service.

Before he walked out on me, he insulted my career experience, called me uneducated, and said I didn't know what I was talking about regarding health care or laws.

It is a shame that in his superiority complex, he forgot, if he ever knew, my career or educational background. You see, I am an adult and geriatric nurse practitioner who holds a doctorate in nursing practice with 55 years of clinical experience, along with 20 years of simultaneous healthcare administration. That physician is about to find out how "uneducated, stupid and wrong" I actually am.

That's the story behind my being abandoned and put in my place for complaining. I tried to be nice and have an adult conversation with this man. What a shame his child showed up!

I completely understand the problems created when patients arbitrarily lose their providers without adequate and proper notice. I live in a community of less than 500 people. The nearest pain management practice that uses oral medication is 45 miles away. The next one is two and a half hours away. Then there's University of Alabama Medical Center, which is six hours away. Right, I'll just pop into the pain center tomorrow. Like that's happening.

I have had it with all the buck passing by politicians, law enforcement agents, and the CDC making doctors too afraid to practice pain management correctly. Putting a sign in the lobby stating that under no circumstance does the practice treat pain is not correct medical intervention. In fact, since pain is a symptom of illness and that the body is imperiled, it is turning a blind eye to abandonment.

I am no longer going to be a good patient and not respect myself. I refuse to play the game anymore. Since I am dying, I am not going quietly into the night. I am going to advocate and do so loudly, visibly and boldly. I will advocate for patients one last time.

CindyLee Calaluca lives in Alabama. Pain News Network invites other readers to share their stories with us. Send them to editor@painnewsnetwork.org.

Ironic Partners: Suicide Prevention and Pain Awareness Month

By Dr. Lynn Webster, PNN Columnist

September is National Suicide Prevention Month. It is also Pain Awareness Month. It may appear coincidental or ironic that we recognize suicide and pain during the same month. However, there is an unfortunate association between the two: pain -- either emotional or physical -- too often leads to suicide. Conversely, awareness and treatment of either type of pain, can often prevent suicide.

According to the World Health Organization, 800,000 people worldwide take their own lives each year. The number of suicide attempts is many times greater. Suicide is a serious problem globally and it is often linked to mental health problems.

Many military veterans, like civilians, suffer from both physical and emotional pain. This can lead to substance abuse and increased suicide risk. Veterans frequently experience post-traumatic stress disorder (PTSD) as a result of their military service, but they often don’t get the help they need because the military's mental health system may not take their struggles seriously. The Pentagon has even refused to award Purple Hearts to veterans with PTSD because it is not considered a physical wound.

Transitioning to civilian life after leaving the military can be stressful due to disruptions in social support, financial strain and changes in access to health care. Between 6 and 12 months after they separate from the military, veterans are at the highest risk of suicide.

Suicides associated with serving in the military are at a crisis level -- perhaps because of a lack of pain awareness and cuts in funding to suicide prevention programs. The Department of Veterans Affairs estimates 17 veterans commit suicide every day. Veterans' suicides account for 18% of all suicides in the U.S., even though veterans only make up 8.5 percent of the adult population.

More People at Risk

It’s not just veterans at risk. Over 48,000 Americans took their own lives in 2018. The suicide rate in the U.S. has increased by about 1.8% annually since the year 2000 and is one of the highest among wealthy nations.

The coronavirus pandemic may be adding to the problem. According to the Centers for Disease Control and Prevention, adults have recently reported considerably increased adverse mental health conditions associated with COVID-19. The CDC says groups that are suffering the greatest numbers of COVID-19 cases, including minorities, essential workers and caregivers, have experienced “disproportionately worse mental health outcomes, increased substance use, and elevated suicidal ideation."

People with substance use disorders are also more likely to contract the coronavirus. Those who do become infected bear the double burden of COVID-19 and addiction.

All suicides are tragic, and the losses affect families and entire communities. But suicides can be prevented by understanding the warning signs. Aggression, mood changes, relationship problems, prolonged stress, another person's suicide, and access to firearms or lethal drugs are all risk factors. Intractable pain, too, is a red flag.

According to the American Foundation for Suicide Prevention, depression, substance use disorders, bipolar disorder, and schizophrenia all elevate the possibility of suicide.

Suicidality has become omnipresent in our society. We probably all know of someone who has committed suicide. Even worse, we may have lost a family member or loved one due to suicide. It affects people of all socio-economic levels.

The National Suicide Prevention Lifeline (1-800-273-8255) provides a hotline for anyone who is having a mental health crisis or suicidal thoughts. Free, confidential help for a loved one, or for you, is only a phone call — or online chat — away. 

We may not always know who is struggling with emotional pain, but it is generally apparent when someone experiences insufferable physical pain. The partnership between suicide ideation and severe untreated pain can be mitigated if society will see people in pain as deserving of treatment. 

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book The Painful Truth, and co-producer of the documentary It Hurts Until You Die. Opinions expressed here are those of the author alone and do not reflect the views or policy of PRA Health Sciences. You can find him on Twitter: @LynnRWebsterMD.