White Patients More Likely Than Blacks to Get Opioids at ER

By Drs. Trevor Thompson and Sofia Stathi, University of Greenwich

White people who visit hospital emergency departments with pain are 26% more likely than Black people to be given opioid pain medications such as morphine. This was a key finding from our recent study, published in the Journal of General Internal Medicine.

We also found that Black patients were 25% more likely than white patients to be given only non-opioid painkillers such as ibuprofen, which are typically available over the counter.

We examined more than 200,000 visit records of patients treated for pain, taken from a representative sample of U.S. emergency departments from 1999 to 2020. Although white patients were far more likely to be prescribed opioid medication for their pain, we found no significant differences across race in either the type or severity of patients’ pain.

Furthermore, racial disparities in pain medication remained even after we adjusted for any differences in insurance status, patient age, census region or other potentially important factors.

Our analysis of prescribing trends spanning over two decades’ worth of records found that opioid prescribing rates rose and fell, reflecting changing attitudes in clinical practice toward the use of opioid drugs. Notably, however, there appeared to be little change over time in the prescribing disparity across race.

These findings are important because they suggest that efforts to promote equitable health care in the U.S. over the past two decades, such as the Affordable Care Act, or “Obamacare,” do not appear to have translated to clinical practice – at least with regards to pain management in hospital emergency departments.

There’s no question that as the ongoing opioid crisis continues to escalate, a careful balance must be struck between the risks and benefits of prescribing opioids. But their appropriate use is an essential component of pain control in the emergency department, and they typically provide superior relief to non-opioids for short-term moderate to severe pain.

Undertreated pain produces unnecessary suffering and can result in a range of negative outcomes, even including a greater likelihood of developing long-term pain. There are over 40 million pain-related emergency department visits annually, so it is clear that equitable pain treatment is a fundamental component of a fair health care system.

We do not know why such marked racial disparities exist. Some researchers have argued that prescribing fewer opioids may be beneficial for Black patients as it reduces the risk of addiction. But this argument doesn’t square with the data, which show that overdose rates have traditionally been lower in Black populations compared with white people. However, this trend has started to change in recent years.

In addition, some evidence suggests that clinicians may hold unconscious biases, incorrectly believing Black patients to be less sensitive to pain or that certain racial groups are less willing to accept pain medication.

While there is preliminary evidence that these factors may be important, there is not enough research that examines the degree to which they influence clinical practice. Researchers like us also know very little about whether promising remedial strategies based on these factors – such as educational training during medical school that challenges stereotypical beliefs – are effective, or indeed even implemented, in the real world.

The need for tackling racial disparities in health was brought into focus once more in February 2023, when the Biden-Harris administration signed an executive order on further advancing racial equity. Given the long history of these issues, it is clear that more research is needed to help develop better strategies for tackling health inequalities.

The most effective strategies for addressing racial disparities in pain treatment are likely to be those that target the underlying causes. We are currently undertaking research to try to better understand these causes, how they contribute to disparities in real-world clinical practice and whether strategies designed to address them are actually effective.

Trevor Thompson, PhD, is an Associate Professor of Clinical Research and works in the Centre for Chronic Illness and Ageing at the University of Greenwich.  

Sofia Stathi, PhD, is a Professor of Social Psychology in the School of Human Sciences at the University of Greenwich, where she leads the Centre for Inequalities.

This article originally appeared in The Conversation and is republished with permission.

Blacks and Hispanics More Likely to Develop Chronic Back Pain

By Pat Anson, PNN Editor

Chronic lower back pain is the leading cause of disability worldwide, with an estimated 72 million people suffering from it in the United States alone.   

New research suggests that Black and Hispanic Americans are significantly more likely to develop “high-impact” lower back pain than Whites. High impact pain is chronic pain that lasts at least six months and is severe enough to interfere with daily life or work activities.

Researchers at Boston Medical Center analyzed health data for over 9,000 patients experiencing acute lower back pain, who were being treated at primary care practices in the Baltimore, Boston, Pittsburgh and Salt Lake City areas.

After six months, patients who were Black (30%) or Hispanic (25%) were more likely than White patients (15%) to develop high impact chronic lower back pain. The Black and Hispanic patients were more likely to be younger, female, obese, have Medicaid insurance, and at higher risk of disability. They were also about half as likely to be prescribed opioids than Whites after their initial visit to a doctor.

“Our study has highlighted both a concern in the absolute number of patients with acute low back pain who develop chronic low back pain and concerns about racial and ethnic disparities in outcomes,” said lead author Eric Roseen, DC, director of the Program for Integrative Medicine and Health Disparities at Boston Medical Center.

“High-impact chronic pain has a negative impact on the lives of millions of Americans, particularly Black Americans, yet possible and significant causes of racial and ethnic disparities in long-term pain outcomes remain understudied and largely unaddressed. The disparities that emerged in this study shed light on the direct correlation among lived experiences, physical, and mental health, which must be addressed in order to improve patient outcomes.”

Roseen and his colleagues reported in the journal Pain Medicine that the risk of developing high-impact chronic pain was highest among Black women. They attribute that partially to socioeconomic reasons, suggesting that racial and ethnic differences in health insurance or neighborhood resources may impact the long-term outcomes of patients with new episodes of low back pain. 

Getting effective treatment for low back pain is problematic, regardless of race or ethnic group. A recent Harris Poll of over 5,000 U.S. adults found that over a third of those with chronic low back pain have never been told by a healthcare professional what causes their pain. Nearly half said they’ve experienced back pain for at least five years.

The survey found the typical back pain sufferer had sought relief from at least three different healthcare providers. About one in five had epidural steroid injections, which were rated as one of the least effective treatments for chronic low back pain. Opioid pain medication was rated as the most effective treatment, slightly ahead of physical therapy, chiropractic care and acupuncture.

Honoring Black Pioneers in Medicine

By Dr. Lynn Webster, PNN Columnist

There have been countless Black pioneers in the medical profession, but few of us know their names or the contributions they made. This column acknowledges the impact these men and women have had on healthcare, despite the inequalities they faced in pursuing their vocations.

DR. JAMES MCCUNE SMITH

In 1837, James McCune Smith graduated from the University of Glasgow in Scotland, becoming the first African American to earn a medical degree.

Dr. Smith had been denied access to an American medical school, so he was forced to seek his medical career overseas. According to the University of Glasgow website, Smith was a noted abolitionist, educator, scholar and "one of the foremost intellectuals in 19th century America of any race."

Besides graduating at the top of his class, Smith was also the first Black to run a pharmacy in the United States.

In 1847, David Jones Peck became the first African American student to graduate from a U.S. medical school, receiving his degree from Rush Medical College in Chicago. 

Rebecca Lee Crumpler was the first Black woman to receive a degree from a medical school in America. That was in 1863.

Alexander Augusta was the first Black to be commissioned as a medical officer in the Union army during the Civil War. He was the "surgeon in charge" (in other words, the director) of the Contraband Hospital in Washington, DC.

Biddy Mason was a former slave not formally trained in medicine, but she helped deliver hundreds of babies as a midwife in Los Angeles in the 1860’s. Mason was also an entrepreneur and philanthropist, who donated generously to charity and helped establish the first black church in the city.

In 1879, Mary Mahoney was the first Black woman to be awarded a nursing degree. She is also credited as one of the first women in Boston to vote after the 19th Amendment was ratified.

Daniel Williams was one of the first physicians of any color to perform a successful open-heart surgery. In 1893, he opened Provident Hospital in Chicago, the first interracial and Black-owned hospital.

BIDDY MASON

In 1895, Robert Boyd co-founded the National Medical Association. This is the oldest and largest organization representing Black physicians and healthcare professionals in the United States. Dr. Boyd served as its first president.

Vivien Thomas, the grandson of a slave, worked as a laboratory assistant rather than as a doctor. Yet, in the 1940s, he created a surgical technique to correct the congenital heart malformation that causes blue baby syndrome. His white associate, Dr. Alfred Blalock, received the credit.

Charles R. Drew established large-scale blood banks at the beginning of World War II and saved thousands of lives. He also created the first bloodmobiles. The Charles R. Drew University of Medicine in Los Angeles is named after him. Over 80 percent of its students are from communities of color.

William Hinton, who received his medical degree from Harvard in 1912, was the first Black physician to teach at Harvard Medical School. He developed the Hinton test to diagnose syphilis and wrote Syphilis and Its Treatment, the first medical textbook published by a Black physician.

DR. RICHARD PAYNE

The world of doctors who specialize in pain management is small, because it is a relatively new specialty. That means only a limited number of Black physicians have focused on treating patients with pain in the modern era. Richard Payne was among those pain specialists.

In 2006, Payne was Professor Emeritus of Medicine and Divinity at Duke University Divinity School and held the John B. Francis Chair at the Center for Practical Bioethics. An internationally recognized expert in palliative care, Payne devoted his career to making palliative care standard practice for people with late-stage illness. He was the first African American to become president of the American Pain Society.

In 2019, Patrice Harris became the first African-American woman to be elected president of the American Medical Association. Dr. Harris has been chair of the AMA’s Opioid Task Force since its inception in 2014.

You may have heard some of these names before; others, you may be hearing for the first time. In any case, these men and women saved the lives of thousands of Americans at a time when racial discrimination was a legal, acceptable part of U.S. culture.

Skin Color Still Matters

We may tell ourselves that skin color no longer matters. We may take for granted the fact that the Black pioneers in healthcare laid the foundation for people of all races to be able to make their own contributions to the medical world. But recent history does not support that perspective.

In 2017, a white woman walked into a clinic in Ontario, Canada and demanded that a white doctor be found to treat her sick son. She was escorted out of the building by security and, presumably, continued her search for that elusive white doctor. The "Karen" video of the incident went viral.

Just this month in STAT News, Dr. Ruth Shim explained that she is leaving organized psychiatry because of its structural racism. She wrote about experiencing "countless microaggressions" as a Black leader in the psychiatric community. She also expressed her belief that the American Psychiatric Association seems to have unwritten policies to deliberately "impede progress toward achieving racial equity."

In another STAT News article last January, Uché Blackstock wrote about why Black doctors are leaving their jobs as faculty members at academic medical centers. Blackstock felt compelled to resign from her job because she "could no longer stand the lack of mentorship, promotion denial, and work environments embedded in racism and sexism." It was a difficult decision for her to make, since there were few Black role models among the faculty. However, she found the workplace toxic, oppressive and racist.

"If academic medical centers and their leaders cannot adequately support Black students and promote Black faculty," Dr. Blackstock wrote, "then they will continue to leave."

We've come a long way since 1837, when James McCune Smith became the first African American doctor. Jim Crow laws have been abolished and schools — in theory, anyway — have been integrated. Recently, we’ve seen a huge wave of support for the Black Lives Matter movement.

Still, only 5 percent of physicians in the United States are Black, despite the fact that the population includes more than double that number of African Americans. That needs to change, but it is important to understand that parity representation in the medical profession alone would be insufficient. To honor the contributions of Black pioneers in medicine, we need to recognize their contributions to science and society, regardless of skin color.

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.” You can find Lynn on Twitter: @LynnRWebsterMD

White Privilege and People in Pain

By Dr. Lynn Webster, PNN Columnist

I am a beneficiary of white privilege. That doesn't mean I was born into money. On the contrary, I grew up in a poor, uneducated family in a rural community. I felt the world looked down on my family because of our socio-economic circumstances.

As a child, I feared I would never escape poverty or its stigma. The system seemed to favor those with money and education. Yet I was able to climb out of poverty because of a supportive family.

In retrospect, I believe the opportunities that opened up to me were due to more than family support. Although I had good grades in college, my acceptance to medical school may have been due, in part, to where I grew up.

The medical school to which I applied hoped to increase the number of family physicians willing to set up practices in rural communities. Their strategy was to choose students who had grown up in rural areas, assuming they would be likely to return to those communities to practice medicine.

I was never aware of a similar strategy for enticing doctors to practice in inner city or other predominately African American communities. There were no African Americans in my class of 120.

Shortly before entering medical school, I was in a serious car accident. I rolled my car during a thunderstorm on the highway from Lincoln to Omaha, Nebraska. The seat belt I was wearing saved my life, but in doing so, it produced a compression fracture of a lumbar vertebra. I was in excruciating pain until the emergency room physician gave me morphine.

If I had been of a different race, would I have been treated with the same compassion? Research today suggests I probably would not have been.

Myths About Black People and Pain

For centuries, there has been a false belief that blacks could tolerate more pain than whites. In 1851, a prominent southern physician wrote in the New Orleans Medical and Surgical Journal that due to “physical peculiarities of the Negro race,” black slaves were “insensitive to pain when subject to punishment.”

Even today, a young black man who goes to the emergency room with an injury is likely to be treated differently than a young white man. For example, a 2000 Annals of Emergency Medicine article reported that in an Atlanta emergency department, 74% of white patients with bone fractures received an opioid, but only 57% of African American patients with the same condition received the same treatment.

A 2016 study in The Proceedings National Academy of Sciences reported that a significant number of University of Virginia medical students believed there was a biological difference in pain perception between blacks and whites. The study exposed myths such as the common belief that "black people’s nerve endings are less sensitive than white people’s." In fact, 40% of first- and second-year medical students in the study agreed with the statement, "Black people’s skin is thicker than white people’s."

Another way of expressing the same opinion is to say that whites are more sensitive to pain than blacks. These myths are embedded in American culture and have been fomented by institutional racism.

A more recent study found that black children with appendicitis were less likely to be prescribed an opioid for their pain than white children.

Since blacks who are in pain are regarded with greater suspicion than whites, they tend to underplay the intensity of their pain in clinical settings. They are also more inclined than their white counterparts to try to pray their pain away or to consider pain to be a personal failing.

Despite common folklore, African Americans and Hispanics are less likely than white people to abuse prescription opioids. Yet blacks of all ages usually receive less pain medication than their white counterparts. They wait longer in emergency rooms for painkillers and receive less effective pain management when in hospice care.

The disturbing belief that blacks are more tolerant of pain is a form of racism. However, ER doctors who discriminate against blacks may not be racists. Their behavior, instead, may be due to the systemic racism in our culture. The difference is this: A racist acts upon an intent to discriminate based on race or ethnicity. Racism, on the other hand, is when actions are based upon false beliefs.

As Cory Collins writes in Teaching Tolerance, "Having white privilege and recognizing it is not racist."

Racism Isn't Over

On November 4, 2008, Barack Obama was elected as the first African American president of the United States. He said, at the time, "Change has come to America," and many Americans wanted to believe it had. Many hoped the election signaled that, finally, Americans perceived blacks as equal to whites, and racists had lost their influence in this country.

However, according to the Pew Research Center, Americans’ views of racist behavior have become polarized along party and racial lines. In 2019, about 58% of all Americans believed that race relations were bad and unlikely to improve. Then came the killing of George Floyd and the subsequent protests about the racial disparity demonstrated by law enforcement.

Increased awareness of the pervasiveness of institutional racism throughout our culture may be growing, but racism is certainly not over. Research clearly shows that racism, unconscious or not, keeps people of color from getting the pain treatment they need and deserve. White medical students and health care professionals must recognize the role white privilege plays in passive but brutal discriminatory practices, and actively work to rectify and remedy them.

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.” You can find Lynn on Twitter: @LynnRWebsterMD

Does Discrimination Cause Blacks to Feel More Pain?

By Pat Anson, PNN Editor

Racial and ethnic bias is a fact of life that impacts almost every aspect of our society – and healthcare is no exception. Research has shown that African-Americans are more likely to be undertreated for pain compared to white Americans, and that blacks are less likely to be prescribed opioid pain medication than whites.

Part of that stems from a false belief that there are biological differences between blacks and whites that cause African-Americans to feel less pain.

New research published in the journal Nature Human Behaviour disputes that stereotype, suggesting that African-Americans experience more pain due to the lasting effects of discrimination and other stressful life experiences.

In a small study led by researchers at the University of Miami, 28 African-Americans, 30 Latinos and 30 whites were subjected to a series of painful heat tests on their forearms while undergoing MRI brain scans.

The African-Americans not only rated their pain more intense and unpleasant than the other two groups, but the MRI’s found that the parts of their brains that process pain signals became more active than their counterparts’ as the temperature of the heat probes increased.

“There's evidence that both the general public and clinicians believe that African Americans are less sensitive to pain than non-Hispanic whites; yet research, including our own, shows exactly the opposite." said lead author Elizabeth Losin, PhD, an assistant professor of psychology at the University of Miami.  "Minorities, particularly African Americans, actually report more pain."

Losin began her research eight years ago while at the University of Colorado, recruiting volunteers in the Denver area. In addition to the heat tests and MRI scans, all participants completed questionnaires about various aspects of their lives, including unfair social treatment, discrimination and their trust in doctors.

Using the MRI brain scans, Losin and her colleagues identified two areas of the brain, the ventral striatum and ventromedial prefrontal cortex, which responded to pain more strongly in African Americans than the other two groups. Prior research has found that these two brain regions also respond more to pain signals in chronic pain patients.

“Our findings suggest that the link between chronic pain and ethnic differences in pain sensitivity may lie in the chronic stress associated with discrimination. Discrimination has been consistently associated with chronic stress and other adverse health outcomes in AA (African Americans) and other minority groups,” Losin wrote.

“It is also plausible that the higher pain sensitivity we and others have observed in AA compared to WA (White Americans) participants may be related to previous negative experiences with medical care in particular, which are more common in AA compared to non-Hispanic WA populations.”

Previous studies have found that childhood trauma, domestic violence and other stressful life situations can also increase the likelihood of chronic pain – so this new research does not prove that discrimination alone contributes to the increased risk of pain. Nevertheless, it lays the groundwork for future studies on the relationship between pain and discrimination.

"These findings exemplify how neuroimaging is teaching us that there are multiple contributions to pain," said co-author Tor Wager, PhD, a professor of neuroscience at Dartmouth College. "We need to consider the broader psychological and cultural setting when we think about what is underlying pain and how to address it."

Losin is continuing her research by studying the relationship between patients' trust in their doctors and their experience with pain.

"It's a common misconception that any difference you see between groups of people must be an intrinsic difference, rooted in our biology. But the differences we found in this study were related to people's life experiences," she said. "It reaffirms our similarities and provides hope that racial and ethnic disparities in pain can be reduced."

Study Finds Racial Bias in Drug Testing

By Pat Anson, Editor

African-American patients on long-term opioid therapy are more likely to be drug tested by their doctors and significantly more likely to have their opioid prescriptions stopped if an illicit drug is detected, according to a new study.

Yale researchers analyzed the health records of more than 15,000 patients who received opioids from the Veterans Administration between 2000 and 2010. About half of the VA patients were white and half black.

Over 25 percent of the black patients had a urine drug test within the first six months of opioid treatment, compared to nearly 16% of whites.

When patients tested positive for either marijuana or cocaine, the vast majority – 90 percent -- continued to receive their opioid prescriptions. But there were significant differences in how patients were treated depending on their race.

Black patients that tested positive for marijuana were twice as likely as whites to have opioid therapy stopped and three times more likely to have opioids discontinued if cocaine was detected in their urine.

The findings, published in the journal Drug and Alcohol Dependence, are consistent with previous research showing disparities in how blacks and whites are treated by the healthcare system in general, and particularly when opioids are involved.

“There is no mandate to immediately stop a patient from taking prescription opioids if they test positive for illicit drugs,” said first author Julie Gaither, PhD, a pediatrics instructor at the Yale School of Medicine.

“It’s our feeling that without clear guidance, physicians are falling back on ingrained stereotypes, including racial stereotyping. When faced with evidence of illicit drug use, clinicians are more likely to discontinue opioids when a patient is black, even though research has shown that whites are the group at highest risk for overdose and death.”

A 2016 study of emergency room patients found that blacks were significantly less likely to get an opioid for abdominal pain than whites. Another study of white medical students and residents found that half had at least one false belief about black patients. Those that did were more likely to report lower pain ratings for black patients.

Drug Testing for Marijuana Not Recommended

The 2016 CDC opioid guideline encourages doctors to conduct urine drug tests before starting opioid therapy and at least annually after patients start taking the drugs. But the guideline also urges physicians not to test opioid patients for tetrahyrdocannabinol (THC), the psychoactive ingredient in marijuana that makes people high.

“Clinicians should not test for substances for which results would not affect patient management or for which implications for patient management are unclear. For example, experts noted that there might be uncertainty about the clinical implications of a positive urine drug test for tetrahyrdocannabinol (THC).” the guideline states.

"Clinicians should not dismiss patients from care based on a urine drug test result because this could constitute patient abandonment and could have adverse consequences for patient safety, potentially including the patient obtaining opioids from alternative sources and the clinician missing opportunities to facilitate treatment for substance use disorder."

Another factor to consider is the unreliability of urine drug tests. As PNN has reported, “point-of care” (POC) urine drug tests, the kind widely used in doctor’s offices, frequently giving false positive or false negative results for marijuana, cocaine and other drugs. 

A 2015 study found that 21% of POC tests for marijuana and 12% of those for cocaine produced a false positive result.

Race and Economic Insecurity Play Key Roles in Pain

By Pat Anson, Editor

Two new studies are adding to the growing evidence that links pain with economic, social and racial differences in the United States.

Researchers at Indiana University-Purdue University say African-Americans use coping strategies that often make their pain worse; while researchers at the University of Virginia found that people who feel that their financial outlook is shaky experience more physical pain.

“The past decade has seen a rise in both economic insecurity and frequency of physical pain. The current research reveals a causal connection between these two growing and consequential social trends,” wrote lead author Eileen Chou of the University of Virginia in the journal Psychological Science.

Chou and her colleagues looked at six different studies and found that economic insecurity produces physical pain, reduces pain tolerance, and predicts consumption of over-the-counter pain relievers. The researchers believe economic insecurity also leads people to feel a lack of control in their lives, which activates psychological processes associated with anxiety, fear, and stress.

Data from a consumer panel of nearly 34,000 individuals revealed that households in which both adults were unemployed spent 20% more on over-the-counter pain relievers than households in which at least one adult was working.

Smaller studies also found that unemployment was correlated with reports of pain. And people who recalled periods of economic instability reported almost double the amount of physical pain than those who recalled economically stable periods.

“Overall, the findings show that it physically hurts to be economically insecure,” Chou said.

Financial stress and economic insecurity were also blamed in a recent landmark study by Princeton University researchers who found that nearly half a million middle aged white Americans died prematurely in the last 15 years. The rising death rate for whites was also attributed to drug and alcohol poisoning, suicide, chronic pain and disability.

Blacks and Whites Cope with Pain Differently

The researchers at Indiana University-Purdue University also used a meta-analysis (a study of studies) to reach their conclusion that black and white Americans cope with pain differently. The review of 19 studies, which included 2,719 black and 3,770 white adults, is the first to quantify the relationship between race and the use of pain-coping strategies.

"Coping" was broadly defined as the use of behavioral and cognitive techniques to manage stress.

Blacks were significantly more likely to use prayer and hoping as pain-coping strategies than whites, according to researchers. Blacks were also more likely than whites to think about their pain in a catastrophic manner.

"Our findings suggest that blacks frequently use coping strategies that are associated with worse pain and functioning," said Adam Hirsh, a clinical health psychologist. "They view themselves as helpless in the face of pain. They see the pain as magnified -- the worst pain ever. They ruminate, think about the pain all the time, and it occupies a lot of their mind space."

While that kind of coping might be considered a negative approach to pain, Hirsch says it also may have benefits.

“It may also be a potent communication strategy -- it tells others in a culture with a strong communal component that the person is really suffering and needs help. Thus, it may be helpful in some ways, such as eliciting support from other people, and unhelpful in other ways. In future studies, we will give this more nuanced investigation," said Hirsch, whose study is published in the Journal of Pain.

Ignoring pain rather than allowing it to interfere with the task at hand was the only coping strategy employed by whites more than blacks. Several studies reviewed by researchers found that ignoring strategies are associated with less pain, whereas praying, hoping and catastrophizing are associated with higher pain levels.

"How people think about their pain matters," said Hirsh. "For example, religion can be used as a passive coping strategy -- asking a higher authority to take the pain away -- or as an active coping strategy -- asking to be given strength to manage pain.”

Blacks reported higher levels of pain than whites for a number of conditions including arthritis, post-operative pain and lower-back pain. Blacks also experience greater pain in both clinical and experimental studies. Blacks reported less-effective pain care, are unable to return to work for a longer time due to pain, and have worse functional outcomes.

Hirsch says understanding how different racial groups cope with pain may improve pain care and support individually tailored treatment.