Pain

TOPLINE:

Taking a prescription opioid for pain management during pregnancy is associated with an increased risk for spontaneous preterm birth, data from a new case-control study of over 25,000 Medicaid patients showed.

METHODOLOGY:

• Researchers retrospectively reviewed data on pregnant patients enrolled in Tennessee Medicaid who experienced birth of a single baby at ≥ 24 weeks gestation (25,391 with opioid use disorder and 225,696 without).
• Median age of participants was 23 years; 58.1% were non-Hispanic White, 38.7% Black, 2.6% Hispanic, and 0.5% Asian.
• Controls were matched based on pregnancy start date, race, ethnicity, age at delivery (within 2 years), and history of prior preterm birth.
• Sensitivity analysis included the exclusion of opioid prescriptions dispensed within 3 days of the index date to account for potential opioid prescribing associated with labor pain.

TAKEAWAY:

• A total of 18,702 patients (7.4%) filled an opioid prescription during the 60 days prior to the index date.
• Each doubling of opioid morphine milligram equivalents (MMEs) prescribed during the 60 days was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure in the matched controls (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01-1.08).
• Overall, 1573 pregnancies filled prescriptions for 900 MMEs or greater, which was associated with at least a 21% increased risk for spontaneous preterm birth compared with no opioid exposure (aOR, 1.21; 95% CI, 1.10-1.33).
• Researchers found no significant difference in odds of spontaneous preterm birth among included opioid types after adjusting for confounders and opioid MMD.

IN PRACTICE:

“This association may appear modest, especially considering that common, one-time prescriptions often fall in the 150-225 MME range, but these findings may provide more caution when prescribing multiple, higher strength opioids,” the authors wrote. “We also caution against the conclusion that lower doses, especially those below 100 MME, are safe; the confidence bands over the low dose range still include odds ratios that are consistent with meaningful harm.”

SOURCE:

Sarah S. Osmundson, MD, MS, of the Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, was the senior and corresponding author on the study. The study was published online on February 14 in JAMA Network Open.

LIMITATIONS:

Data are based on opioids prescribed and lack detail on actual use of opioids and nonprescription analgesics. Findings may not be generalizable to other populations or settings outside Medicaid.

DISCLOSURES:

No source of study funding listed. Dr. Osmundson reported receiving grant support from the National Institute on Drug Abuse during the conduct of the study. The other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Taking a prescription opioid for pain management during pregnancy is associated with an increased risk for spontaneous preterm birth, data from a new case-control study of over 25,000 Medicaid patients showed.

METHODOLOGY:

• Researchers retrospectively reviewed data on pregnant patients enrolled in Tennessee Medicaid who experienced birth of a single baby at ≥ 24 weeks gestation (25,391 with opioid use disorder and 225,696 without).
• Median age of participants was 23 years; 58.1% were non-Hispanic White, 38.7% Black, 2.6% Hispanic, and 0.5% Asian.
• Controls were matched based on pregnancy start date, race, ethnicity, age at delivery (within 2 years), and history of prior preterm birth.
• Sensitivity analysis included the exclusion of opioid prescriptions dispensed within 3 days of the index date to account for potential opioid prescribing associated with labor pain.

TAKEAWAY:

• A total of 18,702 patients (7.4%) filled an opioid prescription during the 60 days prior to the index date.
• Each doubling of opioid morphine milligram equivalents (MMEs) prescribed during the 60 days was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure in the matched controls (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01-1.08).
• Overall, 1573 pregnancies filled prescriptions for 900 MMEs or greater, which was associated with at least a 21% increased risk for spontaneous preterm birth compared with no opioid exposure (aOR, 1.21; 95% CI, 1.10-1.33).
• Researchers found no significant difference in odds of spontaneous preterm birth among included opioid types after adjusting for confounders and opioid MMD.

IN PRACTICE:

“This association may appear modest, especially considering that common, one-time prescriptions often fall in the 150-225 MME range, but these findings may provide more caution when prescribing multiple, higher strength opioids,” the authors wrote. “We also caution against the conclusion that lower doses, especially those below 100 MME, are safe; the confidence bands over the low dose range still include odds ratios that are consistent with meaningful harm.”

SOURCE:

Sarah S. Osmundson, MD, MS, of the Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, was the senior and corresponding author on the study. The study was published online on February 14 in JAMA Network Open.

LIMITATIONS:

Data are based on opioids prescribed and lack detail on actual use of opioids and nonprescription analgesics. Findings may not be generalizable to other populations or settings outside Medicaid.

DISCLOSURES:

No source of study funding listed. Dr. Osmundson reported receiving grant support from the National Institute on Drug Abuse during the conduct of the study. The other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Taking a prescription opioid for pain management during pregnancy is associated with an increased risk for spontaneous preterm birth, data from a new case-control study of over 25,000 Medicaid patients showed.

METHODOLOGY:

• Researchers retrospectively reviewed data on pregnant patients enrolled in Tennessee Medicaid who experienced birth of a single baby at ≥ 24 weeks gestation (25,391 with opioid use disorder and 225,696 without).
• Median age of participants was 23 years; 58.1% were non-Hispanic White, 38.7% Black, 2.6% Hispanic, and 0.5% Asian.
• Controls were matched based on pregnancy start date, race, ethnicity, age at delivery (within 2 years), and history of prior preterm birth.
• Sensitivity analysis included the exclusion of opioid prescriptions dispensed within 3 days of the index date to account for potential opioid prescribing associated with labor pain.

TAKEAWAY:

• A total of 18,702 patients (7.4%) filled an opioid prescription during the 60 days prior to the index date.
• Each doubling of opioid morphine milligram equivalents (MMEs) prescribed during the 60 days was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure in the matched controls (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01-1.08).
• Overall, 1573 pregnancies filled prescriptions for 900 MMEs or greater, which was associated with at least a 21% increased risk for spontaneous preterm birth compared with no opioid exposure (aOR, 1.21; 95% CI, 1.10-1.33).
• Researchers found no significant difference in odds of spontaneous preterm birth among included opioid types after adjusting for confounders and opioid MMD.

IN PRACTICE:

“This association may appear modest, especially considering that common, one-time prescriptions often fall in the 150-225 MME range, but these findings may provide more caution when prescribing multiple, higher strength opioids,” the authors wrote. “We also caution against the conclusion that lower doses, especially those below 100 MME, are safe; the confidence bands over the low dose range still include odds ratios that are consistent with meaningful harm.”

SOURCE:

Sarah S. Osmundson, MD, MS, of the Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, was the senior and corresponding author on the study. The study was published online on February 14 in JAMA Network Open.

LIMITATIONS:

Data are based on opioids prescribed and lack detail on actual use of opioids and nonprescription analgesics. Findings may not be generalizable to other populations or settings outside Medicaid.

DISCLOSURES:

No source of study funding listed. Dr. Osmundson reported receiving grant support from the National Institute on Drug Abuse during the conduct of the study. The other authors’ disclosures are listed on the original paper.
 

A version of this article appeared on Medscape.com.

Postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a distinct, centrally mediated condition, with evidence of autonomic, immune, and metabolic dysfunction, new "deep phenotyping" data suggested.

The study was initiated in 2016 at the US National Institutes of Health. Its aim was to better elucidate the underlying pathophysiology of ME/CFS, a multisystem disorder characterized by persistent and disabling fatigue, post-exertional malaise, cognitive complaints, and other physical symptoms. A total of 17 carefully selected individuals with PI-ME/CFS onset within the prior 5 years were compared with 21 healthy volunteers on a more extensive set of biologic measurements than has been examined in any prior study of the condition.

Overall, the findings suggested that ME/CFS is “a distinct entity characterized by somatic and cognitive complaints that are centrally mediated,” with fatigue that is “defined by effort preferences and central autonomic dysfunction,” Brian T. Walitt, MD, of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland, and colleagues wrote in the paper, published on February 21 in Nature Communications.

In addition, “there are distinct sex signatures of immune and metabolic dysregulation which suggest persistent antigenic stimulation.” Physical deconditioning over time, while not the source of the condition, “is an important consequence,” the authors added.

Asked to comment, Hector Bonilla, MD, director of the ME/CFS Clinic and codirector of the Stanford Post-Acute COVID-19 Syndrome Clinic, Atherton, California, pointed out that the sample was small and the study was cross-sectional and therefore likely missed dynamic changes in the patients.

Nonetheless, Dr. Bonilla told this news organization, “they have shown clear objective changes in patients with ME/CFS not seen in the controls. These are present in the microbiome, in the immune system, and in metabolites, especially in spinal fluid, that lead to a neuroinflammatory condition. And these are linked with autonomic dysfunction that can explain many of the symptoms that patients experience ... The symptoms are not manufactured by them.”

Thus far, the only treatments for ME/CFS are symptomatic. Understanding the pathophysiology is essential to identifying disease-modifying therapy, study lead author Avindra Nath, MD, Senior Investigator and Clinical Director of Intramural Research at NINDS, told this news organization.

“The disease is real. But our medical profession is limited in what they can do to diagnose or impact them ... The first thing we need to do is try to understand the pathophysiology. So that’s why the study was put together,” Dr. Nath said.

Postinfectious syndromes including ME/CFS have been given many names, including post-Lyme disease, Gulf War illness, and more recently, long COVID. With ME/CFS, the Epstein-Barr virus has historically been one of the most commonly associated triggers, although several other viral, bacterial, and environmental toxins have been implicated.

“There are a whole host of these things that have very similar symptoms or overlapping symptoms ... It’s quite possible that the underlying pathophysiology overlaps between all these syndromes,” Dr. Nath noted.

Another ME/CFS expert not involved in the study, researcher Michael VanElzakker, PhD, of the Neurotherapeutics Division at Harvard Medical School and Massachusetts General Hospital, Boston, said that the possibility of antigen persistence of the infectious pathogen arising from the immune system profiling conducted in the study is noteworthy and merits further study.

“To me, the obvious next step would be techniques like tissue-based assays and T-cell sequencing to try and understand what exactly those antigens are and what their source might be. Importantly, it is probably not the same antigen or pathogen source in all patients, but that’s a question that needs an answer,” Dr. VanElzakker said.

Of note, the 17 study participants had been adjudicated by an expert panel from an initial 484 inquiries and 217 who underwent detailed case reviews. They had to meet at least one of three published ME/CFS criteria and to have moderate to severe clinical symptom severity as determined by several fatigue scores. None met the criteria for psychiatric diagnoses.

Yet, even in the cases that met study criteria, underlying causes emerged in 20% of the participants over time, suggesting diagnostic misattribution. “This misclassification bias has important ramifications on the interpretation of the existing ME/CFS research literature,” the authors wrote.

Dr. VanElzakker noted, “The fact that this research study was probably the most detailed workup many of these patients had ever gotten is a serious indictment of our current profit-based healthcare system’s prioritization of 15-minute doctor’s appointments. It is almost certain that other patients would also benefit from an intensive detailed workup.”
 

Multiple Abnormalities Identified

There were no differences between the PI-ME/CFS and control groups in ventilatory function, muscle oxygenation, mechanical efficiency, resting energy expenditure, basal mitochondrial function of immune cells, muscle fiber composition, or body composition, suggesting the absence of a resting low-energy state, the authors said.

In 40-minute head-up tilt-table testing, there were no differences between the ME/CFS and control groups in frequency or orthostatic hypotension or extensive orthostatic tachycardia. However, a 24-hour ambulatory electrocardiogram showed that the patients with PI-ME/CFS had diminished heart rate variability. They also showed increased heart rate throughout the day, suggesting increased sympathetic activity, and a diminished drop in nighttime heart rate, suggesting decreased parasympathetic activity.

“Considered together, these data suggest that there is an alteration in autonomic tone, implying central nervous system regulatory change,” Dr. Walitt and colleagues wrote.

On the “Effort-Expenditure for Rewards Task,” the participants with PI-ME/CFS showed significant differences in “effort preference,” or a tendency to avoid the harder tasks, as well as a slowing of button-pushing over time, compared with the controls, even with easier tasks. This pattern suggests that those with PI-ME/CFS were “pacing to limit exertion and associated feelings of discomfort,” the authors wrote.

Dr. Nath describes this behavior as akin to “if you develop a flu, you feel that you just want to lay down in bed and not hurt yourself. It’s not that you’re not capable of doing [the task], but your body tells you don’t do it. Your body just wants to fight the infection ... these people just never bounce back.”

Compared with the controls, the participants with PI-ME/CFS failed to maintain a moderate grip force even though there was no difference in maximum grip strength or arm muscle mass. This performance difference correlated with decreased activity of the right temporal-parietal junction, a novel observation suggesting that the fatigue in the PI-ME/CFS group “is due to dysfunction of integrative brain regions that drive the motor cortex, the cause of which needs to be further explored,” Dr. Walitt and colleagues wrote.

On cardiopulmonary testing, peak power, peak respiratory rate, peak heart rate, and peak VO₂ were all lower in the PI-ME/CFS group, correlating to a difference of approximately 3.3 metabolic equivalent of task units. The differential cardiorespiratory performance relates to “autonomic function, hypothalamic-pituitary-adrenal axis hyporesponsiveness, and muscular deconditioning from disuse that clinically impacts activities of daily life,” they said.

In the participants with PI-ME/CFS, catechol levels in cerebrospinal fluid correlated with grip strength and effort preference, and several metabolites of the dopamine pathway correlated with several cognitive symptoms.

“This suggests that central nervous system catechol pathways are dysregulated in PI-ME/CFS and may play a role in effort preference and cognitive complaints,” as well as decreased central catecholamine biosynthesis. Similar findings have been seen in patients with long COVID, the authors noted.

There were increased naive B cells and decreased switched memory B cells in blood of participants with PI-ME/CFS. Contrary to prior studies, there was no consistent pattern of autoimmunity across all participants with PI-ME/CFS, and no previously undescribed antibodies were identified.

However, programmed cell death protein 1, a marker of T-cell exhaustion and activation, was elevated in the cerebrospinal fluid of the patients with PI-ME/CFS.

Several sex-based differences were noted, including in immune cell expression in cerebrospinal fluid, peripheral blood mononuclear cell gene expression, and muscle gene expression. Males and females also differed in the cerebrospinal metabolomics that distinguished the participants with PI-ME/CFS from controls.
 

What Do These Findings Suggest About Treatment?

The data point to several treatment implications. For one, the finding of possible immune exhaustion suggests that immune checkpoint inhibitors may be therapeutic by promoting clearance of foreign antigens. Immune dysfunction leads to neurochemical alterations that affect neuronal circuits, which may be another point of intervention, the authors suggested.

On the other hand, “attempting to target downstream mechanisms with exercise, cognitive behavioral therapy, or autonomic directed therapies may have limited impact on symptom burden, as it would not address the root cause of PI-ME/CFS,” they noted.

Combination therapy targeting multiple pathways along with a personalized medicine approach should be considered, they said.

“I think the most important thing is not to discount these patients,” Dr. Nath told this news organization. “They have a real disease, and we need to be empathetic towards them. We also need to make sure that they don’t have something underlying that is treatable, and then treat them symptomatically the best that you can. If not, then refer them to ME/CFS studies or clinics where people specialize in these conditions and work with them.”

The study authors and Dr. VanElzakker reported no relevant financial relationships. Dr. Bonilla consults for United Health and Resverlogix.
 

A version of this article appeared on Medscape.com.

Postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a distinct, centrally mediated condition, with evidence of autonomic, immune, and metabolic dysfunction, new "deep phenotyping" data suggested.

The study was initiated in 2016 at the US National Institutes of Health. Its aim was to better elucidate the underlying pathophysiology of ME/CFS, a multisystem disorder characterized by persistent and disabling fatigue, post-exertional malaise, cognitive complaints, and other physical symptoms. A total of 17 carefully selected individuals with PI-ME/CFS onset within the prior 5 years were compared with 21 healthy volunteers on a more extensive set of biologic measurements than has been examined in any prior study of the condition.

Overall, the findings suggested that ME/CFS is “a distinct entity characterized by somatic and cognitive complaints that are centrally mediated,” with fatigue that is “defined by effort preferences and central autonomic dysfunction,” Brian T. Walitt, MD, of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland, and colleagues wrote in the paper, published on February 21 in Nature Communications.

In addition, “there are distinct sex signatures of immune and metabolic dysregulation which suggest persistent antigenic stimulation.” Physical deconditioning over time, while not the source of the condition, “is an important consequence,” the authors added.

Asked to comment, Hector Bonilla, MD, director of the ME/CFS Clinic and codirector of the Stanford Post-Acute COVID-19 Syndrome Clinic, Atherton, California, pointed out that the sample was small and the study was cross-sectional and therefore likely missed dynamic changes in the patients.

Nonetheless, Dr. Bonilla told this news organization, “they have shown clear objective changes in patients with ME/CFS not seen in the controls. These are present in the microbiome, in the immune system, and in metabolites, especially in spinal fluid, that lead to a neuroinflammatory condition. And these are linked with autonomic dysfunction that can explain many of the symptoms that patients experience ... The symptoms are not manufactured by them.”

Thus far, the only treatments for ME/CFS are symptomatic. Understanding the pathophysiology is essential to identifying disease-modifying therapy, study lead author Avindra Nath, MD, Senior Investigator and Clinical Director of Intramural Research at NINDS, told this news organization.

“The disease is real. But our medical profession is limited in what they can do to diagnose or impact them ... The first thing we need to do is try to understand the pathophysiology. So that’s why the study was put together,” Dr. Nath said.

Postinfectious syndromes including ME/CFS have been given many names, including post-Lyme disease, Gulf War illness, and more recently, long COVID. With ME/CFS, the Epstein-Barr virus has historically been one of the most commonly associated triggers, although several other viral, bacterial, and environmental toxins have been implicated.

“There are a whole host of these things that have very similar symptoms or overlapping symptoms ... It’s quite possible that the underlying pathophysiology overlaps between all these syndromes,” Dr. Nath noted.

Another ME/CFS expert not involved in the study, researcher Michael VanElzakker, PhD, of the Neurotherapeutics Division at Harvard Medical School and Massachusetts General Hospital, Boston, said that the possibility of antigen persistence of the infectious pathogen arising from the immune system profiling conducted in the study is noteworthy and merits further study.

“To me, the obvious next step would be techniques like tissue-based assays and T-cell sequencing to try and understand what exactly those antigens are and what their source might be. Importantly, it is probably not the same antigen or pathogen source in all patients, but that’s a question that needs an answer,” Dr. VanElzakker said.

Of note, the 17 study participants had been adjudicated by an expert panel from an initial 484 inquiries and 217 who underwent detailed case reviews. They had to meet at least one of three published ME/CFS criteria and to have moderate to severe clinical symptom severity as determined by several fatigue scores. None met the criteria for psychiatric diagnoses.

Yet, even in the cases that met study criteria, underlying causes emerged in 20% of the participants over time, suggesting diagnostic misattribution. “This misclassification bias has important ramifications on the interpretation of the existing ME/CFS research literature,” the authors wrote.

Dr. VanElzakker noted, “The fact that this research study was probably the most detailed workup many of these patients had ever gotten is a serious indictment of our current profit-based healthcare system’s prioritization of 15-minute doctor’s appointments. It is almost certain that other patients would also benefit from an intensive detailed workup.”
 

Multiple Abnormalities Identified

There were no differences between the PI-ME/CFS and control groups in ventilatory function, muscle oxygenation, mechanical efficiency, resting energy expenditure, basal mitochondrial function of immune cells, muscle fiber composition, or body composition, suggesting the absence of a resting low-energy state, the authors said.

In 40-minute head-up tilt-table testing, there were no differences between the ME/CFS and control groups in frequency or orthostatic hypotension or extensive orthostatic tachycardia. However, a 24-hour ambulatory electrocardiogram showed that the patients with PI-ME/CFS had diminished heart rate variability. They also showed increased heart rate throughout the day, suggesting increased sympathetic activity, and a diminished drop in nighttime heart rate, suggesting decreased parasympathetic activity.

“Considered together, these data suggest that there is an alteration in autonomic tone, implying central nervous system regulatory change,” Dr. Walitt and colleagues wrote.

On the “Effort-Expenditure for Rewards Task,” the participants with PI-ME/CFS showed significant differences in “effort preference,” or a tendency to avoid the harder tasks, as well as a slowing of button-pushing over time, compared with the controls, even with easier tasks. This pattern suggests that those with PI-ME/CFS were “pacing to limit exertion and associated feelings of discomfort,” the authors wrote.

Dr. Nath describes this behavior as akin to “if you develop a flu, you feel that you just want to lay down in bed and not hurt yourself. It’s not that you’re not capable of doing [the task], but your body tells you don’t do it. Your body just wants to fight the infection ... these people just never bounce back.”

Compared with the controls, the participants with PI-ME/CFS failed to maintain a moderate grip force even though there was no difference in maximum grip strength or arm muscle mass. This performance difference correlated with decreased activity of the right temporal-parietal junction, a novel observation suggesting that the fatigue in the PI-ME/CFS group “is due to dysfunction of integrative brain regions that drive the motor cortex, the cause of which needs to be further explored,” Dr. Walitt and colleagues wrote.

On cardiopulmonary testing, peak power, peak respiratory rate, peak heart rate, and peak VO₂ were all lower in the PI-ME/CFS group, correlating to a difference of approximately 3.3 metabolic equivalent of task units. The differential cardiorespiratory performance relates to “autonomic function, hypothalamic-pituitary-adrenal axis hyporesponsiveness, and muscular deconditioning from disuse that clinically impacts activities of daily life,” they said.

In the participants with PI-ME/CFS, catechol levels in cerebrospinal fluid correlated with grip strength and effort preference, and several metabolites of the dopamine pathway correlated with several cognitive symptoms.

“This suggests that central nervous system catechol pathways are dysregulated in PI-ME/CFS and may play a role in effort preference and cognitive complaints,” as well as decreased central catecholamine biosynthesis. Similar findings have been seen in patients with long COVID, the authors noted.

There were increased naive B cells and decreased switched memory B cells in blood of participants with PI-ME/CFS. Contrary to prior studies, there was no consistent pattern of autoimmunity across all participants with PI-ME/CFS, and no previously undescribed antibodies were identified.

However, programmed cell death protein 1, a marker of T-cell exhaustion and activation, was elevated in the cerebrospinal fluid of the patients with PI-ME/CFS.

Several sex-based differences were noted, including in immune cell expression in cerebrospinal fluid, peripheral blood mononuclear cell gene expression, and muscle gene expression. Males and females also differed in the cerebrospinal metabolomics that distinguished the participants with PI-ME/CFS from controls.
 

What Do These Findings Suggest About Treatment?

The data point to several treatment implications. For one, the finding of possible immune exhaustion suggests that immune checkpoint inhibitors may be therapeutic by promoting clearance of foreign antigens. Immune dysfunction leads to neurochemical alterations that affect neuronal circuits, which may be another point of intervention, the authors suggested.

On the other hand, “attempting to target downstream mechanisms with exercise, cognitive behavioral therapy, or autonomic directed therapies may have limited impact on symptom burden, as it would not address the root cause of PI-ME/CFS,” they noted.

Combination therapy targeting multiple pathways along with a personalized medicine approach should be considered, they said.

“I think the most important thing is not to discount these patients,” Dr. Nath told this news organization. “They have a real disease, and we need to be empathetic towards them. We also need to make sure that they don’t have something underlying that is treatable, and then treat them symptomatically the best that you can. If not, then refer them to ME/CFS studies or clinics where people specialize in these conditions and work with them.”

The study authors and Dr. VanElzakker reported no relevant financial relationships. Dr. Bonilla consults for United Health and Resverlogix.
 

A version of this article appeared on Medscape.com.

Postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a distinct, centrally mediated condition, with evidence of autonomic, immune, and metabolic dysfunction, new "deep phenotyping" data suggested.

The study was initiated in 2016 at the US National Institutes of Health. Its aim was to better elucidate the underlying pathophysiology of ME/CFS, a multisystem disorder characterized by persistent and disabling fatigue, post-exertional malaise, cognitive complaints, and other physical symptoms. A total of 17 carefully selected individuals with PI-ME/CFS onset within the prior 5 years were compared with 21 healthy volunteers on a more extensive set of biologic measurements than has been examined in any prior study of the condition.

Overall, the findings suggested that ME/CFS is “a distinct entity characterized by somatic and cognitive complaints that are centrally mediated,” with fatigue that is “defined by effort preferences and central autonomic dysfunction,” Brian T. Walitt, MD, of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland, and colleagues wrote in the paper, published on February 21 in Nature Communications.

In addition, “there are distinct sex signatures of immune and metabolic dysregulation which suggest persistent antigenic stimulation.” Physical deconditioning over time, while not the source of the condition, “is an important consequence,” the authors added.

Asked to comment, Hector Bonilla, MD, director of the ME/CFS Clinic and codirector of the Stanford Post-Acute COVID-19 Syndrome Clinic, Atherton, California, pointed out that the sample was small and the study was cross-sectional and therefore likely missed dynamic changes in the patients.

Nonetheless, Dr. Bonilla told this news organization, “they have shown clear objective changes in patients with ME/CFS not seen in the controls. These are present in the microbiome, in the immune system, and in metabolites, especially in spinal fluid, that lead to a neuroinflammatory condition. And these are linked with autonomic dysfunction that can explain many of the symptoms that patients experience ... The symptoms are not manufactured by them.”

Thus far, the only treatments for ME/CFS are symptomatic. Understanding the pathophysiology is essential to identifying disease-modifying therapy, study lead author Avindra Nath, MD, Senior Investigator and Clinical Director of Intramural Research at NINDS, told this news organization.

“The disease is real. But our medical profession is limited in what they can do to diagnose or impact them ... The first thing we need to do is try to understand the pathophysiology. So that’s why the study was put together,” Dr. Nath said.

Postinfectious syndromes including ME/CFS have been given many names, including post-Lyme disease, Gulf War illness, and more recently, long COVID. With ME/CFS, the Epstein-Barr virus has historically been one of the most commonly associated triggers, although several other viral, bacterial, and environmental toxins have been implicated.

“There are a whole host of these things that have very similar symptoms or overlapping symptoms ... It’s quite possible that the underlying pathophysiology overlaps between all these syndromes,” Dr. Nath noted.

Another ME/CFS expert not involved in the study, researcher Michael VanElzakker, PhD, of the Neurotherapeutics Division at Harvard Medical School and Massachusetts General Hospital, Boston, said that the possibility of antigen persistence of the infectious pathogen arising from the immune system profiling conducted in the study is noteworthy and merits further study.

“To me, the obvious next step would be techniques like tissue-based assays and T-cell sequencing to try and understand what exactly those antigens are and what their source might be. Importantly, it is probably not the same antigen or pathogen source in all patients, but that’s a question that needs an answer,” Dr. VanElzakker said.

Of note, the 17 study participants had been adjudicated by an expert panel from an initial 484 inquiries and 217 who underwent detailed case reviews. They had to meet at least one of three published ME/CFS criteria and to have moderate to severe clinical symptom severity as determined by several fatigue scores. None met the criteria for psychiatric diagnoses.

Yet, even in the cases that met study criteria, underlying causes emerged in 20% of the participants over time, suggesting diagnostic misattribution. “This misclassification bias has important ramifications on the interpretation of the existing ME/CFS research literature,” the authors wrote.

Dr. VanElzakker noted, “The fact that this research study was probably the most detailed workup many of these patients had ever gotten is a serious indictment of our current profit-based healthcare system’s prioritization of 15-minute doctor’s appointments. It is almost certain that other patients would also benefit from an intensive detailed workup.”
 

Multiple Abnormalities Identified

There were no differences between the PI-ME/CFS and control groups in ventilatory function, muscle oxygenation, mechanical efficiency, resting energy expenditure, basal mitochondrial function of immune cells, muscle fiber composition, or body composition, suggesting the absence of a resting low-energy state, the authors said.

In 40-minute head-up tilt-table testing, there were no differences between the ME/CFS and control groups in frequency or orthostatic hypotension or extensive orthostatic tachycardia. However, a 24-hour ambulatory electrocardiogram showed that the patients with PI-ME/CFS had diminished heart rate variability. They also showed increased heart rate throughout the day, suggesting increased sympathetic activity, and a diminished drop in nighttime heart rate, suggesting decreased parasympathetic activity.

“Considered together, these data suggest that there is an alteration in autonomic tone, implying central nervous system regulatory change,” Dr. Walitt and colleagues wrote.

On the “Effort-Expenditure for Rewards Task,” the participants with PI-ME/CFS showed significant differences in “effort preference,” or a tendency to avoid the harder tasks, as well as a slowing of button-pushing over time, compared with the controls, even with easier tasks. This pattern suggests that those with PI-ME/CFS were “pacing to limit exertion and associated feelings of discomfort,” the authors wrote.

Dr. Nath describes this behavior as akin to “if you develop a flu, you feel that you just want to lay down in bed and not hurt yourself. It’s not that you’re not capable of doing [the task], but your body tells you don’t do it. Your body just wants to fight the infection ... these people just never bounce back.”

Compared with the controls, the participants with PI-ME/CFS failed to maintain a moderate grip force even though there was no difference in maximum grip strength or arm muscle mass. This performance difference correlated with decreased activity of the right temporal-parietal junction, a novel observation suggesting that the fatigue in the PI-ME/CFS group “is due to dysfunction of integrative brain regions that drive the motor cortex, the cause of which needs to be further explored,” Dr. Walitt and colleagues wrote.

On cardiopulmonary testing, peak power, peak respiratory rate, peak heart rate, and peak VO₂ were all lower in the PI-ME/CFS group, correlating to a difference of approximately 3.3 metabolic equivalent of task units. The differential cardiorespiratory performance relates to “autonomic function, hypothalamic-pituitary-adrenal axis hyporesponsiveness, and muscular deconditioning from disuse that clinically impacts activities of daily life,” they said.

In the participants with PI-ME/CFS, catechol levels in cerebrospinal fluid correlated with grip strength and effort preference, and several metabolites of the dopamine pathway correlated with several cognitive symptoms.

“This suggests that central nervous system catechol pathways are dysregulated in PI-ME/CFS and may play a role in effort preference and cognitive complaints,” as well as decreased central catecholamine biosynthesis. Similar findings have been seen in patients with long COVID, the authors noted.

There were increased naive B cells and decreased switched memory B cells in blood of participants with PI-ME/CFS. Contrary to prior studies, there was no consistent pattern of autoimmunity across all participants with PI-ME/CFS, and no previously undescribed antibodies were identified.

However, programmed cell death protein 1, a marker of T-cell exhaustion and activation, was elevated in the cerebrospinal fluid of the patients with PI-ME/CFS.

Several sex-based differences were noted, including in immune cell expression in cerebrospinal fluid, peripheral blood mononuclear cell gene expression, and muscle gene expression. Males and females also differed in the cerebrospinal metabolomics that distinguished the participants with PI-ME/CFS from controls.
 

What Do These Findings Suggest About Treatment?

The data point to several treatment implications. For one, the finding of possible immune exhaustion suggests that immune checkpoint inhibitors may be therapeutic by promoting clearance of foreign antigens. Immune dysfunction leads to neurochemical alterations that affect neuronal circuits, which may be another point of intervention, the authors suggested.

On the other hand, “attempting to target downstream mechanisms with exercise, cognitive behavioral therapy, or autonomic directed therapies may have limited impact on symptom burden, as it would not address the root cause of PI-ME/CFS,” they noted.

Combination therapy targeting multiple pathways along with a personalized medicine approach should be considered, they said.

“I think the most important thing is not to discount these patients,” Dr. Nath told this news organization. “They have a real disease, and we need to be empathetic towards them. We also need to make sure that they don’t have something underlying that is treatable, and then treat them symptomatically the best that you can. If not, then refer them to ME/CFS studies or clinics where people specialize in these conditions and work with them.”

The study authors and Dr. VanElzakker reported no relevant financial relationships. Dr. Bonilla consults for United Health and Resverlogix.
 

A version of this article appeared on Medscape.com.

Exercising for upwards of 30 minutes most days may help relieve pain in patients who’ve been diagnosed with cancer, according to a study of exercise and pain outcomes from more than 60,000 people, including 10,000 with a history of cancer. 

Study participants who’d been diagnosed with cancer and surpassed 150 minutes of moderate activity a week were 16% less likely to report pain than those who did not exercise or who exercised less. Exercise was particularly helpful for those with moderate to severe pain. In general, the more people exercised, the less pain they felt — and that was true for those with and without a history of cancer.

“This adds to a large evidence base regarding other benefits of exercise after cancer,” said lead study author Christopher Swain, PhD, a researcher at the University of Melbourne, Australia, who studies how physical activity can protect against cancer. “It would be great for physicians to encourage physical activity” for anyone who’s ever been diagnosed with cancer. 

The findings also add to mounting evidence — including observational and experimental studies — that physical activity may help ease people’s pain. One large cross-sectional study of Norwegian adults found that the prevalence of chronic pain was 10%-38% lower among people who exercised. Randomized trials suggest exercise could be an effective pain management tool for a range of conditions, including neck and low-back pain, osteoarthritis, myofascial pain, and fibromyalgia. 

Still, the analgesic effects of exercise are less established for cancer-related pain, the authors wrote in the recent study published in Cancer — even though cancer pain remains a common and critical issue. 

Cancer-related pain is unique, stemming from multiple potential causes, said Shakil Ahmed, MB, an anesthesiologist at Weill Cornell Medicine who specializes in treating cancer pain. (Dr. Ahmed was not involved in the study.) Patients “might be having pain from the tumor itself,” — such as a tumor pressing on nerves — “or as a result of treatment, including surgery, radiation, chemotherapy, or complications from long-term medications,” Dr. Ahmed said. Indeed, some 40% of patients have chronic pain post cancer diagnosis, and it›s often undertreated and underdiagnosed.
 

How Does Exercise Reduce Pain?

Researchers aren’t exactly sure how exercise modulates pain, but they have some theories.

A 2021 meta-analysis found that exercise training can raise a person›s pain threshold, particularly at the pain site, suggesting adaptations in central inhibition, a process in the central nervous system that suppresses the perception of pain. This echoes a 2017 review that suggests exercise may help relieve pain by activating central inhibitory pathways. 

“There’s definitely evidence that there is improvement in the pain-reduction chemicals and augmentation of the pain inhibitory process in the central nervous system,” said Dr. Ahmed. That is, exercise may induce chemical changes that alter how much pain the brain’s sensory neurons can detect. 

Regular exercise can also reduce inflammation and improve blood flow, noted William McCarthy, PhD, a public health researcher with UCLA Health — both effects that may help to reduce pain.

Psychological factors may be another part of it. “There’s a lot of psychological stress as a result of a cancer diagnosis, which can lower the pain threshold,” said Dr. Ahmed. Exercise may help boost mood and reduce stress, increasing pain tolerance.

“People who are physically active also tend to be more socially active,” Dr. McCarthy added. “Engaging in social networks that provide social support can often palliate a sense of constant battling with fatigue, pain, and other negative effects of cancer.” Social activity, in turn, may promote physical activity: Studies show that when sedentary people socialize with active people, they become more active themselves — often by joining in walks or sports.

 

Help Patients Reap the Pain-Relieving Benefits of Exercise 

For beginners, the key to establishing a long-term exercise routine is to start low and slow, said Dr. Ahmed. That is, start with low-intensity activities like walking (walking was the most common activity reported in the study) or using light weights. Then, build slowly from there. 

Keep in mind that some pain or stiffness is normal at first, as one’s muscles and joints get used to the new activity. But be sure to investigate any new pain, Dr. Ahmed said. “Especially for patients who have had cancer, you want to see if the patient has any recurrence of disease,” Dr. Ahmed said. “That has to be kept in mind when you recommend any kind of exercise. “ 

It’s worth acknowledging that pain can be a significant barrier to exercise. If appropriate, you may consider referring out to exercise or physical therapy professionals in your network. Emphasizing the benefits of exercise — like the pain relief — may help motivate patients as well. 

For Dr. Swain, encouraging exercise is less about prescribing specific quantities and more about helping patients find activities “that give them enjoyment, that they feel comfortable doing, and that they can sustain over time.”

“The field needs to consider the different ways of supporting physical activity after a cancer diagnosis and treatment,” Dr. Swain said. “We have a lot of great research that shows the benefit of physical activity but not as strong an understanding of how to encourage and support it.”

A version of this article appeared on Medscape.com.

Exercising for upwards of 30 minutes most days may help relieve pain in patients who’ve been diagnosed with cancer, according to a study of exercise and pain outcomes from more than 60,000 people, including 10,000 with a history of cancer. 

Study participants who’d been diagnosed with cancer and surpassed 150 minutes of moderate activity a week were 16% less likely to report pain than those who did not exercise or who exercised less. Exercise was particularly helpful for those with moderate to severe pain. In general, the more people exercised, the less pain they felt — and that was true for those with and without a history of cancer.

“This adds to a large evidence base regarding other benefits of exercise after cancer,” said lead study author Christopher Swain, PhD, a researcher at the University of Melbourne, Australia, who studies how physical activity can protect against cancer. “It would be great for physicians to encourage physical activity” for anyone who’s ever been diagnosed with cancer. 

The findings also add to mounting evidence — including observational and experimental studies — that physical activity may help ease people’s pain. One large cross-sectional study of Norwegian adults found that the prevalence of chronic pain was 10%-38% lower among people who exercised. Randomized trials suggest exercise could be an effective pain management tool for a range of conditions, including neck and low-back pain, osteoarthritis, myofascial pain, and fibromyalgia. 

Still, the analgesic effects of exercise are less established for cancer-related pain, the authors wrote in the recent study published in Cancer — even though cancer pain remains a common and critical issue. 

Cancer-related pain is unique, stemming from multiple potential causes, said Shakil Ahmed, MB, an anesthesiologist at Weill Cornell Medicine who specializes in treating cancer pain. (Dr. Ahmed was not involved in the study.) Patients “might be having pain from the tumor itself,” — such as a tumor pressing on nerves — “or as a result of treatment, including surgery, radiation, chemotherapy, or complications from long-term medications,” Dr. Ahmed said. Indeed, some 40% of patients have chronic pain post cancer diagnosis, and it›s often undertreated and underdiagnosed.
 

How Does Exercise Reduce Pain?

Researchers aren’t exactly sure how exercise modulates pain, but they have some theories.

A 2021 meta-analysis found that exercise training can raise a person›s pain threshold, particularly at the pain site, suggesting adaptations in central inhibition, a process in the central nervous system that suppresses the perception of pain. This echoes a 2017 review that suggests exercise may help relieve pain by activating central inhibitory pathways. 

“There’s definitely evidence that there is improvement in the pain-reduction chemicals and augmentation of the pain inhibitory process in the central nervous system,” said Dr. Ahmed. That is, exercise may induce chemical changes that alter how much pain the brain’s sensory neurons can detect. 

Regular exercise can also reduce inflammation and improve blood flow, noted William McCarthy, PhD, a public health researcher with UCLA Health — both effects that may help to reduce pain.

Psychological factors may be another part of it. “There’s a lot of psychological stress as a result of a cancer diagnosis, which can lower the pain threshold,” said Dr. Ahmed. Exercise may help boost mood and reduce stress, increasing pain tolerance.

“People who are physically active also tend to be more socially active,” Dr. McCarthy added. “Engaging in social networks that provide social support can often palliate a sense of constant battling with fatigue, pain, and other negative effects of cancer.” Social activity, in turn, may promote physical activity: Studies show that when sedentary people socialize with active people, they become more active themselves — often by joining in walks or sports.

 

Help Patients Reap the Pain-Relieving Benefits of Exercise 

For beginners, the key to establishing a long-term exercise routine is to start low and slow, said Dr. Ahmed. That is, start with low-intensity activities like walking (walking was the most common activity reported in the study) or using light weights. Then, build slowly from there. 

Keep in mind that some pain or stiffness is normal at first, as one’s muscles and joints get used to the new activity. But be sure to investigate any new pain, Dr. Ahmed said. “Especially for patients who have had cancer, you want to see if the patient has any recurrence of disease,” Dr. Ahmed said. “That has to be kept in mind when you recommend any kind of exercise. “ 

It’s worth acknowledging that pain can be a significant barrier to exercise. If appropriate, you may consider referring out to exercise or physical therapy professionals in your network. Emphasizing the benefits of exercise — like the pain relief — may help motivate patients as well. 

For Dr. Swain, encouraging exercise is less about prescribing specific quantities and more about helping patients find activities “that give them enjoyment, that they feel comfortable doing, and that they can sustain over time.”

“The field needs to consider the different ways of supporting physical activity after a cancer diagnosis and treatment,” Dr. Swain said. “We have a lot of great research that shows the benefit of physical activity but not as strong an understanding of how to encourage and support it.”

A version of this article appeared on Medscape.com.

Exercising for upwards of 30 minutes most days may help relieve pain in patients who’ve been diagnosed with cancer, according to a study of exercise and pain outcomes from more than 60,000 people, including 10,000 with a history of cancer. 

Study participants who’d been diagnosed with cancer and surpassed 150 minutes of moderate activity a week were 16% less likely to report pain than those who did not exercise or who exercised less. Exercise was particularly helpful for those with moderate to severe pain. In general, the more people exercised, the less pain they felt — and that was true for those with and without a history of cancer.

“This adds to a large evidence base regarding other benefits of exercise after cancer,” said lead study author Christopher Swain, PhD, a researcher at the University of Melbourne, Australia, who studies how physical activity can protect against cancer. “It would be great for physicians to encourage physical activity” for anyone who’s ever been diagnosed with cancer. 

The findings also add to mounting evidence — including observational and experimental studies — that physical activity may help ease people’s pain. One large cross-sectional study of Norwegian adults found that the prevalence of chronic pain was 10%-38% lower among people who exercised. Randomized trials suggest exercise could be an effective pain management tool for a range of conditions, including neck and low-back pain, osteoarthritis, myofascial pain, and fibromyalgia. 

Still, the analgesic effects of exercise are less established for cancer-related pain, the authors wrote in the recent study published in Cancer — even though cancer pain remains a common and critical issue. 

Cancer-related pain is unique, stemming from multiple potential causes, said Shakil Ahmed, MB, an anesthesiologist at Weill Cornell Medicine who specializes in treating cancer pain. (Dr. Ahmed was not involved in the study.) Patients “might be having pain from the tumor itself,” — such as a tumor pressing on nerves — “or as a result of treatment, including surgery, radiation, chemotherapy, or complications from long-term medications,” Dr. Ahmed said. Indeed, some 40% of patients have chronic pain post cancer diagnosis, and it›s often undertreated and underdiagnosed.
 

How Does Exercise Reduce Pain?

Researchers aren’t exactly sure how exercise modulates pain, but they have some theories.

A 2021 meta-analysis found that exercise training can raise a person›s pain threshold, particularly at the pain site, suggesting adaptations in central inhibition, a process in the central nervous system that suppresses the perception of pain. This echoes a 2017 review that suggests exercise may help relieve pain by activating central inhibitory pathways. 

“There’s definitely evidence that there is improvement in the pain-reduction chemicals and augmentation of the pain inhibitory process in the central nervous system,” said Dr. Ahmed. That is, exercise may induce chemical changes that alter how much pain the brain’s sensory neurons can detect. 

Regular exercise can also reduce inflammation and improve blood flow, noted William McCarthy, PhD, a public health researcher with UCLA Health — both effects that may help to reduce pain.

Psychological factors may be another part of it. “There’s a lot of psychological stress as a result of a cancer diagnosis, which can lower the pain threshold,” said Dr. Ahmed. Exercise may help boost mood and reduce stress, increasing pain tolerance.

“People who are physically active also tend to be more socially active,” Dr. McCarthy added. “Engaging in social networks that provide social support can often palliate a sense of constant battling with fatigue, pain, and other negative effects of cancer.” Social activity, in turn, may promote physical activity: Studies show that when sedentary people socialize with active people, they become more active themselves — often by joining in walks or sports.

 

Help Patients Reap the Pain-Relieving Benefits of Exercise 

For beginners, the key to establishing a long-term exercise routine is to start low and slow, said Dr. Ahmed. That is, start with low-intensity activities like walking (walking was the most common activity reported in the study) or using light weights. Then, build slowly from there. 

Keep in mind that some pain or stiffness is normal at first, as one’s muscles and joints get used to the new activity. But be sure to investigate any new pain, Dr. Ahmed said. “Especially for patients who have had cancer, you want to see if the patient has any recurrence of disease,” Dr. Ahmed said. “That has to be kept in mind when you recommend any kind of exercise. “ 

It’s worth acknowledging that pain can be a significant barrier to exercise. If appropriate, you may consider referring out to exercise or physical therapy professionals in your network. Emphasizing the benefits of exercise — like the pain relief — may help motivate patients as well. 

For Dr. Swain, encouraging exercise is less about prescribing specific quantities and more about helping patients find activities “that give them enjoyment, that they feel comfortable doing, and that they can sustain over time.”

“The field needs to consider the different ways of supporting physical activity after a cancer diagnosis and treatment,” Dr. Swain said. “We have a lot of great research that shows the benefit of physical activity but not as strong an understanding of how to encourage and support it.”

A version of this article appeared on Medscape.com.

Jill Schneiderhan, MD, remembers only receiving one or two lectures on basic pain physiology during medical school.

That time was not enough, Dr. Schneiderhan said, who is now a primary care physician and codirector of Integrative Family Medicine at Michigan Medicine in Ann Arbor, Michigan. Medical schools in the United States spend an average of 11 hours on pain management training.

“I think that the understanding of different types of pain and the nervous system is improving,” Dr. Schneiderhan said. “But how we as primary care providers can sit with patients with complicated pain experiences, and integrate various treatments into the primary care setting, is where the system falls apart.”

Despite one in five Americans experiencing chronic pain, a gap exists in the pain management training of primary care providers (PCPs). Pain specialists are calling for the empowerment of their first-line-of-defense counterparts with the knowledge and tools necessary to navigate the intricate challenges posed by chronic pain.

Treatment beyond medication is the primary challenge — particularly with pressures and time constraints inherent in family medicine.

“It’s so difficult to teach a PCP how to treat pain because pain management is an entire fellowship,” said Shravani Durbhakula, MD, MPH, MBA, who is on the Board of Directors for the American Academy of Pain Medicine Foundation. But “we encourage a multidisciplinary approach: This includes physical therapy, medication, injections, and other methods. Those different elements coming together typically give some relief.”
 

Categories of Chronic Pain

Experts sort pain into three broad categories: Nociceptive (from tissue injury), neuropathic (from a nerve injury), and nociplastic (from a sensitized nervous system).

Tissue injury is the most common cause of pain and is characterized by aching and throbbing, while nerve injury causes more burning and shooting sensations.

Nociplastic pain, which arises from abnormal processing of pain signals without clear evidence of tissue damage, is often hardest to understand and trickier to treat. These types of conditions include fibromyalgia, irritable bowel syndrome, and nonspecific back pain, according to Dr. Durbhakula.

“One of the really big challenges is that it’s an invisible condition — you don’t have a cast on or crutches,” Dr. Durbhakula said. “We don’t have great objective measures for pain, and sometimes pain patients feel stigmatized and like their pain is dismissed.”

Primary care specialists should consider six steps to guide their pain assessments, including properly assessing the pain, identifying the pain generator, discussing sensible medications, considering appropriate procedures, recommending appropriate behavioral techniques, and focusing on multidisciplinary management, according to Dr. Durbhakula.

Persistent pain is often too complex to treat with singular methods. For instance, studies have shown pain can lead to structural changes in the brain, such as a decrease in gray matter and differences in neural areas that modulate pain. These neurologic changes illustrate the complicated nature of chronic pain and the need for a multipronged treatment plan.
 

Don’t Discount the ‘Fluffy Stuff’

One of the biggest challenges in managing chronic pain is the dearth of effective remedies, said Michael Kaplan, MD, a rheumatologist at Mount Sinai Health System in New York City.

While other debilitating conditions have seen breakthroughs — insulin for diabetes, penicillin for pneumonia — pain remains without a cure.

“In the world of centralized pains, we’re lagging behind,” Dr. Kaplan said. “Opioids didn’t work, and here we are in the aftermath of an opioid epidemic.”

Patients can make significant headway with nonpharmacologic management, or what some consider to be the “fluffy stuff,” including yoga, meditation, acupuncture, dry needling, massage therapy, and acupuncture, according to Dr. Kaplan.

But these approaches are often financially unfeasible for patients because insurance companies sporadically cover them. However, free apps can help patients practice things like better sleep and meditation.

“These things actually work, and there is very low risk in trying them,” Dr. Kaplan said. To be sure, medication has an important place in pain management. Neuropathic pain medications or nonsteroidal anti-inflammatory drugs can be effective options for some patients, said Christopher Gilligan, MD, Chief of the Division of Pain Medicine at Brigham and Women’s Hospital in Boston, Massachusetts.

Drugs that target nerve pain include gabapentin and pregabalin, certain antidepressants, and anticonvulsants, which can help dull pain signals in the nerves.

“When a patient has not responded to a first- or second-line medication in those categories, that can be a time when referral to a pain medicine physician can be helpful,” Dr. Gilligan said.

Procedural options that are less invasive than surgery may also be appropriate, Dr. Gilligan said. These include nerve ablation and restorative neurostimulators for people with lower back pain and ganglion stimulation for patients experiencing neuropathic pain.

“The efficacy of interventions for specific pain conditions has gotten better over the years,” he said.
 

Learn to Listen

The two most important activities to recommend when treating chronic pain patients also can be the most difficult: Sleeping and exercise. For people experiencing unrelenting discomfort, both can feel impossible, according to Dan Clauw, MD, professor of anesthesiology at the University of Michigan in Ann Arbor, Michigan.

“If you stop moving, your pain is going to get worse and worse and worse,” Dr. Clauw said. “But you have to be careful about how you talk about it. For example, don’t use the word ‘exercise’ when you’re talking to a chronic pain patient, use the word ‘activity.’ ”

As people become more active, they begin sleeping better, he said.

Most importantly, Dr. Clauw said, clinicians must demonstrate empathy and listening skills. Patients with chronic pain often are used to being dismissed and have become isolated in their personal lives.

“There is a lack of properly trained providers who can listen rather than do procedures,” Dr. Clauw said. “What happens is people just constrict their lives over the course of having pain, and they fall into this shell of themselves. They need their doctors to hear them.”

For primary care doctors seeking more information on pain management, online resources can be helpful, said Robert L. Rich Jr, MD, former chair of the American Academy of Family Physicians Commission on Health of the Public and Science.

“One suggestion I’d begin with is to look at pain guidelines, not just from the CDC and AAFP but also from local medical boards,” Dr. Rich said, adding that California and Washington State have done extensive work on chronic pain. “I am seeing more of a movement again toward teaching the management of chronic pain, but we still need more training.”

A version of this article appeared on Medscape.com.

Jill Schneiderhan, MD, remembers only receiving one or two lectures on basic pain physiology during medical school.

That time was not enough, Dr. Schneiderhan said, who is now a primary care physician and codirector of Integrative Family Medicine at Michigan Medicine in Ann Arbor, Michigan. Medical schools in the United States spend an average of 11 hours on pain management training.

“I think that the understanding of different types of pain and the nervous system is improving,” Dr. Schneiderhan said. “But how we as primary care providers can sit with patients with complicated pain experiences, and integrate various treatments into the primary care setting, is where the system falls apart.”

Despite one in five Americans experiencing chronic pain, a gap exists in the pain management training of primary care providers (PCPs). Pain specialists are calling for the empowerment of their first-line-of-defense counterparts with the knowledge and tools necessary to navigate the intricate challenges posed by chronic pain.

Treatment beyond medication is the primary challenge — particularly with pressures and time constraints inherent in family medicine.

“It’s so difficult to teach a PCP how to treat pain because pain management is an entire fellowship,” said Shravani Durbhakula, MD, MPH, MBA, who is on the Board of Directors for the American Academy of Pain Medicine Foundation. But “we encourage a multidisciplinary approach: This includes physical therapy, medication, injections, and other methods. Those different elements coming together typically give some relief.”
 

Categories of Chronic Pain

Experts sort pain into three broad categories: Nociceptive (from tissue injury), neuropathic (from a nerve injury), and nociplastic (from a sensitized nervous system).

Tissue injury is the most common cause of pain and is characterized by aching and throbbing, while nerve injury causes more burning and shooting sensations.

Nociplastic pain, which arises from abnormal processing of pain signals without clear evidence of tissue damage, is often hardest to understand and trickier to treat. These types of conditions include fibromyalgia, irritable bowel syndrome, and nonspecific back pain, according to Dr. Durbhakula.

“One of the really big challenges is that it’s an invisible condition — you don’t have a cast on or crutches,” Dr. Durbhakula said. “We don’t have great objective measures for pain, and sometimes pain patients feel stigmatized and like their pain is dismissed.”

Primary care specialists should consider six steps to guide their pain assessments, including properly assessing the pain, identifying the pain generator, discussing sensible medications, considering appropriate procedures, recommending appropriate behavioral techniques, and focusing on multidisciplinary management, according to Dr. Durbhakula.

Persistent pain is often too complex to treat with singular methods. For instance, studies have shown pain can lead to structural changes in the brain, such as a decrease in gray matter and differences in neural areas that modulate pain. These neurologic changes illustrate the complicated nature of chronic pain and the need for a multipronged treatment plan.
 

Don’t Discount the ‘Fluffy Stuff’

One of the biggest challenges in managing chronic pain is the dearth of effective remedies, said Michael Kaplan, MD, a rheumatologist at Mount Sinai Health System in New York City.

While other debilitating conditions have seen breakthroughs — insulin for diabetes, penicillin for pneumonia — pain remains without a cure.

“In the world of centralized pains, we’re lagging behind,” Dr. Kaplan said. “Opioids didn’t work, and here we are in the aftermath of an opioid epidemic.”

Patients can make significant headway with nonpharmacologic management, or what some consider to be the “fluffy stuff,” including yoga, meditation, acupuncture, dry needling, massage therapy, and acupuncture, according to Dr. Kaplan.

But these approaches are often financially unfeasible for patients because insurance companies sporadically cover them. However, free apps can help patients practice things like better sleep and meditation.

“These things actually work, and there is very low risk in trying them,” Dr. Kaplan said. To be sure, medication has an important place in pain management. Neuropathic pain medications or nonsteroidal anti-inflammatory drugs can be effective options for some patients, said Christopher Gilligan, MD, Chief of the Division of Pain Medicine at Brigham and Women’s Hospital in Boston, Massachusetts.

Drugs that target nerve pain include gabapentin and pregabalin, certain antidepressants, and anticonvulsants, which can help dull pain signals in the nerves.

“When a patient has not responded to a first- or second-line medication in those categories, that can be a time when referral to a pain medicine physician can be helpful,” Dr. Gilligan said.

Procedural options that are less invasive than surgery may also be appropriate, Dr. Gilligan said. These include nerve ablation and restorative neurostimulators for people with lower back pain and ganglion stimulation for patients experiencing neuropathic pain.

“The efficacy of interventions for specific pain conditions has gotten better over the years,” he said.
 

Learn to Listen

The two most important activities to recommend when treating chronic pain patients also can be the most difficult: Sleeping and exercise. For people experiencing unrelenting discomfort, both can feel impossible, according to Dan Clauw, MD, professor of anesthesiology at the University of Michigan in Ann Arbor, Michigan.

“If you stop moving, your pain is going to get worse and worse and worse,” Dr. Clauw said. “But you have to be careful about how you talk about it. For example, don’t use the word ‘exercise’ when you’re talking to a chronic pain patient, use the word ‘activity.’ ”

As people become more active, they begin sleeping better, he said.

Most importantly, Dr. Clauw said, clinicians must demonstrate empathy and listening skills. Patients with chronic pain often are used to being dismissed and have become isolated in their personal lives.

“There is a lack of properly trained providers who can listen rather than do procedures,” Dr. Clauw said. “What happens is people just constrict their lives over the course of having pain, and they fall into this shell of themselves. They need their doctors to hear them.”

For primary care doctors seeking more information on pain management, online resources can be helpful, said Robert L. Rich Jr, MD, former chair of the American Academy of Family Physicians Commission on Health of the Public and Science.

“One suggestion I’d begin with is to look at pain guidelines, not just from the CDC and AAFP but also from local medical boards,” Dr. Rich said, adding that California and Washington State have done extensive work on chronic pain. “I am seeing more of a movement again toward teaching the management of chronic pain, but we still need more training.”

A version of this article appeared on Medscape.com.

Jill Schneiderhan, MD, remembers only receiving one or two lectures on basic pain physiology during medical school.

That time was not enough, Dr. Schneiderhan said, who is now a primary care physician and codirector of Integrative Family Medicine at Michigan Medicine in Ann Arbor, Michigan. Medical schools in the United States spend an average of 11 hours on pain management training.

“I think that the understanding of different types of pain and the nervous system is improving,” Dr. Schneiderhan said. “But how we as primary care providers can sit with patients with complicated pain experiences, and integrate various treatments into the primary care setting, is where the system falls apart.”

Despite one in five Americans experiencing chronic pain, a gap exists in the pain management training of primary care providers (PCPs). Pain specialists are calling for the empowerment of their first-line-of-defense counterparts with the knowledge and tools necessary to navigate the intricate challenges posed by chronic pain.

Treatment beyond medication is the primary challenge — particularly with pressures and time constraints inherent in family medicine.

“It’s so difficult to teach a PCP how to treat pain because pain management is an entire fellowship,” said Shravani Durbhakula, MD, MPH, MBA, who is on the Board of Directors for the American Academy of Pain Medicine Foundation. But “we encourage a multidisciplinary approach: This includes physical therapy, medication, injections, and other methods. Those different elements coming together typically give some relief.”
 

Categories of Chronic Pain

Experts sort pain into three broad categories: Nociceptive (from tissue injury), neuropathic (from a nerve injury), and nociplastic (from a sensitized nervous system).

Tissue injury is the most common cause of pain and is characterized by aching and throbbing, while nerve injury causes more burning and shooting sensations.

Nociplastic pain, which arises from abnormal processing of pain signals without clear evidence of tissue damage, is often hardest to understand and trickier to treat. These types of conditions include fibromyalgia, irritable bowel syndrome, and nonspecific back pain, according to Dr. Durbhakula.

“One of the really big challenges is that it’s an invisible condition — you don’t have a cast on or crutches,” Dr. Durbhakula said. “We don’t have great objective measures for pain, and sometimes pain patients feel stigmatized and like their pain is dismissed.”

Primary care specialists should consider six steps to guide their pain assessments, including properly assessing the pain, identifying the pain generator, discussing sensible medications, considering appropriate procedures, recommending appropriate behavioral techniques, and focusing on multidisciplinary management, according to Dr. Durbhakula.

Persistent pain is often too complex to treat with singular methods. For instance, studies have shown pain can lead to structural changes in the brain, such as a decrease in gray matter and differences in neural areas that modulate pain. These neurologic changes illustrate the complicated nature of chronic pain and the need for a multipronged treatment plan.
 

Don’t Discount the ‘Fluffy Stuff’

One of the biggest challenges in managing chronic pain is the dearth of effective remedies, said Michael Kaplan, MD, a rheumatologist at Mount Sinai Health System in New York City.

While other debilitating conditions have seen breakthroughs — insulin for diabetes, penicillin for pneumonia — pain remains without a cure.

“In the world of centralized pains, we’re lagging behind,” Dr. Kaplan said. “Opioids didn’t work, and here we are in the aftermath of an opioid epidemic.”

Patients can make significant headway with nonpharmacologic management, or what some consider to be the “fluffy stuff,” including yoga, meditation, acupuncture, dry needling, massage therapy, and acupuncture, according to Dr. Kaplan.

But these approaches are often financially unfeasible for patients because insurance companies sporadically cover them. However, free apps can help patients practice things like better sleep and meditation.

“These things actually work, and there is very low risk in trying them,” Dr. Kaplan said. To be sure, medication has an important place in pain management. Neuropathic pain medications or nonsteroidal anti-inflammatory drugs can be effective options for some patients, said Christopher Gilligan, MD, Chief of the Division of Pain Medicine at Brigham and Women’s Hospital in Boston, Massachusetts.

Drugs that target nerve pain include gabapentin and pregabalin, certain antidepressants, and anticonvulsants, which can help dull pain signals in the nerves.

“When a patient has not responded to a first- or second-line medication in those categories, that can be a time when referral to a pain medicine physician can be helpful,” Dr. Gilligan said.

Procedural options that are less invasive than surgery may also be appropriate, Dr. Gilligan said. These include nerve ablation and restorative neurostimulators for people with lower back pain and ganglion stimulation for patients experiencing neuropathic pain.

“The efficacy of interventions for specific pain conditions has gotten better over the years,” he said.
 

Learn to Listen

The two most important activities to recommend when treating chronic pain patients also can be the most difficult: Sleeping and exercise. For people experiencing unrelenting discomfort, both can feel impossible, according to Dan Clauw, MD, professor of anesthesiology at the University of Michigan in Ann Arbor, Michigan.

“If you stop moving, your pain is going to get worse and worse and worse,” Dr. Clauw said. “But you have to be careful about how you talk about it. For example, don’t use the word ‘exercise’ when you’re talking to a chronic pain patient, use the word ‘activity.’ ”

As people become more active, they begin sleeping better, he said.

Most importantly, Dr. Clauw said, clinicians must demonstrate empathy and listening skills. Patients with chronic pain often are used to being dismissed and have become isolated in their personal lives.

“There is a lack of properly trained providers who can listen rather than do procedures,” Dr. Clauw said. “What happens is people just constrict their lives over the course of having pain, and they fall into this shell of themselves. They need their doctors to hear them.”

For primary care doctors seeking more information on pain management, online resources can be helpful, said Robert L. Rich Jr, MD, former chair of the American Academy of Family Physicians Commission on Health of the Public and Science.

“One suggestion I’d begin with is to look at pain guidelines, not just from the CDC and AAFP but also from local medical boards,” Dr. Rich said, adding that California and Washington State have done extensive work on chronic pain. “I am seeing more of a movement again toward teaching the management of chronic pain, but we still need more training.”

A version of this article appeared on Medscape.com.

TOPLINE:

Adults with axial spondyloarthritis (axSpA) with longstanding back pain symptoms had response rates to nonsteroidal anti-inflammatory drugs (NSAIDs) that were no different from patients with non-axSpA back pain of similar duration, according to findings from a prospective study.

METHODOLOGY:

The researchers recruited 233 consecutive outpatients with chronic back pain, including 68 with axSpA and 165 with non-axSpA back pain.

The mean ages of the participants in the axSpA and non-axSpA groups were 42.7 years and 49.3 years, respectively; symptom durations were approximately 15 years in both groups.

Participants were given NSAIDs and “any response” was defined as back pain improvement of more than two units on the Numerical Rating Scale, while “good response” was defined as an improvement of > 50% compared with baseline.

TAKEAWAY: 

After 4 weeks, 30.9% of patients with axSpA and 29.1% of patients with non-axSpA back pain had any response, and 23.5% and 16.4% of patients with axSpA and non-axSpA back pain, respectively, had a good response.

The proportion of patients showing improvement ranged from 19% to 31% in both groups after 4 weeks of treatment.

No significant differences in response appeared in subgroups of patients based on inflammatory back pain stage or in different axSpA stages.

IN PRACTICE:

“We think that this information has an effect on clinical practice since a response to NSAIDs is an important criterion in the ASAS [Assessment of SpondyloArthritis international Society]/European Alliance of Associations for Rheumatology treatment recommendations that may influence decisions to initiate treatment with biologic or targeted-synthetic DMARDs [disease-modifying antirheumatic drugs]. Further, a good response to NSAIDs is also an important clinical feature in the ASAS classification criteria,” the researchers wrote.

SOURCE: 

The lead author on the study was Xenofon Baraliakos, MD, of Ruhr University Bochum, Germany. The study was published online on January 15, 2024, in The Journal of Rheumatology.

LIMITATIONS:

The uneven sex match in the diagnoses and the history of NSAID treatment among patients in both groups were potential limiting factors. The researchers also noted that a similarly conducted study in patients with early disease could have findings that are “much different.”

DISCLOSURES:

The study was sponsored in part by Novartis. The researchers reported no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Adults with axial spondyloarthritis (axSpA) with longstanding back pain symptoms had response rates to nonsteroidal anti-inflammatory drugs (NSAIDs) that were no different from patients with non-axSpA back pain of similar duration, according to findings from a prospective study.

METHODOLOGY:

The researchers recruited 233 consecutive outpatients with chronic back pain, including 68 with axSpA and 165 with non-axSpA back pain.

The mean ages of the participants in the axSpA and non-axSpA groups were 42.7 years and 49.3 years, respectively; symptom durations were approximately 15 years in both groups.

Participants were given NSAIDs and “any response” was defined as back pain improvement of more than two units on the Numerical Rating Scale, while “good response” was defined as an improvement of > 50% compared with baseline.

TAKEAWAY: 

After 4 weeks, 30.9% of patients with axSpA and 29.1% of patients with non-axSpA back pain had any response, and 23.5% and 16.4% of patients with axSpA and non-axSpA back pain, respectively, had a good response.

The proportion of patients showing improvement ranged from 19% to 31% in both groups after 4 weeks of treatment.

No significant differences in response appeared in subgroups of patients based on inflammatory back pain stage or in different axSpA stages.

IN PRACTICE:

“We think that this information has an effect on clinical practice since a response to NSAIDs is an important criterion in the ASAS [Assessment of SpondyloArthritis international Society]/European Alliance of Associations for Rheumatology treatment recommendations that may influence decisions to initiate treatment with biologic or targeted-synthetic DMARDs [disease-modifying antirheumatic drugs]. Further, a good response to NSAIDs is also an important clinical feature in the ASAS classification criteria,” the researchers wrote.

SOURCE: 

The lead author on the study was Xenofon Baraliakos, MD, of Ruhr University Bochum, Germany. The study was published online on January 15, 2024, in The Journal of Rheumatology.

LIMITATIONS:

The uneven sex match in the diagnoses and the history of NSAID treatment among patients in both groups were potential limiting factors. The researchers also noted that a similarly conducted study in patients with early disease could have findings that are “much different.”

DISCLOSURES:

The study was sponsored in part by Novartis. The researchers reported no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Adults with axial spondyloarthritis (axSpA) with longstanding back pain symptoms had response rates to nonsteroidal anti-inflammatory drugs (NSAIDs) that were no different from patients with non-axSpA back pain of similar duration, according to findings from a prospective study.

METHODOLOGY:

The researchers recruited 233 consecutive outpatients with chronic back pain, including 68 with axSpA and 165 with non-axSpA back pain.

The mean ages of the participants in the axSpA and non-axSpA groups were 42.7 years and 49.3 years, respectively; symptom durations were approximately 15 years in both groups.

Participants were given NSAIDs and “any response” was defined as back pain improvement of more than two units on the Numerical Rating Scale, while “good response” was defined as an improvement of > 50% compared with baseline.

TAKEAWAY: 

After 4 weeks, 30.9% of patients with axSpA and 29.1% of patients with non-axSpA back pain had any response, and 23.5% and 16.4% of patients with axSpA and non-axSpA back pain, respectively, had a good response.

The proportion of patients showing improvement ranged from 19% to 31% in both groups after 4 weeks of treatment.

No significant differences in response appeared in subgroups of patients based on inflammatory back pain stage or in different axSpA stages.

IN PRACTICE:

“We think that this information has an effect on clinical practice since a response to NSAIDs is an important criterion in the ASAS [Assessment of SpondyloArthritis international Society]/European Alliance of Associations for Rheumatology treatment recommendations that may influence decisions to initiate treatment with biologic or targeted-synthetic DMARDs [disease-modifying antirheumatic drugs]. Further, a good response to NSAIDs is also an important clinical feature in the ASAS classification criteria,” the researchers wrote.

SOURCE: 

The lead author on the study was Xenofon Baraliakos, MD, of Ruhr University Bochum, Germany. The study was published online on January 15, 2024, in The Journal of Rheumatology.

LIMITATIONS:

The uneven sex match in the diagnoses and the history of NSAID treatment among patients in both groups were potential limiting factors. The researchers also noted that a similarly conducted study in patients with early disease could have findings that are “much different.”

DISCLOSURES:

The study was sponsored in part by Novartis. The researchers reported no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Legalization of recreational and medical cannabis is not associated with a reduction in opioid prescriptions or overall opioid overdose mortality, a new study suggested. However, investigators did find that recreational cannabis laws may be tied to a potential reduction in synthetic opioid deaths.

METHODOLOGY:

• Investigators analyzed state-level data from the US Centers for Disease Control and Prevention and other databases (2006-2020) on the number of opioid prescriptions (per 100,000 persons).
• Prescription opioids included buprenorphine (except products to treat opioid use disorder), codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, propoxyphene, tapentadol, and tramadol.
• Researchers used regression analyses to account for poverty rates and real gross domestic product and a generalized difference-in-differences method that accounted for staggered implementation of cannabis laws.

TAKEAWAY:

• During the full study period, 13 states legalized recreational cannabis and 23 legalized medical cannabis.
• No statistically significant association was found between recreational cannabis laws and opioid prescriptions (3.08 fewer prescriptions per 100 persons; P = .17) or overall opioid overdose mortality (3.05 fewer deaths per 100,000; P = .24).
• The changes in outcomes associated with medical cannabis laws were larger in magnitude than those for recreational cannabis laws but also not statistically significant (3.54 additional prescriptions per 100 persons; P = .17 and 3.09 additional deaths per 100,000; P = .07).
• A potential reduction was found in synthetic opioid deaths associated specifically with states that had recreational cannabis laws (4.9 fewer deaths per 100,000; P = .04), but there were no differences in overdose deaths with other opioids.

IN PRACTICE:

“These results contrast with recent studies that suggested that recreational and medical cannabis legalization are associated with reductions in opioid prescriptions and medical cannabis legalization is associated with an increase in opioid mortality,” the authors wrote.

SOURCE:

Hai V. Nguyen, PhD, of the School of Pharmacy, Memorial University of Newfoundland, St. John’s, Canada, was the lead and corresponding author of the study. It was published online on January 19, 2024, in JAMA Health Forum.

A version of this article appeared on Medscape.com.

TOPLINE:

Legalization of recreational and medical cannabis is not associated with a reduction in opioid prescriptions or overall opioid overdose mortality, a new study suggested. However, investigators did find that recreational cannabis laws may be tied to a potential reduction in synthetic opioid deaths.

METHODOLOGY:

• Investigators analyzed state-level data from the US Centers for Disease Control and Prevention and other databases (2006-2020) on the number of opioid prescriptions (per 100,000 persons).
• Prescription opioids included buprenorphine (except products to treat opioid use disorder), codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, propoxyphene, tapentadol, and tramadol.
• Researchers used regression analyses to account for poverty rates and real gross domestic product and a generalized difference-in-differences method that accounted for staggered implementation of cannabis laws.

TAKEAWAY:

• During the full study period, 13 states legalized recreational cannabis and 23 legalized medical cannabis.
• No statistically significant association was found between recreational cannabis laws and opioid prescriptions (3.08 fewer prescriptions per 100 persons; P = .17) or overall opioid overdose mortality (3.05 fewer deaths per 100,000; P = .24).
• The changes in outcomes associated with medical cannabis laws were larger in magnitude than those for recreational cannabis laws but also not statistically significant (3.54 additional prescriptions per 100 persons; P = .17 and 3.09 additional deaths per 100,000; P = .07).
• A potential reduction was found in synthetic opioid deaths associated specifically with states that had recreational cannabis laws (4.9 fewer deaths per 100,000; P = .04), but there were no differences in overdose deaths with other opioids.

IN PRACTICE:

“These results contrast with recent studies that suggested that recreational and medical cannabis legalization are associated with reductions in opioid prescriptions and medical cannabis legalization is associated with an increase in opioid mortality,” the authors wrote.

SOURCE:

Hai V. Nguyen, PhD, of the School of Pharmacy, Memorial University of Newfoundland, St. John’s, Canada, was the lead and corresponding author of the study. It was published online on January 19, 2024, in JAMA Health Forum.

A version of this article appeared on Medscape.com.

TOPLINE:

Legalization of recreational and medical cannabis is not associated with a reduction in opioid prescriptions or overall opioid overdose mortality, a new study suggested. However, investigators did find that recreational cannabis laws may be tied to a potential reduction in synthetic opioid deaths.

METHODOLOGY:

• Investigators analyzed state-level data from the US Centers for Disease Control and Prevention and other databases (2006-2020) on the number of opioid prescriptions (per 100,000 persons).
• Prescription opioids included buprenorphine (except products to treat opioid use disorder), codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, propoxyphene, tapentadol, and tramadol.
• Researchers used regression analyses to account for poverty rates and real gross domestic product and a generalized difference-in-differences method that accounted for staggered implementation of cannabis laws.

TAKEAWAY:

• During the full study period, 13 states legalized recreational cannabis and 23 legalized medical cannabis.
• No statistically significant association was found between recreational cannabis laws and opioid prescriptions (3.08 fewer prescriptions per 100 persons; P = .17) or overall opioid overdose mortality (3.05 fewer deaths per 100,000; P = .24).
• The changes in outcomes associated with medical cannabis laws were larger in magnitude than those for recreational cannabis laws but also not statistically significant (3.54 additional prescriptions per 100 persons; P = .17 and 3.09 additional deaths per 100,000; P = .07).
• A potential reduction was found in synthetic opioid deaths associated specifically with states that had recreational cannabis laws (4.9 fewer deaths per 100,000; P = .04), but there were no differences in overdose deaths with other opioids.

IN PRACTICE:

“These results contrast with recent studies that suggested that recreational and medical cannabis legalization are associated with reductions in opioid prescriptions and medical cannabis legalization is associated with an increase in opioid mortality,” the authors wrote.

SOURCE:

Hai V. Nguyen, PhD, of the School of Pharmacy, Memorial University of Newfoundland, St. John’s, Canada, was the lead and corresponding author of the study. It was published online on January 19, 2024, in JAMA Health Forum.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Neha Pathak, MD: Hello. Today, we’re talking to Dr. Daniel Clauw, a professor at the University of Michigan in Ann Arbor, who is running a major trial on treatments for chronic back pain. We’re talking today about managing back pain in the post-opioid world. Thank you so much, Dr. Clauw, for taking the time to be our resident pain consultant today. Managing chronic pain can lead to a large amount of burnout and helplessness in the clinic setting. That’s the reality with some of the modalities that patients are requesting; there is still confusion about what is optimal for a particular type of patient, this feeling that we’re not really helping people get better, and whenever patients come in, that’s always still their chief complaint.

How would you advise providers to think about that and to settle into their role as communicators about better strategies without the burnout?

Daniel Clauw, MD: The first thing is to broaden the number of other providers that you get involved in these individuals’ care as the evidence base for all of these nonpharmacologic therapies being effective in chronic pain increases and increases. As third-party payers begin to reimburse for more and more of these therapies, it’s really difficult to manage chronic pain patients if you’re trying to do it alone on an island.

If you can, identify the good physical therapists in your community that are going to really work with people to give them an exercise program that they can use at home; find a pain psychologist that can offer some cognitive-behavioral therapy (CBT) for insomnia and some CBT for pain; and in the subset of patients with trauma, give them the emotional awareness of the neural reprocessing therapy for that specific subset.

As you start to identify more and more of these nonpharmacologic therapies that you want your patients to try, each of those has a set of providers and they can be incredibly helpful so that you, as the primary care provider (PCP), don’t really feel overwhelmed that you’re it, that you’re the only one.

Many of these individuals have more time to spend, and they have more one-on-one in-person time than you do as a primary care physician in the current healthcare system. Many of those providers have become really good at doing amateur CBT, goal-setting, and some of the other things that you need to do when you manage chronic pain patients. Try to find that other group of people that you can send your patients to that are going to be offering some of these nonpharmacologic therapies, and they’ll really help you manage these individuals.

Dr. Pathak: I think a couple of things come up for me. One is that we have to maybe broaden thinking about pain management, not only as multimodal strategies but also as multidisciplinary strategies. To your point, I think that’s really important. I also worry and wonder about health equity concerns, because just as overburdened as many PCPs are, we’re seeing it’s very difficult to get into physical therapy or to get into a setting where you’d be able to receive CBT for your pain. Any thoughts on those types of considerations?

Dr. Clauw: That’s a huge problem. Our group and many other groups in the pain space are developing websites, smartphone apps, and things like that to try to get some of these things directly to individuals with pain, not only for the reasons that you stated but also so that persons with pain don’t have to become patients. Our healthcare systems often make pain worse rather than better.

There were some great articles in The Lancet about 5 years ago talking about low back pain and that in different countries, the healthcare systems, for different reasons, have a tendency to actually make low back pain worse because they do too much surgery, immobilize people, or things like that rather than just not make them better. I think we’ve overmedicalized chronic pain in some settings, and much of what we’re trying to lead people to are things that are parts of wellness programs. The NIH National Center for Complementary and Integrative Health director talks about whole person health often.

I think that these interdisciplinary, integrative approaches are what we have to be using for chronic pain patients. I tell pain patients that, among acupuncture, acupressure, mindfulness, five different forms of CBT, yoga, and tai chi, I don’t know which of those is going to work, but I know that about 1 in 3 individuals that tries each of those therapies gets a benefit. What I really should be doing most is incentivizing people and motivating people to keep trying some of those nonpharmacologic approaches that they haven’t yet tried, because when they find one that works for them, then they will integrate it into their day-to-day life.

The other trick I would use for primary care physicians or anyone managing chronic pain patients is, don’t try to incentivize a pain patient to go try a new nonpharmacologic therapy or start an exercise program because you want their pain score to go from a 6 to a 3. Incentivize them by asking them, what are two or three things that you’re not able to do now because you have chronic pain that you’d really like to be able to do?

You’d like to play nine holes of golf; you’d like to be able to hug your grandchild; or you’d like to be able to do something else. Use those functional goals that are patient0driven to motivate your patients to do these things, because that will work much better. Again, any of us are inherently more likely to take the time and the effort to do some of these nonpharmacologic therapies if it’s for a reason that internally motivates us.

Dr. Pathak: I think that’s great. I’m very privileged to work within the Veterans Affairs (VA) healthcare system. I think that there’s been a huge shift within VA healthcare to provide these ancillary services, whether it’s yoga, tai chi, or acupuncture, as an adjunct to the pain management strategy.

Also, what comes up for me, as you’re saying, is grounding the point that instead of relying on a pain score — which can be objective and different from patient to patient and even within a patient — we should choose a smart goal that is almost more objective when it’s functional. Your goal is to walk two blocks to the mailbox. Can we achieve that as part of your pain control strategy?

I so appreciate your taking the time to be our pain consultant today. I really appreciate our discussion, and I’d like to hand it over to you for any final thoughts.

Dr. Clauw: I’d add that when you’re seeing chronic pain patients, many of them are going to have comorbid sleep problems. They’re going to have comorbid problems with fatigue and memory problems, especially the central nervous system–driven forms of pain that we now call nociplastic pain. Look at those as therapeutic targets.

If you’re befuddled because you’ve tried many different things for pain in this individual you’ve been seeing for a while, focus on their sleep and focus on getting them more active. Don’t use the word exercise — because that scares chronic pain patients — but focus on getting them more active.

There are many different tactics and strategies that you can use to motivate the patients to try some of these new nonpharmacologic approaches as the evidence base continues to increase.

Dr. Pathak: Thank you so much, again, to Dr. Clauw for joining us and being our pain consultant, really helping us to think about managing back pain in the postopioid world.
 

Dr. Pathak is Chief Physician Editor, Health and Lifestyle Medicine, WebMD. She has disclosed no relevant financial relationships. Dr. Clauw is Director, Chronic Pain and Fatigue Research Center, Department of Anesthesia, University of Michigan, Ann Arbor. He disclosed ties with Tonix and Viatris.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Neha Pathak, MD: Hello. Today, we’re talking to Dr. Daniel Clauw, a professor at the University of Michigan in Ann Arbor, who is running a major trial on treatments for chronic back pain. We’re talking today about managing back pain in the post-opioid world. Thank you so much, Dr. Clauw, for taking the time to be our resident pain consultant today. Managing chronic pain can lead to a large amount of burnout and helplessness in the clinic setting. That’s the reality with some of the modalities that patients are requesting; there is still confusion about what is optimal for a particular type of patient, this feeling that we’re not really helping people get better, and whenever patients come in, that’s always still their chief complaint.

How would you advise providers to think about that and to settle into their role as communicators about better strategies without the burnout?

Daniel Clauw, MD: The first thing is to broaden the number of other providers that you get involved in these individuals’ care as the evidence base for all of these nonpharmacologic therapies being effective in chronic pain increases and increases. As third-party payers begin to reimburse for more and more of these therapies, it’s really difficult to manage chronic pain patients if you’re trying to do it alone on an island.

If you can, identify the good physical therapists in your community that are going to really work with people to give them an exercise program that they can use at home; find a pain psychologist that can offer some cognitive-behavioral therapy (CBT) for insomnia and some CBT for pain; and in the subset of patients with trauma, give them the emotional awareness of the neural reprocessing therapy for that specific subset.

As you start to identify more and more of these nonpharmacologic therapies that you want your patients to try, each of those has a set of providers and they can be incredibly helpful so that you, as the primary care provider (PCP), don’t really feel overwhelmed that you’re it, that you’re the only one.

Many of these individuals have more time to spend, and they have more one-on-one in-person time than you do as a primary care physician in the current healthcare system. Many of those providers have become really good at doing amateur CBT, goal-setting, and some of the other things that you need to do when you manage chronic pain patients. Try to find that other group of people that you can send your patients to that are going to be offering some of these nonpharmacologic therapies, and they’ll really help you manage these individuals.

Dr. Pathak: I think a couple of things come up for me. One is that we have to maybe broaden thinking about pain management, not only as multimodal strategies but also as multidisciplinary strategies. To your point, I think that’s really important. I also worry and wonder about health equity concerns, because just as overburdened as many PCPs are, we’re seeing it’s very difficult to get into physical therapy or to get into a setting where you’d be able to receive CBT for your pain. Any thoughts on those types of considerations?

Dr. Clauw: That’s a huge problem. Our group and many other groups in the pain space are developing websites, smartphone apps, and things like that to try to get some of these things directly to individuals with pain, not only for the reasons that you stated but also so that persons with pain don’t have to become patients. Our healthcare systems often make pain worse rather than better.

There were some great articles in The Lancet about 5 years ago talking about low back pain and that in different countries, the healthcare systems, for different reasons, have a tendency to actually make low back pain worse because they do too much surgery, immobilize people, or things like that rather than just not make them better. I think we’ve overmedicalized chronic pain in some settings, and much of what we’re trying to lead people to are things that are parts of wellness programs. The NIH National Center for Complementary and Integrative Health director talks about whole person health often.

I think that these interdisciplinary, integrative approaches are what we have to be using for chronic pain patients. I tell pain patients that, among acupuncture, acupressure, mindfulness, five different forms of CBT, yoga, and tai chi, I don’t know which of those is going to work, but I know that about 1 in 3 individuals that tries each of those therapies gets a benefit. What I really should be doing most is incentivizing people and motivating people to keep trying some of those nonpharmacologic approaches that they haven’t yet tried, because when they find one that works for them, then they will integrate it into their day-to-day life.

The other trick I would use for primary care physicians or anyone managing chronic pain patients is, don’t try to incentivize a pain patient to go try a new nonpharmacologic therapy or start an exercise program because you want their pain score to go from a 6 to a 3. Incentivize them by asking them, what are two or three things that you’re not able to do now because you have chronic pain that you’d really like to be able to do?

You’d like to play nine holes of golf; you’d like to be able to hug your grandchild; or you’d like to be able to do something else. Use those functional goals that are patient0driven to motivate your patients to do these things, because that will work much better. Again, any of us are inherently more likely to take the time and the effort to do some of these nonpharmacologic therapies if it’s for a reason that internally motivates us.

Dr. Pathak: I think that’s great. I’m very privileged to work within the Veterans Affairs (VA) healthcare system. I think that there’s been a huge shift within VA healthcare to provide these ancillary services, whether it’s yoga, tai chi, or acupuncture, as an adjunct to the pain management strategy.

Also, what comes up for me, as you’re saying, is grounding the point that instead of relying on a pain score — which can be objective and different from patient to patient and even within a patient — we should choose a smart goal that is almost more objective when it’s functional. Your goal is to walk two blocks to the mailbox. Can we achieve that as part of your pain control strategy?

I so appreciate your taking the time to be our pain consultant today. I really appreciate our discussion, and I’d like to hand it over to you for any final thoughts.

Dr. Clauw: I’d add that when you’re seeing chronic pain patients, many of them are going to have comorbid sleep problems. They’re going to have comorbid problems with fatigue and memory problems, especially the central nervous system–driven forms of pain that we now call nociplastic pain. Look at those as therapeutic targets.

If you’re befuddled because you’ve tried many different things for pain in this individual you’ve been seeing for a while, focus on their sleep and focus on getting them more active. Don’t use the word exercise — because that scares chronic pain patients — but focus on getting them more active.

There are many different tactics and strategies that you can use to motivate the patients to try some of these new nonpharmacologic approaches as the evidence base continues to increase.

Dr. Pathak: Thank you so much, again, to Dr. Clauw for joining us and being our pain consultant, really helping us to think about managing back pain in the postopioid world.
 

Dr. Pathak is Chief Physician Editor, Health and Lifestyle Medicine, WebMD. She has disclosed no relevant financial relationships. Dr. Clauw is Director, Chronic Pain and Fatigue Research Center, Department of Anesthesia, University of Michigan, Ann Arbor. He disclosed ties with Tonix and Viatris.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Neha Pathak, MD: Hello. Today, we’re talking to Dr. Daniel Clauw, a professor at the University of Michigan in Ann Arbor, who is running a major trial on treatments for chronic back pain. We’re talking today about managing back pain in the post-opioid world. Thank you so much, Dr. Clauw, for taking the time to be our resident pain consultant today. Managing chronic pain can lead to a large amount of burnout and helplessness in the clinic setting. That’s the reality with some of the modalities that patients are requesting; there is still confusion about what is optimal for a particular type of patient, this feeling that we’re not really helping people get better, and whenever patients come in, that’s always still their chief complaint.

How would you advise providers to think about that and to settle into their role as communicators about better strategies without the burnout?

Daniel Clauw, MD: The first thing is to broaden the number of other providers that you get involved in these individuals’ care as the evidence base for all of these nonpharmacologic therapies being effective in chronic pain increases and increases. As third-party payers begin to reimburse for more and more of these therapies, it’s really difficult to manage chronic pain patients if you’re trying to do it alone on an island.

If you can, identify the good physical therapists in your community that are going to really work with people to give them an exercise program that they can use at home; find a pain psychologist that can offer some cognitive-behavioral therapy (CBT) for insomnia and some CBT for pain; and in the subset of patients with trauma, give them the emotional awareness of the neural reprocessing therapy for that specific subset.

As you start to identify more and more of these nonpharmacologic therapies that you want your patients to try, each of those has a set of providers and they can be incredibly helpful so that you, as the primary care provider (PCP), don’t really feel overwhelmed that you’re it, that you’re the only one.

Many of these individuals have more time to spend, and they have more one-on-one in-person time than you do as a primary care physician in the current healthcare system. Many of those providers have become really good at doing amateur CBT, goal-setting, and some of the other things that you need to do when you manage chronic pain patients. Try to find that other group of people that you can send your patients to that are going to be offering some of these nonpharmacologic therapies, and they’ll really help you manage these individuals.

Dr. Pathak: I think a couple of things come up for me. One is that we have to maybe broaden thinking about pain management, not only as multimodal strategies but also as multidisciplinary strategies. To your point, I think that’s really important. I also worry and wonder about health equity concerns, because just as overburdened as many PCPs are, we’re seeing it’s very difficult to get into physical therapy or to get into a setting where you’d be able to receive CBT for your pain. Any thoughts on those types of considerations?

Dr. Clauw: That’s a huge problem. Our group and many other groups in the pain space are developing websites, smartphone apps, and things like that to try to get some of these things directly to individuals with pain, not only for the reasons that you stated but also so that persons with pain don’t have to become patients. Our healthcare systems often make pain worse rather than better.

There were some great articles in The Lancet about 5 years ago talking about low back pain and that in different countries, the healthcare systems, for different reasons, have a tendency to actually make low back pain worse because they do too much surgery, immobilize people, or things like that rather than just not make them better. I think we’ve overmedicalized chronic pain in some settings, and much of what we’re trying to lead people to are things that are parts of wellness programs. The NIH National Center for Complementary and Integrative Health director talks about whole person health often.

I think that these interdisciplinary, integrative approaches are what we have to be using for chronic pain patients. I tell pain patients that, among acupuncture, acupressure, mindfulness, five different forms of CBT, yoga, and tai chi, I don’t know which of those is going to work, but I know that about 1 in 3 individuals that tries each of those therapies gets a benefit. What I really should be doing most is incentivizing people and motivating people to keep trying some of those nonpharmacologic approaches that they haven’t yet tried, because when they find one that works for them, then they will integrate it into their day-to-day life.

The other trick I would use for primary care physicians or anyone managing chronic pain patients is, don’t try to incentivize a pain patient to go try a new nonpharmacologic therapy or start an exercise program because you want their pain score to go from a 6 to a 3. Incentivize them by asking them, what are two or three things that you’re not able to do now because you have chronic pain that you’d really like to be able to do?

You’d like to play nine holes of golf; you’d like to be able to hug your grandchild; or you’d like to be able to do something else. Use those functional goals that are patient0driven to motivate your patients to do these things, because that will work much better. Again, any of us are inherently more likely to take the time and the effort to do some of these nonpharmacologic therapies if it’s for a reason that internally motivates us.

Dr. Pathak: I think that’s great. I’m very privileged to work within the Veterans Affairs (VA) healthcare system. I think that there’s been a huge shift within VA healthcare to provide these ancillary services, whether it’s yoga, tai chi, or acupuncture, as an adjunct to the pain management strategy.

Also, what comes up for me, as you’re saying, is grounding the point that instead of relying on a pain score — which can be objective and different from patient to patient and even within a patient — we should choose a smart goal that is almost more objective when it’s functional. Your goal is to walk two blocks to the mailbox. Can we achieve that as part of your pain control strategy?

I so appreciate your taking the time to be our pain consultant today. I really appreciate our discussion, and I’d like to hand it over to you for any final thoughts.

Dr. Clauw: I’d add that when you’re seeing chronic pain patients, many of them are going to have comorbid sleep problems. They’re going to have comorbid problems with fatigue and memory problems, especially the central nervous system–driven forms of pain that we now call nociplastic pain. Look at those as therapeutic targets.

If you’re befuddled because you’ve tried many different things for pain in this individual you’ve been seeing for a while, focus on their sleep and focus on getting them more active. Don’t use the word exercise — because that scares chronic pain patients — but focus on getting them more active.

There are many different tactics and strategies that you can use to motivate the patients to try some of these new nonpharmacologic approaches as the evidence base continues to increase.

Dr. Pathak: Thank you so much, again, to Dr. Clauw for joining us and being our pain consultant, really helping us to think about managing back pain in the postopioid world.
 

Dr. Pathak is Chief Physician Editor, Health and Lifestyle Medicine, WebMD. She has disclosed no relevant financial relationships. Dr. Clauw is Director, Chronic Pain and Fatigue Research Center, Department of Anesthesia, University of Michigan, Ann Arbor. He disclosed ties with Tonix and Viatris.

A version of this article appeared on Medscape.com.

Newly released documents show that the US Food and Drug Administration (FDA) has determined that cannabis has a legitimate medical use and that it should be moved from Schedule I to Schedule III on the controlled substances list.

The FDA’s recommendation was contained in a 252-page report that was sent to the US Drug Enforcement Administration (DEA) in August 2023. The report, which Bloomberg News reported on in late August and may have been leaked to that news outlet, was released to Houston attorney Matthew Zorn. He filed suit in September to pressure the FDA to make its recommendation public. The FDA responded days before a court-ordered deadline, said Zorn.

The attorney was not representing any client. “This document belongs in the public sphere,” Zorn told this news organization. “I found it farcical that public policy was being debated on the basis of a document recommendation that literally no one had seen,” he said.

The Bloomberg report ignited debate, but no other advocate, attorney, or news organization had been able to obtain an unredacted version of FDA’s recommendation. 

Now that the full report is public, the DEA may be under more pressure to act. However, it is not required to do anything, and there is no set timeline for any action. Still, lawyers expect to quickly see a rule proposing moving cannabis from Schedule I to III.

“I expect it to come fairly soon and the reason I expect that is because the President told the agencies to do this expeditiously,” said Shane Pennington, an attorney with Porter Wright who has worked with Zorn on cases challenging DEA’s scheduling process but was not involved in this suit.

In October 2022, President Joe Biden said that he was asking the Department of Health and Human Services and the US Attorney General “to review expeditiously how marijuana is scheduled under federal law.”

Howard Sklamberg, a lawyer with Arnold & Porter in Washington, DC, said that the Biden directive “certainly made the agencies reconsider” rescheduling cannabis but that it likely was going to happen anyway, given a wealth of supportive information generated since the DEA last rejected a rescheduling petition in 2016. 

Mr. Sklamberg told this news organization that he thought a proposed rule would be issued soon, with a final rule issued by mid-summer. 

“Agencies generally want to get their important rulemaking done before you get too much into the political season and the potential end of a presidency,” said Mr. Sklamberg, a former FDA deputy commissioner.
 

Credible Medical Use

The FDA said in its report that cannabis is a low-risk threat to public health and that it poses less potential for misuse than drugs in schedule I or II, such as heroin or cocaine.

Though the evidence showed that some people are using cannabis “in amounts sufficient to create a hazard to their health and to the safety of other individuals and the community evidence also exists showing that the vast majority of individuals who use marijuana are doing so in a manner that does not lead to dangerous outcomes to themselves or others,” the FDA noted. 

The agency stated that “the risks to the public health posed by marijuana are low compared to other drugs of abuse (e.g., heroin, cocaine, benzodiazepines), based on an evaluation of various epidemiological databases for [emergency department] visits, hospitalizations, unintentional exposures, and most importantly, for overdose deaths.”

The FDA assessed cannabis’s commonly accepted medical use in seven indications: anorexia, anxiety, epilepsy, inflammatory bowel disease, nausea and vomiting, pain, and posttraumatic stress disorder. It concluded that the strongest evidence existed for anorexia related to a medical condition, nausea and vomiting, and pain.

Of interest, the agency said that when it assessed the harms and benefits, it also used alcohol as a comparator even though it is not a controlled substance. The agency said that it did so because of alcohol’s extensive availability and use, “which is also observed for nonmedical use of marijuana.” 

Mr. Sklamberg found that interesting. A majority of adults have consumed cannabis or know someone who has, making it similar to alcohol, he said. And just as with alcohol, “those adults have formed their own conclusions about what marijuana is and what it isn’t,” he said.

“A lot of Americans make their judgment and think schedule I overstates the health risks,” he added.
 

Opposition in Congress 

It is not certain whether cannabis will be rescheduled; after the Bloomberg report in August, Republican members of Congress sent a letter to DEA Administrator Anne Milgram telling her that the agency should not reschedule the drug.

“The recommendation to remove cannabis from the DEA’s list of dangerous Schedule I drugs is not based on science — it’s based on an irresponsible pro-pot agenda,” said Oklahoma Senator James Lankford (R) on X, in September.

The letter contended that there is no accepted medical use for cannabis and that “the known facts about marijuana have not changed since 2016.”

The FDA, however, based its recommendations in part in looking at data from more than 30,000 healthcare providers and six million patients who have used medical marijuana in state programs, largely established since 2016. Congress has directed the agency to evaluate more of that kind of real-world evidence when evaluating products, said Mr. Sklamberg.

He said that the FDA report will be taken seriously: “It’s a thorough and impressive document.”

“It’s not a document that looks like it was just put together by policy people or political people,” Mr. Sklamberg added. “It’s heavily grounded in science and medicine.”

A version of this article appeared on Medscape.com.

Newly released documents show that the US Food and Drug Administration (FDA) has determined that cannabis has a legitimate medical use and that it should be moved from Schedule I to Schedule III on the controlled substances list.

The FDA’s recommendation was contained in a 252-page report that was sent to the US Drug Enforcement Administration (DEA) in August 2023. The report, which Bloomberg News reported on in late August and may have been leaked to that news outlet, was released to Houston attorney Matthew Zorn. He filed suit in September to pressure the FDA to make its recommendation public. The FDA responded days before a court-ordered deadline, said Zorn.

The attorney was not representing any client. “This document belongs in the public sphere,” Zorn told this news organization. “I found it farcical that public policy was being debated on the basis of a document recommendation that literally no one had seen,” he said.

The Bloomberg report ignited debate, but no other advocate, attorney, or news organization had been able to obtain an unredacted version of FDA’s recommendation. 

Now that the full report is public, the DEA may be under more pressure to act. However, it is not required to do anything, and there is no set timeline for any action. Still, lawyers expect to quickly see a rule proposing moving cannabis from Schedule I to III.

“I expect it to come fairly soon and the reason I expect that is because the President told the agencies to do this expeditiously,” said Shane Pennington, an attorney with Porter Wright who has worked with Zorn on cases challenging DEA’s scheduling process but was not involved in this suit.

In October 2022, President Joe Biden said that he was asking the Department of Health and Human Services and the US Attorney General “to review expeditiously how marijuana is scheduled under federal law.”

Howard Sklamberg, a lawyer with Arnold & Porter in Washington, DC, said that the Biden directive “certainly made the agencies reconsider” rescheduling cannabis but that it likely was going to happen anyway, given a wealth of supportive information generated since the DEA last rejected a rescheduling petition in 2016. 

Mr. Sklamberg told this news organization that he thought a proposed rule would be issued soon, with a final rule issued by mid-summer. 

“Agencies generally want to get their important rulemaking done before you get too much into the political season and the potential end of a presidency,” said Mr. Sklamberg, a former FDA deputy commissioner.
 

Credible Medical Use

The FDA said in its report that cannabis is a low-risk threat to public health and that it poses less potential for misuse than drugs in schedule I or II, such as heroin or cocaine.

Though the evidence showed that some people are using cannabis “in amounts sufficient to create a hazard to their health and to the safety of other individuals and the community evidence also exists showing that the vast majority of individuals who use marijuana are doing so in a manner that does not lead to dangerous outcomes to themselves or others,” the FDA noted. 

The agency stated that “the risks to the public health posed by marijuana are low compared to other drugs of abuse (e.g., heroin, cocaine, benzodiazepines), based on an evaluation of various epidemiological databases for [emergency department] visits, hospitalizations, unintentional exposures, and most importantly, for overdose deaths.”

The FDA assessed cannabis’s commonly accepted medical use in seven indications: anorexia, anxiety, epilepsy, inflammatory bowel disease, nausea and vomiting, pain, and posttraumatic stress disorder. It concluded that the strongest evidence existed for anorexia related to a medical condition, nausea and vomiting, and pain.

Of interest, the agency said that when it assessed the harms and benefits, it also used alcohol as a comparator even though it is not a controlled substance. The agency said that it did so because of alcohol’s extensive availability and use, “which is also observed for nonmedical use of marijuana.” 

Mr. Sklamberg found that interesting. A majority of adults have consumed cannabis or know someone who has, making it similar to alcohol, he said. And just as with alcohol, “those adults have formed their own conclusions about what marijuana is and what it isn’t,” he said.

“A lot of Americans make their judgment and think schedule I overstates the health risks,” he added.
 

Opposition in Congress 

It is not certain whether cannabis will be rescheduled; after the Bloomberg report in August, Republican members of Congress sent a letter to DEA Administrator Anne Milgram telling her that the agency should not reschedule the drug.

“The recommendation to remove cannabis from the DEA’s list of dangerous Schedule I drugs is not based on science — it’s based on an irresponsible pro-pot agenda,” said Oklahoma Senator James Lankford (R) on X, in September.

The letter contended that there is no accepted medical use for cannabis and that “the known facts about marijuana have not changed since 2016.”

The FDA, however, based its recommendations in part in looking at data from more than 30,000 healthcare providers and six million patients who have used medical marijuana in state programs, largely established since 2016. Congress has directed the agency to evaluate more of that kind of real-world evidence when evaluating products, said Mr. Sklamberg.

He said that the FDA report will be taken seriously: “It’s a thorough and impressive document.”

“It’s not a document that looks like it was just put together by policy people or political people,” Mr. Sklamberg added. “It’s heavily grounded in science and medicine.”

A version of this article appeared on Medscape.com.

Newly released documents show that the US Food and Drug Administration (FDA) has determined that cannabis has a legitimate medical use and that it should be moved from Schedule I to Schedule III on the controlled substances list.

The FDA’s recommendation was contained in a 252-page report that was sent to the US Drug Enforcement Administration (DEA) in August 2023. The report, which Bloomberg News reported on in late August and may have been leaked to that news outlet, was released to Houston attorney Matthew Zorn. He filed suit in September to pressure the FDA to make its recommendation public. The FDA responded days before a court-ordered deadline, said Zorn.

The attorney was not representing any client. “This document belongs in the public sphere,” Zorn told this news organization. “I found it farcical that public policy was being debated on the basis of a document recommendation that literally no one had seen,” he said.

The Bloomberg report ignited debate, but no other advocate, attorney, or news organization had been able to obtain an unredacted version of FDA’s recommendation. 

Now that the full report is public, the DEA may be under more pressure to act. However, it is not required to do anything, and there is no set timeline for any action. Still, lawyers expect to quickly see a rule proposing moving cannabis from Schedule I to III.

“I expect it to come fairly soon and the reason I expect that is because the President told the agencies to do this expeditiously,” said Shane Pennington, an attorney with Porter Wright who has worked with Zorn on cases challenging DEA’s scheduling process but was not involved in this suit.

In October 2022, President Joe Biden said that he was asking the Department of Health and Human Services and the US Attorney General “to review expeditiously how marijuana is scheduled under federal law.”

Howard Sklamberg, a lawyer with Arnold & Porter in Washington, DC, said that the Biden directive “certainly made the agencies reconsider” rescheduling cannabis but that it likely was going to happen anyway, given a wealth of supportive information generated since the DEA last rejected a rescheduling petition in 2016. 

Mr. Sklamberg told this news organization that he thought a proposed rule would be issued soon, with a final rule issued by mid-summer. 

“Agencies generally want to get their important rulemaking done before you get too much into the political season and the potential end of a presidency,” said Mr. Sklamberg, a former FDA deputy commissioner.
 

Credible Medical Use

The FDA said in its report that cannabis is a low-risk threat to public health and that it poses less potential for misuse than drugs in schedule I or II, such as heroin or cocaine.

Though the evidence showed that some people are using cannabis “in amounts sufficient to create a hazard to their health and to the safety of other individuals and the community evidence also exists showing that the vast majority of individuals who use marijuana are doing so in a manner that does not lead to dangerous outcomes to themselves or others,” the FDA noted. 

The agency stated that “the risks to the public health posed by marijuana are low compared to other drugs of abuse (e.g., heroin, cocaine, benzodiazepines), based on an evaluation of various epidemiological databases for [emergency department] visits, hospitalizations, unintentional exposures, and most importantly, for overdose deaths.”

The FDA assessed cannabis’s commonly accepted medical use in seven indications: anorexia, anxiety, epilepsy, inflammatory bowel disease, nausea and vomiting, pain, and posttraumatic stress disorder. It concluded that the strongest evidence existed for anorexia related to a medical condition, nausea and vomiting, and pain.

Of interest, the agency said that when it assessed the harms and benefits, it also used alcohol as a comparator even though it is not a controlled substance. The agency said that it did so because of alcohol’s extensive availability and use, “which is also observed for nonmedical use of marijuana.” 

Mr. Sklamberg found that interesting. A majority of adults have consumed cannabis or know someone who has, making it similar to alcohol, he said. And just as with alcohol, “those adults have formed their own conclusions about what marijuana is and what it isn’t,” he said.

“A lot of Americans make their judgment and think schedule I overstates the health risks,” he added.
 

Opposition in Congress 

It is not certain whether cannabis will be rescheduled; after the Bloomberg report in August, Republican members of Congress sent a letter to DEA Administrator Anne Milgram telling her that the agency should not reschedule the drug.

“The recommendation to remove cannabis from the DEA’s list of dangerous Schedule I drugs is not based on science — it’s based on an irresponsible pro-pot agenda,” said Oklahoma Senator James Lankford (R) on X, in September.

The letter contended that there is no accepted medical use for cannabis and that “the known facts about marijuana have not changed since 2016.”

The FDA, however, based its recommendations in part in looking at data from more than 30,000 healthcare providers and six million patients who have used medical marijuana in state programs, largely established since 2016. Congress has directed the agency to evaluate more of that kind of real-world evidence when evaluating products, said Mr. Sklamberg.

He said that the FDA report will be taken seriously: “It’s a thorough and impressive document.”

“It’s not a document that looks like it was just put together by policy people or political people,” Mr. Sklamberg added. “It’s heavily grounded in science and medicine.”

A version of this article appeared on Medscape.com.

Patients with back pain that has persisted for less than 12 weeks have a high probability of substantial pain reduction over time, but patients with back pain that has persisted for 12 or more weeks have a lower chance of improvement, new data suggest.

In a systematic review and meta-analysis of 95 studies, pain score decreased by 35 points on a 100-point scale from baseline to 52 weeks among patients with acute pain (ie, pain lasting for less than 6 weeks). Patients with persistent pain (ie, pain lasting for more than 12 weeks but less than 52 weeks) had smaller improvements at 52 weeks, however. 

“The outcomes for acute pain are better than we thought they were,” study author Lorimer Moseley, AO, DSc, PhD, professor of clinical neurosciences and chair of physiotherapy at the University of South Australia in Adelaide, told this news organization. 

The study was published in the Canadian Medical Association Journal. 

Good Prognoses 

The current analysis represents an update to and advance on a 2012 systematic review and meta-analysis, said Moseley. That study found that patients with subacute low back pain and those with persistent low back pain had similar decreases in pain over 6 weeks. The previous analysis “may have resulted in improved outcomes in the persistent group,” the investigators wrote in the current analysis.

For the current study, the researchers examined 95 studies to understand the clinical course of acute, subacute (ie, lasting for 6 to less than 12 weeks), and persistent low back pain. They excluded retrospective cohorts and interventional studies, as well as studies of patients with low back pain for more than 12 months. The researchers also conducted meta-analyses on aggregate data, where possible, using pain and disability outcome data. 

In patients with acute pain, the mean pain score improved from 56 at baseline to 26 at 6 weeks and 21 at 52 weeks. Patients with subacute pain had a mean pain score of 63 at baseline that improved to 29 at 6 weeks and was maintained at 31 at 52 weeks. Patients with persistent pain had a mean pain score of 56 at baseline that improved to 48 at six weeks and 40 at 52 weeks.

“I don’t think we need to do any more studies to clarify recovery from acute back pain,” said Dr. Moseley. “For subacute back pain, I think there is a moderate to high level of certainty, so the prognosis is pretty good there. The bad news is that the data suggest that if someone’s got back pain 3 months after onset, the likelihood of recovery is much less, but those data are the ones we can’t be certain of on the basis of this meta-analysis.”

Dr. Moseley noted that the current analysis is not highly detailed, because individual patient data are absent. This is “the biggest limitation from a methodological perspective,” he said. “Individual patient analysis is a lot more powerful.”

Comprehensive Literature Search 

Commenting on the findings for this news organization, David Borenstein, MD, clinical professor of rheumatology at the George Washington University Medical Center and partner at Arthritis and Rheumatism Associates in Washington, DC, described the literature search as comprehensive. Dr. Borenstein did not participate in the study. The assessment of low back pain as either short-lived or lasting is worth investigating, he added, given that low back pain impairs a patient’s function and carries a hefty price tag at a societal level.

The study results suggest “that people with acute low back pain do pretty well, and people with subacute low back pain will do less well but still have a chance of healing,” said Dr. Borenstein. “People who have chronic low back pain do not do as well, and they have some increase in disability.” It would be important to develop ways to identify patients whose low back pain will persist beyond 3 months, as well as ways to identify the criteria or characteristics that might prevent those patients from having prolonged difficulties and persistent low back pain, he added.

Dr. Borenstein noted that the authors failed to mention specific approaches that could decrease progression from subacute to persistent low back pain. “They really don’t point anyone in a direction to what would make a difference,” he said. “It would have really improved the impact of the paper if they had seen anything along the way in their review of these articles that might have suggested how someone or a group might have been able to impact this progression.” 

The study was funded by supported by a National Health and Medical Research Council Leadership Investigator Grant to Dr. Moseley. Dr. Moseley and Dr. Borenstein reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Patients with back pain that has persisted for less than 12 weeks have a high probability of substantial pain reduction over time, but patients with back pain that has persisted for 12 or more weeks have a lower chance of improvement, new data suggest.

In a systematic review and meta-analysis of 95 studies, pain score decreased by 35 points on a 100-point scale from baseline to 52 weeks among patients with acute pain (ie, pain lasting for less than 6 weeks). Patients with persistent pain (ie, pain lasting for more than 12 weeks but less than 52 weeks) had smaller improvements at 52 weeks, however. 

“The outcomes for acute pain are better than we thought they were,” study author Lorimer Moseley, AO, DSc, PhD, professor of clinical neurosciences and chair of physiotherapy at the University of South Australia in Adelaide, told this news organization. 

The study was published in the Canadian Medical Association Journal. 

Good Prognoses 

The current analysis represents an update to and advance on a 2012 systematic review and meta-analysis, said Moseley. That study found that patients with subacute low back pain and those with persistent low back pain had similar decreases in pain over 6 weeks. The previous analysis “may have resulted in improved outcomes in the persistent group,” the investigators wrote in the current analysis.

For the current study, the researchers examined 95 studies to understand the clinical course of acute, subacute (ie, lasting for 6 to less than 12 weeks), and persistent low back pain. They excluded retrospective cohorts and interventional studies, as well as studies of patients with low back pain for more than 12 months. The researchers also conducted meta-analyses on aggregate data, where possible, using pain and disability outcome data. 

In patients with acute pain, the mean pain score improved from 56 at baseline to 26 at 6 weeks and 21 at 52 weeks. Patients with subacute pain had a mean pain score of 63 at baseline that improved to 29 at 6 weeks and was maintained at 31 at 52 weeks. Patients with persistent pain had a mean pain score of 56 at baseline that improved to 48 at six weeks and 40 at 52 weeks.

“I don’t think we need to do any more studies to clarify recovery from acute back pain,” said Dr. Moseley. “For subacute back pain, I think there is a moderate to high level of certainty, so the prognosis is pretty good there. The bad news is that the data suggest that if someone’s got back pain 3 months after onset, the likelihood of recovery is much less, but those data are the ones we can’t be certain of on the basis of this meta-analysis.”

Dr. Moseley noted that the current analysis is not highly detailed, because individual patient data are absent. This is “the biggest limitation from a methodological perspective,” he said. “Individual patient analysis is a lot more powerful.”

Comprehensive Literature Search 

Commenting on the findings for this news organization, David Borenstein, MD, clinical professor of rheumatology at the George Washington University Medical Center and partner at Arthritis and Rheumatism Associates in Washington, DC, described the literature search as comprehensive. Dr. Borenstein did not participate in the study. The assessment of low back pain as either short-lived or lasting is worth investigating, he added, given that low back pain impairs a patient’s function and carries a hefty price tag at a societal level.

The study results suggest “that people with acute low back pain do pretty well, and people with subacute low back pain will do less well but still have a chance of healing,” said Dr. Borenstein. “People who have chronic low back pain do not do as well, and they have some increase in disability.” It would be important to develop ways to identify patients whose low back pain will persist beyond 3 months, as well as ways to identify the criteria or characteristics that might prevent those patients from having prolonged difficulties and persistent low back pain, he added.

Dr. Borenstein noted that the authors failed to mention specific approaches that could decrease progression from subacute to persistent low back pain. “They really don’t point anyone in a direction to what would make a difference,” he said. “It would have really improved the impact of the paper if they had seen anything along the way in their review of these articles that might have suggested how someone or a group might have been able to impact this progression.” 

The study was funded by supported by a National Health and Medical Research Council Leadership Investigator Grant to Dr. Moseley. Dr. Moseley and Dr. Borenstein reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Patients with back pain that has persisted for less than 12 weeks have a high probability of substantial pain reduction over time, but patients with back pain that has persisted for 12 or more weeks have a lower chance of improvement, new data suggest.

In a systematic review and meta-analysis of 95 studies, pain score decreased by 35 points on a 100-point scale from baseline to 52 weeks among patients with acute pain (ie, pain lasting for less than 6 weeks). Patients with persistent pain (ie, pain lasting for more than 12 weeks but less than 52 weeks) had smaller improvements at 52 weeks, however. 

“The outcomes for acute pain are better than we thought they were,” study author Lorimer Moseley, AO, DSc, PhD, professor of clinical neurosciences and chair of physiotherapy at the University of South Australia in Adelaide, told this news organization. 

The study was published in the Canadian Medical Association Journal. 

Good Prognoses 

The current analysis represents an update to and advance on a 2012 systematic review and meta-analysis, said Moseley. That study found that patients with subacute low back pain and those with persistent low back pain had similar decreases in pain over 6 weeks. The previous analysis “may have resulted in improved outcomes in the persistent group,” the investigators wrote in the current analysis.

For the current study, the researchers examined 95 studies to understand the clinical course of acute, subacute (ie, lasting for 6 to less than 12 weeks), and persistent low back pain. They excluded retrospective cohorts and interventional studies, as well as studies of patients with low back pain for more than 12 months. The researchers also conducted meta-analyses on aggregate data, where possible, using pain and disability outcome data. 

In patients with acute pain, the mean pain score improved from 56 at baseline to 26 at 6 weeks and 21 at 52 weeks. Patients with subacute pain had a mean pain score of 63 at baseline that improved to 29 at 6 weeks and was maintained at 31 at 52 weeks. Patients with persistent pain had a mean pain score of 56 at baseline that improved to 48 at six weeks and 40 at 52 weeks.

“I don’t think we need to do any more studies to clarify recovery from acute back pain,” said Dr. Moseley. “For subacute back pain, I think there is a moderate to high level of certainty, so the prognosis is pretty good there. The bad news is that the data suggest that if someone’s got back pain 3 months after onset, the likelihood of recovery is much less, but those data are the ones we can’t be certain of on the basis of this meta-analysis.”

Dr. Moseley noted that the current analysis is not highly detailed, because individual patient data are absent. This is “the biggest limitation from a methodological perspective,” he said. “Individual patient analysis is a lot more powerful.”

Comprehensive Literature Search 

Commenting on the findings for this news organization, David Borenstein, MD, clinical professor of rheumatology at the George Washington University Medical Center and partner at Arthritis and Rheumatism Associates in Washington, DC, described the literature search as comprehensive. Dr. Borenstein did not participate in the study. The assessment of low back pain as either short-lived or lasting is worth investigating, he added, given that low back pain impairs a patient’s function and carries a hefty price tag at a societal level.

The study results suggest “that people with acute low back pain do pretty well, and people with subacute low back pain will do less well but still have a chance of healing,” said Dr. Borenstein. “People who have chronic low back pain do not do as well, and they have some increase in disability.” It would be important to develop ways to identify patients whose low back pain will persist beyond 3 months, as well as ways to identify the criteria or characteristics that might prevent those patients from having prolonged difficulties and persistent low back pain, he added.

Dr. Borenstein noted that the authors failed to mention specific approaches that could decrease progression from subacute to persistent low back pain. “They really don’t point anyone in a direction to what would make a difference,” he said. “It would have really improved the impact of the paper if they had seen anything along the way in their review of these articles that might have suggested how someone or a group might have been able to impact this progression.” 

The study was funded by supported by a National Health and Medical Research Council Leadership Investigator Grant to Dr. Moseley. Dr. Moseley and Dr. Borenstein reported no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

New data link smoking and heavy drinking with an increased risk for diverticulitis, with the greatest risk seen in adults who smoke and consume two or more drinks daily.

METHODOLOGY:

• Researchers studied 84,232 women in the Nurses’ Health Study II who were 39-52 years old and without known diverticulitis at baseline in 2003. 
• In 2015 and 2017, participants were asked via questionnaire whether they had been diagnosed with diverticulitis requiring antibiotic therapy or hospitalization. Diverticulitis was defined as a computed tomography scan or pathology report of diverticulitis or a provider diagnosis with a clinical presentation consistent with diverticulitis. 
• Smoking was assessed every 2 years and alcohol consumption every 4 years using standard questionnaires. 
• Consistent with prior studies on risk factors for diverticulitis, multivariable models adjusted for age, menopausal hormone status and hormone use, body mass index, physical activity, aspirin/nonsteroidal anti-inflammatory drug use, intake of fiber and red/processed meat, and other factors were used. 

TAKEAWAY:

• During more than 1 million person-years of follow-up, 3018 incident cases of diverticulitis were identified. 
• Both current and past smoking were associated with increased risk for diverticulitis (hazard ratio [HR], 1.2) compared with never smoking, although no dose-response relationship was evident. In an analysis restricted to participants who had surgery for diverticulitis, the magnitude of the association was strengthened (HR, 1.48 for current smokers and 1.46 for past smokers vs never smokers). 
• Consumption of ≥ 30 g/d of alcohol (2+ drinks/day) was associated with an increased risk for incident diverticulitis (HR, 1.26) compared with not drinking. 
• A joint analysis of smoking and alcohol found that individuals who ever smoked and consumed ≥ 30 g/d of alcohol were at the highest risk for diverticulitis (multivariate HR, 1.53) compared with individuals who never smoked and reported no alcohol use. 

IN PRACTICE:

“As there are currently no medical means to prevent diverticulitis other than dietary and lifestyle interventions, counseling patients about the avoidance of smoking and alcohol may help lower the risk for developing diverticulitis,” the authors concluded.

SOURCE:

The study, with first author Sara Gunby, MD, University of Washington School of Medicine, Seattle, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

Diverticulitis diagnoses were self-reported, although a review of a subset of medical records confirmed the diagnosis in more than 90% of cases establishing the validity of self-report in this population. The study was limited to female nurses, so it is possible the findings may not be generalizable to men or other populations. Residual confounding may have impacted the results.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

New data link smoking and heavy drinking with an increased risk for diverticulitis, with the greatest risk seen in adults who smoke and consume two or more drinks daily.

METHODOLOGY:

• Researchers studied 84,232 women in the Nurses’ Health Study II who were 39-52 years old and without known diverticulitis at baseline in 2003. 
• In 2015 and 2017, participants were asked via questionnaire whether they had been diagnosed with diverticulitis requiring antibiotic therapy or hospitalization. Diverticulitis was defined as a computed tomography scan or pathology report of diverticulitis or a provider diagnosis with a clinical presentation consistent with diverticulitis. 
• Smoking was assessed every 2 years and alcohol consumption every 4 years using standard questionnaires. 
• Consistent with prior studies on risk factors for diverticulitis, multivariable models adjusted for age, menopausal hormone status and hormone use, body mass index, physical activity, aspirin/nonsteroidal anti-inflammatory drug use, intake of fiber and red/processed meat, and other factors were used. 

TAKEAWAY:

• During more than 1 million person-years of follow-up, 3018 incident cases of diverticulitis were identified. 
• Both current and past smoking were associated with increased risk for diverticulitis (hazard ratio [HR], 1.2) compared with never smoking, although no dose-response relationship was evident. In an analysis restricted to participants who had surgery for diverticulitis, the magnitude of the association was strengthened (HR, 1.48 for current smokers and 1.46 for past smokers vs never smokers). 
• Consumption of ≥ 30 g/d of alcohol (2+ drinks/day) was associated with an increased risk for incident diverticulitis (HR, 1.26) compared with not drinking. 
• A joint analysis of smoking and alcohol found that individuals who ever smoked and consumed ≥ 30 g/d of alcohol were at the highest risk for diverticulitis (multivariate HR, 1.53) compared with individuals who never smoked and reported no alcohol use. 

IN PRACTICE:

“As there are currently no medical means to prevent diverticulitis other than dietary and lifestyle interventions, counseling patients about the avoidance of smoking and alcohol may help lower the risk for developing diverticulitis,” the authors concluded.

SOURCE:

The study, with first author Sara Gunby, MD, University of Washington School of Medicine, Seattle, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

Diverticulitis diagnoses were self-reported, although a review of a subset of medical records confirmed the diagnosis in more than 90% of cases establishing the validity of self-report in this population. The study was limited to female nurses, so it is possible the findings may not be generalizable to men or other populations. Residual confounding may have impacted the results.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

New data link smoking and heavy drinking with an increased risk for diverticulitis, with the greatest risk seen in adults who smoke and consume two or more drinks daily.

METHODOLOGY:

• Researchers studied 84,232 women in the Nurses’ Health Study II who were 39-52 years old and without known diverticulitis at baseline in 2003. 
• In 2015 and 2017, participants were asked via questionnaire whether they had been diagnosed with diverticulitis requiring antibiotic therapy or hospitalization. Diverticulitis was defined as a computed tomography scan or pathology report of diverticulitis or a provider diagnosis with a clinical presentation consistent with diverticulitis. 
• Smoking was assessed every 2 years and alcohol consumption every 4 years using standard questionnaires. 
• Consistent with prior studies on risk factors for diverticulitis, multivariable models adjusted for age, menopausal hormone status and hormone use, body mass index, physical activity, aspirin/nonsteroidal anti-inflammatory drug use, intake of fiber and red/processed meat, and other factors were used. 

TAKEAWAY:

• During more than 1 million person-years of follow-up, 3018 incident cases of diverticulitis were identified. 
• Both current and past smoking were associated with increased risk for diverticulitis (hazard ratio [HR], 1.2) compared with never smoking, although no dose-response relationship was evident. In an analysis restricted to participants who had surgery for diverticulitis, the magnitude of the association was strengthened (HR, 1.48 for current smokers and 1.46 for past smokers vs never smokers). 
• Consumption of ≥ 30 g/d of alcohol (2+ drinks/day) was associated with an increased risk for incident diverticulitis (HR, 1.26) compared with not drinking. 
• A joint analysis of smoking and alcohol found that individuals who ever smoked and consumed ≥ 30 g/d of alcohol were at the highest risk for diverticulitis (multivariate HR, 1.53) compared with individuals who never smoked and reported no alcohol use. 

IN PRACTICE:

“As there are currently no medical means to prevent diverticulitis other than dietary and lifestyle interventions, counseling patients about the avoidance of smoking and alcohol may help lower the risk for developing diverticulitis,” the authors concluded.

SOURCE:

The study, with first author Sara Gunby, MD, University of Washington School of Medicine, Seattle, was published online in Clinical Gastroenterology and Hepatology.

LIMITATIONS:

Diverticulitis diagnoses were self-reported, although a review of a subset of medical records confirmed the diagnosis in more than 90% of cases establishing the validity of self-report in this population. The study was limited to female nurses, so it is possible the findings may not be generalizable to men or other populations. Residual confounding may have impacted the results.

DISCLOSURES:

The study was supported by grants from the National Institutes of Health. The authors declared no relevant conflicts of interest.

A version of this article appeared on Medscape.com.