Pain

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women's Hospital

A version of this article first appeared on Medscape.com.

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women's Hospital

A version of this article first appeared on Medscape.com.

New clinical practice guidelines for cannabis in chronic pain management have been released.

Developed by a group of Canadian researchers, clinicians, and patients, the guidelines note that cannabinoid-based medicines (CBM) may help clinicians offer an effective, less addictive, alternative to opioids in patients with chronic noncancer pain and comorbid conditions.

“We don’t recommend using CBM first line for anything pretty much because there are other alternatives that may be more effective and also offer fewer side effects,” lead guideline author Alan Bell, MD, assistant professor of family and community medicine at the University of Toronto, told this news organization.

University of Toronto

Examining the evidence

A consistent criticism of CBM has been the lack of quality research supporting its therapeutic utility. To develop the current recommendations, the task force reviewed 47 pain management studies enrolling more than 11,000 patients. Almost half of the studies (n = 22) were randomized controlled trials (RCTs) and 12 of the 19 included systematic reviews focused solely on RCTs.

Overall, 38 of the 47 included studies demonstrated that CBM provided at least moderate benefits for chronic pain, resulting in a “strong” recommendation – mostly as an adjunct or replacement treatment in individuals living with chronic pain.

Overall, the guidelines place a high value on improving chronic pain and functionality, and addressing co-occurring conditions such as insomnia, anxiety and depression, mobility, and inflammation. They also provide practical dosing and formulation tips to support the use of CBM in the clinical setting.

When it comes to chronic pain, CBM is not a panacea. However, prior research suggests cannabinoids and opioids share several pharmacologic properties, including independent but possibly related mechanisms for antinociception, making them an intriguing combination.

In the current guidelines, all of the four studies specifically addressing combined opioids and vaporized cannabis flower demonstrated further pain reduction, reinforcing the conclusion that the benefits of CBM for improving pain control in patients taking opioids outweigh the risk of nonserious adverse events (AEs), such as dry mouth, dizziness, increased appetite, sedation, and concentration difficulties.

The recommendations also highlighted evidence demonstrating that a majority of participants were able to reduce use of routine pain medications with concomitant CBM/opioid administration, while simultaneously offering secondary benefits such as improved sleep, anxiety, and mood, as well as prevention of opioid tolerance and dose escalation.

Importantly, the guidelines offer an evidence-based algorithm with a clear framework for tapering patients off opioids, especially those who are on > 50 mg MED, which places them with a twofold greater risk for fatal overdose.

An effective alternative

Commenting on the new guidelines, Mark Wallace, MD, who has extensive experience researching and treating pain patients with medical cannabis, said the genesis of his interest in medical cannabis mirrors the guidelines’ focus.

“What got me interested in medical cannabis was trying to get patients off of opioids,” said Dr. Wallace, professor of anesthesiology and chief of the division of pain medicine in the department of anesthesiology at the University of California, San Diego. Dr. Wallace, who was not involved in the guidelines’ development study, said that he’s “titrated hundreds of patients off of opioids using cannabis.”

Dr. Wallace said he found the guidelines’ dosing recommendations helpful.

“If you stay within the 1- to 5-mg dosing range, the risks are so incredibly low, you’re not going to harm the patient.”

While there are patients who abuse cannabis and CBMs, Dr. Wallace noted that he has seen only one patient in the past 20 years who was overusing the medical cannabis. He added that his patient population does not use medical cannabis to get high and, in fact, wants to avoid doses that produce that effect at all costs.

Also commenting on the guidelines, Christopher Gilligan, MD, MBA, associate chief medical officer and a pain medicine physician at Brigham and Women’s Hospital in Boston, who was not involved in the guidelines’ development, points to the risks.

Brigham and Women's Hospital

A version of this article first appeared on Medscape.com.

Cluster headache and migraine have strong ties to the circadian system at multiple levels, say new findings that could have significant treatment implications.

A meta-analysis of 16 studies showed a circadian pattern in 71% of cluster headache attacks (3,490 of 4,953), with a clear circadian peak between 9:00 p.m. and 3:00 a.m.

Migraine was also associated with a circadian pattern in 50% of cases (2,698 of 5,385) across eight studies, with a clear circadian trough between 11:00 p.m. and 7:00 a.m.

Seasonal peaks were also evident for cluster headache (spring and autumn) and migraine (April to October).

“In the short term, these findings help us explain the timing to patients – for example, it is possible that a headache at 8 a.m. is due to their internal body clock instead of their pillow, or breakfast food, or morning medications,” lead investigator Mark Burish, MD, PhD, associate professor, department of neurosurgery, at University of Texas Health Houston, told this news organization.

“In the long term, these findings do suggest that medications that target the circadian system could be effective in migraine and headache patients,” Dr. Burish added.

The study was published online in Neurology.


 

Treatment implications?

Across studies, chronotype was “highly variable” for both cluster headache and migraine, the investigators report.

Cluster headache was associated with lower melatonin and higher cortisol levels, compared with non–cluster headache controls.

On a genetic level, cluster headache was associated with two core circadian genes (CLOCK and REV-ERB–alpha), and five of the nine genes that increase the likelihood of having cluster headache are genes with a circadian pattern of expression.

Migraine headache was associated with lower urinary melatonin levels and with the core circadian genes, CK1-delta and ROR-alpha, and 110 of the 168 genes associated with migraine were clock-controlled genes.

“The data suggest that both of these headache disorders are highly circadian at multiple levels, especially cluster headache,” Dr. Burish said in a release.

“This reinforces the importance of the hypothalamus – the area of the brain that houses the primary biological clock – and its role in cluster headache and migraine. It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm,” Dr. Burish said.

“We hope that future research will look into circadian medications as a new treatment option for migraine and cluster headache patients,” Dr. Burish told this news organization.
 

Importance of sleep regulation

The authors of an accompanying editorial note that even though the study doesn’t have immediate clinical implications, it offers a better understanding of the way chronobiologic factors may influence treatment.

“At a minimum, interventions known to regulate and improve sleep (e.g., melatonin, cognitive behavioral therapy), and which are safe and straightforward to introduce, may be useful in some individuals susceptible to circadian misalignment or sleep disorders,” write Heidi Sutherland, PhD, and Lyn Griffiths, PhD, with Queensland University of Technology, Brisbane, Australia.

“Treatment of comorbidities (e.g., insomnia) that result in sleep disturbances may also help headache management. Furthermore, chronobiological aspects of any pharmacological interventions should be considered, as some frequently used headache and migraine drugs can modulate circadian cycles and influence the expression of circadian genes (e.g., verapamil), or have sleep-related side effects,” they add.

A limitation of the study was the lack of information on factors that could influence the circadian cycle, such as medications; other disorders, such as bipolar disorder; or circadian rhythm issues, such as night-shift work.

The study was supported by grants from the Japan Society for the Promotion of Science, the National Institutes of Health, The Welch Foundation, and The Will Erwin Headache Research Foundation. Dr. Burish is an unpaid member of the medical advisory board of Clusterbusters, and a site investigator for a cluster headache clinical trial funded by Lundbeck. Dr. Sutherland has received grant funding from the U.S. Migraine Research Foundation, and received institute support from Queensland University of Technology for genetics research. Dr. Griffiths has received grant funding from the Australian NHMRC, U.S. Department of Defense, and the U.S. Migraine Research Foundation, and consultancy funding from TEVA.

A version of this article first appeared on Medscape.com.

Cluster headache and migraine have strong ties to the circadian system at multiple levels, say new findings that could have significant treatment implications.

A meta-analysis of 16 studies showed a circadian pattern in 71% of cluster headache attacks (3,490 of 4,953), with a clear circadian peak between 9:00 p.m. and 3:00 a.m.

Migraine was also associated with a circadian pattern in 50% of cases (2,698 of 5,385) across eight studies, with a clear circadian trough between 11:00 p.m. and 7:00 a.m.

Seasonal peaks were also evident for cluster headache (spring and autumn) and migraine (April to October).

“In the short term, these findings help us explain the timing to patients – for example, it is possible that a headache at 8 a.m. is due to their internal body clock instead of their pillow, or breakfast food, or morning medications,” lead investigator Mark Burish, MD, PhD, associate professor, department of neurosurgery, at University of Texas Health Houston, told this news organization.

“In the long term, these findings do suggest that medications that target the circadian system could be effective in migraine and headache patients,” Dr. Burish added.

The study was published online in Neurology.


 

Treatment implications?

Across studies, chronotype was “highly variable” for both cluster headache and migraine, the investigators report.

Cluster headache was associated with lower melatonin and higher cortisol levels, compared with non–cluster headache controls.

On a genetic level, cluster headache was associated with two core circadian genes (CLOCK and REV-ERB–alpha), and five of the nine genes that increase the likelihood of having cluster headache are genes with a circadian pattern of expression.

Migraine headache was associated with lower urinary melatonin levels and with the core circadian genes, CK1-delta and ROR-alpha, and 110 of the 168 genes associated with migraine were clock-controlled genes.

“The data suggest that both of these headache disorders are highly circadian at multiple levels, especially cluster headache,” Dr. Burish said in a release.

“This reinforces the importance of the hypothalamus – the area of the brain that houses the primary biological clock – and its role in cluster headache and migraine. It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm,” Dr. Burish said.

“We hope that future research will look into circadian medications as a new treatment option for migraine and cluster headache patients,” Dr. Burish told this news organization.
 

Importance of sleep regulation

The authors of an accompanying editorial note that even though the study doesn’t have immediate clinical implications, it offers a better understanding of the way chronobiologic factors may influence treatment.

“At a minimum, interventions known to regulate and improve sleep (e.g., melatonin, cognitive behavioral therapy), and which are safe and straightforward to introduce, may be useful in some individuals susceptible to circadian misalignment or sleep disorders,” write Heidi Sutherland, PhD, and Lyn Griffiths, PhD, with Queensland University of Technology, Brisbane, Australia.

“Treatment of comorbidities (e.g., insomnia) that result in sleep disturbances may also help headache management. Furthermore, chronobiological aspects of any pharmacological interventions should be considered, as some frequently used headache and migraine drugs can modulate circadian cycles and influence the expression of circadian genes (e.g., verapamil), or have sleep-related side effects,” they add.

A limitation of the study was the lack of information on factors that could influence the circadian cycle, such as medications; other disorders, such as bipolar disorder; or circadian rhythm issues, such as night-shift work.

The study was supported by grants from the Japan Society for the Promotion of Science, the National Institutes of Health, The Welch Foundation, and The Will Erwin Headache Research Foundation. Dr. Burish is an unpaid member of the medical advisory board of Clusterbusters, and a site investigator for a cluster headache clinical trial funded by Lundbeck. Dr. Sutherland has received grant funding from the U.S. Migraine Research Foundation, and received institute support from Queensland University of Technology for genetics research. Dr. Griffiths has received grant funding from the Australian NHMRC, U.S. Department of Defense, and the U.S. Migraine Research Foundation, and consultancy funding from TEVA.

A version of this article first appeared on Medscape.com.

Cluster headache and migraine have strong ties to the circadian system at multiple levels, say new findings that could have significant treatment implications.

A meta-analysis of 16 studies showed a circadian pattern in 71% of cluster headache attacks (3,490 of 4,953), with a clear circadian peak between 9:00 p.m. and 3:00 a.m.

Migraine was also associated with a circadian pattern in 50% of cases (2,698 of 5,385) across eight studies, with a clear circadian trough between 11:00 p.m. and 7:00 a.m.

Seasonal peaks were also evident for cluster headache (spring and autumn) and migraine (April to October).

“In the short term, these findings help us explain the timing to patients – for example, it is possible that a headache at 8 a.m. is due to their internal body clock instead of their pillow, or breakfast food, or morning medications,” lead investigator Mark Burish, MD, PhD, associate professor, department of neurosurgery, at University of Texas Health Houston, told this news organization.

“In the long term, these findings do suggest that medications that target the circadian system could be effective in migraine and headache patients,” Dr. Burish added.

The study was published online in Neurology.


 

Treatment implications?

Across studies, chronotype was “highly variable” for both cluster headache and migraine, the investigators report.

Cluster headache was associated with lower melatonin and higher cortisol levels, compared with non–cluster headache controls.

On a genetic level, cluster headache was associated with two core circadian genes (CLOCK and REV-ERB–alpha), and five of the nine genes that increase the likelihood of having cluster headache are genes with a circadian pattern of expression.

Migraine headache was associated with lower urinary melatonin levels and with the core circadian genes, CK1-delta and ROR-alpha, and 110 of the 168 genes associated with migraine were clock-controlled genes.

“The data suggest that both of these headache disorders are highly circadian at multiple levels, especially cluster headache,” Dr. Burish said in a release.

“This reinforces the importance of the hypothalamus – the area of the brain that houses the primary biological clock – and its role in cluster headache and migraine. It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm,” Dr. Burish said.

“We hope that future research will look into circadian medications as a new treatment option for migraine and cluster headache patients,” Dr. Burish told this news organization.
 

Importance of sleep regulation

The authors of an accompanying editorial note that even though the study doesn’t have immediate clinical implications, it offers a better understanding of the way chronobiologic factors may influence treatment.

“At a minimum, interventions known to regulate and improve sleep (e.g., melatonin, cognitive behavioral therapy), and which are safe and straightforward to introduce, may be useful in some individuals susceptible to circadian misalignment or sleep disorders,” write Heidi Sutherland, PhD, and Lyn Griffiths, PhD, with Queensland University of Technology, Brisbane, Australia.

“Treatment of comorbidities (e.g., insomnia) that result in sleep disturbances may also help headache management. Furthermore, chronobiological aspects of any pharmacological interventions should be considered, as some frequently used headache and migraine drugs can modulate circadian cycles and influence the expression of circadian genes (e.g., verapamil), or have sleep-related side effects,” they add.

A limitation of the study was the lack of information on factors that could influence the circadian cycle, such as medications; other disorders, such as bipolar disorder; or circadian rhythm issues, such as night-shift work.

The study was supported by grants from the Japan Society for the Promotion of Science, the National Institutes of Health, The Welch Foundation, and The Will Erwin Headache Research Foundation. Dr. Burish is an unpaid member of the medical advisory board of Clusterbusters, and a site investigator for a cluster headache clinical trial funded by Lundbeck. Dr. Sutherland has received grant funding from the U.S. Migraine Research Foundation, and received institute support from Queensland University of Technology for genetics research. Dr. Griffiths has received grant funding from the Australian NHMRC, U.S. Department of Defense, and the U.S. Migraine Research Foundation, and consultancy funding from TEVA.

A version of this article first appeared on Medscape.com.

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

DENVER – Metabolic syndrome in both early and mid-adulthood is associated with symptoms of knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress.

©pixologicstudio/Thinkstock

Data at both time points included fasting blood biochemistry, waist circumference, and blood pressure measures. The criteria for metabolic syndrome requires presence of central obesity (a waist circumference of at least 94 cm in males or 80 cm in females) and two of the following four factors:

• Raised triglycerides (at least 150 mg/dL) or specific treatment for this lipid abnormality.
• Reduced HDL cholesterol (below 40 mg/dL in males and below 50 mg/dL in females) or treatment for this.
• Raised blood pressure (at least 130 mm Hg systolic or at least 85 mm Hg diastolic) or treatment of previously diagnosed hypertension.
• Raised fasting blood glucose (at least 100 mg/dL) or previously diagnosed type 2 diabetes.

The researchers grouped the participants on the basis of having no metabolic syndrome at either life stage, having metabolic syndrome in young adulthood but not at follow-up (improved), having developed metabolic syndrome at follow-up (incident), and having metabolic syndrome at both time points (persistent). Most of the participants did not have the metabolic syndrome at either time point (85%), whereas 2% improved in mid-adulthood, 9% developed incident metabolic syndrome in mid-adulthood, and 4% had persistent metabolic syndrome.

At follow-up, 43% of the participants reported pain on the WOMAC, and the average WOMAC score was 10. Prevalence of metabolic syndrome increased from 8% in young adulthood to 13% in mid-adulthood, with an increase in abdominal obesity prevalence from 29% to 47%. Metabolic syndrome at any time point – whether improved later, developed later, or persistent – was associated with more knee symptoms, compared with no metabolic syndrome.

Presence of metabolic syndrome in mid-adulthood was associated with knee symptoms from the total WOMAC score (ratio of means, 1.33; P < .001) after adjustment for age, sex, and body mass index (BMI). Metabolic syndrome was also independently associated in mid-adulthood with knee pain (RoM, 1.29; P < .001) and poor function (RoM, 1.37; P < .001).

Those who developed incident metabolic syndrome in mid-adulthood had the greatest association with overall knee symptoms (RoM, 1.56; P < .001) and with knee pain (RoM, 1.52; P < .001). Although improved and persistent metabolic syndrome were both significantly associated with total WOMAC score, neither was significantly associated with knee pain after adjustment for age, sex, and BMI.

The three individual metabolic criteria independently associated with overall WOMAC score were abdominal obesity (RoM, 1.09), hypertension (RoM, 1.44), and low HDL (RoM, 1.17; P < .001 for all).

Leigh F. Callahan, PhD, a professor of medicine and associate director of the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill, said in an interview that this topic is especially important because there’s so little understanding of the role of comorbid conditions and osteoarthritis.

“There were some key things that I thought were wonderful about this study – the longitudinal nature and the fact that they had collected metabolic syndrome [criteria] at multiple time points and were able to look at persistent versus incident metabolic syndrome,” Dr. Callahan said. “We frequently don’t have that kind of trajectory.”

Jaqueline Lourdes Rios, PhD, an assistant professor of orthopedics at University Medical Center Utrecht (Netherlands), said in an interview that the study raised questions about whether treating metabolic syndrome could help prevent the progression of osteoarthritis to some extent. “Although, if you already have damage in your cartilage, and if you have a lot of inflammation that’s local, it might be a bit trickier than just treating metabolic syndrome,” Dr. Lourdes Rios added. “Then, it might help, it might not.” Either way, she said, it’s certainly worthwhile for physicians to spend time discussing interventions to address metabolic syndrome “because you treat the patient, not a knee.”

Dr. Ding, Dr. Lourdes Rios, and Dr. Callahan had no relevant financial relationships to disclose. The researchers did not note any external funding.

DENVER – Using antidepressants to treat osteoarthritis pain can benefit some individuals but appears to have a clinically unimportant reduction in pain when looking at all patients who have tried them, according to a study presented at the OARSI 2023 World Congress. The review was also published in the Cochrane Database of Systematic Reviews in October 2022.

In terms of implications for clinical practice, the findings “seem to suggest there is a subgroup that is more likely to respond to antidepressants,” Anita Wluka, PhD, MBBS, a professor in the School of Public Health and Preventive Medicine at Monash University in Melbourne, told attendees. The findings also raise an important research question: “How can we identify the patient phenotype likely to benefit so we can [minimize the] risk of those adverse events and effects?”

Osteoarthritis pain is heterogeneous, and an estimated 30% of the pain is neuropathic-like, likely including central and peripheral sensitization, Dr. Wluka said. Given that antidepressants affect multiple sites along these pathways, multiple organizations have issued a conditional recommendation for duloxetine in their osteoarthritis guidelines, including OARSI, the European Alliance of Associations for Rheumatology, and the American College of Rheumatology.

The Cochrane Collaboration therefore conducted a systematic review and meta-analysis of research on the benefits and harms of using antidepressants to treat symptomatic knee and hip osteoarthritis. The review included studies through January 2021 whose participants had knee and/or hip osteoarthritis and which compared antidepressant therapy with placebo or another intervention for at least 6 weeks. The authors looked at seven outcomes: overall pain on a 0-10 scale, clinical response (at least a 50% reduction in 24‐hour mean pain), physical function using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life using the EQ-5D, the proportion of participants withdrawing because of adverse events, the proportion who experienced any adverse events, and the proportion who experienced serious adverse events.

The researchers considered a change on the pain scale of 0.5-1 points to be “slight to small,” a difference above 1 up to 2 to be “moderate,” and a difference greater than 2 points to be “large.” In assessing quality of life function on a scale of 0-100, a slight to small difference was 5-10, a moderate difference was 11-20, and a large difference was above 20.

Of the 18 articles the researchers identified for qualitative synthesis, 9 met the criteria for qualitative synthesis in the meta-analysis, including 7 studies only on the knee and 2 that included the knees and hips. All nine studies compared antidepressants with placebo, with or without NSAIDs. Most focused on serotonin and norepinephrine reuptake inhibitors (SNRIs) – six studies on duloxetine and one on milnacipran – while one included fluvoxamine and one included nortriptyline.

The trials included a combined 2,122 participants who were predominantly female with an average age range of 54-66. Trials ranged from 8 to 16 weeks. Five of the trials carried risk of attrition and reporting bias, and only one trial had low risk of bias across all domains.

In five trials with SNRIs and one trial with tricyclics (nortriptyline) totaling 1,904 participants, 45% of those receiving antidepressants had a clinical response, compared with 29% of patients who received placebo (risk ratio, 1.55; 95% CI, 1.31-1.92). This absolute improvement in pain occurred in 16% more participants taking antidepressants, giving a number needed to treat (NNT) of 6. Average improvement in WOMAC physical function was 10.5 points with placebo and 16.2 points with antidepressants, indicating a “small, clinically unimportant response,” the researchers concluded.

Withdrawals because of adverse events included 11% of the antidepressant group and 5% of the placebo group (RR, 2.15; 95% CI, 1.56-2.87), putting the NNT for a harmful outcome at 17.

For all nine trials together, however, the mean reduction in pain from antidepressants was 2.3 points, compared with 1.7 points with placebo, a statistically significant but ”clinically unimportant improvement,” the researchers concluded. Adverse events occurred in 64% of the antidepressant group, compared with 49% of the placebo group (RR, 1.27; 95% CI, 1.15-1.41), which put the NNT for a harmful outcome at 7. No significant difference in serious adverse events occurred between the groups.

The analysis was limited by the low number of trials, most of which were sponsored by industry and most of which used duloxetine. Further, few of the studies enrolled patients with osteoarthritis of the hip, none assessed medium- or long-term effects, and none stratified the participants for different types of pain (neuropathic-like or central or peripheral pain sensitization).

“My general impression is that there was a statistically significant difference found in favor of duloxetine and the antidepressants,” David J. Hunter, MBBS, PhD, MSc, of the University of Sydney, said after the presentation. “There is a real risk of harm, which I think is important to take into consideration, but at least for me as a clinician and in advising other clinicians, it’s one tool in our armamentarium. I think it’s really important to allow patients to make an informed decision about the potential benefit, the real risk of harm, and the fact that it is quite useful in some patients, and I use it in my clinical practice.”

Jeffrey N. Katz, MD, MS, of Brigham and Women’s Hospital in Boston, said he uses antidepressants in the same way in his practice and that other types of medications, such as TNF inhibitors, also carry risk of harm that may exceed that of antidepressants.

“I’ve had lots of people start duloxetine, and if they stop it, it’s usually because they just don’t tolerate it very well,” Dr. Katz said.

“We don’t want to throw too many things away,” Dr. Hunter added. “Our patients don’t necessarily have a lot of choices here from a pharmacologic perspective, so I think it’s one of those options that I want to keep in my tool kit, and that’s not necessarily going to change.”

The research did not involve outside funding, and Dr. Wluka reported having no industry disclosures. Disclosure information was unavailable for Dr. Katz and Dr. Hunter. The Congress was sponsored by the Osteoarthritis Research Society International.

DENVER – Using antidepressants to treat osteoarthritis pain can benefit some individuals but appears to have a clinically unimportant reduction in pain when looking at all patients who have tried them, according to a study presented at the OARSI 2023 World Congress. The review was also published in the Cochrane Database of Systematic Reviews in October 2022.

In terms of implications for clinical practice, the findings “seem to suggest there is a subgroup that is more likely to respond to antidepressants,” Anita Wluka, PhD, MBBS, a professor in the School of Public Health and Preventive Medicine at Monash University in Melbourne, told attendees. The findings also raise an important research question: “How can we identify the patient phenotype likely to benefit so we can [minimize the] risk of those adverse events and effects?”

Osteoarthritis pain is heterogeneous, and an estimated 30% of the pain is neuropathic-like, likely including central and peripheral sensitization, Dr. Wluka said. Given that antidepressants affect multiple sites along these pathways, multiple organizations have issued a conditional recommendation for duloxetine in their osteoarthritis guidelines, including OARSI, the European Alliance of Associations for Rheumatology, and the American College of Rheumatology.

The Cochrane Collaboration therefore conducted a systematic review and meta-analysis of research on the benefits and harms of using antidepressants to treat symptomatic knee and hip osteoarthritis. The review included studies through January 2021 whose participants had knee and/or hip osteoarthritis and which compared antidepressant therapy with placebo or another intervention for at least 6 weeks. The authors looked at seven outcomes: overall pain on a 0-10 scale, clinical response (at least a 50% reduction in 24‐hour mean pain), physical function using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life using the EQ-5D, the proportion of participants withdrawing because of adverse events, the proportion who experienced any adverse events, and the proportion who experienced serious adverse events.

The researchers considered a change on the pain scale of 0.5-1 points to be “slight to small,” a difference above 1 up to 2 to be “moderate,” and a difference greater than 2 points to be “large.” In assessing quality of life function on a scale of 0-100, a slight to small difference was 5-10, a moderate difference was 11-20, and a large difference was above 20.

Of the 18 articles the researchers identified for qualitative synthesis, 9 met the criteria for qualitative synthesis in the meta-analysis, including 7 studies only on the knee and 2 that included the knees and hips. All nine studies compared antidepressants with placebo, with or without NSAIDs. Most focused on serotonin and norepinephrine reuptake inhibitors (SNRIs) – six studies on duloxetine and one on milnacipran – while one included fluvoxamine and one included nortriptyline.

The trials included a combined 2,122 participants who were predominantly female with an average age range of 54-66. Trials ranged from 8 to 16 weeks. Five of the trials carried risk of attrition and reporting bias, and only one trial had low risk of bias across all domains.

In five trials with SNRIs and one trial with tricyclics (nortriptyline) totaling 1,904 participants, 45% of those receiving antidepressants had a clinical response, compared with 29% of patients who received placebo (risk ratio, 1.55; 95% CI, 1.31-1.92). This absolute improvement in pain occurred in 16% more participants taking antidepressants, giving a number needed to treat (NNT) of 6. Average improvement in WOMAC physical function was 10.5 points with placebo and 16.2 points with antidepressants, indicating a “small, clinically unimportant response,” the researchers concluded.

Withdrawals because of adverse events included 11% of the antidepressant group and 5% of the placebo group (RR, 2.15; 95% CI, 1.56-2.87), putting the NNT for a harmful outcome at 17.

For all nine trials together, however, the mean reduction in pain from antidepressants was 2.3 points, compared with 1.7 points with placebo, a statistically significant but ”clinically unimportant improvement,” the researchers concluded. Adverse events occurred in 64% of the antidepressant group, compared with 49% of the placebo group (RR, 1.27; 95% CI, 1.15-1.41), which put the NNT for a harmful outcome at 7. No significant difference in serious adverse events occurred between the groups.

The analysis was limited by the low number of trials, most of which were sponsored by industry and most of which used duloxetine. Further, few of the studies enrolled patients with osteoarthritis of the hip, none assessed medium- or long-term effects, and none stratified the participants for different types of pain (neuropathic-like or central or peripheral pain sensitization).

“My general impression is that there was a statistically significant difference found in favor of duloxetine and the antidepressants,” David J. Hunter, MBBS, PhD, MSc, of the University of Sydney, said after the presentation. “There is a real risk of harm, which I think is important to take into consideration, but at least for me as a clinician and in advising other clinicians, it’s one tool in our armamentarium. I think it’s really important to allow patients to make an informed decision about the potential benefit, the real risk of harm, and the fact that it is quite useful in some patients, and I use it in my clinical practice.”

Jeffrey N. Katz, MD, MS, of Brigham and Women’s Hospital in Boston, said he uses antidepressants in the same way in his practice and that other types of medications, such as TNF inhibitors, also carry risk of harm that may exceed that of antidepressants.

“I’ve had lots of people start duloxetine, and if they stop it, it’s usually because they just don’t tolerate it very well,” Dr. Katz said.

“We don’t want to throw too many things away,” Dr. Hunter added. “Our patients don’t necessarily have a lot of choices here from a pharmacologic perspective, so I think it’s one of those options that I want to keep in my tool kit, and that’s not necessarily going to change.”

The research did not involve outside funding, and Dr. Wluka reported having no industry disclosures. Disclosure information was unavailable for Dr. Katz and Dr. Hunter. The Congress was sponsored by the Osteoarthritis Research Society International.

DENVER – Using antidepressants to treat osteoarthritis pain can benefit some individuals but appears to have a clinically unimportant reduction in pain when looking at all patients who have tried them, according to a study presented at the OARSI 2023 World Congress. The review was also published in the Cochrane Database of Systematic Reviews in October 2022.

In terms of implications for clinical practice, the findings “seem to suggest there is a subgroup that is more likely to respond to antidepressants,” Anita Wluka, PhD, MBBS, a professor in the School of Public Health and Preventive Medicine at Monash University in Melbourne, told attendees. The findings also raise an important research question: “How can we identify the patient phenotype likely to benefit so we can [minimize the] risk of those adverse events and effects?”

Osteoarthritis pain is heterogeneous, and an estimated 30% of the pain is neuropathic-like, likely including central and peripheral sensitization, Dr. Wluka said. Given that antidepressants affect multiple sites along these pathways, multiple organizations have issued a conditional recommendation for duloxetine in their osteoarthritis guidelines, including OARSI, the European Alliance of Associations for Rheumatology, and the American College of Rheumatology.

The Cochrane Collaboration therefore conducted a systematic review and meta-analysis of research on the benefits and harms of using antidepressants to treat symptomatic knee and hip osteoarthritis. The review included studies through January 2021 whose participants had knee and/or hip osteoarthritis and which compared antidepressant therapy with placebo or another intervention for at least 6 weeks. The authors looked at seven outcomes: overall pain on a 0-10 scale, clinical response (at least a 50% reduction in 24‐hour mean pain), physical function using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life using the EQ-5D, the proportion of participants withdrawing because of adverse events, the proportion who experienced any adverse events, and the proportion who experienced serious adverse events.

The researchers considered a change on the pain scale of 0.5-1 points to be “slight to small,” a difference above 1 up to 2 to be “moderate,” and a difference greater than 2 points to be “large.” In assessing quality of life function on a scale of 0-100, a slight to small difference was 5-10, a moderate difference was 11-20, and a large difference was above 20.

Of the 18 articles the researchers identified for qualitative synthesis, 9 met the criteria for qualitative synthesis in the meta-analysis, including 7 studies only on the knee and 2 that included the knees and hips. All nine studies compared antidepressants with placebo, with or without NSAIDs. Most focused on serotonin and norepinephrine reuptake inhibitors (SNRIs) – six studies on duloxetine and one on milnacipran – while one included fluvoxamine and one included nortriptyline.

The trials included a combined 2,122 participants who were predominantly female with an average age range of 54-66. Trials ranged from 8 to 16 weeks. Five of the trials carried risk of attrition and reporting bias, and only one trial had low risk of bias across all domains.

In five trials with SNRIs and one trial with tricyclics (nortriptyline) totaling 1,904 participants, 45% of those receiving antidepressants had a clinical response, compared with 29% of patients who received placebo (risk ratio, 1.55; 95% CI, 1.31-1.92). This absolute improvement in pain occurred in 16% more participants taking antidepressants, giving a number needed to treat (NNT) of 6. Average improvement in WOMAC physical function was 10.5 points with placebo and 16.2 points with antidepressants, indicating a “small, clinically unimportant response,” the researchers concluded.

Withdrawals because of adverse events included 11% of the antidepressant group and 5% of the placebo group (RR, 2.15; 95% CI, 1.56-2.87), putting the NNT for a harmful outcome at 17.

For all nine trials together, however, the mean reduction in pain from antidepressants was 2.3 points, compared with 1.7 points with placebo, a statistically significant but ”clinically unimportant improvement,” the researchers concluded. Adverse events occurred in 64% of the antidepressant group, compared with 49% of the placebo group (RR, 1.27; 95% CI, 1.15-1.41), which put the NNT for a harmful outcome at 7. No significant difference in serious adverse events occurred between the groups.

The analysis was limited by the low number of trials, most of which were sponsored by industry and most of which used duloxetine. Further, few of the studies enrolled patients with osteoarthritis of the hip, none assessed medium- or long-term effects, and none stratified the participants for different types of pain (neuropathic-like or central or peripheral pain sensitization).

“My general impression is that there was a statistically significant difference found in favor of duloxetine and the antidepressants,” David J. Hunter, MBBS, PhD, MSc, of the University of Sydney, said after the presentation. “There is a real risk of harm, which I think is important to take into consideration, but at least for me as a clinician and in advising other clinicians, it’s one tool in our armamentarium. I think it’s really important to allow patients to make an informed decision about the potential benefit, the real risk of harm, and the fact that it is quite useful in some patients, and I use it in my clinical practice.”

Jeffrey N. Katz, MD, MS, of Brigham and Women’s Hospital in Boston, said he uses antidepressants in the same way in his practice and that other types of medications, such as TNF inhibitors, also carry risk of harm that may exceed that of antidepressants.

“I’ve had lots of people start duloxetine, and if they stop it, it’s usually because they just don’t tolerate it very well,” Dr. Katz said.

“We don’t want to throw too many things away,” Dr. Hunter added. “Our patients don’t necessarily have a lot of choices here from a pharmacologic perspective, so I think it’s one of those options that I want to keep in my tool kit, and that’s not necessarily going to change.”

The research did not involve outside funding, and Dr. Wluka reported having no industry disclosures. Disclosure information was unavailable for Dr. Katz and Dr. Hunter. The Congress was sponsored by the Osteoarthritis Research Society International.

Despite decades of research, there’s still considerable uncertainty about the comparative effectiveness and safety of analgesics for the treatment of acute low back pain, new research shows.

Higher-quality randomized controlled trials of head-to-head comparisons are needed, study investigator Michael A. Wewege, PhD candidate, research fellow, University of New South Wales and Neuroscience Research Australia, Sydney, said in an interview.

“Until then, doctors should use caution when prescribing analgesic medicines for adults with nonspecific acute low back pain. They should use this new evidence in line with their own expertise and the patient sitting in front of them when making any decision about a medication,” he added.

The findings were published online  in the BMJ. 
 

Poor quality evidence

Analgesics such as ibuprofen, acetaminophen, and codeine are widely used to treat nonspecific low-back pain, which is defined as pain lasting less than 6 weeks, but evidence for the comparative efficacy of these agents is limited.

To fill this knowledge gap, the researchers conducted a systematic review and analysis of controlled trials comparing analgesics with another analgesic, placebo, or no treatment in patients with acute, nonspecific low back pain.

The review involved 98 randomized controlled trials that included 15,134 adults (49% women) aged 30-60 years with pain duration ranging from 24 hours to 21 days. The median baseline pain intensity was 65 on a pain scale of 0-100.

Of the included trials, 39% were placebo controlled, 67% masked both participants and clinicians, and 41% reported industry sponsorship.

The studies compared an analgesic medicine with another analgesic, placebo, or no treatment comprised of usual care or being placed on a wait list.

Study medications, which had to be approved in the United States, Europe, or Australia, included nonsteroidal anti-inflammatory drugs, paracetamol, opioids, anticonvulsants, antidepressants, muscle relaxants, and corticosteroids.

These drugs were administered systemically as a single drug or in combination formulations, at any dose.

Researchers used a network meta-analysis, which combines direct and indirect information across a network of randomized clinical trials to estimate the comparative effectiveness of multiple treatments.

The primary outcomes were reductions in low back pain intensity (measured with a visual analogue scale), numerical rating scale or another ordinal scale, and safety as indicated by the number of participants who had any adverse event.

Investigators found several medications were associated with large reductions in pain intensity, compared with placebo, though with low or very low confidence.

Low or very low confidence was found for reduced pain intensity after treatment with tolperisone (mean difference, −26.1; 95% confidence interval, −34.0 to −18.2), aceclofenac plus tizanidine (mean difference, −26.1; 95% CI, −38.5 to −13.6), pregabalin (mean difference, −24.7; 95% CI, −34.6 to −14.7), and 14 other medicines, compared with placebo, the researchers report.

In addition, they found low or very low confidence for no difference between the effects of several of these medications.

Increased adverse events had moderate to very low confidence with tramadol (risk ratio, 2.6; 95% CI, 1.5-4.5), paracetamol plus sustained release tramadol (RR, 2.4; 95% CI, 1.5-3.8), baclofen (RR, 2.3; 95% CI, 1.5-3.4), and paracetamol plus tramadol (RR, 2.1; 95% CI, 1.3-3.4), compared with placebo, the investigators add.

“These medicines could increase the risk of adverse events, compared with other medicines with moderate to low confidence. Moderate to low confidence was also noted for secondary outcomes and secondary analysis of medicine classes,” the researchers note.

The review suggested 14 additional comparisons favored the treatment over placebo, all with very low confidence except for one with low confidence.

In the 68 trials that included the number of participants reporting an adverse event, there was moderate confidence for increased adverse events with the opioid tramadol (RR, 2.6; 95% CI, 1.5-4.5), paracetamol plus sustained release tramadol (RR, 2.4; 95% CI, 1.5-3.8), paracetamol plus tramadol (RR, 2.1; 95% CI, 1.3-3.4), and low confidence for baclofen (RR, 2.3; 1.5-3.4), compared with placebo.

The review also uncovered moderate to low confidence for secondary outcomes, which included low back-specific function, serious adverse events, and acceptability (number of participants who dropped out).
 

Unexpected findings

The new results were somewhat unexpected, said Mr. Wewege.

“When we set out to do this review, we envisioned the evidence would be a lot more comprehensive. We didn’t think it would be so disconnected and there would be so few trials looking at the different comparisons that would lead us to have low confidence in most of the findings.”

Various factors contributed to this low confidence, he said. One was the risk of bias – about 90% of trials had some concerns or high risk of bias. Another factor was the heterogeneity in effect estimates.

Most of the evidence is based on studies comparing different analgesics to placebo, Mr. Wewege noted. The lack of head-to-head drug comparisons is because “the easiest way to get a drug approved is just to demonstrate it’s better than placebo,” he said.

In addition to these new findings, clinicians should consider a medication’s availability, their own expertise, and patient preferences when selecting an analgesic, said Mr. Wewege. He noted most patients with acute low back pain get better within a few weeks without any intervention.

“Patients should be reassured that things will heal naturally and that they are not going to be in pain forever,” he said.
 

Determining optimal treatment is key

Chris Gilligan, MD, associate chief medical officer, Brigham and Women’s Hospital, and associate professor of anesthesia, Harvard Medical School, both in Boston, said determining which medications are optimal is “key,” as acute low back pain is very common and analgesics are used frequently.

The new review does provide information on which medications have the strongest evidence for pain reduction, said Dr. Gilligan. “On the one hand, it directionally points you towards certain medications, and even certain classes of medication, for comparative effectiveness.”

However, he said, the confidence for this effectiveness is low or very low, “so I wouldn’t overweight it.”

The data on adverse effects, where the confidence is mostly moderate to low, might have more of an influence on prescribing, he said.

“For example, there’s some indication tramadol may be more closely associated with adverse events in patients with acute low back pain and that would add to our caution about using tramadol; it’s not that we would never use it, but [we]would take that into account.”

Dr. Gilligan agrees clinicians should be cautious about prescribing analgesics for low back pain. One reason for being conservative in terms of treatments, he noted, is that “acute low back pain has a very favorable natural history.”

While clinical practice guidelines recommend nonpharmacologic therapies as first- and second-line treatment for acute, nonspecific low back pain, Dr. Gilligan noted that as with drugs, evidence for nondrug therapies also has low or very low confidence.

The study received funding from a 2020 Exercise Physiology Research (Consumables) Grant from the University of New South Wales, which was used to obtain translations of studies published in languages other than English.

Mr. Wewege was supported by a Postgraduate Scholarship from the National Health and Medical Research Council of Australia, a School of Medical Sciences Top-Up Scholarship from the University of New South Wales, and a PhD Supplementary Scholarship from Neuroscience Research Australia. Dr. Gilligan reports that he conducts clinical trials with companies and groups, including the National Institutes of Health related to medications, devices, and procedures for pain.

A version of this article first appeared on Medscape.com.

Despite decades of research, there’s still considerable uncertainty about the comparative effectiveness and safety of analgesics for the treatment of acute low back pain, new research shows.

Higher-quality randomized controlled trials of head-to-head comparisons are needed, study investigator Michael A. Wewege, PhD candidate, research fellow, University of New South Wales and Neuroscience Research Australia, Sydney, said in an interview.

“Until then, doctors should use caution when prescribing analgesic medicines for adults with nonspecific acute low back pain. They should use this new evidence in line with their own expertise and the patient sitting in front of them when making any decision about a medication,” he added.

The findings were published online  in the BMJ. 
 

Poor quality evidence

Analgesics such as ibuprofen, acetaminophen, and codeine are widely used to treat nonspecific low-back pain, which is defined as pain lasting less than 6 weeks, but evidence for the comparative efficacy of these agents is limited.

To fill this knowledge gap, the researchers conducted a systematic review and analysis of controlled trials comparing analgesics with another analgesic, placebo, or no treatment in patients with acute, nonspecific low back pain.

The review involved 98 randomized controlled trials that included 15,134 adults (49% women) aged 30-60 years with pain duration ranging from 24 hours to 21 days. The median baseline pain intensity was 65 on a pain scale of 0-100.

Of the included trials, 39% were placebo controlled, 67% masked both participants and clinicians, and 41% reported industry sponsorship.

The studies compared an analgesic medicine with another analgesic, placebo, or no treatment comprised of usual care or being placed on a wait list.

Study medications, which had to be approved in the United States, Europe, or Australia, included nonsteroidal anti-inflammatory drugs, paracetamol, opioids, anticonvulsants, antidepressants, muscle relaxants, and corticosteroids.

These drugs were administered systemically as a single drug or in combination formulations, at any dose.

Researchers used a network meta-analysis, which combines direct and indirect information across a network of randomized clinical trials to estimate the comparative effectiveness of multiple treatments.

The primary outcomes were reductions in low back pain intensity (measured with a visual analogue scale), numerical rating scale or another ordinal scale, and safety as indicated by the number of participants who had any adverse event.

Investigators found several medications were associated with large reductions in pain intensity, compared with placebo, though with low or very low confidence.

Low or very low confidence was found for reduced pain intensity after treatment with tolperisone (mean difference, −26.1; 95% confidence interval, −34.0 to −18.2), aceclofenac plus tizanidine (mean difference, −26.1; 95% CI, −38.5 to −13.6), pregabalin (mean difference, −24.7; 95% CI, −34.6 to −14.7), and 14 other medicines, compared with placebo, the researchers report.

In addition, they found low or very low confidence for no difference between the effects of several of these medications.

Increased adverse events had moderate to very low confidence with tramadol (risk ratio, 2.6; 95% CI, 1.5-4.5), paracetamol plus sustained release tramadol (RR, 2.4; 95% CI, 1.5-3.8), baclofen (RR, 2.3; 95% CI, 1.5-3.4), and paracetamol plus tramadol (RR, 2.1; 95% CI, 1.3-3.4), compared with placebo, the investigators add.

“These medicines could increase the risk of adverse events, compared with other medicines with moderate to low confidence. Moderate to low confidence was also noted for secondary outcomes and secondary analysis of medicine classes,” the researchers note.

The review suggested 14 additional comparisons favored the treatment over placebo, all with very low confidence except for one with low confidence.

In the 68 trials that included the number of participants reporting an adverse event, there was moderate confidence for increased adverse events with the opioid tramadol (RR, 2.6; 95% CI, 1.5-4.5), paracetamol plus sustained release tramadol (RR, 2.4; 95% CI, 1.5-3.8), paracetamol plus tramadol (RR, 2.1; 95% CI, 1.3-3.4), and low confidence for baclofen (RR, 2.3; 1.5-3.4), compared with placebo.

The review also uncovered moderate to low confidence for secondary outcomes, which included low back-specific function, serious adverse events, and acceptability (number of participants who dropped out).
 

Unexpected findings

The new results were somewhat unexpected, said Mr. Wewege.

“When we set out to do this review, we envisioned the evidence would be a lot more comprehensive. We didn’t think it would be so disconnected and there would be so few trials looking at the different comparisons that would lead us to have low confidence in most of the findings.”

Various factors contributed to this low confidence, he said. One was the risk of bias – about 90% of trials had some concerns or high risk of bias. Another factor was the heterogeneity in effect estimates.

Most of the evidence is based on studies comparing different analgesics to placebo, Mr. Wewege noted. The lack of head-to-head drug comparisons is because “the easiest way to get a drug approved is just to demonstrate it’s better than placebo,” he said.

In addition to these new findings, clinicians should consider a medication’s availability, their own expertise, and patient preferences when selecting an analgesic, said Mr. Wewege. He noted most patients with acute low back pain get better within a few weeks without any intervention.

“Patients should be reassured that things will heal naturally and that they are not going to be in pain forever,” he said.
 

Determining optimal treatment is key

Chris Gilligan, MD, associate chief medical officer, Brigham and Women’s Hospital, and associate professor of anesthesia, Harvard Medical School, both in Boston, said determining which medications are optimal is “key,” as acute low back pain is very common and analgesics are used frequently.

The new review does provide information on which medications have the strongest evidence for pain reduction, said Dr. Gilligan. “On the one hand, it directionally points you towards certain medications, and even certain classes of medication, for comparative effectiveness.”

However, he said, the confidence for this effectiveness is low or very low, “so I wouldn’t overweight it.”

The data on adverse effects, where the confidence is mostly moderate to low, might have more of an influence on prescribing, he said.

“For example, there’s some indication tramadol may be more closely associated with adverse events in patients with acute low back pain and that would add to our caution about using tramadol; it’s not that we would never use it, but [we]would take that into account.”

Dr. Gilligan agrees clinicians should be cautious about prescribing analgesics for low back pain. One reason for being conservative in terms of treatments, he noted, is that “acute low back pain has a very favorable natural history.”

While clinical practice guidelines recommend nonpharmacologic therapies as first- and second-line treatment for acute, nonspecific low back pain, Dr. Gilligan noted that as with drugs, evidence for nondrug therapies also has low or very low confidence.

The study received funding from a 2020 Exercise Physiology Research (Consumables) Grant from the University of New South Wales, which was used to obtain translations of studies published in languages other than English.

Mr. Wewege was supported by a Postgraduate Scholarship from the National Health and Medical Research Council of Australia, a School of Medical Sciences Top-Up Scholarship from the University of New South Wales, and a PhD Supplementary Scholarship from Neuroscience Research Australia. Dr. Gilligan reports that he conducts clinical trials with companies and groups, including the National Institutes of Health related to medications, devices, and procedures for pain.

A version of this article first appeared on Medscape.com.

Despite decades of research, there’s still considerable uncertainty about the comparative effectiveness and safety of analgesics for the treatment of acute low back pain, new research shows.

Higher-quality randomized controlled trials of head-to-head comparisons are needed, study investigator Michael A. Wewege, PhD candidate, research fellow, University of New South Wales and Neuroscience Research Australia, Sydney, said in an interview.

“Until then, doctors should use caution when prescribing analgesic medicines for adults with nonspecific acute low back pain. They should use this new evidence in line with their own expertise and the patient sitting in front of them when making any decision about a medication,” he added.

The findings were published online  in the BMJ. 
 

Poor quality evidence

Analgesics such as ibuprofen, acetaminophen, and codeine are widely used to treat nonspecific low-back pain, which is defined as pain lasting less than 6 weeks, but evidence for the comparative efficacy of these agents is limited.

To fill this knowledge gap, the researchers conducted a systematic review and analysis of controlled trials comparing analgesics with another analgesic, placebo, or no treatment in patients with acute, nonspecific low back pain.

The review involved 98 randomized controlled trials that included 15,134 adults (49% women) aged 30-60 years with pain duration ranging from 24 hours to 21 days. The median baseline pain intensity was 65 on a pain scale of 0-100.

Of the included trials, 39% were placebo controlled, 67% masked both participants and clinicians, and 41% reported industry sponsorship.

The studies compared an analgesic medicine with another analgesic, placebo, or no treatment comprised of usual care or being placed on a wait list.

Study medications, which had to be approved in the United States, Europe, or Australia, included nonsteroidal anti-inflammatory drugs, paracetamol, opioids, anticonvulsants, antidepressants, muscle relaxants, and corticosteroids.

These drugs were administered systemically as a single drug or in combination formulations, at any dose.

Researchers used a network meta-analysis, which combines direct and indirect information across a network of randomized clinical trials to estimate the comparative effectiveness of multiple treatments.

The primary outcomes were reductions in low back pain intensity (measured with a visual analogue scale), numerical rating scale or another ordinal scale, and safety as indicated by the number of participants who had any adverse event.

Investigators found several medications were associated with large reductions in pain intensity, compared with placebo, though with low or very low confidence.

Low or very low confidence was found for reduced pain intensity after treatment with tolperisone (mean difference, −26.1; 95% confidence interval, −34.0 to −18.2), aceclofenac plus tizanidine (mean difference, −26.1; 95% CI, −38.5 to −13.6), pregabalin (mean difference, −24.7; 95% CI, −34.6 to −14.7), and 14 other medicines, compared with placebo, the researchers report.

In addition, they found low or very low confidence for no difference between the effects of several of these medications.

Increased adverse events had moderate to very low confidence with tramadol (risk ratio, 2.6; 95% CI, 1.5-4.5), paracetamol plus sustained release tramadol (RR, 2.4; 95% CI, 1.5-3.8), baclofen (RR, 2.3; 95% CI, 1.5-3.4), and paracetamol plus tramadol (RR, 2.1; 95% CI, 1.3-3.4), compared with placebo, the investigators add.

“These medicines could increase the risk of adverse events, compared with other medicines with moderate to low confidence. Moderate to low confidence was also noted for secondary outcomes and secondary analysis of medicine classes,” the researchers note.

The review suggested 14 additional comparisons favored the treatment over placebo, all with very low confidence except for one with low confidence.

In the 68 trials that included the number of participants reporting an adverse event, there was moderate confidence for increased adverse events with the opioid tramadol (RR, 2.6; 95% CI, 1.5-4.5), paracetamol plus sustained release tramadol (RR, 2.4; 95% CI, 1.5-3.8), paracetamol plus tramadol (RR, 2.1; 95% CI, 1.3-3.4), and low confidence for baclofen (RR, 2.3; 1.5-3.4), compared with placebo.

The review also uncovered moderate to low confidence for secondary outcomes, which included low back-specific function, serious adverse events, and acceptability (number of participants who dropped out).
 

Unexpected findings

The new results were somewhat unexpected, said Mr. Wewege.

“When we set out to do this review, we envisioned the evidence would be a lot more comprehensive. We didn’t think it would be so disconnected and there would be so few trials looking at the different comparisons that would lead us to have low confidence in most of the findings.”

Various factors contributed to this low confidence, he said. One was the risk of bias – about 90% of trials had some concerns or high risk of bias. Another factor was the heterogeneity in effect estimates.

Most of the evidence is based on studies comparing different analgesics to placebo, Mr. Wewege noted. The lack of head-to-head drug comparisons is because “the easiest way to get a drug approved is just to demonstrate it’s better than placebo,” he said.

In addition to these new findings, clinicians should consider a medication’s availability, their own expertise, and patient preferences when selecting an analgesic, said Mr. Wewege. He noted most patients with acute low back pain get better within a few weeks without any intervention.

“Patients should be reassured that things will heal naturally and that they are not going to be in pain forever,” he said.
 

Determining optimal treatment is key

Chris Gilligan, MD, associate chief medical officer, Brigham and Women’s Hospital, and associate professor of anesthesia, Harvard Medical School, both in Boston, said determining which medications are optimal is “key,” as acute low back pain is very common and analgesics are used frequently.

The new review does provide information on which medications have the strongest evidence for pain reduction, said Dr. Gilligan. “On the one hand, it directionally points you towards certain medications, and even certain classes of medication, for comparative effectiveness.”

However, he said, the confidence for this effectiveness is low or very low, “so I wouldn’t overweight it.”

The data on adverse effects, where the confidence is mostly moderate to low, might have more of an influence on prescribing, he said.

“For example, there’s some indication tramadol may be more closely associated with adverse events in patients with acute low back pain and that would add to our caution about using tramadol; it’s not that we would never use it, but [we]would take that into account.”

Dr. Gilligan agrees clinicians should be cautious about prescribing analgesics for low back pain. One reason for being conservative in terms of treatments, he noted, is that “acute low back pain has a very favorable natural history.”

While clinical practice guidelines recommend nonpharmacologic therapies as first- and second-line treatment for acute, nonspecific low back pain, Dr. Gilligan noted that as with drugs, evidence for nondrug therapies also has low or very low confidence.

The study received funding from a 2020 Exercise Physiology Research (Consumables) Grant from the University of New South Wales, which was used to obtain translations of studies published in languages other than English.

Mr. Wewege was supported by a Postgraduate Scholarship from the National Health and Medical Research Council of Australia, a School of Medical Sciences Top-Up Scholarship from the University of New South Wales, and a PhD Supplementary Scholarship from Neuroscience Research Australia. Dr. Gilligan reports that he conducts clinical trials with companies and groups, including the National Institutes of Health related to medications, devices, and procedures for pain.

A version of this article first appeared on Medscape.com.

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

Even after endorsement in updated guidelines, hydroxyurea is substantially underused in youth with sickle cell anemia (SCA), new research indicates.

SCA can lead to pain crises, stroke, and early death. Hydroxyurea, an oral disease-modifying medication, can reduce the complications.

In 2014, the National Heart, Lung, and Blood Institute published revised guidelines that hydroxyurea should be offered as the primary therapy to all patients who were at least 9 months old and living with SCA, regardless of disease severity.
 

Low uptake even after guideline revision

Yet, a research team led by Sarah L. Reeves, PhD, MPH, with the Child Health Evaluation and Research Center at University of Michigan, Ann Arbor, found in their study of use in two sample states – Michigan and New York – that hydroxyurea use was low in children and adolescents enrolled in Medicaid and increased only slightly in Michigan and not at all in New York after the guideline revision.

After the guidelines were updated, the researchers observed that, on average, children and adolescents were getting the medication less than a third of the days in a year (32% maximum in the year with the highest uptake). The data were gathered from a study population that included 4,302 youths aged 1-17 years with SCA.

Findings were published online in JAMA Network Open.
 

‘A national issue’

Russell Ware, MD, PhD, chair of hematology translational research at Cincinnati Children’s Hospital, who was not part of the research, says that though data were gathered from Michigan and New York, “this is a national issue.”

Dr. Ware says the main problem is the way the health system describes the importance of hydroxyurea.

“There needs to be a realization that hydroxyurea is the standard of care for children with sickle cell anemia. It’s not just something they should take when they’re sick,” Dr. Ware said.

He added, “If you have diabetes, should you only take insulin if you’re really sick and hospitalized with a diabetic coma? Of course not.”

He said often providers aren’t giving a clear and consistent message to families.

“They’re not all sure they want to recommend it. They might offer it,” Dr. Ware said, which jeopardizes uptake. “Providers need to be more committed to it. They need to know how to dose it.”
 

Bad rap from past indications

Dr. Ware says hydroxyurea also gets a bad rap from use decades ago as a chemotherapeutic agent for cancer and then as an anti-HIV medication.

Now it’s used in a completely different way with SCA, but the fear of the association lingers.

“This label as a chemotherapeutic agent has really dogged hydroxyurea,” he said. “It’s a completely different mechanism. It’s a different dose. It’s a different purpose.”

The message to families should be more direct, he says: “Your child has sickle cell anemia and needs to be on disease-modifying therapy because this is a life-threatening disease.”

The underuse of this drug is particularly ironic, he says, as each capsule, taken daily, “costs about fifty cents.”
 

Medicaid support critical

Authors conclude that multifaceted interventions may be necessary to increase the number of filled prescriptions and use. They also point out that the interventions rely on states’ Medicaid support regarding hydroxyurea use. From 70% to 90% of young people with SCA are covered by Medicaid at some point, the researchers write.

“Variation may exist across states, as well as within states, in the coverage of hydroxyurea, outpatient visits, and associated lab monitoring,” they note.

The authors point to interventions in clinical trials that have had some success in hydroxyurea use.

Creary et al., for example, found that electronic directly observed therapy was associated with high adherence. That involved sending daily texts to patients to take hydroxyurea and patients recording and sending daily videos that show they took the medication.

The authors add that incorporating clinical pharmacists into the care team to provide education and support for families has been shown to be associated with successful outcomes for other chronic conditions – this approach may be particularly well suited to hydroxyurea given that this medication requires significant dosage monitoring.

Dr. Ware, however, says that solutions should focus on the health system more clearly communicating that hydroxyurea is the standard of care for all kids with SCA.

“We need to dispel these myths and these labels that are unfairly attributed to it. Then we’d probably do a lot better,” he said.

He added that children with SCA, “are a marginalized, neglected population of patients historically,” and addressing social determinants of health is also important in getting better uptake.

“Our pharmacy, for example, ships the drug to the families if they’re just getting a refill rather than making them drive all the way in,” Dr. Ware says.

Dr. Ware said given the interruption in doctor/patient relationships in the pandemic, the poor uptake of hydroxyurea could be even worse now.

The work was funded by the Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute. Coauthor Dr. Green was the principal investigator of an NIH-funded trial of hydroxyurea in Uganda with a study drug provided by Siklos. No other author disclosures were reported. In addition to receiving research funding from the National Institutes of Health, Dr. Ware receives research donations from Bristol Myers Squibb, Addmedica, and Hemex Health. He is a medical adviser for Nova Laboratories and Octapharma, and serves on Data Safety Monitoring Boards for Novartis and Editas.
 

Even after endorsement in updated guidelines, hydroxyurea is substantially underused in youth with sickle cell anemia (SCA), new research indicates.

SCA can lead to pain crises, stroke, and early death. Hydroxyurea, an oral disease-modifying medication, can reduce the complications.

In 2014, the National Heart, Lung, and Blood Institute published revised guidelines that hydroxyurea should be offered as the primary therapy to all patients who were at least 9 months old and living with SCA, regardless of disease severity.
 

Low uptake even after guideline revision

Yet, a research team led by Sarah L. Reeves, PhD, MPH, with the Child Health Evaluation and Research Center at University of Michigan, Ann Arbor, found in their study of use in two sample states – Michigan and New York – that hydroxyurea use was low in children and adolescents enrolled in Medicaid and increased only slightly in Michigan and not at all in New York after the guideline revision.

After the guidelines were updated, the researchers observed that, on average, children and adolescents were getting the medication less than a third of the days in a year (32% maximum in the year with the highest uptake). The data were gathered from a study population that included 4,302 youths aged 1-17 years with SCA.

Findings were published online in JAMA Network Open.
 

‘A national issue’

Russell Ware, MD, PhD, chair of hematology translational research at Cincinnati Children’s Hospital, who was not part of the research, says that though data were gathered from Michigan and New York, “this is a national issue.”

Dr. Ware says the main problem is the way the health system describes the importance of hydroxyurea.

“There needs to be a realization that hydroxyurea is the standard of care for children with sickle cell anemia. It’s not just something they should take when they’re sick,” Dr. Ware said.

He added, “If you have diabetes, should you only take insulin if you’re really sick and hospitalized with a diabetic coma? Of course not.”

He said often providers aren’t giving a clear and consistent message to families.

“They’re not all sure they want to recommend it. They might offer it,” Dr. Ware said, which jeopardizes uptake. “Providers need to be more committed to it. They need to know how to dose it.”
 

Bad rap from past indications

Dr. Ware says hydroxyurea also gets a bad rap from use decades ago as a chemotherapeutic agent for cancer and then as an anti-HIV medication.

Now it’s used in a completely different way with SCA, but the fear of the association lingers.

“This label as a chemotherapeutic agent has really dogged hydroxyurea,” he said. “It’s a completely different mechanism. It’s a different dose. It’s a different purpose.”

The message to families should be more direct, he says: “Your child has sickle cell anemia and needs to be on disease-modifying therapy because this is a life-threatening disease.”

The underuse of this drug is particularly ironic, he says, as each capsule, taken daily, “costs about fifty cents.”
 

Medicaid support critical

Authors conclude that multifaceted interventions may be necessary to increase the number of filled prescriptions and use. They also point out that the interventions rely on states’ Medicaid support regarding hydroxyurea use. From 70% to 90% of young people with SCA are covered by Medicaid at some point, the researchers write.

“Variation may exist across states, as well as within states, in the coverage of hydroxyurea, outpatient visits, and associated lab monitoring,” they note.

The authors point to interventions in clinical trials that have had some success in hydroxyurea use.

Creary et al., for example, found that electronic directly observed therapy was associated with high adherence. That involved sending daily texts to patients to take hydroxyurea and patients recording and sending daily videos that show they took the medication.

The authors add that incorporating clinical pharmacists into the care team to provide education and support for families has been shown to be associated with successful outcomes for other chronic conditions – this approach may be particularly well suited to hydroxyurea given that this medication requires significant dosage monitoring.

Dr. Ware, however, says that solutions should focus on the health system more clearly communicating that hydroxyurea is the standard of care for all kids with SCA.

“We need to dispel these myths and these labels that are unfairly attributed to it. Then we’d probably do a lot better,” he said.

He added that children with SCA, “are a marginalized, neglected population of patients historically,” and addressing social determinants of health is also important in getting better uptake.

“Our pharmacy, for example, ships the drug to the families if they’re just getting a refill rather than making them drive all the way in,” Dr. Ware says.

Dr. Ware said given the interruption in doctor/patient relationships in the pandemic, the poor uptake of hydroxyurea could be even worse now.

The work was funded by the Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute. Coauthor Dr. Green was the principal investigator of an NIH-funded trial of hydroxyurea in Uganda with a study drug provided by Siklos. No other author disclosures were reported. In addition to receiving research funding from the National Institutes of Health, Dr. Ware receives research donations from Bristol Myers Squibb, Addmedica, and Hemex Health. He is a medical adviser for Nova Laboratories and Octapharma, and serves on Data Safety Monitoring Boards for Novartis and Editas.
 

Even after endorsement in updated guidelines, hydroxyurea is substantially underused in youth with sickle cell anemia (SCA), new research indicates.

SCA can lead to pain crises, stroke, and early death. Hydroxyurea, an oral disease-modifying medication, can reduce the complications.

In 2014, the National Heart, Lung, and Blood Institute published revised guidelines that hydroxyurea should be offered as the primary therapy to all patients who were at least 9 months old and living with SCA, regardless of disease severity.
 

Low uptake even after guideline revision

Yet, a research team led by Sarah L. Reeves, PhD, MPH, with the Child Health Evaluation and Research Center at University of Michigan, Ann Arbor, found in their study of use in two sample states – Michigan and New York – that hydroxyurea use was low in children and adolescents enrolled in Medicaid and increased only slightly in Michigan and not at all in New York after the guideline revision.

After the guidelines were updated, the researchers observed that, on average, children and adolescents were getting the medication less than a third of the days in a year (32% maximum in the year with the highest uptake). The data were gathered from a study population that included 4,302 youths aged 1-17 years with SCA.

Findings were published online in JAMA Network Open.
 

‘A national issue’

Russell Ware, MD, PhD, chair of hematology translational research at Cincinnati Children’s Hospital, who was not part of the research, says that though data were gathered from Michigan and New York, “this is a national issue.”

Dr. Ware says the main problem is the way the health system describes the importance of hydroxyurea.

“There needs to be a realization that hydroxyurea is the standard of care for children with sickle cell anemia. It’s not just something they should take when they’re sick,” Dr. Ware said.

He added, “If you have diabetes, should you only take insulin if you’re really sick and hospitalized with a diabetic coma? Of course not.”

He said often providers aren’t giving a clear and consistent message to families.

“They’re not all sure they want to recommend it. They might offer it,” Dr. Ware said, which jeopardizes uptake. “Providers need to be more committed to it. They need to know how to dose it.”
 

Bad rap from past indications

Dr. Ware says hydroxyurea also gets a bad rap from use decades ago as a chemotherapeutic agent for cancer and then as an anti-HIV medication.

Now it’s used in a completely different way with SCA, but the fear of the association lingers.

“This label as a chemotherapeutic agent has really dogged hydroxyurea,” he said. “It’s a completely different mechanism. It’s a different dose. It’s a different purpose.”

The message to families should be more direct, he says: “Your child has sickle cell anemia and needs to be on disease-modifying therapy because this is a life-threatening disease.”

The underuse of this drug is particularly ironic, he says, as each capsule, taken daily, “costs about fifty cents.”
 

Medicaid support critical

Authors conclude that multifaceted interventions may be necessary to increase the number of filled prescriptions and use. They also point out that the interventions rely on states’ Medicaid support regarding hydroxyurea use. From 70% to 90% of young people with SCA are covered by Medicaid at some point, the researchers write.

“Variation may exist across states, as well as within states, in the coverage of hydroxyurea, outpatient visits, and associated lab monitoring,” they note.

The authors point to interventions in clinical trials that have had some success in hydroxyurea use.

Creary et al., for example, found that electronic directly observed therapy was associated with high adherence. That involved sending daily texts to patients to take hydroxyurea and patients recording and sending daily videos that show they took the medication.

The authors add that incorporating clinical pharmacists into the care team to provide education and support for families has been shown to be associated with successful outcomes for other chronic conditions – this approach may be particularly well suited to hydroxyurea given that this medication requires significant dosage monitoring.

Dr. Ware, however, says that solutions should focus on the health system more clearly communicating that hydroxyurea is the standard of care for all kids with SCA.

“We need to dispel these myths and these labels that are unfairly attributed to it. Then we’d probably do a lot better,” he said.

He added that children with SCA, “are a marginalized, neglected population of patients historically,” and addressing social determinants of health is also important in getting better uptake.

“Our pharmacy, for example, ships the drug to the families if they’re just getting a refill rather than making them drive all the way in,” Dr. Ware says.

Dr. Ware said given the interruption in doctor/patient relationships in the pandemic, the poor uptake of hydroxyurea could be even worse now.

The work was funded by the Agency for Healthcare Research and Quality and National Heart, Lung, and Blood Institute. Coauthor Dr. Green was the principal investigator of an NIH-funded trial of hydroxyurea in Uganda with a study drug provided by Siklos. No other author disclosures were reported. In addition to receiving research funding from the National Institutes of Health, Dr. Ware receives research donations from Bristol Myers Squibb, Addmedica, and Hemex Health. He is a medical adviser for Nova Laboratories and Octapharma, and serves on Data Safety Monitoring Boards for Novartis and Editas.
 

Urine drug testing can be valuable for monitoring patients undergoing treatment with buprenorphine for opioid use disorder (OUD). However, some patients alter their test results by adding buprenorphine directly to their urine sample to imply adherence, a new study shows.

In the study, nearly 2% of all urine drug test specimens analyzed were suggestive of spiking and nearly 8% of patients had at least one specimen that was possibly spiked.

“I anticipate a much-needed increase” in the number of people gaining access to buprenorphine therapy, given elimination of the X waiver, first author Jarratt D. Pytell, MD, with University of Colorado at Denver, Aurora, said in a statement.

“New prescribers of buprenorphine will need to learn how to conduct the increasingly complex initiation of treatment and then gauge whether it is successful or not,” added Dr. Pytell, a general internist and addiction medicine specialist.

“Spiking suggests that treatment is not working – especially in patients continuing illicit drug use. Detecting spiking allows clinicians to adjust or intensify the treatment plan,” Dr. Pytell said in an interview.

The study was published online in JAMA Psychiatry.
 

A sign of elevated patient risk

In a cross-sectional study using Millennium Health’s proprietary urine drug test (UDT) database, researchers analyzed 507,735 urine specimens from 58,476 OUD patients collected between January 2017 and April 2022.

A total of 9546 (1.9%) specimens from 4,550 patients (7.6%) were suggestive of spiking.

UDT specimens suggestive of spiking had two times the odds of being positive for other opioids (fentanyl or heroin), compared with opioid negative samples.

UDT specimens obtained from primary care clinics, from patients aged 35-44 years, and from patients living in the South Atlantic region of the United States were also more likely to be suggestive of buprenorphine spiking.

“Our study demonstrated that a buprenorphine to norbuprenorphine ratio of less than 0.02 indicates the possibility of spiking,” Dr. Pytell said in an interview.

“Nevertheless, it is important to note that this cutoff is not a definitive standard and further controlled studies are necessary to determine its predictive value for spiking. But recognizing possible spiking is very important since it demonstrates a point of elevated risk for the patient and the treatment approach should be reconsidered,” Dr. Pytell said.

“At Millennium Health, we have been tracking the enormity of the drug use crisis. This study suggests that spiking is an important patient safety issue, and it is not uncommon,” study coauthor Eric Dawson, PharmD, vice president of clinical affairs, Millennium Health, said in a statement.

“Detection of spiking requires definitive drug testing. Immunoassay-based, point-of-care tests cannot detect spiking because they are generally incapable of quantitative analysis and differentiating buprenorphine from norbuprenorphine,” Dr. Dawson said.
 

Best practices?

“We need to develop best practices specific for this situation where a patient has added buprenorphine to the urine drug test specimen,” said Dr. Pytell.

“As with all unexpected findings, it is crucial for clinicians to approach this finding in a nonjudgmental manner and work with the patient to understand what might have motivated them to alter their urine specimen,” he added.

Dr. Pytell said a common reaction for clinicians might be to discontinue treatment. However, this is actually a time to try and engage with the patient.

“Clinicians should work collaboratively with patients to identify potential reasons for spiking and determine what changes may need to be made to better support the patient’s recovery,” Dr. Pytell said.

“This could include more frequent monitoring or referral to a higher level of care. In addition, clinicians should be aware that patients who engage in spiking may be experiencing other challenges that impact their ability to adhere to treatment, such as inadequate housing, mental health issues, or financial strain. Addressing these underlying issues may help patients overcome barriers to treatment adherence and reduce the likelihood of future spiking,” Dr. Pytell said.

This study was supported by Millennium Health. The authors have no relevant disclosures.

A version of this article first appeared on Medscape.com.

Urine drug testing can be valuable for monitoring patients undergoing treatment with buprenorphine for opioid use disorder (OUD). However, some patients alter their test results by adding buprenorphine directly to their urine sample to imply adherence, a new study shows.

In the study, nearly 2% of all urine drug test specimens analyzed were suggestive of spiking and nearly 8% of patients had at least one specimen that was possibly spiked.

“I anticipate a much-needed increase” in the number of people gaining access to buprenorphine therapy, given elimination of the X waiver, first author Jarratt D. Pytell, MD, with University of Colorado at Denver, Aurora, said in a statement.

“New prescribers of buprenorphine will need to learn how to conduct the increasingly complex initiation of treatment and then gauge whether it is successful or not,” added Dr. Pytell, a general internist and addiction medicine specialist.

“Spiking suggests that treatment is not working – especially in patients continuing illicit drug use. Detecting spiking allows clinicians to adjust or intensify the treatment plan,” Dr. Pytell said in an interview.

The study was published online in JAMA Psychiatry.
 

A sign of elevated patient risk

In a cross-sectional study using Millennium Health’s proprietary urine drug test (UDT) database, researchers analyzed 507,735 urine specimens from 58,476 OUD patients collected between January 2017 and April 2022.

A total of 9546 (1.9%) specimens from 4,550 patients (7.6%) were suggestive of spiking.

UDT specimens suggestive of spiking had two times the odds of being positive for other opioids (fentanyl or heroin), compared with opioid negative samples.

UDT specimens obtained from primary care clinics, from patients aged 35-44 years, and from patients living in the South Atlantic region of the United States were also more likely to be suggestive of buprenorphine spiking.

“Our study demonstrated that a buprenorphine to norbuprenorphine ratio of less than 0.02 indicates the possibility of spiking,” Dr. Pytell said in an interview.

“Nevertheless, it is important to note that this cutoff is not a definitive standard and further controlled studies are necessary to determine its predictive value for spiking. But recognizing possible spiking is very important since it demonstrates a point of elevated risk for the patient and the treatment approach should be reconsidered,” Dr. Pytell said.

“At Millennium Health, we have been tracking the enormity of the drug use crisis. This study suggests that spiking is an important patient safety issue, and it is not uncommon,” study coauthor Eric Dawson, PharmD, vice president of clinical affairs, Millennium Health, said in a statement.

“Detection of spiking requires definitive drug testing. Immunoassay-based, point-of-care tests cannot detect spiking because they are generally incapable of quantitative analysis and differentiating buprenorphine from norbuprenorphine,” Dr. Dawson said.
 

Best practices?

“We need to develop best practices specific for this situation where a patient has added buprenorphine to the urine drug test specimen,” said Dr. Pytell.

“As with all unexpected findings, it is crucial for clinicians to approach this finding in a nonjudgmental manner and work with the patient to understand what might have motivated them to alter their urine specimen,” he added.

Dr. Pytell said a common reaction for clinicians might be to discontinue treatment. However, this is actually a time to try and engage with the patient.

“Clinicians should work collaboratively with patients to identify potential reasons for spiking and determine what changes may need to be made to better support the patient’s recovery,” Dr. Pytell said.

“This could include more frequent monitoring or referral to a higher level of care. In addition, clinicians should be aware that patients who engage in spiking may be experiencing other challenges that impact their ability to adhere to treatment, such as inadequate housing, mental health issues, or financial strain. Addressing these underlying issues may help patients overcome barriers to treatment adherence and reduce the likelihood of future spiking,” Dr. Pytell said.

This study was supported by Millennium Health. The authors have no relevant disclosures.

A version of this article first appeared on Medscape.com.

Urine drug testing can be valuable for monitoring patients undergoing treatment with buprenorphine for opioid use disorder (OUD). However, some patients alter their test results by adding buprenorphine directly to their urine sample to imply adherence, a new study shows.

In the study, nearly 2% of all urine drug test specimens analyzed were suggestive of spiking and nearly 8% of patients had at least one specimen that was possibly spiked.

“I anticipate a much-needed increase” in the number of people gaining access to buprenorphine therapy, given elimination of the X waiver, first author Jarratt D. Pytell, MD, with University of Colorado at Denver, Aurora, said in a statement.

“New prescribers of buprenorphine will need to learn how to conduct the increasingly complex initiation of treatment and then gauge whether it is successful or not,” added Dr. Pytell, a general internist and addiction medicine specialist.

“Spiking suggests that treatment is not working – especially in patients continuing illicit drug use. Detecting spiking allows clinicians to adjust or intensify the treatment plan,” Dr. Pytell said in an interview.

The study was published online in JAMA Psychiatry.
 

A sign of elevated patient risk

In a cross-sectional study using Millennium Health’s proprietary urine drug test (UDT) database, researchers analyzed 507,735 urine specimens from 58,476 OUD patients collected between January 2017 and April 2022.

A total of 9546 (1.9%) specimens from 4,550 patients (7.6%) were suggestive of spiking.

UDT specimens suggestive of spiking had two times the odds of being positive for other opioids (fentanyl or heroin), compared with opioid negative samples.

UDT specimens obtained from primary care clinics, from patients aged 35-44 years, and from patients living in the South Atlantic region of the United States were also more likely to be suggestive of buprenorphine spiking.

“Our study demonstrated that a buprenorphine to norbuprenorphine ratio of less than 0.02 indicates the possibility of spiking,” Dr. Pytell said in an interview.

“Nevertheless, it is important to note that this cutoff is not a definitive standard and further controlled studies are necessary to determine its predictive value for spiking. But recognizing possible spiking is very important since it demonstrates a point of elevated risk for the patient and the treatment approach should be reconsidered,” Dr. Pytell said.

“At Millennium Health, we have been tracking the enormity of the drug use crisis. This study suggests that spiking is an important patient safety issue, and it is not uncommon,” study coauthor Eric Dawson, PharmD, vice president of clinical affairs, Millennium Health, said in a statement.

“Detection of spiking requires definitive drug testing. Immunoassay-based, point-of-care tests cannot detect spiking because they are generally incapable of quantitative analysis and differentiating buprenorphine from norbuprenorphine,” Dr. Dawson said.
 

Best practices?

“We need to develop best practices specific for this situation where a patient has added buprenorphine to the urine drug test specimen,” said Dr. Pytell.

“As with all unexpected findings, it is crucial for clinicians to approach this finding in a nonjudgmental manner and work with the patient to understand what might have motivated them to alter their urine specimen,” he added.

Dr. Pytell said a common reaction for clinicians might be to discontinue treatment. However, this is actually a time to try and engage with the patient.

“Clinicians should work collaboratively with patients to identify potential reasons for spiking and determine what changes may need to be made to better support the patient’s recovery,” Dr. Pytell said.

“This could include more frequent monitoring or referral to a higher level of care. In addition, clinicians should be aware that patients who engage in spiking may be experiencing other challenges that impact their ability to adhere to treatment, such as inadequate housing, mental health issues, or financial strain. Addressing these underlying issues may help patients overcome barriers to treatment adherence and reduce the likelihood of future spiking,” Dr. Pytell said.

This study was supported by Millennium Health. The authors have no relevant disclosures.

A version of this article first appeared on Medscape.com.

If a patient’s prostate-specific antigen (PSA) spikes 2 points in just 90 days, what is your first thought? This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter  painkillers are not helping, you’d think, “check for metastases,” right?

That patient was me in late January 2023.

As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.

With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.

To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6. 

But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit. 
 

The COVID effect

I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study² of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.

Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.

That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
 

COVID-19 pain

What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies³ have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.

To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.

References

1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.

2. Cinislioglu AE et al. Urology. 2022;159:16-21.

3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.

Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.

A version of this article first appeared on Medscape.com.

If a patient’s prostate-specific antigen (PSA) spikes 2 points in just 90 days, what is your first thought? This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter  painkillers are not helping, you’d think, “check for metastases,” right?

That patient was me in late January 2023.

As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.

With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.

To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6. 

But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit. 
 

The COVID effect

I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study² of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.

Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.

That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
 

COVID-19 pain

What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies³ have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.

To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.

References

1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.

2. Cinislioglu AE et al. Urology. 2022;159:16-21.

3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.

Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.

A version of this article first appeared on Medscape.com.

If a patient’s prostate-specific antigen (PSA) spikes 2 points in just 90 days, what is your first thought? This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter  painkillers are not helping, you’d think, “check for metastases,” right?

That patient was me in late January 2023.

As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.

With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.

To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6. 

But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit. 
 

The COVID effect

I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study² of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.

Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.

That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
 

COVID-19 pain

What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies³ have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.

To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.

References

1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.

2. Cinislioglu AE et al. Urology. 2022;159:16-21.

3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.

Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.

A version of this article first appeared on Medscape.com.

Patients who are already depressed before they receive a lung cancer diagnosis are more likely to have a worse overall survival (OS), and the driver for this may be inflammation, suggests a new study.

The findings underscore the importance of assessing and treating depression in patients with cancer, particularly given the high rate of depression among those with lung cancer versus other types of cancer, the investigators said.

The study involved 186 patients with newly diagnosed stage IV non–small cell lung cancer (NSCLC), of whom 35% had self-reported moderate to severe depressive symptoms.

Depression was reliably associated with lung-relevant systemic inflammation responses (SIRs), which included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and Advanced Lung Cancer Inflammation Index (ALI) score.

These SIRs were prognostic for 2-year OS.

Overall mortality at 2 years was 61%. Higher NLRs and PLRs and lower ALI scores all predicted worse OS (hazard ratio, 1.91, 2.08, and 0.53, respectively).

The findings were published online in PLoS ONE (2023 Feb 24.

“These patients with high levels of depression are at much higher risk for poor outcomes,” but the key finding was that patients with the highest depression levels were driving the relationship, lead author Barbara Andersen, PhD, professor of psychology at Ohio State University, Columbus, stated in a press release.

“It was patients with high depression levels who had strikingly higher inflammation levels, and that is what really drove the correlation we saw,” she explained.

For example, 56% of patients with no depression symptoms or only mild depression symptoms had a PLR above the cutoff for dangerous levels of inflammation, compared with 42% whose PLR was below the cutoff. However, among those with high depression levels, 77% and 23% had a PLR above and below the cutoff, respectively.

“These highly depressed patients were 1.3-3 times more likely to have high inflammation levels, even after controlling for other factors related to inflammation biomarker levels, including demographics and smoking status,” Dr. Andersen noted.

“Depression levels may be as important or even more important than other factors that have been associated with how people fare with lung cancer,” she suggested.

In a previous study, the team controlled for baseline depression and found that “the trajectory of depression from diagnosis through 2 years (18 assessments) predicted NSCLC patients’ survival (HR, 1.09), above and beyond baseline depression, sociodemographics, smoking status, cell type, and receipt of targeted treatments and immunotherapies.”

“Taken together, data support psychological, behavioral, and biologic toxicities of depression capable of influencing treatment response and/or survival,” they wrote.

“The results may help explain why a substantial portion of lung cancer patients fail to respond to new immunotherapy and targeted treatments that have led to significantly longer survival for many people with the disease,” Dr. Andersen said.

The investigators concluded that “intensive study of depression among patients with NSCLC, combined with measures of cell biology, inflammation, and immunity, is needed to extend these findings and discover their mechanisms, with the long-term aim to improve patients’ quality of life, treatment responses, and longevity.”

This study was funded by the Ohio State University Comprehensive Cancer Center and Pelotonia through grants to individual authors. Dr. Andersen reported having no relevant disclosures.

A version of this article first appeared on Medscape.com.

Patients who are already depressed before they receive a lung cancer diagnosis are more likely to have a worse overall survival (OS), and the driver for this may be inflammation, suggests a new study.

The findings underscore the importance of assessing and treating depression in patients with cancer, particularly given the high rate of depression among those with lung cancer versus other types of cancer, the investigators said.

The study involved 186 patients with newly diagnosed stage IV non–small cell lung cancer (NSCLC), of whom 35% had self-reported moderate to severe depressive symptoms.

Depression was reliably associated with lung-relevant systemic inflammation responses (SIRs), which included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and Advanced Lung Cancer Inflammation Index (ALI) score.

These SIRs were prognostic for 2-year OS.

Overall mortality at 2 years was 61%. Higher NLRs and PLRs and lower ALI scores all predicted worse OS (hazard ratio, 1.91, 2.08, and 0.53, respectively).

The findings were published online in PLoS ONE (2023 Feb 24.

“These patients with high levels of depression are at much higher risk for poor outcomes,” but the key finding was that patients with the highest depression levels were driving the relationship, lead author Barbara Andersen, PhD, professor of psychology at Ohio State University, Columbus, stated in a press release.

“It was patients with high depression levels who had strikingly higher inflammation levels, and that is what really drove the correlation we saw,” she explained.

For example, 56% of patients with no depression symptoms or only mild depression symptoms had a PLR above the cutoff for dangerous levels of inflammation, compared with 42% whose PLR was below the cutoff. However, among those with high depression levels, 77% and 23% had a PLR above and below the cutoff, respectively.

“These highly depressed patients were 1.3-3 times more likely to have high inflammation levels, even after controlling for other factors related to inflammation biomarker levels, including demographics and smoking status,” Dr. Andersen noted.

“Depression levels may be as important or even more important than other factors that have been associated with how people fare with lung cancer,” she suggested.

In a previous study, the team controlled for baseline depression and found that “the trajectory of depression from diagnosis through 2 years (18 assessments) predicted NSCLC patients’ survival (HR, 1.09), above and beyond baseline depression, sociodemographics, smoking status, cell type, and receipt of targeted treatments and immunotherapies.”

“Taken together, data support psychological, behavioral, and biologic toxicities of depression capable of influencing treatment response and/or survival,” they wrote.

“The results may help explain why a substantial portion of lung cancer patients fail to respond to new immunotherapy and targeted treatments that have led to significantly longer survival for many people with the disease,” Dr. Andersen said.

The investigators concluded that “intensive study of depression among patients with NSCLC, combined with measures of cell biology, inflammation, and immunity, is needed to extend these findings and discover their mechanisms, with the long-term aim to improve patients’ quality of life, treatment responses, and longevity.”

This study was funded by the Ohio State University Comprehensive Cancer Center and Pelotonia through grants to individual authors. Dr. Andersen reported having no relevant disclosures.

A version of this article first appeared on Medscape.com.

Patients who are already depressed before they receive a lung cancer diagnosis are more likely to have a worse overall survival (OS), and the driver for this may be inflammation, suggests a new study.

The findings underscore the importance of assessing and treating depression in patients with cancer, particularly given the high rate of depression among those with lung cancer versus other types of cancer, the investigators said.

The study involved 186 patients with newly diagnosed stage IV non–small cell lung cancer (NSCLC), of whom 35% had self-reported moderate to severe depressive symptoms.

Depression was reliably associated with lung-relevant systemic inflammation responses (SIRs), which included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and Advanced Lung Cancer Inflammation Index (ALI) score.

These SIRs were prognostic for 2-year OS.

Overall mortality at 2 years was 61%. Higher NLRs and PLRs and lower ALI scores all predicted worse OS (hazard ratio, 1.91, 2.08, and 0.53, respectively).

The findings were published online in PLoS ONE (2023 Feb 24.

“These patients with high levels of depression are at much higher risk for poor outcomes,” but the key finding was that patients with the highest depression levels were driving the relationship, lead author Barbara Andersen, PhD, professor of psychology at Ohio State University, Columbus, stated in a press release.

“It was patients with high depression levels who had strikingly higher inflammation levels, and that is what really drove the correlation we saw,” she explained.

For example, 56% of patients with no depression symptoms or only mild depression symptoms had a PLR above the cutoff for dangerous levels of inflammation, compared with 42% whose PLR was below the cutoff. However, among those with high depression levels, 77% and 23% had a PLR above and below the cutoff, respectively.

“These highly depressed patients were 1.3-3 times more likely to have high inflammation levels, even after controlling for other factors related to inflammation biomarker levels, including demographics and smoking status,” Dr. Andersen noted.

“Depression levels may be as important or even more important than other factors that have been associated with how people fare with lung cancer,” she suggested.

In a previous study, the team controlled for baseline depression and found that “the trajectory of depression from diagnosis through 2 years (18 assessments) predicted NSCLC patients’ survival (HR, 1.09), above and beyond baseline depression, sociodemographics, smoking status, cell type, and receipt of targeted treatments and immunotherapies.”

“Taken together, data support psychological, behavioral, and biologic toxicities of depression capable of influencing treatment response and/or survival,” they wrote.

“The results may help explain why a substantial portion of lung cancer patients fail to respond to new immunotherapy and targeted treatments that have led to significantly longer survival for many people with the disease,” Dr. Andersen said.

The investigators concluded that “intensive study of depression among patients with NSCLC, combined with measures of cell biology, inflammation, and immunity, is needed to extend these findings and discover their mechanisms, with the long-term aim to improve patients’ quality of life, treatment responses, and longevity.”

This study was funded by the Ohio State University Comprehensive Cancer Center and Pelotonia through grants to individual authors. Dr. Andersen reported having no relevant disclosures.

A version of this article first appeared on Medscape.com.