Pain

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.

Long-distance runners are often warned that they are wearing out their joints, but a new study found that running mileage, frequency, and pace were not associated with an increased risk of osteoarthritis.

Runners who had undergone knee or hip surgery or had a previous hip or knee injury that prevented running were most likely to have arthritis, researchers found. Family history of arthritis, higher body mass index (BMI), and older age were also associated with increased risk of the condition.

The study was presented at the American Academy of Orthopaedic Surgeons 2023 Annual Meeting.

It has generally been thought that running may increase risk of osteoarthritis because it puts more load on joints than walking or standing, noted Grace Hsiao-Wei Lo, MD, an assistant professor of immunology, allergy, and rheumatology at the Baylor College of Medicine, Houston, who was not involved with the work. Research in this area has yielded mixed results: A 2017 analysis of multiple studies found that competitive runners did have higher rates of arthritis than recreational runners, while another study conducted by Dr. Lo found that runners did not have an increased risk of knee osteoarthritis, compared with nonrunners. A 2018 study showed that marathon runners had lower instances of arthritis, compared with the general population.

In this new study, researchers surveyed 3,804 runners who participated in the 2019 or 2021 Chicago Marathon about their running history, average mileage per week, and average running pace. The survey also asked about known risk factors for osteoarthritis, including BMI, family history of arthritis, and past knee and hip injuries that prevented running.

Runners, on average, were about 44 years old and ran 27.9 miles per week. The largest proportion of respondents had completed 2-5 marathons (37.3%), around 21% of respondents had finished 6-10 marathons, and 17% were running their first marathon. Study participants had an average of 15 years of running experience, 1,892 reported a previous hip or knee injury, and 413 had undergone knee or hip surgery. Overall, 36.4% reported experiencing hip or knee pain in the past year, and 7.3% had been diagnosed with arthritis.

Researchers found that there was no association between the risk of osteoarthritis and weekly mileage, years spent running, number of marathons completed, or running pace. Respondents who had undergone knee or hip surgery had the highest risk of osteoarthritis (odds ratio, 5.85; P < .0001), followed by those with a history of knee or hip injuries that prevented running (OR, 5.04; P < .0001). Other identified risk factors were family history of arthritis (OR, 3.47; P < .0001), BMI (OR, 1.10; P < .0001), and older age (OR, 1.08; P < .0001).

The news should be encouraging for runners, said Matthew Hartwell, MD, an orthopedic surgeon at the University of California, San Francisco, who led the research. If someone does not have injuries or surgeries that keep them from running, “you can still continue to run,” he said. “There may not necessarily be this dose-response relationship where the more you run, the more you break down your knee or your hip.”

Still, 24.2% of runners reported that their physician had advised them to reduce their mileage or stop running altogether. Most runners (94.2%) said they planned to run another marathon.

“The results of this study are consistent with the experiences of many lifelong runners and observations of sports medicine professionals that osteoarthritis is not an inevitable consequence of distance running,” said Brett Toresdahl, MD, a sports medicine physician at the Hospital for Special Surgery in New York, who was not involved with the study.

Still, he emphasized that more research is necessary to understand whether running contributes to the risk of developing osteoarthritis. The participants in the study were current marathoners, he noted, so it is likely they have healthy joints that can tolerate running longer distances. “If there is a subset of people who have joints that are negatively affected by running, they wouldn’t likely be registering for a marathon,” he said in an email interview.

Dr. Lo added that comparing these marathoners to a group who did not run would help assess whether running can be harmful to joints. “To be fair, this is a challenging subject to study,” she said. “Osteoarthritis has a long natural history, and so it is difficult to evaluate this kind of question over many years of running and many years of evaluation of arthritis.”

While the research does not answer the question of whether running can lead to osteoarthritis, it helps show the need for long-term research on how running affects joints over time as well as one’s general health, Dr. Toresdahl noted. “I would not be surprised if future longitudinal research will come to the same conclusion that running for the majority of patients is a net benefit for overall health and at least net neutral for joint health when done in moderation,” he said.

Dr. Hartwell, Dr. Lo, and Dr. Toresdahl report no relevant financial relationships.

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

Long-distance runners are often warned that they are wearing out their joints, but a new study found that running mileage, frequency, and pace were not associated with an increased risk of osteoarthritis.

Runners who had undergone knee or hip surgery or had a previous hip or knee injury that prevented running were most likely to have arthritis, researchers found. Family history of arthritis, higher body mass index (BMI), and older age were also associated with increased risk of the condition.

The study was presented at the American Academy of Orthopaedic Surgeons 2023 Annual Meeting.

It has generally been thought that running may increase risk of osteoarthritis because it puts more load on joints than walking or standing, noted Grace Hsiao-Wei Lo, MD, an assistant professor of immunology, allergy, and rheumatology at the Baylor College of Medicine, Houston, who was not involved with the work. Research in this area has yielded mixed results: A 2017 analysis of multiple studies found that competitive runners did have higher rates of arthritis than recreational runners, while another study conducted by Dr. Lo found that runners did not have an increased risk of knee osteoarthritis, compared with nonrunners. A 2018 study showed that marathon runners had lower instances of arthritis, compared with the general population.

In this new study, researchers surveyed 3,804 runners who participated in the 2019 or 2021 Chicago Marathon about their running history, average mileage per week, and average running pace. The survey also asked about known risk factors for osteoarthritis, including BMI, family history of arthritis, and past knee and hip injuries that prevented running.

Runners, on average, were about 44 years old and ran 27.9 miles per week. The largest proportion of respondents had completed 2-5 marathons (37.3%), around 21% of respondents had finished 6-10 marathons, and 17% were running their first marathon. Study participants had an average of 15 years of running experience, 1,892 reported a previous hip or knee injury, and 413 had undergone knee or hip surgery. Overall, 36.4% reported experiencing hip or knee pain in the past year, and 7.3% had been diagnosed with arthritis.

Researchers found that there was no association between the risk of osteoarthritis and weekly mileage, years spent running, number of marathons completed, or running pace. Respondents who had undergone knee or hip surgery had the highest risk of osteoarthritis (odds ratio, 5.85; P < .0001), followed by those with a history of knee or hip injuries that prevented running (OR, 5.04; P < .0001). Other identified risk factors were family history of arthritis (OR, 3.47; P < .0001), BMI (OR, 1.10; P < .0001), and older age (OR, 1.08; P < .0001).

The news should be encouraging for runners, said Matthew Hartwell, MD, an orthopedic surgeon at the University of California, San Francisco, who led the research. If someone does not have injuries or surgeries that keep them from running, “you can still continue to run,” he said. “There may not necessarily be this dose-response relationship where the more you run, the more you break down your knee or your hip.”

Still, 24.2% of runners reported that their physician had advised them to reduce their mileage or stop running altogether. Most runners (94.2%) said they planned to run another marathon.

“The results of this study are consistent with the experiences of many lifelong runners and observations of sports medicine professionals that osteoarthritis is not an inevitable consequence of distance running,” said Brett Toresdahl, MD, a sports medicine physician at the Hospital for Special Surgery in New York, who was not involved with the study.

Still, he emphasized that more research is necessary to understand whether running contributes to the risk of developing osteoarthritis. The participants in the study were current marathoners, he noted, so it is likely they have healthy joints that can tolerate running longer distances. “If there is a subset of people who have joints that are negatively affected by running, they wouldn’t likely be registering for a marathon,” he said in an email interview.

Dr. Lo added that comparing these marathoners to a group who did not run would help assess whether running can be harmful to joints. “To be fair, this is a challenging subject to study,” she said. “Osteoarthritis has a long natural history, and so it is difficult to evaluate this kind of question over many years of running and many years of evaluation of arthritis.”

While the research does not answer the question of whether running can lead to osteoarthritis, it helps show the need for long-term research on how running affects joints over time as well as one’s general health, Dr. Toresdahl noted. “I would not be surprised if future longitudinal research will come to the same conclusion that running for the majority of patients is a net benefit for overall health and at least net neutral for joint health when done in moderation,” he said.

Dr. Hartwell, Dr. Lo, and Dr. Toresdahl report no relevant financial relationships.

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

Long-distance runners are often warned that they are wearing out their joints, but a new study found that running mileage, frequency, and pace were not associated with an increased risk of osteoarthritis.

Runners who had undergone knee or hip surgery or had a previous hip or knee injury that prevented running were most likely to have arthritis, researchers found. Family history of arthritis, higher body mass index (BMI), and older age were also associated with increased risk of the condition.

The study was presented at the American Academy of Orthopaedic Surgeons 2023 Annual Meeting.

It has generally been thought that running may increase risk of osteoarthritis because it puts more load on joints than walking or standing, noted Grace Hsiao-Wei Lo, MD, an assistant professor of immunology, allergy, and rheumatology at the Baylor College of Medicine, Houston, who was not involved with the work. Research in this area has yielded mixed results: A 2017 analysis of multiple studies found that competitive runners did have higher rates of arthritis than recreational runners, while another study conducted by Dr. Lo found that runners did not have an increased risk of knee osteoarthritis, compared with nonrunners. A 2018 study showed that marathon runners had lower instances of arthritis, compared with the general population.

In this new study, researchers surveyed 3,804 runners who participated in the 2019 or 2021 Chicago Marathon about their running history, average mileage per week, and average running pace. The survey also asked about known risk factors for osteoarthritis, including BMI, family history of arthritis, and past knee and hip injuries that prevented running.

Runners, on average, were about 44 years old and ran 27.9 miles per week. The largest proportion of respondents had completed 2-5 marathons (37.3%), around 21% of respondents had finished 6-10 marathons, and 17% were running their first marathon. Study participants had an average of 15 years of running experience, 1,892 reported a previous hip or knee injury, and 413 had undergone knee or hip surgery. Overall, 36.4% reported experiencing hip or knee pain in the past year, and 7.3% had been diagnosed with arthritis.

Researchers found that there was no association between the risk of osteoarthritis and weekly mileage, years spent running, number of marathons completed, or running pace. Respondents who had undergone knee or hip surgery had the highest risk of osteoarthritis (odds ratio, 5.85; P < .0001), followed by those with a history of knee or hip injuries that prevented running (OR, 5.04; P < .0001). Other identified risk factors were family history of arthritis (OR, 3.47; P < .0001), BMI (OR, 1.10; P < .0001), and older age (OR, 1.08; P < .0001).

The news should be encouraging for runners, said Matthew Hartwell, MD, an orthopedic surgeon at the University of California, San Francisco, who led the research. If someone does not have injuries or surgeries that keep them from running, “you can still continue to run,” he said. “There may not necessarily be this dose-response relationship where the more you run, the more you break down your knee or your hip.”

Still, 24.2% of runners reported that their physician had advised them to reduce their mileage or stop running altogether. Most runners (94.2%) said they planned to run another marathon.

“The results of this study are consistent with the experiences of many lifelong runners and observations of sports medicine professionals that osteoarthritis is not an inevitable consequence of distance running,” said Brett Toresdahl, MD, a sports medicine physician at the Hospital for Special Surgery in New York, who was not involved with the study.

Still, he emphasized that more research is necessary to understand whether running contributes to the risk of developing osteoarthritis. The participants in the study were current marathoners, he noted, so it is likely they have healthy joints that can tolerate running longer distances. “If there is a subset of people who have joints that are negatively affected by running, they wouldn’t likely be registering for a marathon,” he said in an email interview.

Dr. Lo added that comparing these marathoners to a group who did not run would help assess whether running can be harmful to joints. “To be fair, this is a challenging subject to study,” she said. “Osteoarthritis has a long natural history, and so it is difficult to evaluate this kind of question over many years of running and many years of evaluation of arthritis.”

While the research does not answer the question of whether running can lead to osteoarthritis, it helps show the need for long-term research on how running affects joints over time as well as one’s general health, Dr. Toresdahl noted. “I would not be surprised if future longitudinal research will come to the same conclusion that running for the majority of patients is a net benefit for overall health and at least net neutral for joint health when done in moderation,” he said.

Dr. Hartwell, Dr. Lo, and Dr. Toresdahl report no relevant financial relationships.

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

Opioid overdose and other preventable causes are important contributors to postpartum death rates, Medicaid claims data show, particularly in women who have a recent history of opioid use disorder (OUD), according to research published in Obstetrics and Gynecology.

Opioid overdose deaths account for up to 10% of pregnancy-associated deaths in the United States, and 75% of the deliveries of women with OUD are covered by Medicaid, according to lead author Elizabeth Suarez, PhD, MPH, with the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues.
 

Nearly 5 million deliveries studied

Researchers studied claims data from Medicaid and the National Death Index database in the United States from 2006 to 2013 for 4,972,061 deliveries. They also identified a subgroup of women with a documented history of OUD in the 3 months before delivery.

They found the incidence of postpartum opioid overdose deaths was 5.4 per 100,000 deliveries (95% confidence interval, 4.5-6.4) among all in the study and 118 per 100,000 (95% CI, 84-163) among individuals with OUD.

Incidence of all-cause postpartum death was six times higher in women with OUD than in all the women studied. Common causes of death of those with OUD were other drug- and alcohol-related deaths (47/100,000); suicide (26/100,000); and other injuries, including accidents and falls (33/100,000).

Risk factors strongly linked with postpartum opioid overdose death included mental health and other substance use disorders.
 

Medication significantly lowers death risk

The authors also documented the benefit of buprenorphine or methadone for OUD.

For women with OUD who used medication to treat OUD post partum, odds of opioid overdose death were 60% lower (odds ratio, 0.4; 95% CI 0.1-0.9).

As important as use of medication, Marcela Smid, MD, MS, writes in an accompanying editorial, is noting that 80% of the women in this study who died of opioid overdoses had contact with a health care provider before death.

“Both of these results indicate that we have the means and opportunity to prevent these deaths,” writes Dr. Smid, with the division of maternal fetal medicine, University of Utah Health in Salt Lake City.
 

Dismal numbers on ob.gyns. trained to prescribe medications

She points out some barriers, however. Most clinicians, she notes, lack time and training to prescribe buprenorphine, and in 2019, fewer than 2% of ob.gyns. who accept Medicaid were able to prescribe it.

Her charge to ob.gyns.: “We need to help identify individuals who are at high risk of OUD or opioid overdose by screening.” A validated screening tool should be used at prenatal and postpartum appointments.

On a bigger scale, she urges Medicaid to be expanded for a full year post partum through the American Rescue Act’s State Plan Amendment, something only 28 states and Washington, D.C., have done so far.

Dr. Smid points out some good news, however: President Joe Biden signed the Consolidated Appropriations Act 2023, which eliminated the “X” waiver.

Now all clinicians who have a Drug Enforcement Administration registration that includes Schedule III authority can prescribe buprenorphine for OUD if applicable state law allows it.

But that calls for medical schools and residency programs to prioritize addiction medicine as a core competency, Dr. Smid says.
 

Getting naloxone to patients, families

One of the potential interventions the study authors suggest is providing naloxone prescriptions and training to pregnant and postpartum women who have a substance use history and to their partners and significant others.

However, Mishka Terplan, MD, MPH, told this publication, “It’s one thing to write a prescription; it’s another thing for the person to actually get the medication.” He is medical director of the Friends Research Institute in Baltimore, an ob.gyn. who specializes in addiction medicine.

“What can we do?” We can think about how to get naloxone into people’s hands at discharge from the hospital after they give birth, instead of prescribing. That would mean that health systems need to prioritize this, he said. “We give people discharge medications all the time.”

Still, naloxone can’t be seen as the answer, he said.

He compares it to defibrillators in public places, which are for rescues, not reversing a population problem.

“Some people think that naloxone reversals are doing something about OUD. It’s doing about as much about OUD as defibrillators do for cardiovascular disease,” he said.

The best help, he says, will be continuation of treatment.

“Addiction is a chronic condition,” he says, “but often we only provide episodic care. We see that particularly in pregnancy. Once the pregnancy is finished, there’s not categorical continuation of insurance.”

Even if you do have insurance, it’s hard to find a clinic that’s family friendly, he notes. “You might not feel comfortable taking your newborn and standing in line in the morning to get your daily methodone dose. We have to make those environments more welcoming.”
 

Problem probably understated

He also says that though the study was well done given the data available, he’s frustrated that researchers still have to depend on billing data and can’t capture factors such as child care availability, living wages, and continuation of health insurance. Additionally, not everyone is coded correctly for OUD.

“It’s all Medicaid, so it’s only people who continued with care,” he pointed out. That means these numbers may actually underrepresent the problem.

Still, he says it’s important to realize the magnitude of deaths this study does highlight in this population.

In people with OUD in the postpartum period, the deaths are more than 1 in 1,000.

“That should be alarming,” Dr. Terplan said. “That’s a very big number from a public health perspective.”

Coauthor Kathryn J. Gray received payment from Aetion Inc., Roche, and BillionToOne. Funds were paid to the University of Utah for Dr. Smid from Alydia Inc. for being the site principal investigator for a study of the JADA device, and from Gilead for Dr. Smid’s study of hepatitis C in pregnancy; she was also a consultant for Organon and Rhia Ventures. Dr. Terplan reports no relevant financial relationships.
 

Opioid overdose and other preventable causes are important contributors to postpartum death rates, Medicaid claims data show, particularly in women who have a recent history of opioid use disorder (OUD), according to research published in Obstetrics and Gynecology.

Opioid overdose deaths account for up to 10% of pregnancy-associated deaths in the United States, and 75% of the deliveries of women with OUD are covered by Medicaid, according to lead author Elizabeth Suarez, PhD, MPH, with the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues.
 

Nearly 5 million deliveries studied

Researchers studied claims data from Medicaid and the National Death Index database in the United States from 2006 to 2013 for 4,972,061 deliveries. They also identified a subgroup of women with a documented history of OUD in the 3 months before delivery.

They found the incidence of postpartum opioid overdose deaths was 5.4 per 100,000 deliveries (95% confidence interval, 4.5-6.4) among all in the study and 118 per 100,000 (95% CI, 84-163) among individuals with OUD.

Incidence of all-cause postpartum death was six times higher in women with OUD than in all the women studied. Common causes of death of those with OUD were other drug- and alcohol-related deaths (47/100,000); suicide (26/100,000); and other injuries, including accidents and falls (33/100,000).

Risk factors strongly linked with postpartum opioid overdose death included mental health and other substance use disorders.
 

Medication significantly lowers death risk

The authors also documented the benefit of buprenorphine or methadone for OUD.

For women with OUD who used medication to treat OUD post partum, odds of opioid overdose death were 60% lower (odds ratio, 0.4; 95% CI 0.1-0.9).

As important as use of medication, Marcela Smid, MD, MS, writes in an accompanying editorial, is noting that 80% of the women in this study who died of opioid overdoses had contact with a health care provider before death.

“Both of these results indicate that we have the means and opportunity to prevent these deaths,” writes Dr. Smid, with the division of maternal fetal medicine, University of Utah Health in Salt Lake City.
 

Dismal numbers on ob.gyns. trained to prescribe medications

She points out some barriers, however. Most clinicians, she notes, lack time and training to prescribe buprenorphine, and in 2019, fewer than 2% of ob.gyns. who accept Medicaid were able to prescribe it.

Her charge to ob.gyns.: “We need to help identify individuals who are at high risk of OUD or opioid overdose by screening.” A validated screening tool should be used at prenatal and postpartum appointments.

On a bigger scale, she urges Medicaid to be expanded for a full year post partum through the American Rescue Act’s State Plan Amendment, something only 28 states and Washington, D.C., have done so far.

Dr. Smid points out some good news, however: President Joe Biden signed the Consolidated Appropriations Act 2023, which eliminated the “X” waiver.

Now all clinicians who have a Drug Enforcement Administration registration that includes Schedule III authority can prescribe buprenorphine for OUD if applicable state law allows it.

But that calls for medical schools and residency programs to prioritize addiction medicine as a core competency, Dr. Smid says.
 

Getting naloxone to patients, families

One of the potential interventions the study authors suggest is providing naloxone prescriptions and training to pregnant and postpartum women who have a substance use history and to their partners and significant others.

However, Mishka Terplan, MD, MPH, told this publication, “It’s one thing to write a prescription; it’s another thing for the person to actually get the medication.” He is medical director of the Friends Research Institute in Baltimore, an ob.gyn. who specializes in addiction medicine.

“What can we do?” We can think about how to get naloxone into people’s hands at discharge from the hospital after they give birth, instead of prescribing. That would mean that health systems need to prioritize this, he said. “We give people discharge medications all the time.”

Still, naloxone can’t be seen as the answer, he said.

He compares it to defibrillators in public places, which are for rescues, not reversing a population problem.

“Some people think that naloxone reversals are doing something about OUD. It’s doing about as much about OUD as defibrillators do for cardiovascular disease,” he said.

The best help, he says, will be continuation of treatment.

“Addiction is a chronic condition,” he says, “but often we only provide episodic care. We see that particularly in pregnancy. Once the pregnancy is finished, there’s not categorical continuation of insurance.”

Even if you do have insurance, it’s hard to find a clinic that’s family friendly, he notes. “You might not feel comfortable taking your newborn and standing in line in the morning to get your daily methodone dose. We have to make those environments more welcoming.”
 

Problem probably understated

He also says that though the study was well done given the data available, he’s frustrated that researchers still have to depend on billing data and can’t capture factors such as child care availability, living wages, and continuation of health insurance. Additionally, not everyone is coded correctly for OUD.

“It’s all Medicaid, so it’s only people who continued with care,” he pointed out. That means these numbers may actually underrepresent the problem.

Still, he says it’s important to realize the magnitude of deaths this study does highlight in this population.

In people with OUD in the postpartum period, the deaths are more than 1 in 1,000.

“That should be alarming,” Dr. Terplan said. “That’s a very big number from a public health perspective.”

Coauthor Kathryn J. Gray received payment from Aetion Inc., Roche, and BillionToOne. Funds were paid to the University of Utah for Dr. Smid from Alydia Inc. for being the site principal investigator for a study of the JADA device, and from Gilead for Dr. Smid’s study of hepatitis C in pregnancy; she was also a consultant for Organon and Rhia Ventures. Dr. Terplan reports no relevant financial relationships.
 

Opioid overdose and other preventable causes are important contributors to postpartum death rates, Medicaid claims data show, particularly in women who have a recent history of opioid use disorder (OUD), according to research published in Obstetrics and Gynecology.

Opioid overdose deaths account for up to 10% of pregnancy-associated deaths in the United States, and 75% of the deliveries of women with OUD are covered by Medicaid, according to lead author Elizabeth Suarez, PhD, MPH, with the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues.
 

Nearly 5 million deliveries studied

Researchers studied claims data from Medicaid and the National Death Index database in the United States from 2006 to 2013 for 4,972,061 deliveries. They also identified a subgroup of women with a documented history of OUD in the 3 months before delivery.

They found the incidence of postpartum opioid overdose deaths was 5.4 per 100,000 deliveries (95% confidence interval, 4.5-6.4) among all in the study and 118 per 100,000 (95% CI, 84-163) among individuals with OUD.

Incidence of all-cause postpartum death was six times higher in women with OUD than in all the women studied. Common causes of death of those with OUD were other drug- and alcohol-related deaths (47/100,000); suicide (26/100,000); and other injuries, including accidents and falls (33/100,000).

Risk factors strongly linked with postpartum opioid overdose death included mental health and other substance use disorders.
 

Medication significantly lowers death risk

The authors also documented the benefit of buprenorphine or methadone for OUD.

For women with OUD who used medication to treat OUD post partum, odds of opioid overdose death were 60% lower (odds ratio, 0.4; 95% CI 0.1-0.9).

As important as use of medication, Marcela Smid, MD, MS, writes in an accompanying editorial, is noting that 80% of the women in this study who died of opioid overdoses had contact with a health care provider before death.

“Both of these results indicate that we have the means and opportunity to prevent these deaths,” writes Dr. Smid, with the division of maternal fetal medicine, University of Utah Health in Salt Lake City.
 

Dismal numbers on ob.gyns. trained to prescribe medications

She points out some barriers, however. Most clinicians, she notes, lack time and training to prescribe buprenorphine, and in 2019, fewer than 2% of ob.gyns. who accept Medicaid were able to prescribe it.

Her charge to ob.gyns.: “We need to help identify individuals who are at high risk of OUD or opioid overdose by screening.” A validated screening tool should be used at prenatal and postpartum appointments.

On a bigger scale, she urges Medicaid to be expanded for a full year post partum through the American Rescue Act’s State Plan Amendment, something only 28 states and Washington, D.C., have done so far.

Dr. Smid points out some good news, however: President Joe Biden signed the Consolidated Appropriations Act 2023, which eliminated the “X” waiver.

Now all clinicians who have a Drug Enforcement Administration registration that includes Schedule III authority can prescribe buprenorphine for OUD if applicable state law allows it.

But that calls for medical schools and residency programs to prioritize addiction medicine as a core competency, Dr. Smid says.
 

Getting naloxone to patients, families

One of the potential interventions the study authors suggest is providing naloxone prescriptions and training to pregnant and postpartum women who have a substance use history and to their partners and significant others.

However, Mishka Terplan, MD, MPH, told this publication, “It’s one thing to write a prescription; it’s another thing for the person to actually get the medication.” He is medical director of the Friends Research Institute in Baltimore, an ob.gyn. who specializes in addiction medicine.

“What can we do?” We can think about how to get naloxone into people’s hands at discharge from the hospital after they give birth, instead of prescribing. That would mean that health systems need to prioritize this, he said. “We give people discharge medications all the time.”

Still, naloxone can’t be seen as the answer, he said.

He compares it to defibrillators in public places, which are for rescues, not reversing a population problem.

“Some people think that naloxone reversals are doing something about OUD. It’s doing about as much about OUD as defibrillators do for cardiovascular disease,” he said.

The best help, he says, will be continuation of treatment.

“Addiction is a chronic condition,” he says, “but often we only provide episodic care. We see that particularly in pregnancy. Once the pregnancy is finished, there’s not categorical continuation of insurance.”

Even if you do have insurance, it’s hard to find a clinic that’s family friendly, he notes. “You might not feel comfortable taking your newborn and standing in line in the morning to get your daily methodone dose. We have to make those environments more welcoming.”
 

Problem probably understated

He also says that though the study was well done given the data available, he’s frustrated that researchers still have to depend on billing data and can’t capture factors such as child care availability, living wages, and continuation of health insurance. Additionally, not everyone is coded correctly for OUD.

“It’s all Medicaid, so it’s only people who continued with care,” he pointed out. That means these numbers may actually underrepresent the problem.

Still, he says it’s important to realize the magnitude of deaths this study does highlight in this population.

In people with OUD in the postpartum period, the deaths are more than 1 in 1,000.

“That should be alarming,” Dr. Terplan said. “That’s a very big number from a public health perspective.”

Coauthor Kathryn J. Gray received payment from Aetion Inc., Roche, and BillionToOne. Funds were paid to the University of Utah for Dr. Smid from Alydia Inc. for being the site principal investigator for a study of the JADA device, and from Gilead for Dr. Smid’s study of hepatitis C in pregnancy; she was also a consultant for Organon and Rhia Ventures. Dr. Terplan reports no relevant financial relationships.
 

Response to buprenorphine among emergency department patients using fentanyl was similar to that in patients using other opioids, based on data from nearly 900 individuals.

California EDs include a facilitation program known as CA Bridge for the treatment of opioid use disorder. Guidelines for CA Bridge call for high-dose buprenorphine to treat patients in drug withdrawal, with doses starting at 8-16 mg, Hannah Snyder, MD, of the University of California, San Francisco, and colleagues wrote.

“Buprenorphine has been repeatedly shown to save lives and prevent overdoses,” Dr. Snyder said in an interview. “We know that emergency department–initiated buprenorphine is an essential tool for increasing access. In the era of fentanyl, both patients and providers have expressed concerns that buprenorphine may not work as well as it did when patients were more likely to be using heroin or opioid pills.

“This retrospective cohort study provides additional information about emergency department buprenorphine as fentanyl becomes increasingly prevalent.” 

In a research letter published in JAMA Network Open, the investigators reviewed data from the electronic health records of 896 patients who presented with opioid use disorder (OUD) at 16 CA Bridge EDs between Jan. 1, 2020, and April 30, 2020. All patients with OUD were included regardless of chief concern, current treatment, treatment desires, or withdrawal. A total of 87 individuals reported fentanyl use; if no fentanyl use was reported, the patient was classified as not using fentanyl. The median age of the patients was 35 years, two thirds were male, approximately 46% were White and non-Hispanic, and 30% had unstable housing.

The primary outcome was follow-up engagement at 7-14 days and 25-37 days.

A total of 492 patients received buprenorphine, including 44 fentanyl users, and 439 initiated high doses of 8-32 mg. At a 30-day follow-up, eight patients had precipitated withdrawal, including two cases in fentanyl users; none of these cases required hospital admission.

The follow-up engagement was similar for both groups, with adjusted odds ratios of 0.60 for administered buprenorphine at the initial ED encounter, 1.09 for 7-day follow-up, and 1.33 for 30-day follow-up.

The findings were limited by the retrospective design and use of clinical documentation, which likely resulted in underreporting of fentanyl use and follow-up, the researchers noted. However, the results supported the effectiveness of buprenorphine for ED patients in withdrawal with a history of fentanyl exposure.

“We were pleased to see that precipitated withdrawal was relatively uncommon in this study, and that patients who did and did not use fentanyl followed up at similar rates,” said Dr. Snyder. “This aligns with our clinical experience and prior research showing that emergency department buprenorphine starts continue to be an essential tool.”

The message for clinicians: “If a patient presents to the emergency department in objective opioid withdrawal and desires buprenorphine, they should be offered treatment in that moment,” Dr. Snyder said. “Treatment protocols used by hospitals in this study are available online. Emergency departments can offer compassionate and evidence-based treatment initiation 24 hours a day, 7 days a week, 365 days a year.”
 

More data needed on dosing strategies

“We need additional research to determine best practices for patients who use fentanyl and want to start buprenorphine, but are not yet in withdrawal,” Dr. Snyder said. “Doses of buprenorphine like those in this study are only appropriate for patients who are in withdrawal with objective signs, so some patients may struggle to wait long enough after their last use to go into sufficient withdrawal.”

Precipitated withdrawal does occur in some cases, said Dr. Snyder. “If it does, the emergency department is a very good place to manage it. We need additional research to determine best practices in management to make patients as comfortable as possible, including additional high-dose buprenorphine as well as additional adjunctive agents.”
 

Findings support buprenorphine

“The classic approach to buprenorphine initiation, which emerged from psychiatry outpatient office visits, is to start with very small doses of buprenorphine [2-4 mg] and titrate up slowly,” Reuben J. Strayer, MD, said in an interview.

“This dose range turns out to be the ‘sour spot’ most likely to cause the most important complication around buprenorphine initiation–precipitated withdrawal,” said Dr. Strayer, the director of addiction medicine in the emergency medicine department at Maimonides Medical Center, New York.

“One of the current focus areas of OUD treatment research is determining how to initiate buprenorphine without entailing a period of spontaneous withdrawal and without causing precipitated withdrawal,” Strayer explained. “The two primary strategies are low-dose buprenorphine initiation [LDBI, less than 2 mg, sometimes called microdosing] and high-dose [HDBI, ≥ 16 mg] buprenorphine initiation. HDBI is attractive because the primary treatment of buprenorphine-precipitated withdrawal is more buprenorphine.

“Additionally, using a high dose up front immediately transitions the patient to therapeutic blood levels, which protects the patient from withdrawal, cravings, and overdose from dangerous opioids (heroin, fentanyl, oxycodone).”

However, “the contamination and now replacement of heroin with fentanyl in the street drug supply has challenged buprenorphine initiation, because fentanyl, when used chronically, accumulates in the body and leaks into the bloodstream slowly over time, preventing the opioid washout that is required to eliminate the risk of precipitated withdrawal when buprenorphine is administered,” said Dr. Strayer.

The current study demonstrates that patients who are initiated with a first dose of 8-16 mg buprenorphine are unlikely to experience precipitated withdrawal and are successfully transitioned to buprenorphine maintenance and clinic follow-up, Dr. Snyder said, but he was surprised by the low rate of precipitated withdrawal in the current study, “which is discordant with what is being anecdotally reported across the country.”

However, the take-home message for clinicians is the support for the initiation of buprenorphine in emergency department settings at a starting dose of 8-16 mg, regardless of reported fentanyl use, he said. “Given the huge impact buprenorphine therapy has on OUD-related mortality, clinicians should make every effort to initiate buprenorphine for OUD patients at every opportunity, and precipitated withdrawal is very unlikely in appropriately selected patients.

“Many clinicians remain reluctant to initiate buprenorphine in ED settings for unfamiliarity with the drug, fear of precipitated withdrawal, or concerns around the certainty of outpatient follow-up,” Dr. Snyder said. “Education, encouragement, systems programming, such as including decision support within the electronic health record, and role-modeling from local champions will promote wider adoption of this lifesaving practice.”

Looking ahead, “more research, including prospective research, is needed to refine best practices around buprenorphine administration,” said Dr. Snyder. Questions to address include which patients are most at risk for precipitated withdrawal and whether there are alternatives to standard initiation dosing that are sufficiently unlikely to cause precipitated withdrawal. “Possibly effective alternatives include buprenorphine initiation by administration of long-acting injectable depot buprenorphine, which accumulates slowly, potentially avoiding precipitated withdrawal, as well as a slow intravenous buprenorphine infusion such as 9 mg given over 12 hours.”

The study received no outside funding. Dr. Snyder disclosed grants from the Substance Abuse and Mental Health Services Administration and the California Department of Health Care Services during the study. Dr. Strayer reported no relevant financial relationships.

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

Response to buprenorphine among emergency department patients using fentanyl was similar to that in patients using other opioids, based on data from nearly 900 individuals.

California EDs include a facilitation program known as CA Bridge for the treatment of opioid use disorder. Guidelines for CA Bridge call for high-dose buprenorphine to treat patients in drug withdrawal, with doses starting at 8-16 mg, Hannah Snyder, MD, of the University of California, San Francisco, and colleagues wrote.

“Buprenorphine has been repeatedly shown to save lives and prevent overdoses,” Dr. Snyder said in an interview. “We know that emergency department–initiated buprenorphine is an essential tool for increasing access. In the era of fentanyl, both patients and providers have expressed concerns that buprenorphine may not work as well as it did when patients were more likely to be using heroin or opioid pills.

“This retrospective cohort study provides additional information about emergency department buprenorphine as fentanyl becomes increasingly prevalent.” 

In a research letter published in JAMA Network Open, the investigators reviewed data from the electronic health records of 896 patients who presented with opioid use disorder (OUD) at 16 CA Bridge EDs between Jan. 1, 2020, and April 30, 2020. All patients with OUD were included regardless of chief concern, current treatment, treatment desires, or withdrawal. A total of 87 individuals reported fentanyl use; if no fentanyl use was reported, the patient was classified as not using fentanyl. The median age of the patients was 35 years, two thirds were male, approximately 46% were White and non-Hispanic, and 30% had unstable housing.

The primary outcome was follow-up engagement at 7-14 days and 25-37 days.

A total of 492 patients received buprenorphine, including 44 fentanyl users, and 439 initiated high doses of 8-32 mg. At a 30-day follow-up, eight patients had precipitated withdrawal, including two cases in fentanyl users; none of these cases required hospital admission.

The follow-up engagement was similar for both groups, with adjusted odds ratios of 0.60 for administered buprenorphine at the initial ED encounter, 1.09 for 7-day follow-up, and 1.33 for 30-day follow-up.

The findings were limited by the retrospective design and use of clinical documentation, which likely resulted in underreporting of fentanyl use and follow-up, the researchers noted. However, the results supported the effectiveness of buprenorphine for ED patients in withdrawal with a history of fentanyl exposure.

“We were pleased to see that precipitated withdrawal was relatively uncommon in this study, and that patients who did and did not use fentanyl followed up at similar rates,” said Dr. Snyder. “This aligns with our clinical experience and prior research showing that emergency department buprenorphine starts continue to be an essential tool.”

The message for clinicians: “If a patient presents to the emergency department in objective opioid withdrawal and desires buprenorphine, they should be offered treatment in that moment,” Dr. Snyder said. “Treatment protocols used by hospitals in this study are available online. Emergency departments can offer compassionate and evidence-based treatment initiation 24 hours a day, 7 days a week, 365 days a year.”
 

More data needed on dosing strategies

“We need additional research to determine best practices for patients who use fentanyl and want to start buprenorphine, but are not yet in withdrawal,” Dr. Snyder said. “Doses of buprenorphine like those in this study are only appropriate for patients who are in withdrawal with objective signs, so some patients may struggle to wait long enough after their last use to go into sufficient withdrawal.”

Precipitated withdrawal does occur in some cases, said Dr. Snyder. “If it does, the emergency department is a very good place to manage it. We need additional research to determine best practices in management to make patients as comfortable as possible, including additional high-dose buprenorphine as well as additional adjunctive agents.”
 

Findings support buprenorphine

“The classic approach to buprenorphine initiation, which emerged from psychiatry outpatient office visits, is to start with very small doses of buprenorphine [2-4 mg] and titrate up slowly,” Reuben J. Strayer, MD, said in an interview.

“This dose range turns out to be the ‘sour spot’ most likely to cause the most important complication around buprenorphine initiation–precipitated withdrawal,” said Dr. Strayer, the director of addiction medicine in the emergency medicine department at Maimonides Medical Center, New York.

“One of the current focus areas of OUD treatment research is determining how to initiate buprenorphine without entailing a period of spontaneous withdrawal and without causing precipitated withdrawal,” Strayer explained. “The two primary strategies are low-dose buprenorphine initiation [LDBI, less than 2 mg, sometimes called microdosing] and high-dose [HDBI, ≥ 16 mg] buprenorphine initiation. HDBI is attractive because the primary treatment of buprenorphine-precipitated withdrawal is more buprenorphine.

“Additionally, using a high dose up front immediately transitions the patient to therapeutic blood levels, which protects the patient from withdrawal, cravings, and overdose from dangerous opioids (heroin, fentanyl, oxycodone).”

However, “the contamination and now replacement of heroin with fentanyl in the street drug supply has challenged buprenorphine initiation, because fentanyl, when used chronically, accumulates in the body and leaks into the bloodstream slowly over time, preventing the opioid washout that is required to eliminate the risk of precipitated withdrawal when buprenorphine is administered,” said Dr. Strayer.

The current study demonstrates that patients who are initiated with a first dose of 8-16 mg buprenorphine are unlikely to experience precipitated withdrawal and are successfully transitioned to buprenorphine maintenance and clinic follow-up, Dr. Snyder said, but he was surprised by the low rate of precipitated withdrawal in the current study, “which is discordant with what is being anecdotally reported across the country.”

However, the take-home message for clinicians is the support for the initiation of buprenorphine in emergency department settings at a starting dose of 8-16 mg, regardless of reported fentanyl use, he said. “Given the huge impact buprenorphine therapy has on OUD-related mortality, clinicians should make every effort to initiate buprenorphine for OUD patients at every opportunity, and precipitated withdrawal is very unlikely in appropriately selected patients.

“Many clinicians remain reluctant to initiate buprenorphine in ED settings for unfamiliarity with the drug, fear of precipitated withdrawal, or concerns around the certainty of outpatient follow-up,” Dr. Snyder said. “Education, encouragement, systems programming, such as including decision support within the electronic health record, and role-modeling from local champions will promote wider adoption of this lifesaving practice.”

Looking ahead, “more research, including prospective research, is needed to refine best practices around buprenorphine administration,” said Dr. Snyder. Questions to address include which patients are most at risk for precipitated withdrawal and whether there are alternatives to standard initiation dosing that are sufficiently unlikely to cause precipitated withdrawal. “Possibly effective alternatives include buprenorphine initiation by administration of long-acting injectable depot buprenorphine, which accumulates slowly, potentially avoiding precipitated withdrawal, as well as a slow intravenous buprenorphine infusion such as 9 mg given over 12 hours.”

The study received no outside funding. Dr. Snyder disclosed grants from the Substance Abuse and Mental Health Services Administration and the California Department of Health Care Services during the study. Dr. Strayer reported no relevant financial relationships.

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

Response to buprenorphine among emergency department patients using fentanyl was similar to that in patients using other opioids, based on data from nearly 900 individuals.

California EDs include a facilitation program known as CA Bridge for the treatment of opioid use disorder. Guidelines for CA Bridge call for high-dose buprenorphine to treat patients in drug withdrawal, with doses starting at 8-16 mg, Hannah Snyder, MD, of the University of California, San Francisco, and colleagues wrote.

“Buprenorphine has been repeatedly shown to save lives and prevent overdoses,” Dr. Snyder said in an interview. “We know that emergency department–initiated buprenorphine is an essential tool for increasing access. In the era of fentanyl, both patients and providers have expressed concerns that buprenorphine may not work as well as it did when patients were more likely to be using heroin or opioid pills.

“This retrospective cohort study provides additional information about emergency department buprenorphine as fentanyl becomes increasingly prevalent.” 

In a research letter published in JAMA Network Open, the investigators reviewed data from the electronic health records of 896 patients who presented with opioid use disorder (OUD) at 16 CA Bridge EDs between Jan. 1, 2020, and April 30, 2020. All patients with OUD were included regardless of chief concern, current treatment, treatment desires, or withdrawal. A total of 87 individuals reported fentanyl use; if no fentanyl use was reported, the patient was classified as not using fentanyl. The median age of the patients was 35 years, two thirds were male, approximately 46% were White and non-Hispanic, and 30% had unstable housing.

The primary outcome was follow-up engagement at 7-14 days and 25-37 days.

A total of 492 patients received buprenorphine, including 44 fentanyl users, and 439 initiated high doses of 8-32 mg. At a 30-day follow-up, eight patients had precipitated withdrawal, including two cases in fentanyl users; none of these cases required hospital admission.

The follow-up engagement was similar for both groups, with adjusted odds ratios of 0.60 for administered buprenorphine at the initial ED encounter, 1.09 for 7-day follow-up, and 1.33 for 30-day follow-up.

The findings were limited by the retrospective design and use of clinical documentation, which likely resulted in underreporting of fentanyl use and follow-up, the researchers noted. However, the results supported the effectiveness of buprenorphine for ED patients in withdrawal with a history of fentanyl exposure.

“We were pleased to see that precipitated withdrawal was relatively uncommon in this study, and that patients who did and did not use fentanyl followed up at similar rates,” said Dr. Snyder. “This aligns with our clinical experience and prior research showing that emergency department buprenorphine starts continue to be an essential tool.”

The message for clinicians: “If a patient presents to the emergency department in objective opioid withdrawal and desires buprenorphine, they should be offered treatment in that moment,” Dr. Snyder said. “Treatment protocols used by hospitals in this study are available online. Emergency departments can offer compassionate and evidence-based treatment initiation 24 hours a day, 7 days a week, 365 days a year.”
 

More data needed on dosing strategies

“We need additional research to determine best practices for patients who use fentanyl and want to start buprenorphine, but are not yet in withdrawal,” Dr. Snyder said. “Doses of buprenorphine like those in this study are only appropriate for patients who are in withdrawal with objective signs, so some patients may struggle to wait long enough after their last use to go into sufficient withdrawal.”

Precipitated withdrawal does occur in some cases, said Dr. Snyder. “If it does, the emergency department is a very good place to manage it. We need additional research to determine best practices in management to make patients as comfortable as possible, including additional high-dose buprenorphine as well as additional adjunctive agents.”
 

Findings support buprenorphine

“The classic approach to buprenorphine initiation, which emerged from psychiatry outpatient office visits, is to start with very small doses of buprenorphine [2-4 mg] and titrate up slowly,” Reuben J. Strayer, MD, said in an interview.

“This dose range turns out to be the ‘sour spot’ most likely to cause the most important complication around buprenorphine initiation–precipitated withdrawal,” said Dr. Strayer, the director of addiction medicine in the emergency medicine department at Maimonides Medical Center, New York.

“One of the current focus areas of OUD treatment research is determining how to initiate buprenorphine without entailing a period of spontaneous withdrawal and without causing precipitated withdrawal,” Strayer explained. “The two primary strategies are low-dose buprenorphine initiation [LDBI, less than 2 mg, sometimes called microdosing] and high-dose [HDBI, ≥ 16 mg] buprenorphine initiation. HDBI is attractive because the primary treatment of buprenorphine-precipitated withdrawal is more buprenorphine.

“Additionally, using a high dose up front immediately transitions the patient to therapeutic blood levels, which protects the patient from withdrawal, cravings, and overdose from dangerous opioids (heroin, fentanyl, oxycodone).”

However, “the contamination and now replacement of heroin with fentanyl in the street drug supply has challenged buprenorphine initiation, because fentanyl, when used chronically, accumulates in the body and leaks into the bloodstream slowly over time, preventing the opioid washout that is required to eliminate the risk of precipitated withdrawal when buprenorphine is administered,” said Dr. Strayer.

The current study demonstrates that patients who are initiated with a first dose of 8-16 mg buprenorphine are unlikely to experience precipitated withdrawal and are successfully transitioned to buprenorphine maintenance and clinic follow-up, Dr. Snyder said, but he was surprised by the low rate of precipitated withdrawal in the current study, “which is discordant with what is being anecdotally reported across the country.”

However, the take-home message for clinicians is the support for the initiation of buprenorphine in emergency department settings at a starting dose of 8-16 mg, regardless of reported fentanyl use, he said. “Given the huge impact buprenorphine therapy has on OUD-related mortality, clinicians should make every effort to initiate buprenorphine for OUD patients at every opportunity, and precipitated withdrawal is very unlikely in appropriately selected patients.

“Many clinicians remain reluctant to initiate buprenorphine in ED settings for unfamiliarity with the drug, fear of precipitated withdrawal, or concerns around the certainty of outpatient follow-up,” Dr. Snyder said. “Education, encouragement, systems programming, such as including decision support within the electronic health record, and role-modeling from local champions will promote wider adoption of this lifesaving practice.”

Looking ahead, “more research, including prospective research, is needed to refine best practices around buprenorphine administration,” said Dr. Snyder. Questions to address include which patients are most at risk for precipitated withdrawal and whether there are alternatives to standard initiation dosing that are sufficiently unlikely to cause precipitated withdrawal. “Possibly effective alternatives include buprenorphine initiation by administration of long-acting injectable depot buprenorphine, which accumulates slowly, potentially avoiding precipitated withdrawal, as well as a slow intravenous buprenorphine infusion such as 9 mg given over 12 hours.”

The study received no outside funding. Dr. Snyder disclosed grants from the Substance Abuse and Mental Health Services Administration and the California Department of Health Care Services during the study. Dr. Strayer reported no relevant financial relationships.

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

A Michigan physician has been indicted by a federal grand jury on charges of health care fraud and conspiracy to distribute controlled substances.

Sangita Patel, MD, 50, practiced at Advance Medical Home Physicians in Troy.

According to court documents, between July 2020 and June 2022 Patel was responsible for submitting Medicare claims for improper telehealth visits she didn’t conduct herself.

Dr. Patel, who accepted patients who paid in cash as well as those with Medicare and Medicaid coverage, billed approximately $3.4 million to Medicare between 2018 and 2022, according to court documents. An unusual number of these visits were billed using complex codes, an indication of health care fraud. The investigation also found that on many days, Dr. Patel billed for more than 24 hours of services. During this period, according to the document, 76% of Dr. Patel’s Medicare reimbursements were for telehealth.

Prosecutors say that Dr. Patel prescribed Schedule II controlled substances to more than 90% of the patients in these telehealth visits. She delegated her prescription authority to an unlicensed medical assistant. Through undercover visits and cell site search warrant data, the investigation found that Dr. Patel directed patients to contact, via cell phone, this assistant, who then entered electronic prescriptions into the electronic medical records system. Dr. Patel then signed the prescriptions and sent them to the pharmacies without ever interacting with the patients. Prosecutors also used text messages, obtained by search warrant, between Dr. Patel and her assistant and between the assistant and undercover informers to build their case.

Dr. Patel is also accused of referring patients to other providers, who in turn billed Medicare for claims associated with those patients. Advance Medical received $143,000 from these providers, potentially in violation of anti-kickback laws, according to bank records obtained by subpoena.

If convicted, Dr. Patel could be sentenced to up to 10 years in federal prison.

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

A Michigan physician has been indicted by a federal grand jury on charges of health care fraud and conspiracy to distribute controlled substances.

Sangita Patel, MD, 50, practiced at Advance Medical Home Physicians in Troy.

According to court documents, between July 2020 and June 2022 Patel was responsible for submitting Medicare claims for improper telehealth visits she didn’t conduct herself.

Dr. Patel, who accepted patients who paid in cash as well as those with Medicare and Medicaid coverage, billed approximately $3.4 million to Medicare between 2018 and 2022, according to court documents. An unusual number of these visits were billed using complex codes, an indication of health care fraud. The investigation also found that on many days, Dr. Patel billed for more than 24 hours of services. During this period, according to the document, 76% of Dr. Patel’s Medicare reimbursements were for telehealth.

Prosecutors say that Dr. Patel prescribed Schedule II controlled substances to more than 90% of the patients in these telehealth visits. She delegated her prescription authority to an unlicensed medical assistant. Through undercover visits and cell site search warrant data, the investigation found that Dr. Patel directed patients to contact, via cell phone, this assistant, who then entered electronic prescriptions into the electronic medical records system. Dr. Patel then signed the prescriptions and sent them to the pharmacies without ever interacting with the patients. Prosecutors also used text messages, obtained by search warrant, between Dr. Patel and her assistant and between the assistant and undercover informers to build their case.

Dr. Patel is also accused of referring patients to other providers, who in turn billed Medicare for claims associated with those patients. Advance Medical received $143,000 from these providers, potentially in violation of anti-kickback laws, according to bank records obtained by subpoena.

If convicted, Dr. Patel could be sentenced to up to 10 years in federal prison.

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

A Michigan physician has been indicted by a federal grand jury on charges of health care fraud and conspiracy to distribute controlled substances.

Sangita Patel, MD, 50, practiced at Advance Medical Home Physicians in Troy.

According to court documents, between July 2020 and June 2022 Patel was responsible for submitting Medicare claims for improper telehealth visits she didn’t conduct herself.

Dr. Patel, who accepted patients who paid in cash as well as those with Medicare and Medicaid coverage, billed approximately $3.4 million to Medicare between 2018 and 2022, according to court documents. An unusual number of these visits were billed using complex codes, an indication of health care fraud. The investigation also found that on many days, Dr. Patel billed for more than 24 hours of services. During this period, according to the document, 76% of Dr. Patel’s Medicare reimbursements were for telehealth.

Prosecutors say that Dr. Patel prescribed Schedule II controlled substances to more than 90% of the patients in these telehealth visits. She delegated her prescription authority to an unlicensed medical assistant. Through undercover visits and cell site search warrant data, the investigation found that Dr. Patel directed patients to contact, via cell phone, this assistant, who then entered electronic prescriptions into the electronic medical records system. Dr. Patel then signed the prescriptions and sent them to the pharmacies without ever interacting with the patients. Prosecutors also used text messages, obtained by search warrant, between Dr. Patel and her assistant and between the assistant and undercover informers to build their case.

Dr. Patel is also accused of referring patients to other providers, who in turn billed Medicare for claims associated with those patients. Advance Medical received $143,000 from these providers, potentially in violation of anti-kickback laws, according to bank records obtained by subpoena.

If convicted, Dr. Patel could be sentenced to up to 10 years in federal prison.

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