Pain

SAN FRANCISCO – Medical marijuana skipped the usual phased testing of pharmaceuticals, so questions abound about how to counsel patients as legalization rolls out across the country, speakers said at the American Psychiatric Association annual meeting.

M. Alexander Otto/MDedge News

Drug interactions are an issue but remain under the radar. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are inhibitors of cytochrome P450, specifically the CYP2C enzyme and CYP3A liver enzymes, which means possible interactions with drug classes such as antidepressants and antipsychotics might come into play.

Concomitant use could affect, or be affected by, fluoxetine, clozapine, duloxetine, and olanzapine, among other medications. One case study suggested that warfarin doses should be reduced by 30% in a patient who had started with a liquid formulation of CBD for managing epilepsy (Basic Clin Pharmacol Toxicol. 2019 Jan;124[1]:28-31).

At this point, it’s “not clear what the clinic implications are,” but “it’s not unreasonable to consider that your patients’ response to their psychiatric medications might change based on the introduction of cannabinoids,” said Arthur Williams, MD, assistant professor of clinical psychiatry at Columbia University, New York, and one of many researchers playing catch-up as marijuana and its derivatives enter the clinic.

Another question is what, exactly, is a standard dose?

Dosing mostly has been a question of THC, the psychoactive component of marijuana. Washington state and Colorado opted for 10-mg THC when those jurisdictions legalized recreational use; Oregon chose 5 mg. Both are in line with Food and Drug Administration formulations already on the market, including dronabinol (Marinol), a synthetic THC approved in 2.5-mg, 5-mg, and 10-mg doses for AIDS wasting, and chemotherapy nausea and vomiting.

A typical .7-g joint of 8% THC delivers about 5 mg or so, but newer strains range up to 20% THC, and could deliver over 13 mg per joint; occasional users, meanwhile, feel high from just 2-3 mg.

The ratio of THC to CBD matters, as well. Generally, “whole plant marijuana on the black market is much higher in THC and much lower in CBD,” Dr. Williams said. CBD is thought to deliver most of the medical benefits of marijuana.

It’s best to ask people what they’re using, and to counsel new users – especially the elderly – to start low and go slow. But keep in mind that many medical users have years of recreational use and have built up tolerance, he said.

Vaping is not a bad idea for those interested. It heats the plant material to high enough temperatures to release cannabinoids but without combusting. It’s a much more efficient THC delivery system than smoking, and there’s no smoke in the lungs. Vape patients often feel they can titrate their dose exactly.

Edibles are another matter. It can take hours for them to hit. Although THC levels do not spike with edibles as they do when the substance is inhaled, the effects last longer. A lot depends on how much food is in the gut.

The risk with edibles is that people may keep popping gummy bears and brownies because they don’t feel anything but end up overdosing. Children might be tempted by the treats, too, and for those under 4 years old, overdose can lead to fatal encephalopathic comas, “something we never really saw until edibles came around,” Dr. Williams said.

With edibles, “you have no idea what’s actually in the product.” Labels can be “inaccurate by an order of magnitude. Patients should be cautioned about that,” he said.

Pregnant and breastfeeding women, especially, should be warned away from marijuana. Some of the literature suggests a link between exposure to marijuana and preterm birth – in addition to early psychosis in vulnerable children.

Dr. Williams had no relevant disclosures.

[email protected]

SAN FRANCISCO – Medical marijuana skipped the usual phased testing of pharmaceuticals, so questions abound about how to counsel patients as legalization rolls out across the country, speakers said at the American Psychiatric Association annual meeting.

M. Alexander Otto/MDedge News

Drug interactions are an issue but remain under the radar. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are inhibitors of cytochrome P450, specifically the CYP2C enzyme and CYP3A liver enzymes, which means possible interactions with drug classes such as antidepressants and antipsychotics might come into play.

Concomitant use could affect, or be affected by, fluoxetine, clozapine, duloxetine, and olanzapine, among other medications. One case study suggested that warfarin doses should be reduced by 30% in a patient who had started with a liquid formulation of CBD for managing epilepsy (Basic Clin Pharmacol Toxicol. 2019 Jan;124[1]:28-31).

At this point, it’s “not clear what the clinic implications are,” but “it’s not unreasonable to consider that your patients’ response to their psychiatric medications might change based on the introduction of cannabinoids,” said Arthur Williams, MD, assistant professor of clinical psychiatry at Columbia University, New York, and one of many researchers playing catch-up as marijuana and its derivatives enter the clinic.

Another question is what, exactly, is a standard dose?

Dosing mostly has been a question of THC, the psychoactive component of marijuana. Washington state and Colorado opted for 10-mg THC when those jurisdictions legalized recreational use; Oregon chose 5 mg. Both are in line with Food and Drug Administration formulations already on the market, including dronabinol (Marinol), a synthetic THC approved in 2.5-mg, 5-mg, and 10-mg doses for AIDS wasting, and chemotherapy nausea and vomiting.

A typical .7-g joint of 8% THC delivers about 5 mg or so, but newer strains range up to 20% THC, and could deliver over 13 mg per joint; occasional users, meanwhile, feel high from just 2-3 mg.

The ratio of THC to CBD matters, as well. Generally, “whole plant marijuana on the black market is much higher in THC and much lower in CBD,” Dr. Williams said. CBD is thought to deliver most of the medical benefits of marijuana.

It’s best to ask people what they’re using, and to counsel new users – especially the elderly – to start low and go slow. But keep in mind that many medical users have years of recreational use and have built up tolerance, he said.

Vaping is not a bad idea for those interested. It heats the plant material to high enough temperatures to release cannabinoids but without combusting. It’s a much more efficient THC delivery system than smoking, and there’s no smoke in the lungs. Vape patients often feel they can titrate their dose exactly.

Edibles are another matter. It can take hours for them to hit. Although THC levels do not spike with edibles as they do when the substance is inhaled, the effects last longer. A lot depends on how much food is in the gut.

The risk with edibles is that people may keep popping gummy bears and brownies because they don’t feel anything but end up overdosing. Children might be tempted by the treats, too, and for those under 4 years old, overdose can lead to fatal encephalopathic comas, “something we never really saw until edibles came around,” Dr. Williams said.

With edibles, “you have no idea what’s actually in the product.” Labels can be “inaccurate by an order of magnitude. Patients should be cautioned about that,” he said.

Pregnant and breastfeeding women, especially, should be warned away from marijuana. Some of the literature suggests a link between exposure to marijuana and preterm birth – in addition to early psychosis in vulnerable children.

Dr. Williams had no relevant disclosures.

[email protected]

SAN FRANCISCO – Medical marijuana skipped the usual phased testing of pharmaceuticals, so questions abound about how to counsel patients as legalization rolls out across the country, speakers said at the American Psychiatric Association annual meeting.

M. Alexander Otto/MDedge News

Drug interactions are an issue but remain under the radar. Tetrahydrocannabinol (THC) and cannabidiol (CBD) are inhibitors of cytochrome P450, specifically the CYP2C enzyme and CYP3A liver enzymes, which means possible interactions with drug classes such as antidepressants and antipsychotics might come into play.

Concomitant use could affect, or be affected by, fluoxetine, clozapine, duloxetine, and olanzapine, among other medications. One case study suggested that warfarin doses should be reduced by 30% in a patient who had started with a liquid formulation of CBD for managing epilepsy (Basic Clin Pharmacol Toxicol. 2019 Jan;124[1]:28-31).

At this point, it’s “not clear what the clinic implications are,” but “it’s not unreasonable to consider that your patients’ response to their psychiatric medications might change based on the introduction of cannabinoids,” said Arthur Williams, MD, assistant professor of clinical psychiatry at Columbia University, New York, and one of many researchers playing catch-up as marijuana and its derivatives enter the clinic.

Another question is what, exactly, is a standard dose?

Dosing mostly has been a question of THC, the psychoactive component of marijuana. Washington state and Colorado opted for 10-mg THC when those jurisdictions legalized recreational use; Oregon chose 5 mg. Both are in line with Food and Drug Administration formulations already on the market, including dronabinol (Marinol), a synthetic THC approved in 2.5-mg, 5-mg, and 10-mg doses for AIDS wasting, and chemotherapy nausea and vomiting.

A typical .7-g joint of 8% THC delivers about 5 mg or so, but newer strains range up to 20% THC, and could deliver over 13 mg per joint; occasional users, meanwhile, feel high from just 2-3 mg.

The ratio of THC to CBD matters, as well. Generally, “whole plant marijuana on the black market is much higher in THC and much lower in CBD,” Dr. Williams said. CBD is thought to deliver most of the medical benefits of marijuana.

It’s best to ask people what they’re using, and to counsel new users – especially the elderly – to start low and go slow. But keep in mind that many medical users have years of recreational use and have built up tolerance, he said.

Vaping is not a bad idea for those interested. It heats the plant material to high enough temperatures to release cannabinoids but without combusting. It’s a much more efficient THC delivery system than smoking, and there’s no smoke in the lungs. Vape patients often feel they can titrate their dose exactly.

Edibles are another matter. It can take hours for them to hit. Although THC levels do not spike with edibles as they do when the substance is inhaled, the effects last longer. A lot depends on how much food is in the gut.

The risk with edibles is that people may keep popping gummy bears and brownies because they don’t feel anything but end up overdosing. Children might be tempted by the treats, too, and for those under 4 years old, overdose can lead to fatal encephalopathic comas, “something we never really saw until edibles came around,” Dr. Williams said.

With edibles, “you have no idea what’s actually in the product.” Labels can be “inaccurate by an order of magnitude. Patients should be cautioned about that,” he said.

Pregnant and breastfeeding women, especially, should be warned away from marijuana. Some of the literature suggests a link between exposure to marijuana and preterm birth – in addition to early psychosis in vulnerable children.

Dr. Williams had no relevant disclosures.

[email protected]

SEATTLE – Pain, fatigue, depression, and anxiety are common among patients with multiple sclerosis (MS) in the 12 months after diagnosis, researchers reported at the annual meeting of the Consortium of Multiple Sclerosis Centers. In a novel study, about half of patients with MS reported clinically significant symptoms of depression or pain, and approximately 60% reported fatigue during that time.

Michigan Medicine

Pain, fatigue, depression, and anxiety are common in MS, but their prevalence in the first year after diagnosis is not well understood. To examine the rates of these conditions and how often they co-occur during that period, Anna L. Kratz, PhD, associate professor of physical medicine and rehabilitation at the University of Michigan in Ann Arbor, and her research colleagues had 231 adults with MS complete validated surveys at 1, 2, 3, 6, 9, and 12 months after diagnosis to assess symptoms of these conditions.

Overall, 47.2% of patients reported clinically significant levels of depression, 38.5% reported clinically significant levels of anxiety, 50.4% reported clinically significant pain, and 62.2% reported clinically significant fatigue at any point during the year after diagnosis. “Of those who did not have clinically significant symptoms at time of diagnosis, 21.3% went on to develop clinically significant depression, 17.0% anxiety, 30.9% pain, and 34.1% fatigue,” the authors reported.

About 23% of patients did not have clinically significant symptoms for any condition, while 20% had clinically significant symptoms for one condition, 21% for two, 19% for three, and 17% for all four.

Depression and fatigue had the highest rate of comorbidity, whereas pain and anxiety had the lowest rate of comorbidity.

“Important clinical symptoms associated with MS are present at high levels in the first year post diagnosis,” Dr. Kratz and colleagues concluded. “While the rates and severity are marginally lower than have been identified in studies of individuals farther into the MS disease course, this study is a reminder that early MS intervention should incorporate interventions for these symptoms that are known to have strong associations with quality of life.”

The researchers had no disclosures.

[email protected]

SEATTLE – Pain, fatigue, depression, and anxiety are common among patients with multiple sclerosis (MS) in the 12 months after diagnosis, researchers reported at the annual meeting of the Consortium of Multiple Sclerosis Centers. In a novel study, about half of patients with MS reported clinically significant symptoms of depression or pain, and approximately 60% reported fatigue during that time.

Michigan Medicine

Pain, fatigue, depression, and anxiety are common in MS, but their prevalence in the first year after diagnosis is not well understood. To examine the rates of these conditions and how often they co-occur during that period, Anna L. Kratz, PhD, associate professor of physical medicine and rehabilitation at the University of Michigan in Ann Arbor, and her research colleagues had 231 adults with MS complete validated surveys at 1, 2, 3, 6, 9, and 12 months after diagnosis to assess symptoms of these conditions.

Overall, 47.2% of patients reported clinically significant levels of depression, 38.5% reported clinically significant levels of anxiety, 50.4% reported clinically significant pain, and 62.2% reported clinically significant fatigue at any point during the year after diagnosis. “Of those who did not have clinically significant symptoms at time of diagnosis, 21.3% went on to develop clinically significant depression, 17.0% anxiety, 30.9% pain, and 34.1% fatigue,” the authors reported.

About 23% of patients did not have clinically significant symptoms for any condition, while 20% had clinically significant symptoms for one condition, 21% for two, 19% for three, and 17% for all four.

Depression and fatigue had the highest rate of comorbidity, whereas pain and anxiety had the lowest rate of comorbidity.

“Important clinical symptoms associated with MS are present at high levels in the first year post diagnosis,” Dr. Kratz and colleagues concluded. “While the rates and severity are marginally lower than have been identified in studies of individuals farther into the MS disease course, this study is a reminder that early MS intervention should incorporate interventions for these symptoms that are known to have strong associations with quality of life.”

The researchers had no disclosures.

[email protected]

SEATTLE – Pain, fatigue, depression, and anxiety are common among patients with multiple sclerosis (MS) in the 12 months after diagnosis, researchers reported at the annual meeting of the Consortium of Multiple Sclerosis Centers. In a novel study, about half of patients with MS reported clinically significant symptoms of depression or pain, and approximately 60% reported fatigue during that time.

Michigan Medicine

Pain, fatigue, depression, and anxiety are common in MS, but their prevalence in the first year after diagnosis is not well understood. To examine the rates of these conditions and how often they co-occur during that period, Anna L. Kratz, PhD, associate professor of physical medicine and rehabilitation at the University of Michigan in Ann Arbor, and her research colleagues had 231 adults with MS complete validated surveys at 1, 2, 3, 6, 9, and 12 months after diagnosis to assess symptoms of these conditions.

Overall, 47.2% of patients reported clinically significant levels of depression, 38.5% reported clinically significant levels of anxiety, 50.4% reported clinically significant pain, and 62.2% reported clinically significant fatigue at any point during the year after diagnosis. “Of those who did not have clinically significant symptoms at time of diagnosis, 21.3% went on to develop clinically significant depression, 17.0% anxiety, 30.9% pain, and 34.1% fatigue,” the authors reported.

About 23% of patients did not have clinically significant symptoms for any condition, while 20% had clinically significant symptoms for one condition, 21% for two, 19% for three, and 17% for all four.

Depression and fatigue had the highest rate of comorbidity, whereas pain and anxiety had the lowest rate of comorbidity.

“Important clinical symptoms associated with MS are present at high levels in the first year post diagnosis,” Dr. Kratz and colleagues concluded. “While the rates and severity are marginally lower than have been identified in studies of individuals farther into the MS disease course, this study is a reminder that early MS intervention should incorporate interventions for these symptoms that are known to have strong associations with quality of life.”

The researchers had no disclosures.

[email protected]

A little more than 10% of adolescents who visited an emergency department during 2005-2015 received an opioid prescription, although there was a small but significant decrease in prescriptions over that time, according to an analysis of two nationwide ambulatory care surveys.

For adolescents aged 13-17 years, 10.4% of ED visits were associated with a prescription for an opioid versus 1.6% among outpatient visits. There was a slight but significant decrease in the rate of opioid prescriptions in the ED setting over the study period, with an odds ratio of 0.95 (95% confidence interval, 0.92-0.97), but there was no significant change in the trend over time in the outpatient setting (OR, 1.02; 95% CI, 0.99-1.09), Joel D. Hudgins, MD, and associates reported in Pediatrics.

“Opioid prescribing in ambulatory care visits is particularly high in the ED setting and … certain diagnoses appear to be routinely treated with an opioid,” said Dr. Hudgins and associates from Boston Children’s Hospital.

The highest rates of opioid prescribing among adolescents visiting the ED involved dental disorders (60%) and acute injuries such as fractures of the clavicle (47%), ankle (38%), and metacarpals (36%). “However, when considering the total volume of opioid prescriptions dispensed [over 7.8 million during 2005-2015], certain common conditions, including abdominal pain, acute pharyngitis, urinary tract infection, and headache, contributed large numbers of prescriptions as well,” they added.

The study involved data from the National Hospital Ambulatory Medical Care Survey (hospital-based EDs) and the National Ambulatory Medical Care Survey (office-based practices), which both are conducted annually by the National Center for Health Statistics.

The senior investigator is supported by an award from the Burroughs Wellcome Fund by the Harvard-MIT Center for Regulatory Science. The authors said that they have no relevant financial relationships.

[email protected]

SOURCE: Hudgins JD et al. Pediatrics. 2019 June. doi: 10.1542/peds.2018-1578.

A little more than 10% of adolescents who visited an emergency department during 2005-2015 received an opioid prescription, although there was a small but significant decrease in prescriptions over that time, according to an analysis of two nationwide ambulatory care surveys.

For adolescents aged 13-17 years, 10.4% of ED visits were associated with a prescription for an opioid versus 1.6% among outpatient visits. There was a slight but significant decrease in the rate of opioid prescriptions in the ED setting over the study period, with an odds ratio of 0.95 (95% confidence interval, 0.92-0.97), but there was no significant change in the trend over time in the outpatient setting (OR, 1.02; 95% CI, 0.99-1.09), Joel D. Hudgins, MD, and associates reported in Pediatrics.

“Opioid prescribing in ambulatory care visits is particularly high in the ED setting and … certain diagnoses appear to be routinely treated with an opioid,” said Dr. Hudgins and associates from Boston Children’s Hospital.

The highest rates of opioid prescribing among adolescents visiting the ED involved dental disorders (60%) and acute injuries such as fractures of the clavicle (47%), ankle (38%), and metacarpals (36%). “However, when considering the total volume of opioid prescriptions dispensed [over 7.8 million during 2005-2015], certain common conditions, including abdominal pain, acute pharyngitis, urinary tract infection, and headache, contributed large numbers of prescriptions as well,” they added.

The study involved data from the National Hospital Ambulatory Medical Care Survey (hospital-based EDs) and the National Ambulatory Medical Care Survey (office-based practices), which both are conducted annually by the National Center for Health Statistics.

The senior investigator is supported by an award from the Burroughs Wellcome Fund by the Harvard-MIT Center for Regulatory Science. The authors said that they have no relevant financial relationships.

[email protected]

SOURCE: Hudgins JD et al. Pediatrics. 2019 June. doi: 10.1542/peds.2018-1578.

A little more than 10% of adolescents who visited an emergency department during 2005-2015 received an opioid prescription, although there was a small but significant decrease in prescriptions over that time, according to an analysis of two nationwide ambulatory care surveys.

For adolescents aged 13-17 years, 10.4% of ED visits were associated with a prescription for an opioid versus 1.6% among outpatient visits. There was a slight but significant decrease in the rate of opioid prescriptions in the ED setting over the study period, with an odds ratio of 0.95 (95% confidence interval, 0.92-0.97), but there was no significant change in the trend over time in the outpatient setting (OR, 1.02; 95% CI, 0.99-1.09), Joel D. Hudgins, MD, and associates reported in Pediatrics.

“Opioid prescribing in ambulatory care visits is particularly high in the ED setting and … certain diagnoses appear to be routinely treated with an opioid,” said Dr. Hudgins and associates from Boston Children’s Hospital.

The highest rates of opioid prescribing among adolescents visiting the ED involved dental disorders (60%) and acute injuries such as fractures of the clavicle (47%), ankle (38%), and metacarpals (36%). “However, when considering the total volume of opioid prescriptions dispensed [over 7.8 million during 2005-2015], certain common conditions, including abdominal pain, acute pharyngitis, urinary tract infection, and headache, contributed large numbers of prescriptions as well,” they added.

The study involved data from the National Hospital Ambulatory Medical Care Survey (hospital-based EDs) and the National Ambulatory Medical Care Survey (office-based practices), which both are conducted annually by the National Center for Health Statistics.

The senior investigator is supported by an award from the Burroughs Wellcome Fund by the Harvard-MIT Center for Regulatory Science. The authors said that they have no relevant financial relationships.

[email protected]

SOURCE: Hudgins JD et al. Pediatrics. 2019 June. doi: 10.1542/peds.2018-1578.

TORONTO – Tanezumab, a novel investigational nerve growth factor inhibitor, not only proved effective for the treatment of refractory pain in knee and hip osteoarthritis but was also notably rapidly acting, according to a secondary analysis of a phase 3 randomized trial.

Bruce Jancin/MDedge News

“The onset is relatively quick. It’s a monoclonal antibody, so it doesn’t work overnight, but by 3-5 days you see a significant difference,” Thomas J. Schnitzer, MD, PhD, reported at the OARSI 2019 World Congress.

He had previously presented the primary outcomes of this 696-patient, phase 3, randomized trial at the 2018 annual meeting of the American College of Rheumatology. At OARSI 2019, the rheumatologist presented new data focusing on the speed and durability of the pain relief provided by tanezumab, a humanized monoclonal antibody designed to help keep pain signals produced in the periphery from reaching the CNS.

The double-blind trial included U.S. patients with an average 9.3-year disease duration who were randomized to either two 2.5-mg subcutaneous injections of the nerve growth factor inhibitor 8 weeks apart, a 2.5-mg dose followed 8 weeks later by a 5-mg dose, or two placebo injections. Eighty-five percent of subjects had knee OA, and the rest had hip OA. The patients had fairly severe pain, with average baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores of 7.1-7.4. Notably, all study participants had to have a documented history of previous failure to respond to at least three pain relievers: acetaminophen, oral NSAIDs, and tramadol or opioids, according to Dr. Schnitzer, a rheumatologist who is professor of physical medicine and rehabilitation, anesthesiology, and medicine at Northwestern University in Chicago.

As previously reported, the co–primary endpoint of change from baseline to week 16 in WOMAC pain was –3.22 points with the 2.5-mg tanezumab regimen and –3.45 with the 2.5/5–mg strategy, both significantly better than the 2.56-point improvement with placebo. Improvement in WOMAC physical function followed suit, he said at the meeting sponsored by the Osteoarthritis Research Society International.

Assessments were made at office visits every 2 weeks during the study. By the first visit at week 2, tanezumab was significantly better than placebo on both WOMAC measures, an advantage maintained for the rest of the 16 weeks. Pain relief in the tanezumab-treated groups was maximum at weeks 4 and 12; that is, 4 weeks following the first and second injections.

“This suggests that there’s an immediate effect of the antibody, which then tends to wane as the antibody begins to get cleared,” Dr. Schnitzer observed.

Study participants kept a structured daily pain diary, which enabled investigators to zero in on the timing of pain relief. Statistically significant separation from placebo was documented by day 3 in one group on tanezumab and by day 5 in the other.

An increased rate of rapidly progressive OA was a concern years ago in earlier studies of a now-abandoned intravenous formulation of tanezumab. However, in the phase 3 trial of the subcutaneous humanized monoclonal antibody, rapidly progressive OA occurred in only six patients, or 1.3%, during the 24-week safety follow-up period. Interestingly, the phenomenon was not dose related, as five of the six cases occurred in patients on the twin 2.5-mg regimen, and only one in the 2.5/5-mg group. No cases of osteonecrosis occurred in the trial.

One audience member rose to say she and her fellow rheumatologists are very excited about the prospect of possible access to a novel and more effective OA therapy. But she took issue with the trial’s reliance on WOMAC pain and physical function scores as primary endpoints, noting that OARSI experts have developed and validated several more comprehensive and globally informative assessment tools. Dr. Schnitzer readily agreed. The investigators utilized WOMAC pain and physical function because that’s what the U.S. and European regulatory agencies insist upon, he explained.

Clinicians should stay tuned because the results of much larger, longer-term phase 3 trials of tanezumab are due to be presented soon, he added.

Dr. Schnitzer reported serving as a consultant to Pfizer and Eli Lilly, which are jointly developing tanezumab and sponsored the trial, as well as to a handful of other pharmaceutical companies.

[email protected]

SOURCE: Bessette L et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S85-6, Abstract 88.

TORONTO – Tanezumab, a novel investigational nerve growth factor inhibitor, not only proved effective for the treatment of refractory pain in knee and hip osteoarthritis but was also notably rapidly acting, according to a secondary analysis of a phase 3 randomized trial.

Bruce Jancin/MDedge News

“The onset is relatively quick. It’s a monoclonal antibody, so it doesn’t work overnight, but by 3-5 days you see a significant difference,” Thomas J. Schnitzer, MD, PhD, reported at the OARSI 2019 World Congress.

He had previously presented the primary outcomes of this 696-patient, phase 3, randomized trial at the 2018 annual meeting of the American College of Rheumatology. At OARSI 2019, the rheumatologist presented new data focusing on the speed and durability of the pain relief provided by tanezumab, a humanized monoclonal antibody designed to help keep pain signals produced in the periphery from reaching the CNS.

The double-blind trial included U.S. patients with an average 9.3-year disease duration who were randomized to either two 2.5-mg subcutaneous injections of the nerve growth factor inhibitor 8 weeks apart, a 2.5-mg dose followed 8 weeks later by a 5-mg dose, or two placebo injections. Eighty-five percent of subjects had knee OA, and the rest had hip OA. The patients had fairly severe pain, with average baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores of 7.1-7.4. Notably, all study participants had to have a documented history of previous failure to respond to at least three pain relievers: acetaminophen, oral NSAIDs, and tramadol or opioids, according to Dr. Schnitzer, a rheumatologist who is professor of physical medicine and rehabilitation, anesthesiology, and medicine at Northwestern University in Chicago.

As previously reported, the co–primary endpoint of change from baseline to week 16 in WOMAC pain was –3.22 points with the 2.5-mg tanezumab regimen and –3.45 with the 2.5/5–mg strategy, both significantly better than the 2.56-point improvement with placebo. Improvement in WOMAC physical function followed suit, he said at the meeting sponsored by the Osteoarthritis Research Society International.

Assessments were made at office visits every 2 weeks during the study. By the first visit at week 2, tanezumab was significantly better than placebo on both WOMAC measures, an advantage maintained for the rest of the 16 weeks. Pain relief in the tanezumab-treated groups was maximum at weeks 4 and 12; that is, 4 weeks following the first and second injections.

“This suggests that there’s an immediate effect of the antibody, which then tends to wane as the antibody begins to get cleared,” Dr. Schnitzer observed.

Study participants kept a structured daily pain diary, which enabled investigators to zero in on the timing of pain relief. Statistically significant separation from placebo was documented by day 3 in one group on tanezumab and by day 5 in the other.

An increased rate of rapidly progressive OA was a concern years ago in earlier studies of a now-abandoned intravenous formulation of tanezumab. However, in the phase 3 trial of the subcutaneous humanized monoclonal antibody, rapidly progressive OA occurred in only six patients, or 1.3%, during the 24-week safety follow-up period. Interestingly, the phenomenon was not dose related, as five of the six cases occurred in patients on the twin 2.5-mg regimen, and only one in the 2.5/5-mg group. No cases of osteonecrosis occurred in the trial.

One audience member rose to say she and her fellow rheumatologists are very excited about the prospect of possible access to a novel and more effective OA therapy. But she took issue with the trial’s reliance on WOMAC pain and physical function scores as primary endpoints, noting that OARSI experts have developed and validated several more comprehensive and globally informative assessment tools. Dr. Schnitzer readily agreed. The investigators utilized WOMAC pain and physical function because that’s what the U.S. and European regulatory agencies insist upon, he explained.

Clinicians should stay tuned because the results of much larger, longer-term phase 3 trials of tanezumab are due to be presented soon, he added.

Dr. Schnitzer reported serving as a consultant to Pfizer and Eli Lilly, which are jointly developing tanezumab and sponsored the trial, as well as to a handful of other pharmaceutical companies.

[email protected]

SOURCE: Bessette L et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S85-6, Abstract 88.

TORONTO – Tanezumab, a novel investigational nerve growth factor inhibitor, not only proved effective for the treatment of refractory pain in knee and hip osteoarthritis but was also notably rapidly acting, according to a secondary analysis of a phase 3 randomized trial.

Bruce Jancin/MDedge News

“The onset is relatively quick. It’s a monoclonal antibody, so it doesn’t work overnight, but by 3-5 days you see a significant difference,” Thomas J. Schnitzer, MD, PhD, reported at the OARSI 2019 World Congress.

He had previously presented the primary outcomes of this 696-patient, phase 3, randomized trial at the 2018 annual meeting of the American College of Rheumatology. At OARSI 2019, the rheumatologist presented new data focusing on the speed and durability of the pain relief provided by tanezumab, a humanized monoclonal antibody designed to help keep pain signals produced in the periphery from reaching the CNS.

The double-blind trial included U.S. patients with an average 9.3-year disease duration who were randomized to either two 2.5-mg subcutaneous injections of the nerve growth factor inhibitor 8 weeks apart, a 2.5-mg dose followed 8 weeks later by a 5-mg dose, or two placebo injections. Eighty-five percent of subjects had knee OA, and the rest had hip OA. The patients had fairly severe pain, with average baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores of 7.1-7.4. Notably, all study participants had to have a documented history of previous failure to respond to at least three pain relievers: acetaminophen, oral NSAIDs, and tramadol or opioids, according to Dr. Schnitzer, a rheumatologist who is professor of physical medicine and rehabilitation, anesthesiology, and medicine at Northwestern University in Chicago.

As previously reported, the co–primary endpoint of change from baseline to week 16 in WOMAC pain was –3.22 points with the 2.5-mg tanezumab regimen and –3.45 with the 2.5/5–mg strategy, both significantly better than the 2.56-point improvement with placebo. Improvement in WOMAC physical function followed suit, he said at the meeting sponsored by the Osteoarthritis Research Society International.

Assessments were made at office visits every 2 weeks during the study. By the first visit at week 2, tanezumab was significantly better than placebo on both WOMAC measures, an advantage maintained for the rest of the 16 weeks. Pain relief in the tanezumab-treated groups was maximum at weeks 4 and 12; that is, 4 weeks following the first and second injections.

“This suggests that there’s an immediate effect of the antibody, which then tends to wane as the antibody begins to get cleared,” Dr. Schnitzer observed.

Study participants kept a structured daily pain diary, which enabled investigators to zero in on the timing of pain relief. Statistically significant separation from placebo was documented by day 3 in one group on tanezumab and by day 5 in the other.

An increased rate of rapidly progressive OA was a concern years ago in earlier studies of a now-abandoned intravenous formulation of tanezumab. However, in the phase 3 trial of the subcutaneous humanized monoclonal antibody, rapidly progressive OA occurred in only six patients, or 1.3%, during the 24-week safety follow-up period. Interestingly, the phenomenon was not dose related, as five of the six cases occurred in patients on the twin 2.5-mg regimen, and only one in the 2.5/5-mg group. No cases of osteonecrosis occurred in the trial.

One audience member rose to say she and her fellow rheumatologists are very excited about the prospect of possible access to a novel and more effective OA therapy. But she took issue with the trial’s reliance on WOMAC pain and physical function scores as primary endpoints, noting that OARSI experts have developed and validated several more comprehensive and globally informative assessment tools. Dr. Schnitzer readily agreed. The investigators utilized WOMAC pain and physical function because that’s what the U.S. and European regulatory agencies insist upon, he explained.

Clinicians should stay tuned because the results of much larger, longer-term phase 3 trials of tanezumab are due to be presented soon, he added.

Dr. Schnitzer reported serving as a consultant to Pfizer and Eli Lilly, which are jointly developing tanezumab and sponsored the trial, as well as to a handful of other pharmaceutical companies.

[email protected]

SOURCE: Bessette L et al. Osteoarthritis Cartilage. 2019 Apr;27[suppl 1]:S85-6, Abstract 88.

WASHINGTON – Implementing an alert on electronic medical records to reinforce a change in public policy appears to be having a positive effect on opioid prescriptions.

Gregory Twachtman/MDedge News

Researchers looked at prescribing patterns of doctors in the Penn Medicine health system, which straddles both the Philadelphia area and southern New Jersey, following the implementation of prescribing limits in New Jersey.

The law in question is a 5-day limit on new opioid prescriptions, which was passed in February 2017 and implemented in May 2017. Penn Medicine implemented an EMR alert in their New Jersey locations to alert physicians within the Penn Medicine system of the change in their state law 2 months after the law went into effect. Researchers looked at prescribing patterns before passage, during the transition between passage and the implementation of the EMR alert and following implementation of the EMR alert, as well as secondary outcomes such as rate of refills, telephone calls, and utilization.

“The implementation of the prescribing limit and EMR alert was associated with a decrease in the volume of opioids prescribed in acute prescriptions without changes in the rates of refills, telephone calls or utilization,” Margaret Lowenstein, MD, of the University of Pennsylvania, Philadelphia, said at the annual meeting of the Society of General Internal Medicine.

“This combination of the policy and the EMR alert may be an effective strategy to influence prescriber behavior,” she added.

Researchers compared outcomes before and after the implementation of the law in New Jersey, using prescribing patterns in Pennsylvania as the control. The cohort of patients was those with a new opioid prescription within Penn Medicine ambulatory nonteaching practices. It excluded specialties not represented in both states as well as patients with cancer, those in hospice and palliative care and those in treatment for opioid use disorder, since the law does not apply to those groups.

In New Jersey, there were 434 patients receiving new prescriptions in the 12 months prior to the implementation of the law, with 234 patients receiving new prescriptions in the 9 months after the EMR alert was implemented in New Jersey. In Pennsylvania, the cohort included 2,961 patients prior to the law going into effect and 1,677 after the EMR intervention went live in New Jersey.

For New Jersey, the morphine milligram equivalent (MME) per prescription was steady at about 350 during the period prior to the law’s implementation, but dropped to nearly 250 by the end of the postintervention period examined. In Pennsylvania, the prelaw implementation period had an MME per prescription a little higher than 200, which leveled off at around 200 during the postintervention period.

“In New Jersey, there is a significantly higher MME than in Pennsylvania and this difference persists in the transition period but what you see in the post period is a significantly greater decline in the MME per prescription in New Jersey as compared to the rate of change in Pa.,” Dr. Lowenstein said. “That difference was statistically significant.”

She said similar results were seen regarding the quantity of tablets prescribed. In New Jersey before the law’s passage, the number of tablets per prescription was close to 50, dropping down to about 35 post period. Pennsylvania saw a slight decrease from about 35 pills per prescription to about 33 during the same period.

No significant changes occurred in the other outcomes measured following implementation of the EMR alert.

Dr. Lowenstein noted that, because the transition period between the law going into effect and the implementation of the EMR alert was so short, whether the greater decreases in opioid prescriptions in New Jersey relative to Pennsylvania was because of the law alone, the EMR alert alone, or both changes is unclear.

Based on the limited amount of change in prescribing patterns during the transition period, it appears that the EMR intervention may be driving the change, “but we weren’t powered to make that determination,” she added.

Dr. Lowenstein and her colleagues reported no disclosures.

[email protected]

WASHINGTON – Implementing an alert on electronic medical records to reinforce a change in public policy appears to be having a positive effect on opioid prescriptions.

Gregory Twachtman/MDedge News

Researchers looked at prescribing patterns of doctors in the Penn Medicine health system, which straddles both the Philadelphia area and southern New Jersey, following the implementation of prescribing limits in New Jersey.

The law in question is a 5-day limit on new opioid prescriptions, which was passed in February 2017 and implemented in May 2017. Penn Medicine implemented an EMR alert in their New Jersey locations to alert physicians within the Penn Medicine system of the change in their state law 2 months after the law went into effect. Researchers looked at prescribing patterns before passage, during the transition between passage and the implementation of the EMR alert and following implementation of the EMR alert, as well as secondary outcomes such as rate of refills, telephone calls, and utilization.

“The implementation of the prescribing limit and EMR alert was associated with a decrease in the volume of opioids prescribed in acute prescriptions without changes in the rates of refills, telephone calls or utilization,” Margaret Lowenstein, MD, of the University of Pennsylvania, Philadelphia, said at the annual meeting of the Society of General Internal Medicine.

“This combination of the policy and the EMR alert may be an effective strategy to influence prescriber behavior,” she added.

Researchers compared outcomes before and after the implementation of the law in New Jersey, using prescribing patterns in Pennsylvania as the control. The cohort of patients was those with a new opioid prescription within Penn Medicine ambulatory nonteaching practices. It excluded specialties not represented in both states as well as patients with cancer, those in hospice and palliative care and those in treatment for opioid use disorder, since the law does not apply to those groups.

In New Jersey, there were 434 patients receiving new prescriptions in the 12 months prior to the implementation of the law, with 234 patients receiving new prescriptions in the 9 months after the EMR alert was implemented in New Jersey. In Pennsylvania, the cohort included 2,961 patients prior to the law going into effect and 1,677 after the EMR intervention went live in New Jersey.

For New Jersey, the morphine milligram equivalent (MME) per prescription was steady at about 350 during the period prior to the law’s implementation, but dropped to nearly 250 by the end of the postintervention period examined. In Pennsylvania, the prelaw implementation period had an MME per prescription a little higher than 200, which leveled off at around 200 during the postintervention period.

“In New Jersey, there is a significantly higher MME than in Pennsylvania and this difference persists in the transition period but what you see in the post period is a significantly greater decline in the MME per prescription in New Jersey as compared to the rate of change in Pa.,” Dr. Lowenstein said. “That difference was statistically significant.”

She said similar results were seen regarding the quantity of tablets prescribed. In New Jersey before the law’s passage, the number of tablets per prescription was close to 50, dropping down to about 35 post period. Pennsylvania saw a slight decrease from about 35 pills per prescription to about 33 during the same period.

No significant changes occurred in the other outcomes measured following implementation of the EMR alert.

Dr. Lowenstein noted that, because the transition period between the law going into effect and the implementation of the EMR alert was so short, whether the greater decreases in opioid prescriptions in New Jersey relative to Pennsylvania was because of the law alone, the EMR alert alone, or both changes is unclear.

Based on the limited amount of change in prescribing patterns during the transition period, it appears that the EMR intervention may be driving the change, “but we weren’t powered to make that determination,” she added.

Dr. Lowenstein and her colleagues reported no disclosures.

[email protected]

WASHINGTON – Implementing an alert on electronic medical records to reinforce a change in public policy appears to be having a positive effect on opioid prescriptions.

Gregory Twachtman/MDedge News

Researchers looked at prescribing patterns of doctors in the Penn Medicine health system, which straddles both the Philadelphia area and southern New Jersey, following the implementation of prescribing limits in New Jersey.

The law in question is a 5-day limit on new opioid prescriptions, which was passed in February 2017 and implemented in May 2017. Penn Medicine implemented an EMR alert in their New Jersey locations to alert physicians within the Penn Medicine system of the change in their state law 2 months after the law went into effect. Researchers looked at prescribing patterns before passage, during the transition between passage and the implementation of the EMR alert and following implementation of the EMR alert, as well as secondary outcomes such as rate of refills, telephone calls, and utilization.

“The implementation of the prescribing limit and EMR alert was associated with a decrease in the volume of opioids prescribed in acute prescriptions without changes in the rates of refills, telephone calls or utilization,” Margaret Lowenstein, MD, of the University of Pennsylvania, Philadelphia, said at the annual meeting of the Society of General Internal Medicine.

“This combination of the policy and the EMR alert may be an effective strategy to influence prescriber behavior,” she added.

Researchers compared outcomes before and after the implementation of the law in New Jersey, using prescribing patterns in Pennsylvania as the control. The cohort of patients was those with a new opioid prescription within Penn Medicine ambulatory nonteaching practices. It excluded specialties not represented in both states as well as patients with cancer, those in hospice and palliative care and those in treatment for opioid use disorder, since the law does not apply to those groups.

In New Jersey, there were 434 patients receiving new prescriptions in the 12 months prior to the implementation of the law, with 234 patients receiving new prescriptions in the 9 months after the EMR alert was implemented in New Jersey. In Pennsylvania, the cohort included 2,961 patients prior to the law going into effect and 1,677 after the EMR intervention went live in New Jersey.

For New Jersey, the morphine milligram equivalent (MME) per prescription was steady at about 350 during the period prior to the law’s implementation, but dropped to nearly 250 by the end of the postintervention period examined. In Pennsylvania, the prelaw implementation period had an MME per prescription a little higher than 200, which leveled off at around 200 during the postintervention period.

“In New Jersey, there is a significantly higher MME than in Pennsylvania and this difference persists in the transition period but what you see in the post period is a significantly greater decline in the MME per prescription in New Jersey as compared to the rate of change in Pa.,” Dr. Lowenstein said. “That difference was statistically significant.”

She said similar results were seen regarding the quantity of tablets prescribed. In New Jersey before the law’s passage, the number of tablets per prescription was close to 50, dropping down to about 35 post period. Pennsylvania saw a slight decrease from about 35 pills per prescription to about 33 during the same period.

No significant changes occurred in the other outcomes measured following implementation of the EMR alert.

Dr. Lowenstein noted that, because the transition period between the law going into effect and the implementation of the EMR alert was so short, whether the greater decreases in opioid prescriptions in New Jersey relative to Pennsylvania was because of the law alone, the EMR alert alone, or both changes is unclear.

Based on the limited amount of change in prescribing patterns during the transition period, it appears that the EMR intervention may be driving the change, “but we weren’t powered to make that determination,” she added.

Dr. Lowenstein and her colleagues reported no disclosures.

[email protected]

For men with inflammatory bowel disease, herpes zoster vaccination was associated with about a 46% decrease in risk of associated infection, according to the results of a retrospective study from the national Veterans Affairs Healthcare System.

Crude rates of herpes zoster infection were 4.09 cases per 1,000 person-years among vaccinated patients versus 6.97 cases per 1,000 person-years among unvaccinated patients, for an adjusted hazard ratio of 0.54 (95% confidence interval, 0.44-0.68), reported Nabeel Khan, MD, of the University of Pennsylvania, Philadelphia, and associates. “This vaccine is therefore effective in patients with IBD, but underused,” they wrote in Clinical Gastroenterology and Hepatology.

Studies have linked IBD with a 1.2- to 1.8-fold increased risk of herpes zoster infection, the researchers noted. Relevant risk factors include older age, disease flare, recent use or high cumulative use of prednisone, and use of thiopurines, either alone or in combination with a tumor necrosis factor (TNF) inhibitor. Although the American College of Gastroenterology recommends that all patients with IBD receive the herpes zoster vaccine by age 50 years, the efficacy of the vaccine in these patients remains unclear.

For their study, Dr. Khan and associates analyzed International Classification of Diseases (ICD) codes and other medical record data from 39,983 veterans with IBD who had not received the herpes zoster vaccine by age 60 years. In all, 97% of patients were male, and 94% were white. Most patients had high rates of health care utilization: Approximately half visited VA clinics or hospitals at least 13 times per year, and another third made 6-12 annual visits.

Despite their many contacts with VA health care systems, only 7,170 (17.9%) patients received the herpes zoster vaccine during 2000-2016, the researchers found. Vaccination rates varied substantially by region – they were highest in the Midwest (35%) and North Atlantic states (29%) but reached only 9% in Montana, Utah, Wyoming, Colorado, Oklahoma, Texas, Arkansas, and Louisiana, collectively.

The crude rate of herpes zoster infection among unvaccinated patients with IBD resembled the incidence reported in prior studies, the researchers said. After researchers accounted for differences in geography, demographics, and health care utilization between vaccinated and unvaccinated veterans with IBD, they found that vaccination was associated with an approximately 46% decrease in the risk of herpes zoster infection.

Very few patients were vaccinated for herpes zoster while on a TNF inhibitor, precluding the ability to study this subgroup. However, the vaccine showed a protective effect (adjusted HR, 0.63) among patients who received thiopurines without a TNF inhibitor. This effect did not reach statistical significance, perhaps because of lack of power, the researchers noted. “Among the 315 patients who were [vaccinated while] on thiopurines, none developed a documented painful or painless vesicular rash within 42 days of herpes zoster vaccination,” they added. One patient developed a painful blister 20 days post vaccination without vesicles or long-term sequelae.

Pfizer provided funding. Dr. Khan disclosed research funding from Pfizer, Luitpold, and Takeda Pharmaceuticals. One coinvestigator disclosed ties to Pfizer, Gilead, Merck, AbbVie, Lilly, Janssen, Johnson & Johnson, UCB, and Nestle Health Science. The remaining researchers disclosed no conflicts.

SOURCE: Khan N et al. Clin Gastroenterol Hepatol. 2018 Oct 13. doi: 10.1016/j.cgh.2018.10.016.

For men with inflammatory bowel disease, herpes zoster vaccination was associated with about a 46% decrease in risk of associated infection, according to the results of a retrospective study from the national Veterans Affairs Healthcare System.

Crude rates of herpes zoster infection were 4.09 cases per 1,000 person-years among vaccinated patients versus 6.97 cases per 1,000 person-years among unvaccinated patients, for an adjusted hazard ratio of 0.54 (95% confidence interval, 0.44-0.68), reported Nabeel Khan, MD, of the University of Pennsylvania, Philadelphia, and associates. “This vaccine is therefore effective in patients with IBD, but underused,” they wrote in Clinical Gastroenterology and Hepatology.

Studies have linked IBD with a 1.2- to 1.8-fold increased risk of herpes zoster infection, the researchers noted. Relevant risk factors include older age, disease flare, recent use or high cumulative use of prednisone, and use of thiopurines, either alone or in combination with a tumor necrosis factor (TNF) inhibitor. Although the American College of Gastroenterology recommends that all patients with IBD receive the herpes zoster vaccine by age 50 years, the efficacy of the vaccine in these patients remains unclear.

For their study, Dr. Khan and associates analyzed International Classification of Diseases (ICD) codes and other medical record data from 39,983 veterans with IBD who had not received the herpes zoster vaccine by age 60 years. In all, 97% of patients were male, and 94% were white. Most patients had high rates of health care utilization: Approximately half visited VA clinics or hospitals at least 13 times per year, and another third made 6-12 annual visits.

Despite their many contacts with VA health care systems, only 7,170 (17.9%) patients received the herpes zoster vaccine during 2000-2016, the researchers found. Vaccination rates varied substantially by region – they were highest in the Midwest (35%) and North Atlantic states (29%) but reached only 9% in Montana, Utah, Wyoming, Colorado, Oklahoma, Texas, Arkansas, and Louisiana, collectively.

The crude rate of herpes zoster infection among unvaccinated patients with IBD resembled the incidence reported in prior studies, the researchers said. After researchers accounted for differences in geography, demographics, and health care utilization between vaccinated and unvaccinated veterans with IBD, they found that vaccination was associated with an approximately 46% decrease in the risk of herpes zoster infection.

Very few patients were vaccinated for herpes zoster while on a TNF inhibitor, precluding the ability to study this subgroup. However, the vaccine showed a protective effect (adjusted HR, 0.63) among patients who received thiopurines without a TNF inhibitor. This effect did not reach statistical significance, perhaps because of lack of power, the researchers noted. “Among the 315 patients who were [vaccinated while] on thiopurines, none developed a documented painful or painless vesicular rash within 42 days of herpes zoster vaccination,” they added. One patient developed a painful blister 20 days post vaccination without vesicles or long-term sequelae.

Pfizer provided funding. Dr. Khan disclosed research funding from Pfizer, Luitpold, and Takeda Pharmaceuticals. One coinvestigator disclosed ties to Pfizer, Gilead, Merck, AbbVie, Lilly, Janssen, Johnson & Johnson, UCB, and Nestle Health Science. The remaining researchers disclosed no conflicts.

SOURCE: Khan N et al. Clin Gastroenterol Hepatol. 2018 Oct 13. doi: 10.1016/j.cgh.2018.10.016.

For men with inflammatory bowel disease, herpes zoster vaccination was associated with about a 46% decrease in risk of associated infection, according to the results of a retrospective study from the national Veterans Affairs Healthcare System.

Crude rates of herpes zoster infection were 4.09 cases per 1,000 person-years among vaccinated patients versus 6.97 cases per 1,000 person-years among unvaccinated patients, for an adjusted hazard ratio of 0.54 (95% confidence interval, 0.44-0.68), reported Nabeel Khan, MD, of the University of Pennsylvania, Philadelphia, and associates. “This vaccine is therefore effective in patients with IBD, but underused,” they wrote in Clinical Gastroenterology and Hepatology.

Studies have linked IBD with a 1.2- to 1.8-fold increased risk of herpes zoster infection, the researchers noted. Relevant risk factors include older age, disease flare, recent use or high cumulative use of prednisone, and use of thiopurines, either alone or in combination with a tumor necrosis factor (TNF) inhibitor. Although the American College of Gastroenterology recommends that all patients with IBD receive the herpes zoster vaccine by age 50 years, the efficacy of the vaccine in these patients remains unclear.

For their study, Dr. Khan and associates analyzed International Classification of Diseases (ICD) codes and other medical record data from 39,983 veterans with IBD who had not received the herpes zoster vaccine by age 60 years. In all, 97% of patients were male, and 94% were white. Most patients had high rates of health care utilization: Approximately half visited VA clinics or hospitals at least 13 times per year, and another third made 6-12 annual visits.

Despite their many contacts with VA health care systems, only 7,170 (17.9%) patients received the herpes zoster vaccine during 2000-2016, the researchers found. Vaccination rates varied substantially by region – they were highest in the Midwest (35%) and North Atlantic states (29%) but reached only 9% in Montana, Utah, Wyoming, Colorado, Oklahoma, Texas, Arkansas, and Louisiana, collectively.

The crude rate of herpes zoster infection among unvaccinated patients with IBD resembled the incidence reported in prior studies, the researchers said. After researchers accounted for differences in geography, demographics, and health care utilization between vaccinated and unvaccinated veterans with IBD, they found that vaccination was associated with an approximately 46% decrease in the risk of herpes zoster infection.

Very few patients were vaccinated for herpes zoster while on a TNF inhibitor, precluding the ability to study this subgroup. However, the vaccine showed a protective effect (adjusted HR, 0.63) among patients who received thiopurines without a TNF inhibitor. This effect did not reach statistical significance, perhaps because of lack of power, the researchers noted. “Among the 315 patients who were [vaccinated while] on thiopurines, none developed a documented painful or painless vesicular rash within 42 days of herpes zoster vaccination,” they added. One patient developed a painful blister 20 days post vaccination without vesicles or long-term sequelae.

Pfizer provided funding. Dr. Khan disclosed research funding from Pfizer, Luitpold, and Takeda Pharmaceuticals. One coinvestigator disclosed ties to Pfizer, Gilead, Merck, AbbVie, Lilly, Janssen, Johnson & Johnson, UCB, and Nestle Health Science. The remaining researchers disclosed no conflicts.

SOURCE: Khan N et al. Clin Gastroenterol Hepatol. 2018 Oct 13. doi: 10.1016/j.cgh.2018.10.016.

NEW ORLEANS – About two thirds of men who chronically use opioids have low testosterone levels, based on a literature search of more than 50 randomized and observational studies that examined endocrine function in patients on chronic opioid therapy.

Hypocortisolism, seen in about 20% of the men in these studies, was among the other potentially significant deficiencies in endocrine function, Amir H. Zamanipoor Najafabadi, PhD, reported at the annual meeting of the Endocrine Society.

Dr. Najafabadi of Leiden University in the Netherlands, and Friso de Vries, PhD, analyzed the link between opioid use and changes in the gonadal axis. Most of the subjects in their study were men (J Endocr Soc. 2019. doi. 10.1210/js.2019-SUN-489).

While the data do not support firm conclusions on the health consequences of these endocrine observations, Dr. Najafabadi said that a prospective trial is needed to determine whether there is a potential benefit from screening patients on chronic opioids for potentially treatable endocrine deficiencies.

NEW ORLEANS – About two thirds of men who chronically use opioids have low testosterone levels, based on a literature search of more than 50 randomized and observational studies that examined endocrine function in patients on chronic opioid therapy.

Hypocortisolism, seen in about 20% of the men in these studies, was among the other potentially significant deficiencies in endocrine function, Amir H. Zamanipoor Najafabadi, PhD, reported at the annual meeting of the Endocrine Society.

Dr. Najafabadi of Leiden University in the Netherlands, and Friso de Vries, PhD, analyzed the link between opioid use and changes in the gonadal axis. Most of the subjects in their study were men (J Endocr Soc. 2019. doi. 10.1210/js.2019-SUN-489).

While the data do not support firm conclusions on the health consequences of these endocrine observations, Dr. Najafabadi said that a prospective trial is needed to determine whether there is a potential benefit from screening patients on chronic opioids for potentially treatable endocrine deficiencies.

NEW ORLEANS – About two thirds of men who chronically use opioids have low testosterone levels, based on a literature search of more than 50 randomized and observational studies that examined endocrine function in patients on chronic opioid therapy.

Hypocortisolism, seen in about 20% of the men in these studies, was among the other potentially significant deficiencies in endocrine function, Amir H. Zamanipoor Najafabadi, PhD, reported at the annual meeting of the Endocrine Society.

Dr. Najafabadi of Leiden University in the Netherlands, and Friso de Vries, PhD, analyzed the link between opioid use and changes in the gonadal axis. Most of the subjects in their study were men (J Endocr Soc. 2019. doi. 10.1210/js.2019-SUN-489).

While the data do not support firm conclusions on the health consequences of these endocrine observations, Dr. Najafabadi said that a prospective trial is needed to determine whether there is a potential benefit from screening patients on chronic opioids for potentially treatable endocrine deficiencies.

ANSWER

The correct interpretation incudes normal sinus rhythm, inferior MI, possible anterior MI, and ST-T wave abnormalities.

Normal sinus rhythm is evidenced by a P wave for every QRS and a QRS for every P wave with a normal PR interval and a rate > 60 and < 100 beats/min.

An old inferior MI is indicated by the Q waves in inferior leads II, III, and aVF. The absence of ST-segment elevation in these leads also contributes to the diagnosis of an old rather than new MI. Possible anterior MI can be inferred from the poor R-wave progression in leads V₁ through V₃ with the absence of ST elevation.

ST-T wave abnormalities are evidenced by the chronic ST-segment elevation in V₁ and V₂ with T-wave inversions in leads V₃ through V₆ and in aVF. These may be due to remodeling and/or ECG lead placement.

The patient was subsequently cleared for his shoulder repair.

ANSWER

The correct interpretation incudes normal sinus rhythm, inferior MI, possible anterior MI, and ST-T wave abnormalities.

Normal sinus rhythm is evidenced by a P wave for every QRS and a QRS for every P wave with a normal PR interval and a rate > 60 and < 100 beats/min.

An old inferior MI is indicated by the Q waves in inferior leads II, III, and aVF. The absence of ST-segment elevation in these leads also contributes to the diagnosis of an old rather than new MI. Possible anterior MI can be inferred from the poor R-wave progression in leads V₁ through V₃ with the absence of ST elevation.

ST-T wave abnormalities are evidenced by the chronic ST-segment elevation in V₁ and V₂ with T-wave inversions in leads V₃ through V₆ and in aVF. These may be due to remodeling and/or ECG lead placement.

The patient was subsequently cleared for his shoulder repair.

ANSWER

The correct interpretation incudes normal sinus rhythm, inferior MI, possible anterior MI, and ST-T wave abnormalities.

Normal sinus rhythm is evidenced by a P wave for every QRS and a QRS for every P wave with a normal PR interval and a rate > 60 and < 100 beats/min.

An old inferior MI is indicated by the Q waves in inferior leads II, III, and aVF. The absence of ST-segment elevation in these leads also contributes to the diagnosis of an old rather than new MI. Possible anterior MI can be inferred from the poor R-wave progression in leads V₁ through V₃ with the absence of ST elevation.

ST-T wave abnormalities are evidenced by the chronic ST-segment elevation in V₁ and V₂ with T-wave inversions in leads V₃ through V₆ and in aVF. These may be due to remodeling and/or ECG lead placement.

The patient was subsequently cleared for his shoulder repair.

WASHINGTON – More lonely elderly patients suffered from health symptoms and received very aggressive end of life care than nonlonely elderly patients, according to a study presented at the annual meeting of the Society of General Internal Medicine.

“Loneliness and social isolation are very common problems, especially in older Americans, and inflict about 30%-40% of older Americans. But while we know that this may have implications for their quality [of] life and may actually lead to premature death, we know very little about the end of life experience,” said Nauzley Abedini, MD, MSc, a hospitalist in internal medicine at the University of Michigan, Ann Arbor.

The study sought to determine the association between loneliness and end of life experience as measured by symptom burden, intensity of care, and advance care planning in adults. The pooled cohort study used data from the Health and Retirement Study (HRS) to analyze older Americans (aged 50 years or more) who died between 2004 and 2014. Investigators conducted postmortem “exit interviews” with the next of kin after each participant’s death. There were 2,896 participants included in the survey. Of these participants, 34% (942) were lonely; the remaining 1,954 of elderly adults were classified as nonlonely.

Loneliness was defined using the three-item Revised University of California, Los Angeles, Loneliness Scale score from a decedent’s last HRS interview prior to death. These items included feeling left out, feeling isolated, and lacking companionship. Investigators used this data to create a loneliness variable on previously established cutpoints for “lonely” and “nonlonely” participants. The data was used from the most recent survey prior to death.

Results showed more lonely older adults suffered from health symptoms in the last year of life, compared with nonlonely older adults (69.1% vs. 59.5%; odds ratio, 1.52; 95% confidence interval, 1.30-1.78). These symptoms included being troubled by pain, having difficulty breathing, experiencing severe fatigue, and having periodic confusion.

Patients with loneliness associated with intensity of health care at the end of life were more likely to die in a nursing home than at home, compared with nonlonely adults (OR, 1.68; 95% CI, 1.25-2.27). The lonely patients also were more likely to use life support during their last 2 years of life (OR, 1.41; 95% CI, 1.16-1.70).

“For clinicians, we need to identify end of life as an additional vulnerable time for people who are lonely. Currently, most of our interventions in terms of screening for loneliness are in the outpatient setting, but I would argue that working in hospitals, hospices, nursing homes, and community organizations, where these folks are living and dying, would be useful places to screen for this,” Dr. Abedini said.

The authors had no disclosures.

WASHINGTON – More lonely elderly patients suffered from health symptoms and received very aggressive end of life care than nonlonely elderly patients, according to a study presented at the annual meeting of the Society of General Internal Medicine.

“Loneliness and social isolation are very common problems, especially in older Americans, and inflict about 30%-40% of older Americans. But while we know that this may have implications for their quality [of] life and may actually lead to premature death, we know very little about the end of life experience,” said Nauzley Abedini, MD, MSc, a hospitalist in internal medicine at the University of Michigan, Ann Arbor.

The study sought to determine the association between loneliness and end of life experience as measured by symptom burden, intensity of care, and advance care planning in adults. The pooled cohort study used data from the Health and Retirement Study (HRS) to analyze older Americans (aged 50 years or more) who died between 2004 and 2014. Investigators conducted postmortem “exit interviews” with the next of kin after each participant’s death. There were 2,896 participants included in the survey. Of these participants, 34% (942) were lonely; the remaining 1,954 of elderly adults were classified as nonlonely.

Loneliness was defined using the three-item Revised University of California, Los Angeles, Loneliness Scale score from a decedent’s last HRS interview prior to death. These items included feeling left out, feeling isolated, and lacking companionship. Investigators used this data to create a loneliness variable on previously established cutpoints for “lonely” and “nonlonely” participants. The data was used from the most recent survey prior to death.

Results showed more lonely older adults suffered from health symptoms in the last year of life, compared with nonlonely older adults (69.1% vs. 59.5%; odds ratio, 1.52; 95% confidence interval, 1.30-1.78). These symptoms included being troubled by pain, having difficulty breathing, experiencing severe fatigue, and having periodic confusion.

Patients with loneliness associated with intensity of health care at the end of life were more likely to die in a nursing home than at home, compared with nonlonely adults (OR, 1.68; 95% CI, 1.25-2.27). The lonely patients also were more likely to use life support during their last 2 years of life (OR, 1.41; 95% CI, 1.16-1.70).

“For clinicians, we need to identify end of life as an additional vulnerable time for people who are lonely. Currently, most of our interventions in terms of screening for loneliness are in the outpatient setting, but I would argue that working in hospitals, hospices, nursing homes, and community organizations, where these folks are living and dying, would be useful places to screen for this,” Dr. Abedini said.

The authors had no disclosures.

WASHINGTON – More lonely elderly patients suffered from health symptoms and received very aggressive end of life care than nonlonely elderly patients, according to a study presented at the annual meeting of the Society of General Internal Medicine.

“Loneliness and social isolation are very common problems, especially in older Americans, and inflict about 30%-40% of older Americans. But while we know that this may have implications for their quality [of] life and may actually lead to premature death, we know very little about the end of life experience,” said Nauzley Abedini, MD, MSc, a hospitalist in internal medicine at the University of Michigan, Ann Arbor.

The study sought to determine the association between loneliness and end of life experience as measured by symptom burden, intensity of care, and advance care planning in adults. The pooled cohort study used data from the Health and Retirement Study (HRS) to analyze older Americans (aged 50 years or more) who died between 2004 and 2014. Investigators conducted postmortem “exit interviews” with the next of kin after each participant’s death. There were 2,896 participants included in the survey. Of these participants, 34% (942) were lonely; the remaining 1,954 of elderly adults were classified as nonlonely.

Loneliness was defined using the three-item Revised University of California, Los Angeles, Loneliness Scale score from a decedent’s last HRS interview prior to death. These items included feeling left out, feeling isolated, and lacking companionship. Investigators used this data to create a loneliness variable on previously established cutpoints for “lonely” and “nonlonely” participants. The data was used from the most recent survey prior to death.

Results showed more lonely older adults suffered from health symptoms in the last year of life, compared with nonlonely older adults (69.1% vs. 59.5%; odds ratio, 1.52; 95% confidence interval, 1.30-1.78). These symptoms included being troubled by pain, having difficulty breathing, experiencing severe fatigue, and having periodic confusion.

Patients with loneliness associated with intensity of health care at the end of life were more likely to die in a nursing home than at home, compared with nonlonely adults (OR, 1.68; 95% CI, 1.25-2.27). The lonely patients also were more likely to use life support during their last 2 years of life (OR, 1.41; 95% CI, 1.16-1.70).

“For clinicians, we need to identify end of life as an additional vulnerable time for people who are lonely. Currently, most of our interventions in terms of screening for loneliness are in the outpatient setting, but I would argue that working in hospitals, hospices, nursing homes, and community organizations, where these folks are living and dying, would be useful places to screen for this,” Dr. Abedini said.

The authors had no disclosures.

ANSWER

The radiograph demonstrates an acute horizontal fracture through the humeral neck. There is some slight lateral displacement of the fracture fragment.

The patient’s right arm was placed in a sling. Prompt orthopedic consultation was then obtained.

ANSWER

The radiograph demonstrates an acute horizontal fracture through the humeral neck. There is some slight lateral displacement of the fracture fragment.

The patient’s right arm was placed in a sling. Prompt orthopedic consultation was then obtained.

ANSWER

The radiograph demonstrates an acute horizontal fracture through the humeral neck. There is some slight lateral displacement of the fracture fragment.

The patient’s right arm was placed in a sling. Prompt orthopedic consultation was then obtained.