Background: CT pulmonary angiography (CTPA) often detects distal, subsegmental pulmonary embolisms (SSPE) for which there is unclear clinical significance. For these isolated SSPEs, the 2016 CHEST guidelines recommend clinical surveillance in lieu of treatment. Such clinical surveillance has not been associated with an increased recurrence of venous thromboembolism (VTE) over 3 months.

Dr. Shaw is an assistant professor in the division of hospital medicine, University of New Mexico.

Background: CT pulmonary angiography (CTPA) often detects distal, subsegmental pulmonary embolisms (SSPE) for which there is unclear clinical significance. For these isolated SSPEs, the 2016 CHEST guidelines recommend clinical surveillance in lieu of treatment. Such clinical surveillance has not been associated with an increased recurrence of venous thromboembolism (VTE) over 3 months.

Dr. Shaw is an assistant professor in the division of hospital medicine, University of New Mexico.

Background: CT pulmonary angiography (CTPA) often detects distal, subsegmental pulmonary embolisms (SSPE) for which there is unclear clinical significance. For these isolated SSPEs, the 2016 CHEST guidelines recommend clinical surveillance in lieu of treatment. Such clinical surveillance has not been associated with an increased recurrence of venous thromboembolism (VTE) over 3 months.

Dr. Shaw is an assistant professor in the division of hospital medicine, University of New Mexico.

Use of aspirin or nonaspirin NSAIDs was not associated with a reduced risk of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), in a large, prospective cohort study of Australian residents.

Fuse/Thinkstock

“Overall, we observed weak and inconsistent inverse associations between use of these medications and incidence of either BCC or SCC,” wrote Nirmala Pandeya, PhD, of the University of Queensland (Australia) and coauthors. “While we did observe a modest reduction in risk of BCC associated with NSAID use among people with high risk of skin cancer ... no statistically significant associations were seen with aspirin use,” they added. The study was published in the British Journal of Dermatology.

While reviews of observational studies have suggested that NSAIDs may have “a potential benefit” in reducing the incidence of BCC and SCC, the results have varied, they noted.

To investigate the potential chemopreventive effects of NSAID use on skin cancer, the investigators used data from the QSkin Sun and Health Study, a prospective cohort of 43,764 residents of Queensland, Australia. Those eligible for the study had a white ethnic background and no history of melanoma; 34,630 participants were available for analysis, their median age was 57 years, and 55% were women

Almost 15,600 (45%) were classified as “high risk” because they had had at least one skin cancer excision or more than five actinic lesions treated; 18,828 participants were classified as “average to low risk;” and data were unavailable for 206 participants. One‐third of the participants in the high-risk group (5,398) used aspirin; of these individuals, 39% (2,132) used aspirin more than once a week (defined as “frequent” users). Also, 60% (9,236) used NSAIDs, and of those, 24% (2,229) were frequent users.

During a median follow-up of 3 years, 3,421 of those in the study (10%) developed one or more BCC, and 1,470 (4%) developed one or more SCC.


Compared with never users, frequent NSAID use in the high-risk group was modestly associated with a reduced risk of BCC (hazard ratio, 0.84; 95% confidence interval, 0.71-0.99), but not with SCC. Aspirin use was weakly associated with a reduced risk of SCC (HR, 0.77; 95% CI, 0.64-0.93) but only among infrequent users and was not associated with BCC risk. In the average- to low-risk group, there was no association with either NSAIDs or aspirin and BCC or SCC occurrence.

The authors noted limitations of their study, including its reliance on self-reported NSAID use and a lack of detail in regard to usage dose and duration. In addition, though the investigators controlled for all likely confounders, “the possibility of some residual confounding cannot be excluded.”

The QSkin Study was funded by a grant from the National Health and Medical Research Council of Australia (NHMRC). The authors declared no conflicts of interest.

SOURCE: Pandeya N et al. Br J Dermatol. 2019 Mar 28. doi: 10.1111/bjd.17938.

Use of aspirin or nonaspirin NSAIDs was not associated with a reduced risk of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), in a large, prospective cohort study of Australian residents.

Fuse/Thinkstock

“Overall, we observed weak and inconsistent inverse associations between use of these medications and incidence of either BCC or SCC,” wrote Nirmala Pandeya, PhD, of the University of Queensland (Australia) and coauthors. “While we did observe a modest reduction in risk of BCC associated with NSAID use among people with high risk of skin cancer ... no statistically significant associations were seen with aspirin use,” they added. The study was published in the British Journal of Dermatology.

While reviews of observational studies have suggested that NSAIDs may have “a potential benefit” in reducing the incidence of BCC and SCC, the results have varied, they noted.

To investigate the potential chemopreventive effects of NSAID use on skin cancer, the investigators used data from the QSkin Sun and Health Study, a prospective cohort of 43,764 residents of Queensland, Australia. Those eligible for the study had a white ethnic background and no history of melanoma; 34,630 participants were available for analysis, their median age was 57 years, and 55% were women

Almost 15,600 (45%) were classified as “high risk” because they had had at least one skin cancer excision or more than five actinic lesions treated; 18,828 participants were classified as “average to low risk;” and data were unavailable for 206 participants. One‐third of the participants in the high-risk group (5,398) used aspirin; of these individuals, 39% (2,132) used aspirin more than once a week (defined as “frequent” users). Also, 60% (9,236) used NSAIDs, and of those, 24% (2,229) were frequent users.

During a median follow-up of 3 years, 3,421 of those in the study (10%) developed one or more BCC, and 1,470 (4%) developed one or more SCC.


Compared with never users, frequent NSAID use in the high-risk group was modestly associated with a reduced risk of BCC (hazard ratio, 0.84; 95% confidence interval, 0.71-0.99), but not with SCC. Aspirin use was weakly associated with a reduced risk of SCC (HR, 0.77; 95% CI, 0.64-0.93) but only among infrequent users and was not associated with BCC risk. In the average- to low-risk group, there was no association with either NSAIDs or aspirin and BCC or SCC occurrence.

The authors noted limitations of their study, including its reliance on self-reported NSAID use and a lack of detail in regard to usage dose and duration. In addition, though the investigators controlled for all likely confounders, “the possibility of some residual confounding cannot be excluded.”

The QSkin Study was funded by a grant from the National Health and Medical Research Council of Australia (NHMRC). The authors declared no conflicts of interest.

SOURCE: Pandeya N et al. Br J Dermatol. 2019 Mar 28. doi: 10.1111/bjd.17938.

Use of aspirin or nonaspirin NSAIDs was not associated with a reduced risk of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), in a large, prospective cohort study of Australian residents.

Fuse/Thinkstock

“Overall, we observed weak and inconsistent inverse associations between use of these medications and incidence of either BCC or SCC,” wrote Nirmala Pandeya, PhD, of the University of Queensland (Australia) and coauthors. “While we did observe a modest reduction in risk of BCC associated with NSAID use among people with high risk of skin cancer ... no statistically significant associations were seen with aspirin use,” they added. The study was published in the British Journal of Dermatology.

While reviews of observational studies have suggested that NSAIDs may have “a potential benefit” in reducing the incidence of BCC and SCC, the results have varied, they noted.

To investigate the potential chemopreventive effects of NSAID use on skin cancer, the investigators used data from the QSkin Sun and Health Study, a prospective cohort of 43,764 residents of Queensland, Australia. Those eligible for the study had a white ethnic background and no history of melanoma; 34,630 participants were available for analysis, their median age was 57 years, and 55% were women

Almost 15,600 (45%) were classified as “high risk” because they had had at least one skin cancer excision or more than five actinic lesions treated; 18,828 participants were classified as “average to low risk;” and data were unavailable for 206 participants. One‐third of the participants in the high-risk group (5,398) used aspirin; of these individuals, 39% (2,132) used aspirin more than once a week (defined as “frequent” users). Also, 60% (9,236) used NSAIDs, and of those, 24% (2,229) were frequent users.

During a median follow-up of 3 years, 3,421 of those in the study (10%) developed one or more BCC, and 1,470 (4%) developed one or more SCC.


Compared with never users, frequent NSAID use in the high-risk group was modestly associated with a reduced risk of BCC (hazard ratio, 0.84; 95% confidence interval, 0.71-0.99), but not with SCC. Aspirin use was weakly associated with a reduced risk of SCC (HR, 0.77; 95% CI, 0.64-0.93) but only among infrequent users and was not associated with BCC risk. In the average- to low-risk group, there was no association with either NSAIDs or aspirin and BCC or SCC occurrence.

The authors noted limitations of their study, including its reliance on self-reported NSAID use and a lack of detail in regard to usage dose and duration. In addition, though the investigators controlled for all likely confounders, “the possibility of some residual confounding cannot be excluded.”

The QSkin Study was funded by a grant from the National Health and Medical Research Council of Australia (NHMRC). The authors declared no conflicts of interest.

SOURCE: Pandeya N et al. Br J Dermatol. 2019 Mar 28. doi: 10.1111/bjd.17938.

CHICAGO – Although at a relatively early stage of research, molecular profiling is showing promise for personalizing treatment of rashes of unknown origin that do not respond to conventional therapies, according to research that was described at the annual meeting of the Society for Investigative Dermatology.

“We now have several cases that suggest single-cell molecular profiling can provide treatment guidance for atypical rashes, providing an opportunity for a rational treatment choice rather than just improvising in a difficult population,” reported Raymond Cho, MD, PhD, of the department of dermatology at the University of California, San Francisco.

Based on a growing cohort of patients with atypical rashes, one goal is to develop “a library of molecular fingerprints” for classifying rashes that are atypical when defined by morphology, histopathology, or therapeutic response, according to Dr. Cho.

“The big focus now is on expanding this patient cohort. We want to move from anecdotal cases to a larger patient population with which we can statistically prove that we can nominate the best first-line therapy through this approach,” he explained.

In describing work he is performing in collaboration with Jeffrey Cheng, MD, also with the department of dermatology at UCSF, Dr. Cho said the profiles are based on RNA sequencing from single immune cells and epitope measurements. Work already performed in rashes of known etiology supports the approach. For example, the profile for atopic dermatitis includes elevated expression of interleukin (IL)-4 and IL-13, whereas that of psoriasis includes elevated expression of IL-17, which fit with the expected molecular signatures of these diseases.


To be considered for inclusion in the cohort of atypical rashes, patients are required to have an idiopathic skin lesion of at least 6 months’ duration with at least two atypical features defined by such characteristics as morphology or location. Many of these patients have already consulted with multiple providers, have undergone multiple biopsies without a diagnosis, and have failed common treatments, such as steroids.

Examples selected from this cohort have already supported the premise that molecular profiles are relevant to treatment choice. Dr. Cho described one patient with unremitting generalized pruritus and another with nodular lesions on the legs. Both had symptoms of long duration that had failed multiple treatments.

In both cases, immune cell profiling identified lesions high in IL-13 expression. Both achieved complete or near complete resolution of their rash and symptoms when treated with dupilumab, a biologic that targets the IL-13 pathway. In one patient with a large symptom burden, Dr. Cho described the response as “remarkable.”

There are more than 40 patients in the expanding cohort, according to Dr. Cho, who emphasized that this work is timely because of “the armamentarium of immunomodulatory drugs that are coming on line.” He said this type of drug development in dermatology is the basis for a potential paradigm shift.

“Personalized therapy has been used in clinical oncology for almost 10 years now, but this is an approach that needs to find a home in our specialty as well,” Dr. Cho said. He cited data suggesting that nearly 15% of rashes are atypical and represent a major source of frustration to both patients and clinicians when conventional treatments fail.

Asked about cost, he acknowledged that the molecular profiling that he and Dr. Cheng are performing is expensive at the current time, but “we are hopeful that we can find cheaper markers and technologies” to bring this cost down. However, he noted that undiagnosed rashes consume a great deal of time of effort from clinicians while generating significant morbidity for patients, which is justifying novel strategies to find effective therapies.

“These are not happy patients,” Dr. Cho said. Although there are technical challenges for building a molecular library that has practical utility across the substantial heterogeneity of idiopathic rashes, he suggested that a larger patient sample is considered one of the important steps toward overcoming hurdles.

Dr. Cho reports no potential conflicts of interest.

CHICAGO – Although at a relatively early stage of research, molecular profiling is showing promise for personalizing treatment of rashes of unknown origin that do not respond to conventional therapies, according to research that was described at the annual meeting of the Society for Investigative Dermatology.

“We now have several cases that suggest single-cell molecular profiling can provide treatment guidance for atypical rashes, providing an opportunity for a rational treatment choice rather than just improvising in a difficult population,” reported Raymond Cho, MD, PhD, of the department of dermatology at the University of California, San Francisco.

Based on a growing cohort of patients with atypical rashes, one goal is to develop “a library of molecular fingerprints” for classifying rashes that are atypical when defined by morphology, histopathology, or therapeutic response, according to Dr. Cho.

“The big focus now is on expanding this patient cohort. We want to move from anecdotal cases to a larger patient population with which we can statistically prove that we can nominate the best first-line therapy through this approach,” he explained.

In describing work he is performing in collaboration with Jeffrey Cheng, MD, also with the department of dermatology at UCSF, Dr. Cho said the profiles are based on RNA sequencing from single immune cells and epitope measurements. Work already performed in rashes of known etiology supports the approach. For example, the profile for atopic dermatitis includes elevated expression of interleukin (IL)-4 and IL-13, whereas that of psoriasis includes elevated expression of IL-17, which fit with the expected molecular signatures of these diseases.


To be considered for inclusion in the cohort of atypical rashes, patients are required to have an idiopathic skin lesion of at least 6 months’ duration with at least two atypical features defined by such characteristics as morphology or location. Many of these patients have already consulted with multiple providers, have undergone multiple biopsies without a diagnosis, and have failed common treatments, such as steroids.

Examples selected from this cohort have already supported the premise that molecular profiles are relevant to treatment choice. Dr. Cho described one patient with unremitting generalized pruritus and another with nodular lesions on the legs. Both had symptoms of long duration that had failed multiple treatments.

In both cases, immune cell profiling identified lesions high in IL-13 expression. Both achieved complete or near complete resolution of their rash and symptoms when treated with dupilumab, a biologic that targets the IL-13 pathway. In one patient with a large symptom burden, Dr. Cho described the response as “remarkable.”

There are more than 40 patients in the expanding cohort, according to Dr. Cho, who emphasized that this work is timely because of “the armamentarium of immunomodulatory drugs that are coming on line.” He said this type of drug development in dermatology is the basis for a potential paradigm shift.

“Personalized therapy has been used in clinical oncology for almost 10 years now, but this is an approach that needs to find a home in our specialty as well,” Dr. Cho said. He cited data suggesting that nearly 15% of rashes are atypical and represent a major source of frustration to both patients and clinicians when conventional treatments fail.

Asked about cost, he acknowledged that the molecular profiling that he and Dr. Cheng are performing is expensive at the current time, but “we are hopeful that we can find cheaper markers and technologies” to bring this cost down. However, he noted that undiagnosed rashes consume a great deal of time of effort from clinicians while generating significant morbidity for patients, which is justifying novel strategies to find effective therapies.

“These are not happy patients,” Dr. Cho said. Although there are technical challenges for building a molecular library that has practical utility across the substantial heterogeneity of idiopathic rashes, he suggested that a larger patient sample is considered one of the important steps toward overcoming hurdles.

Dr. Cho reports no potential conflicts of interest.

CHICAGO – Although at a relatively early stage of research, molecular profiling is showing promise for personalizing treatment of rashes of unknown origin that do not respond to conventional therapies, according to research that was described at the annual meeting of the Society for Investigative Dermatology.

“We now have several cases that suggest single-cell molecular profiling can provide treatment guidance for atypical rashes, providing an opportunity for a rational treatment choice rather than just improvising in a difficult population,” reported Raymond Cho, MD, PhD, of the department of dermatology at the University of California, San Francisco.

Based on a growing cohort of patients with atypical rashes, one goal is to develop “a library of molecular fingerprints” for classifying rashes that are atypical when defined by morphology, histopathology, or therapeutic response, according to Dr. Cho.

“The big focus now is on expanding this patient cohort. We want to move from anecdotal cases to a larger patient population with which we can statistically prove that we can nominate the best first-line therapy through this approach,” he explained.

In describing work he is performing in collaboration with Jeffrey Cheng, MD, also with the department of dermatology at UCSF, Dr. Cho said the profiles are based on RNA sequencing from single immune cells and epitope measurements. Work already performed in rashes of known etiology supports the approach. For example, the profile for atopic dermatitis includes elevated expression of interleukin (IL)-4 and IL-13, whereas that of psoriasis includes elevated expression of IL-17, which fit with the expected molecular signatures of these diseases.


To be considered for inclusion in the cohort of atypical rashes, patients are required to have an idiopathic skin lesion of at least 6 months’ duration with at least two atypical features defined by such characteristics as morphology or location. Many of these patients have already consulted with multiple providers, have undergone multiple biopsies without a diagnosis, and have failed common treatments, such as steroids.

Examples selected from this cohort have already supported the premise that molecular profiles are relevant to treatment choice. Dr. Cho described one patient with unremitting generalized pruritus and another with nodular lesions on the legs. Both had symptoms of long duration that had failed multiple treatments.

In both cases, immune cell profiling identified lesions high in IL-13 expression. Both achieved complete or near complete resolution of their rash and symptoms when treated with dupilumab, a biologic that targets the IL-13 pathway. In one patient with a large symptom burden, Dr. Cho described the response as “remarkable.”

There are more than 40 patients in the expanding cohort, according to Dr. Cho, who emphasized that this work is timely because of “the armamentarium of immunomodulatory drugs that are coming on line.” He said this type of drug development in dermatology is the basis for a potential paradigm shift.

“Personalized therapy has been used in clinical oncology for almost 10 years now, but this is an approach that needs to find a home in our specialty as well,” Dr. Cho said. He cited data suggesting that nearly 15% of rashes are atypical and represent a major source of frustration to both patients and clinicians when conventional treatments fail.

Asked about cost, he acknowledged that the molecular profiling that he and Dr. Cheng are performing is expensive at the current time, but “we are hopeful that we can find cheaper markers and technologies” to bring this cost down. However, he noted that undiagnosed rashes consume a great deal of time of effort from clinicians while generating significant morbidity for patients, which is justifying novel strategies to find effective therapies.

“These are not happy patients,” Dr. Cho said. Although there are technical challenges for building a molecular library that has practical utility across the substantial heterogeneity of idiopathic rashes, he suggested that a larger patient sample is considered one of the important steps toward overcoming hurdles.

Dr. Cho reports no potential conflicts of interest.

The flu virus uses a hemagglutinin (HA) protein to enter and infect cells. The “head” of the protein was thought to be safe from antibody attacks.

Turns out, it has a previously unsuspected chink in its armor. And researchers from National Institute of Allergy and Infectious Diseases may have found an “unexpected new target” for antiflu therapies. They discovered a naturally occurring human antibody (FluA-20) that—to their surprise—binds to the head of the HA protein at a site that was not thought to be vulnerable.

Using FluA-20 isolated from a patient who had received many influenza immunizations, the researchers showed that FluA-20 “reaches into” an otherwise inaccessible part of the HA trimer molecule and “rapidly disrupts” its integrity. In other words, FluA-20 causes it to fall apart, preventing the spread of virus.

Although the researchers also discovered that the window of opportunity is narrow (the region is only briefly exposed to antibody attack), unlike the rest of HA’s head, the open-access region varies little among influenza strains. The critical HA residues recognized by FluA-20, the researchers say, remain conserved across most subtypes of influenza A virus, which explains the antibody’s “extraordinary breadth.” In mouse studies, when used as prophylaxis or therapy, it protected against H1N1, N3N2, H5N1, and H7N9 subtypes.

In theory, the researchers say, direct strikes with antibody-based therapeutics against that part of the HA protein could be effective with many strains of influenza A virus, and—also theoretically—other influenza strains.

The flu virus uses a hemagglutinin (HA) protein to enter and infect cells. The “head” of the protein was thought to be safe from antibody attacks.

Turns out, it has a previously unsuspected chink in its armor. And researchers from National Institute of Allergy and Infectious Diseases may have found an “unexpected new target” for antiflu therapies. They discovered a naturally occurring human antibody (FluA-20) that—to their surprise—binds to the head of the HA protein at a site that was not thought to be vulnerable.

Using FluA-20 isolated from a patient who had received many influenza immunizations, the researchers showed that FluA-20 “reaches into” an otherwise inaccessible part of the HA trimer molecule and “rapidly disrupts” its integrity. In other words, FluA-20 causes it to fall apart, preventing the spread of virus.

Although the researchers also discovered that the window of opportunity is narrow (the region is only briefly exposed to antibody attack), unlike the rest of HA’s head, the open-access region varies little among influenza strains. The critical HA residues recognized by FluA-20, the researchers say, remain conserved across most subtypes of influenza A virus, which explains the antibody’s “extraordinary breadth.” In mouse studies, when used as prophylaxis or therapy, it protected against H1N1, N3N2, H5N1, and H7N9 subtypes.

In theory, the researchers say, direct strikes with antibody-based therapeutics against that part of the HA protein could be effective with many strains of influenza A virus, and—also theoretically—other influenza strains.

The flu virus uses a hemagglutinin (HA) protein to enter and infect cells. The “head” of the protein was thought to be safe from antibody attacks.

Turns out, it has a previously unsuspected chink in its armor. And researchers from National Institute of Allergy and Infectious Diseases may have found an “unexpected new target” for antiflu therapies. They discovered a naturally occurring human antibody (FluA-20) that—to their surprise—binds to the head of the HA protein at a site that was not thought to be vulnerable.

Using FluA-20 isolated from a patient who had received many influenza immunizations, the researchers showed that FluA-20 “reaches into” an otherwise inaccessible part of the HA trimer molecule and “rapidly disrupts” its integrity. In other words, FluA-20 causes it to fall apart, preventing the spread of virus.

Although the researchers also discovered that the window of opportunity is narrow (the region is only briefly exposed to antibody attack), unlike the rest of HA’s head, the open-access region varies little among influenza strains. The critical HA residues recognized by FluA-20, the researchers say, remain conserved across most subtypes of influenza A virus, which explains the antibody’s “extraordinary breadth.” In mouse studies, when used as prophylaxis or therapy, it protected against H1N1, N3N2, H5N1, and H7N9 subtypes.

In theory, the researchers say, direct strikes with antibody-based therapeutics against that part of the HA protein could be effective with many strains of influenza A virus, and—also theoretically—other influenza strains.

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.

rfranki@mdedge.com

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.

rfranki@mdedge.com

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.

rfranki@mdedge.com

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

The potential harms of excessive Internet use are serious enough for the medical community to debate whether it should be included as a disorder associated with addiction. One question is Where do you draw the line between excessive use—considered nonpathologic behavior—and addiction?

Researchers surveyed 374 university students about social network habits, testing for obsession, lack of personal control, and excessive use. The questionnaire included questions such as “I feel a great need to stay connected to social media” and “I feel anxious when I cannot connect to social media.” The researchers also used a questionnaire about suicidal ideation.

More than half the students reported that WhatsApp is their most important social network, followed by Facebook. The respondents used social media for an average of nearly 7 hours a day. They used social media mainly for contact with friends, entertainment, conversing with a partner, maintaining contact with colleagues for academic matters, and contact with family.

The researchers divided the participants into 3 groups, based on their risk of addiction. The majority were considered “moderate risk.” Approximately 10% were considered “high risk.” The high-risk students spent roughly 11 hours a day on social media compared with the low-risk students who spent about 4 hours. Greater risk also implied more depressive symptoms, more mobile use, and less positive suicidal ideation.

Almost 4 in 10 students had thoughts and wishes about their death at least once in the 2 weeks before the survey. Interestingly, however, the researchers found no relationship between suicidal ideation and addictive behavior. But adding depression did make a difference. Unlike excessive use, addictive behavior was significantly related to depression and suicidal ideation.  

The researchers cite other studies that have found addiction to social networks predicts depression and can worsen symptoms. But they also say their findings confirm other research that suggests social media communication can be protective for people who have suicidal thoughts. What looks like addiction may be “an act of escape” from unpleasant thoughts and feelings. Social media, they say, can be a “refuge.”

The potential harms of excessive Internet use are serious enough for the medical community to debate whether it should be included as a disorder associated with addiction. One question is Where do you draw the line between excessive use—considered nonpathologic behavior—and addiction?

Researchers surveyed 374 university students about social network habits, testing for obsession, lack of personal control, and excessive use. The questionnaire included questions such as “I feel a great need to stay connected to social media” and “I feel anxious when I cannot connect to social media.” The researchers also used a questionnaire about suicidal ideation.

More than half the students reported that WhatsApp is their most important social network, followed by Facebook. The respondents used social media for an average of nearly 7 hours a day. They used social media mainly for contact with friends, entertainment, conversing with a partner, maintaining contact with colleagues for academic matters, and contact with family.

The researchers divided the participants into 3 groups, based on their risk of addiction. The majority were considered “moderate risk.” Approximately 10% were considered “high risk.” The high-risk students spent roughly 11 hours a day on social media compared with the low-risk students who spent about 4 hours. Greater risk also implied more depressive symptoms, more mobile use, and less positive suicidal ideation.

Almost 4 in 10 students had thoughts and wishes about their death at least once in the 2 weeks before the survey. Interestingly, however, the researchers found no relationship between suicidal ideation and addictive behavior. But adding depression did make a difference. Unlike excessive use, addictive behavior was significantly related to depression and suicidal ideation.  

The researchers cite other studies that have found addiction to social networks predicts depression and can worsen symptoms. But they also say their findings confirm other research that suggests social media communication can be protective for people who have suicidal thoughts. What looks like addiction may be “an act of escape” from unpleasant thoughts and feelings. Social media, they say, can be a “refuge.”

The potential harms of excessive Internet use are serious enough for the medical community to debate whether it should be included as a disorder associated with addiction. One question is Where do you draw the line between excessive use—considered nonpathologic behavior—and addiction?

Researchers surveyed 374 university students about social network habits, testing for obsession, lack of personal control, and excessive use. The questionnaire included questions such as “I feel a great need to stay connected to social media” and “I feel anxious when I cannot connect to social media.” The researchers also used a questionnaire about suicidal ideation.

More than half the students reported that WhatsApp is their most important social network, followed by Facebook. The respondents used social media for an average of nearly 7 hours a day. They used social media mainly for contact with friends, entertainment, conversing with a partner, maintaining contact with colleagues for academic matters, and contact with family.

The researchers divided the participants into 3 groups, based on their risk of addiction. The majority were considered “moderate risk.” Approximately 10% were considered “high risk.” The high-risk students spent roughly 11 hours a day on social media compared with the low-risk students who spent about 4 hours. Greater risk also implied more depressive symptoms, more mobile use, and less positive suicidal ideation.

Almost 4 in 10 students had thoughts and wishes about their death at least once in the 2 weeks before the survey. Interestingly, however, the researchers found no relationship between suicidal ideation and addictive behavior. But adding depression did make a difference. Unlike excessive use, addictive behavior was significantly related to depression and suicidal ideation.  

The researchers cite other studies that have found addiction to social networks predicts depression and can worsen symptoms. But they also say their findings confirm other research that suggests social media communication can be protective for people who have suicidal thoughts. What looks like addiction may be “an act of escape” from unpleasant thoughts and feelings. Social media, they say, can be a “refuge.”

In 2017, the number of cases of tickborne spotted fever rickettsiosis (SFR) reported to the CDC jumped 46%—from 4,269 in 2016 to a “record” 6,248 cases. The New England, East North Central, and Mid-Atlantic regions in 2017 alone experienced a 215%, 78%, and 65% increase, respectively, although they typically report only a handful of cases each year.

Rocky Mountain spotted fever (RMSF) is the most severe of the SFR. It begins with nonspecific symptoms such as fever and headache, and sometimes rash, but when left untreated, the disease can have serious consequences, including amputation. Roughly 1 in 5 untreated cases is fatal; half of those deaths occur within the first 8 days of illness.

However, RMSF is treatable with doxycycline, which can prevent disability and death if prescribed within the first 5 days of illness, meaning that early recognition and treatment can save lives. Yet cases “often go unrecognized because the signs and symptoms are similar to those of many other diseases,” says CDC Director Robert Redfield, MD. Less than 1% of the reported SFR cases in 2017 had sufficient laboratory evidence to be confirmed. And although the annual incidence of SFR in the US increased from 6.4 to 19.2 cases per million persons between years 2010 and 2017, the proportion of confirmed cases went down.

Citing the need to train health care providers (HCPs) on the best methods to diagnose tickborne diseases, the CDC has created a “first of its kind” clinical education tool that uses scenarios based on real cases to help clinicians recognize and differentiate among the various possibilities. The module is self-directed with knowledge checks, reference materials, and an interactive rash identification tool that allows HCPs to compare the rash seen in RMSF with that of other illnesses.

Continuing education credit is available for physicians, nurse practitioners, physician assistants, veterinarians, nurses, epidemiologists, public health professionals, educators, and health communicators. To access the module, go to https://www.cdc.gov/rmsf/resources/module.html

In 2017, the number of cases of tickborne spotted fever rickettsiosis (SFR) reported to the CDC jumped 46%—from 4,269 in 2016 to a “record” 6,248 cases. The New England, East North Central, and Mid-Atlantic regions in 2017 alone experienced a 215%, 78%, and 65% increase, respectively, although they typically report only a handful of cases each year.

Rocky Mountain spotted fever (RMSF) is the most severe of the SFR. It begins with nonspecific symptoms such as fever and headache, and sometimes rash, but when left untreated, the disease can have serious consequences, including amputation. Roughly 1 in 5 untreated cases is fatal; half of those deaths occur within the first 8 days of illness.

However, RMSF is treatable with doxycycline, which can prevent disability and death if prescribed within the first 5 days of illness, meaning that early recognition and treatment can save lives. Yet cases “often go unrecognized because the signs and symptoms are similar to those of many other diseases,” says CDC Director Robert Redfield, MD. Less than 1% of the reported SFR cases in 2017 had sufficient laboratory evidence to be confirmed. And although the annual incidence of SFR in the US increased from 6.4 to 19.2 cases per million persons between years 2010 and 2017, the proportion of confirmed cases went down.

Citing the need to train health care providers (HCPs) on the best methods to diagnose tickborne diseases, the CDC has created a “first of its kind” clinical education tool that uses scenarios based on real cases to help clinicians recognize and differentiate among the various possibilities. The module is self-directed with knowledge checks, reference materials, and an interactive rash identification tool that allows HCPs to compare the rash seen in RMSF with that of other illnesses.

Continuing education credit is available for physicians, nurse practitioners, physician assistants, veterinarians, nurses, epidemiologists, public health professionals, educators, and health communicators. To access the module, go to https://www.cdc.gov/rmsf/resources/module.html

In 2017, the number of cases of tickborne spotted fever rickettsiosis (SFR) reported to the CDC jumped 46%—from 4,269 in 2016 to a “record” 6,248 cases. The New England, East North Central, and Mid-Atlantic regions in 2017 alone experienced a 215%, 78%, and 65% increase, respectively, although they typically report only a handful of cases each year.

Rocky Mountain spotted fever (RMSF) is the most severe of the SFR. It begins with nonspecific symptoms such as fever and headache, and sometimes rash, but when left untreated, the disease can have serious consequences, including amputation. Roughly 1 in 5 untreated cases is fatal; half of those deaths occur within the first 8 days of illness.

However, RMSF is treatable with doxycycline, which can prevent disability and death if prescribed within the first 5 days of illness, meaning that early recognition and treatment can save lives. Yet cases “often go unrecognized because the signs and symptoms are similar to those of many other diseases,” says CDC Director Robert Redfield, MD. Less than 1% of the reported SFR cases in 2017 had sufficient laboratory evidence to be confirmed. And although the annual incidence of SFR in the US increased from 6.4 to 19.2 cases per million persons between years 2010 and 2017, the proportion of confirmed cases went down.

Citing the need to train health care providers (HCPs) on the best methods to diagnose tickborne diseases, the CDC has created a “first of its kind” clinical education tool that uses scenarios based on real cases to help clinicians recognize and differentiate among the various possibilities. The module is self-directed with knowledge checks, reference materials, and an interactive rash identification tool that allows HCPs to compare the rash seen in RMSF with that of other illnesses.

Continuing education credit is available for physicians, nurse practitioners, physician assistants, veterinarians, nurses, epidemiologists, public health professionals, educators, and health communicators. To access the module, go to https://www.cdc.gov/rmsf/resources/module.html

Methamphetamine (MA) abuse has been linked to psychological problems, such as depression, anxiety, and psychosis. It also has been linked to problems in everyday functioning (eg, impulsivity), and neurocognitive deficits in attention, memory, learning, executive function, and fine motor speed. But researchers from Capital Medical University in Beijing and Fujian Medical University in Fuzhou, both in China, say current understanding is limited about the impact of MA abuse in spatial processing, which affects, among other things, alertness.

The researchers conducted a study with 40 MA abusers and 40 nonusers. Participants performed 3 tasks randomly. During the Simple Reaction Task, they pressed a mouse key as quickly and accurately as possible, discriminating between hand and foot pictures. The Spatial Orientation Task asked them to gauge the direction of fingers or toes shown in pictures. The Mental Rotation Task randomly showed hands and feet in 2 different views (dorsum, palm/plantar) and oriented in 1 of 6 clockwise angles. It also assessed 2 different mental rotation strategies: object based and egocentric based, or the ability to judge which side a body part belongs to in the picture and in the participant’s own body. In this test, the researchers say, the transformation of visuospatial mental image is crucial to action, navigation, and reasoning.

The researchers found no significant difference in either accuracy or reaction time between the 2 groups in the first task. In the second, MA users performed less well on reaction time but not accuracy. The results of that task suggested that MA abuse may induce a deficit in spatial orientation ability, mainly on horizontal surface.

On the third task, however, MA abusers performed worse and committed more errors than did the nonusers. They had worse results at every orientation angle and took longer to judge the orientation of leftward but not rightward foot pictures. Such phenomena likely relate to MA damage to cortical gray and white matter, the researchers say. They note that MA users also have shown less activation in the right hemisphere when performing a facial-affect matching task. MA abuse may mainly target the right hemisphere, the researchers add, but the findings may support other research that has found poor decision-making performance in MA abusers that is related to inadequate activation of many brain areas.

The study confirmed “considerably poor visuospatial ability” in MA users. The Mental Rotation Task findings also showed MA abuse of longer duration had more negative effect on spatial process speed. Because both cognitive speed and accuracy were affected on the Mental Rotation Task, but only cognitive speed on Spatial Orientation, MA abuse may affect visuospatial ability more seriously than spatial orientation ability, the researchers say.

Methamphetamine (MA) abuse has been linked to psychological problems, such as depression, anxiety, and psychosis. It also has been linked to problems in everyday functioning (eg, impulsivity), and neurocognitive deficits in attention, memory, learning, executive function, and fine motor speed. But researchers from Capital Medical University in Beijing and Fujian Medical University in Fuzhou, both in China, say current understanding is limited about the impact of MA abuse in spatial processing, which affects, among other things, alertness.

The researchers conducted a study with 40 MA abusers and 40 nonusers. Participants performed 3 tasks randomly. During the Simple Reaction Task, they pressed a mouse key as quickly and accurately as possible, discriminating between hand and foot pictures. The Spatial Orientation Task asked them to gauge the direction of fingers or toes shown in pictures. The Mental Rotation Task randomly showed hands and feet in 2 different views (dorsum, palm/plantar) and oriented in 1 of 6 clockwise angles. It also assessed 2 different mental rotation strategies: object based and egocentric based, or the ability to judge which side a body part belongs to in the picture and in the participant’s own body. In this test, the researchers say, the transformation of visuospatial mental image is crucial to action, navigation, and reasoning.

The researchers found no significant difference in either accuracy or reaction time between the 2 groups in the first task. In the second, MA users performed less well on reaction time but not accuracy. The results of that task suggested that MA abuse may induce a deficit in spatial orientation ability, mainly on horizontal surface.

On the third task, however, MA abusers performed worse and committed more errors than did the nonusers. They had worse results at every orientation angle and took longer to judge the orientation of leftward but not rightward foot pictures. Such phenomena likely relate to MA damage to cortical gray and white matter, the researchers say. They note that MA users also have shown less activation in the right hemisphere when performing a facial-affect matching task. MA abuse may mainly target the right hemisphere, the researchers add, but the findings may support other research that has found poor decision-making performance in MA abusers that is related to inadequate activation of many brain areas.

The study confirmed “considerably poor visuospatial ability” in MA users. The Mental Rotation Task findings also showed MA abuse of longer duration had more negative effect on spatial process speed. Because both cognitive speed and accuracy were affected on the Mental Rotation Task, but only cognitive speed on Spatial Orientation, MA abuse may affect visuospatial ability more seriously than spatial orientation ability, the researchers say.

Methamphetamine (MA) abuse has been linked to psychological problems, such as depression, anxiety, and psychosis. It also has been linked to problems in everyday functioning (eg, impulsivity), and neurocognitive deficits in attention, memory, learning, executive function, and fine motor speed. But researchers from Capital Medical University in Beijing and Fujian Medical University in Fuzhou, both in China, say current understanding is limited about the impact of MA abuse in spatial processing, which affects, among other things, alertness.

The researchers conducted a study with 40 MA abusers and 40 nonusers. Participants performed 3 tasks randomly. During the Simple Reaction Task, they pressed a mouse key as quickly and accurately as possible, discriminating between hand and foot pictures. The Spatial Orientation Task asked them to gauge the direction of fingers or toes shown in pictures. The Mental Rotation Task randomly showed hands and feet in 2 different views (dorsum, palm/plantar) and oriented in 1 of 6 clockwise angles. It also assessed 2 different mental rotation strategies: object based and egocentric based, or the ability to judge which side a body part belongs to in the picture and in the participant’s own body. In this test, the researchers say, the transformation of visuospatial mental image is crucial to action, navigation, and reasoning.

The researchers found no significant difference in either accuracy or reaction time between the 2 groups in the first task. In the second, MA users performed less well on reaction time but not accuracy. The results of that task suggested that MA abuse may induce a deficit in spatial orientation ability, mainly on horizontal surface.

On the third task, however, MA abusers performed worse and committed more errors than did the nonusers. They had worse results at every orientation angle and took longer to judge the orientation of leftward but not rightward foot pictures. Such phenomena likely relate to MA damage to cortical gray and white matter, the researchers say. They note that MA users also have shown less activation in the right hemisphere when performing a facial-affect matching task. MA abuse may mainly target the right hemisphere, the researchers add, but the findings may support other research that has found poor decision-making performance in MA abusers that is related to inadequate activation of many brain areas.

The study confirmed “considerably poor visuospatial ability” in MA users. The Mental Rotation Task findings also showed MA abuse of longer duration had more negative effect on spatial process speed. Because both cognitive speed and accuracy were affected on the Mental Rotation Task, but only cognitive speed on Spatial Orientation, MA abuse may affect visuospatial ability more seriously than spatial orientation ability, the researchers say.

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.

bjancin@mdedge.com

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.

bjancin@mdedge.com

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.

bjancin@mdedge.com

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

The Trump administration is proposing to roll back discrimination protections for transgender patients who seek medical care.

Gage Skidmore/Wikimedia Commons/CC BY-SA 2.0

In a proposed rule issued May 24, the U.S. Department of Health & Human Services outlined its plan to repeal an Obama-era policy that banned health care providers from discriminating against transgender patients. As part of the Affordable Care Act, Congress had directed HHS to apply existing civil rights and health care regulations to the health law exchanges, including rules that were consistent with Title IX, the federal law that prohibits discrimination on the basis of sex in federally funded programs. The Obama administration’s interpretation of this directive barred health care providers from denying care to transgender patients based on gender identify, defined as a patient’s “internal sense of being male, female, neither, or a combination of male and female.”

Repealing the transgender protections in the antidiscrimination policy will make the regulation more consistent with Title IX, according to HHS. In addition, revoking other provisions in the Obama-era policy associated with non–English speaking patients will reduce regulatory costs for unnecessary paperwork by $3.2 billion, according to a statement from the HHS.

“When Congress prohibited sex discrimination, it did so according to the plain meaning of the term, and we are making our regulations conform,” said Roger Severino, director of the HHS’s Office for Civil Rights, in the statement. “The American people want vigorous protection of civil rights and faithfulness to the text of the laws passed by their representatives. The proposed rule would accomplish both goals.”

In addressing the reasoning for the proposal, Mr. Severino noted two court decisions that have found the Obama-era policy unlawful. In 2016, the U.S. District Court for the Northern District of Texas temporarily barred the protections from being enacted, ruling that HHS had adopted an erroneous interpretation of “sex” under Title IX, and that the regulation was arbitrary and capricious for failing to incorporate Title IX’s religious and abortion exemptions. The U.S. District Court for the District of North Dakota agreed in a subsequent decision. Since the preliminary bans against the provisions, HHS has not enforced the protections. Removal of the discrimination protections for transgender patients would conform with the courts’ plain understanding of federal sex discrimination laws, according to HHS.

HHS emphasized that the proposed rule is not intended to remove any protections provided by Congress or to restrict states’ ability to enact health care discrimination protections that exceed Title IX requirements. Rather, the proposed rule would ensure that Title IX and corresponding regulations “follow the will of Congress with respect to the states by not expanding Title IX’s definition of ‘sex’ beyond the statutory bounds,” according to the proposed rule.

In addition to removing the transgender protections, the HHS also proposed to eliminate provisions under the Obama-era policy that required health care literature to be translated into 15 languages. The proposed revisions would eliminate $3.2 billion in unneeded paperwork burdens imposed by the translations, according to the agency. Mr. Severino indicated that the money saved could be used to more effectively address individual needs of non–English speakers such as by providing increased access to translators and interpreters.

The American College of Physicians expressed concern about the agency’s move to rewrite the discrimination rule.

“ACP believes that discrimination against patients, including those who identify as lesbian, gay, bisexual, and transgender (LGBT), creates social stigma that has been linked to negative physical and mental health outcomes, including anxiety, suicide, and substance or alcohol abuse,” ACP President Robert McLean, MD, said in a statement. “ACP strongly urges the administration to withdraw their proposal, and instead, make meaningful policy changes that will ensure nondiscrimination in health care against all patients, regardless of their sexual orientation, gender or gender identity, disability, or proficiency in the English language.”

agallegos@mdedge.com

The Trump administration is proposing to roll back discrimination protections for transgender patients who seek medical care.

Gage Skidmore/Wikimedia Commons/CC BY-SA 2.0

In a proposed rule issued May 24, the U.S. Department of Health & Human Services outlined its plan to repeal an Obama-era policy that banned health care providers from discriminating against transgender patients. As part of the Affordable Care Act, Congress had directed HHS to apply existing civil rights and health care regulations to the health law exchanges, including rules that were consistent with Title IX, the federal law that prohibits discrimination on the basis of sex in federally funded programs. The Obama administration’s interpretation of this directive barred health care providers from denying care to transgender patients based on gender identify, defined as a patient’s “internal sense of being male, female, neither, or a combination of male and female.”

Repealing the transgender protections in the antidiscrimination policy will make the regulation more consistent with Title IX, according to HHS. In addition, revoking other provisions in the Obama-era policy associated with non–English speaking patients will reduce regulatory costs for unnecessary paperwork by $3.2 billion, according to a statement from the HHS.

“When Congress prohibited sex discrimination, it did so according to the plain meaning of the term, and we are making our regulations conform,” said Roger Severino, director of the HHS’s Office for Civil Rights, in the statement. “The American people want vigorous protection of civil rights and faithfulness to the text of the laws passed by their representatives. The proposed rule would accomplish both goals.”

In addressing the reasoning for the proposal, Mr. Severino noted two court decisions that have found the Obama-era policy unlawful. In 2016, the U.S. District Court for the Northern District of Texas temporarily barred the protections from being enacted, ruling that HHS had adopted an erroneous interpretation of “sex” under Title IX, and that the regulation was arbitrary and capricious for failing to incorporate Title IX’s religious and abortion exemptions. The U.S. District Court for the District of North Dakota agreed in a subsequent decision. Since the preliminary bans against the provisions, HHS has not enforced the protections. Removal of the discrimination protections for transgender patients would conform with the courts’ plain understanding of federal sex discrimination laws, according to HHS.

HHS emphasized that the proposed rule is not intended to remove any protections provided by Congress or to restrict states’ ability to enact health care discrimination protections that exceed Title IX requirements. Rather, the proposed rule would ensure that Title IX and corresponding regulations “follow the will of Congress with respect to the states by not expanding Title IX’s definition of ‘sex’ beyond the statutory bounds,” according to the proposed rule.

In addition to removing the transgender protections, the HHS also proposed to eliminate provisions under the Obama-era policy that required health care literature to be translated into 15 languages. The proposed revisions would eliminate $3.2 billion in unneeded paperwork burdens imposed by the translations, according to the agency. Mr. Severino indicated that the money saved could be used to more effectively address individual needs of non–English speakers such as by providing increased access to translators and interpreters.

The American College of Physicians expressed concern about the agency’s move to rewrite the discrimination rule.

“ACP believes that discrimination against patients, including those who identify as lesbian, gay, bisexual, and transgender (LGBT), creates social stigma that has been linked to negative physical and mental health outcomes, including anxiety, suicide, and substance or alcohol abuse,” ACP President Robert McLean, MD, said in a statement. “ACP strongly urges the administration to withdraw their proposal, and instead, make meaningful policy changes that will ensure nondiscrimination in health care against all patients, regardless of their sexual orientation, gender or gender identity, disability, or proficiency in the English language.”

agallegos@mdedge.com

The Trump administration is proposing to roll back discrimination protections for transgender patients who seek medical care.

Gage Skidmore/Wikimedia Commons/CC BY-SA 2.0

In a proposed rule issued May 24, the U.S. Department of Health & Human Services outlined its plan to repeal an Obama-era policy that banned health care providers from discriminating against transgender patients. As part of the Affordable Care Act, Congress had directed HHS to apply existing civil rights and health care regulations to the health law exchanges, including rules that were consistent with Title IX, the federal law that prohibits discrimination on the basis of sex in federally funded programs. The Obama administration’s interpretation of this directive barred health care providers from denying care to transgender patients based on gender identify, defined as a patient’s “internal sense of being male, female, neither, or a combination of male and female.”

Repealing the transgender protections in the antidiscrimination policy will make the regulation more consistent with Title IX, according to HHS. In addition, revoking other provisions in the Obama-era policy associated with non–English speaking patients will reduce regulatory costs for unnecessary paperwork by $3.2 billion, according to a statement from the HHS.

“When Congress prohibited sex discrimination, it did so according to the plain meaning of the term, and we are making our regulations conform,” said Roger Severino, director of the HHS’s Office for Civil Rights, in the statement. “The American people want vigorous protection of civil rights and faithfulness to the text of the laws passed by their representatives. The proposed rule would accomplish both goals.”

In addressing the reasoning for the proposal, Mr. Severino noted two court decisions that have found the Obama-era policy unlawful. In 2016, the U.S. District Court for the Northern District of Texas temporarily barred the protections from being enacted, ruling that HHS had adopted an erroneous interpretation of “sex” under Title IX, and that the regulation was arbitrary and capricious for failing to incorporate Title IX’s religious and abortion exemptions. The U.S. District Court for the District of North Dakota agreed in a subsequent decision. Since the preliminary bans against the provisions, HHS has not enforced the protections. Removal of the discrimination protections for transgender patients would conform with the courts’ plain understanding of federal sex discrimination laws, according to HHS.

HHS emphasized that the proposed rule is not intended to remove any protections provided by Congress or to restrict states’ ability to enact health care discrimination protections that exceed Title IX requirements. Rather, the proposed rule would ensure that Title IX and corresponding regulations “follow the will of Congress with respect to the states by not expanding Title IX’s definition of ‘sex’ beyond the statutory bounds,” according to the proposed rule.

In addition to removing the transgender protections, the HHS also proposed to eliminate provisions under the Obama-era policy that required health care literature to be translated into 15 languages. The proposed revisions would eliminate $3.2 billion in unneeded paperwork burdens imposed by the translations, according to the agency. Mr. Severino indicated that the money saved could be used to more effectively address individual needs of non–English speakers such as by providing increased access to translators and interpreters.

The American College of Physicians expressed concern about the agency’s move to rewrite the discrimination rule.

“ACP believes that discrimination against patients, including those who identify as lesbian, gay, bisexual, and transgender (LGBT), creates social stigma that has been linked to negative physical and mental health outcomes, including anxiety, suicide, and substance or alcohol abuse,” ACP President Robert McLean, MD, said in a statement. “ACP strongly urges the administration to withdraw their proposal, and instead, make meaningful policy changes that will ensure nondiscrimination in health care against all patients, regardless of their sexual orientation, gender or gender identity, disability, or proficiency in the English language.”

agallegos@mdedge.com