Young patients might be at increased risk of suicidal behavior, unintentional overdose, injuries, and traffic incidents during treatment periods with gabapentinoids, compared with periods without treatment with those medications, a cohort study of almost 200,000 people shows. Pregabalin is associated with higher hazards of those outcomes than is gabapentin, and the associations are strongest in patients aged 15-24 years, the researchers reported.

“If our findings are triangulated with other forms of evidence, clinical guidelines may need review regarding prescriptions for young people and those with substance use disorders,” wrote Yasmina Molero, PhD, and associates. “Further restrictions for off-label prescription may need consideration.” The study was published in BMJ.

The use of gabapentinoids has risen in the United States (JAMA Intern Med. 2018;178[2]:292-4), and overdose deaths tied to gabapentin have led some states to explore reclassification of the drug as a controlled substance (Risk Manag Healthc Policy. 2018;11:109-16). In the United Kingdom, gabapentinoids are being reclassified as a class C controlled drug because of concerns about the risk of addiction, overdose, and safety, wrote Dr. Molero of the department of psychiatry at Warneford Hospital at the University of Oxford, England, and associates.

To study associations between gabapentinoids and adverse outcomes related to coordination, mental health, and criminality, Dr. Molero and her associates analyzed data from 191,973 people from the Swedish Prescribed Drug Register who collected prescriptions for pregabalin or gabapentin between 2006 and 2013. The researchers included patients aged 15 years and older in their analyses.

They examined suicidal behavior, unintentional overdoses, head or body injuries, road traffic incidents and offenses, and arrests for violent crime using the Swedish Patient Register and the National Crime Register. In addition, they defined suicidal behavior as emergency hospital visits attributable to self-injurious behavior or suicide attempt, or death by suicide. Unintentional overdoses were defined as emergency hospital visits or death attributable to poisoning by illicit drugs, medications, or biologic substances; accidental poisoning by noxious substances; or acute intoxications and overdoses by alcohol and illicit drugs, excluding intentional self-poisoning, wrote Dr. Molero, who is affiliated with the Karolinska Institute in Stockholm, and her associates.

Of the nearly 192,000 participants who collected prescriptions of gabapentinoids on at least two consecutive occasions, 120,664 received pregabalin, and 85,360 received gabapentin; 14,051 of the participants received both drugs. Fifty-nine percent were women, and most patients were aged 45 or older.

During the study period, 10,026 participants (5.2%) were treated for suicidal behavior or died from suicide, 17,144 participants (8.9%) experienced an unintentional overdose, and 12,070 participants (6.3%) had a road traffic incident or offense. In addition, 70,522 participants (36.7%) had head or body injuries, and 7,984 participants (4.1%) were arrested for a violent crime.

jremaly@mdedge.com

SOURCE: Molero Y et al. BMJ. 2019 Jun 12. doi: 10.1136/bmj.l2147.

Young patients might be at increased risk of suicidal behavior, unintentional overdose, injuries, and traffic incidents during treatment periods with gabapentinoids, compared with periods without treatment with those medications, a cohort study of almost 200,000 people shows. Pregabalin is associated with higher hazards of those outcomes than is gabapentin, and the associations are strongest in patients aged 15-24 years, the researchers reported.

“If our findings are triangulated with other forms of evidence, clinical guidelines may need review regarding prescriptions for young people and those with substance use disorders,” wrote Yasmina Molero, PhD, and associates. “Further restrictions for off-label prescription may need consideration.” The study was published in BMJ.

The use of gabapentinoids has risen in the United States (JAMA Intern Med. 2018;178[2]:292-4), and overdose deaths tied to gabapentin have led some states to explore reclassification of the drug as a controlled substance (Risk Manag Healthc Policy. 2018;11:109-16). In the United Kingdom, gabapentinoids are being reclassified as a class C controlled drug because of concerns about the risk of addiction, overdose, and safety, wrote Dr. Molero of the department of psychiatry at Warneford Hospital at the University of Oxford, England, and associates.

To study associations between gabapentinoids and adverse outcomes related to coordination, mental health, and criminality, Dr. Molero and her associates analyzed data from 191,973 people from the Swedish Prescribed Drug Register who collected prescriptions for pregabalin or gabapentin between 2006 and 2013. The researchers included patients aged 15 years and older in their analyses.

They examined suicidal behavior, unintentional overdoses, head or body injuries, road traffic incidents and offenses, and arrests for violent crime using the Swedish Patient Register and the National Crime Register. In addition, they defined suicidal behavior as emergency hospital visits attributable to self-injurious behavior or suicide attempt, or death by suicide. Unintentional overdoses were defined as emergency hospital visits or death attributable to poisoning by illicit drugs, medications, or biologic substances; accidental poisoning by noxious substances; or acute intoxications and overdoses by alcohol and illicit drugs, excluding intentional self-poisoning, wrote Dr. Molero, who is affiliated with the Karolinska Institute in Stockholm, and her associates.

Of the nearly 192,000 participants who collected prescriptions of gabapentinoids on at least two consecutive occasions, 120,664 received pregabalin, and 85,360 received gabapentin; 14,051 of the participants received both drugs. Fifty-nine percent were women, and most patients were aged 45 or older.

During the study period, 10,026 participants (5.2%) were treated for suicidal behavior or died from suicide, 17,144 participants (8.9%) experienced an unintentional overdose, and 12,070 participants (6.3%) had a road traffic incident or offense. In addition, 70,522 participants (36.7%) had head or body injuries, and 7,984 participants (4.1%) were arrested for a violent crime.

jremaly@mdedge.com

SOURCE: Molero Y et al. BMJ. 2019 Jun 12. doi: 10.1136/bmj.l2147.

Young patients might be at increased risk of suicidal behavior, unintentional overdose, injuries, and traffic incidents during treatment periods with gabapentinoids, compared with periods without treatment with those medications, a cohort study of almost 200,000 people shows. Pregabalin is associated with higher hazards of those outcomes than is gabapentin, and the associations are strongest in patients aged 15-24 years, the researchers reported.

“If our findings are triangulated with other forms of evidence, clinical guidelines may need review regarding prescriptions for young people and those with substance use disorders,” wrote Yasmina Molero, PhD, and associates. “Further restrictions for off-label prescription may need consideration.” The study was published in BMJ.

The use of gabapentinoids has risen in the United States (JAMA Intern Med. 2018;178[2]:292-4), and overdose deaths tied to gabapentin have led some states to explore reclassification of the drug as a controlled substance (Risk Manag Healthc Policy. 2018;11:109-16). In the United Kingdom, gabapentinoids are being reclassified as a class C controlled drug because of concerns about the risk of addiction, overdose, and safety, wrote Dr. Molero of the department of psychiatry at Warneford Hospital at the University of Oxford, England, and associates.

To study associations between gabapentinoids and adverse outcomes related to coordination, mental health, and criminality, Dr. Molero and her associates analyzed data from 191,973 people from the Swedish Prescribed Drug Register who collected prescriptions for pregabalin or gabapentin between 2006 and 2013. The researchers included patients aged 15 years and older in their analyses.

They examined suicidal behavior, unintentional overdoses, head or body injuries, road traffic incidents and offenses, and arrests for violent crime using the Swedish Patient Register and the National Crime Register. In addition, they defined suicidal behavior as emergency hospital visits attributable to self-injurious behavior or suicide attempt, or death by suicide. Unintentional overdoses were defined as emergency hospital visits or death attributable to poisoning by illicit drugs, medications, or biologic substances; accidental poisoning by noxious substances; or acute intoxications and overdoses by alcohol and illicit drugs, excluding intentional self-poisoning, wrote Dr. Molero, who is affiliated with the Karolinska Institute in Stockholm, and her associates.

Of the nearly 192,000 participants who collected prescriptions of gabapentinoids on at least two consecutive occasions, 120,664 received pregabalin, and 85,360 received gabapentin; 14,051 of the participants received both drugs. Fifty-nine percent were women, and most patients were aged 45 or older.

During the study period, 10,026 participants (5.2%) were treated for suicidal behavior or died from suicide, 17,144 participants (8.9%) experienced an unintentional overdose, and 12,070 participants (6.3%) had a road traffic incident or offense. In addition, 70,522 participants (36.7%) had head or body injuries, and 7,984 participants (4.1%) were arrested for a violent crime.

jremaly@mdedge.com

SOURCE: Molero Y et al. BMJ. 2019 Jun 12. doi: 10.1136/bmj.l2147.

Neoadjuvant and adjuvant targeted therapy with erlotinib (Tarceva) may outperform standard chemotherapy in patients with locally advanced non–small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation, suggests the Chinese Thoracic Oncology Group’s EMERGING trial.

Investigators led by Wen-Zhao Zhong, MD, a professor at Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China, enrolled 72 patients with stage IIIA-N2 EGFR-mutant NSCLC in the phase 2 randomized controlled trial. The patients were randomized to receive either erlotinib, an EGFR tyrosine kinase inhibitor (TKI), or the chemotherapy doublet of gemcitabine (Gemzar) and cisplatin as both neoadjuvant and adjuvant therapy.

Results reported in the Journal of Clinical Oncology showed that the objective response rate was 54.1% with neoadjuvant erlotinib (median, 42 days of therapy) versus 34.3% with neoadjuvant chemotherapy (with most patients receiving two cycles). However, the difference was not significant (odds ratio, 2.26; P = .092).

None of the patients in either arm achieved a pathologic complete response, but 9.7% in the erlotinib arm achieved a major pathologic response (less than 10% residual viable tumor cells) versus none of those in the chemotherapy arm.

With a median follow-up of 14.1 months, median progression-free survival was 21.5 months with erlotinib, nearly double the 11.4 months seen with chemotherapy (hazard ratio for events, 0.39; P less than .001). Overall survival did not differ significantly but was immature at the time of analysis.

Adverse events were largely as expected for each therapy. Incidence of grade 3 or 4 adverse events was 0% with erlotinib versus 29.4% with chemotherapy.

“These results suggest that biomarker-guided neoadjuvant/adjuvant EGFR-TKI treatment strategies in stage IIIA-N2 NSCLC are promising,” Dr. Zhong and colleagues wrote. “Our promising findings warrant additional investigation.”

“The optimal duration of neoadjuvant TKI also warrants additional investigation to validate the role of perioperative TKI therapy in oncogene-driven NSCLC,” they concluded. “Future studies should investigate the translational value of sequential plasma and tissue samples in a neoadjuvant setting using multiomics-based assays to identify predictive characteristics of patients who would benefit from neoadjuvant targeted therapies and predict prognosis.”

Dr. Zhong disclosed receiving honoraria from AstraZeneca, Eli Lilly, Pfizer, Roche, and Sanofi. The trial was supported by the Chinese Thoracic Oncology Group and Shanghai Roche Pharmaceutical.

SOURCE: Zhong W-Z et al. J Clin Oncol. 2019 June 13. doi: 10.1200/JCO.19.00075.

Neoadjuvant and adjuvant targeted therapy with erlotinib (Tarceva) may outperform standard chemotherapy in patients with locally advanced non–small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation, suggests the Chinese Thoracic Oncology Group’s EMERGING trial.

Investigators led by Wen-Zhao Zhong, MD, a professor at Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China, enrolled 72 patients with stage IIIA-N2 EGFR-mutant NSCLC in the phase 2 randomized controlled trial. The patients were randomized to receive either erlotinib, an EGFR tyrosine kinase inhibitor (TKI), or the chemotherapy doublet of gemcitabine (Gemzar) and cisplatin as both neoadjuvant and adjuvant therapy.

Results reported in the Journal of Clinical Oncology showed that the objective response rate was 54.1% with neoadjuvant erlotinib (median, 42 days of therapy) versus 34.3% with neoadjuvant chemotherapy (with most patients receiving two cycles). However, the difference was not significant (odds ratio, 2.26; P = .092).

None of the patients in either arm achieved a pathologic complete response, but 9.7% in the erlotinib arm achieved a major pathologic response (less than 10% residual viable tumor cells) versus none of those in the chemotherapy arm.

With a median follow-up of 14.1 months, median progression-free survival was 21.5 months with erlotinib, nearly double the 11.4 months seen with chemotherapy (hazard ratio for events, 0.39; P less than .001). Overall survival did not differ significantly but was immature at the time of analysis.

Adverse events were largely as expected for each therapy. Incidence of grade 3 or 4 adverse events was 0% with erlotinib versus 29.4% with chemotherapy.

“These results suggest that biomarker-guided neoadjuvant/adjuvant EGFR-TKI treatment strategies in stage IIIA-N2 NSCLC are promising,” Dr. Zhong and colleagues wrote. “Our promising findings warrant additional investigation.”

“The optimal duration of neoadjuvant TKI also warrants additional investigation to validate the role of perioperative TKI therapy in oncogene-driven NSCLC,” they concluded. “Future studies should investigate the translational value of sequential plasma and tissue samples in a neoadjuvant setting using multiomics-based assays to identify predictive characteristics of patients who would benefit from neoadjuvant targeted therapies and predict prognosis.”

Dr. Zhong disclosed receiving honoraria from AstraZeneca, Eli Lilly, Pfizer, Roche, and Sanofi. The trial was supported by the Chinese Thoracic Oncology Group and Shanghai Roche Pharmaceutical.

SOURCE: Zhong W-Z et al. J Clin Oncol. 2019 June 13. doi: 10.1200/JCO.19.00075.

Neoadjuvant and adjuvant targeted therapy with erlotinib (Tarceva) may outperform standard chemotherapy in patients with locally advanced non–small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation, suggests the Chinese Thoracic Oncology Group’s EMERGING trial.

Investigators led by Wen-Zhao Zhong, MD, a professor at Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China, enrolled 72 patients with stage IIIA-N2 EGFR-mutant NSCLC in the phase 2 randomized controlled trial. The patients were randomized to receive either erlotinib, an EGFR tyrosine kinase inhibitor (TKI), or the chemotherapy doublet of gemcitabine (Gemzar) and cisplatin as both neoadjuvant and adjuvant therapy.

Results reported in the Journal of Clinical Oncology showed that the objective response rate was 54.1% with neoadjuvant erlotinib (median, 42 days of therapy) versus 34.3% with neoadjuvant chemotherapy (with most patients receiving two cycles). However, the difference was not significant (odds ratio, 2.26; P = .092).

None of the patients in either arm achieved a pathologic complete response, but 9.7% in the erlotinib arm achieved a major pathologic response (less than 10% residual viable tumor cells) versus none of those in the chemotherapy arm.

With a median follow-up of 14.1 months, median progression-free survival was 21.5 months with erlotinib, nearly double the 11.4 months seen with chemotherapy (hazard ratio for events, 0.39; P less than .001). Overall survival did not differ significantly but was immature at the time of analysis.

Adverse events were largely as expected for each therapy. Incidence of grade 3 or 4 adverse events was 0% with erlotinib versus 29.4% with chemotherapy.

“These results suggest that biomarker-guided neoadjuvant/adjuvant EGFR-TKI treatment strategies in stage IIIA-N2 NSCLC are promising,” Dr. Zhong and colleagues wrote. “Our promising findings warrant additional investigation.”

“The optimal duration of neoadjuvant TKI also warrants additional investigation to validate the role of perioperative TKI therapy in oncogene-driven NSCLC,” they concluded. “Future studies should investigate the translational value of sequential plasma and tissue samples in a neoadjuvant setting using multiomics-based assays to identify predictive characteristics of patients who would benefit from neoadjuvant targeted therapies and predict prognosis.”

Dr. Zhong disclosed receiving honoraria from AstraZeneca, Eli Lilly, Pfizer, Roche, and Sanofi. The trial was supported by the Chinese Thoracic Oncology Group and Shanghai Roche Pharmaceutical.

SOURCE: Zhong W-Z et al. J Clin Oncol. 2019 June 13. doi: 10.1200/JCO.19.00075.

Many performance improvement programs try to create a higher value health system by incentivizing physicians and health systems to behave in particular ways. These have often been pay-for-performance programs that offer bonuses or impose penalties depending on how providers perform on various metrics.

“In theory, this makes sense,” said Dhruv Khullar, MD, MPP, lead author of a JAMA article about the future of incentives, and assistant professor at Weill Cornell Medicine in New York. “But in practice, these programs have not been successful in consistently improving quality, and sometimes they have been counterproductive. In our article, we argued that focusing too narrowly on financial rewards is not the right strategy to improve health system performance – and is sometimes at odds with the physician professionalism and what really motivates most clinicians.”

Pay-for-performance programs suffer from several fundamental flaws: they focus too narrowly on financial incentives and use centralized accountability instead of local culture, for example, Dr. Khullar said.

“A better future state would involve capitalizing on physician professionalism through nonfinancial rewards, resources for quality improvement, team-based assessments, and emphasizing continuous learning and organizational culture,” he noted. Performance programs would take a more global view of clinical care by emphasizing culture, teams, trust, and learning. Such a system would allow hospitalists and other physicians to worry less about meeting specific metrics and focus more on providing high-quality care to their patients.

“I would hope physicians, payers, and administrators would reconsider some previously held beliefs about quality improvement, especially the idea that better quality requires giving people bonus payments or imposing financial penalties,” Dr. Khullar said. “We believe the next wave of performance improvement programs should entertain other paths to better quality, which are more in line with human motivation and physician professionalism.”
 

Reference

1. Khullar D, Wolfson D, Casalino LP. Professionalism, Performance, and the Future of Physician Incentives. JAMA. 2018 Nov 26 (Epub ahead of print). doi: 10.1001/jama.2018.17719. Accessed Dec. 11, 2018.

Many performance improvement programs try to create a higher value health system by incentivizing physicians and health systems to behave in particular ways. These have often been pay-for-performance programs that offer bonuses or impose penalties depending on how providers perform on various metrics.

“In theory, this makes sense,” said Dhruv Khullar, MD, MPP, lead author of a JAMA article about the future of incentives, and assistant professor at Weill Cornell Medicine in New York. “But in practice, these programs have not been successful in consistently improving quality, and sometimes they have been counterproductive. In our article, we argued that focusing too narrowly on financial rewards is not the right strategy to improve health system performance – and is sometimes at odds with the physician professionalism and what really motivates most clinicians.”

Pay-for-performance programs suffer from several fundamental flaws: they focus too narrowly on financial incentives and use centralized accountability instead of local culture, for example, Dr. Khullar said.

“A better future state would involve capitalizing on physician professionalism through nonfinancial rewards, resources for quality improvement, team-based assessments, and emphasizing continuous learning and organizational culture,” he noted. Performance programs would take a more global view of clinical care by emphasizing culture, teams, trust, and learning. Such a system would allow hospitalists and other physicians to worry less about meeting specific metrics and focus more on providing high-quality care to their patients.

“I would hope physicians, payers, and administrators would reconsider some previously held beliefs about quality improvement, especially the idea that better quality requires giving people bonus payments or imposing financial penalties,” Dr. Khullar said. “We believe the next wave of performance improvement programs should entertain other paths to better quality, which are more in line with human motivation and physician professionalism.”
 

Reference

1. Khullar D, Wolfson D, Casalino LP. Professionalism, Performance, and the Future of Physician Incentives. JAMA. 2018 Nov 26 (Epub ahead of print). doi: 10.1001/jama.2018.17719. Accessed Dec. 11, 2018.

Many performance improvement programs try to create a higher value health system by incentivizing physicians and health systems to behave in particular ways. These have often been pay-for-performance programs that offer bonuses or impose penalties depending on how providers perform on various metrics.

“In theory, this makes sense,” said Dhruv Khullar, MD, MPP, lead author of a JAMA article about the future of incentives, and assistant professor at Weill Cornell Medicine in New York. “But in practice, these programs have not been successful in consistently improving quality, and sometimes they have been counterproductive. In our article, we argued that focusing too narrowly on financial rewards is not the right strategy to improve health system performance – and is sometimes at odds with the physician professionalism and what really motivates most clinicians.”

Pay-for-performance programs suffer from several fundamental flaws: they focus too narrowly on financial incentives and use centralized accountability instead of local culture, for example, Dr. Khullar said.

“A better future state would involve capitalizing on physician professionalism through nonfinancial rewards, resources for quality improvement, team-based assessments, and emphasizing continuous learning and organizational culture,” he noted. Performance programs would take a more global view of clinical care by emphasizing culture, teams, trust, and learning. Such a system would allow hospitalists and other physicians to worry less about meeting specific metrics and focus more on providing high-quality care to their patients.

“I would hope physicians, payers, and administrators would reconsider some previously held beliefs about quality improvement, especially the idea that better quality requires giving people bonus payments or imposing financial penalties,” Dr. Khullar said. “We believe the next wave of performance improvement programs should entertain other paths to better quality, which are more in line with human motivation and physician professionalism.”
 

Reference

1. Khullar D, Wolfson D, Casalino LP. Professionalism, Performance, and the Future of Physician Incentives. JAMA. 2018 Nov 26 (Epub ahead of print). doi: 10.1001/jama.2018.17719. Accessed Dec. 11, 2018.

Two researchers have joined Stand Up To Cancer’s scientific advisory committee, which directs the organization’s research initiatives, reviews grant proposals, and oversees active grants.

One new committee member is John D. Carpten, PhD, of the University of Southern California in Los Angeles. Dr. Carpten’s research encompasses several cancer types and focuses on the use of genomic technologies and bioinformatics analysis.

The other new committee member is Roderic I. Pettigrew, MD, PhD, of Texas A&M University in College Station. Dr. Pettigrew is known for pioneering four-dimensional imaging of the cardiovascular system using MRI.

jensmith@mdedge.com

Two researchers have joined Stand Up To Cancer’s scientific advisory committee, which directs the organization’s research initiatives, reviews grant proposals, and oversees active grants.

One new committee member is John D. Carpten, PhD, of the University of Southern California in Los Angeles. Dr. Carpten’s research encompasses several cancer types and focuses on the use of genomic technologies and bioinformatics analysis.

The other new committee member is Roderic I. Pettigrew, MD, PhD, of Texas A&M University in College Station. Dr. Pettigrew is known for pioneering four-dimensional imaging of the cardiovascular system using MRI.

jensmith@mdedge.com

Two researchers have joined Stand Up To Cancer’s scientific advisory committee, which directs the organization’s research initiatives, reviews grant proposals, and oversees active grants.

One new committee member is John D. Carpten, PhD, of the University of Southern California in Los Angeles. Dr. Carpten’s research encompasses several cancer types and focuses on the use of genomic technologies and bioinformatics analysis.

The other new committee member is Roderic I. Pettigrew, MD, PhD, of Texas A&M University in College Station. Dr. Pettigrew is known for pioneering four-dimensional imaging of the cardiovascular system using MRI.

jensmith@mdedge.com

Metatarsal bones are an unusual subsite for small bone involvement in osteosarcomas. This subgroup is often misdiagnosed and hence associated with significant treatment delays. The standard treatment of metatarsal osteosarcomas remains the same as for those treated at other sites, namely neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy. Limb salvage surgery or metatarsectomy in the foot is often a challenge owing to the poor compartmentalization of the disease. We hereby describe the case of a young girl with a metatarsal osteosarcoma who was managed with neoadjuvant chemotherapy and limb salvage surgery.

Introduction

Osteosarcomas are the most common primary malignant bone tumor in children and adolescents. Although predominantly occurring in pediatric and adolescent age groups, bimodal distribution (with a second incidence peak occurring in the sixth and seventh decades) is not uncommon.¹ Osteosarcomas of the foot and small bones represent a rare and distinct clinical entity. This must have been a well-known observation for years that led to Watson-Jones stating, “Sarcoma of this [metatarsal] bone has not yet been reported in thousands of years in any country.”² The incidence of osteosarcomas of the foot is estimated to be from 0.2% to 2%.³

These tumors, owing to their rarity, often lead to diagnostic dilemmas and hence treatment delays.⁴ They are usually mistaken for inflammatory conditions and often treated with—but not limited to—curettages and drainage procedures.⁵ The following case of osteosarcoma of the metatarsal bone in a young girl highlights the importance of having a high index of clinical suspicion prior to treatment.

Case Presentation and Summary

A 10-year-old girl visited our outpatient clinic with a painful progressive swelling on the dorsum of the left foot of 2 months’ duration. There was no history of antecedent trauma or fever. Physical examination revealed a bony hard swelling measuring around 5 x 6 cm on the dorsum of the left foot around the region of the second metatarsal. There was no regional lymphadenopathy or distal neurovascular deficit. She was evaluated with a plain radiograph that demonstrated a lytic lesion in the left second metatarsal associated with cortical destruction and periosteal reaction (Figure 1). A subsequent magnetic resonance image (MRI) revealed a bony lesion destroying part of the left second metatarsal with cortical destruction and marrow involvement and affecting the soft tissue around the adjacent third metatarsal (Figure 2). Needle biopsy showed chondroblastic osteosarcoma. Computed tomography (CT) of the thorax and bone scan were both negative for distant metastases.

She received 3 cycles of a MAP (highdose methotrexate, doxorubicin, and cisplatin) regimen as neoadjuvant chemotherapy. Response assessment scans showed partial response (Figures 3A and B). We performed a wide excision of the second and third metatarsal with reconstruction using a segment of non-vascularized fibular graft as rigid fixation (Figure 4). The postoperative period was uneventful. She was able to begin partial weight bearing on the fourth postoperative day and her sutures were removed on the twelfth postoperative day. She received adjuvant chemotherapy following surgery. The final histopathology report showed residual disease with Huvos grade III response (>90% necrosis) with all margins negative for malignancy (Figure 5). At present, the child is disease-free at 5 months of treatment completion and is undergoing regular follow-up visits.

Discussion

Metatarsal involvement amongst smallbone osteosarcomas is uncommon.³ There are about 32 cases of osteosarcomas reported in the literature from 1940 to 2018 involving the metatarsal bones (Table 1). According to a review article from the Mayo Clinic, the most common bone of the foot involved is the calcaneum.⁶ While the incidence of osteosarcomas of the foot as a whole is around 0.2% to 2%,3 metatarsal involvement is documented in 0.5% of these patients.⁷ However, a recent study depicted metatarsal involvement in 33% of all osteosarcomas of the foot.⁸

Osteosarcomas at conventional sites tend to have a bimodal age distribution with respect to disease affliction.⁹ Metatarsal osteosarcomas, however, are more common in an older age group.^4,10 Our patient is probably the second youngest reported case of metatarsal osteosarcoma in the literature.¹¹

Biscaglia et al propounded that osteosarcomas of the metatarsal were a distinct subgroup due to the rarity of occurrence, anatomical location, and prognosis.⁴ This often led to misdiagnosis and subsequent inadequate or inappropriate surgery. In six out of the ten cases (60%) described in Table 1, an incorrect pretreatment diagnosis was made that led to treatment delay. None, except one patient, received neoadjuvant chemotherapy, which is currently the standard of care. The average duration from symptom onset to diagnosis was found to be 2 years.⁴ However, in our case, the duration of symptoms was approximately 2 months.

Surgery for metatarsal osteosarcomas can be challenging, as the compartments of the foot are narrow spaces with poor demarcation. Limb salvage surgery in the form of metatarsectomy needs proper preoperative planning and execution. Neoadjuvant chemotherapy will serve to downstage the tumor within the fascial barriers of the metatarsal compartment.It has also been postulated that osteosarcoma of the foot may have a better prognosis and survival compared to other osteosarcoma subsites.¹⁰ This can be extrapolated from the fact that the majority are found to be low grade, and despite a long delay in treatment, there was no rapid increase in size and/or metastatic spread. However, tumor grade remains an important factor affecting survival— patients with higher grade tumors have worse survival.⁸

A number of differentials, including benign tumors, are to be kept in mind when diagnosing and treating such patients (Table 2). The most common benign tumors affecting the metatarsal are giant cell tumors (GCT) followed by chondromyxoid fibroma. Osteosarcomas and Ewing sarcomas constitute the malignant tumors.¹² Occasionally, infections like osteomyelitis of the small bones may mimic malignancy. The absence of an extensive soft tissue component and/or calcifications with the presence of bony changes (like sequestrum) favors a diagnosis of infection/osteomyelitis. In addition, clinical findings like fever, skin redness, and presence of a painful swelling (especially after onset of fever) point to an inflammatory pathology rather than malignancy. Stress fractures rarely simulate tumors. MRI showing marrow and soft tissue edema with a visible fracture line points to the diagnosis.

A plane radiograph showing cortical bone destruction with a soft tissue component and calcification should be considered suspicious and must be thoroughly evaluated prior to surgical treatment.¹³ In a young patient such as ours, the important differentials that need to be considered include Ewing sarcoma, chronic osteomyelitis, and eosinophilic granuloma, which can radiologically mimic osteosarcoma at this location.

Conclusions

Osteosarcoma of the metatarsal is rare. Our case remains unique as it reports the second youngest patient in the literature. Erroneous or delayed diagnosis resulting in inadequate tumor excision and limb loss (amputation) often occurs in a majority of the cases. Proper pretreatment radiological imaging becomes imperative, and when clinical suspicion is high, a needle biopsy must follow in those cases. Early diagnosis with administration of neoadjuvant chemotherapy may allow us to perform limb salvage surgery or wide excision in these cases.

Acknowledgement
We would like to thank Dr. Sithara Aravind, Associate Professor, Department of Pathology, Malabar Cancer Center, for the photomicrographs.

Metatarsal bones are an unusual subsite for small bone involvement in osteosarcomas. This subgroup is often misdiagnosed and hence associated with significant treatment delays. The standard treatment of metatarsal osteosarcomas remains the same as for those treated at other sites, namely neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy. Limb salvage surgery or metatarsectomy in the foot is often a challenge owing to the poor compartmentalization of the disease. We hereby describe the case of a young girl with a metatarsal osteosarcoma who was managed with neoadjuvant chemotherapy and limb salvage surgery.

Introduction

Osteosarcomas are the most common primary malignant bone tumor in children and adolescents. Although predominantly occurring in pediatric and adolescent age groups, bimodal distribution (with a second incidence peak occurring in the sixth and seventh decades) is not uncommon.¹ Osteosarcomas of the foot and small bones represent a rare and distinct clinical entity. This must have been a well-known observation for years that led to Watson-Jones stating, “Sarcoma of this [metatarsal] bone has not yet been reported in thousands of years in any country.”² The incidence of osteosarcomas of the foot is estimated to be from 0.2% to 2%.³

These tumors, owing to their rarity, often lead to diagnostic dilemmas and hence treatment delays.⁴ They are usually mistaken for inflammatory conditions and often treated with—but not limited to—curettages and drainage procedures.⁵ The following case of osteosarcoma of the metatarsal bone in a young girl highlights the importance of having a high index of clinical suspicion prior to treatment.

Case Presentation and Summary

A 10-year-old girl visited our outpatient clinic with a painful progressive swelling on the dorsum of the left foot of 2 months’ duration. There was no history of antecedent trauma or fever. Physical examination revealed a bony hard swelling measuring around 5 x 6 cm on the dorsum of the left foot around the region of the second metatarsal. There was no regional lymphadenopathy or distal neurovascular deficit. She was evaluated with a plain radiograph that demonstrated a lytic lesion in the left second metatarsal associated with cortical destruction and periosteal reaction (Figure 1). A subsequent magnetic resonance image (MRI) revealed a bony lesion destroying part of the left second metatarsal with cortical destruction and marrow involvement and affecting the soft tissue around the adjacent third metatarsal (Figure 2). Needle biopsy showed chondroblastic osteosarcoma. Computed tomography (CT) of the thorax and bone scan were both negative for distant metastases.

She received 3 cycles of a MAP (highdose methotrexate, doxorubicin, and cisplatin) regimen as neoadjuvant chemotherapy. Response assessment scans showed partial response (Figures 3A and B). We performed a wide excision of the second and third metatarsal with reconstruction using a segment of non-vascularized fibular graft as rigid fixation (Figure 4). The postoperative period was uneventful. She was able to begin partial weight bearing on the fourth postoperative day and her sutures were removed on the twelfth postoperative day. She received adjuvant chemotherapy following surgery. The final histopathology report showed residual disease with Huvos grade III response (>90% necrosis) with all margins negative for malignancy (Figure 5). At present, the child is disease-free at 5 months of treatment completion and is undergoing regular follow-up visits.

Discussion

Metatarsal involvement amongst smallbone osteosarcomas is uncommon.³ There are about 32 cases of osteosarcomas reported in the literature from 1940 to 2018 involving the metatarsal bones (Table 1). According to a review article from the Mayo Clinic, the most common bone of the foot involved is the calcaneum.⁶ While the incidence of osteosarcomas of the foot as a whole is around 0.2% to 2%,3 metatarsal involvement is documented in 0.5% of these patients.⁷ However, a recent study depicted metatarsal involvement in 33% of all osteosarcomas of the foot.⁸

Osteosarcomas at conventional sites tend to have a bimodal age distribution with respect to disease affliction.⁹ Metatarsal osteosarcomas, however, are more common in an older age group.^4,10 Our patient is probably the second youngest reported case of metatarsal osteosarcoma in the literature.¹¹

Biscaglia et al propounded that osteosarcomas of the metatarsal were a distinct subgroup due to the rarity of occurrence, anatomical location, and prognosis.⁴ This often led to misdiagnosis and subsequent inadequate or inappropriate surgery. In six out of the ten cases (60%) described in Table 1, an incorrect pretreatment diagnosis was made that led to treatment delay. None, except one patient, received neoadjuvant chemotherapy, which is currently the standard of care. The average duration from symptom onset to diagnosis was found to be 2 years.⁴ However, in our case, the duration of symptoms was approximately 2 months.

Surgery for metatarsal osteosarcomas can be challenging, as the compartments of the foot are narrow spaces with poor demarcation. Limb salvage surgery in the form of metatarsectomy needs proper preoperative planning and execution. Neoadjuvant chemotherapy will serve to downstage the tumor within the fascial barriers of the metatarsal compartment.It has also been postulated that osteosarcoma of the foot may have a better prognosis and survival compared to other osteosarcoma subsites.¹⁰ This can be extrapolated from the fact that the majority are found to be low grade, and despite a long delay in treatment, there was no rapid increase in size and/or metastatic spread. However, tumor grade remains an important factor affecting survival— patients with higher grade tumors have worse survival.⁸

A number of differentials, including benign tumors, are to be kept in mind when diagnosing and treating such patients (Table 2). The most common benign tumors affecting the metatarsal are giant cell tumors (GCT) followed by chondromyxoid fibroma. Osteosarcomas and Ewing sarcomas constitute the malignant tumors.¹² Occasionally, infections like osteomyelitis of the small bones may mimic malignancy. The absence of an extensive soft tissue component and/or calcifications with the presence of bony changes (like sequestrum) favors a diagnosis of infection/osteomyelitis. In addition, clinical findings like fever, skin redness, and presence of a painful swelling (especially after onset of fever) point to an inflammatory pathology rather than malignancy. Stress fractures rarely simulate tumors. MRI showing marrow and soft tissue edema with a visible fracture line points to the diagnosis.

A plane radiograph showing cortical bone destruction with a soft tissue component and calcification should be considered suspicious and must be thoroughly evaluated prior to surgical treatment.¹³ In a young patient such as ours, the important differentials that need to be considered include Ewing sarcoma, chronic osteomyelitis, and eosinophilic granuloma, which can radiologically mimic osteosarcoma at this location.

Conclusions

Osteosarcoma of the metatarsal is rare. Our case remains unique as it reports the second youngest patient in the literature. Erroneous or delayed diagnosis resulting in inadequate tumor excision and limb loss (amputation) often occurs in a majority of the cases. Proper pretreatment radiological imaging becomes imperative, and when clinical suspicion is high, a needle biopsy must follow in those cases. Early diagnosis with administration of neoadjuvant chemotherapy may allow us to perform limb salvage surgery or wide excision in these cases.

Acknowledgement
We would like to thank Dr. Sithara Aravind, Associate Professor, Department of Pathology, Malabar Cancer Center, for the photomicrographs.

Metatarsal bones are an unusual subsite for small bone involvement in osteosarcomas. This subgroup is often misdiagnosed and hence associated with significant treatment delays. The standard treatment of metatarsal osteosarcomas remains the same as for those treated at other sites, namely neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy. Limb salvage surgery or metatarsectomy in the foot is often a challenge owing to the poor compartmentalization of the disease. We hereby describe the case of a young girl with a metatarsal osteosarcoma who was managed with neoadjuvant chemotherapy and limb salvage surgery.

Introduction

Osteosarcomas are the most common primary malignant bone tumor in children and adolescents. Although predominantly occurring in pediatric and adolescent age groups, bimodal distribution (with a second incidence peak occurring in the sixth and seventh decades) is not uncommon.¹ Osteosarcomas of the foot and small bones represent a rare and distinct clinical entity. This must have been a well-known observation for years that led to Watson-Jones stating, “Sarcoma of this [metatarsal] bone has not yet been reported in thousands of years in any country.”² The incidence of osteosarcomas of the foot is estimated to be from 0.2% to 2%.³

These tumors, owing to their rarity, often lead to diagnostic dilemmas and hence treatment delays.⁴ They are usually mistaken for inflammatory conditions and often treated with—but not limited to—curettages and drainage procedures.⁵ The following case of osteosarcoma of the metatarsal bone in a young girl highlights the importance of having a high index of clinical suspicion prior to treatment.

Case Presentation and Summary

A 10-year-old girl visited our outpatient clinic with a painful progressive swelling on the dorsum of the left foot of 2 months’ duration. There was no history of antecedent trauma or fever. Physical examination revealed a bony hard swelling measuring around 5 x 6 cm on the dorsum of the left foot around the region of the second metatarsal. There was no regional lymphadenopathy or distal neurovascular deficit. She was evaluated with a plain radiograph that demonstrated a lytic lesion in the left second metatarsal associated with cortical destruction and periosteal reaction (Figure 1). A subsequent magnetic resonance image (MRI) revealed a bony lesion destroying part of the left second metatarsal with cortical destruction and marrow involvement and affecting the soft tissue around the adjacent third metatarsal (Figure 2). Needle biopsy showed chondroblastic osteosarcoma. Computed tomography (CT) of the thorax and bone scan were both negative for distant metastases.

She received 3 cycles of a MAP (highdose methotrexate, doxorubicin, and cisplatin) regimen as neoadjuvant chemotherapy. Response assessment scans showed partial response (Figures 3A and B). We performed a wide excision of the second and third metatarsal with reconstruction using a segment of non-vascularized fibular graft as rigid fixation (Figure 4). The postoperative period was uneventful. She was able to begin partial weight bearing on the fourth postoperative day and her sutures were removed on the twelfth postoperative day. She received adjuvant chemotherapy following surgery. The final histopathology report showed residual disease with Huvos grade III response (>90% necrosis) with all margins negative for malignancy (Figure 5). At present, the child is disease-free at 5 months of treatment completion and is undergoing regular follow-up visits.

Discussion

Metatarsal involvement amongst smallbone osteosarcomas is uncommon.³ There are about 32 cases of osteosarcomas reported in the literature from 1940 to 2018 involving the metatarsal bones (Table 1). According to a review article from the Mayo Clinic, the most common bone of the foot involved is the calcaneum.⁶ While the incidence of osteosarcomas of the foot as a whole is around 0.2% to 2%,3 metatarsal involvement is documented in 0.5% of these patients.⁷ However, a recent study depicted metatarsal involvement in 33% of all osteosarcomas of the foot.⁸

Osteosarcomas at conventional sites tend to have a bimodal age distribution with respect to disease affliction.⁹ Metatarsal osteosarcomas, however, are more common in an older age group.^4,10 Our patient is probably the second youngest reported case of metatarsal osteosarcoma in the literature.¹¹

Biscaglia et al propounded that osteosarcomas of the metatarsal were a distinct subgroup due to the rarity of occurrence, anatomical location, and prognosis.⁴ This often led to misdiagnosis and subsequent inadequate or inappropriate surgery. In six out of the ten cases (60%) described in Table 1, an incorrect pretreatment diagnosis was made that led to treatment delay. None, except one patient, received neoadjuvant chemotherapy, which is currently the standard of care. The average duration from symptom onset to diagnosis was found to be 2 years.⁴ However, in our case, the duration of symptoms was approximately 2 months.

Surgery for metatarsal osteosarcomas can be challenging, as the compartments of the foot are narrow spaces with poor demarcation. Limb salvage surgery in the form of metatarsectomy needs proper preoperative planning and execution. Neoadjuvant chemotherapy will serve to downstage the tumor within the fascial barriers of the metatarsal compartment.It has also been postulated that osteosarcoma of the foot may have a better prognosis and survival compared to other osteosarcoma subsites.¹⁰ This can be extrapolated from the fact that the majority are found to be low grade, and despite a long delay in treatment, there was no rapid increase in size and/or metastatic spread. However, tumor grade remains an important factor affecting survival— patients with higher grade tumors have worse survival.⁸

A number of differentials, including benign tumors, are to be kept in mind when diagnosing and treating such patients (Table 2). The most common benign tumors affecting the metatarsal are giant cell tumors (GCT) followed by chondromyxoid fibroma. Osteosarcomas and Ewing sarcomas constitute the malignant tumors.¹² Occasionally, infections like osteomyelitis of the small bones may mimic malignancy. The absence of an extensive soft tissue component and/or calcifications with the presence of bony changes (like sequestrum) favors a diagnosis of infection/osteomyelitis. In addition, clinical findings like fever, skin redness, and presence of a painful swelling (especially after onset of fever) point to an inflammatory pathology rather than malignancy. Stress fractures rarely simulate tumors. MRI showing marrow and soft tissue edema with a visible fracture line points to the diagnosis.

A plane radiograph showing cortical bone destruction with a soft tissue component and calcification should be considered suspicious and must be thoroughly evaluated prior to surgical treatment.¹³ In a young patient such as ours, the important differentials that need to be considered include Ewing sarcoma, chronic osteomyelitis, and eosinophilic granuloma, which can radiologically mimic osteosarcoma at this location.

Conclusions

Osteosarcoma of the metatarsal is rare. Our case remains unique as it reports the second youngest patient in the literature. Erroneous or delayed diagnosis resulting in inadequate tumor excision and limb loss (amputation) often occurs in a majority of the cases. Proper pretreatment radiological imaging becomes imperative, and when clinical suspicion is high, a needle biopsy must follow in those cases. Early diagnosis with administration of neoadjuvant chemotherapy may allow us to perform limb salvage surgery or wide excision in these cases.

Acknowledgement
We would like to thank Dr. Sithara Aravind, Associate Professor, Department of Pathology, Malabar Cancer Center, for the photomicrographs.

Patients with pediatric-onset multiple sclerosis are more likely than those with adult-onset disease to have impairment in information processing in adulthood, independent of age or disease duration, according to a study published in JAMA Neurology.

designer491/Thinkstock

Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).

“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.

Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.

Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.

To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.

SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.

The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.

The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.

Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).

“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

jremaly@mdedge.com

SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.
 

Patients with pediatric-onset multiple sclerosis are more likely than those with adult-onset disease to have impairment in information processing in adulthood, independent of age or disease duration, according to a study published in JAMA Neurology.

designer491/Thinkstock

Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).

“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.

Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.

Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.

To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.

SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.

The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.

The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.

Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).

“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

jremaly@mdedge.com

SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.
 

Patients with pediatric-onset multiple sclerosis are more likely than those with adult-onset disease to have impairment in information processing in adulthood, independent of age or disease duration, according to a study published in JAMA Neurology.

designer491/Thinkstock

Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).

“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.

Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.

Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.

To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.

SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.

The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.

The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.

Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).

“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

jremaly@mdedge.com

SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.
 

Women in their 80s who have osteoporosis are at greater risk of fracture than their counterparts without the disease and therefore have more to gain from osteoporosis treatment, regardless of the presence of any comorbidities, according to a new study.

To determine how and when to treat older women for osteoporosis, Kristine E. Ensrud, MD, of the University of Minnesota, Minneapolis, and coauthors studied active surviving participants in the Study of Osteoporotic Fractures. The cohort comprised 1,528 women who met criteria for either osteoporosis (n = 761) or without osteoporosis but at high fracture risk (n = 767). Mean age at the time of examination was 84 years and mean femoral neck bone mineral density (BMD) T-score was −2.24.

During an average follow-up period of 4.4 years after initial examination, 125 women (9%) experienced a hip fracture and 287 (19%) died without experiencing that outcome. The 5-year absolute probability of mortality was 25% (95% confidence interval, 21.8%-28.1%) in women with osteoporosis and 19% (95% CI, 16.6%-22.3%) in women without osteoporosis but at high fracture risk. Although both groups saw mortality probability increase with more comorbidities and poorer prognosis, 5-year hip fracture probability was 13% (95% CI, 10.7%-15.5%) among women with osteoporosis and 4% (95% CI, 2.8%-5.6%) among women without osteoporosis but at high fracture risk.

Bojan89/iStock/Getty Images Plus

This probability of the women with osteoporosis experiencing a hip fracture, “even after considering their competing mortality risk” suggests that “initiation of drug treatment in late-life women with osteoporosis may still be effective in the prevention of subsequent hip fracture,” the researchers wrote in JAMA Internal Medicine.

Dr. Ensrud and associates acknowledged their study’s limitations, including the cohort being made up of community-dwelling white women and thus the results not being generalizable to men or women of other racial or ethnic groups. But the researchers noted that the mean femoral neck BMD of women in the study “was essentially identical to that of a nationally representative sample of community-dwelling women 80 years and older enrolled in the 2005 to 2008 NHANES [National Health and Nutrition Examination Survey].”

Dr. Cynthia M. Boyd reported receiving royalties from UpToDate and a grant from the National Institutes of Aging Dr. Katie L. Stone reported receiving grant support from Merck, and Dr. Lisa Langsetmo reported receiving grants from the National Institutes of Health and Merck. No other authors reported any relevant financial disclosures. The Study of Osteoporotic Fractures was supported by NIH and grants from NIA.

SOURCE: Ensrud KE et al. JAMA Intern Med. 2019 Jun 17. doi: 10.1001/jamainternmed.2019.0682.

Women in their 80s who have osteoporosis are at greater risk of fracture than their counterparts without the disease and therefore have more to gain from osteoporosis treatment, regardless of the presence of any comorbidities, according to a new study.

To determine how and when to treat older women for osteoporosis, Kristine E. Ensrud, MD, of the University of Minnesota, Minneapolis, and coauthors studied active surviving participants in the Study of Osteoporotic Fractures. The cohort comprised 1,528 women who met criteria for either osteoporosis (n = 761) or without osteoporosis but at high fracture risk (n = 767). Mean age at the time of examination was 84 years and mean femoral neck bone mineral density (BMD) T-score was −2.24.

During an average follow-up period of 4.4 years after initial examination, 125 women (9%) experienced a hip fracture and 287 (19%) died without experiencing that outcome. The 5-year absolute probability of mortality was 25% (95% confidence interval, 21.8%-28.1%) in women with osteoporosis and 19% (95% CI, 16.6%-22.3%) in women without osteoporosis but at high fracture risk. Although both groups saw mortality probability increase with more comorbidities and poorer prognosis, 5-year hip fracture probability was 13% (95% CI, 10.7%-15.5%) among women with osteoporosis and 4% (95% CI, 2.8%-5.6%) among women without osteoporosis but at high fracture risk.

Bojan89/iStock/Getty Images Plus

This probability of the women with osteoporosis experiencing a hip fracture, “even after considering their competing mortality risk” suggests that “initiation of drug treatment in late-life women with osteoporosis may still be effective in the prevention of subsequent hip fracture,” the researchers wrote in JAMA Internal Medicine.

Dr. Ensrud and associates acknowledged their study’s limitations, including the cohort being made up of community-dwelling white women and thus the results not being generalizable to men or women of other racial or ethnic groups. But the researchers noted that the mean femoral neck BMD of women in the study “was essentially identical to that of a nationally representative sample of community-dwelling women 80 years and older enrolled in the 2005 to 2008 NHANES [National Health and Nutrition Examination Survey].”

Dr. Cynthia M. Boyd reported receiving royalties from UpToDate and a grant from the National Institutes of Aging Dr. Katie L. Stone reported receiving grant support from Merck, and Dr. Lisa Langsetmo reported receiving grants from the National Institutes of Health and Merck. No other authors reported any relevant financial disclosures. The Study of Osteoporotic Fractures was supported by NIH and grants from NIA.

SOURCE: Ensrud KE et al. JAMA Intern Med. 2019 Jun 17. doi: 10.1001/jamainternmed.2019.0682.

Women in their 80s who have osteoporosis are at greater risk of fracture than their counterparts without the disease and therefore have more to gain from osteoporosis treatment, regardless of the presence of any comorbidities, according to a new study.

To determine how and when to treat older women for osteoporosis, Kristine E. Ensrud, MD, of the University of Minnesota, Minneapolis, and coauthors studied active surviving participants in the Study of Osteoporotic Fractures. The cohort comprised 1,528 women who met criteria for either osteoporosis (n = 761) or without osteoporosis but at high fracture risk (n = 767). Mean age at the time of examination was 84 years and mean femoral neck bone mineral density (BMD) T-score was −2.24.

During an average follow-up period of 4.4 years after initial examination, 125 women (9%) experienced a hip fracture and 287 (19%) died without experiencing that outcome. The 5-year absolute probability of mortality was 25% (95% confidence interval, 21.8%-28.1%) in women with osteoporosis and 19% (95% CI, 16.6%-22.3%) in women without osteoporosis but at high fracture risk. Although both groups saw mortality probability increase with more comorbidities and poorer prognosis, 5-year hip fracture probability was 13% (95% CI, 10.7%-15.5%) among women with osteoporosis and 4% (95% CI, 2.8%-5.6%) among women without osteoporosis but at high fracture risk.

Bojan89/iStock/Getty Images Plus

This probability of the women with osteoporosis experiencing a hip fracture, “even after considering their competing mortality risk” suggests that “initiation of drug treatment in late-life women with osteoporosis may still be effective in the prevention of subsequent hip fracture,” the researchers wrote in JAMA Internal Medicine.

Dr. Ensrud and associates acknowledged their study’s limitations, including the cohort being made up of community-dwelling white women and thus the results not being generalizable to men or women of other racial or ethnic groups. But the researchers noted that the mean femoral neck BMD of women in the study “was essentially identical to that of a nationally representative sample of community-dwelling women 80 years and older enrolled in the 2005 to 2008 NHANES [National Health and Nutrition Examination Survey].”

Dr. Cynthia M. Boyd reported receiving royalties from UpToDate and a grant from the National Institutes of Aging Dr. Katie L. Stone reported receiving grant support from Merck, and Dr. Lisa Langsetmo reported receiving grants from the National Institutes of Health and Merck. No other authors reported any relevant financial disclosures. The Study of Osteoporotic Fractures was supported by NIH and grants from NIA.

SOURCE: Ensrud KE et al. JAMA Intern Med. 2019 Jun 17. doi: 10.1001/jamainternmed.2019.0682.

It’s time to revisit legislation that exempts certain U.S. specialized cancer centers from the Medicare Prospective Payment System and from fully reporting measures of care and outcomes to the Centers for Medicare & Medicaid Services, a retrospective cohort study suggests.

The Prospective Payment System (PPS) exemption dates back to 1983 and allows exempted centers to be reimbursed on a reasonable cost basis rather than on a diagnosis-related group basis. Unlike centers that are a part of PPS, exempted centers are not required to report all process-of-care, outcome, and patient experience measures to CMS through its pay-for-performance programs.

In the new study, investigators working under senior author Karl Y. Bilimoria, MD, MS, director of the Surgical Outcomes and Quality Improvement Center and John B. Murphy Professor of Surgery at Northwestern University, Chicago, compared a variety of measures across hospital types. Data came from the American Hospital Association Annual Survey, U.S. News Best Hospitals rankings, and a sample of Medicare beneficiaries who underwent nine cancer operations.

Analyses were based on 15 hospitals affiliated with PPS-exempt cancer centers, 54 hospitals affiliated with National Cancer Institute–designated cancer centers, and 3,578 other U.S. hospitals providing cancer care. The results reported in JAMA Internal Medicine showed that hospitals affiliated with PPS-exempt cancer centers and hospitals affiliated with NCI cancer centers were similar on characteristics other than bed size and overall volume, which were larger for the latter, and on basic cancer-related services such as full-field digital mammography, genetic testing/counseling, chemotherapy, image-guided radiation, and hospice/palliative services.

U.S. News reputation scores averaged 17.5 for the PPS-exempt cancer center hospitals versus just 2.6 for the NCI cancer center hospitals (P less than .001). However, the two types of centers were statistically indistinguishable on oncology patient volume, patient safety ratings, comorbidity burden, nurse staffing, and U.S. News survival scores.

When it came to cancer operations, hospitals affiliated with PPS-exempt cancer centers and with NCI cancer centers had essentially the same adjusted postoperative outcomes for 15 of 18 measures, including mortality, readmission, and surgical site infections. Patients treated at the latter more often developed postoperative sepsis (3.1% vs. 1.7%; P = .002), acute renal failure (6.2% vs. 3.9%; P = .01), and urinary tract infection (6.4% vs. 4.0%; P = .002).

PPS-exempt cancer center hospitals had better outcomes than the group of other U.S. hospitals providing cancer care for 7 of the 18 oncology surgery measures, including mortality, sepsis, acute renal failure, pulmonary failure, and failure to rescue.

“Although PPS-exempt cancer centers may serve an important purpose by advancing the science and quality of cancer care, limited information is available on the selection of PPS-exempt cancer centers, their reimbursement, and how these centers compare with other hospitals with regard to quality of care,” Dr. Bilimoria and colleagues wrote.

“Our findings suggest the need for additional transparency, periodic reviews of the program by CMS, and consideration of whether the classification of PPS exemption should continue. Moreover, the requirement to publicly report cancer care–quality metrics should be uniformly applied across all types of hospitals, not just PPS-exempt cancer centers,” they concluded.

Dr. Bilimoria reported receiving support from the National Institutes of Health; Agency for Healthcare Research and Quality; American Board of Surgery; American College of Surgeons; and the Accreditation Council for Graduate Medical Education, Health Care. The study was supported by the Northwestern Institute for Comparative Effectiveness Research in Oncology of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

SOURCE: Bilimoria KY et al. JAMA Intern Med. 2019 June 17. doi: 10.1001/jamainternmed.2019.0914.

It’s time to revisit legislation that exempts certain U.S. specialized cancer centers from the Medicare Prospective Payment System and from fully reporting measures of care and outcomes to the Centers for Medicare & Medicaid Services, a retrospective cohort study suggests.

The Prospective Payment System (PPS) exemption dates back to 1983 and allows exempted centers to be reimbursed on a reasonable cost basis rather than on a diagnosis-related group basis. Unlike centers that are a part of PPS, exempted centers are not required to report all process-of-care, outcome, and patient experience measures to CMS through its pay-for-performance programs.

In the new study, investigators working under senior author Karl Y. Bilimoria, MD, MS, director of the Surgical Outcomes and Quality Improvement Center and John B. Murphy Professor of Surgery at Northwestern University, Chicago, compared a variety of measures across hospital types. Data came from the American Hospital Association Annual Survey, U.S. News Best Hospitals rankings, and a sample of Medicare beneficiaries who underwent nine cancer operations.

Analyses were based on 15 hospitals affiliated with PPS-exempt cancer centers, 54 hospitals affiliated with National Cancer Institute–designated cancer centers, and 3,578 other U.S. hospitals providing cancer care. The results reported in JAMA Internal Medicine showed that hospitals affiliated with PPS-exempt cancer centers and hospitals affiliated with NCI cancer centers were similar on characteristics other than bed size and overall volume, which were larger for the latter, and on basic cancer-related services such as full-field digital mammography, genetic testing/counseling, chemotherapy, image-guided radiation, and hospice/palliative services.

U.S. News reputation scores averaged 17.5 for the PPS-exempt cancer center hospitals versus just 2.6 for the NCI cancer center hospitals (P less than .001). However, the two types of centers were statistically indistinguishable on oncology patient volume, patient safety ratings, comorbidity burden, nurse staffing, and U.S. News survival scores.

When it came to cancer operations, hospitals affiliated with PPS-exempt cancer centers and with NCI cancer centers had essentially the same adjusted postoperative outcomes for 15 of 18 measures, including mortality, readmission, and surgical site infections. Patients treated at the latter more often developed postoperative sepsis (3.1% vs. 1.7%; P = .002), acute renal failure (6.2% vs. 3.9%; P = .01), and urinary tract infection (6.4% vs. 4.0%; P = .002).

PPS-exempt cancer center hospitals had better outcomes than the group of other U.S. hospitals providing cancer care for 7 of the 18 oncology surgery measures, including mortality, sepsis, acute renal failure, pulmonary failure, and failure to rescue.

“Although PPS-exempt cancer centers may serve an important purpose by advancing the science and quality of cancer care, limited information is available on the selection of PPS-exempt cancer centers, their reimbursement, and how these centers compare with other hospitals with regard to quality of care,” Dr. Bilimoria and colleagues wrote.

“Our findings suggest the need for additional transparency, periodic reviews of the program by CMS, and consideration of whether the classification of PPS exemption should continue. Moreover, the requirement to publicly report cancer care–quality metrics should be uniformly applied across all types of hospitals, not just PPS-exempt cancer centers,” they concluded.

Dr. Bilimoria reported receiving support from the National Institutes of Health; Agency for Healthcare Research and Quality; American Board of Surgery; American College of Surgeons; and the Accreditation Council for Graduate Medical Education, Health Care. The study was supported by the Northwestern Institute for Comparative Effectiveness Research in Oncology of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

SOURCE: Bilimoria KY et al. JAMA Intern Med. 2019 June 17. doi: 10.1001/jamainternmed.2019.0914.

It’s time to revisit legislation that exempts certain U.S. specialized cancer centers from the Medicare Prospective Payment System and from fully reporting measures of care and outcomes to the Centers for Medicare & Medicaid Services, a retrospective cohort study suggests.

The Prospective Payment System (PPS) exemption dates back to 1983 and allows exempted centers to be reimbursed on a reasonable cost basis rather than on a diagnosis-related group basis. Unlike centers that are a part of PPS, exempted centers are not required to report all process-of-care, outcome, and patient experience measures to CMS through its pay-for-performance programs.

In the new study, investigators working under senior author Karl Y. Bilimoria, MD, MS, director of the Surgical Outcomes and Quality Improvement Center and John B. Murphy Professor of Surgery at Northwestern University, Chicago, compared a variety of measures across hospital types. Data came from the American Hospital Association Annual Survey, U.S. News Best Hospitals rankings, and a sample of Medicare beneficiaries who underwent nine cancer operations.

Analyses were based on 15 hospitals affiliated with PPS-exempt cancer centers, 54 hospitals affiliated with National Cancer Institute–designated cancer centers, and 3,578 other U.S. hospitals providing cancer care. The results reported in JAMA Internal Medicine showed that hospitals affiliated with PPS-exempt cancer centers and hospitals affiliated with NCI cancer centers were similar on characteristics other than bed size and overall volume, which were larger for the latter, and on basic cancer-related services such as full-field digital mammography, genetic testing/counseling, chemotherapy, image-guided radiation, and hospice/palliative services.

U.S. News reputation scores averaged 17.5 for the PPS-exempt cancer center hospitals versus just 2.6 for the NCI cancer center hospitals (P less than .001). However, the two types of centers were statistically indistinguishable on oncology patient volume, patient safety ratings, comorbidity burden, nurse staffing, and U.S. News survival scores.

When it came to cancer operations, hospitals affiliated with PPS-exempt cancer centers and with NCI cancer centers had essentially the same adjusted postoperative outcomes for 15 of 18 measures, including mortality, readmission, and surgical site infections. Patients treated at the latter more often developed postoperative sepsis (3.1% vs. 1.7%; P = .002), acute renal failure (6.2% vs. 3.9%; P = .01), and urinary tract infection (6.4% vs. 4.0%; P = .002).

PPS-exempt cancer center hospitals had better outcomes than the group of other U.S. hospitals providing cancer care for 7 of the 18 oncology surgery measures, including mortality, sepsis, acute renal failure, pulmonary failure, and failure to rescue.

“Although PPS-exempt cancer centers may serve an important purpose by advancing the science and quality of cancer care, limited information is available on the selection of PPS-exempt cancer centers, their reimbursement, and how these centers compare with other hospitals with regard to quality of care,” Dr. Bilimoria and colleagues wrote.

“Our findings suggest the need for additional transparency, periodic reviews of the program by CMS, and consideration of whether the classification of PPS exemption should continue. Moreover, the requirement to publicly report cancer care–quality metrics should be uniformly applied across all types of hospitals, not just PPS-exempt cancer centers,” they concluded.

Dr. Bilimoria reported receiving support from the National Institutes of Health; Agency for Healthcare Research and Quality; American Board of Surgery; American College of Surgeons; and the Accreditation Council for Graduate Medical Education, Health Care. The study was supported by the Northwestern Institute for Comparative Effectiveness Research in Oncology of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

SOURCE: Bilimoria KY et al. JAMA Intern Med. 2019 June 17. doi: 10.1001/jamainternmed.2019.0914.

Many cardiac catheterization and electrophysiology laboratory directors receive significant payments from industry that could create conflicts of interest, according to a new study of payments to lab directors at top hospitals.

adventtr/iStock/Getty Images Plus

“With continued concerns about rising health care costs, it is important to ensure that physician decisions regarding choice of devices and other pharmaceutical therapies be driven by clinical and cost effectiveness, not industry influence,” Amarnath Annapureddy, MD, of the Yale School of Medicine, New Haven, Conn. and coauthors wrote in their study published in JAMA Internal Medicine.

Dr. Annapureddy and fellow researchers analyzed Open Payments Program data from 2017 to determine payments made to cardiac catheterization and electrophysiology laboratory directors the top 100 hospitals based on US News and World Report’s ranking. They compared those payments to payments made to local interventional cardiologists and electrophysiologists, along with payments to interventional cardiologists and electrophysiologists from across the country.

In 2017, the directors of the top cardiac catheterization and electrophysiology labs received $1,416,232 and $2,307,504 from industry, respectively. The median payments to cardiac catheterization lab directors were significantly higher ($3,203 [$388-$14,156]), compared with interventional cardiologists ($1,064 [$206-$4,104]). The results were similar comparing electrophysiology lab directors with electrophysiology physicians practicing in the same zip codes ($10,521 [$1,159-$35,076] versus $2,900 [$549-$13,101]).

Overall, nearly one-third of cardiac catheterization lab directors and nearly half of electrophysiology lab directors received payments of $10,000 or more, an amount the National Academy of Medicine noted as constituting “a significant conflict of interest.”

The coauthors acknowledged their study’s limitations, including the possibility that they misclassified some lab directors and the fact that Open Payments Program’s data may have been inaccurate. However, they also anticipated that “inaccuracies would not vary between laboratory directors and other clinicians.”

Dr. Nihar R. Desai reported receiving funding from the Centers for Medicare & Medicaid Services, financial support from Johnson & Johnson, and research support from the American College of Cardiology Foundation. Dr. Jeptha P. Curtis reported receiving salary support from the American College of Cardiology, funding from the Centers for Medicare & Medicaid Services, and equity interest in Medtronic. No other authors reported any relevant financial disclosures. No funding for the study was reported.

SOURCE: Annapureddy A et al. JAMA Intern Med. 2019 Jun 17. doi:10.1001/jamainternmed.2018.8775.

Many cardiac catheterization and electrophysiology laboratory directors receive significant payments from industry that could create conflicts of interest, according to a new study of payments to lab directors at top hospitals.

adventtr/iStock/Getty Images Plus

“With continued concerns about rising health care costs, it is important to ensure that physician decisions regarding choice of devices and other pharmaceutical therapies be driven by clinical and cost effectiveness, not industry influence,” Amarnath Annapureddy, MD, of the Yale School of Medicine, New Haven, Conn. and coauthors wrote in their study published in JAMA Internal Medicine.

Dr. Annapureddy and fellow researchers analyzed Open Payments Program data from 2017 to determine payments made to cardiac catheterization and electrophysiology laboratory directors the top 100 hospitals based on US News and World Report’s ranking. They compared those payments to payments made to local interventional cardiologists and electrophysiologists, along with payments to interventional cardiologists and electrophysiologists from across the country.

In 2017, the directors of the top cardiac catheterization and electrophysiology labs received $1,416,232 and $2,307,504 from industry, respectively. The median payments to cardiac catheterization lab directors were significantly higher ($3,203 [$388-$14,156]), compared with interventional cardiologists ($1,064 [$206-$4,104]). The results were similar comparing electrophysiology lab directors with electrophysiology physicians practicing in the same zip codes ($10,521 [$1,159-$35,076] versus $2,900 [$549-$13,101]).

Overall, nearly one-third of cardiac catheterization lab directors and nearly half of electrophysiology lab directors received payments of $10,000 or more, an amount the National Academy of Medicine noted as constituting “a significant conflict of interest.”

The coauthors acknowledged their study’s limitations, including the possibility that they misclassified some lab directors and the fact that Open Payments Program’s data may have been inaccurate. However, they also anticipated that “inaccuracies would not vary between laboratory directors and other clinicians.”

Dr. Nihar R. Desai reported receiving funding from the Centers for Medicare & Medicaid Services, financial support from Johnson & Johnson, and research support from the American College of Cardiology Foundation. Dr. Jeptha P. Curtis reported receiving salary support from the American College of Cardiology, funding from the Centers for Medicare & Medicaid Services, and equity interest in Medtronic. No other authors reported any relevant financial disclosures. No funding for the study was reported.

SOURCE: Annapureddy A et al. JAMA Intern Med. 2019 Jun 17. doi:10.1001/jamainternmed.2018.8775.

Many cardiac catheterization and electrophysiology laboratory directors receive significant payments from industry that could create conflicts of interest, according to a new study of payments to lab directors at top hospitals.

adventtr/iStock/Getty Images Plus

“With continued concerns about rising health care costs, it is important to ensure that physician decisions regarding choice of devices and other pharmaceutical therapies be driven by clinical and cost effectiveness, not industry influence,” Amarnath Annapureddy, MD, of the Yale School of Medicine, New Haven, Conn. and coauthors wrote in their study published in JAMA Internal Medicine.

Dr. Annapureddy and fellow researchers analyzed Open Payments Program data from 2017 to determine payments made to cardiac catheterization and electrophysiology laboratory directors the top 100 hospitals based on US News and World Report’s ranking. They compared those payments to payments made to local interventional cardiologists and electrophysiologists, along with payments to interventional cardiologists and electrophysiologists from across the country.

In 2017, the directors of the top cardiac catheterization and electrophysiology labs received $1,416,232 and $2,307,504 from industry, respectively. The median payments to cardiac catheterization lab directors were significantly higher ($3,203 [$388-$14,156]), compared with interventional cardiologists ($1,064 [$206-$4,104]). The results were similar comparing electrophysiology lab directors with electrophysiology physicians practicing in the same zip codes ($10,521 [$1,159-$35,076] versus $2,900 [$549-$13,101]).

Overall, nearly one-third of cardiac catheterization lab directors and nearly half of electrophysiology lab directors received payments of $10,000 or more, an amount the National Academy of Medicine noted as constituting “a significant conflict of interest.”

The coauthors acknowledged their study’s limitations, including the possibility that they misclassified some lab directors and the fact that Open Payments Program’s data may have been inaccurate. However, they also anticipated that “inaccuracies would not vary between laboratory directors and other clinicians.”

Dr. Nihar R. Desai reported receiving funding from the Centers for Medicare & Medicaid Services, financial support from Johnson & Johnson, and research support from the American College of Cardiology Foundation. Dr. Jeptha P. Curtis reported receiving salary support from the American College of Cardiology, funding from the Centers for Medicare & Medicaid Services, and equity interest in Medtronic. No other authors reported any relevant financial disclosures. No funding for the study was reported.

SOURCE: Annapureddy A et al. JAMA Intern Med. 2019 Jun 17. doi:10.1001/jamainternmed.2018.8775.

SAN ANTONIO – Lemborexant was effective in treating both sleep onset and maintenance variables in male and female subjects with insomnia, and it was well tolerated by both sexes, results from a pooled analysis showed.

Doug Brunk/MDedge News

A dual orexin receptor antagonist developed by Eisai, lemborexant is being studied as a treatment for insomnia disorder and irregular sleep-wake rhythm disorder. Early in 2019, the Food and Drug Administration accepted for review the New Drug Application for lemborexant for the treatment of insomnia. A target Prescription Drug User Fee Act date is set for Dec. 27, 2019.

“We evaluated early on whether exposure to lemborexant was going to be different between men and women,” lead study author Margaret Moline, PhD, said during an interview at the annual meeting of the Associated Professional Sleep Societies. “With some drugs, like zolpidem and other so-called Z drugs, because exposure is different, clinical studies could involve different dosing for different sexes. Because we knew the exposure to lemborexant wasn’t different between the sexes, we expected to see similar results in both sexes. That was the case.”

Dr. Moline, executive director of the Neurology Business Group and International Project Team Lead for the lemborexant clinical development program at Eisai, and colleagues presented pooled analyses of subject-reported sleep onset latency (sSOL) and subject-reported wake after sleep onset (sWASO) from lemborexant phase 3 studies, SUNRISE-1 and SUNRISE-2. SUNRISE-1 was a 1-month, double-blind, placebo- and active-controlled, parallel-group study in 1,006 subjects. Participants were females aged 55 years and older and males aged 65 years and older with a primary complaint of sleep maintenance difficulties and an Insomnia Severity Index (ISI) total score of 13 or higher. SUNRISE-2 was a placebo-controlled, 6-month, active treatment, double-blind, parallel-group study in 949 subjects with insomnia disorder. Participants were females and males aged 18 years and older with a primary complaint of sleep onset and/or sleep maintenance difficulties and an ISI total score of 15 or higher. Both analyses included subjects randomized to placebo, lemborexant 5 mg, or lemborexant 10 mg. Each study included a single-blind placebo run-in period prior to randomization.

The pooled analysis of 1,693 subjects included 402 (23.7%) men and 1,291 (76.3%) women. Results on sSOL and sWASO were consistent with the significant results on sleep diary in the individual studies. In both sexes, sSOL for lemborexant 5 mg and lemborexant 10 mg was significantly reduced versus that for placebo during the first 7 days and end of month 1 (P less than .05 for all comparisons). In women, the researchers observed significantly greater reductions in sWASO placebo for both lemborexant doses versus that with placebo (first 7 days and end of month 1; P less than .0001 for all comparisons). In males, sWASO decreased significantly, compared with placebo, for the first 7 days (lemborexant 5 mg and lemborexant 10 mg; P equal to or less than .0001) and at end of month 1 (lemborexant 10 mg only; P = .0032). For placebo, lemborexant 5 mg, and lemborexant 10 mg, the overall incidence of treatment-emergent adverse events was similar across sexes. Incidence of treatment-emergent serious adverse events was low for both sex subgroups; most events occurred in one subject each. Treatment-emergent adverse events leading to study drug withdrawal or interruption were few and similar across sexes for all treatments and was highest in males receiving lemborexant 10 mg. The most frequent treatment-emergent adverse events reported in males were somnolence, fatigue, and headache, while the most common in females were somnolence, headache, and urinary tract infection. About 3% of females (no males) reported a urinary tract infection; the incidence in females was similar across treatment groups.

“Overall, sleep diary outcomes in males and females were consistent with the significant results observed in the total populations of the individual studies,” Dr. Moline concluded. “A dose adjustment based on sex is not anticipated.”

The research was supported by Eisai. Dr. Moline is an employee of the company.

dbrunk@mdedge.com

SOURCE: Moline M et al. Sleep 2019, Abstract 0368.

SAN ANTONIO – Lemborexant was effective in treating both sleep onset and maintenance variables in male and female subjects with insomnia, and it was well tolerated by both sexes, results from a pooled analysis showed.

Doug Brunk/MDedge News

A dual orexin receptor antagonist developed by Eisai, lemborexant is being studied as a treatment for insomnia disorder and irregular sleep-wake rhythm disorder. Early in 2019, the Food and Drug Administration accepted for review the New Drug Application for lemborexant for the treatment of insomnia. A target Prescription Drug User Fee Act date is set for Dec. 27, 2019.

“We evaluated early on whether exposure to lemborexant was going to be different between men and women,” lead study author Margaret Moline, PhD, said during an interview at the annual meeting of the Associated Professional Sleep Societies. “With some drugs, like zolpidem and other so-called Z drugs, because exposure is different, clinical studies could involve different dosing for different sexes. Because we knew the exposure to lemborexant wasn’t different between the sexes, we expected to see similar results in both sexes. That was the case.”

Dr. Moline, executive director of the Neurology Business Group and International Project Team Lead for the lemborexant clinical development program at Eisai, and colleagues presented pooled analyses of subject-reported sleep onset latency (sSOL) and subject-reported wake after sleep onset (sWASO) from lemborexant phase 3 studies, SUNRISE-1 and SUNRISE-2. SUNRISE-1 was a 1-month, double-blind, placebo- and active-controlled, parallel-group study in 1,006 subjects. Participants were females aged 55 years and older and males aged 65 years and older with a primary complaint of sleep maintenance difficulties and an Insomnia Severity Index (ISI) total score of 13 or higher. SUNRISE-2 was a placebo-controlled, 6-month, active treatment, double-blind, parallel-group study in 949 subjects with insomnia disorder. Participants were females and males aged 18 years and older with a primary complaint of sleep onset and/or sleep maintenance difficulties and an ISI total score of 15 or higher. Both analyses included subjects randomized to placebo, lemborexant 5 mg, or lemborexant 10 mg. Each study included a single-blind placebo run-in period prior to randomization.

The pooled analysis of 1,693 subjects included 402 (23.7%) men and 1,291 (76.3%) women. Results on sSOL and sWASO were consistent with the significant results on sleep diary in the individual studies. In both sexes, sSOL for lemborexant 5 mg and lemborexant 10 mg was significantly reduced versus that for placebo during the first 7 days and end of month 1 (P less than .05 for all comparisons). In women, the researchers observed significantly greater reductions in sWASO placebo for both lemborexant doses versus that with placebo (first 7 days and end of month 1; P less than .0001 for all comparisons). In males, sWASO decreased significantly, compared with placebo, for the first 7 days (lemborexant 5 mg and lemborexant 10 mg; P equal to or less than .0001) and at end of month 1 (lemborexant 10 mg only; P = .0032). For placebo, lemborexant 5 mg, and lemborexant 10 mg, the overall incidence of treatment-emergent adverse events was similar across sexes. Incidence of treatment-emergent serious adverse events was low for both sex subgroups; most events occurred in one subject each. Treatment-emergent adverse events leading to study drug withdrawal or interruption were few and similar across sexes for all treatments and was highest in males receiving lemborexant 10 mg. The most frequent treatment-emergent adverse events reported in males were somnolence, fatigue, and headache, while the most common in females were somnolence, headache, and urinary tract infection. About 3% of females (no males) reported a urinary tract infection; the incidence in females was similar across treatment groups.

“Overall, sleep diary outcomes in males and females were consistent with the significant results observed in the total populations of the individual studies,” Dr. Moline concluded. “A dose adjustment based on sex is not anticipated.”

The research was supported by Eisai. Dr. Moline is an employee of the company.

dbrunk@mdedge.com

SOURCE: Moline M et al. Sleep 2019, Abstract 0368.

SAN ANTONIO – Lemborexant was effective in treating both sleep onset and maintenance variables in male and female subjects with insomnia, and it was well tolerated by both sexes, results from a pooled analysis showed.

Doug Brunk/MDedge News

A dual orexin receptor antagonist developed by Eisai, lemborexant is being studied as a treatment for insomnia disorder and irregular sleep-wake rhythm disorder. Early in 2019, the Food and Drug Administration accepted for review the New Drug Application for lemborexant for the treatment of insomnia. A target Prescription Drug User Fee Act date is set for Dec. 27, 2019.

“We evaluated early on whether exposure to lemborexant was going to be different between men and women,” lead study author Margaret Moline, PhD, said during an interview at the annual meeting of the Associated Professional Sleep Societies. “With some drugs, like zolpidem and other so-called Z drugs, because exposure is different, clinical studies could involve different dosing for different sexes. Because we knew the exposure to lemborexant wasn’t different between the sexes, we expected to see similar results in both sexes. That was the case.”

Dr. Moline, executive director of the Neurology Business Group and International Project Team Lead for the lemborexant clinical development program at Eisai, and colleagues presented pooled analyses of subject-reported sleep onset latency (sSOL) and subject-reported wake after sleep onset (sWASO) from lemborexant phase 3 studies, SUNRISE-1 and SUNRISE-2. SUNRISE-1 was a 1-month, double-blind, placebo- and active-controlled, parallel-group study in 1,006 subjects. Participants were females aged 55 years and older and males aged 65 years and older with a primary complaint of sleep maintenance difficulties and an Insomnia Severity Index (ISI) total score of 13 or higher. SUNRISE-2 was a placebo-controlled, 6-month, active treatment, double-blind, parallel-group study in 949 subjects with insomnia disorder. Participants were females and males aged 18 years and older with a primary complaint of sleep onset and/or sleep maintenance difficulties and an ISI total score of 15 or higher. Both analyses included subjects randomized to placebo, lemborexant 5 mg, or lemborexant 10 mg. Each study included a single-blind placebo run-in period prior to randomization.

The pooled analysis of 1,693 subjects included 402 (23.7%) men and 1,291 (76.3%) women. Results on sSOL and sWASO were consistent with the significant results on sleep diary in the individual studies. In both sexes, sSOL for lemborexant 5 mg and lemborexant 10 mg was significantly reduced versus that for placebo during the first 7 days and end of month 1 (P less than .05 for all comparisons). In women, the researchers observed significantly greater reductions in sWASO placebo for both lemborexant doses versus that with placebo (first 7 days and end of month 1; P less than .0001 for all comparisons). In males, sWASO decreased significantly, compared with placebo, for the first 7 days (lemborexant 5 mg and lemborexant 10 mg; P equal to or less than .0001) and at end of month 1 (lemborexant 10 mg only; P = .0032). For placebo, lemborexant 5 mg, and lemborexant 10 mg, the overall incidence of treatment-emergent adverse events was similar across sexes. Incidence of treatment-emergent serious adverse events was low for both sex subgroups; most events occurred in one subject each. Treatment-emergent adverse events leading to study drug withdrawal or interruption were few and similar across sexes for all treatments and was highest in males receiving lemborexant 10 mg. The most frequent treatment-emergent adverse events reported in males were somnolence, fatigue, and headache, while the most common in females were somnolence, headache, and urinary tract infection. About 3% of females (no males) reported a urinary tract infection; the incidence in females was similar across treatment groups.

“Overall, sleep diary outcomes in males and females were consistent with the significant results observed in the total populations of the individual studies,” Dr. Moline concluded. “A dose adjustment based on sex is not anticipated.”

The research was supported by Eisai. Dr. Moline is an employee of the company.

dbrunk@mdedge.com

SOURCE: Moline M et al. Sleep 2019, Abstract 0368.