The Hospital Readmissions Reduction Program and COPD: More Answers, More Questions

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Many provisions of the Affordable Care Act (ACA) have served to support the hospitalized patient. The expansion of Medicaid and the creation of state and federal insurance exchanges for the individual insurance market both significantly lessened the financial burden of hospital care for millions of Americans. Other aspects have proven more controversial, as many of the ACA’s health policy interventions linked to cost and quality in new ways, implementing untested concepts derived from healthcare services research on a national scale.

The Hospital Readmissions Reduction Program (HRRP) was no exception. Based on early research examining readmissions,1 the ACA included a mandate for the Centers for Medicare and Medicaid Services (CMS) to establish the HRRP. Beginning in Fiscal Year 2013, the HRRP reduced payments for excessive, 30-day, risk-standardized readmissions covering six conditions and procedures. As the third leading cause of 30-day readmissions, chronic obstructive pulmonary disease (COPD) was included in the list of designated HRRP conditions.

This inclusion of COPD in HRRP was not without controversy; analysis of Medicare data from before the ACA’s implementation demonstrated that only half of all readmissions for acute exacerbations of COPD were respiratory-related and only a third were directly related to COPD.2 Unsurprisingly, the high proportion of readmissions due to non-COPD-related causes is considered to be one of the leading factors for the failure of COPD readmission reduction programs to find significant reductions in readmissions.3 In this month’s issue of the Journal of Hospital Medicine, Buhr and colleagues explore differential readmission diagnoses following acute exacerbations of COPD using a validated, national, all-payer database.4

Like many analyses of payer datasets, this study has several limitations. First, although a large area of the US was included, the data did not include all US states. Further, as the study used multiple cross-sectional data using pooling techniques, it was not truly a longitudinal study. It was additionally limited to 10 months out of the calendar year, missing December and January, which have a high seasonal prevalence of viral respiratory illness. Finally, due to the nature of the data, COPD diagnoses were identified through administrative data known to be highly unreliable for fully capturing admissions for acute exacerbation of COPD.

Despite these limitations, the analysis by Buhr and colleagues provides additional value. They found an overall readmission rate of 17%, with just under half (7.69%) due to recurrent COPD. Patients with COPD-related readmissions were younger, had a higher proportion with Medicaid as the payer, were more frequently discharged home without services, had a shorter length of stay, and had fewer comorbidities.

Most critically, Buhr and colleagues—with a multipayer database—confirmed what researchers found in uni-payer5 and site-specific6 datasets: over half of readmissions are due to diagnoses other than COPD or respiratory-related causes. Patients readmitted due to other, unrelated diagnoses had a higher mean Elixhauser Comorbidity Index score along with higher rates of congestive heart failure and renal failure. To the practicing hospitalist, this finding supports what our internal clinical voice tells us: sicker patients are readmitted more often and more frequently with conditions unrelated to their index admission diagnosis.

The reaffirmation of the finding that the majority of readmissions are due to nonrespiratory-related causes suggests that perhaps we have a different problem than physicians and policymakers originally thought when adding COPD to the HRRP. Many COPD patients suffer from a polychronic disease, requiring a more holistic approach rather than a traditional, disease-driven, siloed approach focused solely on improving COPD-related care. It may also be true that for other subpopulations of patients with COPD, additional in-hospital and transition of care interventions are required to address patients’ multimorbidity and social determinants of health.

As physicians on the front lines of the readmitted patient, hospitalists are uniquely situated to see the challenges of populations with increasing disease complexity and disease combinations.7 The HRRP policy remains controversial. This is due in large part to recent work suggesting that while the HRRP may have helped reduce readmissions, its implementation may have driven the unintended consequence of increased mortality.8 Thus, our profession faces an existential challenge to traditional care delivery models targeting diseases. What has not been well parsed by the hospital industry or policymakers is what to do about it.

Readmission of the multimorbid patient, coupled with the challenges of the HRRP, focuses our attention on the need to transition care delivery to a model that is better suited to our patients’ needs: mass-customized, mass-produced service delivery. As physicians, we know that care delivery must be oriented around patients who have many diseases and unique life circumstances. It is our profession’s greatest challenge to collaborate with researchers and administrators to help do this with scale.

 

 

Acknowledgments

The authors thank Mary Akel for her assistance with manuscript submission.

References

1. Jencks SF, Williams MV, Coleman EA. Rehospitalization among patients in the Medicare Fee-for-Service Program. N Engl J Med. 2009;360(14):1418-1428. https://doi.org/10.1056/NEJMsa0803563.
2. Shah T, Churpek MM, Coca Perraillon M, Konetzka RT. Understanding why patients with COPD get readmitted: a large national study to delineate the Medicare population for the readmissions penalty expansion. Chest. 2015;147(5):1219-1226. https://doi.org/10.1378/chest.14-2181.
3. Press VG, Au DH, Bourbeau J, Dransfield MT, Gershon AS, Krishnan JA, et al. An American thoracic society workshop report: reducing COPD hospital readmissions. Ann Am Thorac Soc. 2019;16(2):161-170. https://doi.org/10.1513/AnnalsATS.201811-755WS.
4. Buhr R, Jackson N, Kominski G, Ong M, Mangione C. Factors associated with differential readmission diagnoses following acute exacerbations of COPD. J Hosp Med. 2020;15(4):252-253. https://doi.org/10.12788/jhm.3367.
5. Sharif R, Parekh TM, Pierson KS, Kuo Y-F, Sharma G. Predictors of early readmission among patients 40 to 64 years of age hospitalized for chronic obstructive pulmonary disease. Annals ATS. 2014;11(5):685-694. https://doi.org/10.1513/AnnalsATS.201310-358OC.
6. Glaser JB, El-Haddad H. Exploring novel Medicare readmission risk variables in chronic obstructive pulmonary disease patients at high risk of readmission within 30 days of hospital discharge. Ann Am Thorac Soc. 2015;12(9):1288-1293. https://doi.org/10.1513/AnnalsATS.201504-228OC.
7. Sorace J, Wong HH, Worrall C, Kelman J, Saneinejad S, MaCurdy T. The complexity of disease combinations in the Medicare population. Popul Health Manag. 2011;14(4):161-166. https://doi.org/10.1089/pop.2010.0044
8. Wadhera RK, Joynt Maddox KE, Wasfy JH, Haneuse S, Shen C, Yeh RW. Association of the hospital readmissions reduction program with mortality among medicare beneficiaries hospitalized for heart failure, acute myocardial infarction, and pneumonia. JAMA. 2018;320(24):2542-2552. https://doi.org/10.1001/jama.2018.19232.

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1Department of Medicine, University of Chicago Medicine, Chicago, Illinois; 2Department of Medicine, MedStar Georgetown University Hospital, Washington, DC; 3University of North Carolina Kenan-Flagler Business School, Chapel Hill, North Carolina.

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Dr. Press reports consulting for Vizient outside the submitted work. Dr. Miller reports consulting for the Federal Trade Commission and serving as a member of the CMS Medicare Evidence Development Coverage Advisory Committee.

Funding

Dr. Press reports funding from an NIH NHLBI R03.

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1Department of Medicine, University of Chicago Medicine, Chicago, Illinois; 2Department of Medicine, MedStar Georgetown University Hospital, Washington, DC; 3University of North Carolina Kenan-Flagler Business School, Chapel Hill, North Carolina.

Disclosures

Dr. Press reports consulting for Vizient outside the submitted work. Dr. Miller reports consulting for the Federal Trade Commission and serving as a member of the CMS Medicare Evidence Development Coverage Advisory Committee.

Funding

Dr. Press reports funding from an NIH NHLBI R03.

Author and Disclosure Information

1Department of Medicine, University of Chicago Medicine, Chicago, Illinois; 2Department of Medicine, MedStar Georgetown University Hospital, Washington, DC; 3University of North Carolina Kenan-Flagler Business School, Chapel Hill, North Carolina.

Disclosures

Dr. Press reports consulting for Vizient outside the submitted work. Dr. Miller reports consulting for the Federal Trade Commission and serving as a member of the CMS Medicare Evidence Development Coverage Advisory Committee.

Funding

Dr. Press reports funding from an NIH NHLBI R03.

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Related Articles

Many provisions of the Affordable Care Act (ACA) have served to support the hospitalized patient. The expansion of Medicaid and the creation of state and federal insurance exchanges for the individual insurance market both significantly lessened the financial burden of hospital care for millions of Americans. Other aspects have proven more controversial, as many of the ACA’s health policy interventions linked to cost and quality in new ways, implementing untested concepts derived from healthcare services research on a national scale.

The Hospital Readmissions Reduction Program (HRRP) was no exception. Based on early research examining readmissions,1 the ACA included a mandate for the Centers for Medicare and Medicaid Services (CMS) to establish the HRRP. Beginning in Fiscal Year 2013, the HRRP reduced payments for excessive, 30-day, risk-standardized readmissions covering six conditions and procedures. As the third leading cause of 30-day readmissions, chronic obstructive pulmonary disease (COPD) was included in the list of designated HRRP conditions.

This inclusion of COPD in HRRP was not without controversy; analysis of Medicare data from before the ACA’s implementation demonstrated that only half of all readmissions for acute exacerbations of COPD were respiratory-related and only a third were directly related to COPD.2 Unsurprisingly, the high proportion of readmissions due to non-COPD-related causes is considered to be one of the leading factors for the failure of COPD readmission reduction programs to find significant reductions in readmissions.3 In this month’s issue of the Journal of Hospital Medicine, Buhr and colleagues explore differential readmission diagnoses following acute exacerbations of COPD using a validated, national, all-payer database.4

Like many analyses of payer datasets, this study has several limitations. First, although a large area of the US was included, the data did not include all US states. Further, as the study used multiple cross-sectional data using pooling techniques, it was not truly a longitudinal study. It was additionally limited to 10 months out of the calendar year, missing December and January, which have a high seasonal prevalence of viral respiratory illness. Finally, due to the nature of the data, COPD diagnoses were identified through administrative data known to be highly unreliable for fully capturing admissions for acute exacerbation of COPD.

Despite these limitations, the analysis by Buhr and colleagues provides additional value. They found an overall readmission rate of 17%, with just under half (7.69%) due to recurrent COPD. Patients with COPD-related readmissions were younger, had a higher proportion with Medicaid as the payer, were more frequently discharged home without services, had a shorter length of stay, and had fewer comorbidities.

Most critically, Buhr and colleagues—with a multipayer database—confirmed what researchers found in uni-payer5 and site-specific6 datasets: over half of readmissions are due to diagnoses other than COPD or respiratory-related causes. Patients readmitted due to other, unrelated diagnoses had a higher mean Elixhauser Comorbidity Index score along with higher rates of congestive heart failure and renal failure. To the practicing hospitalist, this finding supports what our internal clinical voice tells us: sicker patients are readmitted more often and more frequently with conditions unrelated to their index admission diagnosis.

The reaffirmation of the finding that the majority of readmissions are due to nonrespiratory-related causes suggests that perhaps we have a different problem than physicians and policymakers originally thought when adding COPD to the HRRP. Many COPD patients suffer from a polychronic disease, requiring a more holistic approach rather than a traditional, disease-driven, siloed approach focused solely on improving COPD-related care. It may also be true that for other subpopulations of patients with COPD, additional in-hospital and transition of care interventions are required to address patients’ multimorbidity and social determinants of health.

As physicians on the front lines of the readmitted patient, hospitalists are uniquely situated to see the challenges of populations with increasing disease complexity and disease combinations.7 The HRRP policy remains controversial. This is due in large part to recent work suggesting that while the HRRP may have helped reduce readmissions, its implementation may have driven the unintended consequence of increased mortality.8 Thus, our profession faces an existential challenge to traditional care delivery models targeting diseases. What has not been well parsed by the hospital industry or policymakers is what to do about it.

Readmission of the multimorbid patient, coupled with the challenges of the HRRP, focuses our attention on the need to transition care delivery to a model that is better suited to our patients’ needs: mass-customized, mass-produced service delivery. As physicians, we know that care delivery must be oriented around patients who have many diseases and unique life circumstances. It is our profession’s greatest challenge to collaborate with researchers and administrators to help do this with scale.

 

 

Acknowledgments

The authors thank Mary Akel for her assistance with manuscript submission.

Many provisions of the Affordable Care Act (ACA) have served to support the hospitalized patient. The expansion of Medicaid and the creation of state and federal insurance exchanges for the individual insurance market both significantly lessened the financial burden of hospital care for millions of Americans. Other aspects have proven more controversial, as many of the ACA’s health policy interventions linked to cost and quality in new ways, implementing untested concepts derived from healthcare services research on a national scale.

The Hospital Readmissions Reduction Program (HRRP) was no exception. Based on early research examining readmissions,1 the ACA included a mandate for the Centers for Medicare and Medicaid Services (CMS) to establish the HRRP. Beginning in Fiscal Year 2013, the HRRP reduced payments for excessive, 30-day, risk-standardized readmissions covering six conditions and procedures. As the third leading cause of 30-day readmissions, chronic obstructive pulmonary disease (COPD) was included in the list of designated HRRP conditions.

This inclusion of COPD in HRRP was not without controversy; analysis of Medicare data from before the ACA’s implementation demonstrated that only half of all readmissions for acute exacerbations of COPD were respiratory-related and only a third were directly related to COPD.2 Unsurprisingly, the high proportion of readmissions due to non-COPD-related causes is considered to be one of the leading factors for the failure of COPD readmission reduction programs to find significant reductions in readmissions.3 In this month’s issue of the Journal of Hospital Medicine, Buhr and colleagues explore differential readmission diagnoses following acute exacerbations of COPD using a validated, national, all-payer database.4

Like many analyses of payer datasets, this study has several limitations. First, although a large area of the US was included, the data did not include all US states. Further, as the study used multiple cross-sectional data using pooling techniques, it was not truly a longitudinal study. It was additionally limited to 10 months out of the calendar year, missing December and January, which have a high seasonal prevalence of viral respiratory illness. Finally, due to the nature of the data, COPD diagnoses were identified through administrative data known to be highly unreliable for fully capturing admissions for acute exacerbation of COPD.

Despite these limitations, the analysis by Buhr and colleagues provides additional value. They found an overall readmission rate of 17%, with just under half (7.69%) due to recurrent COPD. Patients with COPD-related readmissions were younger, had a higher proportion with Medicaid as the payer, were more frequently discharged home without services, had a shorter length of stay, and had fewer comorbidities.

Most critically, Buhr and colleagues—with a multipayer database—confirmed what researchers found in uni-payer5 and site-specific6 datasets: over half of readmissions are due to diagnoses other than COPD or respiratory-related causes. Patients readmitted due to other, unrelated diagnoses had a higher mean Elixhauser Comorbidity Index score along with higher rates of congestive heart failure and renal failure. To the practicing hospitalist, this finding supports what our internal clinical voice tells us: sicker patients are readmitted more often and more frequently with conditions unrelated to their index admission diagnosis.

The reaffirmation of the finding that the majority of readmissions are due to nonrespiratory-related causes suggests that perhaps we have a different problem than physicians and policymakers originally thought when adding COPD to the HRRP. Many COPD patients suffer from a polychronic disease, requiring a more holistic approach rather than a traditional, disease-driven, siloed approach focused solely on improving COPD-related care. It may also be true that for other subpopulations of patients with COPD, additional in-hospital and transition of care interventions are required to address patients’ multimorbidity and social determinants of health.

As physicians on the front lines of the readmitted patient, hospitalists are uniquely situated to see the challenges of populations with increasing disease complexity and disease combinations.7 The HRRP policy remains controversial. This is due in large part to recent work suggesting that while the HRRP may have helped reduce readmissions, its implementation may have driven the unintended consequence of increased mortality.8 Thus, our profession faces an existential challenge to traditional care delivery models targeting diseases. What has not been well parsed by the hospital industry or policymakers is what to do about it.

Readmission of the multimorbid patient, coupled with the challenges of the HRRP, focuses our attention on the need to transition care delivery to a model that is better suited to our patients’ needs: mass-customized, mass-produced service delivery. As physicians, we know that care delivery must be oriented around patients who have many diseases and unique life circumstances. It is our profession’s greatest challenge to collaborate with researchers and administrators to help do this with scale.

 

 

Acknowledgments

The authors thank Mary Akel for her assistance with manuscript submission.

References

1. Jencks SF, Williams MV, Coleman EA. Rehospitalization among patients in the Medicare Fee-for-Service Program. N Engl J Med. 2009;360(14):1418-1428. https://doi.org/10.1056/NEJMsa0803563.
2. Shah T, Churpek MM, Coca Perraillon M, Konetzka RT. Understanding why patients with COPD get readmitted: a large national study to delineate the Medicare population for the readmissions penalty expansion. Chest. 2015;147(5):1219-1226. https://doi.org/10.1378/chest.14-2181.
3. Press VG, Au DH, Bourbeau J, Dransfield MT, Gershon AS, Krishnan JA, et al. An American thoracic society workshop report: reducing COPD hospital readmissions. Ann Am Thorac Soc. 2019;16(2):161-170. https://doi.org/10.1513/AnnalsATS.201811-755WS.
4. Buhr R, Jackson N, Kominski G, Ong M, Mangione C. Factors associated with differential readmission diagnoses following acute exacerbations of COPD. J Hosp Med. 2020;15(4):252-253. https://doi.org/10.12788/jhm.3367.
5. Sharif R, Parekh TM, Pierson KS, Kuo Y-F, Sharma G. Predictors of early readmission among patients 40 to 64 years of age hospitalized for chronic obstructive pulmonary disease. Annals ATS. 2014;11(5):685-694. https://doi.org/10.1513/AnnalsATS.201310-358OC.
6. Glaser JB, El-Haddad H. Exploring novel Medicare readmission risk variables in chronic obstructive pulmonary disease patients at high risk of readmission within 30 days of hospital discharge. Ann Am Thorac Soc. 2015;12(9):1288-1293. https://doi.org/10.1513/AnnalsATS.201504-228OC.
7. Sorace J, Wong HH, Worrall C, Kelman J, Saneinejad S, MaCurdy T. The complexity of disease combinations in the Medicare population. Popul Health Manag. 2011;14(4):161-166. https://doi.org/10.1089/pop.2010.0044
8. Wadhera RK, Joynt Maddox KE, Wasfy JH, Haneuse S, Shen C, Yeh RW. Association of the hospital readmissions reduction program with mortality among medicare beneficiaries hospitalized for heart failure, acute myocardial infarction, and pneumonia. JAMA. 2018;320(24):2542-2552. https://doi.org/10.1001/jama.2018.19232.

References

1. Jencks SF, Williams MV, Coleman EA. Rehospitalization among patients in the Medicare Fee-for-Service Program. N Engl J Med. 2009;360(14):1418-1428. https://doi.org/10.1056/NEJMsa0803563.
2. Shah T, Churpek MM, Coca Perraillon M, Konetzka RT. Understanding why patients with COPD get readmitted: a large national study to delineate the Medicare population for the readmissions penalty expansion. Chest. 2015;147(5):1219-1226. https://doi.org/10.1378/chest.14-2181.
3. Press VG, Au DH, Bourbeau J, Dransfield MT, Gershon AS, Krishnan JA, et al. An American thoracic society workshop report: reducing COPD hospital readmissions. Ann Am Thorac Soc. 2019;16(2):161-170. https://doi.org/10.1513/AnnalsATS.201811-755WS.
4. Buhr R, Jackson N, Kominski G, Ong M, Mangione C. Factors associated with differential readmission diagnoses following acute exacerbations of COPD. J Hosp Med. 2020;15(4):252-253. https://doi.org/10.12788/jhm.3367.
5. Sharif R, Parekh TM, Pierson KS, Kuo Y-F, Sharma G. Predictors of early readmission among patients 40 to 64 years of age hospitalized for chronic obstructive pulmonary disease. Annals ATS. 2014;11(5):685-694. https://doi.org/10.1513/AnnalsATS.201310-358OC.
6. Glaser JB, El-Haddad H. Exploring novel Medicare readmission risk variables in chronic obstructive pulmonary disease patients at high risk of readmission within 30 days of hospital discharge. Ann Am Thorac Soc. 2015;12(9):1288-1293. https://doi.org/10.1513/AnnalsATS.201504-228OC.
7. Sorace J, Wong HH, Worrall C, Kelman J, Saneinejad S, MaCurdy T. The complexity of disease combinations in the Medicare population. Popul Health Manag. 2011;14(4):161-166. https://doi.org/10.1089/pop.2010.0044
8. Wadhera RK, Joynt Maddox KE, Wasfy JH, Haneuse S, Shen C, Yeh RW. Association of the hospital readmissions reduction program with mortality among medicare beneficiaries hospitalized for heart failure, acute myocardial infarction, and pneumonia. JAMA. 2018;320(24):2542-2552. https://doi.org/10.1001/jama.2018.19232.

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Hypofractionated radiotherapy for prostate cancer stands the test of time

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AN FRANCISCO – In men with localized prostate cancer, a hypofractionated radiotherapy regimen that cuts treatment time in half continues to have noninferior efficacy long-term relative to a conventional radiotherapy regimen, an update of the CHHiP trial shows.

Susan London/MDedge News
Dr. David P. Dearnaley

The 3,216 men in the phase 3 trial had node-negative T1b-T3a prostate cancer and were evenly assigned to a conventional regimen of 74 Gy delivered in 37 fractions, a hypofractionated regimen of 60 Gy in 20 fractions, or a hypofractionated regimen of 57 Gy in 19 fractions. All regimens were delivered with intensity-modulated techniques.

The trial’s 5-year results, previously reported, showed noninferiority of the 60-Gy regimen, compared with the 74-Gy regimen on risk of biochemical or clinical failure (hazard ratio, 0.84), prompting recommendation of the former as a new standard of care for localized prostate cancer (Lancet Oncol. 2016;17:1047-60). Noninferiority could not be established for the 57-Gy regimen.

The 8-year results were essentially the same, confirming noninferiority of the 60-Gy regimen (HR, 0.85) but not the 57-Gy regimen. Meanwhile, bowel and bladder toxicity continued to be low across regimens.

David P. Dearnaley, MB BCh, MD, of the Royal Marsden NHS Foundation Trust, London, reported the 8-year results at the 2020 Genitourinary Cancers Symposium, sponsored by the American Society for Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Study details

At a median follow-up of 9.3 years, the 8-year rate of freedom from biochemical failure (defined by Phoenix consensus guidelines) or clinical failure (cancer recurrence) was 80.6% with 74 Gy, 83.7% with 60 Gy, and 78.5% with 57 Gy, Dr. Dearnaley reported.

Analyses confirmed noninferiority of the 60-Gy regimen (HR, 0.85; 95% confidence interval, 0.72-1.01; P = .11), but not the 57-Gy regimen (HR, 1.17; 95% CI, 1.00-1.36; P = .10), as the upper bound of the confidence interval crossed the predefined 1.21 boundary for noninferiority.

In an unplanned analysis, the pattern among men younger than 75 years was similar to that in the entire trial population. But among men 75 years of age and older, the 57-Gy arm is actually outperforming the 74-Gy arm (HR, 0.77).

The three regimens yielded a similarly high rate of freedom from metastases, at about 95% in each arm. The 60-Gy regimen had an edge in overall survival relative to the 74-Gy regimen (88.6% vs. 85.9%; HR, 0.84) that is hard to explain, according to Dr. Dearnaley.

“Because there is an 8:1 ratio of non–prostate cancer deaths to prostate cancer deaths, you would have to postulate something other than prostate cancer being affected by the radiotherapy fractionation,” he said. “The answers on a postcard, because I can’t think of one.”

On central pathology review, nearly a fifth of evaluated trial patients had high-risk disease. “I know everybody wants to know about high-risk patients, but I’d rather take the trial results as a whole and look to see if there is any heterogeneity between those groups rather than perform a specific high-risk subgroup analysis,” Dr. Dearnaley said, expressing concern about performing too many subgroup analyses.

That said, older patients on the trial tended to have higher risk. “It does seem hypofractionation was particularly useful in those patients,” he noted. “Now, whether that’s anything to do with their pathology or whether it’s due to their age per se, I really don’t know.”

There were no differences between groups on rates of Radiation Therapy Oncology Group toxicity at 5 years, with grade 2 or worse bowel toxicity and bladder toxicity each seen in about 2% of patients.

There were no significant differences in rates of patient-reported “moderate or big” bowel bother (roughly 5%-8%) and urinary bother (roughly 7%-9%). For all regimens, bowel and urinary symptoms remained stable from 2-5 years.

 

 

Reassuring for practice

These updated findings “support the continued use of 60 Gy in 20 fractions as the standard of care,” Dr. Dearnaley said.

When the math is run to permit comparison, efficacy findings of the CHHiP trial show “amazing agreement” with those of the similar multinational PROFIT trial, he noted (J Clin Oncol. 2017 Jun 10;35(17):1884-90).

The absolute advantage in the failure-free rate of 3.1% and the overall survival rate of 2.7% for the 60-Gy regimen in CHHiP generated interest among symposium attendees about its possible superiority. “I think the 60 Gy is marginally more effective than the 74 Gy,” Dr. Dearnaley said, but he acknowledged that there are no statistics to prove that.

Susan London/MDedge News
Dr. Paul L. Nguyen

“This CHHiP update is fantastic,” said session cochair Paul L. Nguyen, MD, of the Dana-Farber Cancer Institute in Boston. “It is very reassuring that the initial results the investigators presented several years ago still hold up in the long term. It’s even more reassuring for the use of hypofractionation, and it’s great to know that we can use it across the age spectrum and it works well.”

This trial is the only noninferiority hypofractionation trial in prostate cancer that includes a sizable share of patients at high risk for poor outcomes, a population for whom efficacy of this strategy is of particular interest, Dr. Nguyen noted.

“That’s always been a question,” he said. “The majority of the data from the noninferiority trials is for the low- and intermediate-risk patients. So it really would be interesting to learn whatever we can about high-risk patients from this trial.”

The trial was funded by Cancer Research UK, Department of Health (UK), and the National Institute for Health Research Cancer Research Network. Dr. Dearnaley and Dr. Nguyen disclosed relationships with a range of pharmaceutical companies.
 

SOURCE: Dearnaley DP et al. GUCS 2020. Abstract 325.

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AN FRANCISCO – In men with localized prostate cancer, a hypofractionated radiotherapy regimen that cuts treatment time in half continues to have noninferior efficacy long-term relative to a conventional radiotherapy regimen, an update of the CHHiP trial shows.

Susan London/MDedge News
Dr. David P. Dearnaley

The 3,216 men in the phase 3 trial had node-negative T1b-T3a prostate cancer and were evenly assigned to a conventional regimen of 74 Gy delivered in 37 fractions, a hypofractionated regimen of 60 Gy in 20 fractions, or a hypofractionated regimen of 57 Gy in 19 fractions. All regimens were delivered with intensity-modulated techniques.

The trial’s 5-year results, previously reported, showed noninferiority of the 60-Gy regimen, compared with the 74-Gy regimen on risk of biochemical or clinical failure (hazard ratio, 0.84), prompting recommendation of the former as a new standard of care for localized prostate cancer (Lancet Oncol. 2016;17:1047-60). Noninferiority could not be established for the 57-Gy regimen.

The 8-year results were essentially the same, confirming noninferiority of the 60-Gy regimen (HR, 0.85) but not the 57-Gy regimen. Meanwhile, bowel and bladder toxicity continued to be low across regimens.

David P. Dearnaley, MB BCh, MD, of the Royal Marsden NHS Foundation Trust, London, reported the 8-year results at the 2020 Genitourinary Cancers Symposium, sponsored by the American Society for Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Study details

At a median follow-up of 9.3 years, the 8-year rate of freedom from biochemical failure (defined by Phoenix consensus guidelines) or clinical failure (cancer recurrence) was 80.6% with 74 Gy, 83.7% with 60 Gy, and 78.5% with 57 Gy, Dr. Dearnaley reported.

Analyses confirmed noninferiority of the 60-Gy regimen (HR, 0.85; 95% confidence interval, 0.72-1.01; P = .11), but not the 57-Gy regimen (HR, 1.17; 95% CI, 1.00-1.36; P = .10), as the upper bound of the confidence interval crossed the predefined 1.21 boundary for noninferiority.

In an unplanned analysis, the pattern among men younger than 75 years was similar to that in the entire trial population. But among men 75 years of age and older, the 57-Gy arm is actually outperforming the 74-Gy arm (HR, 0.77).

The three regimens yielded a similarly high rate of freedom from metastases, at about 95% in each arm. The 60-Gy regimen had an edge in overall survival relative to the 74-Gy regimen (88.6% vs. 85.9%; HR, 0.84) that is hard to explain, according to Dr. Dearnaley.

“Because there is an 8:1 ratio of non–prostate cancer deaths to prostate cancer deaths, you would have to postulate something other than prostate cancer being affected by the radiotherapy fractionation,” he said. “The answers on a postcard, because I can’t think of one.”

On central pathology review, nearly a fifth of evaluated trial patients had high-risk disease. “I know everybody wants to know about high-risk patients, but I’d rather take the trial results as a whole and look to see if there is any heterogeneity between those groups rather than perform a specific high-risk subgroup analysis,” Dr. Dearnaley said, expressing concern about performing too many subgroup analyses.

That said, older patients on the trial tended to have higher risk. “It does seem hypofractionation was particularly useful in those patients,” he noted. “Now, whether that’s anything to do with their pathology or whether it’s due to their age per se, I really don’t know.”

There were no differences between groups on rates of Radiation Therapy Oncology Group toxicity at 5 years, with grade 2 or worse bowel toxicity and bladder toxicity each seen in about 2% of patients.

There were no significant differences in rates of patient-reported “moderate or big” bowel bother (roughly 5%-8%) and urinary bother (roughly 7%-9%). For all regimens, bowel and urinary symptoms remained stable from 2-5 years.

 

 

Reassuring for practice

These updated findings “support the continued use of 60 Gy in 20 fractions as the standard of care,” Dr. Dearnaley said.

When the math is run to permit comparison, efficacy findings of the CHHiP trial show “amazing agreement” with those of the similar multinational PROFIT trial, he noted (J Clin Oncol. 2017 Jun 10;35(17):1884-90).

The absolute advantage in the failure-free rate of 3.1% and the overall survival rate of 2.7% for the 60-Gy regimen in CHHiP generated interest among symposium attendees about its possible superiority. “I think the 60 Gy is marginally more effective than the 74 Gy,” Dr. Dearnaley said, but he acknowledged that there are no statistics to prove that.

Susan London/MDedge News
Dr. Paul L. Nguyen

“This CHHiP update is fantastic,” said session cochair Paul L. Nguyen, MD, of the Dana-Farber Cancer Institute in Boston. “It is very reassuring that the initial results the investigators presented several years ago still hold up in the long term. It’s even more reassuring for the use of hypofractionation, and it’s great to know that we can use it across the age spectrum and it works well.”

This trial is the only noninferiority hypofractionation trial in prostate cancer that includes a sizable share of patients at high risk for poor outcomes, a population for whom efficacy of this strategy is of particular interest, Dr. Nguyen noted.

“That’s always been a question,” he said. “The majority of the data from the noninferiority trials is for the low- and intermediate-risk patients. So it really would be interesting to learn whatever we can about high-risk patients from this trial.”

The trial was funded by Cancer Research UK, Department of Health (UK), and the National Institute for Health Research Cancer Research Network. Dr. Dearnaley and Dr. Nguyen disclosed relationships with a range of pharmaceutical companies.
 

SOURCE: Dearnaley DP et al. GUCS 2020. Abstract 325.

AN FRANCISCO – In men with localized prostate cancer, a hypofractionated radiotherapy regimen that cuts treatment time in half continues to have noninferior efficacy long-term relative to a conventional radiotherapy regimen, an update of the CHHiP trial shows.

Susan London/MDedge News
Dr. David P. Dearnaley

The 3,216 men in the phase 3 trial had node-negative T1b-T3a prostate cancer and were evenly assigned to a conventional regimen of 74 Gy delivered in 37 fractions, a hypofractionated regimen of 60 Gy in 20 fractions, or a hypofractionated regimen of 57 Gy in 19 fractions. All regimens were delivered with intensity-modulated techniques.

The trial’s 5-year results, previously reported, showed noninferiority of the 60-Gy regimen, compared with the 74-Gy regimen on risk of biochemical or clinical failure (hazard ratio, 0.84), prompting recommendation of the former as a new standard of care for localized prostate cancer (Lancet Oncol. 2016;17:1047-60). Noninferiority could not be established for the 57-Gy regimen.

The 8-year results were essentially the same, confirming noninferiority of the 60-Gy regimen (HR, 0.85) but not the 57-Gy regimen. Meanwhile, bowel and bladder toxicity continued to be low across regimens.

David P. Dearnaley, MB BCh, MD, of the Royal Marsden NHS Foundation Trust, London, reported the 8-year results at the 2020 Genitourinary Cancers Symposium, sponsored by the American Society for Clinical Oncology, ASTRO, and the Society of Urologic Oncology.

Study details

At a median follow-up of 9.3 years, the 8-year rate of freedom from biochemical failure (defined by Phoenix consensus guidelines) or clinical failure (cancer recurrence) was 80.6% with 74 Gy, 83.7% with 60 Gy, and 78.5% with 57 Gy, Dr. Dearnaley reported.

Analyses confirmed noninferiority of the 60-Gy regimen (HR, 0.85; 95% confidence interval, 0.72-1.01; P = .11), but not the 57-Gy regimen (HR, 1.17; 95% CI, 1.00-1.36; P = .10), as the upper bound of the confidence interval crossed the predefined 1.21 boundary for noninferiority.

In an unplanned analysis, the pattern among men younger than 75 years was similar to that in the entire trial population. But among men 75 years of age and older, the 57-Gy arm is actually outperforming the 74-Gy arm (HR, 0.77).

The three regimens yielded a similarly high rate of freedom from metastases, at about 95% in each arm. The 60-Gy regimen had an edge in overall survival relative to the 74-Gy regimen (88.6% vs. 85.9%; HR, 0.84) that is hard to explain, according to Dr. Dearnaley.

“Because there is an 8:1 ratio of non–prostate cancer deaths to prostate cancer deaths, you would have to postulate something other than prostate cancer being affected by the radiotherapy fractionation,” he said. “The answers on a postcard, because I can’t think of one.”

On central pathology review, nearly a fifth of evaluated trial patients had high-risk disease. “I know everybody wants to know about high-risk patients, but I’d rather take the trial results as a whole and look to see if there is any heterogeneity between those groups rather than perform a specific high-risk subgroup analysis,” Dr. Dearnaley said, expressing concern about performing too many subgroup analyses.

That said, older patients on the trial tended to have higher risk. “It does seem hypofractionation was particularly useful in those patients,” he noted. “Now, whether that’s anything to do with their pathology or whether it’s due to their age per se, I really don’t know.”

There were no differences between groups on rates of Radiation Therapy Oncology Group toxicity at 5 years, with grade 2 or worse bowel toxicity and bladder toxicity each seen in about 2% of patients.

There were no significant differences in rates of patient-reported “moderate or big” bowel bother (roughly 5%-8%) and urinary bother (roughly 7%-9%). For all regimens, bowel and urinary symptoms remained stable from 2-5 years.

 

 

Reassuring for practice

These updated findings “support the continued use of 60 Gy in 20 fractions as the standard of care,” Dr. Dearnaley said.

When the math is run to permit comparison, efficacy findings of the CHHiP trial show “amazing agreement” with those of the similar multinational PROFIT trial, he noted (J Clin Oncol. 2017 Jun 10;35(17):1884-90).

The absolute advantage in the failure-free rate of 3.1% and the overall survival rate of 2.7% for the 60-Gy regimen in CHHiP generated interest among symposium attendees about its possible superiority. “I think the 60 Gy is marginally more effective than the 74 Gy,” Dr. Dearnaley said, but he acknowledged that there are no statistics to prove that.

Susan London/MDedge News
Dr. Paul L. Nguyen

“This CHHiP update is fantastic,” said session cochair Paul L. Nguyen, MD, of the Dana-Farber Cancer Institute in Boston. “It is very reassuring that the initial results the investigators presented several years ago still hold up in the long term. It’s even more reassuring for the use of hypofractionation, and it’s great to know that we can use it across the age spectrum and it works well.”

This trial is the only noninferiority hypofractionation trial in prostate cancer that includes a sizable share of patients at high risk for poor outcomes, a population for whom efficacy of this strategy is of particular interest, Dr. Nguyen noted.

“That’s always been a question,” he said. “The majority of the data from the noninferiority trials is for the low- and intermediate-risk patients. So it really would be interesting to learn whatever we can about high-risk patients from this trial.”

The trial was funded by Cancer Research UK, Department of Health (UK), and the National Institute for Health Research Cancer Research Network. Dr. Dearnaley and Dr. Nguyen disclosed relationships with a range of pharmaceutical companies.
 

SOURCE: Dearnaley DP et al. GUCS 2020. Abstract 325.

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Brain imaging offers new insight into persistent antisocial behavior

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Individuals who exhibit antisocial behavior over a lifetime have a thinner cortex and smaller surface area in key brain regions relative to their counterparts who do not engage in antisocial behavior, new research shows.

However, investigators found no widespread structural brain abnormalities in the group of individuals who exhibited antisocial behavior only during adolescence.

These brain differences seem to be “quite specific and unique” to individuals who exhibit persistent antisocial behavior over their life, lead researcher Christina O. Carlisi, PhD, of University College London, said during a press briefing.

“Critically, the findings don’t directly link brain structure abnormalities to antisocial behavior,” she said. Nor do they mean that anyone with a smaller brain or brain area is destined to be antisocial or to commit a crime.

“Our findings support the idea that, for the small proportion of individuals with life-course–persistent antisocial behavior, there may be differences in their brain structure that make it difficult for them to develop social skills that prevent them from engaging in antisocial behavior,” Dr. Carlisi said in a news release. “These people could benefit from more support throughout their lives.”

The study, the investigators noted, provides the first robust evidence to suggest that underlying neuropsychological differences are primarily associated with life-course-persistent persistent antisocial behavior. It was published online Feb. 17 in the Lancet Psychiatry (doi: 10.1016/S2215-0366[20]30002-X).

Support for second chances

Speaking at the press briefing, coauthor Terrie E. Moffitt, PhD, of Duke University, Durham, N.C., said it’s well known that most young criminals are between the ages of 16 and 25.

Breaking the law is not at all rare in this age group, but not all of these young offenders are alike, she noted. Only a few become persistent repeat offenders.

“They start as a young child with aggressive conduct problems and eventually sink into a long-term lifestyle of repetitive serious crime that lasts well into adulthood, but this is a small group,” Dr. Moffitt explained. “In contrast, the larger majority of offenders will have only a short-term brush with lawbreaking and then grow up to become law-abiding members of society.”

The current study suggests that what makes short-term offenders behave differently from long-term offenders might involve some vulnerability at the level of the structure of the brain, Dr. Moffitt said.

The findings stem from 672 individuals in the Dunedin Multidisciplinary Health and Development Study, a population-representative, longitudinal birth cohort that assesses health and behavior.

On the basis of reports from parents, care givers, and teachers, as well as self-reports of conduct problems in persons aged 7-26 years, 80 participants (12%) had “life-course–persistent” antisocial behavior, 151 (23%) had adolescent-only antisocial behavior, and 441 (66%) had “low” antisocial behavior (control group, whose members never had a pervasive or persistent pattern of antisocial behavior).

Brain MRI obtained at age 45 years showed that, among individuals with persistent antisocial behavior, mean surface area was smaller (95% confidence interval, –0.24 to –0.11; P less than .0001) and mean cortical thickness was lower (95% CI, –0.19 to –0.02; P = .020) than was those of their peers in the control group.

For those in the life-course–persistent group, surface area was reduced in 282 of 360 anatomically defined brain parcels, and cortex was thinner in 11 of 360 parcels encompassing frontal and temporal regions (which were associated with executive function, emotion regulation, and motivation), compared with the control group.

Widespread differences in brain surface morphometry were not found in those who exhibited antisocial behavior during adolescence only. Such behavior was likely the result of their having to navigate through socially tough years.

“These findings underscore prior research that really highlights that there are different types of young offenders. They are not all the same; they should not all be treated the same,” coauthor Essi Viding, PhD, who also is affiliated with University College London, told reporters.

The findings support current strategies aimed at giving young offenders “a second chance” as opposed to enforcing harsher policies that prioritize incarceration for all young offenders, Dr. Viding added.

 

 

Important contribution

The authors of an accompanying commentary noted that, despite “remarkable progress in the past 3 decades, the etiology of antisocial behavior remains elusive” (Lancet Psychiatry. 2020 Feb 17. doi: 10.1016/S2215-0366[20]30035-3).

This study makes “an important contribution by identifying structural brain correlates of antisocial behavior that could be used to differentiate among individuals with life-course-persistent antisocial behavior, those with adolescence-limited antisocial behavior, and non-antisocial controls,” write Inti A. Brazil, PhD, of the Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, the Netherlands, and Macià Buades-Rotger, PhD, of the Institute of Psychology II, University of Lübeck, Germany.

They noted that the findings might help to move the field closer to achieving the long-standing goal of incorporating neural data into assessment protocols for antisocial behavior.

The discovery of “meaningful morphologic differences between individuals with life-course–persistent and adolescence-limited antisocial behavior offers an important advance in the use of brain metrics for differentiating among individuals with antisocial dispositions.

“Importantly, however, it remains to be determined whether and how measuring the brain can be used to bridge the different taxometric views and theories on the etiology of antisocial behavior,” Dr. Brazil and Dr. Buades-Rotger concluded.

The study was funded by the U.S. National Institute on Aging; the Health Research Council of New Zealand; the New Zealand Ministry of Business, Innovation and Employment; the U.K. Medical Research Council; the Avielle Foundation; and the Wellcome Trust. The study authors and the authors of the commentary disclosed no relevant financial relationships.
 

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

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Individuals who exhibit antisocial behavior over a lifetime have a thinner cortex and smaller surface area in key brain regions relative to their counterparts who do not engage in antisocial behavior, new research shows.

However, investigators found no widespread structural brain abnormalities in the group of individuals who exhibited antisocial behavior only during adolescence.

These brain differences seem to be “quite specific and unique” to individuals who exhibit persistent antisocial behavior over their life, lead researcher Christina O. Carlisi, PhD, of University College London, said during a press briefing.

“Critically, the findings don’t directly link brain structure abnormalities to antisocial behavior,” she said. Nor do they mean that anyone with a smaller brain or brain area is destined to be antisocial or to commit a crime.

“Our findings support the idea that, for the small proportion of individuals with life-course–persistent antisocial behavior, there may be differences in their brain structure that make it difficult for them to develop social skills that prevent them from engaging in antisocial behavior,” Dr. Carlisi said in a news release. “These people could benefit from more support throughout their lives.”

The study, the investigators noted, provides the first robust evidence to suggest that underlying neuropsychological differences are primarily associated with life-course-persistent persistent antisocial behavior. It was published online Feb. 17 in the Lancet Psychiatry (doi: 10.1016/S2215-0366[20]30002-X).

Support for second chances

Speaking at the press briefing, coauthor Terrie E. Moffitt, PhD, of Duke University, Durham, N.C., said it’s well known that most young criminals are between the ages of 16 and 25.

Breaking the law is not at all rare in this age group, but not all of these young offenders are alike, she noted. Only a few become persistent repeat offenders.

“They start as a young child with aggressive conduct problems and eventually sink into a long-term lifestyle of repetitive serious crime that lasts well into adulthood, but this is a small group,” Dr. Moffitt explained. “In contrast, the larger majority of offenders will have only a short-term brush with lawbreaking and then grow up to become law-abiding members of society.”

The current study suggests that what makes short-term offenders behave differently from long-term offenders might involve some vulnerability at the level of the structure of the brain, Dr. Moffitt said.

The findings stem from 672 individuals in the Dunedin Multidisciplinary Health and Development Study, a population-representative, longitudinal birth cohort that assesses health and behavior.

On the basis of reports from parents, care givers, and teachers, as well as self-reports of conduct problems in persons aged 7-26 years, 80 participants (12%) had “life-course–persistent” antisocial behavior, 151 (23%) had adolescent-only antisocial behavior, and 441 (66%) had “low” antisocial behavior (control group, whose members never had a pervasive or persistent pattern of antisocial behavior).

Brain MRI obtained at age 45 years showed that, among individuals with persistent antisocial behavior, mean surface area was smaller (95% confidence interval, –0.24 to –0.11; P less than .0001) and mean cortical thickness was lower (95% CI, –0.19 to –0.02; P = .020) than was those of their peers in the control group.

For those in the life-course–persistent group, surface area was reduced in 282 of 360 anatomically defined brain parcels, and cortex was thinner in 11 of 360 parcels encompassing frontal and temporal regions (which were associated with executive function, emotion regulation, and motivation), compared with the control group.

Widespread differences in brain surface morphometry were not found in those who exhibited antisocial behavior during adolescence only. Such behavior was likely the result of their having to navigate through socially tough years.

“These findings underscore prior research that really highlights that there are different types of young offenders. They are not all the same; they should not all be treated the same,” coauthor Essi Viding, PhD, who also is affiliated with University College London, told reporters.

The findings support current strategies aimed at giving young offenders “a second chance” as opposed to enforcing harsher policies that prioritize incarceration for all young offenders, Dr. Viding added.

 

 

Important contribution

The authors of an accompanying commentary noted that, despite “remarkable progress in the past 3 decades, the etiology of antisocial behavior remains elusive” (Lancet Psychiatry. 2020 Feb 17. doi: 10.1016/S2215-0366[20]30035-3).

This study makes “an important contribution by identifying structural brain correlates of antisocial behavior that could be used to differentiate among individuals with life-course-persistent antisocial behavior, those with adolescence-limited antisocial behavior, and non-antisocial controls,” write Inti A. Brazil, PhD, of the Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, the Netherlands, and Macià Buades-Rotger, PhD, of the Institute of Psychology II, University of Lübeck, Germany.

They noted that the findings might help to move the field closer to achieving the long-standing goal of incorporating neural data into assessment protocols for antisocial behavior.

The discovery of “meaningful morphologic differences between individuals with life-course–persistent and adolescence-limited antisocial behavior offers an important advance in the use of brain metrics for differentiating among individuals with antisocial dispositions.

“Importantly, however, it remains to be determined whether and how measuring the brain can be used to bridge the different taxometric views and theories on the etiology of antisocial behavior,” Dr. Brazil and Dr. Buades-Rotger concluded.

The study was funded by the U.S. National Institute on Aging; the Health Research Council of New Zealand; the New Zealand Ministry of Business, Innovation and Employment; the U.K. Medical Research Council; the Avielle Foundation; and the Wellcome Trust. The study authors and the authors of the commentary disclosed no relevant financial relationships.
 

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

Individuals who exhibit antisocial behavior over a lifetime have a thinner cortex and smaller surface area in key brain regions relative to their counterparts who do not engage in antisocial behavior, new research shows.

However, investigators found no widespread structural brain abnormalities in the group of individuals who exhibited antisocial behavior only during adolescence.

These brain differences seem to be “quite specific and unique” to individuals who exhibit persistent antisocial behavior over their life, lead researcher Christina O. Carlisi, PhD, of University College London, said during a press briefing.

“Critically, the findings don’t directly link brain structure abnormalities to antisocial behavior,” she said. Nor do they mean that anyone with a smaller brain or brain area is destined to be antisocial or to commit a crime.

“Our findings support the idea that, for the small proportion of individuals with life-course–persistent antisocial behavior, there may be differences in their brain structure that make it difficult for them to develop social skills that prevent them from engaging in antisocial behavior,” Dr. Carlisi said in a news release. “These people could benefit from more support throughout their lives.”

The study, the investigators noted, provides the first robust evidence to suggest that underlying neuropsychological differences are primarily associated with life-course-persistent persistent antisocial behavior. It was published online Feb. 17 in the Lancet Psychiatry (doi: 10.1016/S2215-0366[20]30002-X).

Support for second chances

Speaking at the press briefing, coauthor Terrie E. Moffitt, PhD, of Duke University, Durham, N.C., said it’s well known that most young criminals are between the ages of 16 and 25.

Breaking the law is not at all rare in this age group, but not all of these young offenders are alike, she noted. Only a few become persistent repeat offenders.

“They start as a young child with aggressive conduct problems and eventually sink into a long-term lifestyle of repetitive serious crime that lasts well into adulthood, but this is a small group,” Dr. Moffitt explained. “In contrast, the larger majority of offenders will have only a short-term brush with lawbreaking and then grow up to become law-abiding members of society.”

The current study suggests that what makes short-term offenders behave differently from long-term offenders might involve some vulnerability at the level of the structure of the brain, Dr. Moffitt said.

The findings stem from 672 individuals in the Dunedin Multidisciplinary Health and Development Study, a population-representative, longitudinal birth cohort that assesses health and behavior.

On the basis of reports from parents, care givers, and teachers, as well as self-reports of conduct problems in persons aged 7-26 years, 80 participants (12%) had “life-course–persistent” antisocial behavior, 151 (23%) had adolescent-only antisocial behavior, and 441 (66%) had “low” antisocial behavior (control group, whose members never had a pervasive or persistent pattern of antisocial behavior).

Brain MRI obtained at age 45 years showed that, among individuals with persistent antisocial behavior, mean surface area was smaller (95% confidence interval, –0.24 to –0.11; P less than .0001) and mean cortical thickness was lower (95% CI, –0.19 to –0.02; P = .020) than was those of their peers in the control group.

For those in the life-course–persistent group, surface area was reduced in 282 of 360 anatomically defined brain parcels, and cortex was thinner in 11 of 360 parcels encompassing frontal and temporal regions (which were associated with executive function, emotion regulation, and motivation), compared with the control group.

Widespread differences in brain surface morphometry were not found in those who exhibited antisocial behavior during adolescence only. Such behavior was likely the result of their having to navigate through socially tough years.

“These findings underscore prior research that really highlights that there are different types of young offenders. They are not all the same; they should not all be treated the same,” coauthor Essi Viding, PhD, who also is affiliated with University College London, told reporters.

The findings support current strategies aimed at giving young offenders “a second chance” as opposed to enforcing harsher policies that prioritize incarceration for all young offenders, Dr. Viding added.

 

 

Important contribution

The authors of an accompanying commentary noted that, despite “remarkable progress in the past 3 decades, the etiology of antisocial behavior remains elusive” (Lancet Psychiatry. 2020 Feb 17. doi: 10.1016/S2215-0366[20]30035-3).

This study makes “an important contribution by identifying structural brain correlates of antisocial behavior that could be used to differentiate among individuals with life-course-persistent antisocial behavior, those with adolescence-limited antisocial behavior, and non-antisocial controls,” write Inti A. Brazil, PhD, of the Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, the Netherlands, and Macià Buades-Rotger, PhD, of the Institute of Psychology II, University of Lübeck, Germany.

They noted that the findings might help to move the field closer to achieving the long-standing goal of incorporating neural data into assessment protocols for antisocial behavior.

The discovery of “meaningful morphologic differences between individuals with life-course–persistent and adolescence-limited antisocial behavior offers an important advance in the use of brain metrics for differentiating among individuals with antisocial dispositions.

“Importantly, however, it remains to be determined whether and how measuring the brain can be used to bridge the different taxometric views and theories on the etiology of antisocial behavior,” Dr. Brazil and Dr. Buades-Rotger concluded.

The study was funded by the U.S. National Institute on Aging; the Health Research Council of New Zealand; the New Zealand Ministry of Business, Innovation and Employment; the U.K. Medical Research Council; the Avielle Foundation; and the Wellcome Trust. The study authors and the authors of the commentary disclosed no relevant financial relationships.
 

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

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My inspiration

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Kobe Bryant knew me. Not personally, of course. I never received an autograph or shook his hand. But once in a while if I was up early enough, I’d run into Kobe at the gym in Newport Beach where he and I both worked out. As he did for all his fans at the gym, he’d make eye contact with me and nod hello. He was always focused on his workout – working with a trainer, never with headphones on. In person, he appeared enormous. Unlike most retired professional athletes, he still was in great shape. No doubt he could have suited up in purple and gold, and played against the Clippers that night if needed.

Featureflash Photo Agency
Kobe Bryant at the 90th Academy Awards at the Dolby Theatre, Hollywood, Calf., on March 4, 2018.

Being from New England, I never was a Laker fan. But at Kobe’s peak around 2000, I found him inspiring. I recall watching him play right around the time I was studying for my U.S. medical licensing exams. I thought, if Kobe can head to the gym after midnight and take a 1,000 shots to prepare for a game, then I could set my alarm for 4 a.m. and take a few dozen more questions from my First Aid books. Head down, “Kryptonite” cranked on my iPod, I wasn’t going to let anyone in that test room outwork me. Neither did he. I put in the time and, like Kobe in the 2002 conference finals against Sacramento, I crushed it.*

When we moved to California, I followed Kobe and the Lakers until he retired. To be clear, I didn’t aspire to be like him, firstly because I’m slightly shorter than Michael Bloomberg, but also because although accomplished, Kobe made some poor choices at times. Indeed, it seems he might have been kinder and more considerate when he was at the top. But in his retirement he looked to be toiling to make reparations, refocusing his prodigious energy and talent for the benefit of others rather than for just for scoring 81 points. His Rolls Royce was there before mine at the gym, and I was there early. He was still getting up early and now preparing to be a great venture capitalist, podcaster, author, and father to his girls.

Dr. Jeffrey Benabio

Watching him carry kettle bells across the floor one morning, I wondered, do people like Kobe Bryant look to others for inspiration? Or are they are born with an endless supply of it? For me, I seemed to push harder and faster when watching idols pass by. Whether it was Kobe or Clayton Christensen (author of “The Innovator’s Dilemma”), Joe Jorizzo, or Barack Obama, I found I could do just a bit more if I had them in mind.

On game days, Kobe spoke of arriving at the arena early, long before anyone. He would use the silent, solo time to reflect on what he needed to do perform that night. I tried this last week, arriving at our clinic early, before any patients or staff. I turned the lights on and took a few minutes to think about what we needed to accomplish that day. I previewed patients on my schedule, searched Up to Date for the latest recommendations on a difficult case. I didn’t know Kobe, but I felt like I did.

CC0 1.0 Universal Public Domain Dedication

When I received the text that Kobe Bryant had died, I was actually working on this column. So I decided to change the topic to write about people who inspire me, ironically inspired by him again. May he rest in peace.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

*This article was updated 2/19/2020.

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Kobe Bryant knew me. Not personally, of course. I never received an autograph or shook his hand. But once in a while if I was up early enough, I’d run into Kobe at the gym in Newport Beach where he and I both worked out. As he did for all his fans at the gym, he’d make eye contact with me and nod hello. He was always focused on his workout – working with a trainer, never with headphones on. In person, he appeared enormous. Unlike most retired professional athletes, he still was in great shape. No doubt he could have suited up in purple and gold, and played against the Clippers that night if needed.

Featureflash Photo Agency
Kobe Bryant at the 90th Academy Awards at the Dolby Theatre, Hollywood, Calf., on March 4, 2018.

Being from New England, I never was a Laker fan. But at Kobe’s peak around 2000, I found him inspiring. I recall watching him play right around the time I was studying for my U.S. medical licensing exams. I thought, if Kobe can head to the gym after midnight and take a 1,000 shots to prepare for a game, then I could set my alarm for 4 a.m. and take a few dozen more questions from my First Aid books. Head down, “Kryptonite” cranked on my iPod, I wasn’t going to let anyone in that test room outwork me. Neither did he. I put in the time and, like Kobe in the 2002 conference finals against Sacramento, I crushed it.*

When we moved to California, I followed Kobe and the Lakers until he retired. To be clear, I didn’t aspire to be like him, firstly because I’m slightly shorter than Michael Bloomberg, but also because although accomplished, Kobe made some poor choices at times. Indeed, it seems he might have been kinder and more considerate when he was at the top. But in his retirement he looked to be toiling to make reparations, refocusing his prodigious energy and talent for the benefit of others rather than for just for scoring 81 points. His Rolls Royce was there before mine at the gym, and I was there early. He was still getting up early and now preparing to be a great venture capitalist, podcaster, author, and father to his girls.

Dr. Jeffrey Benabio

Watching him carry kettle bells across the floor one morning, I wondered, do people like Kobe Bryant look to others for inspiration? Or are they are born with an endless supply of it? For me, I seemed to push harder and faster when watching idols pass by. Whether it was Kobe or Clayton Christensen (author of “The Innovator’s Dilemma”), Joe Jorizzo, or Barack Obama, I found I could do just a bit more if I had them in mind.

On game days, Kobe spoke of arriving at the arena early, long before anyone. He would use the silent, solo time to reflect on what he needed to do perform that night. I tried this last week, arriving at our clinic early, before any patients or staff. I turned the lights on and took a few minutes to think about what we needed to accomplish that day. I previewed patients on my schedule, searched Up to Date for the latest recommendations on a difficult case. I didn’t know Kobe, but I felt like I did.

CC0 1.0 Universal Public Domain Dedication

When I received the text that Kobe Bryant had died, I was actually working on this column. So I decided to change the topic to write about people who inspire me, ironically inspired by him again. May he rest in peace.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

*This article was updated 2/19/2020.

Kobe Bryant knew me. Not personally, of course. I never received an autograph or shook his hand. But once in a while if I was up early enough, I’d run into Kobe at the gym in Newport Beach where he and I both worked out. As he did for all his fans at the gym, he’d make eye contact with me and nod hello. He was always focused on his workout – working with a trainer, never with headphones on. In person, he appeared enormous. Unlike most retired professional athletes, he still was in great shape. No doubt he could have suited up in purple and gold, and played against the Clippers that night if needed.

Featureflash Photo Agency
Kobe Bryant at the 90th Academy Awards at the Dolby Theatre, Hollywood, Calf., on March 4, 2018.

Being from New England, I never was a Laker fan. But at Kobe’s peak around 2000, I found him inspiring. I recall watching him play right around the time I was studying for my U.S. medical licensing exams. I thought, if Kobe can head to the gym after midnight and take a 1,000 shots to prepare for a game, then I could set my alarm for 4 a.m. and take a few dozen more questions from my First Aid books. Head down, “Kryptonite” cranked on my iPod, I wasn’t going to let anyone in that test room outwork me. Neither did he. I put in the time and, like Kobe in the 2002 conference finals against Sacramento, I crushed it.*

When we moved to California, I followed Kobe and the Lakers until he retired. To be clear, I didn’t aspire to be like him, firstly because I’m slightly shorter than Michael Bloomberg, but also because although accomplished, Kobe made some poor choices at times. Indeed, it seems he might have been kinder and more considerate when he was at the top. But in his retirement he looked to be toiling to make reparations, refocusing his prodigious energy and talent for the benefit of others rather than for just for scoring 81 points. His Rolls Royce was there before mine at the gym, and I was there early. He was still getting up early and now preparing to be a great venture capitalist, podcaster, author, and father to his girls.

Dr. Jeffrey Benabio

Watching him carry kettle bells across the floor one morning, I wondered, do people like Kobe Bryant look to others for inspiration? Or are they are born with an endless supply of it? For me, I seemed to push harder and faster when watching idols pass by. Whether it was Kobe or Clayton Christensen (author of “The Innovator’s Dilemma”), Joe Jorizzo, or Barack Obama, I found I could do just a bit more if I had them in mind.

On game days, Kobe spoke of arriving at the arena early, long before anyone. He would use the silent, solo time to reflect on what he needed to do perform that night. I tried this last week, arriving at our clinic early, before any patients or staff. I turned the lights on and took a few minutes to think about what we needed to accomplish that day. I previewed patients on my schedule, searched Up to Date for the latest recommendations on a difficult case. I didn’t know Kobe, but I felt like I did.

CC0 1.0 Universal Public Domain Dedication

When I received the text that Kobe Bryant had died, I was actually working on this column. So I decided to change the topic to write about people who inspire me, ironically inspired by him again. May he rest in peace.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

*This article was updated 2/19/2020.

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Hyperhidrosis treatment options include glycopyrrolate

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LAHAINA, HAWAII – Hyperhidrosis affects nearly 5% of the U.S. population, and in a survey of U.S. teenagers, about 17% reported excessive sweating, Jashin Wu, MD, said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

In an interview with MDedge reporter Bruce Jancin, Dr. Wu, founder of the Dermatology Research and Education Foundation, Irvine, Calif., discussed the off-label use of oral agents to treat hyperhidrosis. Dr. Wu said he is a fan of oral glycopyrrolate in particular, which he tends to use even earlier than suggested in the International Hyperhidrosis Society guidelines.

Glycopyrrolate is available in 1 mg and 2 mg tablets; Dr. Wu starts patients at a dose of 1 mg twice a day, escalating by 1 mg per week until the “desired effects occur” or the patient has problems tolerating treatment because of side effects.

Other oral options include oxybutynin and propranolol. Sofpironium bromide, an analog of glycopyrrolate, is in the pipeline, he said.

During the interview, Dr. Wu discussed mydriasis, an adverse effect associated with both topical and systemic anticholinergic treatment. In the two pivotal phase 3 randomized trials of prescription glycopyrronium cloth (Qbrexza) for axillary hyperhidrosis, the incidence of mydriasis was 6.8% in 463 patients on active treatment for 4 weeks. Three-quarters of cases were unilateral. The mydriasis resolved without permanent treatment discontinuation in 27 of the 31 patients (J Am Acad Dermatol. 2019 Jan;80[1]:128-138.e2).

“The most important point is that patients need to be educated that they need to wash their hands very well after they apply it to the affected areas” to prevent accidental medication contact with the eyes, he advised.

Alarm bells can go off when a patient with anticholinergic therapy–induced mydriasis presents to an ED without mentioning their treatment status, Dr. Wu observed.

Dr. Wu had no relevant disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

To listen to the interview, click the play button below.

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LAHAINA, HAWAII – Hyperhidrosis affects nearly 5% of the U.S. population, and in a survey of U.S. teenagers, about 17% reported excessive sweating, Jashin Wu, MD, said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

In an interview with MDedge reporter Bruce Jancin, Dr. Wu, founder of the Dermatology Research and Education Foundation, Irvine, Calif., discussed the off-label use of oral agents to treat hyperhidrosis. Dr. Wu said he is a fan of oral glycopyrrolate in particular, which he tends to use even earlier than suggested in the International Hyperhidrosis Society guidelines.

Glycopyrrolate is available in 1 mg and 2 mg tablets; Dr. Wu starts patients at a dose of 1 mg twice a day, escalating by 1 mg per week until the “desired effects occur” or the patient has problems tolerating treatment because of side effects.

Other oral options include oxybutynin and propranolol. Sofpironium bromide, an analog of glycopyrrolate, is in the pipeline, he said.

During the interview, Dr. Wu discussed mydriasis, an adverse effect associated with both topical and systemic anticholinergic treatment. In the two pivotal phase 3 randomized trials of prescription glycopyrronium cloth (Qbrexza) for axillary hyperhidrosis, the incidence of mydriasis was 6.8% in 463 patients on active treatment for 4 weeks. Three-quarters of cases were unilateral. The mydriasis resolved without permanent treatment discontinuation in 27 of the 31 patients (J Am Acad Dermatol. 2019 Jan;80[1]:128-138.e2).

“The most important point is that patients need to be educated that they need to wash their hands very well after they apply it to the affected areas” to prevent accidental medication contact with the eyes, he advised.

Alarm bells can go off when a patient with anticholinergic therapy–induced mydriasis presents to an ED without mentioning their treatment status, Dr. Wu observed.

Dr. Wu had no relevant disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

To listen to the interview, click the play button below.

LAHAINA, HAWAII – Hyperhidrosis affects nearly 5% of the U.S. population, and in a survey of U.S. teenagers, about 17% reported excessive sweating, Jashin Wu, MD, said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

In an interview with MDedge reporter Bruce Jancin, Dr. Wu, founder of the Dermatology Research and Education Foundation, Irvine, Calif., discussed the off-label use of oral agents to treat hyperhidrosis. Dr. Wu said he is a fan of oral glycopyrrolate in particular, which he tends to use even earlier than suggested in the International Hyperhidrosis Society guidelines.

Glycopyrrolate is available in 1 mg and 2 mg tablets; Dr. Wu starts patients at a dose of 1 mg twice a day, escalating by 1 mg per week until the “desired effects occur” or the patient has problems tolerating treatment because of side effects.

Other oral options include oxybutynin and propranolol. Sofpironium bromide, an analog of glycopyrrolate, is in the pipeline, he said.

During the interview, Dr. Wu discussed mydriasis, an adverse effect associated with both topical and systemic anticholinergic treatment. In the two pivotal phase 3 randomized trials of prescription glycopyrronium cloth (Qbrexza) for axillary hyperhidrosis, the incidence of mydriasis was 6.8% in 463 patients on active treatment for 4 weeks. Three-quarters of cases were unilateral. The mydriasis resolved without permanent treatment discontinuation in 27 of the 31 patients (J Am Acad Dermatol. 2019 Jan;80[1]:128-138.e2).

“The most important point is that patients need to be educated that they need to wash their hands very well after they apply it to the affected areas” to prevent accidental medication contact with the eyes, he advised.

Alarm bells can go off when a patient with anticholinergic therapy–induced mydriasis presents to an ED without mentioning their treatment status, Dr. Wu observed.

Dr. Wu had no relevant disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

To listen to the interview, click the play button below.

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REPORTING FROM THE HAWAII DERMATOLOGY SEMINAR

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TENS Can Treat Migraine Attacks in the Emergency Department

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Key clinical point: Transcutaneous electrical nerve stimulation (TENS) is an effective option for treating migraine attacks in the emergency department.

Major finding: The verum group showed significant improvements on the visual analog scale change from 0 to 120 minutes (P less than .001) and a Likert-type verbal pain scale (P less than .001) compared with the sham group. The need for additional analgesics after 120 minutes was lower in the verum group vs. sham group (2.6% vs. 76.9%).

Study details: A randomized-controlled study evaluated the effectiveness of TENS for emergency treatment of migraine in the verum (n=39) and sham (n=39) groups.

Disclosures: The authors declared no conflicts of interest.

Citation: Hokenek NM et al. Am J Emerg Med. 2020 Jan 15. doi: 10.1016/j.ajem.2020.01.024.

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Key clinical point: Transcutaneous electrical nerve stimulation (TENS) is an effective option for treating migraine attacks in the emergency department.

Major finding: The verum group showed significant improvements on the visual analog scale change from 0 to 120 minutes (P less than .001) and a Likert-type verbal pain scale (P less than .001) compared with the sham group. The need for additional analgesics after 120 minutes was lower in the verum group vs. sham group (2.6% vs. 76.9%).

Study details: A randomized-controlled study evaluated the effectiveness of TENS for emergency treatment of migraine in the verum (n=39) and sham (n=39) groups.

Disclosures: The authors declared no conflicts of interest.

Citation: Hokenek NM et al. Am J Emerg Med. 2020 Jan 15. doi: 10.1016/j.ajem.2020.01.024.

 

Key clinical point: Transcutaneous electrical nerve stimulation (TENS) is an effective option for treating migraine attacks in the emergency department.

Major finding: The verum group showed significant improvements on the visual analog scale change from 0 to 120 minutes (P less than .001) and a Likert-type verbal pain scale (P less than .001) compared with the sham group. The need for additional analgesics after 120 minutes was lower in the verum group vs. sham group (2.6% vs. 76.9%).

Study details: A randomized-controlled study evaluated the effectiveness of TENS for emergency treatment of migraine in the verum (n=39) and sham (n=39) groups.

Disclosures: The authors declared no conflicts of interest.

Citation: Hokenek NM et al. Am J Emerg Med. 2020 Jan 15. doi: 10.1016/j.ajem.2020.01.024.

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Migraine is Bidirectionally Associated With Asthma

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Key clinical point: Migraine and asthma have a reciprocal association with each other.

Major finding: Patients with asthma had a 47% higher risk for migraine (P less than .001) than control participants, and patients with migraine had a 37% higher risk for asthma (P less than .001).

Study details: The data were obtained from 2 Korean longitudinal follow-up studies (Study 1: 113,059 patients with asthma and 113,059 control participants; Study 2: 36,044 patients with migraine and 114,176 control participants).

Disclosures: This study was partly supported by a grant from the National Research Foundation of Korea. The authors declared no conflicts of interest.

Citation: Kim SY et al. Sci Rep. 2019 Dec 4. doi: 10.1038/s41598-019-54972-8.

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Key clinical point: Migraine and asthma have a reciprocal association with each other.

Major finding: Patients with asthma had a 47% higher risk for migraine (P less than .001) than control participants, and patients with migraine had a 37% higher risk for asthma (P less than .001).

Study details: The data were obtained from 2 Korean longitudinal follow-up studies (Study 1: 113,059 patients with asthma and 113,059 control participants; Study 2: 36,044 patients with migraine and 114,176 control participants).

Disclosures: This study was partly supported by a grant from the National Research Foundation of Korea. The authors declared no conflicts of interest.

Citation: Kim SY et al. Sci Rep. 2019 Dec 4. doi: 10.1038/s41598-019-54972-8.

 

Key clinical point: Migraine and asthma have a reciprocal association with each other.

Major finding: Patients with asthma had a 47% higher risk for migraine (P less than .001) than control participants, and patients with migraine had a 37% higher risk for asthma (P less than .001).

Study details: The data were obtained from 2 Korean longitudinal follow-up studies (Study 1: 113,059 patients with asthma and 113,059 control participants; Study 2: 36,044 patients with migraine and 114,176 control participants).

Disclosures: This study was partly supported by a grant from the National Research Foundation of Korea. The authors declared no conflicts of interest.

Citation: Kim SY et al. Sci Rep. 2019 Dec 4. doi: 10.1038/s41598-019-54972-8.

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Higher Prevalence of Migraine in Women with Endometriosis

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Key clinical point: Women of reproductive age experiencing migraines should be screened for endometriosis.

Major finding: Migraine headache was more frequent in women with endometriosis than in those without endometriosis (35.2% vs. 17.4%; P = .003).

Study details: The data were obtained from a French case-control study of 314 nonpregnant women younger than 42 years.

Disclosures: The authors declared no conflicts of interest.

Citation: Maitrot-Mantelet L et al. Cephalalgia. 2019 Dec 6. doi: 10.1177/0333102419893965.

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Key clinical point: Women of reproductive age experiencing migraines should be screened for endometriosis.

Major finding: Migraine headache was more frequent in women with endometriosis than in those without endometriosis (35.2% vs. 17.4%; P = .003).

Study details: The data were obtained from a French case-control study of 314 nonpregnant women younger than 42 years.

Disclosures: The authors declared no conflicts of interest.

Citation: Maitrot-Mantelet L et al. Cephalalgia. 2019 Dec 6. doi: 10.1177/0333102419893965.

 

Key clinical point: Women of reproductive age experiencing migraines should be screened for endometriosis.

Major finding: Migraine headache was more frequent in women with endometriosis than in those without endometriosis (35.2% vs. 17.4%; P = .003).

Study details: The data were obtained from a French case-control study of 314 nonpregnant women younger than 42 years.

Disclosures: The authors declared no conflicts of interest.

Citation: Maitrot-Mantelet L et al. Cephalalgia. 2019 Dec 6. doi: 10.1177/0333102419893965.

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Shift Work Tied to Higher Migraine and Headache Risk

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Key clinical point: Shift workers are more likely to develop migraines and headaches than day workers.

Major finding: Shift workers had a 72% and 25% higher risk of developing migraine and unspecified headache, respectively, compared with day workers.

Study details: A longitudinal study included 2,952 individuals for the analyses of shift work and headache and 2,272 individuals for the analyses of shift work and migraine from the Danish PRISME cohort.

Disclosures: The study was funded by NordForsk, Nordic Program on Health and Welfare. The original PRISME study was supported by the Danish Working Environment Research Fund. The authors declared no conflicts of interest.

 

Citation: Appel AM et al. Int Arch Occup Environ Health. 2020 Jan 11. doi: 10.1007/s00420-019-01512-6.

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Key clinical point: Shift workers are more likely to develop migraines and headaches than day workers.

Major finding: Shift workers had a 72% and 25% higher risk of developing migraine and unspecified headache, respectively, compared with day workers.

Study details: A longitudinal study included 2,952 individuals for the analyses of shift work and headache and 2,272 individuals for the analyses of shift work and migraine from the Danish PRISME cohort.

Disclosures: The study was funded by NordForsk, Nordic Program on Health and Welfare. The original PRISME study was supported by the Danish Working Environment Research Fund. The authors declared no conflicts of interest.

 

Citation: Appel AM et al. Int Arch Occup Environ Health. 2020 Jan 11. doi: 10.1007/s00420-019-01512-6.

 

Key clinical point: Shift workers are more likely to develop migraines and headaches than day workers.

Major finding: Shift workers had a 72% and 25% higher risk of developing migraine and unspecified headache, respectively, compared with day workers.

Study details: A longitudinal study included 2,952 individuals for the analyses of shift work and headache and 2,272 individuals for the analyses of shift work and migraine from the Danish PRISME cohort.

Disclosures: The study was funded by NordForsk, Nordic Program on Health and Welfare. The original PRISME study was supported by the Danish Working Environment Research Fund. The authors declared no conflicts of interest.

 

Citation: Appel AM et al. Int Arch Occup Environ Health. 2020 Jan 11. doi: 10.1007/s00420-019-01512-6.

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For OUD patients, ‘a lot of work to be done’

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Most Americans who need medication-assisted treatment not getting it

– For Karen J. Hartwell, MD, few things in her clinical work bring more reward than providing medication-assisted treatment (MAT) to patients with opioid use disorder.

Doug Brunk/MDedge News
Dr. Karen J. Hartwell

“Seeing people get into recovery on buprenorphine is as exciting as seeing your first person respond to clozapine, or to see a depression remit on your selection of an antidepressant,” she said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “We know that medication-assisted treatment is underused and, sadly, relapse rates remain high.”

According to the Centers for Disease Control and Prevention, there were 70,237 drug-related overdose deaths in 2017 – 47,600 from prescription and illicit opioids. “This is being driven predominately by fentanyl and other high-potency synthetic opioids, followed by prescription opioids and heroin,” said Dr. Hartwell, an associate professor in the addiction sciences division in the department of psychiatry and behavioral sciences at the Medical University of South Carolina, Charleston.

There were an estimated 2 million Americans with an opioid use disorder (OUD) in 2018, she said, and more than 10 million misused prescription opioids. At the same time, prescriptions for opioids have dropped to lowest level in 10 years from a peak in 2012 of 81.3 prescriptions per 100 persons to 58.7 prescriptions per 100 persons in 2017 – total of more than 191 million scripts. “There is a decline in the number of opioid prescriptions, but there is still a lot of diversion, and there are some prescription ‘hot spots’ in the Southeast,” Dr. Hartwell said. “Heroin is a very low cost, and we’re wrestling with the issue of fentanyl.”

To complicate matters, most Americans with opioid use disorder are not in treatment. “In many people, the disorder is never diagnosed, and even fewer engage in care,” she said. “There are challenges with treatment retention, and even fewer achieve remission. There’s a lot of work to be done. One of which is the availability of medication-assisted treatment.”

Dr. Hartwell said that she knows of physician colleagues who have obtained a waiver to prescribe buprenorphine but have yet to prescribe it. “Some people may prefer to avoid the dance [of buprenorphine prescribing],” she said. “I’m here to advise you to dance.” Clinicians can learn about MAT waiver training opportunities by visiting the website of the Providers Clinical Support System, a program funded by the Substance Abuse and Mental Health Services Administration (SAMHSA).

Another option is to join a telementoring session on the topic facilitated by Project ECHO, or Extension for Community Healthcare Outcomes, which is being used by the University of New Mexico, Albuquerque. The goal of this model is to break down the walls between specialty and primary care by linking experts at an academic “hub” with primary care doctors and nurses in nearby communities.

“Our Project ECHO at the Medical University of South Carolina is twice a month on Fridays,” Dr. Hartwell said. “The first half is a case. The second half is a didactic [session], and you get a free hour of CME.”

The most common drugs used for medication-assisted treatment of opioid disorder are buprenorphine (a partial agonist), naltrexone (an antagonist), and methadone (a full agonist). Methadone retention generally is better than buprenorphine or naltrexone. The recommended treatment duration is 6-12 months, yet many studies demonstrate that many only stay on treatment for 30-60 days.



“You want to keep patients on treatment as long as they benefit from the medication,” Dr. Hartwell said. One large study of Medicaid claims data found that the risk of acute care service use and overdose were high following buprenorphine discontinuation, regardless of treatment duration. Superior outcomes became significant with treatment duration beyond 15 months, although rates of the primary adverse outcomes remained high (Am J Psychiatry. 2020 Feb 1;177[2]:117-24). About 5% of patients across all cohorts experienced one or more medically treated overdoses.

“One thing I don’t want is for people to drop out of treatment and not come back to see me,” Dr. Hartwell said. “This is a time for us to use our shared decision-making skills. I like to use the Tapering Readiness Inventory, a list of 16 questions. It asks such things as ‘Are you able to cope with difficult situations without using?’ and ‘Do you have all of the [drug] paraphernalia out of the house?’ We then have a discussion. If the patient decides to go ahead and do a taper, I always leave the door open. So, as that taper persists and someone says, ‘I’m starting to think about using, Doctor,’ I’ll put them back on [buprenorphine]. Or, if they come off the drug and they find themselves at risk of relapsing, they come back in and see me.”

There’s also some evidence that contingency management might be helpful, both in terms of opioid negative urines, and retention and treatment. Meanwhile, extended-release forms of buprenorphine are emerging.

In 2017, the Food and Drug Administration approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe OUD in adult patients who have initiated treatment with a transmucosal buprenorphine-containing product. “The recommendations are that you have about a 7-day lead-in of sublingual buprenorphine, and then 2 months of a 300-mg IV injection,” Dr. Hartwell said. “This is followed by either 100-mg injections monthly or 300-mg maintenance in select cases. There is some pain at the injection site. Some clinicians are getting around this by using a little bit of lidocaine prior to giving the injection.”

Another product, Brixadi, is an extended-release weekly (8 mg, 16 mg, 24 mg, 32 mg) and monthly (64 mg, 96 mg, 128 mg) buprenorphine injection used for the treatment of moderate to severe OUD. It is expected to be available in December 2020.

In 2016, the FDA approved Probuphine, the first buprenorphine implant for the maintenance treatment of opioid dependence. Probuphine is designed to provide a constant, low-level dose of buprenorphine for 6 months in patients who are already stable on low to moderate doses of other forms of buprenorphine, as part of a complete treatment program. “The 6-month duration kind of takes the issue of adherence off the table,” Dr. Hartwell said. “The caveat with this is that you have to be stable on 8 mg of buprenorphine per day or less. The majority of my patients require much higher doses.”

Dr. Hartwell reported having no relevant disclosures.

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Most Americans who need medication-assisted treatment not getting it

Most Americans who need medication-assisted treatment not getting it

– For Karen J. Hartwell, MD, few things in her clinical work bring more reward than providing medication-assisted treatment (MAT) to patients with opioid use disorder.

Doug Brunk/MDedge News
Dr. Karen J. Hartwell

“Seeing people get into recovery on buprenorphine is as exciting as seeing your first person respond to clozapine, or to see a depression remit on your selection of an antidepressant,” she said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “We know that medication-assisted treatment is underused and, sadly, relapse rates remain high.”

According to the Centers for Disease Control and Prevention, there were 70,237 drug-related overdose deaths in 2017 – 47,600 from prescription and illicit opioids. “This is being driven predominately by fentanyl and other high-potency synthetic opioids, followed by prescription opioids and heroin,” said Dr. Hartwell, an associate professor in the addiction sciences division in the department of psychiatry and behavioral sciences at the Medical University of South Carolina, Charleston.

There were an estimated 2 million Americans with an opioid use disorder (OUD) in 2018, she said, and more than 10 million misused prescription opioids. At the same time, prescriptions for opioids have dropped to lowest level in 10 years from a peak in 2012 of 81.3 prescriptions per 100 persons to 58.7 prescriptions per 100 persons in 2017 – total of more than 191 million scripts. “There is a decline in the number of opioid prescriptions, but there is still a lot of diversion, and there are some prescription ‘hot spots’ in the Southeast,” Dr. Hartwell said. “Heroin is a very low cost, and we’re wrestling with the issue of fentanyl.”

To complicate matters, most Americans with opioid use disorder are not in treatment. “In many people, the disorder is never diagnosed, and even fewer engage in care,” she said. “There are challenges with treatment retention, and even fewer achieve remission. There’s a lot of work to be done. One of which is the availability of medication-assisted treatment.”

Dr. Hartwell said that she knows of physician colleagues who have obtained a waiver to prescribe buprenorphine but have yet to prescribe it. “Some people may prefer to avoid the dance [of buprenorphine prescribing],” she said. “I’m here to advise you to dance.” Clinicians can learn about MAT waiver training opportunities by visiting the website of the Providers Clinical Support System, a program funded by the Substance Abuse and Mental Health Services Administration (SAMHSA).

Another option is to join a telementoring session on the topic facilitated by Project ECHO, or Extension for Community Healthcare Outcomes, which is being used by the University of New Mexico, Albuquerque. The goal of this model is to break down the walls between specialty and primary care by linking experts at an academic “hub” with primary care doctors and nurses in nearby communities.

“Our Project ECHO at the Medical University of South Carolina is twice a month on Fridays,” Dr. Hartwell said. “The first half is a case. The second half is a didactic [session], and you get a free hour of CME.”

The most common drugs used for medication-assisted treatment of opioid disorder are buprenorphine (a partial agonist), naltrexone (an antagonist), and methadone (a full agonist). Methadone retention generally is better than buprenorphine or naltrexone. The recommended treatment duration is 6-12 months, yet many studies demonstrate that many only stay on treatment for 30-60 days.



“You want to keep patients on treatment as long as they benefit from the medication,” Dr. Hartwell said. One large study of Medicaid claims data found that the risk of acute care service use and overdose were high following buprenorphine discontinuation, regardless of treatment duration. Superior outcomes became significant with treatment duration beyond 15 months, although rates of the primary adverse outcomes remained high (Am J Psychiatry. 2020 Feb 1;177[2]:117-24). About 5% of patients across all cohorts experienced one or more medically treated overdoses.

“One thing I don’t want is for people to drop out of treatment and not come back to see me,” Dr. Hartwell said. “This is a time for us to use our shared decision-making skills. I like to use the Tapering Readiness Inventory, a list of 16 questions. It asks such things as ‘Are you able to cope with difficult situations without using?’ and ‘Do you have all of the [drug] paraphernalia out of the house?’ We then have a discussion. If the patient decides to go ahead and do a taper, I always leave the door open. So, as that taper persists and someone says, ‘I’m starting to think about using, Doctor,’ I’ll put them back on [buprenorphine]. Or, if they come off the drug and they find themselves at risk of relapsing, they come back in and see me.”

There’s also some evidence that contingency management might be helpful, both in terms of opioid negative urines, and retention and treatment. Meanwhile, extended-release forms of buprenorphine are emerging.

In 2017, the Food and Drug Administration approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe OUD in adult patients who have initiated treatment with a transmucosal buprenorphine-containing product. “The recommendations are that you have about a 7-day lead-in of sublingual buprenorphine, and then 2 months of a 300-mg IV injection,” Dr. Hartwell said. “This is followed by either 100-mg injections monthly or 300-mg maintenance in select cases. There is some pain at the injection site. Some clinicians are getting around this by using a little bit of lidocaine prior to giving the injection.”

Another product, Brixadi, is an extended-release weekly (8 mg, 16 mg, 24 mg, 32 mg) and monthly (64 mg, 96 mg, 128 mg) buprenorphine injection used for the treatment of moderate to severe OUD. It is expected to be available in December 2020.

In 2016, the FDA approved Probuphine, the first buprenorphine implant for the maintenance treatment of opioid dependence. Probuphine is designed to provide a constant, low-level dose of buprenorphine for 6 months in patients who are already stable on low to moderate doses of other forms of buprenorphine, as part of a complete treatment program. “The 6-month duration kind of takes the issue of adherence off the table,” Dr. Hartwell said. “The caveat with this is that you have to be stable on 8 mg of buprenorphine per day or less. The majority of my patients require much higher doses.”

Dr. Hartwell reported having no relevant disclosures.

– For Karen J. Hartwell, MD, few things in her clinical work bring more reward than providing medication-assisted treatment (MAT) to patients with opioid use disorder.

Doug Brunk/MDedge News
Dr. Karen J. Hartwell

“Seeing people get into recovery on buprenorphine is as exciting as seeing your first person respond to clozapine, or to see a depression remit on your selection of an antidepressant,” she said at an annual psychopharmacology update held by the Nevada Psychiatric Association. “We know that medication-assisted treatment is underused and, sadly, relapse rates remain high.”

According to the Centers for Disease Control and Prevention, there were 70,237 drug-related overdose deaths in 2017 – 47,600 from prescription and illicit opioids. “This is being driven predominately by fentanyl and other high-potency synthetic opioids, followed by prescription opioids and heroin,” said Dr. Hartwell, an associate professor in the addiction sciences division in the department of psychiatry and behavioral sciences at the Medical University of South Carolina, Charleston.

There were an estimated 2 million Americans with an opioid use disorder (OUD) in 2018, she said, and more than 10 million misused prescription opioids. At the same time, prescriptions for opioids have dropped to lowest level in 10 years from a peak in 2012 of 81.3 prescriptions per 100 persons to 58.7 prescriptions per 100 persons in 2017 – total of more than 191 million scripts. “There is a decline in the number of opioid prescriptions, but there is still a lot of diversion, and there are some prescription ‘hot spots’ in the Southeast,” Dr. Hartwell said. “Heroin is a very low cost, and we’re wrestling with the issue of fentanyl.”

To complicate matters, most Americans with opioid use disorder are not in treatment. “In many people, the disorder is never diagnosed, and even fewer engage in care,” she said. “There are challenges with treatment retention, and even fewer achieve remission. There’s a lot of work to be done. One of which is the availability of medication-assisted treatment.”

Dr. Hartwell said that she knows of physician colleagues who have obtained a waiver to prescribe buprenorphine but have yet to prescribe it. “Some people may prefer to avoid the dance [of buprenorphine prescribing],” she said. “I’m here to advise you to dance.” Clinicians can learn about MAT waiver training opportunities by visiting the website of the Providers Clinical Support System, a program funded by the Substance Abuse and Mental Health Services Administration (SAMHSA).

Another option is to join a telementoring session on the topic facilitated by Project ECHO, or Extension for Community Healthcare Outcomes, which is being used by the University of New Mexico, Albuquerque. The goal of this model is to break down the walls between specialty and primary care by linking experts at an academic “hub” with primary care doctors and nurses in nearby communities.

“Our Project ECHO at the Medical University of South Carolina is twice a month on Fridays,” Dr. Hartwell said. “The first half is a case. The second half is a didactic [session], and you get a free hour of CME.”

The most common drugs used for medication-assisted treatment of opioid disorder are buprenorphine (a partial agonist), naltrexone (an antagonist), and methadone (a full agonist). Methadone retention generally is better than buprenorphine or naltrexone. The recommended treatment duration is 6-12 months, yet many studies demonstrate that many only stay on treatment for 30-60 days.



“You want to keep patients on treatment as long as they benefit from the medication,” Dr. Hartwell said. One large study of Medicaid claims data found that the risk of acute care service use and overdose were high following buprenorphine discontinuation, regardless of treatment duration. Superior outcomes became significant with treatment duration beyond 15 months, although rates of the primary adverse outcomes remained high (Am J Psychiatry. 2020 Feb 1;177[2]:117-24). About 5% of patients across all cohorts experienced one or more medically treated overdoses.

“One thing I don’t want is for people to drop out of treatment and not come back to see me,” Dr. Hartwell said. “This is a time for us to use our shared decision-making skills. I like to use the Tapering Readiness Inventory, a list of 16 questions. It asks such things as ‘Are you able to cope with difficult situations without using?’ and ‘Do you have all of the [drug] paraphernalia out of the house?’ We then have a discussion. If the patient decides to go ahead and do a taper, I always leave the door open. So, as that taper persists and someone says, ‘I’m starting to think about using, Doctor,’ I’ll put them back on [buprenorphine]. Or, if they come off the drug and they find themselves at risk of relapsing, they come back in and see me.”

There’s also some evidence that contingency management might be helpful, both in terms of opioid negative urines, and retention and treatment. Meanwhile, extended-release forms of buprenorphine are emerging.

In 2017, the Food and Drug Administration approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe OUD in adult patients who have initiated treatment with a transmucosal buprenorphine-containing product. “The recommendations are that you have about a 7-day lead-in of sublingual buprenorphine, and then 2 months of a 300-mg IV injection,” Dr. Hartwell said. “This is followed by either 100-mg injections monthly or 300-mg maintenance in select cases. There is some pain at the injection site. Some clinicians are getting around this by using a little bit of lidocaine prior to giving the injection.”

Another product, Brixadi, is an extended-release weekly (8 mg, 16 mg, 24 mg, 32 mg) and monthly (64 mg, 96 mg, 128 mg) buprenorphine injection used for the treatment of moderate to severe OUD. It is expected to be available in December 2020.

In 2016, the FDA approved Probuphine, the first buprenorphine implant for the maintenance treatment of opioid dependence. Probuphine is designed to provide a constant, low-level dose of buprenorphine for 6 months in patients who are already stable on low to moderate doses of other forms of buprenorphine, as part of a complete treatment program. “The 6-month duration kind of takes the issue of adherence off the table,” Dr. Hartwell said. “The caveat with this is that you have to be stable on 8 mg of buprenorphine per day or less. The majority of my patients require much higher doses.”

Dr. Hartwell reported having no relevant disclosures.

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