Patients with bipolar disorder who had undergone multiple manic episodes had significantly lower regional activation in the prefrontal‐striatal‐amygdala networks than single-episode patients, according to Logan Borgelt of the department of psychiatry and behavioral neuroscience at the University of Cincinnati and associates.

For the study, the investigators collected functional MRI data from 57 first‐episode manic patients (mean age, 19 years; mean Young Mania Rating Scale [YMRS] score, 26) and 50 multiepisode patients (mean age, 32 years; mean YMRS score, 21) who performed a continuous task with emotional distractions, as well as MR spectroscopy from 52 first-episode patients (mean age, 19 years; mean YMRS score, 26) and 54 multiepisode patients (mean age, 32 years; mean YMRS, 22). The study was published in Bipolar Disorders.

The investigation found that activation of the bilateral ventrolateral prefrontal cortex (P = .0122 for left; P = .0007 for right), anterior cingulate cortex (P less than .0001), orbitofrontal cortex (P = .0133), putamen (P = .0032), caudate (P = .0008), and amygdala (P = .0215) was significantly lower in multiepisode patients than in single-episode patients. Glutamate and N‐acetylaspartate concentration in the anterior cingulate cortex was also lower in multiepisode patients.

The age of multiepisode patients was, in general, not heavily associated with worse activation; only the right putamen (r = 0.30) and right thalamus (r = 0.30) reached a moderate effect size.

“Our findings are consistent with a hypothesized vicious cycle in which progressive atrophic changes in the prefrontal cortex are associated with functional decrements in affective networks, which in turn contribute to both further neuronal loss and clinical observations of accelerating symptomatic recurrence. Particularly striking is the widespread and unidirectional nature of the observed differences in activity, inviting speculation that these findings support suggestions of mitochondrial impairment or other metabolic inefficiency,” the investigators wrote.

Mr. Borgelt reported no conflicts. Three coauthors reported consulting with, receiving support and honoraria from, or serving on the speaker’s bureaus for numerous sources. The remaining coauthors did not report any conflicts of interest.

[email protected]

SOURCE: Borgelt L et al. Bipolar Disord. 2019 Apr 26. doi: 10.1111/bdi.12782.

Patients with bipolar disorder who had undergone multiple manic episodes had significantly lower regional activation in the prefrontal‐striatal‐amygdala networks than single-episode patients, according to Logan Borgelt of the department of psychiatry and behavioral neuroscience at the University of Cincinnati and associates.

For the study, the investigators collected functional MRI data from 57 first‐episode manic patients (mean age, 19 years; mean Young Mania Rating Scale [YMRS] score, 26) and 50 multiepisode patients (mean age, 32 years; mean YMRS score, 21) who performed a continuous task with emotional distractions, as well as MR spectroscopy from 52 first-episode patients (mean age, 19 years; mean YMRS score, 26) and 54 multiepisode patients (mean age, 32 years; mean YMRS, 22). The study was published in Bipolar Disorders.

The investigation found that activation of the bilateral ventrolateral prefrontal cortex (P = .0122 for left; P = .0007 for right), anterior cingulate cortex (P less than .0001), orbitofrontal cortex (P = .0133), putamen (P = .0032), caudate (P = .0008), and amygdala (P = .0215) was significantly lower in multiepisode patients than in single-episode patients. Glutamate and N‐acetylaspartate concentration in the anterior cingulate cortex was also lower in multiepisode patients.

The age of multiepisode patients was, in general, not heavily associated with worse activation; only the right putamen (r = 0.30) and right thalamus (r = 0.30) reached a moderate effect size.

“Our findings are consistent with a hypothesized vicious cycle in which progressive atrophic changes in the prefrontal cortex are associated with functional decrements in affective networks, which in turn contribute to both further neuronal loss and clinical observations of accelerating symptomatic recurrence. Particularly striking is the widespread and unidirectional nature of the observed differences in activity, inviting speculation that these findings support suggestions of mitochondrial impairment or other metabolic inefficiency,” the investigators wrote.

Mr. Borgelt reported no conflicts. Three coauthors reported consulting with, receiving support and honoraria from, or serving on the speaker’s bureaus for numerous sources. The remaining coauthors did not report any conflicts of interest.

[email protected]

SOURCE: Borgelt L et al. Bipolar Disord. 2019 Apr 26. doi: 10.1111/bdi.12782.

Patients with bipolar disorder who had undergone multiple manic episodes had significantly lower regional activation in the prefrontal‐striatal‐amygdala networks than single-episode patients, according to Logan Borgelt of the department of psychiatry and behavioral neuroscience at the University of Cincinnati and associates.

For the study, the investigators collected functional MRI data from 57 first‐episode manic patients (mean age, 19 years; mean Young Mania Rating Scale [YMRS] score, 26) and 50 multiepisode patients (mean age, 32 years; mean YMRS score, 21) who performed a continuous task with emotional distractions, as well as MR spectroscopy from 52 first-episode patients (mean age, 19 years; mean YMRS score, 26) and 54 multiepisode patients (mean age, 32 years; mean YMRS, 22). The study was published in Bipolar Disorders.

The investigation found that activation of the bilateral ventrolateral prefrontal cortex (P = .0122 for left; P = .0007 for right), anterior cingulate cortex (P less than .0001), orbitofrontal cortex (P = .0133), putamen (P = .0032), caudate (P = .0008), and amygdala (P = .0215) was significantly lower in multiepisode patients than in single-episode patients. Glutamate and N‐acetylaspartate concentration in the anterior cingulate cortex was also lower in multiepisode patients.

The age of multiepisode patients was, in general, not heavily associated with worse activation; only the right putamen (r = 0.30) and right thalamus (r = 0.30) reached a moderate effect size.

“Our findings are consistent with a hypothesized vicious cycle in which progressive atrophic changes in the prefrontal cortex are associated with functional decrements in affective networks, which in turn contribute to both further neuronal loss and clinical observations of accelerating symptomatic recurrence. Particularly striking is the widespread and unidirectional nature of the observed differences in activity, inviting speculation that these findings support suggestions of mitochondrial impairment or other metabolic inefficiency,” the investigators wrote.

Mr. Borgelt reported no conflicts. Three coauthors reported consulting with, receiving support and honoraria from, or serving on the speaker’s bureaus for numerous sources. The remaining coauthors did not report any conflicts of interest.

[email protected]

SOURCE: Borgelt L et al. Bipolar Disord. 2019 Apr 26. doi: 10.1111/bdi.12782.

Patients with sickle cell disease are 2.5 times more likely to be readmitted within 30 days of a hospital stay than those without SCD, according to the Agency for Healthcare Research and Quality.

The 30-day all-cause readmission rate for index stays with a principal diagnosis of SCD was 33.5% in 2016, compared with 12.5% for non-SCD hospital stays. Patients with a secondary diagnosis of SCD had readmission rates of 32.9% with a pain crisis and 21.0% without one, and the overall readmission rate for an index stay with any SCD diagnosis was 31.1%, Kathryn R. Fingar, PhD, MPH, of IBM Watson Health, Sacramento, Calif., and associates wrote in an AHRQ statistical brief.

When age is factored in, the readmission gap between a principal SCD diagnosis and non-SCD becomes even greater – and smaller. The difference was greatest for patients aged 18-34 years – 39.4% with a principal diagnosis of SCD versus 7.8% without any SCD – and then narrowed as patients got older. For those aged 65 years and older, the rates were 22.6% with a principal diagnosis of SCD and 15.9% without, the investigators reported.

The approximately 100,000 Americans with SCD accounted for 134,000 admissions in 2016, and more than three-quarters of those stays involved a pain crisis. A principal diagnosis of SCD was recorded for almost 96,000 of those visits, and nearly all (96%) of those stays involved a pain crisis. For those with a secondary diagnosis of SCD, the most common reasons for hospitalization were diseases of the respiratory system (14.3% of those stays) and infectious and parasitic diseases (13.2%).

Patients with SCD were more likely than non-SCD patients to be admitted from the ED (79.6% vs. 51.3%), and they were more likely to discharged against medical advice (4.1% vs. 1.2%). Among those who left the hospital against medical advice, patients with SCD were much more likely to be readmitted than those without SCD (46.6% vs. 26.5%), based on data from the AHRQ’s Nationwide Readmissions Database.

Improved treatment of complications has “reduced mortality rates so that nearly 95% of individuals born with SCD in the United States reach 18 years of age [but] limited knowledge of SCD treatment guidelines among healthcare professionals continues to pose a barrier to effective patient-provider relationships, and this barrier contributes to lower quality of life,” Dr. Fingar and associates wrote.

[email protected]

Patients with sickle cell disease are 2.5 times more likely to be readmitted within 30 days of a hospital stay than those without SCD, according to the Agency for Healthcare Research and Quality.

The 30-day all-cause readmission rate for index stays with a principal diagnosis of SCD was 33.5% in 2016, compared with 12.5% for non-SCD hospital stays. Patients with a secondary diagnosis of SCD had readmission rates of 32.9% with a pain crisis and 21.0% without one, and the overall readmission rate for an index stay with any SCD diagnosis was 31.1%, Kathryn R. Fingar, PhD, MPH, of IBM Watson Health, Sacramento, Calif., and associates wrote in an AHRQ statistical brief.

When age is factored in, the readmission gap between a principal SCD diagnosis and non-SCD becomes even greater – and smaller. The difference was greatest for patients aged 18-34 years – 39.4% with a principal diagnosis of SCD versus 7.8% without any SCD – and then narrowed as patients got older. For those aged 65 years and older, the rates were 22.6% with a principal diagnosis of SCD and 15.9% without, the investigators reported.

The approximately 100,000 Americans with SCD accounted for 134,000 admissions in 2016, and more than three-quarters of those stays involved a pain crisis. A principal diagnosis of SCD was recorded for almost 96,000 of those visits, and nearly all (96%) of those stays involved a pain crisis. For those with a secondary diagnosis of SCD, the most common reasons for hospitalization were diseases of the respiratory system (14.3% of those stays) and infectious and parasitic diseases (13.2%).

Patients with SCD were more likely than non-SCD patients to be admitted from the ED (79.6% vs. 51.3%), and they were more likely to discharged against medical advice (4.1% vs. 1.2%). Among those who left the hospital against medical advice, patients with SCD were much more likely to be readmitted than those without SCD (46.6% vs. 26.5%), based on data from the AHRQ’s Nationwide Readmissions Database.

Improved treatment of complications has “reduced mortality rates so that nearly 95% of individuals born with SCD in the United States reach 18 years of age [but] limited knowledge of SCD treatment guidelines among healthcare professionals continues to pose a barrier to effective patient-provider relationships, and this barrier contributes to lower quality of life,” Dr. Fingar and associates wrote.

[email protected]

Patients with sickle cell disease are 2.5 times more likely to be readmitted within 30 days of a hospital stay than those without SCD, according to the Agency for Healthcare Research and Quality.

The 30-day all-cause readmission rate for index stays with a principal diagnosis of SCD was 33.5% in 2016, compared with 12.5% for non-SCD hospital stays. Patients with a secondary diagnosis of SCD had readmission rates of 32.9% with a pain crisis and 21.0% without one, and the overall readmission rate for an index stay with any SCD diagnosis was 31.1%, Kathryn R. Fingar, PhD, MPH, of IBM Watson Health, Sacramento, Calif., and associates wrote in an AHRQ statistical brief.

When age is factored in, the readmission gap between a principal SCD diagnosis and non-SCD becomes even greater – and smaller. The difference was greatest for patients aged 18-34 years – 39.4% with a principal diagnosis of SCD versus 7.8% without any SCD – and then narrowed as patients got older. For those aged 65 years and older, the rates were 22.6% with a principal diagnosis of SCD and 15.9% without, the investigators reported.

The approximately 100,000 Americans with SCD accounted for 134,000 admissions in 2016, and more than three-quarters of those stays involved a pain crisis. A principal diagnosis of SCD was recorded for almost 96,000 of those visits, and nearly all (96%) of those stays involved a pain crisis. For those with a secondary diagnosis of SCD, the most common reasons for hospitalization were diseases of the respiratory system (14.3% of those stays) and infectious and parasitic diseases (13.2%).

Patients with SCD were more likely than non-SCD patients to be admitted from the ED (79.6% vs. 51.3%), and they were more likely to discharged against medical advice (4.1% vs. 1.2%). Among those who left the hospital against medical advice, patients with SCD were much more likely to be readmitted than those without SCD (46.6% vs. 26.5%), based on data from the AHRQ’s Nationwide Readmissions Database.

Improved treatment of complications has “reduced mortality rates so that nearly 95% of individuals born with SCD in the United States reach 18 years of age [but] limited knowledge of SCD treatment guidelines among healthcare professionals continues to pose a barrier to effective patient-provider relationships, and this barrier contributes to lower quality of life,” Dr. Fingar and associates wrote.

[email protected]

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

Federal health officials are seeking to update provisions of the Stark Physician Self-Referral law and the federal Anti-Kickback Statute in an effort to encourage more physicians to enter into value-based care arrangements.

The long-awaited reforms would create permanent exemptions and safe harbors to protect doctors participating in legitimate value-based arrangements. If finalized, the proposals also would offer flexibility for innovation and improved care coordination, while easing the compliance burden for health care professionals and maintaining safeguards against actual fraud and abuse, according to the U.S. Department of Health & Human Services.

The proposals acknowledge that the Stark Law has been an unintentional roadblock to value-based programs in part because it circumscribed parties’ exchanges of rewards for good behavior, said Donna K. Thiel, a Washington-based health law attorney.

“This should be helpful to doctors in that it removes some of the risk in such arrangements under the existing law,” she said in an interview. “If finalized, the new regulations will alleviate some roadblocks created by the Stark Law with respect to hospital-physician and other arrangements designed to enhance care coordination, improve quality, and reduce waste. Likewise, the changes to the [Anti-Kickback Statute] and Beneficiary Inducement laws loosen the reins on compensation arrangements that might be technical violations of those laws where the arrangement fosters [value-based payments] or efficiency, transparency, or innovation in the provision of health care.”

“These proposed rules would be a historic reform of how healthcare is regulated in America,” HHS Deputy Secretary Eric Hargan said in a statement. “They are part of a much broader effort to update, reform, and cut back our regulations to allow innovation toward a more affordable, higher quality, value-based health care system, while maintaining the important protections patients need.”

The two proposed measures – one rule by the Centers for Medicare and Medicaid Services and the other rule by the Office of Inspector General – include safe harbors for certain remuneration exchanged among participants in a value-based arrangement that fosters better coordinated and managed patient care. This includes care arrangements that improve quality, health outcomes, and efficiency, value-based arrangements with substantial downside financial risk, and value-based arrangements with full financial risk.

In addition, the proposals would protect certain tools and supports shared or delivered under patient engagement and support arrangements to improve quality, health outcomes, and efficiency. For example, a specialty physician practice could share data analytics services with a primary care physician practice in an effort to coordinate care and better manage shared patients, according to the HHS.

If finalized, the changes would modify existing safe harbor for personal services and management contracts to add flexibility with respect to outcomes-based payments and part-time arrangements, according to a fact sheet by the OIG. The rule would also modify existing safe harbors for local transportation to expand and modify mileage limits for rural areas and for transportation for discharged patients.

The proposals include guidance on several requirements that must be met for physicians and health care providers to comply with the Stark Law. For example, compensation provided to a doctor by another health care provider generally must be at fair-market value. As part of the proposals, the HHS offers guidance on how to determine if compensation meets this requirement and provides clarity on a range of other technical compliance requirements.

If the rules are approved, more physicians may be encouraged to become part of value-based arrangements, according to Anjali N.C. Downs, a health law attorney based in Washington.

[email protected]

Federal health officials are seeking to update provisions of the Stark Physician Self-Referral law and the federal Anti-Kickback Statute in an effort to encourage more physicians to enter into value-based care arrangements.

The long-awaited reforms would create permanent exemptions and safe harbors to protect doctors participating in legitimate value-based arrangements. If finalized, the proposals also would offer flexibility for innovation and improved care coordination, while easing the compliance burden for health care professionals and maintaining safeguards against actual fraud and abuse, according to the U.S. Department of Health & Human Services.

The proposals acknowledge that the Stark Law has been an unintentional roadblock to value-based programs in part because it circumscribed parties’ exchanges of rewards for good behavior, said Donna K. Thiel, a Washington-based health law attorney.

“This should be helpful to doctors in that it removes some of the risk in such arrangements under the existing law,” she said in an interview. “If finalized, the new regulations will alleviate some roadblocks created by the Stark Law with respect to hospital-physician and other arrangements designed to enhance care coordination, improve quality, and reduce waste. Likewise, the changes to the [Anti-Kickback Statute] and Beneficiary Inducement laws loosen the reins on compensation arrangements that might be technical violations of those laws where the arrangement fosters [value-based payments] or efficiency, transparency, or innovation in the provision of health care.”

“These proposed rules would be a historic reform of how healthcare is regulated in America,” HHS Deputy Secretary Eric Hargan said in a statement. “They are part of a much broader effort to update, reform, and cut back our regulations to allow innovation toward a more affordable, higher quality, value-based health care system, while maintaining the important protections patients need.”

The two proposed measures – one rule by the Centers for Medicare and Medicaid Services and the other rule by the Office of Inspector General – include safe harbors for certain remuneration exchanged among participants in a value-based arrangement that fosters better coordinated and managed patient care. This includes care arrangements that improve quality, health outcomes, and efficiency, value-based arrangements with substantial downside financial risk, and value-based arrangements with full financial risk.

In addition, the proposals would protect certain tools and supports shared or delivered under patient engagement and support arrangements to improve quality, health outcomes, and efficiency. For example, a specialty physician practice could share data analytics services with a primary care physician practice in an effort to coordinate care and better manage shared patients, according to the HHS.

If finalized, the changes would modify existing safe harbor for personal services and management contracts to add flexibility with respect to outcomes-based payments and part-time arrangements, according to a fact sheet by the OIG. The rule would also modify existing safe harbors for local transportation to expand and modify mileage limits for rural areas and for transportation for discharged patients.

The proposals include guidance on several requirements that must be met for physicians and health care providers to comply with the Stark Law. For example, compensation provided to a doctor by another health care provider generally must be at fair-market value. As part of the proposals, the HHS offers guidance on how to determine if compensation meets this requirement and provides clarity on a range of other technical compliance requirements.

If the rules are approved, more physicians may be encouraged to become part of value-based arrangements, according to Anjali N.C. Downs, a health law attorney based in Washington.

[email protected]

Federal health officials are seeking to update provisions of the Stark Physician Self-Referral law and the federal Anti-Kickback Statute in an effort to encourage more physicians to enter into value-based care arrangements.

The long-awaited reforms would create permanent exemptions and safe harbors to protect doctors participating in legitimate value-based arrangements. If finalized, the proposals also would offer flexibility for innovation and improved care coordination, while easing the compliance burden for health care professionals and maintaining safeguards against actual fraud and abuse, according to the U.S. Department of Health & Human Services.

The proposals acknowledge that the Stark Law has been an unintentional roadblock to value-based programs in part because it circumscribed parties’ exchanges of rewards for good behavior, said Donna K. Thiel, a Washington-based health law attorney.

“This should be helpful to doctors in that it removes some of the risk in such arrangements under the existing law,” she said in an interview. “If finalized, the new regulations will alleviate some roadblocks created by the Stark Law with respect to hospital-physician and other arrangements designed to enhance care coordination, improve quality, and reduce waste. Likewise, the changes to the [Anti-Kickback Statute] and Beneficiary Inducement laws loosen the reins on compensation arrangements that might be technical violations of those laws where the arrangement fosters [value-based payments] or efficiency, transparency, or innovation in the provision of health care.”

“These proposed rules would be a historic reform of how healthcare is regulated in America,” HHS Deputy Secretary Eric Hargan said in a statement. “They are part of a much broader effort to update, reform, and cut back our regulations to allow innovation toward a more affordable, higher quality, value-based health care system, while maintaining the important protections patients need.”

The two proposed measures – one rule by the Centers for Medicare and Medicaid Services and the other rule by the Office of Inspector General – include safe harbors for certain remuneration exchanged among participants in a value-based arrangement that fosters better coordinated and managed patient care. This includes care arrangements that improve quality, health outcomes, and efficiency, value-based arrangements with substantial downside financial risk, and value-based arrangements with full financial risk.

In addition, the proposals would protect certain tools and supports shared or delivered under patient engagement and support arrangements to improve quality, health outcomes, and efficiency. For example, a specialty physician practice could share data analytics services with a primary care physician practice in an effort to coordinate care and better manage shared patients, according to the HHS.

If finalized, the changes would modify existing safe harbor for personal services and management contracts to add flexibility with respect to outcomes-based payments and part-time arrangements, according to a fact sheet by the OIG. The rule would also modify existing safe harbors for local transportation to expand and modify mileage limits for rural areas and for transportation for discharged patients.

The proposals include guidance on several requirements that must be met for physicians and health care providers to comply with the Stark Law. For example, compensation provided to a doctor by another health care provider generally must be at fair-market value. As part of the proposals, the HHS offers guidance on how to determine if compensation meets this requirement and provides clarity on a range of other technical compliance requirements.

If the rules are approved, more physicians may be encouraged to become part of value-based arrangements, according to Anjali N.C. Downs, a health law attorney based in Washington.

[email protected]

Patients with stress urinary incontinence treated with synthetic mesh midurethral sling surgery had low reoperation rates at up to 9 years after surgery, according to a study published in Obstetrics & Gynecology.

Alexander A. Berger, MD, MPH, of the division of female pelvic medicine and reconstructive surgery at Kaiser Permanente in San Diego, and colleagues performed a retrospective cohort study of 17,030 patients with stress urinary incontinence (SUI) who underwent midurethral sling surgery between 2005 and 2016, examining the reoperation rate at 1 year, 5 years, and 9 years after the procedure, as well as secondary outcomes of mesh revision, mesh removal, and recurrence of SUI.

Overall, the rate of reoperation at 1 year was 2.1% (95% confidence interval, 1.9%-2.4%), was 4.5% at 5 years (95% CI, 4.1%-4.8%) and 6.0% at 9 years (95% CI, 5.5%-6.5%). Compared with white patients, there was a lower rate of reoperation among Asian or Pacific Islander patients.

The rate of reoperation involving mesh removal was 0.7% at 1 year (95% CI, 0.6%-0.8%), 1.0% at 5 years (95% CI, 0.8%-1.1%) and 1.1% at 9 years (95% CI, 0.9%-1.3%).

The rate of recurrent SUI leading to operation was 1.6% at 1 year (95% CI, 1.4%-1.8%), 3.9% at 5 years (95% CI, 3.5%-4.2%) and 5.2% at 9 years (95% CI, 4.7%-5.7%), with more reoperations occurring for patients who received a single-incision sling, rather than a retropubic sling (adjusted hazard ratio, 1.5; 95% CI, 1.06-2.11; P = .03), Dr. Berger and associates wrote.

Urogynecologists, ob.gyns., and urologists who use mesh for slings and reconstructive surgery have struggled to recommend synthetic mesh slings to their patients with SUI, said Patrick J. Woodman, DO, MS, program director of obstetrics and gynecology residency at Providence Health Ascension Macomb-Oakland, Warren (Mich.) Campus, said in an interview. In 2008, the Food and Drug Administration issued a public health notification for transvaginal placement of surgical mesh in patients with pelvic organ prolapse and SUI.

“Although some of the recommendations first made by the FDA were reasoned and reasonable, such as the need for direct, premarket, patient studies instead of the mostly administrative 510(k) ‘similar-to’ process that had been used previously, physicians and patients had been eagerly awaiting the outcomes of some of these clinical studies that would help answer some of the safety and efficacy questions that had been dogging the transvaginal use of mesh material for years,” he said.

“But, to everyone’s surprise, in April [2019] they called for a recall of all vaginal mesh products, even before the study data could be analyzed, written up and released,” added Dr. Woodman. “Companies were forced to halt production, pull stocks from the shelves, and halt and reverse shipments.”

One reason the results by Berger et al. show midurethral slings have had a good safety record is because of a small incision size and low amount of mesh, noted Dr. Woodman, who was not involved with the study. “This article seems to underline and highlight the fact that reoperation is rare for midurethral slings (for all reasons), but particularly for mesh erosion or exposure. This is well within the experience of most female pelvic medicine and reconstructive surgery and urologic surgeons, and incredibly less than the 8%-24% of mesh exposures reported in the variety of mesh exposure literature on vaginal mesh procedures.”

Despite this safety record, some women may still experience adverse events with midurethral slings, admitted Dr. Woodman. “The fact remains, if a surgeon drags a large piece of synthetic fabric through a ‘clean-contaminated’ vaginal environment, and buries this mesh under the skin of the vagina, and then rests this mesh against a long incision, some women’s immune systems will not be able to handle the resultant inflammation and bacterial load, despite antibiotics, vaginal prepping, and any number of coatings or soakings of the mesh.”

The researchers noted the study’s retrospective nature is one potential limitation, and the data has not been compiled by surgeon type or skill, or considered patients with complications that did not choose reoperations.

“But, the flip side is also true,” said Dr. Woodman, an Ob.Gyn News editorial advisor. “There may have been a number of individuals who had a surgical removal who did not need or warrant it due to the societal, family, or legal ‘suggestion’ that the mesh is now ‘dangerous’ and must be removed at all costs.”

Berger et al. “hit the nail on the head” with the study, including a large amount of patients that demonstrates the safety of midurethral slings, he said. “We need a solid body of unquestioned evidence of safety and effectiveness from which to base solid, evidence-based medical decisions. If there is a way to effectively use mesh to reinforce a vaginal repair in a high-risk woman (for example, with previous failed surgeries), then we have to take the stigma away from its use: because no one wants to use it now, even if it could help.

“The best we can hope for, as physicians, is a rehabilitation of reputation for vaginal mesh,” he concluded.

The study was supported by a grant from the Regional Research Committee of Kaiser Permanente Southern California. One coauthor reported receiving royalties from UptoDate and the American Urogynecologic Society Board Member for travel for board meetings. The other authors reported no relevant conflicts of interest. Dr. Woodman said he had no relevant financial disclosures.*

SOURCE: Berger AA et al. Obstet Gynecol. 2019 Oct 10. doi:10.1097/AOG.0000000000003526.

* Updated 10/14/2019

Patients with stress urinary incontinence treated with synthetic mesh midurethral sling surgery had low reoperation rates at up to 9 years after surgery, according to a study published in Obstetrics & Gynecology.

Alexander A. Berger, MD, MPH, of the division of female pelvic medicine and reconstructive surgery at Kaiser Permanente in San Diego, and colleagues performed a retrospective cohort study of 17,030 patients with stress urinary incontinence (SUI) who underwent midurethral sling surgery between 2005 and 2016, examining the reoperation rate at 1 year, 5 years, and 9 years after the procedure, as well as secondary outcomes of mesh revision, mesh removal, and recurrence of SUI.

Overall, the rate of reoperation at 1 year was 2.1% (95% confidence interval, 1.9%-2.4%), was 4.5% at 5 years (95% CI, 4.1%-4.8%) and 6.0% at 9 years (95% CI, 5.5%-6.5%). Compared with white patients, there was a lower rate of reoperation among Asian or Pacific Islander patients.

The rate of reoperation involving mesh removal was 0.7% at 1 year (95% CI, 0.6%-0.8%), 1.0% at 5 years (95% CI, 0.8%-1.1%) and 1.1% at 9 years (95% CI, 0.9%-1.3%).

The rate of recurrent SUI leading to operation was 1.6% at 1 year (95% CI, 1.4%-1.8%), 3.9% at 5 years (95% CI, 3.5%-4.2%) and 5.2% at 9 years (95% CI, 4.7%-5.7%), with more reoperations occurring for patients who received a single-incision sling, rather than a retropubic sling (adjusted hazard ratio, 1.5; 95% CI, 1.06-2.11; P = .03), Dr. Berger and associates wrote.

Urogynecologists, ob.gyns., and urologists who use mesh for slings and reconstructive surgery have struggled to recommend synthetic mesh slings to their patients with SUI, said Patrick J. Woodman, DO, MS, program director of obstetrics and gynecology residency at Providence Health Ascension Macomb-Oakland, Warren (Mich.) Campus, said in an interview. In 2008, the Food and Drug Administration issued a public health notification for transvaginal placement of surgical mesh in patients with pelvic organ prolapse and SUI.

“Although some of the recommendations first made by the FDA were reasoned and reasonable, such as the need for direct, premarket, patient studies instead of the mostly administrative 510(k) ‘similar-to’ process that had been used previously, physicians and patients had been eagerly awaiting the outcomes of some of these clinical studies that would help answer some of the safety and efficacy questions that had been dogging the transvaginal use of mesh material for years,” he said.

“But, to everyone’s surprise, in April [2019] they called for a recall of all vaginal mesh products, even before the study data could be analyzed, written up and released,” added Dr. Woodman. “Companies were forced to halt production, pull stocks from the shelves, and halt and reverse shipments.”

One reason the results by Berger et al. show midurethral slings have had a good safety record is because of a small incision size and low amount of mesh, noted Dr. Woodman, who was not involved with the study. “This article seems to underline and highlight the fact that reoperation is rare for midurethral slings (for all reasons), but particularly for mesh erosion or exposure. This is well within the experience of most female pelvic medicine and reconstructive surgery and urologic surgeons, and incredibly less than the 8%-24% of mesh exposures reported in the variety of mesh exposure literature on vaginal mesh procedures.”

Despite this safety record, some women may still experience adverse events with midurethral slings, admitted Dr. Woodman. “The fact remains, if a surgeon drags a large piece of synthetic fabric through a ‘clean-contaminated’ vaginal environment, and buries this mesh under the skin of the vagina, and then rests this mesh against a long incision, some women’s immune systems will not be able to handle the resultant inflammation and bacterial load, despite antibiotics, vaginal prepping, and any number of coatings or soakings of the mesh.”

The researchers noted the study’s retrospective nature is one potential limitation, and the data has not been compiled by surgeon type or skill, or considered patients with complications that did not choose reoperations.

“But, the flip side is also true,” said Dr. Woodman, an Ob.Gyn News editorial advisor. “There may have been a number of individuals who had a surgical removal who did not need or warrant it due to the societal, family, or legal ‘suggestion’ that the mesh is now ‘dangerous’ and must be removed at all costs.”

Berger et al. “hit the nail on the head” with the study, including a large amount of patients that demonstrates the safety of midurethral slings, he said. “We need a solid body of unquestioned evidence of safety and effectiveness from which to base solid, evidence-based medical decisions. If there is a way to effectively use mesh to reinforce a vaginal repair in a high-risk woman (for example, with previous failed surgeries), then we have to take the stigma away from its use: because no one wants to use it now, even if it could help.

“The best we can hope for, as physicians, is a rehabilitation of reputation for vaginal mesh,” he concluded.

The study was supported by a grant from the Regional Research Committee of Kaiser Permanente Southern California. One coauthor reported receiving royalties from UptoDate and the American Urogynecologic Society Board Member for travel for board meetings. The other authors reported no relevant conflicts of interest. Dr. Woodman said he had no relevant financial disclosures.*

SOURCE: Berger AA et al. Obstet Gynecol. 2019 Oct 10. doi:10.1097/AOG.0000000000003526.

* Updated 10/14/2019

Patients with stress urinary incontinence treated with synthetic mesh midurethral sling surgery had low reoperation rates at up to 9 years after surgery, according to a study published in Obstetrics & Gynecology.

Alexander A. Berger, MD, MPH, of the division of female pelvic medicine and reconstructive surgery at Kaiser Permanente in San Diego, and colleagues performed a retrospective cohort study of 17,030 patients with stress urinary incontinence (SUI) who underwent midurethral sling surgery between 2005 and 2016, examining the reoperation rate at 1 year, 5 years, and 9 years after the procedure, as well as secondary outcomes of mesh revision, mesh removal, and recurrence of SUI.

Overall, the rate of reoperation at 1 year was 2.1% (95% confidence interval, 1.9%-2.4%), was 4.5% at 5 years (95% CI, 4.1%-4.8%) and 6.0% at 9 years (95% CI, 5.5%-6.5%). Compared with white patients, there was a lower rate of reoperation among Asian or Pacific Islander patients.

The rate of reoperation involving mesh removal was 0.7% at 1 year (95% CI, 0.6%-0.8%), 1.0% at 5 years (95% CI, 0.8%-1.1%) and 1.1% at 9 years (95% CI, 0.9%-1.3%).

The rate of recurrent SUI leading to operation was 1.6% at 1 year (95% CI, 1.4%-1.8%), 3.9% at 5 years (95% CI, 3.5%-4.2%) and 5.2% at 9 years (95% CI, 4.7%-5.7%), with more reoperations occurring for patients who received a single-incision sling, rather than a retropubic sling (adjusted hazard ratio, 1.5; 95% CI, 1.06-2.11; P = .03), Dr. Berger and associates wrote.

Urogynecologists, ob.gyns., and urologists who use mesh for slings and reconstructive surgery have struggled to recommend synthetic mesh slings to their patients with SUI, said Patrick J. Woodman, DO, MS, program director of obstetrics and gynecology residency at Providence Health Ascension Macomb-Oakland, Warren (Mich.) Campus, said in an interview. In 2008, the Food and Drug Administration issued a public health notification for transvaginal placement of surgical mesh in patients with pelvic organ prolapse and SUI.

“Although some of the recommendations first made by the FDA were reasoned and reasonable, such as the need for direct, premarket, patient studies instead of the mostly administrative 510(k) ‘similar-to’ process that had been used previously, physicians and patients had been eagerly awaiting the outcomes of some of these clinical studies that would help answer some of the safety and efficacy questions that had been dogging the transvaginal use of mesh material for years,” he said.

“But, to everyone’s surprise, in April [2019] they called for a recall of all vaginal mesh products, even before the study data could be analyzed, written up and released,” added Dr. Woodman. “Companies were forced to halt production, pull stocks from the shelves, and halt and reverse shipments.”

One reason the results by Berger et al. show midurethral slings have had a good safety record is because of a small incision size and low amount of mesh, noted Dr. Woodman, who was not involved with the study. “This article seems to underline and highlight the fact that reoperation is rare for midurethral slings (for all reasons), but particularly for mesh erosion or exposure. This is well within the experience of most female pelvic medicine and reconstructive surgery and urologic surgeons, and incredibly less than the 8%-24% of mesh exposures reported in the variety of mesh exposure literature on vaginal mesh procedures.”

Despite this safety record, some women may still experience adverse events with midurethral slings, admitted Dr. Woodman. “The fact remains, if a surgeon drags a large piece of synthetic fabric through a ‘clean-contaminated’ vaginal environment, and buries this mesh under the skin of the vagina, and then rests this mesh against a long incision, some women’s immune systems will not be able to handle the resultant inflammation and bacterial load, despite antibiotics, vaginal prepping, and any number of coatings or soakings of the mesh.”

The researchers noted the study’s retrospective nature is one potential limitation, and the data has not been compiled by surgeon type or skill, or considered patients with complications that did not choose reoperations.

“But, the flip side is also true,” said Dr. Woodman, an Ob.Gyn News editorial advisor. “There may have been a number of individuals who had a surgical removal who did not need or warrant it due to the societal, family, or legal ‘suggestion’ that the mesh is now ‘dangerous’ and must be removed at all costs.”

Berger et al. “hit the nail on the head” with the study, including a large amount of patients that demonstrates the safety of midurethral slings, he said. “We need a solid body of unquestioned evidence of safety and effectiveness from which to base solid, evidence-based medical decisions. If there is a way to effectively use mesh to reinforce a vaginal repair in a high-risk woman (for example, with previous failed surgeries), then we have to take the stigma away from its use: because no one wants to use it now, even if it could help.

“The best we can hope for, as physicians, is a rehabilitation of reputation for vaginal mesh,” he concluded.

The study was supported by a grant from the Regional Research Committee of Kaiser Permanente Southern California. One coauthor reported receiving royalties from UptoDate and the American Urogynecologic Society Board Member for travel for board meetings. The other authors reported no relevant conflicts of interest. Dr. Woodman said he had no relevant financial disclosures.*

SOURCE: Berger AA et al. Obstet Gynecol. 2019 Oct 10. doi:10.1097/AOG.0000000000003526.

* Updated 10/14/2019

SAN FRANCISCO – Reducing the dual antiplatelet therapy period to 3 months after implantation of Ultimaster sirolimus-eluting stent was noninferior to a longer duration of DAPT in a historical cohort, results from a prospective study showed.

Doug Brunk/MDedge News

In addition, P2Y12 inhibitor monotherapy was almost equivalent to aspirin monotherapy after 3 months in terms of both bleeding and thrombotic events.

“Recent guidelines recommend short DAPT up to 3 months, only in high bleeding risk patients,” lead investigator Ken Kozuma, MD, said during a media briefing at the Transcatheter Cardiovascular Therapeutics annual meeting. “However, short-term DAPT may be beneficial for any patients. Aspirin may be more associated with bleeding complication than P2Y12 receptor inhibitors.”

In a single-arm registry trial known as MODEL U-SES, Dr. Kozuma, of Teikyo University Hospital in Tokyo, and colleagues at 65 sites in Japan prospectively evaluated the safety of 3-month DAPT after implantation of the Ultimaster bioresorbable polymer sirolimus-eluting stent (BP-SES). The secondary objective was to investigate the appropriateness of P2Y12 receptor inhibitor monotherapy compared with aspirin monotherapy after 3 months. The researchers enrolled 1,695 patients with a mean age of 70 years who were treated with U-SES and considered appropriate for 3-month DAPT after implantation.

The primary endpoint was a composite endpoint of all-cause death, myocardial infarction, stroke (ischemic and hemorrhagic), Academic Research Consortium (ARC) definite/probable stent thrombosis, and serious bleeding (Bleeding Academic Research Consortium [BARC] 3 or 5) during the 12 months after stent implantation. Major secondary endpoints included a comparison of the incidence of each event for each continued antiplatelet drug.

Of the 1,695 patients enrolled, 1,686 completed 3-month clinical follow-up while 1,616 completed 1-year clinical follow-up. Patient-level adjusted historical data from 542 subjects in the CENTURY II cohort was used as the control group. Patients in that trial received the same stent but took DAPT for 1 year.

Dr. Kozuma reported that the primary endpoint occurred in 4.3% of patients in the MODEL U-SES group, compared with 5.7% of patients in the CENTURY II BP-SES group, a difference of –3.17%, which demonstrated noninferiority of the trial (P less than .001). At 3 months, P2Y12 inhibitor monotherapy was equivalent to aspirin monotherapy in terms of both bleeding and thrombotic events (2.5% in each modality; hazard ratio, 1.14; P = 0.71).

Dr. Kozuma acknowledged certain limitations of the trial, including the fact that propensity score adjusted analysis “may not compensate the selection bias of this study sufficiently, since considerable baseline difference was observed. Also, comparison between aspirin and P2Y12 receptor inhibitors was not randomized so that the safety and efficacy of each antiplatelet monotherapy cannot be conclusive.”

Despite these limitations, he concluded that the trial “demonstrated that 3-month DAPT was noninferior to an adjusted cohort of longer DAPT after BP-SES implantation in net adverse clinical events. Direct comparison between P2Y12 inhibitor and aspirin would be necessary to confirm the efficacy and safety of P2Y12 inhibitor monotherapy in a randomized fashion.”

The meeting was sponsored by the Cardiovascular Research Foundation.

Terumo sponsored the trial. Dr. Kozuma disclosed that he serves on the scientific advisory boards for and has received honoraria from Terumo, Abbott Vascular Japan, Boston Scientific Japan, Daiichi-Sankyo, Sanofi, Bayer, Boehringer Ingelheim and Bristol-Meyers Squibb.

[email protected]

SOURCE: Kozuma K et al. TCT 2019, late-breaking presentation.

SAN FRANCISCO – Reducing the dual antiplatelet therapy period to 3 months after implantation of Ultimaster sirolimus-eluting stent was noninferior to a longer duration of DAPT in a historical cohort, results from a prospective study showed.

Doug Brunk/MDedge News

In addition, P2Y12 inhibitor monotherapy was almost equivalent to aspirin monotherapy after 3 months in terms of both bleeding and thrombotic events.

“Recent guidelines recommend short DAPT up to 3 months, only in high bleeding risk patients,” lead investigator Ken Kozuma, MD, said during a media briefing at the Transcatheter Cardiovascular Therapeutics annual meeting. “However, short-term DAPT may be beneficial for any patients. Aspirin may be more associated with bleeding complication than P2Y12 receptor inhibitors.”

In a single-arm registry trial known as MODEL U-SES, Dr. Kozuma, of Teikyo University Hospital in Tokyo, and colleagues at 65 sites in Japan prospectively evaluated the safety of 3-month DAPT after implantation of the Ultimaster bioresorbable polymer sirolimus-eluting stent (BP-SES). The secondary objective was to investigate the appropriateness of P2Y12 receptor inhibitor monotherapy compared with aspirin monotherapy after 3 months. The researchers enrolled 1,695 patients with a mean age of 70 years who were treated with U-SES and considered appropriate for 3-month DAPT after implantation.

The primary endpoint was a composite endpoint of all-cause death, myocardial infarction, stroke (ischemic and hemorrhagic), Academic Research Consortium (ARC) definite/probable stent thrombosis, and serious bleeding (Bleeding Academic Research Consortium [BARC] 3 or 5) during the 12 months after stent implantation. Major secondary endpoints included a comparison of the incidence of each event for each continued antiplatelet drug.

Of the 1,695 patients enrolled, 1,686 completed 3-month clinical follow-up while 1,616 completed 1-year clinical follow-up. Patient-level adjusted historical data from 542 subjects in the CENTURY II cohort was used as the control group. Patients in that trial received the same stent but took DAPT for 1 year.

Dr. Kozuma reported that the primary endpoint occurred in 4.3% of patients in the MODEL U-SES group, compared with 5.7% of patients in the CENTURY II BP-SES group, a difference of –3.17%, which demonstrated noninferiority of the trial (P less than .001). At 3 months, P2Y12 inhibitor monotherapy was equivalent to aspirin monotherapy in terms of both bleeding and thrombotic events (2.5% in each modality; hazard ratio, 1.14; P = 0.71).

Dr. Kozuma acknowledged certain limitations of the trial, including the fact that propensity score adjusted analysis “may not compensate the selection bias of this study sufficiently, since considerable baseline difference was observed. Also, comparison between aspirin and P2Y12 receptor inhibitors was not randomized so that the safety and efficacy of each antiplatelet monotherapy cannot be conclusive.”

Despite these limitations, he concluded that the trial “demonstrated that 3-month DAPT was noninferior to an adjusted cohort of longer DAPT after BP-SES implantation in net adverse clinical events. Direct comparison between P2Y12 inhibitor and aspirin would be necessary to confirm the efficacy and safety of P2Y12 inhibitor monotherapy in a randomized fashion.”

The meeting was sponsored by the Cardiovascular Research Foundation.

Terumo sponsored the trial. Dr. Kozuma disclosed that he serves on the scientific advisory boards for and has received honoraria from Terumo, Abbott Vascular Japan, Boston Scientific Japan, Daiichi-Sankyo, Sanofi, Bayer, Boehringer Ingelheim and Bristol-Meyers Squibb.

[email protected]

SOURCE: Kozuma K et al. TCT 2019, late-breaking presentation.

SAN FRANCISCO – Reducing the dual antiplatelet therapy period to 3 months after implantation of Ultimaster sirolimus-eluting stent was noninferior to a longer duration of DAPT in a historical cohort, results from a prospective study showed.

Doug Brunk/MDedge News

In addition, P2Y12 inhibitor monotherapy was almost equivalent to aspirin monotherapy after 3 months in terms of both bleeding and thrombotic events.

“Recent guidelines recommend short DAPT up to 3 months, only in high bleeding risk patients,” lead investigator Ken Kozuma, MD, said during a media briefing at the Transcatheter Cardiovascular Therapeutics annual meeting. “However, short-term DAPT may be beneficial for any patients. Aspirin may be more associated with bleeding complication than P2Y12 receptor inhibitors.”

In a single-arm registry trial known as MODEL U-SES, Dr. Kozuma, of Teikyo University Hospital in Tokyo, and colleagues at 65 sites in Japan prospectively evaluated the safety of 3-month DAPT after implantation of the Ultimaster bioresorbable polymer sirolimus-eluting stent (BP-SES). The secondary objective was to investigate the appropriateness of P2Y12 receptor inhibitor monotherapy compared with aspirin monotherapy after 3 months. The researchers enrolled 1,695 patients with a mean age of 70 years who were treated with U-SES and considered appropriate for 3-month DAPT after implantation.

The primary endpoint was a composite endpoint of all-cause death, myocardial infarction, stroke (ischemic and hemorrhagic), Academic Research Consortium (ARC) definite/probable stent thrombosis, and serious bleeding (Bleeding Academic Research Consortium [BARC] 3 or 5) during the 12 months after stent implantation. Major secondary endpoints included a comparison of the incidence of each event for each continued antiplatelet drug.

Of the 1,695 patients enrolled, 1,686 completed 3-month clinical follow-up while 1,616 completed 1-year clinical follow-up. Patient-level adjusted historical data from 542 subjects in the CENTURY II cohort was used as the control group. Patients in that trial received the same stent but took DAPT for 1 year.

Dr. Kozuma reported that the primary endpoint occurred in 4.3% of patients in the MODEL U-SES group, compared with 5.7% of patients in the CENTURY II BP-SES group, a difference of –3.17%, which demonstrated noninferiority of the trial (P less than .001). At 3 months, P2Y12 inhibitor monotherapy was equivalent to aspirin monotherapy in terms of both bleeding and thrombotic events (2.5% in each modality; hazard ratio, 1.14; P = 0.71).

Dr. Kozuma acknowledged certain limitations of the trial, including the fact that propensity score adjusted analysis “may not compensate the selection bias of this study sufficiently, since considerable baseline difference was observed. Also, comparison between aspirin and P2Y12 receptor inhibitors was not randomized so that the safety and efficacy of each antiplatelet monotherapy cannot be conclusive.”

Despite these limitations, he concluded that the trial “demonstrated that 3-month DAPT was noninferior to an adjusted cohort of longer DAPT after BP-SES implantation in net adverse clinical events. Direct comparison between P2Y12 inhibitor and aspirin would be necessary to confirm the efficacy and safety of P2Y12 inhibitor monotherapy in a randomized fashion.”

The meeting was sponsored by the Cardiovascular Research Foundation.

Terumo sponsored the trial. Dr. Kozuma disclosed that he serves on the scientific advisory boards for and has received honoraria from Terumo, Abbott Vascular Japan, Boston Scientific Japan, Daiichi-Sankyo, Sanofi, Bayer, Boehringer Ingelheim and Bristol-Meyers Squibb.

[email protected]

SOURCE: Kozuma K et al. TCT 2019, late-breaking presentation.

Almost all of Medicare’s 58 million enrollees had a blood pressure screening in 2017, and just under 90% saw a physician during the year, according to new data released by the Centers for Medicare & Medicaid Services.

The latest edition of Medicare Beneficiaries at a Glance takes a look at some of the services provided in 2017, and BP checks were high on the list, with 96% of enrollees getting screened. BP was also prominent on another list featured in the Medicare snapshot for 2017, as hypertension was the most common chronic condition among beneficiaries with a prevalence of 58%, the CMS said.

A second glance at the report shows that 41% of enrollees had high cholesterol that year, making it the next-most common chronic condition, with arthritis third at 33%, the CMS said. Diabetes was fourth and heart disease was fifth, but rounding gives them the same prevalence of 27%.

[email protected]

Almost all of Medicare’s 58 million enrollees had a blood pressure screening in 2017, and just under 90% saw a physician during the year, according to new data released by the Centers for Medicare & Medicaid Services.

The latest edition of Medicare Beneficiaries at a Glance takes a look at some of the services provided in 2017, and BP checks were high on the list, with 96% of enrollees getting screened. BP was also prominent on another list featured in the Medicare snapshot for 2017, as hypertension was the most common chronic condition among beneficiaries with a prevalence of 58%, the CMS said.

A second glance at the report shows that 41% of enrollees had high cholesterol that year, making it the next-most common chronic condition, with arthritis third at 33%, the CMS said. Diabetes was fourth and heart disease was fifth, but rounding gives them the same prevalence of 27%.

[email protected]

Almost all of Medicare’s 58 million enrollees had a blood pressure screening in 2017, and just under 90% saw a physician during the year, according to new data released by the Centers for Medicare & Medicaid Services.

The latest edition of Medicare Beneficiaries at a Glance takes a look at some of the services provided in 2017, and BP checks were high on the list, with 96% of enrollees getting screened. BP was also prominent on another list featured in the Medicare snapshot for 2017, as hypertension was the most common chronic condition among beneficiaries with a prevalence of 58%, the CMS said.

A second glance at the report shows that 41% of enrollees had high cholesterol that year, making it the next-most common chronic condition, with arthritis third at 33%, the CMS said. Diabetes was fourth and heart disease was fifth, but rounding gives them the same prevalence of 27%.

[email protected]

It is rare in this modern era for medicine to confront an infectious disease for which there is no cure. Today, there are comparatively few infectious diseases (in the developed world and in places where money is no object) for which medicine cannot offer at least a glimmer of hope to infected patients. Even at its most futile, modern medicine has achieved vast improvements in the efficacy of palliative care. But it wasn’t that long ago that HIV infection was a nearly inevitable death sentence from the complications of AIDS, with no available treatments. And however monstrous that suffering and death, which still continues in many areas of the developing world, it was decades rather than centuries before modern medicine came up with effective treatments. Recently, there is even significant hope on the Ebola virus front that curative treatments may soon become available.

Wellcome Library, London. Wellcome Images/Wikimedia Commons/CCA-4.0 International

Medicine has always been in the business of hope, even when true cures were not available. Today that hope is less often misplaced. But in previous centuries, the need to offer hope to – and perhaps to make money from – desperate patients was a hallmark of the doctor’s trade.

It was this need to give patients hope and for doctors to feel that they were being effective that led to some highly dubious and desperate efforts to cure syphilis throughout history. These efforts meant centuries of fruitless torture for countless patients until the rise of modern antibiotics.

For the most part, what we now look upon as horrors and insanity in treatment were the result of misguided scientific theories, half-baked folk wisdom, and the generally well-intentioned efforts of medical practitioners at a cure. There were the charlatans as well, seeking a quick buck from the truly hopeless.

However, the social stigma of syphilis as a venereal disease played a role in the courses of treatment.

By the 15th century, syphilis was recognized as being spread by sexual intercourse, and in a situation analogous with the early AIDS epidemic, “16th- and 17th-century writers and physicians were divided on the moral aspects of syphilis. Some thought it was a divine punishment for sin – and as such only harsh treatments would cure it – or that people with syphilis shouldn’t be treated at all.”
 

Mercury rising

In its earliest manifestations, syphilis was considered untreatable. In 1496, Sebastian Brandt, wrote a poem entitled “De pestilentiali Scorra sive mala de Franzos” detailing the disease’s early spread across Europe and how doctors had no remedy for it.

Science Museum, London. Wellcome Images/Wikimedia Commons/CCA-4.0 International

However, it wasn’t long before desperate physicians turned their quest for a cure to a reliable old standby treatment of the period – mercury, which had a history of being used for skin diseases. Mercury salves had been in use in the Arab world for leprosy and eczema, among other skin afflictions, and had been brought to Europe with the return of the medieval crusaders. Another way elemental mercury was administered was through the use of heated cinnabar (HgS), which gave off mercury vapors that could be absorbed by breathing and through the skin. In the 16th century, doctors would place a syphilis-infected individual inside an ovenlike chamber over pans of cinnabar, which were then heated at the person’s feet.

Oral mercury treatments were promoted by Paracelsus (1493?-1541), an alchemist and physician who prescribed calomel (HgCl), or mercury chloride, pills. Mercury treatment, administered at almost inevitably toxic doses, led to ulcerations of the lips, tongue, palate, and jaw; tooth loss; and fetid breath and excessive salivation. This last symptom was, in fact, considered the endpoint in mercury therapy for syphilis, which was “originally judged to be a copious secretion of saliva – ‘some few liters per diem.’ ” Even as recent as the late 19th century and early 20th century, syphilitic patients such as Oscar Wilde (whose teeth were blackened by the treatment), were prescribed calomel.

Looking to the “holy wood”

By 1519, an alternative treatment to mercury was available. In that year, Ulrich von Hutton, a German scholar who suffered from the “great pox,” described its treatment with guaiacum sanctum, or holy wood, in “De Morbo Gallico.” Four years later, despite such treatment, he was dead from the disease himself. But the lack of efficacy did not stop the faith that doctors placed in this botanical cure.

Wellcome Library, London. Wellcome Images/Wikimedia Commons/CCA-4.0 International

Holy wood was an herbal treatment derived from the bark of trees from the Guaiacum family. It was brought back on trading ships from the Caribbean and South America, the origin of syphilis’s foothold in Europe and the rest of the world. The use of holy wood matched a then-current theory that the cure to a disease could be found in the area from which it came. Other botanicals from around the world were also tried, but never came into routine use.

Guaiacum was the first treatment given to sufferers of syphilis in the Blatterhaus (pox hospital) in Augsburg after 1522, according to information from the archives at the Edward Worth Library in Dublin. The botanical therapy was given as a hot drink and followed by a sweating cure. Guaiacum extract acted as a sudorific, a compound which induces sweating when ingested. Even though the use of Guaiacum was initially popular, it was replaced almost exclusively by the use of mercury.

“Give me fever”

In the late 1800s, Julius Wagner von Jauregg (1857-1940), a Viennese neurologist, observed that Austrian army officers with neurosyphilis did not become partially paralyzed if they had also contracted malaria or relapsing fever. He initiated clinical trials in which he induced fever in syphilitics with tuberculin (1-10 mg) and observed in many the remissions their neuropsychiatric symptoms and signs. He also injected neurosyphilitic patients with a mild form of malaria to induce fever, which could then be suppressed with quinine treatment.

“Other physicians soon began using malariotherapy in uncontrolled studies of neurosyphilitics and reported clinical success rates of 33%-51% and only a 5% mortality. Persons with tabes dorsalis (the “wasting” paralysis of neurosyphilis) were hospitalized for 3 weeks of alternate-day fever therapy involving 5-hour long hot baths and extended periods wrapped in heavy blankets,” according to C.T. Ambrose, MD, of the University of Kentucky, Lexington.

A 1931 medical text summarizes in 35 studies involving 2,356 cases of general paresis treated with malaria and reported a 27.5% “full remission,” he added. A bacterial treatment developed in this period used a course of 18-23 injections of killed typhoid cells administered every 2-3 days in order to produce a fever of 103°–104^°F. Animal studies of rabbits infected with syphilis showed that high temperatures could be curative.

Dr. Ambrose suggests that 16th-century syphilitics who had been subjected to mercury fumigation in ovenlike chambers endured severe sweating conditions and – for those who survived – the prolonged elevated body temperature (not the mercury) may have proved curative. Fever “was the common therapeutic denominator in the cinnabar-oven treatment, botanical sudorifics (guaiacum, China root), malarial infections (natural and iatrogenic), and bacterial (tuberculin) vaccine therapy.”

Prelude to modern antibiotics

German bacteriologist/immunologist Paul Ehrlich, MD, (1854-1915) investigated the use of atoxyl (sodium arsanilate) in syphilis, but the metallic drug had severe side effects, injuring the optic nerve and causing blindness. To overcome this problem, Ehrlich and his coworkers synthesized and tested related organic arsenicals. The antisyphilitic activity of arsphenamine (compound 606) was discovered by Sahachiro Hata, MD, (1879-1938) in 1909. This compound, known as Salvarsan, became “Dr. Ehrlich’s Magic Bullet,” for the treatment of syphilis in the 1910s, and it, and later, the less-toxic compound neoarsphenamine (compound 914) became mainstays of successful clinical treatment until the development and use of penicillin in the 1940s.

[email protected]
 

Selected sources

Ambrose, CT. Pre-antibiotic therapy of syphilis. NESSA J Infect Dis Immunology. 2016. 1(1);1-20.

Frith J. Syphilis: Its early history and treatment until penicillin and the debate on its origins. J Mil Veterans Health. 2012;20(4):49-58.

Tognotti B. The rise and fall of syphilis in Renaissance Italy. J Med Humanit. 2009 Jun;30(2):99-113.

Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor in the department of biochemistry and molecular & cellular biology at Georgetown University, Washington.

It is rare in this modern era for medicine to confront an infectious disease for which there is no cure. Today, there are comparatively few infectious diseases (in the developed world and in places where money is no object) for which medicine cannot offer at least a glimmer of hope to infected patients. Even at its most futile, modern medicine has achieved vast improvements in the efficacy of palliative care. But it wasn’t that long ago that HIV infection was a nearly inevitable death sentence from the complications of AIDS, with no available treatments. And however monstrous that suffering and death, which still continues in many areas of the developing world, it was decades rather than centuries before modern medicine came up with effective treatments. Recently, there is even significant hope on the Ebola virus front that curative treatments may soon become available.

Wellcome Library, London. Wellcome Images/Wikimedia Commons/CCA-4.0 International

Medicine has always been in the business of hope, even when true cures were not available. Today that hope is less often misplaced. But in previous centuries, the need to offer hope to – and perhaps to make money from – desperate patients was a hallmark of the doctor’s trade.

It was this need to give patients hope and for doctors to feel that they were being effective that led to some highly dubious and desperate efforts to cure syphilis throughout history. These efforts meant centuries of fruitless torture for countless patients until the rise of modern antibiotics.

For the most part, what we now look upon as horrors and insanity in treatment were the result of misguided scientific theories, half-baked folk wisdom, and the generally well-intentioned efforts of medical practitioners at a cure. There were the charlatans as well, seeking a quick buck from the truly hopeless.

However, the social stigma of syphilis as a venereal disease played a role in the courses of treatment.

By the 15th century, syphilis was recognized as being spread by sexual intercourse, and in a situation analogous with the early AIDS epidemic, “16th- and 17th-century writers and physicians were divided on the moral aspects of syphilis. Some thought it was a divine punishment for sin – and as such only harsh treatments would cure it – or that people with syphilis shouldn’t be treated at all.”
 

Mercury rising

In its earliest manifestations, syphilis was considered untreatable. In 1496, Sebastian Brandt, wrote a poem entitled “De pestilentiali Scorra sive mala de Franzos” detailing the disease’s early spread across Europe and how doctors had no remedy for it.

Science Museum, London. Wellcome Images/Wikimedia Commons/CCA-4.0 International

However, it wasn’t long before desperate physicians turned their quest for a cure to a reliable old standby treatment of the period – mercury, which had a history of being used for skin diseases. Mercury salves had been in use in the Arab world for leprosy and eczema, among other skin afflictions, and had been brought to Europe with the return of the medieval crusaders. Another way elemental mercury was administered was through the use of heated cinnabar (HgS), which gave off mercury vapors that could be absorbed by breathing and through the skin. In the 16th century, doctors would place a syphilis-infected individual inside an ovenlike chamber over pans of cinnabar, which were then heated at the person’s feet.

Oral mercury treatments were promoted by Paracelsus (1493?-1541), an alchemist and physician who prescribed calomel (HgCl), or mercury chloride, pills. Mercury treatment, administered at almost inevitably toxic doses, led to ulcerations of the lips, tongue, palate, and jaw; tooth loss; and fetid breath and excessive salivation. This last symptom was, in fact, considered the endpoint in mercury therapy for syphilis, which was “originally judged to be a copious secretion of saliva – ‘some few liters per diem.’ ” Even as recent as the late 19th century and early 20th century, syphilitic patients such as Oscar Wilde (whose teeth were blackened by the treatment), were prescribed calomel.

Looking to the “holy wood”

By 1519, an alternative treatment to mercury was available. In that year, Ulrich von Hutton, a German scholar who suffered from the “great pox,” described its treatment with guaiacum sanctum, or holy wood, in “De Morbo Gallico.” Four years later, despite such treatment, he was dead from the disease himself. But the lack of efficacy did not stop the faith that doctors placed in this botanical cure.

Wellcome Library, London. Wellcome Images/Wikimedia Commons/CCA-4.0 International

Holy wood was an herbal treatment derived from the bark of trees from the Guaiacum family. It was brought back on trading ships from the Caribbean and South America, the origin of syphilis’s foothold in Europe and the rest of the world. The use of holy wood matched a then-current theory that the cure to a disease could be found in the area from which it came. Other botanicals from around the world were also tried, but never came into routine use.

Guaiacum was the first treatment given to sufferers of syphilis in the Blatterhaus (pox hospital) in Augsburg after 1522, according to information from the archives at the Edward Worth Library in Dublin. The botanical therapy was given as a hot drink and followed by a sweating cure. Guaiacum extract acted as a sudorific, a compound which induces sweating when ingested. Even though the use of Guaiacum was initially popular, it was replaced almost exclusively by the use of mercury.

“Give me fever”

In the late 1800s, Julius Wagner von Jauregg (1857-1940), a Viennese neurologist, observed that Austrian army officers with neurosyphilis did not become partially paralyzed if they had also contracted malaria or relapsing fever. He initiated clinical trials in which he induced fever in syphilitics with tuberculin (1-10 mg) and observed in many the remissions their neuropsychiatric symptoms and signs. He also injected neurosyphilitic patients with a mild form of malaria to induce fever, which could then be suppressed with quinine treatment.

“Other physicians soon began using malariotherapy in uncontrolled studies of neurosyphilitics and reported clinical success rates of 33%-51% and only a 5% mortality. Persons with tabes dorsalis (the “wasting” paralysis of neurosyphilis) were hospitalized for 3 weeks of alternate-day fever therapy involving 5-hour long hot baths and extended periods wrapped in heavy blankets,” according to C.T. Ambrose, MD, of the University of Kentucky, Lexington.

A 1931 medical text summarizes in 35 studies involving 2,356 cases of general paresis treated with malaria and reported a 27.5% “full remission,” he added. A bacterial treatment developed in this period used a course of 18-23 injections of killed typhoid cells administered every 2-3 days in order to produce a fever of 103°–104^°F. Animal studies of rabbits infected with syphilis showed that high temperatures could be curative.

Dr. Ambrose suggests that 16th-century syphilitics who had been subjected to mercury fumigation in ovenlike chambers endured severe sweating conditions and – for those who survived – the prolonged elevated body temperature (not the mercury) may have proved curative. Fever “was the common therapeutic denominator in the cinnabar-oven treatment, botanical sudorifics (guaiacum, China root), malarial infections (natural and iatrogenic), and bacterial (tuberculin) vaccine therapy.”

Prelude to modern antibiotics

German bacteriologist/immunologist Paul Ehrlich, MD, (1854-1915) investigated the use of atoxyl (sodium arsanilate) in syphilis, but the metallic drug had severe side effects, injuring the optic nerve and causing blindness. To overcome this problem, Ehrlich and his coworkers synthesized and tested related organic arsenicals. The antisyphilitic activity of arsphenamine (compound 606) was discovered by Sahachiro Hata, MD, (1879-1938) in 1909. This compound, known as Salvarsan, became “Dr. Ehrlich’s Magic Bullet,” for the treatment of syphilis in the 1910s, and it, and later, the less-toxic compound neoarsphenamine (compound 914) became mainstays of successful clinical treatment until the development and use of penicillin in the 1940s.

[email protected]
 

Selected sources

Ambrose, CT. Pre-antibiotic therapy of syphilis. NESSA J Infect Dis Immunology. 2016. 1(1);1-20.

Frith J. Syphilis: Its early history and treatment until penicillin and the debate on its origins. J Mil Veterans Health. 2012;20(4):49-58.

Tognotti B. The rise and fall of syphilis in Renaissance Italy. J Med Humanit. 2009 Jun;30(2):99-113.

Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor in the department of biochemistry and molecular & cellular biology at Georgetown University, Washington.

It is rare in this modern era for medicine to confront an infectious disease for which there is no cure. Today, there are comparatively few infectious diseases (in the developed world and in places where money is no object) for which medicine cannot offer at least a glimmer of hope to infected patients. Even at its most futile, modern medicine has achieved vast improvements in the efficacy of palliative care. But it wasn’t that long ago that HIV infection was a nearly inevitable death sentence from the complications of AIDS, with no available treatments. And however monstrous that suffering and death, which still continues in many areas of the developing world, it was decades rather than centuries before modern medicine came up with effective treatments. Recently, there is even significant hope on the Ebola virus front that curative treatments may soon become available.

Wellcome Library, London. Wellcome Images/Wikimedia Commons/CCA-4.0 International

Medicine has always been in the business of hope, even when true cures were not available. Today that hope is less often misplaced. But in previous centuries, the need to offer hope to – and perhaps to make money from – desperate patients was a hallmark of the doctor’s trade.

It was this need to give patients hope and for doctors to feel that they were being effective that led to some highly dubious and desperate efforts to cure syphilis throughout history. These efforts meant centuries of fruitless torture for countless patients until the rise of modern antibiotics.

For the most part, what we now look upon as horrors and insanity in treatment were the result of misguided scientific theories, half-baked folk wisdom, and the generally well-intentioned efforts of medical practitioners at a cure. There were the charlatans as well, seeking a quick buck from the truly hopeless.

However, the social stigma of syphilis as a venereal disease played a role in the courses of treatment.

By the 15th century, syphilis was recognized as being spread by sexual intercourse, and in a situation analogous with the early AIDS epidemic, “16th- and 17th-century writers and physicians were divided on the moral aspects of syphilis. Some thought it was a divine punishment for sin – and as such only harsh treatments would cure it – or that people with syphilis shouldn’t be treated at all.”
 

Mercury rising

In its earliest manifestations, syphilis was considered untreatable. In 1496, Sebastian Brandt, wrote a poem entitled “De pestilentiali Scorra sive mala de Franzos” detailing the disease’s early spread across Europe and how doctors had no remedy for it.

Science Museum, London. Wellcome Images/Wikimedia Commons/CCA-4.0 International

However, it wasn’t long before desperate physicians turned their quest for a cure to a reliable old standby treatment of the period – mercury, which had a history of being used for skin diseases. Mercury salves had been in use in the Arab world for leprosy and eczema, among other skin afflictions, and had been brought to Europe with the return of the medieval crusaders. Another way elemental mercury was administered was through the use of heated cinnabar (HgS), which gave off mercury vapors that could be absorbed by breathing and through the skin. In the 16th century, doctors would place a syphilis-infected individual inside an ovenlike chamber over pans of cinnabar, which were then heated at the person’s feet.

Oral mercury treatments were promoted by Paracelsus (1493?-1541), an alchemist and physician who prescribed calomel (HgCl), or mercury chloride, pills. Mercury treatment, administered at almost inevitably toxic doses, led to ulcerations of the lips, tongue, palate, and jaw; tooth loss; and fetid breath and excessive salivation. This last symptom was, in fact, considered the endpoint in mercury therapy for syphilis, which was “originally judged to be a copious secretion of saliva – ‘some few liters per diem.’ ” Even as recent as the late 19th century and early 20th century, syphilitic patients such as Oscar Wilde (whose teeth were blackened by the treatment), were prescribed calomel.

Looking to the “holy wood”

By 1519, an alternative treatment to mercury was available. In that year, Ulrich von Hutton, a German scholar who suffered from the “great pox,” described its treatment with guaiacum sanctum, or holy wood, in “De Morbo Gallico.” Four years later, despite such treatment, he was dead from the disease himself. But the lack of efficacy did not stop the faith that doctors placed in this botanical cure.

Wellcome Library, London. Wellcome Images/Wikimedia Commons/CCA-4.0 International

Holy wood was an herbal treatment derived from the bark of trees from the Guaiacum family. It was brought back on trading ships from the Caribbean and South America, the origin of syphilis’s foothold in Europe and the rest of the world. The use of holy wood matched a then-current theory that the cure to a disease could be found in the area from which it came. Other botanicals from around the world were also tried, but never came into routine use.

Guaiacum was the first treatment given to sufferers of syphilis in the Blatterhaus (pox hospital) in Augsburg after 1522, according to information from the archives at the Edward Worth Library in Dublin. The botanical therapy was given as a hot drink and followed by a sweating cure. Guaiacum extract acted as a sudorific, a compound which induces sweating when ingested. Even though the use of Guaiacum was initially popular, it was replaced almost exclusively by the use of mercury.

“Give me fever”

In the late 1800s, Julius Wagner von Jauregg (1857-1940), a Viennese neurologist, observed that Austrian army officers with neurosyphilis did not become partially paralyzed if they had also contracted malaria or relapsing fever. He initiated clinical trials in which he induced fever in syphilitics with tuberculin (1-10 mg) and observed in many the remissions their neuropsychiatric symptoms and signs. He also injected neurosyphilitic patients with a mild form of malaria to induce fever, which could then be suppressed with quinine treatment.

“Other physicians soon began using malariotherapy in uncontrolled studies of neurosyphilitics and reported clinical success rates of 33%-51% and only a 5% mortality. Persons with tabes dorsalis (the “wasting” paralysis of neurosyphilis) were hospitalized for 3 weeks of alternate-day fever therapy involving 5-hour long hot baths and extended periods wrapped in heavy blankets,” according to C.T. Ambrose, MD, of the University of Kentucky, Lexington.

A 1931 medical text summarizes in 35 studies involving 2,356 cases of general paresis treated with malaria and reported a 27.5% “full remission,” he added. A bacterial treatment developed in this period used a course of 18-23 injections of killed typhoid cells administered every 2-3 days in order to produce a fever of 103°–104^°F. Animal studies of rabbits infected with syphilis showed that high temperatures could be curative.

Dr. Ambrose suggests that 16th-century syphilitics who had been subjected to mercury fumigation in ovenlike chambers endured severe sweating conditions and – for those who survived – the prolonged elevated body temperature (not the mercury) may have proved curative. Fever “was the common therapeutic denominator in the cinnabar-oven treatment, botanical sudorifics (guaiacum, China root), malarial infections (natural and iatrogenic), and bacterial (tuberculin) vaccine therapy.”

Prelude to modern antibiotics

German bacteriologist/immunologist Paul Ehrlich, MD, (1854-1915) investigated the use of atoxyl (sodium arsanilate) in syphilis, but the metallic drug had severe side effects, injuring the optic nerve and causing blindness. To overcome this problem, Ehrlich and his coworkers synthesized and tested related organic arsenicals. The antisyphilitic activity of arsphenamine (compound 606) was discovered by Sahachiro Hata, MD, (1879-1938) in 1909. This compound, known as Salvarsan, became “Dr. Ehrlich’s Magic Bullet,” for the treatment of syphilis in the 1910s, and it, and later, the less-toxic compound neoarsphenamine (compound 914) became mainstays of successful clinical treatment until the development and use of penicillin in the 1940s.

[email protected]
 

Selected sources

Ambrose, CT. Pre-antibiotic therapy of syphilis. NESSA J Infect Dis Immunology. 2016. 1(1);1-20.

Frith J. Syphilis: Its early history and treatment until penicillin and the debate on its origins. J Mil Veterans Health. 2012;20(4):49-58.

Tognotti B. The rise and fall of syphilis in Renaissance Italy. J Med Humanit. 2009 Jun;30(2):99-113.

Mark Lesney is the managing editor of MDedge.com/IDPractioner. He has a PhD in plant virology and a PhD in the history of science, with a focus on the history of biotechnology and medicine. He has served as an adjunct assistant professor in the department of biochemistry and molecular & cellular biology at Georgetown University, Washington.

In this edition of “How I will treat my next patient,” I focus on a recent presentation at the American Society for Radiation Oncology meeting regarding the association of recent closures in women’s health clinics with cervical cancer outcomes and on a publication regarding guideline-concordant radiation exposure and organizational characteristics of lung cancer screening programs.

Cervical cancer screening and outcomes

Between 2010 and 2013, nearly 100 women’s health clinics closed in the United States because of a variety of factors, including concerns by state legislatures about reproductive services. Amar J. Srivastava, MD, and colleagues, performed a database search to determine the effect of closures on cervical cancer screening, stage, and mortality (ASTRO 2019, Abstract 202). The researchers used the Behavioral Risk Factors Surveillance Study, which provided data from 197,143 cases, to assess differences in screening availability in 2008-2009 (before the closures). They used the Surveillance, Epidemiology, and End Results (SEER) registry data from 2014-2015 (after) on 10,652 patients to compare stage at diagnosis and disease-specific mortality in states with women’s health clinic closures and states without closures.

They found that the cervical cancer screening rate in states that had a decline in the number of women’s health clinics was 1.63% lower than in states that did not lose clinics. The disparity was greater in medically underserved subgroups: Hispanic women, women aged 21-34 years, unmarried women, and uninsured women.

Early-stage diagnosis was also significantly less common in states that had a decreased number of women’s health clinics – a 13.2% drop – and the overall mortality rate from cervical cancer was 36% higher. The difference was even higher (40%) when comparing only metro residents. All of these differences between states with and without closures were statistically significant.

How these results influence clinical practice

The law of unintended consequences is that the actions of people, and especially of governments, will have effects that are unanticipated or unintended. All oncologists understand this law – we live it every day.

The data generated by Dr. Srivastava and colleagues bring to mind two presentations at the 2019 annual meeting of the American Society of Clinical Oncology: the impact of Medicaid Expansion on racial disparities in time to cancer treatment (LBA 1) and the impact of the Affordable Care Act on early-stage diagnosis and treatment for women with ovarian cancer (LBA 5563). Collectively, they remind us that health care policy changes influence the timeliness of cancer care delivery and disparities in cancer care. Of course, these analyses describe associations, not necessarily causation. Large databases have quality and completeness limitations. Nonetheless, these abstracts and the associated presentations and discussions support the concept that improved access can be associated with improved cancer care outcomes.

In 1936, American sociologist Robert K. Merton described “imperious immediacy of interest,” referring to instances in which an individual wants the intended consequence of an action so badly that he or she purposefully chooses to ignore unintended effects. As a clinical and research community, we are obliged to highlight those effects when they influence our patients’ suffering.
 

Lung cancer screening

As a component of the Centers for Medicare & Medicaid Services’ requirements for lung cancer screening payment, institutions performing screening must use low-dose techniques and participate in a dose registry. The American College of Radiology (ACR) recommends the dose levels per CT slice (CTDIvol; 3 mGy or lower) and the effective dose (ED; 1 mSr or lower) that would qualify an examination as “low dose,” thereby hoping to minimize the risk of radiation-induced cancers.

Joshua Demb, PhD, and colleagues prospectively collected lung cancer screening examination dose metrics at U.S. institutions in the University of California, San Francisco, International Dose Registry (JAMA Intern Med. 2019 Sep 23. doi: 10.1001/jamainternmed.2019.3893). Only U.S. institutions that performed more than 24 lung cancer screening scans from 2016-2017 were included in the survey (n = 72, more than 12,500 patients). Institution-level factors were collected via the Partnership for Dose trial, including how CT scans are performed and how CT protocols are established at the institutional level.

In a data-dense analysis, the authors found that 65% of institutions delivered, and more than half of patients received, radiation doses above ACR targets. This suggests that both the potential screening benefits and the margins of benefits over risks might be reduced for patients at those institutions. Factors associated with exceeding ACR guidelines for radiation dose were using an “external” medical physicist, although having a medical physicist of any type was more beneficial than not having one; allowing any radiologist to establish or modify the screening protocol, instead of limiting that role to “lead” radiologists; and updating CT protocols as needed, compared with updating the protocols annually.

How these results influence clinical practice

As with the ASTRO 2019 presentation, the law of unintended consequences applies here. Whenever potentially healthy people are subjected to medical procedures to prevent illness or detect disease at early stages, protecting safety is paramount. For that reason, National Comprehensive Cancer Network (NCCN) guidelines are explicit that all lung cancer screening and follow-up scans should use low-dose techniques, unless evaluating mediastinal abnormalities or adenopathy.

The study by Dr. Demb and colleagues critically examined the proportion of lung cancer screening participants receiving guideline-concordant, low-dose examinations and several factors that could influence conformance with ACR guidelines. The results are instructive despite some of the study’s limits including the fact that the database used did not enable long-term follow-up of screened individuals for lung cancer detection or mortality, the survey relied on self-reporting, and the institutional level data was not solely focused on lung cancer screening examinations.

The survey reminds us that the logistics, quality control, and periodic review of well-intentioned programs like lung cancer screening require the thoughtful, regular involvement of teams of professionals who are cognizant of, adherent to, and vigilant about the guidelines that protect the individuals who entrust their care to us.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I focus on a recent presentation at the American Society for Radiation Oncology meeting regarding the association of recent closures in women’s health clinics with cervical cancer outcomes and on a publication regarding guideline-concordant radiation exposure and organizational characteristics of lung cancer screening programs.

Cervical cancer screening and outcomes

Between 2010 and 2013, nearly 100 women’s health clinics closed in the United States because of a variety of factors, including concerns by state legislatures about reproductive services. Amar J. Srivastava, MD, and colleagues, performed a database search to determine the effect of closures on cervical cancer screening, stage, and mortality (ASTRO 2019, Abstract 202). The researchers used the Behavioral Risk Factors Surveillance Study, which provided data from 197,143 cases, to assess differences in screening availability in 2008-2009 (before the closures). They used the Surveillance, Epidemiology, and End Results (SEER) registry data from 2014-2015 (after) on 10,652 patients to compare stage at diagnosis and disease-specific mortality in states with women’s health clinic closures and states without closures.

They found that the cervical cancer screening rate in states that had a decline in the number of women’s health clinics was 1.63% lower than in states that did not lose clinics. The disparity was greater in medically underserved subgroups: Hispanic women, women aged 21-34 years, unmarried women, and uninsured women.

Early-stage diagnosis was also significantly less common in states that had a decreased number of women’s health clinics – a 13.2% drop – and the overall mortality rate from cervical cancer was 36% higher. The difference was even higher (40%) when comparing only metro residents. All of these differences between states with and without closures were statistically significant.

How these results influence clinical practice

The law of unintended consequences is that the actions of people, and especially of governments, will have effects that are unanticipated or unintended. All oncologists understand this law – we live it every day.

The data generated by Dr. Srivastava and colleagues bring to mind two presentations at the 2019 annual meeting of the American Society of Clinical Oncology: the impact of Medicaid Expansion on racial disparities in time to cancer treatment (LBA 1) and the impact of the Affordable Care Act on early-stage diagnosis and treatment for women with ovarian cancer (LBA 5563). Collectively, they remind us that health care policy changes influence the timeliness of cancer care delivery and disparities in cancer care. Of course, these analyses describe associations, not necessarily causation. Large databases have quality and completeness limitations. Nonetheless, these abstracts and the associated presentations and discussions support the concept that improved access can be associated with improved cancer care outcomes.

In 1936, American sociologist Robert K. Merton described “imperious immediacy of interest,” referring to instances in which an individual wants the intended consequence of an action so badly that he or she purposefully chooses to ignore unintended effects. As a clinical and research community, we are obliged to highlight those effects when they influence our patients’ suffering.
 

Lung cancer screening

As a component of the Centers for Medicare & Medicaid Services’ requirements for lung cancer screening payment, institutions performing screening must use low-dose techniques and participate in a dose registry. The American College of Radiology (ACR) recommends the dose levels per CT slice (CTDIvol; 3 mGy or lower) and the effective dose (ED; 1 mSr or lower) that would qualify an examination as “low dose,” thereby hoping to minimize the risk of radiation-induced cancers.

Joshua Demb, PhD, and colleagues prospectively collected lung cancer screening examination dose metrics at U.S. institutions in the University of California, San Francisco, International Dose Registry (JAMA Intern Med. 2019 Sep 23. doi: 10.1001/jamainternmed.2019.3893). Only U.S. institutions that performed more than 24 lung cancer screening scans from 2016-2017 were included in the survey (n = 72, more than 12,500 patients). Institution-level factors were collected via the Partnership for Dose trial, including how CT scans are performed and how CT protocols are established at the institutional level.

In a data-dense analysis, the authors found that 65% of institutions delivered, and more than half of patients received, radiation doses above ACR targets. This suggests that both the potential screening benefits and the margins of benefits over risks might be reduced for patients at those institutions. Factors associated with exceeding ACR guidelines for radiation dose were using an “external” medical physicist, although having a medical physicist of any type was more beneficial than not having one; allowing any radiologist to establish or modify the screening protocol, instead of limiting that role to “lead” radiologists; and updating CT protocols as needed, compared with updating the protocols annually.

How these results influence clinical practice

As with the ASTRO 2019 presentation, the law of unintended consequences applies here. Whenever potentially healthy people are subjected to medical procedures to prevent illness or detect disease at early stages, protecting safety is paramount. For that reason, National Comprehensive Cancer Network (NCCN) guidelines are explicit that all lung cancer screening and follow-up scans should use low-dose techniques, unless evaluating mediastinal abnormalities or adenopathy.

The study by Dr. Demb and colleagues critically examined the proportion of lung cancer screening participants receiving guideline-concordant, low-dose examinations and several factors that could influence conformance with ACR guidelines. The results are instructive despite some of the study’s limits including the fact that the database used did not enable long-term follow-up of screened individuals for lung cancer detection or mortality, the survey relied on self-reporting, and the institutional level data was not solely focused on lung cancer screening examinations.

The survey reminds us that the logistics, quality control, and periodic review of well-intentioned programs like lung cancer screening require the thoughtful, regular involvement of teams of professionals who are cognizant of, adherent to, and vigilant about the guidelines that protect the individuals who entrust their care to us.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I focus on a recent presentation at the American Society for Radiation Oncology meeting regarding the association of recent closures in women’s health clinics with cervical cancer outcomes and on a publication regarding guideline-concordant radiation exposure and organizational characteristics of lung cancer screening programs.

Cervical cancer screening and outcomes

Between 2010 and 2013, nearly 100 women’s health clinics closed in the United States because of a variety of factors, including concerns by state legislatures about reproductive services. Amar J. Srivastava, MD, and colleagues, performed a database search to determine the effect of closures on cervical cancer screening, stage, and mortality (ASTRO 2019, Abstract 202). The researchers used the Behavioral Risk Factors Surveillance Study, which provided data from 197,143 cases, to assess differences in screening availability in 2008-2009 (before the closures). They used the Surveillance, Epidemiology, and End Results (SEER) registry data from 2014-2015 (after) on 10,652 patients to compare stage at diagnosis and disease-specific mortality in states with women’s health clinic closures and states without closures.

They found that the cervical cancer screening rate in states that had a decline in the number of women’s health clinics was 1.63% lower than in states that did not lose clinics. The disparity was greater in medically underserved subgroups: Hispanic women, women aged 21-34 years, unmarried women, and uninsured women.

Early-stage diagnosis was also significantly less common in states that had a decreased number of women’s health clinics – a 13.2% drop – and the overall mortality rate from cervical cancer was 36% higher. The difference was even higher (40%) when comparing only metro residents. All of these differences between states with and without closures were statistically significant.

How these results influence clinical practice

The law of unintended consequences is that the actions of people, and especially of governments, will have effects that are unanticipated or unintended. All oncologists understand this law – we live it every day.

The data generated by Dr. Srivastava and colleagues bring to mind two presentations at the 2019 annual meeting of the American Society of Clinical Oncology: the impact of Medicaid Expansion on racial disparities in time to cancer treatment (LBA 1) and the impact of the Affordable Care Act on early-stage diagnosis and treatment for women with ovarian cancer (LBA 5563). Collectively, they remind us that health care policy changes influence the timeliness of cancer care delivery and disparities in cancer care. Of course, these analyses describe associations, not necessarily causation. Large databases have quality and completeness limitations. Nonetheless, these abstracts and the associated presentations and discussions support the concept that improved access can be associated with improved cancer care outcomes.

In 1936, American sociologist Robert K. Merton described “imperious immediacy of interest,” referring to instances in which an individual wants the intended consequence of an action so badly that he or she purposefully chooses to ignore unintended effects. As a clinical and research community, we are obliged to highlight those effects when they influence our patients’ suffering.
 

Lung cancer screening

As a component of the Centers for Medicare & Medicaid Services’ requirements for lung cancer screening payment, institutions performing screening must use low-dose techniques and participate in a dose registry. The American College of Radiology (ACR) recommends the dose levels per CT slice (CTDIvol; 3 mGy or lower) and the effective dose (ED; 1 mSr or lower) that would qualify an examination as “low dose,” thereby hoping to minimize the risk of radiation-induced cancers.

Joshua Demb, PhD, and colleagues prospectively collected lung cancer screening examination dose metrics at U.S. institutions in the University of California, San Francisco, International Dose Registry (JAMA Intern Med. 2019 Sep 23. doi: 10.1001/jamainternmed.2019.3893). Only U.S. institutions that performed more than 24 lung cancer screening scans from 2016-2017 were included in the survey (n = 72, more than 12,500 patients). Institution-level factors were collected via the Partnership for Dose trial, including how CT scans are performed and how CT protocols are established at the institutional level.

In a data-dense analysis, the authors found that 65% of institutions delivered, and more than half of patients received, radiation doses above ACR targets. This suggests that both the potential screening benefits and the margins of benefits over risks might be reduced for patients at those institutions. Factors associated with exceeding ACR guidelines for radiation dose were using an “external” medical physicist, although having a medical physicist of any type was more beneficial than not having one; allowing any radiologist to establish or modify the screening protocol, instead of limiting that role to “lead” radiologists; and updating CT protocols as needed, compared with updating the protocols annually.

How these results influence clinical practice

As with the ASTRO 2019 presentation, the law of unintended consequences applies here. Whenever potentially healthy people are subjected to medical procedures to prevent illness or detect disease at early stages, protecting safety is paramount. For that reason, National Comprehensive Cancer Network (NCCN) guidelines are explicit that all lung cancer screening and follow-up scans should use low-dose techniques, unless evaluating mediastinal abnormalities or adenopathy.

The study by Dr. Demb and colleagues critically examined the proportion of lung cancer screening participants receiving guideline-concordant, low-dose examinations and several factors that could influence conformance with ACR guidelines. The results are instructive despite some of the study’s limits including the fact that the database used did not enable long-term follow-up of screened individuals for lung cancer detection or mortality, the survey relied on self-reporting, and the institutional level data was not solely focused on lung cancer screening examinations.

The survey reminds us that the logistics, quality control, and periodic review of well-intentioned programs like lung cancer screening require the thoughtful, regular involvement of teams of professionals who are cognizant of, adherent to, and vigilant about the guidelines that protect the individuals who entrust their care to us.
 

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

Even a mild blast to the brain can cause long-term, life-changing health problems, says Riyi Shi, professor of neuroscience and biomedical engineering at Purdue University in Lafayette, Indiana. However, the effects can be subtle: “The individual appears to be fine, and it’s difficult to tell if you just look at a person. But the fact is that these types of hits are multiplied over years and often ignored until someone reaches an age when other factors come into play.”

Treating the incidents sooner can help mitigate later-life issues, such as Parkinson disease (PD). Shi led a study that found checking the urine within 7 days following a blast incident—even a mild one—provides faster diagnosis when brain injury is suspected.

A simple urine analysis reveals elevations in the neurotoxin acrolein, Shi says, which is a biomarker for brain injury. In the study, the researchers evaluated the changes of α-synuclein and tyrosine hydroxylase, hallmarks of PD, and acrolein, a marker of oxidative stress. The researchers say in animal models of PD and traumatic brain injury (TBI), acrolein is “likely a point of pathogenic convergence.”

They found that after a single mild blast TBI, acrolein was elevated for up to a week, systemically in urine, and in whole brain tissue, specifically the substantia nigra and striatum. The elevation was accompanied by heightened α-synuclein oligomerization, dopaminergic dysregulation, and acrolein/α-synuclein interaction in the same brain regions. Taken together, the researchers say, the data suggest that acrolein likely plays a key role in inducing PD following blast TBI.

The presence of the biomarker “alerts us to the injury, creating an opportunity for intervention,” Shi says. “This early detection and subsequent treatment window could offer tremendous benefits for long-term patient neurologic health.”

Even a mild blast to the brain can cause long-term, life-changing health problems, says Riyi Shi, professor of neuroscience and biomedical engineering at Purdue University in Lafayette, Indiana. However, the effects can be subtle: “The individual appears to be fine, and it’s difficult to tell if you just look at a person. But the fact is that these types of hits are multiplied over years and often ignored until someone reaches an age when other factors come into play.”

Treating the incidents sooner can help mitigate later-life issues, such as Parkinson disease (PD). Shi led a study that found checking the urine within 7 days following a blast incident—even a mild one—provides faster diagnosis when brain injury is suspected.

A simple urine analysis reveals elevations in the neurotoxin acrolein, Shi says, which is a biomarker for brain injury. In the study, the researchers evaluated the changes of α-synuclein and tyrosine hydroxylase, hallmarks of PD, and acrolein, a marker of oxidative stress. The researchers say in animal models of PD and traumatic brain injury (TBI), acrolein is “likely a point of pathogenic convergence.”

They found that after a single mild blast TBI, acrolein was elevated for up to a week, systemically in urine, and in whole brain tissue, specifically the substantia nigra and striatum. The elevation was accompanied by heightened α-synuclein oligomerization, dopaminergic dysregulation, and acrolein/α-synuclein interaction in the same brain regions. Taken together, the researchers say, the data suggest that acrolein likely plays a key role in inducing PD following blast TBI.

The presence of the biomarker “alerts us to the injury, creating an opportunity for intervention,” Shi says. “This early detection and subsequent treatment window could offer tremendous benefits for long-term patient neurologic health.”

Even a mild blast to the brain can cause long-term, life-changing health problems, says Riyi Shi, professor of neuroscience and biomedical engineering at Purdue University in Lafayette, Indiana. However, the effects can be subtle: “The individual appears to be fine, and it’s difficult to tell if you just look at a person. But the fact is that these types of hits are multiplied over years and often ignored until someone reaches an age when other factors come into play.”

Treating the incidents sooner can help mitigate later-life issues, such as Parkinson disease (PD). Shi led a study that found checking the urine within 7 days following a blast incident—even a mild one—provides faster diagnosis when brain injury is suspected.

A simple urine analysis reveals elevations in the neurotoxin acrolein, Shi says, which is a biomarker for brain injury. In the study, the researchers evaluated the changes of α-synuclein and tyrosine hydroxylase, hallmarks of PD, and acrolein, a marker of oxidative stress. The researchers say in animal models of PD and traumatic brain injury (TBI), acrolein is “likely a point of pathogenic convergence.”

They found that after a single mild blast TBI, acrolein was elevated for up to a week, systemically in urine, and in whole brain tissue, specifically the substantia nigra and striatum. The elevation was accompanied by heightened α-synuclein oligomerization, dopaminergic dysregulation, and acrolein/α-synuclein interaction in the same brain regions. Taken together, the researchers say, the data suggest that acrolein likely plays a key role in inducing PD following blast TBI.

The presence of the biomarker “alerts us to the injury, creating an opportunity for intervention,” Shi says. “This early detection and subsequent treatment window could offer tremendous benefits for long-term patient neurologic health.”