Photo by Larry Young

LA JOLLA, CA—Mogamulizumab is a valuable new therapeutic option for patients with cutaneous T-cell lymphoma (CTCL), according to researchers.

Results of the phase 3 MAVORIC study indicated that mogamulizumab is more effective than vorinostat in previously treated patients with CTCL.

Mogamulizumab produced a better overall response rate (ORR) and prolonged progression-free survival (PFS) in these patients.

Infusion-related reactions and drug eruptions were more common in patients who received mogamulizumab.

Youn H. Kim, MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues presented these results in a poster at the 10th Annual T-cell Lymphoma Forum. The study was funded by Kyowa Kirin Pharmaceutical Development, Inc.

MAVORIC enrolled 372 adults with histologically confirmed mycosis fungoides (MF) or Sézary syndrome (SS) who had failed at least 1 systemic therapy. They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily.

Patients were treated until disease progression or unacceptable toxicity. Those receiving vorinostat could crossover to mogamulizumab if they progressed or experienced intolerable toxicity.

Baseline characteristics were similar between the treatment arms. The median age was 64 (range, 54-73) in the mogamulizumab arm and 65 (range, 56-72) in the vorinostat arm. Ninety-nine percent and 100% of patients, respectively, had an ECOG performance status of 0 to 1.

A little more than half of patients in each arm had MF—57% in the mogamulizumab arm and 53% in the vorinostat arm.

The median number of prior systemic therapies was 3 in both arms (range, 1-18 in the mogamulizumab arm and 0-14 in the vorinostat arm).

Efficacy

The primary endpoint was PFS, and mogamulizumab provided a significant improvement there. The median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

The researchers also observed a significant improvement in global ORR with mogamulizumab. It was 28% (52/189) in that arm and 5% (9/186) in the vorinostat arm (P<0.0001).

For patients with MF, the ORR was 21% with mogamulizumab and 7% with vorinostat. For SS patients, the ORR was 37% and 2%, respectively.

Responses by disease compartment were superior with mogamulizumab as well.

“Especially in the blood compartment, mogamulizumab had very striking activity over vorinostat,” Dr Kim said.

The blood ORR was 68% with mogamulizumab and 19% with vorinostat. The skin ORR was 42% and 16%, respectively. The lymph node ORR was 17% and 4%, respectively. The viscera ORR was 0% in both arms.

After crossover, the ORR in the mogamulizumab arm was 30% (41/136).

The median duration of response (DOR) was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm.

For MF patients, the median DOR was 13 months with mogamulizumab and 9 months with vorinostat. For SS patients, the median DOR was 17 months and 7 months, respectively.

Safety

“Side effects [of mogamulizumab] were very well tolerable,” Dr Kim said. “Most significant is rash and infusion reactions, but, in terms of severe adverse events, [they] were very minimal.”

The most common treatment-emergent adverse events (AEs), occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:

• Infusion-related reactions (33.2% vs 0.5%)
• Drug eruptions (23.9% vs 0.5%)
• Diarrhea (23.4% vs 61.8%)
• Nausea (15.2% vs 42.5%)
• Thrombocytopenia (11.4% vs 30.6%)
• Dysgeusia (3.3% vs 28.0%)
• Increased blood creatinine (3.3% vs 28.0%)
• Decreased appetite (7.6% vs 24.7%).

There were no grade 4 AEs in the mogamulizumab arm and 2 cases of grade 4 thrombocytopenia in the vorinostat arm.

Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), infusion-related reactions (n=3), fatigue (n=3), decreased appetite (n=2), nausea (n=1), pyrexia (n=1), and diarrhea (n=1).

Grade 3 AEs in the vorinostat arm included thrombocytopenia (n=11), fatigue (n=11), diarrhea (n=9), nausea (n=3), decreased appetite (n=2), and dysgeusia (n=1).

“So the results are, overall, positive,” Dr Kim said. “The data is submitted to the [US Food and Drug Administration]. We are really hoping that [mogamulizumab] will be approved so that we would have a new, exciting treatment for our patients with mycosis fungoides and Sézary syndrome.”

Photo by Larry Young

LA JOLLA, CA—Mogamulizumab is a valuable new therapeutic option for patients with cutaneous T-cell lymphoma (CTCL), according to researchers.

Results of the phase 3 MAVORIC study indicated that mogamulizumab is more effective than vorinostat in previously treated patients with CTCL.

Mogamulizumab produced a better overall response rate (ORR) and prolonged progression-free survival (PFS) in these patients.

Infusion-related reactions and drug eruptions were more common in patients who received mogamulizumab.

Youn H. Kim, MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues presented these results in a poster at the 10th Annual T-cell Lymphoma Forum. The study was funded by Kyowa Kirin Pharmaceutical Development, Inc.

MAVORIC enrolled 372 adults with histologically confirmed mycosis fungoides (MF) or Sézary syndrome (SS) who had failed at least 1 systemic therapy. They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily.

Patients were treated until disease progression or unacceptable toxicity. Those receiving vorinostat could crossover to mogamulizumab if they progressed or experienced intolerable toxicity.

Baseline characteristics were similar between the treatment arms. The median age was 64 (range, 54-73) in the mogamulizumab arm and 65 (range, 56-72) in the vorinostat arm. Ninety-nine percent and 100% of patients, respectively, had an ECOG performance status of 0 to 1.

A little more than half of patients in each arm had MF—57% in the mogamulizumab arm and 53% in the vorinostat arm.

The median number of prior systemic therapies was 3 in both arms (range, 1-18 in the mogamulizumab arm and 0-14 in the vorinostat arm).

Efficacy

The primary endpoint was PFS, and mogamulizumab provided a significant improvement there. The median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

The researchers also observed a significant improvement in global ORR with mogamulizumab. It was 28% (52/189) in that arm and 5% (9/186) in the vorinostat arm (P<0.0001).

For patients with MF, the ORR was 21% with mogamulizumab and 7% with vorinostat. For SS patients, the ORR was 37% and 2%, respectively.

Responses by disease compartment were superior with mogamulizumab as well.

“Especially in the blood compartment, mogamulizumab had very striking activity over vorinostat,” Dr Kim said.

The blood ORR was 68% with mogamulizumab and 19% with vorinostat. The skin ORR was 42% and 16%, respectively. The lymph node ORR was 17% and 4%, respectively. The viscera ORR was 0% in both arms.

After crossover, the ORR in the mogamulizumab arm was 30% (41/136).

The median duration of response (DOR) was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm.

For MF patients, the median DOR was 13 months with mogamulizumab and 9 months with vorinostat. For SS patients, the median DOR was 17 months and 7 months, respectively.

Safety

“Side effects [of mogamulizumab] were very well tolerable,” Dr Kim said. “Most significant is rash and infusion reactions, but, in terms of severe adverse events, [they] were very minimal.”

The most common treatment-emergent adverse events (AEs), occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:

• Infusion-related reactions (33.2% vs 0.5%)
• Drug eruptions (23.9% vs 0.5%)
• Diarrhea (23.4% vs 61.8%)
• Nausea (15.2% vs 42.5%)
• Thrombocytopenia (11.4% vs 30.6%)
• Dysgeusia (3.3% vs 28.0%)
• Increased blood creatinine (3.3% vs 28.0%)
• Decreased appetite (7.6% vs 24.7%).

There were no grade 4 AEs in the mogamulizumab arm and 2 cases of grade 4 thrombocytopenia in the vorinostat arm.

Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), infusion-related reactions (n=3), fatigue (n=3), decreased appetite (n=2), nausea (n=1), pyrexia (n=1), and diarrhea (n=1).

Grade 3 AEs in the vorinostat arm included thrombocytopenia (n=11), fatigue (n=11), diarrhea (n=9), nausea (n=3), decreased appetite (n=2), and dysgeusia (n=1).

“So the results are, overall, positive,” Dr Kim said. “The data is submitted to the [US Food and Drug Administration]. We are really hoping that [mogamulizumab] will be approved so that we would have a new, exciting treatment for our patients with mycosis fungoides and Sézary syndrome.”

Photo by Larry Young

LA JOLLA, CA—Mogamulizumab is a valuable new therapeutic option for patients with cutaneous T-cell lymphoma (CTCL), according to researchers.

Results of the phase 3 MAVORIC study indicated that mogamulizumab is more effective than vorinostat in previously treated patients with CTCL.

Mogamulizumab produced a better overall response rate (ORR) and prolonged progression-free survival (PFS) in these patients.

Infusion-related reactions and drug eruptions were more common in patients who received mogamulizumab.

Youn H. Kim, MD, of the Stanford Cancer Institute in Palo Alto, California, and her colleagues presented these results in a poster at the 10th Annual T-cell Lymphoma Forum. The study was funded by Kyowa Kirin Pharmaceutical Development, Inc.

MAVORIC enrolled 372 adults with histologically confirmed mycosis fungoides (MF) or Sézary syndrome (SS) who had failed at least 1 systemic therapy. They were randomized to receive mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle and then every 2 weeks) or vorinostat at 400 mg daily.

Patients were treated until disease progression or unacceptable toxicity. Those receiving vorinostat could crossover to mogamulizumab if they progressed or experienced intolerable toxicity.

Baseline characteristics were similar between the treatment arms. The median age was 64 (range, 54-73) in the mogamulizumab arm and 65 (range, 56-72) in the vorinostat arm. Ninety-nine percent and 100% of patients, respectively, had an ECOG performance status of 0 to 1.

A little more than half of patients in each arm had MF—57% in the mogamulizumab arm and 53% in the vorinostat arm.

The median number of prior systemic therapies was 3 in both arms (range, 1-18 in the mogamulizumab arm and 0-14 in the vorinostat arm).

Efficacy

The primary endpoint was PFS, and mogamulizumab provided a significant improvement there. The median PFS was 7.7 months with mogamulizumab and 3.1 months with vorinostat (hazard ratio=0.53, P<0.0001).

The researchers also observed a significant improvement in global ORR with mogamulizumab. It was 28% (52/189) in that arm and 5% (9/186) in the vorinostat arm (P<0.0001).

For patients with MF, the ORR was 21% with mogamulizumab and 7% with vorinostat. For SS patients, the ORR was 37% and 2%, respectively.

Responses by disease compartment were superior with mogamulizumab as well.

“Especially in the blood compartment, mogamulizumab had very striking activity over vorinostat,” Dr Kim said.

The blood ORR was 68% with mogamulizumab and 19% with vorinostat. The skin ORR was 42% and 16%, respectively. The lymph node ORR was 17% and 4%, respectively. The viscera ORR was 0% in both arms.

After crossover, the ORR in the mogamulizumab arm was 30% (41/136).

The median duration of response (DOR) was 14 months in the mogamulizumab arm and 9 months in the vorinostat arm.

For MF patients, the median DOR was 13 months with mogamulizumab and 9 months with vorinostat. For SS patients, the median DOR was 17 months and 7 months, respectively.

Safety

“Side effects [of mogamulizumab] were very well tolerable,” Dr Kim said. “Most significant is rash and infusion reactions, but, in terms of severe adverse events, [they] were very minimal.”

The most common treatment-emergent adverse events (AEs), occurring in at least 20% of patients in either arm (mogamulizumab and vorinostat, respectively), were:

• Infusion-related reactions (33.2% vs 0.5%)
• Drug eruptions (23.9% vs 0.5%)
• Diarrhea (23.4% vs 61.8%)
• Nausea (15.2% vs 42.5%)
• Thrombocytopenia (11.4% vs 30.6%)
• Dysgeusia (3.3% vs 28.0%)
• Increased blood creatinine (3.3% vs 28.0%)
• Decreased appetite (7.6% vs 24.7%).

There were no grade 4 AEs in the mogamulizumab arm and 2 cases of grade 4 thrombocytopenia in the vorinostat arm.

Grade 3 AEs in the mogamulizumab arm included drug eruptions (n=8), infusion-related reactions (n=3), fatigue (n=3), decreased appetite (n=2), nausea (n=1), pyrexia (n=1), and diarrhea (n=1).

Grade 3 AEs in the vorinostat arm included thrombocytopenia (n=11), fatigue (n=11), diarrhea (n=9), nausea (n=3), decreased appetite (n=2), and dysgeusia (n=1).

“So the results are, overall, positive,” Dr Kim said. “The data is submitted to the [US Food and Drug Administration]. We are really hoping that [mogamulizumab] will be approved so that we would have a new, exciting treatment for our patients with mycosis fungoides and Sézary syndrome.”

Despite the increased risk for invasive pneumococcal disease, prophylactic antibiotics are underused in children with sickle cell anemia, according to data from more than 2,000 children in six states.

Less than one-fifth (18%) of young children (aged 3 months to 5 years) with sickle cell anemia (SCA) receive at least 300 days of prophylactic antibiotics to reduce their risk of pneumococcal infections, the analysis found.

“Although the effectiveness of daily penicillin prophylaxis has been known for decades, limited evidence indicates low rates of compliance among children,” wrote Sarah L. Reeves, PhD, of the University of Michigan, Ann Arbor, and her colleagues. The report was published in Pediatrics.

The researchers reviewed Medicaid claims for 2,821 children with SCA from the period of 2005-2012 for a total of 5,014 person-years. The data were taken from six states: Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. Antibiotic prophylaxis was defined as four different treatment protocols: oral penicillin; oral penicillin or erythromycin; oral penicillin, erythromycin, or amoxicillin; or any antibiotic that could protect against Streptococcus pneumoniae.

Overall, the children in the study averaged 1.7 sickle cell disease–related inpatient hospitalizations annually, as well as 13.2 sickle cell disease–related outpatient visits and 3.8 emergency department visits per year.

The proportion of children who received 300 days or more of prophylactic antibiotics varied by state, by year, and by type of treatment. “In this multistate analysis, receipt of antibiotic prophylaxis among children with SCA was persistently low, irrespective of year or state,” the researchers noted.

The odds that a child received 300 days or more of prophylactic antibiotics increased with each outpatient visit, including well child visits and sickle cell disease–related visits (odds ratios 1.08 and 1.01, respectively).

A child in the third quartile of sickle cell disease–related outpatient visits (defined as 17 annual visits) was 15% more likely than was a child in the first quartile (defined as six annual visits) to receive at least 300 days of antibiotics.

The study findings were limited by several factors including potential overestimation of how many children received medication, the researchers said. However, the results suggest the need for practical and effective intervention that targets barriers to treatment adherence, they said.

“Provider-focused strategies to increase adherence could capitalize on the numerous annual outpatient encounters with the health care system that children with SCA are already experiencing,” they wrote.

The study was supported by a grant from the Agency for Healthcare Research and Quality and the Centers for Medicare and Medicaid Services. The researchers reported having no financial disclosures.

SOURCE: Reeves S et al. Pediatrics. 2018;141(3):e20172182. doi: 10.1542/peds.2017-2182.

Despite the increased risk for invasive pneumococcal disease, prophylactic antibiotics are underused in children with sickle cell anemia, according to data from more than 2,000 children in six states.

Less than one-fifth (18%) of young children (aged 3 months to 5 years) with sickle cell anemia (SCA) receive at least 300 days of prophylactic antibiotics to reduce their risk of pneumococcal infections, the analysis found.

“Although the effectiveness of daily penicillin prophylaxis has been known for decades, limited evidence indicates low rates of compliance among children,” wrote Sarah L. Reeves, PhD, of the University of Michigan, Ann Arbor, and her colleagues. The report was published in Pediatrics.

The researchers reviewed Medicaid claims for 2,821 children with SCA from the period of 2005-2012 for a total of 5,014 person-years. The data were taken from six states: Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. Antibiotic prophylaxis was defined as four different treatment protocols: oral penicillin; oral penicillin or erythromycin; oral penicillin, erythromycin, or amoxicillin; or any antibiotic that could protect against Streptococcus pneumoniae.

Overall, the children in the study averaged 1.7 sickle cell disease–related inpatient hospitalizations annually, as well as 13.2 sickle cell disease–related outpatient visits and 3.8 emergency department visits per year.

The proportion of children who received 300 days or more of prophylactic antibiotics varied by state, by year, and by type of treatment. “In this multistate analysis, receipt of antibiotic prophylaxis among children with SCA was persistently low, irrespective of year or state,” the researchers noted.

The odds that a child received 300 days or more of prophylactic antibiotics increased with each outpatient visit, including well child visits and sickle cell disease–related visits (odds ratios 1.08 and 1.01, respectively).

A child in the third quartile of sickle cell disease–related outpatient visits (defined as 17 annual visits) was 15% more likely than was a child in the first quartile (defined as six annual visits) to receive at least 300 days of antibiotics.

The study findings were limited by several factors including potential overestimation of how many children received medication, the researchers said. However, the results suggest the need for practical and effective intervention that targets barriers to treatment adherence, they said.

“Provider-focused strategies to increase adherence could capitalize on the numerous annual outpatient encounters with the health care system that children with SCA are already experiencing,” they wrote.

The study was supported by a grant from the Agency for Healthcare Research and Quality and the Centers for Medicare and Medicaid Services. The researchers reported having no financial disclosures.

SOURCE: Reeves S et al. Pediatrics. 2018;141(3):e20172182. doi: 10.1542/peds.2017-2182.

Despite the increased risk for invasive pneumococcal disease, prophylactic antibiotics are underused in children with sickle cell anemia, according to data from more than 2,000 children in six states.

Less than one-fifth (18%) of young children (aged 3 months to 5 years) with sickle cell anemia (SCA) receive at least 300 days of prophylactic antibiotics to reduce their risk of pneumococcal infections, the analysis found.

“Although the effectiveness of daily penicillin prophylaxis has been known for decades, limited evidence indicates low rates of compliance among children,” wrote Sarah L. Reeves, PhD, of the University of Michigan, Ann Arbor, and her colleagues. The report was published in Pediatrics.

The researchers reviewed Medicaid claims for 2,821 children with SCA from the period of 2005-2012 for a total of 5,014 person-years. The data were taken from six states: Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. Antibiotic prophylaxis was defined as four different treatment protocols: oral penicillin; oral penicillin or erythromycin; oral penicillin, erythromycin, or amoxicillin; or any antibiotic that could protect against Streptococcus pneumoniae.

Overall, the children in the study averaged 1.7 sickle cell disease–related inpatient hospitalizations annually, as well as 13.2 sickle cell disease–related outpatient visits and 3.8 emergency department visits per year.

The proportion of children who received 300 days or more of prophylactic antibiotics varied by state, by year, and by type of treatment. “In this multistate analysis, receipt of antibiotic prophylaxis among children with SCA was persistently low, irrespective of year or state,” the researchers noted.

The odds that a child received 300 days or more of prophylactic antibiotics increased with each outpatient visit, including well child visits and sickle cell disease–related visits (odds ratios 1.08 and 1.01, respectively).

A child in the third quartile of sickle cell disease–related outpatient visits (defined as 17 annual visits) was 15% more likely than was a child in the first quartile (defined as six annual visits) to receive at least 300 days of antibiotics.

The study findings were limited by several factors including potential overestimation of how many children received medication, the researchers said. However, the results suggest the need for practical and effective intervention that targets barriers to treatment adherence, they said.

“Provider-focused strategies to increase adherence could capitalize on the numerous annual outpatient encounters with the health care system that children with SCA are already experiencing,” they wrote.

The study was supported by a grant from the Agency for Healthcare Research and Quality and the Centers for Medicare and Medicaid Services. The researchers reported having no financial disclosures.

SOURCE: Reeves S et al. Pediatrics. 2018;141(3):e20172182. doi: 10.1542/peds.2017-2182.

Sexual harassment is one of the most insidious and caustic evils in the US workplace—and it knows no bounds, judging by the rampant allegations throughout 2017 and into 2018. While sexual harassment affects both sexes, the majority of cases target women.

In a recent survey, the New York Times asked 615 men about objectionable behavior toward colleagues, including whether they have made uninvited attempts to stroke, fondle, or kiss a coworker. Twenty-five percent admitted to telling crude jokes or sharing inappropriate videos. Two percent said they had pressured people into sexual acts by offering rewards or threatening retaliation—that means 12 men admitted to this.¹

Sadly, the health care industry is not immune from this corruption. In fact, sexual harassment is a major problem in health care—one that is particularly prevalent in nursing, according to Fiedler and Hamby.² More than 50% of female nurses, physicians, and students report experiencing sexual harassment.³ And even that, I believe, is an underreported percentage.

Sexual harassment in the workplace includes any situation in which there is a demand for sexual favors in exchange for a job benefit or where an unwanted condition on any person’s employment is imposed because of that person’s sex. Since 1964, Title VII of the Civil Rights Act (42 USC Sec.2000e-2[a]) has prohibited discrimination in places of employment based on an individual’s sex.⁴ In 1976, it was acknowledged that this also prohibits sexual harassment as a form of sex discrimination. In 1991, amendments (42 USC Sec.1981 [a][1]) authorized compensatory and punitive damages as well as jury trials.⁵

The Equal Employment Opportunity Commission (EEOC), the federal agency that enforces Title VII, stipulates that

• Harassment can include unwelcome sexual advances, requests for sexual favors, and other verbal or physical harassment—but it does not have to be sexual in nature (eg, making offensive comments about women in general).
• Both women and men can be victims and harassers—and the victim and harasser can be the same sex.
• Harassment is illegal when it is so frequent or severe that it creates a hostile or offensive work environment, or when it results in an adverse employment decision (eg, the victim being fired or demoted).⁶

Although the EEOC guidelines are not law, they do guide the judicial interpretation of what constitutes sexual harassment. Sexual harassment is an increasing source of workplace lawsuits that often result in large judgments against employers. Clinicians can file class-action suits against hospitals and other institutions, and juries may render verdicts on harassment complaints to the tune of millions of dollars.

Unfortunately, it is common for workplace harassment to go unreported. According to the EEOC, standard responses to workplace sexual harassment include avoiding the harasser, denying or downplaying the gravity of the situation, or attempting to ignore, forget, or endure the behavior. The least common response is to take formal action—either by reporting it internally or filing a legal complaint. Further, roughly three of four individuals who experience harassment in the workplace never tell a supervisor, manager, or union representative due to fear of disbelief, inaction, blame, or social or professional retaliation.⁷

How can we, as clinicians, protect ourselves and others from this type of harassment? Establishing a strong zero-tolerance policy on sexual harassment and reporting unacceptable behavior is the only answer. I realize this is no easy issue, but we must be firm in our resolve. Although 2017 was a watershed year with “Silence Breaker” or “#MeToo,” there are still many voices not being heard.⁸

So, here is my request: If you have been directly affected by, or have observed, objectionable behavior that violates your organization’s policy or code of conduct (or your personal sense of decency), document the incident and report it. You may be hesitant; maybe you think the behavior is an isolated act, or maybe the offender is a well-liked colleague who usually acts professionally. But your role is not to decide whether this behavior is acute or chronic—the human resources department will determine that. Maybe you are reluctant to report harassment because you fear reprisal. This is understandable, but remember that intimidation allows the behavior to persist. If the incident was upsetting and objectionable, it needs to be reported—no matter what.

The process of documenting and reporting varies depending on your institution’s policy but typically involves writing a factual description of the incident, including the time, place, and a list of any witnesses (including patients). Make sure your report is objective, and include any effect the behavior has had on patient care. Document any verbal exchanges verbatim, if possible. File the report as soon as possible, and remember to document everything. Nothing is trivial when it comes to building a case against sexual harassment. After you document and report the incident, continue to act professionally.⁹

If you are unable to resolve a harassment-related issue through your employer’s internal procedure, you may need to pursue the matter via the EEOC or your state’s human rights or civil rights enforcement agency.¹⁰ But know that any time and effort you put into reporting this is worthwhile; predatory behavior often crosses the workplace to other social realms. The other people being affected will be grateful that you came forward.

Some of you may be reading this and thinking, “Easy for you to say, Randy. You are not the one being harassed!” I know. This is not an easy topic for anyone. I have been shocked and appalled by the level and prevalence of sexual harassment in the workplace. I was always taught (by my grandmother—thank you!) to respect women. My hope is that by introducing this sensitive topic, we can open the discussion and encourage everyone to speak up. Please share your thoughts, comments, and ideas with me at PAeditor@frontlinemedcom.com—let’s start a conversation.

Sexual harassment is one of the most insidious and caustic evils in the US workplace—and it knows no bounds, judging by the rampant allegations throughout 2017 and into 2018. While sexual harassment affects both sexes, the majority of cases target women.

In a recent survey, the New York Times asked 615 men about objectionable behavior toward colleagues, including whether they have made uninvited attempts to stroke, fondle, or kiss a coworker. Twenty-five percent admitted to telling crude jokes or sharing inappropriate videos. Two percent said they had pressured people into sexual acts by offering rewards or threatening retaliation—that means 12 men admitted to this.¹

Sadly, the health care industry is not immune from this corruption. In fact, sexual harassment is a major problem in health care—one that is particularly prevalent in nursing, according to Fiedler and Hamby.² More than 50% of female nurses, physicians, and students report experiencing sexual harassment.³ And even that, I believe, is an underreported percentage.

Sexual harassment in the workplace includes any situation in which there is a demand for sexual favors in exchange for a job benefit or where an unwanted condition on any person’s employment is imposed because of that person’s sex. Since 1964, Title VII of the Civil Rights Act (42 USC Sec.2000e-2[a]) has prohibited discrimination in places of employment based on an individual’s sex.⁴ In 1976, it was acknowledged that this also prohibits sexual harassment as a form of sex discrimination. In 1991, amendments (42 USC Sec.1981 [a][1]) authorized compensatory and punitive damages as well as jury trials.⁵

The Equal Employment Opportunity Commission (EEOC), the federal agency that enforces Title VII, stipulates that

• Harassment can include unwelcome sexual advances, requests for sexual favors, and other verbal or physical harassment—but it does not have to be sexual in nature (eg, making offensive comments about women in general).
• Both women and men can be victims and harassers—and the victim and harasser can be the same sex.
• Harassment is illegal when it is so frequent or severe that it creates a hostile or offensive work environment, or when it results in an adverse employment decision (eg, the victim being fired or demoted).⁶

Although the EEOC guidelines are not law, they do guide the judicial interpretation of what constitutes sexual harassment. Sexual harassment is an increasing source of workplace lawsuits that often result in large judgments against employers. Clinicians can file class-action suits against hospitals and other institutions, and juries may render verdicts on harassment complaints to the tune of millions of dollars.

Unfortunately, it is common for workplace harassment to go unreported. According to the EEOC, standard responses to workplace sexual harassment include avoiding the harasser, denying or downplaying the gravity of the situation, or attempting to ignore, forget, or endure the behavior. The least common response is to take formal action—either by reporting it internally or filing a legal complaint. Further, roughly three of four individuals who experience harassment in the workplace never tell a supervisor, manager, or union representative due to fear of disbelief, inaction, blame, or social or professional retaliation.⁷

How can we, as clinicians, protect ourselves and others from this type of harassment? Establishing a strong zero-tolerance policy on sexual harassment and reporting unacceptable behavior is the only answer. I realize this is no easy issue, but we must be firm in our resolve. Although 2017 was a watershed year with “Silence Breaker” or “#MeToo,” there are still many voices not being heard.⁸

So, here is my request: If you have been directly affected by, or have observed, objectionable behavior that violates your organization’s policy or code of conduct (or your personal sense of decency), document the incident and report it. You may be hesitant; maybe you think the behavior is an isolated act, or maybe the offender is a well-liked colleague who usually acts professionally. But your role is not to decide whether this behavior is acute or chronic—the human resources department will determine that. Maybe you are reluctant to report harassment because you fear reprisal. This is understandable, but remember that intimidation allows the behavior to persist. If the incident was upsetting and objectionable, it needs to be reported—no matter what.

The process of documenting and reporting varies depending on your institution’s policy but typically involves writing a factual description of the incident, including the time, place, and a list of any witnesses (including patients). Make sure your report is objective, and include any effect the behavior has had on patient care. Document any verbal exchanges verbatim, if possible. File the report as soon as possible, and remember to document everything. Nothing is trivial when it comes to building a case against sexual harassment. After you document and report the incident, continue to act professionally.⁹

If you are unable to resolve a harassment-related issue through your employer’s internal procedure, you may need to pursue the matter via the EEOC or your state’s human rights or civil rights enforcement agency.¹⁰ But know that any time and effort you put into reporting this is worthwhile; predatory behavior often crosses the workplace to other social realms. The other people being affected will be grateful that you came forward.

Some of you may be reading this and thinking, “Easy for you to say, Randy. You are not the one being harassed!” I know. This is not an easy topic for anyone. I have been shocked and appalled by the level and prevalence of sexual harassment in the workplace. I was always taught (by my grandmother—thank you!) to respect women. My hope is that by introducing this sensitive topic, we can open the discussion and encourage everyone to speak up. Please share your thoughts, comments, and ideas with me at PAeditor@frontlinemedcom.com—let’s start a conversation.

Sexual harassment is one of the most insidious and caustic evils in the US workplace—and it knows no bounds, judging by the rampant allegations throughout 2017 and into 2018. While sexual harassment affects both sexes, the majority of cases target women.

In a recent survey, the New York Times asked 615 men about objectionable behavior toward colleagues, including whether they have made uninvited attempts to stroke, fondle, or kiss a coworker. Twenty-five percent admitted to telling crude jokes or sharing inappropriate videos. Two percent said they had pressured people into sexual acts by offering rewards or threatening retaliation—that means 12 men admitted to this.¹

Sadly, the health care industry is not immune from this corruption. In fact, sexual harassment is a major problem in health care—one that is particularly prevalent in nursing, according to Fiedler and Hamby.² More than 50% of female nurses, physicians, and students report experiencing sexual harassment.³ And even that, I believe, is an underreported percentage.

Sexual harassment in the workplace includes any situation in which there is a demand for sexual favors in exchange for a job benefit or where an unwanted condition on any person’s employment is imposed because of that person’s sex. Since 1964, Title VII of the Civil Rights Act (42 USC Sec.2000e-2[a]) has prohibited discrimination in places of employment based on an individual’s sex.⁴ In 1976, it was acknowledged that this also prohibits sexual harassment as a form of sex discrimination. In 1991, amendments (42 USC Sec.1981 [a][1]) authorized compensatory and punitive damages as well as jury trials.⁵

The Equal Employment Opportunity Commission (EEOC), the federal agency that enforces Title VII, stipulates that

• Harassment can include unwelcome sexual advances, requests for sexual favors, and other verbal or physical harassment—but it does not have to be sexual in nature (eg, making offensive comments about women in general).
• Both women and men can be victims and harassers—and the victim and harasser can be the same sex.
• Harassment is illegal when it is so frequent or severe that it creates a hostile or offensive work environment, or when it results in an adverse employment decision (eg, the victim being fired or demoted).⁶

Although the EEOC guidelines are not law, they do guide the judicial interpretation of what constitutes sexual harassment. Sexual harassment is an increasing source of workplace lawsuits that often result in large judgments against employers. Clinicians can file class-action suits against hospitals and other institutions, and juries may render verdicts on harassment complaints to the tune of millions of dollars.

Unfortunately, it is common for workplace harassment to go unreported. According to the EEOC, standard responses to workplace sexual harassment include avoiding the harasser, denying or downplaying the gravity of the situation, or attempting to ignore, forget, or endure the behavior. The least common response is to take formal action—either by reporting it internally or filing a legal complaint. Further, roughly three of four individuals who experience harassment in the workplace never tell a supervisor, manager, or union representative due to fear of disbelief, inaction, blame, or social or professional retaliation.⁷

How can we, as clinicians, protect ourselves and others from this type of harassment? Establishing a strong zero-tolerance policy on sexual harassment and reporting unacceptable behavior is the only answer. I realize this is no easy issue, but we must be firm in our resolve. Although 2017 was a watershed year with “Silence Breaker” or “#MeToo,” there are still many voices not being heard.⁸

So, here is my request: If you have been directly affected by, or have observed, objectionable behavior that violates your organization’s policy or code of conduct (or your personal sense of decency), document the incident and report it. You may be hesitant; maybe you think the behavior is an isolated act, or maybe the offender is a well-liked colleague who usually acts professionally. But your role is not to decide whether this behavior is acute or chronic—the human resources department will determine that. Maybe you are reluctant to report harassment because you fear reprisal. This is understandable, but remember that intimidation allows the behavior to persist. If the incident was upsetting and objectionable, it needs to be reported—no matter what.

The process of documenting and reporting varies depending on your institution’s policy but typically involves writing a factual description of the incident, including the time, place, and a list of any witnesses (including patients). Make sure your report is objective, and include any effect the behavior has had on patient care. Document any verbal exchanges verbatim, if possible. File the report as soon as possible, and remember to document everything. Nothing is trivial when it comes to building a case against sexual harassment. After you document and report the incident, continue to act professionally.⁹

If you are unable to resolve a harassment-related issue through your employer’s internal procedure, you may need to pursue the matter via the EEOC or your state’s human rights or civil rights enforcement agency.¹⁰ But know that any time and effort you put into reporting this is worthwhile; predatory behavior often crosses the workplace to other social realms. The other people being affected will be grateful that you came forward.

Some of you may be reading this and thinking, “Easy for you to say, Randy. You are not the one being harassed!” I know. This is not an easy topic for anyone. I have been shocked and appalled by the level and prevalence of sexual harassment in the workplace. I was always taught (by my grandmother—thank you!) to respect women. My hope is that by introducing this sensitive topic, we can open the discussion and encourage everyone to speak up. Please share your thoughts, comments, and ideas with me at PAeditor@frontlinemedcom.com—let’s start a conversation.

This video was filmed at Metabolic & Endocrine Disease Summit (MEDS). Click here to learn more.

This video was filmed at Metabolic & Endocrine Disease Summit (MEDS). Click here to learn more.

This video was filmed at Metabolic & Endocrine Disease Summit (MEDS). Click here to learn more.

The evidence has been accumulating for decades: Practicing surgery can exact a toll on surgeons’ physical well-being in ways that can shorten careers and contribute to professional dissatisfaction.

“Ergonomists have described the surgeon’s work environment and working conditions as equal to, if not at times harsher than, those of certain industrial workers,” wrote Sherise Epstein, MPH, and the coauthors of the systematic review and meta-analysis of studies addressing the issue. Ms. Epstein, currently a 4th-year medical student at the University of California, San Diego, and her team found a high prevalence of work-related musculoskeletal disorders and pain among surgeons and interventionalists, with pooled prevalence estimates for pain among these physicians ranging from 35% to 60% of all respondents. Cervical spine disease, rotator cuff pathology, and degenerative lumbar spine disease were each reported by nearly one in five respondents in the pooled analyses, with increasing prevalence over the duration of the study period (JAMA Surg. 2017 Dec 27. doi:10.1001/jamasurg.2017.49).

These findings, called “worrisome” by the study’s authors, come at a time when the demand for surgeons and interventionalists is expected soon to outstrip supply, and point to a major stressor for a profession already plagued by high rates of burnout and depression.

The results of the study are in line with previous work that finds a high – and increasing – rate of pain and disability among at-risk physicians, who endure long work hours, awkward positioning, and few opportunities for breaks.

The study also suggested a possible linkage between work-related pain and other factors, such as burnout and depression, that lead to attrition in the surgical profession.

Anne Arundel Medical Center

Adrian Park, MD, FACS, a general surgeon who has long studied the issue of work-related musculoskeletal disorders (MSDs) among surgeons and interventionalists, was not surprised by the study’s findings. “This just goes to further the narrative, which is a consistent one: These aren’t just sporadic instances of individual surgeons having a tough time; this is an increasingly broadly recognized problem. ... These are the consequences of surgeons simply getting up and going to work each week,” Dr. Park said in an interview.

To take a long view of the published data on work-related injury and pain for at-risk physicians, Ms. Epstein and her collaborators identified 126 articles reporting physician work-related MSDs that met quality standards; the studies spanned 1974 to 2016, and 23 countries were represented.

A total of 21 articles were eventually included in the meta-analysis, which included responses from 5,828 physicians. Most of the respondents were male (78.5%), with a mean age of 46 years and a mean 12.8 years in practice. The mean number of hours spent in procedures per week was 14.4.

Sixteen cross-sectional studies included in the meta-analysis examined injury prevalence, with 14 studies eventually meeting eligibility criteria for quantitative synthesis. A total of 4,245 physicians were included in this portion of the analysis; 1,232 were orthopedic surgeons, 1,118 were interventional cardiologists, and 582 were general surgeons (a variety of other subspecialties made up the remainder).

The career prevalence of degenerative lumbar spine disease was estimated at 19%, with prevalence increasing over time in a series of surveys of interventional cardiologists, said Ms. Epstein and her colleagues. Among this group, the prevalence climbed from 6.5% in 1997 to 24.7% in 2015, an increase in prevalence of over 18%, they said. The investigators’ estimate of lumbar spine disease prevalence from their own data also showed an increase, to 21%, for studies published within the past decade.

Rotator cuff pathology during the study period was estimated at 18% overall, and carpal tunnel syndrome at 9% overall; carpal tunnel syndrome also appears to be increasing in prevalence, estimated at 12% within the last decade.

Musculoskeletal pain that was judged to be work related was common, as reported in 18 cross-sectional studies. Taken together, the studies used a total of five validated tools that measured both pain prevalence and related disability. Twelve of the studies met criteria for inclusion in the quantitative synthesis.

Neck, back, and shoulder pain were all common in this group of surgeons and interventionalists. Neck pain had a 60% estimated 12-month prevalence, and shoulder pain was almost as common, with a 52% prevalence; back pain was reported for about half (49%) of respondents.

Just 10 of the included studies addressed disability burden, said Ms. Epstein and her colleagues. Overall, 12% of physicians responding in this subset of studies reported that they required work modification, leave of absence, or early retirement because of work-related MSDs.

In a separate arm of the analysis, Ms. Epstein and her collaborators looked at studies that discussed ergonomic assessments and interventions, using a qualitative approach. A total of 101 studies, 50 of them in the United States, were included. None of the studies, they said, “included long-term surveillance for work-related MSDs”; rather, they focused on short-term outcomes and, in some cases, on real-time electromyographic data.

Of the 101 studies looking at ergonomics, about a third (n = 38) looked primarily at ergonomically designed devices or technology, while another third (n = 37) focused on educational or behavioral interventions and modifications. These were the studies included in the investigators’ analysis.

A lack of awareness of ergonomic recommendations on the part of the surgeons themselves was identified in several studies. Several specialties, publishing in a total of eight countries, have put forward “at least one article describing a need for ergonomics education during medical training.” And, said the investigators, “A few studies have found that ergonomics education during medical training appears feasible, accepted, and effective at changing behaviors and reducing symptoms.”

In addition to the usual limitations inherent to the meta-analysis research design (selection bias, self-reported data, small samples of individual studies), the study was limited by the elusive nature of the topic. Work-related pain and disability among surgeons remains underreported and underestimated, according to both Dr. Park and the study investigators. Further research is needed, and the investigators wrote: “Ultimately, this work should be integrated with research on preventing surgeon burnout and attrition given shared risk factors.”
 

Micro breaks can help

What’s the solution? Dr. Park says that some fixes are low tech, and can be put in place immediately. He and his team implemented a series of brief breaks, taken every half hour during a procedure, that they dubbed “targeted stretching micro breaks.” These are 45- to 50-second breaks during which a series of exercise physiologist–designed brief stretches are undertaken that do not require breaking scrub.

In a study of 66 surgeons and operating room staff, Dr. Park, chair of the department of surgery at Anne Arundel Medical Center, Annapolis, Md., and his collaborators found that surgeons reported less pain and fatigue, and improved mental focus, when they took micro breaks during a procedure. When surgeons took micro breaks, operative time was no longer than when they didn’t take the breaks (Ann Surg. 2017 Feb;265[2]:340-6).

“We do this all the time in our operating room now,” said Dr. Park. “And it makes a difference in terms of pain, in terms of alertness, in terms of stamina. And it costs nothing.”
 

Major redesign of tools and workspace

Other targets for technological improvement include offering better-designed handles for laparoscopic instruments. “We’ve had one size fits all forever. Why has it taken us so long to recognize that there’s not one size of surgical hand?” asked Dr. Park. He made the point that the influx of women – whose hands are smaller on average than men’s – into the surgical professions makes this a particularly pressing issue.

“The high-tech piece is going to be a better understanding of the operative work flow,” said Dr. Park, calling for “a meaningful revisiting of the surgeon-device interface and the surgeon-patient interface.”

A fundamental redesign of the operating room will eventually be in order, he said, contrasting the surgeon’s environments with that of an airline pilot. In the cockpit, the pilot sees a “heads-up” display of a limited amount of data, with an eye to controlling the cognitive workload for the operator. By contrast, said Dr. Park, in the OR, there are “lights flashing, and things pinging,” and pieces of equipment don’t “talk” to each other, presenting sometimes overwhelming sensory input that just potentiates the stress of the environment. Operating room design, he said, should move toward an ergonomically improved and stimulus-controlled environment.

As the leader of the surgical team, and as a physician whose foremost concern is the patient on the table, the surgeon may inadvertently have fallen into a role where his or her well-being is neglected.

Dr. Park suggested that, in the surgical profession, “it has never felt safe or appropriate to talk about ourselves.” But for the good of the profession, and ultimately for patient care, “this has to change.”

Ms. Epstein and her coauthors reported no conflicts of interest. .
 

koakes@frontlinemedcom.com

The evidence has been accumulating for decades: Practicing surgery can exact a toll on surgeons’ physical well-being in ways that can shorten careers and contribute to professional dissatisfaction.

“Ergonomists have described the surgeon’s work environment and working conditions as equal to, if not at times harsher than, those of certain industrial workers,” wrote Sherise Epstein, MPH, and the coauthors of the systematic review and meta-analysis of studies addressing the issue. Ms. Epstein, currently a 4th-year medical student at the University of California, San Diego, and her team found a high prevalence of work-related musculoskeletal disorders and pain among surgeons and interventionalists, with pooled prevalence estimates for pain among these physicians ranging from 35% to 60% of all respondents. Cervical spine disease, rotator cuff pathology, and degenerative lumbar spine disease were each reported by nearly one in five respondents in the pooled analyses, with increasing prevalence over the duration of the study period (JAMA Surg. 2017 Dec 27. doi:10.1001/jamasurg.2017.49).

These findings, called “worrisome” by the study’s authors, come at a time when the demand for surgeons and interventionalists is expected soon to outstrip supply, and point to a major stressor for a profession already plagued by high rates of burnout and depression.

The results of the study are in line with previous work that finds a high – and increasing – rate of pain and disability among at-risk physicians, who endure long work hours, awkward positioning, and few opportunities for breaks.

The study also suggested a possible linkage between work-related pain and other factors, such as burnout and depression, that lead to attrition in the surgical profession.

Anne Arundel Medical Center

Adrian Park, MD, FACS, a general surgeon who has long studied the issue of work-related musculoskeletal disorders (MSDs) among surgeons and interventionalists, was not surprised by the study’s findings. “This just goes to further the narrative, which is a consistent one: These aren’t just sporadic instances of individual surgeons having a tough time; this is an increasingly broadly recognized problem. ... These are the consequences of surgeons simply getting up and going to work each week,” Dr. Park said in an interview.

To take a long view of the published data on work-related injury and pain for at-risk physicians, Ms. Epstein and her collaborators identified 126 articles reporting physician work-related MSDs that met quality standards; the studies spanned 1974 to 2016, and 23 countries were represented.

A total of 21 articles were eventually included in the meta-analysis, which included responses from 5,828 physicians. Most of the respondents were male (78.5%), with a mean age of 46 years and a mean 12.8 years in practice. The mean number of hours spent in procedures per week was 14.4.

Sixteen cross-sectional studies included in the meta-analysis examined injury prevalence, with 14 studies eventually meeting eligibility criteria for quantitative synthesis. A total of 4,245 physicians were included in this portion of the analysis; 1,232 were orthopedic surgeons, 1,118 were interventional cardiologists, and 582 were general surgeons (a variety of other subspecialties made up the remainder).

The career prevalence of degenerative lumbar spine disease was estimated at 19%, with prevalence increasing over time in a series of surveys of interventional cardiologists, said Ms. Epstein and her colleagues. Among this group, the prevalence climbed from 6.5% in 1997 to 24.7% in 2015, an increase in prevalence of over 18%, they said. The investigators’ estimate of lumbar spine disease prevalence from their own data also showed an increase, to 21%, for studies published within the past decade.

Rotator cuff pathology during the study period was estimated at 18% overall, and carpal tunnel syndrome at 9% overall; carpal tunnel syndrome also appears to be increasing in prevalence, estimated at 12% within the last decade.

Musculoskeletal pain that was judged to be work related was common, as reported in 18 cross-sectional studies. Taken together, the studies used a total of five validated tools that measured both pain prevalence and related disability. Twelve of the studies met criteria for inclusion in the quantitative synthesis.

Neck, back, and shoulder pain were all common in this group of surgeons and interventionalists. Neck pain had a 60% estimated 12-month prevalence, and shoulder pain was almost as common, with a 52% prevalence; back pain was reported for about half (49%) of respondents.

Just 10 of the included studies addressed disability burden, said Ms. Epstein and her colleagues. Overall, 12% of physicians responding in this subset of studies reported that they required work modification, leave of absence, or early retirement because of work-related MSDs.

In a separate arm of the analysis, Ms. Epstein and her collaborators looked at studies that discussed ergonomic assessments and interventions, using a qualitative approach. A total of 101 studies, 50 of them in the United States, were included. None of the studies, they said, “included long-term surveillance for work-related MSDs”; rather, they focused on short-term outcomes and, in some cases, on real-time electromyographic data.

Of the 101 studies looking at ergonomics, about a third (n = 38) looked primarily at ergonomically designed devices or technology, while another third (n = 37) focused on educational or behavioral interventions and modifications. These were the studies included in the investigators’ analysis.

A lack of awareness of ergonomic recommendations on the part of the surgeons themselves was identified in several studies. Several specialties, publishing in a total of eight countries, have put forward “at least one article describing a need for ergonomics education during medical training.” And, said the investigators, “A few studies have found that ergonomics education during medical training appears feasible, accepted, and effective at changing behaviors and reducing symptoms.”

In addition to the usual limitations inherent to the meta-analysis research design (selection bias, self-reported data, small samples of individual studies), the study was limited by the elusive nature of the topic. Work-related pain and disability among surgeons remains underreported and underestimated, according to both Dr. Park and the study investigators. Further research is needed, and the investigators wrote: “Ultimately, this work should be integrated with research on preventing surgeon burnout and attrition given shared risk factors.”
 

Micro breaks can help

What’s the solution? Dr. Park says that some fixes are low tech, and can be put in place immediately. He and his team implemented a series of brief breaks, taken every half hour during a procedure, that they dubbed “targeted stretching micro breaks.” These are 45- to 50-second breaks during which a series of exercise physiologist–designed brief stretches are undertaken that do not require breaking scrub.

In a study of 66 surgeons and operating room staff, Dr. Park, chair of the department of surgery at Anne Arundel Medical Center, Annapolis, Md., and his collaborators found that surgeons reported less pain and fatigue, and improved mental focus, when they took micro breaks during a procedure. When surgeons took micro breaks, operative time was no longer than when they didn’t take the breaks (Ann Surg. 2017 Feb;265[2]:340-6).

“We do this all the time in our operating room now,” said Dr. Park. “And it makes a difference in terms of pain, in terms of alertness, in terms of stamina. And it costs nothing.”
 

Major redesign of tools and workspace

Other targets for technological improvement include offering better-designed handles for laparoscopic instruments. “We’ve had one size fits all forever. Why has it taken us so long to recognize that there’s not one size of surgical hand?” asked Dr. Park. He made the point that the influx of women – whose hands are smaller on average than men’s – into the surgical professions makes this a particularly pressing issue.

“The high-tech piece is going to be a better understanding of the operative work flow,” said Dr. Park, calling for “a meaningful revisiting of the surgeon-device interface and the surgeon-patient interface.”

A fundamental redesign of the operating room will eventually be in order, he said, contrasting the surgeon’s environments with that of an airline pilot. In the cockpit, the pilot sees a “heads-up” display of a limited amount of data, with an eye to controlling the cognitive workload for the operator. By contrast, said Dr. Park, in the OR, there are “lights flashing, and things pinging,” and pieces of equipment don’t “talk” to each other, presenting sometimes overwhelming sensory input that just potentiates the stress of the environment. Operating room design, he said, should move toward an ergonomically improved and stimulus-controlled environment.

As the leader of the surgical team, and as a physician whose foremost concern is the patient on the table, the surgeon may inadvertently have fallen into a role where his or her well-being is neglected.

Dr. Park suggested that, in the surgical profession, “it has never felt safe or appropriate to talk about ourselves.” But for the good of the profession, and ultimately for patient care, “this has to change.”

Ms. Epstein and her coauthors reported no conflicts of interest. .
 

koakes@frontlinemedcom.com

The evidence has been accumulating for decades: Practicing surgery can exact a toll on surgeons’ physical well-being in ways that can shorten careers and contribute to professional dissatisfaction.

“Ergonomists have described the surgeon’s work environment and working conditions as equal to, if not at times harsher than, those of certain industrial workers,” wrote Sherise Epstein, MPH, and the coauthors of the systematic review and meta-analysis of studies addressing the issue. Ms. Epstein, currently a 4th-year medical student at the University of California, San Diego, and her team found a high prevalence of work-related musculoskeletal disorders and pain among surgeons and interventionalists, with pooled prevalence estimates for pain among these physicians ranging from 35% to 60% of all respondents. Cervical spine disease, rotator cuff pathology, and degenerative lumbar spine disease were each reported by nearly one in five respondents in the pooled analyses, with increasing prevalence over the duration of the study period (JAMA Surg. 2017 Dec 27. doi:10.1001/jamasurg.2017.49).

These findings, called “worrisome” by the study’s authors, come at a time when the demand for surgeons and interventionalists is expected soon to outstrip supply, and point to a major stressor for a profession already plagued by high rates of burnout and depression.

The results of the study are in line with previous work that finds a high – and increasing – rate of pain and disability among at-risk physicians, who endure long work hours, awkward positioning, and few opportunities for breaks.

The study also suggested a possible linkage between work-related pain and other factors, such as burnout and depression, that lead to attrition in the surgical profession.

Anne Arundel Medical Center

Adrian Park, MD, FACS, a general surgeon who has long studied the issue of work-related musculoskeletal disorders (MSDs) among surgeons and interventionalists, was not surprised by the study’s findings. “This just goes to further the narrative, which is a consistent one: These aren’t just sporadic instances of individual surgeons having a tough time; this is an increasingly broadly recognized problem. ... These are the consequences of surgeons simply getting up and going to work each week,” Dr. Park said in an interview.

To take a long view of the published data on work-related injury and pain for at-risk physicians, Ms. Epstein and her collaborators identified 126 articles reporting physician work-related MSDs that met quality standards; the studies spanned 1974 to 2016, and 23 countries were represented.

A total of 21 articles were eventually included in the meta-analysis, which included responses from 5,828 physicians. Most of the respondents were male (78.5%), with a mean age of 46 years and a mean 12.8 years in practice. The mean number of hours spent in procedures per week was 14.4.

Sixteen cross-sectional studies included in the meta-analysis examined injury prevalence, with 14 studies eventually meeting eligibility criteria for quantitative synthesis. A total of 4,245 physicians were included in this portion of the analysis; 1,232 were orthopedic surgeons, 1,118 were interventional cardiologists, and 582 were general surgeons (a variety of other subspecialties made up the remainder).

The career prevalence of degenerative lumbar spine disease was estimated at 19%, with prevalence increasing over time in a series of surveys of interventional cardiologists, said Ms. Epstein and her colleagues. Among this group, the prevalence climbed from 6.5% in 1997 to 24.7% in 2015, an increase in prevalence of over 18%, they said. The investigators’ estimate of lumbar spine disease prevalence from their own data also showed an increase, to 21%, for studies published within the past decade.

Rotator cuff pathology during the study period was estimated at 18% overall, and carpal tunnel syndrome at 9% overall; carpal tunnel syndrome also appears to be increasing in prevalence, estimated at 12% within the last decade.

Musculoskeletal pain that was judged to be work related was common, as reported in 18 cross-sectional studies. Taken together, the studies used a total of five validated tools that measured both pain prevalence and related disability. Twelve of the studies met criteria for inclusion in the quantitative synthesis.

Neck, back, and shoulder pain were all common in this group of surgeons and interventionalists. Neck pain had a 60% estimated 12-month prevalence, and shoulder pain was almost as common, with a 52% prevalence; back pain was reported for about half (49%) of respondents.

Just 10 of the included studies addressed disability burden, said Ms. Epstein and her colleagues. Overall, 12% of physicians responding in this subset of studies reported that they required work modification, leave of absence, or early retirement because of work-related MSDs.

In a separate arm of the analysis, Ms. Epstein and her collaborators looked at studies that discussed ergonomic assessments and interventions, using a qualitative approach. A total of 101 studies, 50 of them in the United States, were included. None of the studies, they said, “included long-term surveillance for work-related MSDs”; rather, they focused on short-term outcomes and, in some cases, on real-time electromyographic data.

Of the 101 studies looking at ergonomics, about a third (n = 38) looked primarily at ergonomically designed devices or technology, while another third (n = 37) focused on educational or behavioral interventions and modifications. These were the studies included in the investigators’ analysis.

A lack of awareness of ergonomic recommendations on the part of the surgeons themselves was identified in several studies. Several specialties, publishing in a total of eight countries, have put forward “at least one article describing a need for ergonomics education during medical training.” And, said the investigators, “A few studies have found that ergonomics education during medical training appears feasible, accepted, and effective at changing behaviors and reducing symptoms.”

In addition to the usual limitations inherent to the meta-analysis research design (selection bias, self-reported data, small samples of individual studies), the study was limited by the elusive nature of the topic. Work-related pain and disability among surgeons remains underreported and underestimated, according to both Dr. Park and the study investigators. Further research is needed, and the investigators wrote: “Ultimately, this work should be integrated with research on preventing surgeon burnout and attrition given shared risk factors.”
 

Micro breaks can help

What’s the solution? Dr. Park says that some fixes are low tech, and can be put in place immediately. He and his team implemented a series of brief breaks, taken every half hour during a procedure, that they dubbed “targeted stretching micro breaks.” These are 45- to 50-second breaks during which a series of exercise physiologist–designed brief stretches are undertaken that do not require breaking scrub.

In a study of 66 surgeons and operating room staff, Dr. Park, chair of the department of surgery at Anne Arundel Medical Center, Annapolis, Md., and his collaborators found that surgeons reported less pain and fatigue, and improved mental focus, when they took micro breaks during a procedure. When surgeons took micro breaks, operative time was no longer than when they didn’t take the breaks (Ann Surg. 2017 Feb;265[2]:340-6).

“We do this all the time in our operating room now,” said Dr. Park. “And it makes a difference in terms of pain, in terms of alertness, in terms of stamina. And it costs nothing.”
 

Major redesign of tools and workspace

Other targets for technological improvement include offering better-designed handles for laparoscopic instruments. “We’ve had one size fits all forever. Why has it taken us so long to recognize that there’s not one size of surgical hand?” asked Dr. Park. He made the point that the influx of women – whose hands are smaller on average than men’s – into the surgical professions makes this a particularly pressing issue.

“The high-tech piece is going to be a better understanding of the operative work flow,” said Dr. Park, calling for “a meaningful revisiting of the surgeon-device interface and the surgeon-patient interface.”

A fundamental redesign of the operating room will eventually be in order, he said, contrasting the surgeon’s environments with that of an airline pilot. In the cockpit, the pilot sees a “heads-up” display of a limited amount of data, with an eye to controlling the cognitive workload for the operator. By contrast, said Dr. Park, in the OR, there are “lights flashing, and things pinging,” and pieces of equipment don’t “talk” to each other, presenting sometimes overwhelming sensory input that just potentiates the stress of the environment. Operating room design, he said, should move toward an ergonomically improved and stimulus-controlled environment.

As the leader of the surgical team, and as a physician whose foremost concern is the patient on the table, the surgeon may inadvertently have fallen into a role where his or her well-being is neglected.

Dr. Park suggested that, in the surgical profession, “it has never felt safe or appropriate to talk about ourselves.” But for the good of the profession, and ultimately for patient care, “this has to change.”

Ms. Epstein and her coauthors reported no conflicts of interest. .
 

koakes@frontlinemedcom.com

Cantharidin is an effective therapy for facial molluscum contagiosum lesions if applied by dermatologists who are experienced with its application, said Marla N. Jahnke, MD, of the Henry Ford Health System, Detroit, and her associates.

It is important to be careful when applying or handling cantharidin near the eyes, they noted. Also, parents must be counseled about possible side effects such as painful blistering, dyspigmentation, scarring, and itching, and that multiple treatment sessions may be needed.

The researchers did a retrospective chart review on patients under age 18 years treated with a cantharidin 0.7% solution between March 2013 and March 2014 at their institution, and performed a telephone survey to collect treatment outcomes from caregivers. Of the 62 caregivers contacted, the pediatric patients’ median age was 5 years (range 1.7-13), and 45% of the patients were white, 26% were black, 20% were Middle Eastern, 6% were Latino, and 3% were Asian, Pacific Islander, or Indian.

After cantharidin treatment, the caregivers most often described temporary discoloration (18%), severe blistering (10%), and pain that was excessive or greater than the caregiver expected (10%). Other outcomes described included itching (8%), scarring (6%), irritation (5%), bleeding (3%), and spreading of lesions (2%).

“Two patients returned to the office within 1 week of treatment because of excessive localized blistering that healed without long-term complications when topical emollients were used. ... Caregivers often could not confirm that they had washed off the cantharidin as recommended (1.5-2 hours after in-office application),” Dr. Jahnke and her associates noted in a research letter, which was published in the Journal of the American Academy of Dermatology.

Treatment satisfaction was high, with 94% of caregivers saying they would request cantharidin again if molluscum contagiosum were to recur on the child’s face, and 92% saying they would recommend it to others whose children had facial molluscum contagiosum. On a scale of 1 to 10, the average treatment satisfaction score was 8.7. The caregivers said that cantharidin was well tolerated by their children because it was painless when applied. The need for multiple office visits was the biggest complaint, the researchers revealed.

cnellist@frontlinemedcom.com

SOURCE: J Am Acad Dermatol. 2018 Jan. doi: 10.1016/j.jaad.2017.09.006.

Cantharidin is an effective therapy for facial molluscum contagiosum lesions if applied by dermatologists who are experienced with its application, said Marla N. Jahnke, MD, of the Henry Ford Health System, Detroit, and her associates.

It is important to be careful when applying or handling cantharidin near the eyes, they noted. Also, parents must be counseled about possible side effects such as painful blistering, dyspigmentation, scarring, and itching, and that multiple treatment sessions may be needed.

The researchers did a retrospective chart review on patients under age 18 years treated with a cantharidin 0.7% solution between March 2013 and March 2014 at their institution, and performed a telephone survey to collect treatment outcomes from caregivers. Of the 62 caregivers contacted, the pediatric patients’ median age was 5 years (range 1.7-13), and 45% of the patients were white, 26% were black, 20% were Middle Eastern, 6% were Latino, and 3% were Asian, Pacific Islander, or Indian.

After cantharidin treatment, the caregivers most often described temporary discoloration (18%), severe blistering (10%), and pain that was excessive or greater than the caregiver expected (10%). Other outcomes described included itching (8%), scarring (6%), irritation (5%), bleeding (3%), and spreading of lesions (2%).

“Two patients returned to the office within 1 week of treatment because of excessive localized blistering that healed without long-term complications when topical emollients were used. ... Caregivers often could not confirm that they had washed off the cantharidin as recommended (1.5-2 hours after in-office application),” Dr. Jahnke and her associates noted in a research letter, which was published in the Journal of the American Academy of Dermatology.

Treatment satisfaction was high, with 94% of caregivers saying they would request cantharidin again if molluscum contagiosum were to recur on the child’s face, and 92% saying they would recommend it to others whose children had facial molluscum contagiosum. On a scale of 1 to 10, the average treatment satisfaction score was 8.7. The caregivers said that cantharidin was well tolerated by their children because it was painless when applied. The need for multiple office visits was the biggest complaint, the researchers revealed.

cnellist@frontlinemedcom.com

SOURCE: J Am Acad Dermatol. 2018 Jan. doi: 10.1016/j.jaad.2017.09.006.

Cantharidin is an effective therapy for facial molluscum contagiosum lesions if applied by dermatologists who are experienced with its application, said Marla N. Jahnke, MD, of the Henry Ford Health System, Detroit, and her associates.

It is important to be careful when applying or handling cantharidin near the eyes, they noted. Also, parents must be counseled about possible side effects such as painful blistering, dyspigmentation, scarring, and itching, and that multiple treatment sessions may be needed.

The researchers did a retrospective chart review on patients under age 18 years treated with a cantharidin 0.7% solution between March 2013 and March 2014 at their institution, and performed a telephone survey to collect treatment outcomes from caregivers. Of the 62 caregivers contacted, the pediatric patients’ median age was 5 years (range 1.7-13), and 45% of the patients were white, 26% were black, 20% were Middle Eastern, 6% were Latino, and 3% were Asian, Pacific Islander, or Indian.

After cantharidin treatment, the caregivers most often described temporary discoloration (18%), severe blistering (10%), and pain that was excessive or greater than the caregiver expected (10%). Other outcomes described included itching (8%), scarring (6%), irritation (5%), bleeding (3%), and spreading of lesions (2%).

“Two patients returned to the office within 1 week of treatment because of excessive localized blistering that healed without long-term complications when topical emollients were used. ... Caregivers often could not confirm that they had washed off the cantharidin as recommended (1.5-2 hours after in-office application),” Dr. Jahnke and her associates noted in a research letter, which was published in the Journal of the American Academy of Dermatology.

Treatment satisfaction was high, with 94% of caregivers saying they would request cantharidin again if molluscum contagiosum were to recur on the child’s face, and 92% saying they would recommend it to others whose children had facial molluscum contagiosum. On a scale of 1 to 10, the average treatment satisfaction score was 8.7. The caregivers said that cantharidin was well tolerated by their children because it was painless when applied. The need for multiple office visits was the biggest complaint, the researchers revealed.

cnellist@frontlinemedcom.com

SOURCE: J Am Acad Dermatol. 2018 Jan. doi: 10.1016/j.jaad.2017.09.006.

Bans keeping minors from using commercial tanning beds may be depriving dermatology patients of an alternative way to access phototherapy, said Daniel J. Lewis and Madeleine Duvic, MD, of the University of Texas MD Anderson Cancer Center, Houston.

To prevent skin cancer, many states and the District of Columbia have set in place age restrictions on the use of commercial tanning beds and banned minors from indoor tanning; another 12 states put in place bans at younger ages. The Food and Drug Administration proposed a policy in 2015 that would keep all minors from indoor tanning, according to Mr. Lewis and Dr. Duvic.

Phototherapy is known to be an effective treatment for psoriasis, mycosis fungoides, and vitiligo. Phototherapy usually is given in physician offices and administered in ultraviolet B for treatment of psoriasis, but studies have found that tanning beds, which emit primarily ultraviolet A, can produce a clinical response in 80% of psoriasis patients, and 53% of patients report using tanning beds for psoriasis treatment, Mr. Lewis and Dr. Duvic said in a letter to the editor in Clinics in Dermatology.

The demanding schedule of visiting a physician’s office three times a week for phototherapy can be hard for some patients, especially children attending school during regular office hours and patients in rural areas. High copayments also can limit access, the authors said.

©Vidmantas Goldbergas/iStockphoto.com

cnellist@frontlinemedcom.com

SOURCE: Lewis, DJ and Duvic, M. Clin Dermatol. 2018 Jan-Feb;36(1):104-5

Bans keeping minors from using commercial tanning beds may be depriving dermatology patients of an alternative way to access phototherapy, said Daniel J. Lewis and Madeleine Duvic, MD, of the University of Texas MD Anderson Cancer Center, Houston.

To prevent skin cancer, many states and the District of Columbia have set in place age restrictions on the use of commercial tanning beds and banned minors from indoor tanning; another 12 states put in place bans at younger ages. The Food and Drug Administration proposed a policy in 2015 that would keep all minors from indoor tanning, according to Mr. Lewis and Dr. Duvic.

Phototherapy is known to be an effective treatment for psoriasis, mycosis fungoides, and vitiligo. Phototherapy usually is given in physician offices and administered in ultraviolet B for treatment of psoriasis, but studies have found that tanning beds, which emit primarily ultraviolet A, can produce a clinical response in 80% of psoriasis patients, and 53% of patients report using tanning beds for psoriasis treatment, Mr. Lewis and Dr. Duvic said in a letter to the editor in Clinics in Dermatology.

The demanding schedule of visiting a physician’s office three times a week for phototherapy can be hard for some patients, especially children attending school during regular office hours and patients in rural areas. High copayments also can limit access, the authors said.

©Vidmantas Goldbergas/iStockphoto.com

cnellist@frontlinemedcom.com

SOURCE: Lewis, DJ and Duvic, M. Clin Dermatol. 2018 Jan-Feb;36(1):104-5

Bans keeping minors from using commercial tanning beds may be depriving dermatology patients of an alternative way to access phototherapy, said Daniel J. Lewis and Madeleine Duvic, MD, of the University of Texas MD Anderson Cancer Center, Houston.

To prevent skin cancer, many states and the District of Columbia have set in place age restrictions on the use of commercial tanning beds and banned minors from indoor tanning; another 12 states put in place bans at younger ages. The Food and Drug Administration proposed a policy in 2015 that would keep all minors from indoor tanning, according to Mr. Lewis and Dr. Duvic.

Phototherapy is known to be an effective treatment for psoriasis, mycosis fungoides, and vitiligo. Phototherapy usually is given in physician offices and administered in ultraviolet B for treatment of psoriasis, but studies have found that tanning beds, which emit primarily ultraviolet A, can produce a clinical response in 80% of psoriasis patients, and 53% of patients report using tanning beds for psoriasis treatment, Mr. Lewis and Dr. Duvic said in a letter to the editor in Clinics in Dermatology.

The demanding schedule of visiting a physician’s office three times a week for phototherapy can be hard for some patients, especially children attending school during regular office hours and patients in rural areas. High copayments also can limit access, the authors said.

©Vidmantas Goldbergas/iStockphoto.com

cnellist@frontlinemedcom.com

SOURCE: Lewis, DJ and Duvic, M. Clin Dermatol. 2018 Jan-Feb;36(1):104-5

Topical fluticasone propionate twice a week effectively reduces the risk of mild to moderate atopic dermatitis relapse in children, according to Elena Rubio-Gomis of the Consorcio Hospital General Universitario de Valencia, Spain, and her associates.

Most atopic disease management is based on managing active disease, but atopic dermatitis is a chronic relapsing disease for which long-term maintenance therapies are being sought.

“Fluticasone 0.05% cream is a potent topical corticosteroid with a low systemic absorption and rapid metabolism and clearance,” which argues for low likelihood of causing systemic side effects and possible use in preventing atopic dermatitis relapse, the investigators wrote. And it is not very expensive.

© -aniaostudio-/Thinkstock

cnellist@frontlinemedcom.com

SOURCE: Rubio-Gomis E et al. Allergol Immunopathol (Madr). 2018. doi: 10.1016/j.aller.2017.12.001.

Topical fluticasone propionate twice a week effectively reduces the risk of mild to moderate atopic dermatitis relapse in children, according to Elena Rubio-Gomis of the Consorcio Hospital General Universitario de Valencia, Spain, and her associates.

Most atopic disease management is based on managing active disease, but atopic dermatitis is a chronic relapsing disease for which long-term maintenance therapies are being sought.

“Fluticasone 0.05% cream is a potent topical corticosteroid with a low systemic absorption and rapid metabolism and clearance,” which argues for low likelihood of causing systemic side effects and possible use in preventing atopic dermatitis relapse, the investigators wrote. And it is not very expensive.

© -aniaostudio-/Thinkstock

cnellist@frontlinemedcom.com

SOURCE: Rubio-Gomis E et al. Allergol Immunopathol (Madr). 2018. doi: 10.1016/j.aller.2017.12.001.

Topical fluticasone propionate twice a week effectively reduces the risk of mild to moderate atopic dermatitis relapse in children, according to Elena Rubio-Gomis of the Consorcio Hospital General Universitario de Valencia, Spain, and her associates.

Most atopic disease management is based on managing active disease, but atopic dermatitis is a chronic relapsing disease for which long-term maintenance therapies are being sought.

“Fluticasone 0.05% cream is a potent topical corticosteroid with a low systemic absorption and rapid metabolism and clearance,” which argues for low likelihood of causing systemic side effects and possible use in preventing atopic dermatitis relapse, the investigators wrote. And it is not very expensive.

© -aniaostudio-/Thinkstock

cnellist@frontlinemedcom.com

SOURCE: Rubio-Gomis E et al. Allergol Immunopathol (Madr). 2018. doi: 10.1016/j.aller.2017.12.001.

SAN FRANCISCO – Immune-enriched acute myeloid leukemias might be amenable to immunotherapy that is tailored to the bone marrow tumor microenvironment, according to findings from a pan-cancer analysis of bone marrow samples.

The analysis, performed with 3D biology technology and an RNA pan-cancer immune profiling panel to characterize bone marrow specimens from 46 children and 28 adults with acute myeloid leukemia (AML), identified heterogeneous immune profiles that correlated with relapse-free survival (RFS) and overall survival (OS), Jayakumar Vadakekolathu, PhD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The specimens, including 63 from nonpromyelocytic de novo AML, 7 from AML in children with complete remission, 3 from adults with secondary AML, and 1 from an adult with treatment-related AML, were analyzed with the nCounter system from NanoString Technologies, and were visualized via digital spatial profiling, said Dr. Vadakekolathu of Nottingham Trent University in England.

Sharon Worcester/Frontline Medical News

“Prognosis is determined by cytogenetic and molecular abnormalities, as well as by response to chemotherapy. De novo AML is cured in roughly 70% of children, 35%-40% of adults, and 5%-15% of elderly patients,” he said. Some patients with AML fail to respond to induction chemotherapy, and others eventually relapse despite the lack of adverse risk factors, he added.

The general therapeutic strategy in patients with AML has not changed substantially in more than 30 years, he said.

“High degrees of molecular complexity in AML present a considerable challenge in clinical implementation, and there is an urgent need to discover better biomarkers to identify high-risk patients before starting chemotherapy, which would enable testing of investigational therapeutic strategies in clinical trials,” he said.

In an effort to identify immune gene signatures across the spectrum of AML genotypes and to correlate transcriptomic and proteomic profiles with patient outcomes, he and his colleagues used a pediatric cohort from Children’s Hospital of Philadelphia (median age at diagnosis of 10 years), and an adult cohort from the Technical University of Dresden, Germany (median age at diagnosis, 55.5 years). Bone marrow samples were collected and analyzed at diagnosis.

Hierarchical clustering identified the two distinct clusters. The immune-enriched cluster A had heightened expression of T cells, natural killer cells, and cytotoxic cells, and also expressed CD8A, IFNG, FOXP3, the cell chemoattractants CXCL9 and CXCL10, and inhibitory molecules including IDO1 and the immune checkpoints LAG3, CTLA4, and PD-L1. The immune-depleted cluster B overexpressed genes associated with mast cell functions and CD8 T-cell exhaustion, and showed low expression of T-cell and B-cell genes.

Further analysis of 10 of the inflamed samples from patients with newly diagnosed AML was performed with digital spatial profiling (DSP) to visualize in situ leukemia–immune system interactions, Dr. Vadakekolathu said.

Surface antigens CD123 and CD3 were used as a visualization marker for leukemia cells and to identify bone marrow-infiltrating T cells, respectively. Protein quantification showed a higher concentration of CD3 counts in T-cell-rich versus T-cell-poor areas, and protein expression profiles showed strong correlations with various immunologically relevant molecules. The co-localization of CD8 T cells with FoxP3 Treg cells and PD-L1- and VISTA-expressing cell types evident on DSP represents an immune landscape consistent with the establishment of adaptive immune resistance mechanisms of immune escape, he noted.

The findings suggest immune enriched AMLs might be amenable to combination immunotherapies tailored to the bone marrow tumor microenvironment, such as IDO1 inhibitors and checkpoint blockade, Dr. Vadakekolathu said. “Immune gene expression profiles of AML might support rapid prediction of patient outcomes, discovery of novel immune biomarkers and therapeutic targets, and development of integrated patient stratifications,” he said.

This study was supported by grants from the Roger Counter Foundation and the Qatar National Research Fund. Dr. Vadakekolathu reported having no disclosures. Some authors reported employment or other financial relationships with NanoString Technologies.

sworcester@frontlinemedcom.com

SOURCE: Rutella S et al. ASCO-SITC Abstract 50

SAN FRANCISCO – Immune-enriched acute myeloid leukemias might be amenable to immunotherapy that is tailored to the bone marrow tumor microenvironment, according to findings from a pan-cancer analysis of bone marrow samples.

The analysis, performed with 3D biology technology and an RNA pan-cancer immune profiling panel to characterize bone marrow specimens from 46 children and 28 adults with acute myeloid leukemia (AML), identified heterogeneous immune profiles that correlated with relapse-free survival (RFS) and overall survival (OS), Jayakumar Vadakekolathu, PhD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The specimens, including 63 from nonpromyelocytic de novo AML, 7 from AML in children with complete remission, 3 from adults with secondary AML, and 1 from an adult with treatment-related AML, were analyzed with the nCounter system from NanoString Technologies, and were visualized via digital spatial profiling, said Dr. Vadakekolathu of Nottingham Trent University in England.

Sharon Worcester/Frontline Medical News

“Prognosis is determined by cytogenetic and molecular abnormalities, as well as by response to chemotherapy. De novo AML is cured in roughly 70% of children, 35%-40% of adults, and 5%-15% of elderly patients,” he said. Some patients with AML fail to respond to induction chemotherapy, and others eventually relapse despite the lack of adverse risk factors, he added.

The general therapeutic strategy in patients with AML has not changed substantially in more than 30 years, he said.

“High degrees of molecular complexity in AML present a considerable challenge in clinical implementation, and there is an urgent need to discover better biomarkers to identify high-risk patients before starting chemotherapy, which would enable testing of investigational therapeutic strategies in clinical trials,” he said.

In an effort to identify immune gene signatures across the spectrum of AML genotypes and to correlate transcriptomic and proteomic profiles with patient outcomes, he and his colleagues used a pediatric cohort from Children’s Hospital of Philadelphia (median age at diagnosis of 10 years), and an adult cohort from the Technical University of Dresden, Germany (median age at diagnosis, 55.5 years). Bone marrow samples were collected and analyzed at diagnosis.

Hierarchical clustering identified the two distinct clusters. The immune-enriched cluster A had heightened expression of T cells, natural killer cells, and cytotoxic cells, and also expressed CD8A, IFNG, FOXP3, the cell chemoattractants CXCL9 and CXCL10, and inhibitory molecules including IDO1 and the immune checkpoints LAG3, CTLA4, and PD-L1. The immune-depleted cluster B overexpressed genes associated with mast cell functions and CD8 T-cell exhaustion, and showed low expression of T-cell and B-cell genes.

Further analysis of 10 of the inflamed samples from patients with newly diagnosed AML was performed with digital spatial profiling (DSP) to visualize in situ leukemia–immune system interactions, Dr. Vadakekolathu said.

Surface antigens CD123 and CD3 were used as a visualization marker for leukemia cells and to identify bone marrow-infiltrating T cells, respectively. Protein quantification showed a higher concentration of CD3 counts in T-cell-rich versus T-cell-poor areas, and protein expression profiles showed strong correlations with various immunologically relevant molecules. The co-localization of CD8 T cells with FoxP3 Treg cells and PD-L1- and VISTA-expressing cell types evident on DSP represents an immune landscape consistent with the establishment of adaptive immune resistance mechanisms of immune escape, he noted.

The findings suggest immune enriched AMLs might be amenable to combination immunotherapies tailored to the bone marrow tumor microenvironment, such as IDO1 inhibitors and checkpoint blockade, Dr. Vadakekolathu said. “Immune gene expression profiles of AML might support rapid prediction of patient outcomes, discovery of novel immune biomarkers and therapeutic targets, and development of integrated patient stratifications,” he said.

This study was supported by grants from the Roger Counter Foundation and the Qatar National Research Fund. Dr. Vadakekolathu reported having no disclosures. Some authors reported employment or other financial relationships with NanoString Technologies.

sworcester@frontlinemedcom.com

SOURCE: Rutella S et al. ASCO-SITC Abstract 50

SAN FRANCISCO – Immune-enriched acute myeloid leukemias might be amenable to immunotherapy that is tailored to the bone marrow tumor microenvironment, according to findings from a pan-cancer analysis of bone marrow samples.

The analysis, performed with 3D biology technology and an RNA pan-cancer immune profiling panel to characterize bone marrow specimens from 46 children and 28 adults with acute myeloid leukemia (AML), identified heterogeneous immune profiles that correlated with relapse-free survival (RFS) and overall survival (OS), Jayakumar Vadakekolathu, PhD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The specimens, including 63 from nonpromyelocytic de novo AML, 7 from AML in children with complete remission, 3 from adults with secondary AML, and 1 from an adult with treatment-related AML, were analyzed with the nCounter system from NanoString Technologies, and were visualized via digital spatial profiling, said Dr. Vadakekolathu of Nottingham Trent University in England.

Sharon Worcester/Frontline Medical News

“Prognosis is determined by cytogenetic and molecular abnormalities, as well as by response to chemotherapy. De novo AML is cured in roughly 70% of children, 35%-40% of adults, and 5%-15% of elderly patients,” he said. Some patients with AML fail to respond to induction chemotherapy, and others eventually relapse despite the lack of adverse risk factors, he added.

The general therapeutic strategy in patients with AML has not changed substantially in more than 30 years, he said.

“High degrees of molecular complexity in AML present a considerable challenge in clinical implementation, and there is an urgent need to discover better biomarkers to identify high-risk patients before starting chemotherapy, which would enable testing of investigational therapeutic strategies in clinical trials,” he said.

In an effort to identify immune gene signatures across the spectrum of AML genotypes and to correlate transcriptomic and proteomic profiles with patient outcomes, he and his colleagues used a pediatric cohort from Children’s Hospital of Philadelphia (median age at diagnosis of 10 years), and an adult cohort from the Technical University of Dresden, Germany (median age at diagnosis, 55.5 years). Bone marrow samples were collected and analyzed at diagnosis.

Hierarchical clustering identified the two distinct clusters. The immune-enriched cluster A had heightened expression of T cells, natural killer cells, and cytotoxic cells, and also expressed CD8A, IFNG, FOXP3, the cell chemoattractants CXCL9 and CXCL10, and inhibitory molecules including IDO1 and the immune checkpoints LAG3, CTLA4, and PD-L1. The immune-depleted cluster B overexpressed genes associated with mast cell functions and CD8 T-cell exhaustion, and showed low expression of T-cell and B-cell genes.

Further analysis of 10 of the inflamed samples from patients with newly diagnosed AML was performed with digital spatial profiling (DSP) to visualize in situ leukemia–immune system interactions, Dr. Vadakekolathu said.

Surface antigens CD123 and CD3 were used as a visualization marker for leukemia cells and to identify bone marrow-infiltrating T cells, respectively. Protein quantification showed a higher concentration of CD3 counts in T-cell-rich versus T-cell-poor areas, and protein expression profiles showed strong correlations with various immunologically relevant molecules. The co-localization of CD8 T cells with FoxP3 Treg cells and PD-L1- and VISTA-expressing cell types evident on DSP represents an immune landscape consistent with the establishment of adaptive immune resistance mechanisms of immune escape, he noted.

The findings suggest immune enriched AMLs might be amenable to combination immunotherapies tailored to the bone marrow tumor microenvironment, such as IDO1 inhibitors and checkpoint blockade, Dr. Vadakekolathu said. “Immune gene expression profiles of AML might support rapid prediction of patient outcomes, discovery of novel immune biomarkers and therapeutic targets, and development of integrated patient stratifications,” he said.

This study was supported by grants from the Roger Counter Foundation and the Qatar National Research Fund. Dr. Vadakekolathu reported having no disclosures. Some authors reported employment or other financial relationships with NanoString Technologies.

sworcester@frontlinemedcom.com

SOURCE: Rutella S et al. ASCO-SITC Abstract 50

DALLAS – Though cervical pessaries didn’t significantly reduce the rate of births before 34 weeks’ gestation when compared to vaginal progesterone for women with short cervixes and twin pregnancies, neonatal outcomes were improved with pessary use, according to the first randomized controlled trial that directly compared the two therapies.

Of 148 women who received pessaries, 24 (16.2%) delivered before 34 weeks’ gestation, compared with 33 of 149 women (22.1%) who received vaginal progesterone (relative risk 0.73, 95% confidence interval, 0.46-1.18; P = .24). Women who received pessaries were slightly more likely to carry their twin gestations to at least 37 weeks (79/148 versus 91/149; P = .05).

Certain perinatal outcomes were also better among the pessary group. The study measured a composite poor perinatal outcome of neonatal intensive care unit (NICU) admission, intraventricular hemorrhage, respiratory distress syndrome, necrotizing enterocolitis, and neonatal sepsis. This composite poor outcome occurred in 18.6% of the pessary group, compared with 26.5% of the progesterone group (P = .02). Neonatal admissions were more common in the progesterone than in the pessary group (22.1% vs. 13.2%, P = .01)

The odds of having a baby with birth weight less than 2,500 g was also higher for those receiving progesterone, with 22.1% of the progesterone group and 13.2% of the pessary group delivering infants in this range (P less than .001).

Previous work has shown that vaginal progesterone was efficacious when compared with placebo in preventing preterm births for women who have a twin gestation and a short cervix, according to Vinh Dang, MD, the study’s first author. Similarly, he said, studies have shown that placement of a cervical pessary also reduces preterm births in the scenario of twin gestation and a short cervix.

“No randomized controlled trial has directly compared cervical pessary versus vaginal progesterone for the prevention of preterm birth” in this population, Dr. Dang said during a presentation at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Accordingly, he and his colleagues at My Duc Hospital in Ho Chi Minh City, Vietnam, conducted a comparative effectiveness trial to provide a head-to-head comparison of the use of cervical pessaries versus vaginal progesterone for women with twin gestations and short cervixes.

The investigators conducted a single-center, randomized controlled trial, enrolling women with either monochorionic or dichorionic twin pregnancies at between 16 and 22 weeks of gestation, with a cervix length of less than 38 mm, as assessed by two trained ultrasonographers.

At My Duc Hospital, 28.4% of women with twin pregnancies and cervical length less than 38 mm delivered earlier than 34 weeks. This meant that in order to detect a 14% reduction in preterm birth, the study would need to include 290 women for sufficient statistical power, Dr. Dang said.

Patients (n = 300) were randomized 1:1 to receive vaginal progesterone, begun on the day of enrollment, or cervical pessary placed within 1 week of study enrollment. Two patients in the pessary arm and one in the progesterone arm were lost to follow-up.

Patients were permitted to receive other therapies; 14 women in the pessary arm also received antibiotics and 1 received progesterone. In the progesterone group, 12 received antibiotics, and 4 patients were cotreated with cervical cerclage.

The study excluded women under 18 years of age, and those with a prior history of cervical surgery or cervical cerclage. Major known complications in the current pregnancy, such as twin-to-twin transfusion syndrome, major congenital anomaly, fetal demise, and any symptoms of labor or late miscarriage were also grounds for exclusion.

Patient characteristics were similar between groups. The average age was 32 years. Most of the patients (83%-90%) were nulliparous, and more than 90% of the pregnancies were the result of assisted reproduction.

In addition to the primary outcome measure of preterm birth earlier than 34 weeks, the investigators tracked a number of obstetric and neonatal outcomes as secondary endpoints.

For the obstetric measures, Dr. Dang and his colleagues recorded deliveries that occurred before 28, 32, and 27 weeks’ gestation, whether labor was induced and if tocolytics or corticosteroids were used, mode of delivery, and proportion of live births. The number of days of admission for preterm labor, presence of chorioamnionitis, and occurrence of other maternal morbidity were also measured.

Dr. Dang and his colleagues also tracked birth weight, congenital anomalies, and 1- and 5-minute Apgar scores.

A prespecified subgroup analysis of women with even shorter cervixes – less than 28 mm – showed a significant reduction in preterm birth before 34 weeks in addition to the significant improvement in neonatal outcomes.

One author reported being a consultant for ObsEva, Merck, and Guerbet. The other authors had no disclosures.

koakes@frontlinemedcom.com

SOURCE: Dang V et al. The Pregnancy Meeting Abstract LB03

DALLAS – Though cervical pessaries didn’t significantly reduce the rate of births before 34 weeks’ gestation when compared to vaginal progesterone for women with short cervixes and twin pregnancies, neonatal outcomes were improved with pessary use, according to the first randomized controlled trial that directly compared the two therapies.

Of 148 women who received pessaries, 24 (16.2%) delivered before 34 weeks’ gestation, compared with 33 of 149 women (22.1%) who received vaginal progesterone (relative risk 0.73, 95% confidence interval, 0.46-1.18; P = .24). Women who received pessaries were slightly more likely to carry their twin gestations to at least 37 weeks (79/148 versus 91/149; P = .05).

Certain perinatal outcomes were also better among the pessary group. The study measured a composite poor perinatal outcome of neonatal intensive care unit (NICU) admission, intraventricular hemorrhage, respiratory distress syndrome, necrotizing enterocolitis, and neonatal sepsis. This composite poor outcome occurred in 18.6% of the pessary group, compared with 26.5% of the progesterone group (P = .02). Neonatal admissions were more common in the progesterone than in the pessary group (22.1% vs. 13.2%, P = .01)

The odds of having a baby with birth weight less than 2,500 g was also higher for those receiving progesterone, with 22.1% of the progesterone group and 13.2% of the pessary group delivering infants in this range (P less than .001).

Previous work has shown that vaginal progesterone was efficacious when compared with placebo in preventing preterm births for women who have a twin gestation and a short cervix, according to Vinh Dang, MD, the study’s first author. Similarly, he said, studies have shown that placement of a cervical pessary also reduces preterm births in the scenario of twin gestation and a short cervix.

“No randomized controlled trial has directly compared cervical pessary versus vaginal progesterone for the prevention of preterm birth” in this population, Dr. Dang said during a presentation at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Accordingly, he and his colleagues at My Duc Hospital in Ho Chi Minh City, Vietnam, conducted a comparative effectiveness trial to provide a head-to-head comparison of the use of cervical pessaries versus vaginal progesterone for women with twin gestations and short cervixes.

The investigators conducted a single-center, randomized controlled trial, enrolling women with either monochorionic or dichorionic twin pregnancies at between 16 and 22 weeks of gestation, with a cervix length of less than 38 mm, as assessed by two trained ultrasonographers.

At My Duc Hospital, 28.4% of women with twin pregnancies and cervical length less than 38 mm delivered earlier than 34 weeks. This meant that in order to detect a 14% reduction in preterm birth, the study would need to include 290 women for sufficient statistical power, Dr. Dang said.

Patients (n = 300) were randomized 1:1 to receive vaginal progesterone, begun on the day of enrollment, or cervical pessary placed within 1 week of study enrollment. Two patients in the pessary arm and one in the progesterone arm were lost to follow-up.

Patients were permitted to receive other therapies; 14 women in the pessary arm also received antibiotics and 1 received progesterone. In the progesterone group, 12 received antibiotics, and 4 patients were cotreated with cervical cerclage.

The study excluded women under 18 years of age, and those with a prior history of cervical surgery or cervical cerclage. Major known complications in the current pregnancy, such as twin-to-twin transfusion syndrome, major congenital anomaly, fetal demise, and any symptoms of labor or late miscarriage were also grounds for exclusion.

Patient characteristics were similar between groups. The average age was 32 years. Most of the patients (83%-90%) were nulliparous, and more than 90% of the pregnancies were the result of assisted reproduction.

In addition to the primary outcome measure of preterm birth earlier than 34 weeks, the investigators tracked a number of obstetric and neonatal outcomes as secondary endpoints.

For the obstetric measures, Dr. Dang and his colleagues recorded deliveries that occurred before 28, 32, and 27 weeks’ gestation, whether labor was induced and if tocolytics or corticosteroids were used, mode of delivery, and proportion of live births. The number of days of admission for preterm labor, presence of chorioamnionitis, and occurrence of other maternal morbidity were also measured.

Dr. Dang and his colleagues also tracked birth weight, congenital anomalies, and 1- and 5-minute Apgar scores.

A prespecified subgroup analysis of women with even shorter cervixes – less than 28 mm – showed a significant reduction in preterm birth before 34 weeks in addition to the significant improvement in neonatal outcomes.

One author reported being a consultant for ObsEva, Merck, and Guerbet. The other authors had no disclosures.

koakes@frontlinemedcom.com

SOURCE: Dang V et al. The Pregnancy Meeting Abstract LB03

DALLAS – Though cervical pessaries didn’t significantly reduce the rate of births before 34 weeks’ gestation when compared to vaginal progesterone for women with short cervixes and twin pregnancies, neonatal outcomes were improved with pessary use, according to the first randomized controlled trial that directly compared the two therapies.

Of 148 women who received pessaries, 24 (16.2%) delivered before 34 weeks’ gestation, compared with 33 of 149 women (22.1%) who received vaginal progesterone (relative risk 0.73, 95% confidence interval, 0.46-1.18; P = .24). Women who received pessaries were slightly more likely to carry their twin gestations to at least 37 weeks (79/148 versus 91/149; P = .05).

Certain perinatal outcomes were also better among the pessary group. The study measured a composite poor perinatal outcome of neonatal intensive care unit (NICU) admission, intraventricular hemorrhage, respiratory distress syndrome, necrotizing enterocolitis, and neonatal sepsis. This composite poor outcome occurred in 18.6% of the pessary group, compared with 26.5% of the progesterone group (P = .02). Neonatal admissions were more common in the progesterone than in the pessary group (22.1% vs. 13.2%, P = .01)

The odds of having a baby with birth weight less than 2,500 g was also higher for those receiving progesterone, with 22.1% of the progesterone group and 13.2% of the pessary group delivering infants in this range (P less than .001).

Previous work has shown that vaginal progesterone was efficacious when compared with placebo in preventing preterm births for women who have a twin gestation and a short cervix, according to Vinh Dang, MD, the study’s first author. Similarly, he said, studies have shown that placement of a cervical pessary also reduces preterm births in the scenario of twin gestation and a short cervix.

“No randomized controlled trial has directly compared cervical pessary versus vaginal progesterone for the prevention of preterm birth” in this population, Dr. Dang said during a presentation at the Pregnancy Meeting, sponsored by the Society for Maternal-Fetal Medicine.

Accordingly, he and his colleagues at My Duc Hospital in Ho Chi Minh City, Vietnam, conducted a comparative effectiveness trial to provide a head-to-head comparison of the use of cervical pessaries versus vaginal progesterone for women with twin gestations and short cervixes.

The investigators conducted a single-center, randomized controlled trial, enrolling women with either monochorionic or dichorionic twin pregnancies at between 16 and 22 weeks of gestation, with a cervix length of less than 38 mm, as assessed by two trained ultrasonographers.

At My Duc Hospital, 28.4% of women with twin pregnancies and cervical length less than 38 mm delivered earlier than 34 weeks. This meant that in order to detect a 14% reduction in preterm birth, the study would need to include 290 women for sufficient statistical power, Dr. Dang said.

Patients (n = 300) were randomized 1:1 to receive vaginal progesterone, begun on the day of enrollment, or cervical pessary placed within 1 week of study enrollment. Two patients in the pessary arm and one in the progesterone arm were lost to follow-up.

Patients were permitted to receive other therapies; 14 women in the pessary arm also received antibiotics and 1 received progesterone. In the progesterone group, 12 received antibiotics, and 4 patients were cotreated with cervical cerclage.

The study excluded women under 18 years of age, and those with a prior history of cervical surgery or cervical cerclage. Major known complications in the current pregnancy, such as twin-to-twin transfusion syndrome, major congenital anomaly, fetal demise, and any symptoms of labor or late miscarriage were also grounds for exclusion.

Patient characteristics were similar between groups. The average age was 32 years. Most of the patients (83%-90%) were nulliparous, and more than 90% of the pregnancies were the result of assisted reproduction.

In addition to the primary outcome measure of preterm birth earlier than 34 weeks, the investigators tracked a number of obstetric and neonatal outcomes as secondary endpoints.

For the obstetric measures, Dr. Dang and his colleagues recorded deliveries that occurred before 28, 32, and 27 weeks’ gestation, whether labor was induced and if tocolytics or corticosteroids were used, mode of delivery, and proportion of live births. The number of days of admission for preterm labor, presence of chorioamnionitis, and occurrence of other maternal morbidity were also measured.

Dr. Dang and his colleagues also tracked birth weight, congenital anomalies, and 1- and 5-minute Apgar scores.

A prespecified subgroup analysis of women with even shorter cervixes – less than 28 mm – showed a significant reduction in preterm birth before 34 weeks in addition to the significant improvement in neonatal outcomes.

One author reported being a consultant for ObsEva, Merck, and Guerbet. The other authors had no disclosures.

koakes@frontlinemedcom.com

SOURCE: Dang V et al. The Pregnancy Meeting Abstract LB03