Question: A medical assistant alleged that Dr. Y sexually harassed her by sending anonymous gifts and messages such as, “you’re gorgeous,” and “I love your figure.” It was a repeat of Dr. Y’s previous behavior pattern directed at a different worker, who had lodged a complaint with the human resources department. The medical assistant now files a sexual harassment action under Title VII of the federal Civil Rights Act of 1964 against the health care institution, alleging a hostile work environment.

Which of the following is false?

A. Sexual harassment is a form of sexual misconduct regulated by state medical boards.

B. Mere words, without physical action, may suffice to be deemed sexual harassment.

C. A hostile environment arises when offensive conduct is so severe and pervasive as to amount to job discrimination.

D. Sexual harassment is a civil rights violation unique to the workplace.

E. Liability may attach to the supervisor, institution, or the harasser.

Answer: D. This hypothetical is modified from an actual Connecticut case that was recently decided in favor of the plaintiff.¹ In that case, which involved a dentist, the federal Second Circuit unanimously rejected the University of Connecticut Health Center’s appeal against a jury’s verdict holding it responsible for its employee’s sexual harassment of a coworker, who was awarded $125,000. It ruled that the health center should have known of its employee’s harassing behavior.

Sexual harassment, a current hot topic, is pervasive, affecting a diversity of individuals in the fields of media, sports, politics, judiciary, education, entertainment, and others. The medical profession is no exception, and studies indicate that sexual harassment affects patients and physicians alike, occurring in hospitals, private offices, and academic centers.

In a large questionnaire study involving 4,501 female physicians, the authors found a prevalence rate of 47.7%. Harassment was more common while in medical school or during internship, residency, or fellowship than in practice.² Patients may be the harassers. In 599 of the 1,064 licensed female family physicians in Ontario, more than 75% reported sexual harassment by patients at some time during their careers, either in their own offices by their own patients, or in settings such as emergency departments and clinics, where unknown patients presented an even higher risk.³

When physicians sexually harass fellow workers such as nurses, they distract their victims from providing attentive and competent care. In a review of the subject, researchers cited a study of 188 critical care nurses in hospitals, where nearly half (46%) reported experiencing sexual harassment that included “offensive sexual remarks, unwanted physical contact, unwanted nonverbal attention, requests for unwanted dates, sexual propositions, and physical assault.”⁴ To this list must now be added misconduct via the use of social media. In the study, physicians (82%), coworkers (20%), and immediate supervisors (7%) accounted for most of the incidents.

Neglecting to look seriously into complaints or to monitor and remedy the situation may create a hostile environment and trigger liability.

An example is the recent well-publicized case of Olympics team physician Dr. Larry Nassar, who was also a faculty member at Michigan State University. Olympic gold medalist McKayla Maroney named both the university and the U.S. Olympic Committee as codefendants in a lawsuit alleging that the institutions failed to properly investigate the team doctor’s criminal sexual conduct.

In Anania v. Daubenspeck Chiropractic, two employees of a chiropractor alleged that his patients sexually harassed them, but he did not remedy the situation.⁵ The trial court initially dismissed their lawsuit, holding that Ohio law did not recognize a cause of action for sexual harassment by a nonemployee patient, and that liability for sexual harassment can only exist in the context of respondeat superior (employer-employee) liability.

However, the court of appeals held that so long as the chiropractor knew or should have known of the harassment, and failed to take corrective action, he could be liable for allowing a hostile environment to exist.

Negligent supervision is another favorite plaintiff’s cause of action. In Doe v. Borromeo, a patient sought to hold the hospital liable for sexual assault by a physician during a medical exam.⁶ The lower state court had summarily dismissed the case, which was based on vicarious liability, but the state court of appeals reversed, finding the patient’s complaint against the hospital included a negligent supervision claim.

The appeals court reasoned that this was distinguishable from one based upon vicarious liability, so long as the supervising entity had a duty to protect the victim – and such a duty can only be established if the supervising entity knew or should have known of the existence of the harasser’s propensities, if any, to commit criminal and tortious acts.

Sexual harassment is a form of sex discrimination under Title VII of the Civil Rights Act of 1964, which is enforced by the Equal Employment Opportunity Commission. The commission’s website explains the law in clear and simple language:

“It is unlawful to harass a person (an applicant or employee) because of that person’s sex. Harassment can include ‘sexual harassment’ or unwelcome sexual advances, requests for sexual favors, and other verbal or physical harassment of a sexual nature. Harassment does not have to be of a sexual nature, however, and can include offensive remarks about a person’s sex.

“For example, it is illegal to harass a woman by making offensive comments about women in general. Both victim and the harasser can be either a woman or a man, and the victim and harasser can be the same sex.

“Although the law doesn’t prohibit simple teasing, offhand comments, or isolated incidents that are not very serious, 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 (such as the victim being fired or demoted). The harasser can be the victim’s supervisor, a supervisor in another area, a coworker, or someone who is not an employee of the employer, such as a client or customer.”⁷

For sexual harassment to occur, the aggrieved party must either show a “hostile environment” or “quid pro quo” situation.

In a hostile environment case, the harassment is serious and persistent, creating unacceptable and offensive work conditions. The plaintiff has to show that the employer knew or should have known of the situation but failed to remedy it.

The “quid pro quo” type of case requires a showing that a person in authority conditioned some aspect of the employee’s employment, such as promotion or retention, upon a sexual favor or relationship.

The U.S. Supreme Court has both clarified and muddied the law’s position on these two previously distinct types of sexual harassment.

In the landmark case of Burlington Industries v. Ellerth, the plaintiff, who was a salesperson, alleged that a supervisor made advances to her and threatened to deny her certain job benefits if she did not cooperate.⁸ The threats were never carried out, and she was in fact promoted; but her lawsuit alleged that the harassment caused her resignation and amounted to a “constructive” discharge.

Likewise, in Faragher v. City of Boca Raton, the plaintiff, employed as a lifeguard, alleged that her work environment was riddled with crude remarks and obscenities.⁹ One of the two supervisors reportedly once said to Faragher, “Date me or clean toilets for a year.” Another lifeguard had previously lodged similar complaints. The plaintiff ultimately resigned and brought suit.

The U.S. Supreme Court characterized both of these as “hostile environment” rather than “quid pro quo” cases, because the plaintiffs did not suffer any direct adverse job action. In its decisions, the court defined the scope of liability and affirmative defenses, holding that employers can be subject to vicarious liability when supervisors create actionable hostile work environments.

In other cases, the Supreme Court has ruled for the use of “the reasonable person in the plaintiff’s position” standard in judging the severity of sexual harassment. The court has also held that the genders of the harasser and the harassed employee are not material in determining whether sexual harassment has occurred.

A physician can be accused of harassing an employee, a nurse, an assistant, a fellow worker, a third party, or a patient. Focusing on misconduct within the doctor-patient relationship, the Federation of State Medical Boards adopted in May 2006 a policy entitled “Addressing Sexual Boundaries: Guidelines for State Medical Boards.”¹⁰

Although it did not use the term sexual harassment, the policy emphasized that physician sexual misconduct may include behavior that is verbal or physical, and may include expressions of thoughts and feelings or gestures that are sexual. It used the term “sexual impropriety” to denote behavior, gestures, or expressions that are seductive, sexually suggestive, disrespectful of patient privacy, or sexually demeaning to a patient. Together with “sexual violation,” a term the FSMB used when referring to physical sexual contact, they form the basis for disciplinary action by a state medical board.

Caveat: When performing a physical exam, physicians should always use good judgment and sensitivity, relying on the presence of a medical assistant to ensure patient comfort and to alleviate possible embarrassment or anxiety.

Under the federal EEOC rules, the employer rather than the harasser is the defendant. But there are other legal recourses, including tort and criminal actions, that directly target the harasser. Successful plaintiffs may be awarded lost wages, as well as damages for emotional distress, medical expenses, and punitive damages. They may also recover attorney fees.

In one case, a psychiatric nurse was awarded $1.2 million (later reduced to $850,000); in another, a nurse successfully sued a physician’s medical practice and received $150,000 in damages.⁴ And in an unusual case, a plaintiff was awarded only $1 in damages, but her counsel was paid $41,598 in fees.¹¹ For the practicing doctor, medical board sanction, notoriety, and loss of professional standing and privileges constitute additional costs.

The medical profession is as susceptible as any other – perhaps more so – to allegations of sexual harassment. The magic words for actionable sexual harassment are severe, pervasive, and unwelcome. Although laws in the workplace generally do not prohibit simple teasing, offhand comments, or minor isolated incidents, the line separating these behaviors from bona fide sexual harassment is thin.

Erring on the side of strict and sober professional propriety seems prudent, given the current climate of zero tolerance.


 

References

1. MacCluskey v. University of Connecticut Health Center, United States Court of Appeals, Second Circuit, No. 17-0807-cv, Dec. 19, 2017.

2. Arch Intern Med. 1998 Feb 23;158(4):352-8.

3. N Engl J Med. 1993 Dec 23;329(26):1936-9.

4. J Nurs Care Qual. 2004 Jul-Sep;19(3):234-41.

5. Anania v. Daubenspeck Chiropractic, 718 N.E. 2d 480 (Ohio 1998).

6. Doe v. Borromeo, Nos. 305162, 305163 (Mich. Ct. App. Sept. 20, 2012).

7. Available at https://www.eeoc.gov/laws/types/sexual_harassment.cfm.

8. Burlington Industries, Inc. v. Ellerth, 524 US 742 (1998).

9. Faragher v. City of Boca Raton, 524 U.S. 775 (1998).

10. Federation of State Medical Boards, “Addressing Sexual Boundaries: Guidelines for State Medical Boards.”

11. J Healthc Risk Manag. 1999 Summer;19(3):14-25.

Question: A medical assistant alleged that Dr. Y sexually harassed her by sending anonymous gifts and messages such as, “you’re gorgeous,” and “I love your figure.” It was a repeat of Dr. Y’s previous behavior pattern directed at a different worker, who had lodged a complaint with the human resources department. The medical assistant now files a sexual harassment action under Title VII of the federal Civil Rights Act of 1964 against the health care institution, alleging a hostile work environment.

Which of the following is false?

A. Sexual harassment is a form of sexual misconduct regulated by state medical boards.

B. Mere words, without physical action, may suffice to be deemed sexual harassment.

C. A hostile environment arises when offensive conduct is so severe and pervasive as to amount to job discrimination.

D. Sexual harassment is a civil rights violation unique to the workplace.

E. Liability may attach to the supervisor, institution, or the harasser.

Answer: D. This hypothetical is modified from an actual Connecticut case that was recently decided in favor of the plaintiff.¹ In that case, which involved a dentist, the federal Second Circuit unanimously rejected the University of Connecticut Health Center’s appeal against a jury’s verdict holding it responsible for its employee’s sexual harassment of a coworker, who was awarded $125,000. It ruled that the health center should have known of its employee’s harassing behavior.

Sexual harassment, a current hot topic, is pervasive, affecting a diversity of individuals in the fields of media, sports, politics, judiciary, education, entertainment, and others. The medical profession is no exception, and studies indicate that sexual harassment affects patients and physicians alike, occurring in hospitals, private offices, and academic centers.

In a large questionnaire study involving 4,501 female physicians, the authors found a prevalence rate of 47.7%. Harassment was more common while in medical school or during internship, residency, or fellowship than in practice.² Patients may be the harassers. In 599 of the 1,064 licensed female family physicians in Ontario, more than 75% reported sexual harassment by patients at some time during their careers, either in their own offices by their own patients, or in settings such as emergency departments and clinics, where unknown patients presented an even higher risk.³

When physicians sexually harass fellow workers such as nurses, they distract their victims from providing attentive and competent care. In a review of the subject, researchers cited a study of 188 critical care nurses in hospitals, where nearly half (46%) reported experiencing sexual harassment that included “offensive sexual remarks, unwanted physical contact, unwanted nonverbal attention, requests for unwanted dates, sexual propositions, and physical assault.”⁴ To this list must now be added misconduct via the use of social media. In the study, physicians (82%), coworkers (20%), and immediate supervisors (7%) accounted for most of the incidents.

Neglecting to look seriously into complaints or to monitor and remedy the situation may create a hostile environment and trigger liability.

An example is the recent well-publicized case of Olympics team physician Dr. Larry Nassar, who was also a faculty member at Michigan State University. Olympic gold medalist McKayla Maroney named both the university and the U.S. Olympic Committee as codefendants in a lawsuit alleging that the institutions failed to properly investigate the team doctor’s criminal sexual conduct.

In Anania v. Daubenspeck Chiropractic, two employees of a chiropractor alleged that his patients sexually harassed them, but he did not remedy the situation.⁵ The trial court initially dismissed their lawsuit, holding that Ohio law did not recognize a cause of action for sexual harassment by a nonemployee patient, and that liability for sexual harassment can only exist in the context of respondeat superior (employer-employee) liability.

However, the court of appeals held that so long as the chiropractor knew or should have known of the harassment, and failed to take corrective action, he could be liable for allowing a hostile environment to exist.

Negligent supervision is another favorite plaintiff’s cause of action. In Doe v. Borromeo, a patient sought to hold the hospital liable for sexual assault by a physician during a medical exam.⁶ The lower state court had summarily dismissed the case, which was based on vicarious liability, but the state court of appeals reversed, finding the patient’s complaint against the hospital included a negligent supervision claim.

The appeals court reasoned that this was distinguishable from one based upon vicarious liability, so long as the supervising entity had a duty to protect the victim – and such a duty can only be established if the supervising entity knew or should have known of the existence of the harasser’s propensities, if any, to commit criminal and tortious acts.

Sexual harassment is a form of sex discrimination under Title VII of the Civil Rights Act of 1964, which is enforced by the Equal Employment Opportunity Commission. The commission’s website explains the law in clear and simple language:

“It is unlawful to harass a person (an applicant or employee) because of that person’s sex. Harassment can include ‘sexual harassment’ or unwelcome sexual advances, requests for sexual favors, and other verbal or physical harassment of a sexual nature. Harassment does not have to be of a sexual nature, however, and can include offensive remarks about a person’s sex.

“For example, it is illegal to harass a woman by making offensive comments about women in general. Both victim and the harasser can be either a woman or a man, and the victim and harasser can be the same sex.

“Although the law doesn’t prohibit simple teasing, offhand comments, or isolated incidents that are not very serious, 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 (such as the victim being fired or demoted). The harasser can be the victim’s supervisor, a supervisor in another area, a coworker, or someone who is not an employee of the employer, such as a client or customer.”⁷

For sexual harassment to occur, the aggrieved party must either show a “hostile environment” or “quid pro quo” situation.

In a hostile environment case, the harassment is serious and persistent, creating unacceptable and offensive work conditions. The plaintiff has to show that the employer knew or should have known of the situation but failed to remedy it.

The “quid pro quo” type of case requires a showing that a person in authority conditioned some aspect of the employee’s employment, such as promotion or retention, upon a sexual favor or relationship.

The U.S. Supreme Court has both clarified and muddied the law’s position on these two previously distinct types of sexual harassment.

In the landmark case of Burlington Industries v. Ellerth, the plaintiff, who was a salesperson, alleged that a supervisor made advances to her and threatened to deny her certain job benefits if she did not cooperate.⁸ The threats were never carried out, and she was in fact promoted; but her lawsuit alleged that the harassment caused her resignation and amounted to a “constructive” discharge.

Likewise, in Faragher v. City of Boca Raton, the plaintiff, employed as a lifeguard, alleged that her work environment was riddled with crude remarks and obscenities.⁹ One of the two supervisors reportedly once said to Faragher, “Date me or clean toilets for a year.” Another lifeguard had previously lodged similar complaints. The plaintiff ultimately resigned and brought suit.

The U.S. Supreme Court characterized both of these as “hostile environment” rather than “quid pro quo” cases, because the plaintiffs did not suffer any direct adverse job action. In its decisions, the court defined the scope of liability and affirmative defenses, holding that employers can be subject to vicarious liability when supervisors create actionable hostile work environments.

In other cases, the Supreme Court has ruled for the use of “the reasonable person in the plaintiff’s position” standard in judging the severity of sexual harassment. The court has also held that the genders of the harasser and the harassed employee are not material in determining whether sexual harassment has occurred.

A physician can be accused of harassing an employee, a nurse, an assistant, a fellow worker, a third party, or a patient. Focusing on misconduct within the doctor-patient relationship, the Federation of State Medical Boards adopted in May 2006 a policy entitled “Addressing Sexual Boundaries: Guidelines for State Medical Boards.”¹⁰

Although it did not use the term sexual harassment, the policy emphasized that physician sexual misconduct may include behavior that is verbal or physical, and may include expressions of thoughts and feelings or gestures that are sexual. It used the term “sexual impropriety” to denote behavior, gestures, or expressions that are seductive, sexually suggestive, disrespectful of patient privacy, or sexually demeaning to a patient. Together with “sexual violation,” a term the FSMB used when referring to physical sexual contact, they form the basis for disciplinary action by a state medical board.

Caveat: When performing a physical exam, physicians should always use good judgment and sensitivity, relying on the presence of a medical assistant to ensure patient comfort and to alleviate possible embarrassment or anxiety.

Under the federal EEOC rules, the employer rather than the harasser is the defendant. But there are other legal recourses, including tort and criminal actions, that directly target the harasser. Successful plaintiffs may be awarded lost wages, as well as damages for emotional distress, medical expenses, and punitive damages. They may also recover attorney fees.

In one case, a psychiatric nurse was awarded $1.2 million (later reduced to $850,000); in another, a nurse successfully sued a physician’s medical practice and received $150,000 in damages.⁴ And in an unusual case, a plaintiff was awarded only $1 in damages, but her counsel was paid $41,598 in fees.¹¹ For the practicing doctor, medical board sanction, notoriety, and loss of professional standing and privileges constitute additional costs.

The medical profession is as susceptible as any other – perhaps more so – to allegations of sexual harassment. The magic words for actionable sexual harassment are severe, pervasive, and unwelcome. Although laws in the workplace generally do not prohibit simple teasing, offhand comments, or minor isolated incidents, the line separating these behaviors from bona fide sexual harassment is thin.

Erring on the side of strict and sober professional propriety seems prudent, given the current climate of zero tolerance.


 

References

1. MacCluskey v. University of Connecticut Health Center, United States Court of Appeals, Second Circuit, No. 17-0807-cv, Dec. 19, 2017.

2. Arch Intern Med. 1998 Feb 23;158(4):352-8.

3. N Engl J Med. 1993 Dec 23;329(26):1936-9.

4. J Nurs Care Qual. 2004 Jul-Sep;19(3):234-41.

5. Anania v. Daubenspeck Chiropractic, 718 N.E. 2d 480 (Ohio 1998).

6. Doe v. Borromeo, Nos. 305162, 305163 (Mich. Ct. App. Sept. 20, 2012).

7. Available at https://www.eeoc.gov/laws/types/sexual_harassment.cfm.

8. Burlington Industries, Inc. v. Ellerth, 524 US 742 (1998).

9. Faragher v. City of Boca Raton, 524 U.S. 775 (1998).

10. Federation of State Medical Boards, “Addressing Sexual Boundaries: Guidelines for State Medical Boards.”

11. J Healthc Risk Manag. 1999 Summer;19(3):14-25.

Question: A medical assistant alleged that Dr. Y sexually harassed her by sending anonymous gifts and messages such as, “you’re gorgeous,” and “I love your figure.” It was a repeat of Dr. Y’s previous behavior pattern directed at a different worker, who had lodged a complaint with the human resources department. The medical assistant now files a sexual harassment action under Title VII of the federal Civil Rights Act of 1964 against the health care institution, alleging a hostile work environment.

Which of the following is false?

A. Sexual harassment is a form of sexual misconduct regulated by state medical boards.

B. Mere words, without physical action, may suffice to be deemed sexual harassment.

C. A hostile environment arises when offensive conduct is so severe and pervasive as to amount to job discrimination.

D. Sexual harassment is a civil rights violation unique to the workplace.

E. Liability may attach to the supervisor, institution, or the harasser.

Answer: D. This hypothetical is modified from an actual Connecticut case that was recently decided in favor of the plaintiff.¹ In that case, which involved a dentist, the federal Second Circuit unanimously rejected the University of Connecticut Health Center’s appeal against a jury’s verdict holding it responsible for its employee’s sexual harassment of a coworker, who was awarded $125,000. It ruled that the health center should have known of its employee’s harassing behavior.

Sexual harassment, a current hot topic, is pervasive, affecting a diversity of individuals in the fields of media, sports, politics, judiciary, education, entertainment, and others. The medical profession is no exception, and studies indicate that sexual harassment affects patients and physicians alike, occurring in hospitals, private offices, and academic centers.

In a large questionnaire study involving 4,501 female physicians, the authors found a prevalence rate of 47.7%. Harassment was more common while in medical school or during internship, residency, or fellowship than in practice.² Patients may be the harassers. In 599 of the 1,064 licensed female family physicians in Ontario, more than 75% reported sexual harassment by patients at some time during their careers, either in their own offices by their own patients, or in settings such as emergency departments and clinics, where unknown patients presented an even higher risk.³

When physicians sexually harass fellow workers such as nurses, they distract their victims from providing attentive and competent care. In a review of the subject, researchers cited a study of 188 critical care nurses in hospitals, where nearly half (46%) reported experiencing sexual harassment that included “offensive sexual remarks, unwanted physical contact, unwanted nonverbal attention, requests for unwanted dates, sexual propositions, and physical assault.”⁴ To this list must now be added misconduct via the use of social media. In the study, physicians (82%), coworkers (20%), and immediate supervisors (7%) accounted for most of the incidents.

Neglecting to look seriously into complaints or to monitor and remedy the situation may create a hostile environment and trigger liability.

An example is the recent well-publicized case of Olympics team physician Dr. Larry Nassar, who was also a faculty member at Michigan State University. Olympic gold medalist McKayla Maroney named both the university and the U.S. Olympic Committee as codefendants in a lawsuit alleging that the institutions failed to properly investigate the team doctor’s criminal sexual conduct.

In Anania v. Daubenspeck Chiropractic, two employees of a chiropractor alleged that his patients sexually harassed them, but he did not remedy the situation.⁵ The trial court initially dismissed their lawsuit, holding that Ohio law did not recognize a cause of action for sexual harassment by a nonemployee patient, and that liability for sexual harassment can only exist in the context of respondeat superior (employer-employee) liability.

However, the court of appeals held that so long as the chiropractor knew or should have known of the harassment, and failed to take corrective action, he could be liable for allowing a hostile environment to exist.

Negligent supervision is another favorite plaintiff’s cause of action. In Doe v. Borromeo, a patient sought to hold the hospital liable for sexual assault by a physician during a medical exam.⁶ The lower state court had summarily dismissed the case, which was based on vicarious liability, but the state court of appeals reversed, finding the patient’s complaint against the hospital included a negligent supervision claim.

The appeals court reasoned that this was distinguishable from one based upon vicarious liability, so long as the supervising entity had a duty to protect the victim – and such a duty can only be established if the supervising entity knew or should have known of the existence of the harasser’s propensities, if any, to commit criminal and tortious acts.

Sexual harassment is a form of sex discrimination under Title VII of the Civil Rights Act of 1964, which is enforced by the Equal Employment Opportunity Commission. The commission’s website explains the law in clear and simple language:

“It is unlawful to harass a person (an applicant or employee) because of that person’s sex. Harassment can include ‘sexual harassment’ or unwelcome sexual advances, requests for sexual favors, and other verbal or physical harassment of a sexual nature. Harassment does not have to be of a sexual nature, however, and can include offensive remarks about a person’s sex.

“For example, it is illegal to harass a woman by making offensive comments about women in general. Both victim and the harasser can be either a woman or a man, and the victim and harasser can be the same sex.

“Although the law doesn’t prohibit simple teasing, offhand comments, or isolated incidents that are not very serious, 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 (such as the victim being fired or demoted). The harasser can be the victim’s supervisor, a supervisor in another area, a coworker, or someone who is not an employee of the employer, such as a client or customer.”⁷

For sexual harassment to occur, the aggrieved party must either show a “hostile environment” or “quid pro quo” situation.

In a hostile environment case, the harassment is serious and persistent, creating unacceptable and offensive work conditions. The plaintiff has to show that the employer knew or should have known of the situation but failed to remedy it.

The “quid pro quo” type of case requires a showing that a person in authority conditioned some aspect of the employee’s employment, such as promotion or retention, upon a sexual favor or relationship.

The U.S. Supreme Court has both clarified and muddied the law’s position on these two previously distinct types of sexual harassment.

In the landmark case of Burlington Industries v. Ellerth, the plaintiff, who was a salesperson, alleged that a supervisor made advances to her and threatened to deny her certain job benefits if she did not cooperate.⁸ The threats were never carried out, and she was in fact promoted; but her lawsuit alleged that the harassment caused her resignation and amounted to a “constructive” discharge.

Likewise, in Faragher v. City of Boca Raton, the plaintiff, employed as a lifeguard, alleged that her work environment was riddled with crude remarks and obscenities.⁹ One of the two supervisors reportedly once said to Faragher, “Date me or clean toilets for a year.” Another lifeguard had previously lodged similar complaints. The plaintiff ultimately resigned and brought suit.

The U.S. Supreme Court characterized both of these as “hostile environment” rather than “quid pro quo” cases, because the plaintiffs did not suffer any direct adverse job action. In its decisions, the court defined the scope of liability and affirmative defenses, holding that employers can be subject to vicarious liability when supervisors create actionable hostile work environments.

In other cases, the Supreme Court has ruled for the use of “the reasonable person in the plaintiff’s position” standard in judging the severity of sexual harassment. The court has also held that the genders of the harasser and the harassed employee are not material in determining whether sexual harassment has occurred.

A physician can be accused of harassing an employee, a nurse, an assistant, a fellow worker, a third party, or a patient. Focusing on misconduct within the doctor-patient relationship, the Federation of State Medical Boards adopted in May 2006 a policy entitled “Addressing Sexual Boundaries: Guidelines for State Medical Boards.”¹⁰

Although it did not use the term sexual harassment, the policy emphasized that physician sexual misconduct may include behavior that is verbal or physical, and may include expressions of thoughts and feelings or gestures that are sexual. It used the term “sexual impropriety” to denote behavior, gestures, or expressions that are seductive, sexually suggestive, disrespectful of patient privacy, or sexually demeaning to a patient. Together with “sexual violation,” a term the FSMB used when referring to physical sexual contact, they form the basis for disciplinary action by a state medical board.

Caveat: When performing a physical exam, physicians should always use good judgment and sensitivity, relying on the presence of a medical assistant to ensure patient comfort and to alleviate possible embarrassment or anxiety.

Under the federal EEOC rules, the employer rather than the harasser is the defendant. But there are other legal recourses, including tort and criminal actions, that directly target the harasser. Successful plaintiffs may be awarded lost wages, as well as damages for emotional distress, medical expenses, and punitive damages. They may also recover attorney fees.

In one case, a psychiatric nurse was awarded $1.2 million (later reduced to $850,000); in another, a nurse successfully sued a physician’s medical practice and received $150,000 in damages.⁴ And in an unusual case, a plaintiff was awarded only $1 in damages, but her counsel was paid $41,598 in fees.¹¹ For the practicing doctor, medical board sanction, notoriety, and loss of professional standing and privileges constitute additional costs.

The medical profession is as susceptible as any other – perhaps more so – to allegations of sexual harassment. The magic words for actionable sexual harassment are severe, pervasive, and unwelcome. Although laws in the workplace generally do not prohibit simple teasing, offhand comments, or minor isolated incidents, the line separating these behaviors from bona fide sexual harassment is thin.

Erring on the side of strict and sober professional propriety seems prudent, given the current climate of zero tolerance.


 

References

1. MacCluskey v. University of Connecticut Health Center, United States Court of Appeals, Second Circuit, No. 17-0807-cv, Dec. 19, 2017.

2. Arch Intern Med. 1998 Feb 23;158(4):352-8.

3. N Engl J Med. 1993 Dec 23;329(26):1936-9.

4. J Nurs Care Qual. 2004 Jul-Sep;19(3):234-41.

5. Anania v. Daubenspeck Chiropractic, 718 N.E. 2d 480 (Ohio 1998).

6. Doe v. Borromeo, Nos. 305162, 305163 (Mich. Ct. App. Sept. 20, 2012).

7. Available at https://www.eeoc.gov/laws/types/sexual_harassment.cfm.

8. Burlington Industries, Inc. v. Ellerth, 524 US 742 (1998).

9. Faragher v. City of Boca Raton, 524 U.S. 775 (1998).

10. Federation of State Medical Boards, “Addressing Sexual Boundaries: Guidelines for State Medical Boards.”

11. J Healthc Risk Manag. 1999 Summer;19(3):14-25.

Systemic corticosteroids (SCSs) should be limited to short courses as a transition to steroid-sparing therapies in patients with atopic dermatitis because of the potential for adverse effects, reported Sherry Yu, MD, of Massachusetts General Hospital, Boston, and her associates.

Michail_Petrov-96/Thinkstock

Dr. Yu reported no relevant financial disclosures. The other three authors reported relationships with various companies in the industry.

[email protected]

SOURCE: Yu S et al. J Am Acad Dermatol. 2017 Oct 13. doi: 10.1016/j.jaad.2017.09.074.

Systemic corticosteroids (SCSs) should be limited to short courses as a transition to steroid-sparing therapies in patients with atopic dermatitis because of the potential for adverse effects, reported Sherry Yu, MD, of Massachusetts General Hospital, Boston, and her associates.

Michail_Petrov-96/Thinkstock

Dr. Yu reported no relevant financial disclosures. The other three authors reported relationships with various companies in the industry.

[email protected]

SOURCE: Yu S et al. J Am Acad Dermatol. 2017 Oct 13. doi: 10.1016/j.jaad.2017.09.074.

Systemic corticosteroids (SCSs) should be limited to short courses as a transition to steroid-sparing therapies in patients with atopic dermatitis because of the potential for adverse effects, reported Sherry Yu, MD, of Massachusetts General Hospital, Boston, and her associates.

Michail_Petrov-96/Thinkstock

Dr. Yu reported no relevant financial disclosures. The other three authors reported relationships with various companies in the industry.

[email protected]

SOURCE: Yu S et al. J Am Acad Dermatol. 2017 Oct 13. doi: 10.1016/j.jaad.2017.09.074.

The U.S. Preventive Services Task Force neither recommended for nor recommended against routine screening for adolescent idiopathic scoliosis in new guidelines published Jan. 9 in JAMA.

The determination applies to asymptomatic adolescents 10-18 years old; it does not apply to children and adolescents who present with back pain, breathing difficulties, obvious spine deformities, or abnormal imaging.

Draw05/Thinkstock

[email protected]

SOURCE: US Preventive Services Task Force. JAMA. 2018 Jan 9;319(2):165-72; Dunn J et al. JAMA. 2018;319(2):173-87.

The U.S. Preventive Services Task Force neither recommended for nor recommended against routine screening for adolescent idiopathic scoliosis in new guidelines published Jan. 9 in JAMA.

The determination applies to asymptomatic adolescents 10-18 years old; it does not apply to children and adolescents who present with back pain, breathing difficulties, obvious spine deformities, or abnormal imaging.

Draw05/Thinkstock

[email protected]

SOURCE: US Preventive Services Task Force. JAMA. 2018 Jan 9;319(2):165-72; Dunn J et al. JAMA. 2018;319(2):173-87.

The U.S. Preventive Services Task Force neither recommended for nor recommended against routine screening for adolescent idiopathic scoliosis in new guidelines published Jan. 9 in JAMA.

The determination applies to asymptomatic adolescents 10-18 years old; it does not apply to children and adolescents who present with back pain, breathing difficulties, obvious spine deformities, or abnormal imaging.

Draw05/Thinkstock

[email protected]

SOURCE: US Preventive Services Task Force. JAMA. 2018 Jan 9;319(2):165-72; Dunn J et al. JAMA. 2018;319(2):173-87.

Idalopirdine suffered the final nail in its coffin with the complete release of its phase 3 data detailing its failure to improve cognitive outcomes in patients with mild to moderate Alzheimer’s disease.

The 5-HT₆ receptor antagonist idalopirdine was given on a background of stable cholinesterase inhibitor therapy in three Lundbeck-sponsored phase 3 trials: STARSHINE, STARBEAM, and STARBRIGHT. But none of the STAR studies reproduced the results of idalopirdine’s modestly successful phase 2 study, LADDER, wrote Alireza Atri, MD, PhD, and his colleagues. The report appears Jan. 9 in JAMA.

©roberthyrons/thinkstockphotos.com

This article was updated 1/12/18.

[email protected]

SOURCE: Atri A et al., JAMA. 2018;319(2):130-42

Idalopirdine suffered the final nail in its coffin with the complete release of its phase 3 data detailing its failure to improve cognitive outcomes in patients with mild to moderate Alzheimer’s disease.

The 5-HT₆ receptor antagonist idalopirdine was given on a background of stable cholinesterase inhibitor therapy in three Lundbeck-sponsored phase 3 trials: STARSHINE, STARBEAM, and STARBRIGHT. But none of the STAR studies reproduced the results of idalopirdine’s modestly successful phase 2 study, LADDER, wrote Alireza Atri, MD, PhD, and his colleagues. The report appears Jan. 9 in JAMA.

©roberthyrons/thinkstockphotos.com

This article was updated 1/12/18.

[email protected]

SOURCE: Atri A et al., JAMA. 2018;319(2):130-42

Idalopirdine suffered the final nail in its coffin with the complete release of its phase 3 data detailing its failure to improve cognitive outcomes in patients with mild to moderate Alzheimer’s disease.

The 5-HT₆ receptor antagonist idalopirdine was given on a background of stable cholinesterase inhibitor therapy in three Lundbeck-sponsored phase 3 trials: STARSHINE, STARBEAM, and STARBRIGHT. But none of the STAR studies reproduced the results of idalopirdine’s modestly successful phase 2 study, LADDER, wrote Alireza Atri, MD, PhD, and his colleagues. The report appears Jan. 9 in JAMA.

©roberthyrons/thinkstockphotos.com

This article was updated 1/12/18.

[email protected]

SOURCE: Atri A et al., JAMA. 2018;319(2):130-42

Decreases in breast cancer mortality between 2000 and 2012 were associated with advances in screening and adjuvant therapy but varied by breast cancer molecular subtype, according to a simulation modeling study.

The estimated rate of reduction in overall breast cancer mortality in 2000 was 37% from an estimated baseline rate of 64 deaths per 100,000 women, with 44% and 56% of that associated with screening and treatment, respectively. In 2012 the estimated reduction was 49% from an estimated baseline rate of 63 per 100,000 women, with 37% and 63% associated with screening and treatment, respectively (estimated 12% difference in 2012 vs. 2000), Sylvia K. Plevritis, PhD, of Stanford (Calif.) University and her colleagues reported in JAMA.

Screening and treatment were estimated to contribute to the reductions at varying rates. For example, the relative contributions of screening vs. treatment were 36% vs. 64% for ER+/ERBB2– disease; 31% vs. 69% for ER+/ERBB2+ disease; 40% vs. 60% for ER–/ERBB2+ disease; and 48% vs. 52% for ER–/ERBB2– disease.

The model-based analysis provides clinically relevant insights about the contributions of screening and treatment to reductions in breast cancer mortality by molecular subtype, showing a greater relative contribution of treatment in 2012 overall and for all subtypes except ER–/ERBB2– disease, the authors said.

“Because ER+ cancers are the most prevalent and this group is expected to increase with time, additional advances for this subtype could have the largest effect on reducing the overall population burden of breast cancer,” they noted.

This study was supported by grants from the National Cancer Institute and the American Cancer Society. Dr. Plevritis reported consulting for GRAIL.

[email protected]

SOURCE: Plevritis S et al. JAMA. 2018 Jan 9;319(2):154-64. doi: 10.1001/jama.2017.19130.

.
 

Decreases in breast cancer mortality between 2000 and 2012 were associated with advances in screening and adjuvant therapy but varied by breast cancer molecular subtype, according to a simulation modeling study.

The estimated rate of reduction in overall breast cancer mortality in 2000 was 37% from an estimated baseline rate of 64 deaths per 100,000 women, with 44% and 56% of that associated with screening and treatment, respectively. In 2012 the estimated reduction was 49% from an estimated baseline rate of 63 per 100,000 women, with 37% and 63% associated with screening and treatment, respectively (estimated 12% difference in 2012 vs. 2000), Sylvia K. Plevritis, PhD, of Stanford (Calif.) University and her colleagues reported in JAMA.

Screening and treatment were estimated to contribute to the reductions at varying rates. For example, the relative contributions of screening vs. treatment were 36% vs. 64% for ER+/ERBB2– disease; 31% vs. 69% for ER+/ERBB2+ disease; 40% vs. 60% for ER–/ERBB2+ disease; and 48% vs. 52% for ER–/ERBB2– disease.

The model-based analysis provides clinically relevant insights about the contributions of screening and treatment to reductions in breast cancer mortality by molecular subtype, showing a greater relative contribution of treatment in 2012 overall and for all subtypes except ER–/ERBB2– disease, the authors said.

“Because ER+ cancers are the most prevalent and this group is expected to increase with time, additional advances for this subtype could have the largest effect on reducing the overall population burden of breast cancer,” they noted.

This study was supported by grants from the National Cancer Institute and the American Cancer Society. Dr. Plevritis reported consulting for GRAIL.

[email protected]

SOURCE: Plevritis S et al. JAMA. 2018 Jan 9;319(2):154-64. doi: 10.1001/jama.2017.19130.

.
 

Decreases in breast cancer mortality between 2000 and 2012 were associated with advances in screening and adjuvant therapy but varied by breast cancer molecular subtype, according to a simulation modeling study.

The estimated rate of reduction in overall breast cancer mortality in 2000 was 37% from an estimated baseline rate of 64 deaths per 100,000 women, with 44% and 56% of that associated with screening and treatment, respectively. In 2012 the estimated reduction was 49% from an estimated baseline rate of 63 per 100,000 women, with 37% and 63% associated with screening and treatment, respectively (estimated 12% difference in 2012 vs. 2000), Sylvia K. Plevritis, PhD, of Stanford (Calif.) University and her colleagues reported in JAMA.

Screening and treatment were estimated to contribute to the reductions at varying rates. For example, the relative contributions of screening vs. treatment were 36% vs. 64% for ER+/ERBB2– disease; 31% vs. 69% for ER+/ERBB2+ disease; 40% vs. 60% for ER–/ERBB2+ disease; and 48% vs. 52% for ER–/ERBB2– disease.

The model-based analysis provides clinically relevant insights about the contributions of screening and treatment to reductions in breast cancer mortality by molecular subtype, showing a greater relative contribution of treatment in 2012 overall and for all subtypes except ER–/ERBB2– disease, the authors said.

“Because ER+ cancers are the most prevalent and this group is expected to increase with time, additional advances for this subtype could have the largest effect on reducing the overall population burden of breast cancer,” they noted.

This study was supported by grants from the National Cancer Institute and the American Cancer Society. Dr. Plevritis reported consulting for GRAIL.

[email protected]

SOURCE: Plevritis S et al. JAMA. 2018 Jan 9;319(2):154-64. doi: 10.1001/jama.2017.19130.

.
 

DENVER – Distal embolic protection using a filter device during primary PCI for acute MI significantly reduced the incidence of the no-reflow phenomenon and serious adverse events in the randomized VAMPIRE 3 trial.

The reason VAMPIRE 3 (Vacuum Aspiration Thrombus Removal) was a positive trial when other studies of distal embolic protection during coronary intervention have failed was that VAMPIRE 3 targeted a high-risk, high-benefit population: the subset of acute MI patients with attenuated, high-risk coronary plaque identified by intravascular ultrasound, Kiyoshi Hibi, MD, explained at the Transcatheter Cardiovascular Therapeutics annual educational meeting.

Also, the filter device used in the trial was easily deployed and problem free, which doesn’t appear to be true of distal protection devices used in some earlier trials.

Bruce Jancin/Frontline Medical News

[email protected]

SOURCE: Hibi K. TCT 2017

DENVER – Distal embolic protection using a filter device during primary PCI for acute MI significantly reduced the incidence of the no-reflow phenomenon and serious adverse events in the randomized VAMPIRE 3 trial.

The reason VAMPIRE 3 (Vacuum Aspiration Thrombus Removal) was a positive trial when other studies of distal embolic protection during coronary intervention have failed was that VAMPIRE 3 targeted a high-risk, high-benefit population: the subset of acute MI patients with attenuated, high-risk coronary plaque identified by intravascular ultrasound, Kiyoshi Hibi, MD, explained at the Transcatheter Cardiovascular Therapeutics annual educational meeting.

Also, the filter device used in the trial was easily deployed and problem free, which doesn’t appear to be true of distal protection devices used in some earlier trials.

Bruce Jancin/Frontline Medical News

[email protected]

SOURCE: Hibi K. TCT 2017

DENVER – Distal embolic protection using a filter device during primary PCI for acute MI significantly reduced the incidence of the no-reflow phenomenon and serious adverse events in the randomized VAMPIRE 3 trial.

The reason VAMPIRE 3 (Vacuum Aspiration Thrombus Removal) was a positive trial when other studies of distal embolic protection during coronary intervention have failed was that VAMPIRE 3 targeted a high-risk, high-benefit population: the subset of acute MI patients with attenuated, high-risk coronary plaque identified by intravascular ultrasound, Kiyoshi Hibi, MD, explained at the Transcatheter Cardiovascular Therapeutics annual educational meeting.

Also, the filter device used in the trial was easily deployed and problem free, which doesn’t appear to be true of distal protection devices used in some earlier trials.

Bruce Jancin/Frontline Medical News

[email protected]

SOURCE: Hibi K. TCT 2017

Lab mouse

Researchers say they have found a way to target the oncogenic transcription factor MYB in acute myeloid leukemia (AML).

By inducing the expression of a peptide in mouse models of AML, the researchers were able to prevent MYB from promoting leukemia growth.

In fact, the team observed AML regression with no harmful impact on the function of normal cells.

Christopher Vakoc, MD, PhD, of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and his colleagues described these findings in Cancer Cell.

“MYB is a dream target in cancer research because it’s involved in so many cancers,” Dr Vakoc said. “In leukemia, it’s special because we know from previous research that, by targeting MYB, you can get AML not just to stop growing but actually to regress.”

With the current research, Dr Vakoc and his colleagues discovered how to selectively target MYB.

First, the researchers found that MYB activates gene expression by docking at a giant gene-co-activation protein called TFIID.

Specifically, the MYB transactivation domain binds to the TAF12/TAF4 histone-fold domain (HFD) heterodimer. TAF12 and TAF4 are subunits of TFIID.

Based on this finding, the researchers hypothesized that “a minimal HFD fragment of TAF4 would be an ideal probe for blocking MYB function, since this peptide binds with high affinity and specificity to the TAF12 HFD.”

The team thought the peptide would form an ineffective complex with TAF12 and MYB, interfering with the endogenous MYB-TFIID interaction.

In in vitro experiments, TAF4-HFD expression inhibited AML growth and blast colony formation, induced differentiation, and destabilized MYB protein.

For their in vivo experiments, the researchers transduced RN2 cells with a dox-inducible TAF4-HFD retroviral vector and transplanted the cells in mice.

The team observed “marked” AML regression and prolonged survival in these mice compared to controls.

While the peptide is not itself a drug, Dr Vakoc said its action could be replicated by a drug.

“It’s a concept we’re now discussing with the pharmaceutical industry,” he said. “It is going to take lots of work before it can result in a medicine leukemia patients might take. But we’re excited about this new approach because MYB is such an important player in many cancers and, until now, has eluded efforts to selectively target it.”

Lab mouse

Researchers say they have found a way to target the oncogenic transcription factor MYB in acute myeloid leukemia (AML).

By inducing the expression of a peptide in mouse models of AML, the researchers were able to prevent MYB from promoting leukemia growth.

In fact, the team observed AML regression with no harmful impact on the function of normal cells.

Christopher Vakoc, MD, PhD, of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and his colleagues described these findings in Cancer Cell.

“MYB is a dream target in cancer research because it’s involved in so many cancers,” Dr Vakoc said. “In leukemia, it’s special because we know from previous research that, by targeting MYB, you can get AML not just to stop growing but actually to regress.”

With the current research, Dr Vakoc and his colleagues discovered how to selectively target MYB.

First, the researchers found that MYB activates gene expression by docking at a giant gene-co-activation protein called TFIID.

Specifically, the MYB transactivation domain binds to the TAF12/TAF4 histone-fold domain (HFD) heterodimer. TAF12 and TAF4 are subunits of TFIID.

Based on this finding, the researchers hypothesized that “a minimal HFD fragment of TAF4 would be an ideal probe for blocking MYB function, since this peptide binds with high affinity and specificity to the TAF12 HFD.”

The team thought the peptide would form an ineffective complex with TAF12 and MYB, interfering with the endogenous MYB-TFIID interaction.

In in vitro experiments, TAF4-HFD expression inhibited AML growth and blast colony formation, induced differentiation, and destabilized MYB protein.

For their in vivo experiments, the researchers transduced RN2 cells with a dox-inducible TAF4-HFD retroviral vector and transplanted the cells in mice.

The team observed “marked” AML regression and prolonged survival in these mice compared to controls.

While the peptide is not itself a drug, Dr Vakoc said its action could be replicated by a drug.

“It’s a concept we’re now discussing with the pharmaceutical industry,” he said. “It is going to take lots of work before it can result in a medicine leukemia patients might take. But we’re excited about this new approach because MYB is such an important player in many cancers and, until now, has eluded efforts to selectively target it.”

Lab mouse

Researchers say they have found a way to target the oncogenic transcription factor MYB in acute myeloid leukemia (AML).

By inducing the expression of a peptide in mouse models of AML, the researchers were able to prevent MYB from promoting leukemia growth.

In fact, the team observed AML regression with no harmful impact on the function of normal cells.

Christopher Vakoc, MD, PhD, of Cold Spring Harbor Laboratory in Cold Spring Harbor, New York, and his colleagues described these findings in Cancer Cell.

“MYB is a dream target in cancer research because it’s involved in so many cancers,” Dr Vakoc said. “In leukemia, it’s special because we know from previous research that, by targeting MYB, you can get AML not just to stop growing but actually to regress.”

With the current research, Dr Vakoc and his colleagues discovered how to selectively target MYB.

First, the researchers found that MYB activates gene expression by docking at a giant gene-co-activation protein called TFIID.

Specifically, the MYB transactivation domain binds to the TAF12/TAF4 histone-fold domain (HFD) heterodimer. TAF12 and TAF4 are subunits of TFIID.

Based on this finding, the researchers hypothesized that “a minimal HFD fragment of TAF4 would be an ideal probe for blocking MYB function, since this peptide binds with high affinity and specificity to the TAF12 HFD.”

The team thought the peptide would form an ineffective complex with TAF12 and MYB, interfering with the endogenous MYB-TFIID interaction.

In in vitro experiments, TAF4-HFD expression inhibited AML growth and blast colony formation, induced differentiation, and destabilized MYB protein.

For their in vivo experiments, the researchers transduced RN2 cells with a dox-inducible TAF4-HFD retroviral vector and transplanted the cells in mice.

The team observed “marked” AML regression and prolonged survival in these mice compared to controls.

While the peptide is not itself a drug, Dr Vakoc said its action could be replicated by a drug.

“It’s a concept we’re now discussing with the pharmaceutical industry,” he said. “It is going to take lots of work before it can result in a medicine leukemia patients might take. But we’re excited about this new approach because MYB is such an important player in many cancers and, until now, has eluded efforts to selectively target it.”

© Todd Buchanan 2017

ATLANTA—Updated trial results have shown that gene therapy can increase factor VIII (FVIII) levels and reduce the need for FVIII infusions in patients with severe hemophilia A.

Most patients who received the gene therapy, valoctocogene roxaparvovec (VR, formerly BMN 270), were able to achieve normal or near-normal FVIII levels.

In addition, patients were able to discontinue prophylactic FVIII infusions and greatly reduce the number of on-demand FVIII infusions they received.

“We have seen mind-blowing results, which have far exceeded our expectations,” said study investigator K. John Pasi, MBChB, PhD, of Barts and the London School of Medicine and Dentistry in the UK.

“When we started out, we thought it would be a huge achievement to show a 5% improvement [in FVIII levels], so to actually be seeing normal or near-normal factor levels with dramatic reduction in bleeding is, quite simply, amazing.”

Dr Pasi presented these results—with 1.5 years of follow-up—at the 2017 ASH Annual Meeting (abstract 603*).

One-year results from this phase 1/2 trial were simultaneously published in NEJM. Previous results were reported at the ISTH 2017 Congress.

The trial was sponsored by BioMarin Pharmaceuticals, Inc., the company developing VR.

The trial included 13 patients with previously treated, severe hemophilia A (defined as less than or equal to 1% of FVIII activity levels, expressed as a percentage of normal factor activity in blood).

Seven of the patients received VR at a 6e13 vg/kg dose, and 6 received VR at a 4e13 vg/kg dose.

The data presented at ASH had a cutoff date of November 16, 2017.

4e13 vg/kg-dose group

All 6 patients in the 4e13 vg/kg-dose group had 36 weeks of follow-up. At that point, the median FVIII level for the group was 38%, and the mean was 35% (range, 4-55).

For the 3 patients who had 48 weeks of follow-up, the median and mean FVIII levels were both 49% (range, 38-60).

Before receiving VR, these patients (all 6) had a median annualized bleeding rate (ABR) of 8.0 and a mean ABR of 12.2.

Four weeks after receiving VR, the median ABR was 0.0 and the mean ABR was 0.6.

Before receiving VR, each patient received a median of 155.5 FVIII infusions per year and a mean of 146.5 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean of 2.0 FVIII infusions.

6e13 vg/kg-dose group

All 7 patients in this group had at least 78 weeks of follow-up. At this point, the median FVIII level for the group was 90%, and the mean was 89% (range, 11-179).

One patient received on-demand FVIII treatment while on study and was excluded from the analysis of ABR and FVIII infusions.

The remaining 6 patients, before VR, had a median ABR of 16.5 and a mean ABR of 16.3.

Four weeks after VR infusion, the median ABR was 0.0, and the mean was 0.5.

Before receiving VR, each patient received a median of 138.5 FVIII infusions per year and a mean 136.7 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean 6.1 FVIII infusions.

Five patients had 0 bleeds requiring FVIII infusions and 0 FVIII infusions from week 4 after VR infusion until last follow-up.

“The clinical data, to date, for this investigational gene therapy exceeded our expectations, in terms of increasing FVIII levels and reducing the annualized bleed rate,” Dr Pasi said.

“Many clinical trial participants have seen FVIII levels at or close to normal. With this experimental treatment, we are researching whether it may be possible for hemophilia A patients to reduce or eliminate FVIII treatment over an extended timeline.”

Safety

The safety data included 2 patients who received VR at 6e12 vg/kg and 2e13 vg/kg, respectively, as well as the 13 patients for whom efficacy data were reported at ASH.

None of the patients developed inhibitors to FVIII, and none withdrew from the study.

The most common adverse events (AEs) across all dose cohorts were alanine aminotransferase elevation (n=11, 73%), arthralgia (n=9, 60%), aspartate aminotransferase elevation (n=8, 53%), headache (n=7, 47%), back pain (n=5, 33%), fatigue (n=5, 33%), and upper respiratory tract infection (n=5, 33%).

Serious AEs were reported in 2 patients. One of these events was considered related to VR.

The patient with the VR-related serious AE was hospitalized for observation after developing grade 2 pyrexia with myalgia and headache within 24 hours of receiving VR. The event resolved within 48 hours of treatment with paracetamol.

The other serious AE was attributed to a planned knee surgery to treat hemophilic arthropathy, and it was grade 1 in severity. No complications were reported. 

*Data in the presentation differ from the abstract.

© Todd Buchanan 2017

ATLANTA—Updated trial results have shown that gene therapy can increase factor VIII (FVIII) levels and reduce the need for FVIII infusions in patients with severe hemophilia A.

Most patients who received the gene therapy, valoctocogene roxaparvovec (VR, formerly BMN 270), were able to achieve normal or near-normal FVIII levels.

In addition, patients were able to discontinue prophylactic FVIII infusions and greatly reduce the number of on-demand FVIII infusions they received.

“We have seen mind-blowing results, which have far exceeded our expectations,” said study investigator K. John Pasi, MBChB, PhD, of Barts and the London School of Medicine and Dentistry in the UK.

“When we started out, we thought it would be a huge achievement to show a 5% improvement [in FVIII levels], so to actually be seeing normal or near-normal factor levels with dramatic reduction in bleeding is, quite simply, amazing.”

Dr Pasi presented these results—with 1.5 years of follow-up—at the 2017 ASH Annual Meeting (abstract 603*).

One-year results from this phase 1/2 trial were simultaneously published in NEJM. Previous results were reported at the ISTH 2017 Congress.

The trial was sponsored by BioMarin Pharmaceuticals, Inc., the company developing VR.

The trial included 13 patients with previously treated, severe hemophilia A (defined as less than or equal to 1% of FVIII activity levels, expressed as a percentage of normal factor activity in blood).

Seven of the patients received VR at a 6e13 vg/kg dose, and 6 received VR at a 4e13 vg/kg dose.

The data presented at ASH had a cutoff date of November 16, 2017.

4e13 vg/kg-dose group

All 6 patients in the 4e13 vg/kg-dose group had 36 weeks of follow-up. At that point, the median FVIII level for the group was 38%, and the mean was 35% (range, 4-55).

For the 3 patients who had 48 weeks of follow-up, the median and mean FVIII levels were both 49% (range, 38-60).

Before receiving VR, these patients (all 6) had a median annualized bleeding rate (ABR) of 8.0 and a mean ABR of 12.2.

Four weeks after receiving VR, the median ABR was 0.0 and the mean ABR was 0.6.

Before receiving VR, each patient received a median of 155.5 FVIII infusions per year and a mean of 146.5 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean of 2.0 FVIII infusions.

6e13 vg/kg-dose group

All 7 patients in this group had at least 78 weeks of follow-up. At this point, the median FVIII level for the group was 90%, and the mean was 89% (range, 11-179).

One patient received on-demand FVIII treatment while on study and was excluded from the analysis of ABR and FVIII infusions.

The remaining 6 patients, before VR, had a median ABR of 16.5 and a mean ABR of 16.3.

Four weeks after VR infusion, the median ABR was 0.0, and the mean was 0.5.

Before receiving VR, each patient received a median of 138.5 FVIII infusions per year and a mean 136.7 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean 6.1 FVIII infusions.

Five patients had 0 bleeds requiring FVIII infusions and 0 FVIII infusions from week 4 after VR infusion until last follow-up.

“The clinical data, to date, for this investigational gene therapy exceeded our expectations, in terms of increasing FVIII levels and reducing the annualized bleed rate,” Dr Pasi said.

“Many clinical trial participants have seen FVIII levels at or close to normal. With this experimental treatment, we are researching whether it may be possible for hemophilia A patients to reduce or eliminate FVIII treatment over an extended timeline.”

Safety

The safety data included 2 patients who received VR at 6e12 vg/kg and 2e13 vg/kg, respectively, as well as the 13 patients for whom efficacy data were reported at ASH.

None of the patients developed inhibitors to FVIII, and none withdrew from the study.

The most common adverse events (AEs) across all dose cohorts were alanine aminotransferase elevation (n=11, 73%), arthralgia (n=9, 60%), aspartate aminotransferase elevation (n=8, 53%), headache (n=7, 47%), back pain (n=5, 33%), fatigue (n=5, 33%), and upper respiratory tract infection (n=5, 33%).

Serious AEs were reported in 2 patients. One of these events was considered related to VR.

The patient with the VR-related serious AE was hospitalized for observation after developing grade 2 pyrexia with myalgia and headache within 24 hours of receiving VR. The event resolved within 48 hours of treatment with paracetamol.

The other serious AE was attributed to a planned knee surgery to treat hemophilic arthropathy, and it was grade 1 in severity. No complications were reported. 

*Data in the presentation differ from the abstract.

© Todd Buchanan 2017

ATLANTA—Updated trial results have shown that gene therapy can increase factor VIII (FVIII) levels and reduce the need for FVIII infusions in patients with severe hemophilia A.

Most patients who received the gene therapy, valoctocogene roxaparvovec (VR, formerly BMN 270), were able to achieve normal or near-normal FVIII levels.

In addition, patients were able to discontinue prophylactic FVIII infusions and greatly reduce the number of on-demand FVIII infusions they received.

“We have seen mind-blowing results, which have far exceeded our expectations,” said study investigator K. John Pasi, MBChB, PhD, of Barts and the London School of Medicine and Dentistry in the UK.

“When we started out, we thought it would be a huge achievement to show a 5% improvement [in FVIII levels], so to actually be seeing normal or near-normal factor levels with dramatic reduction in bleeding is, quite simply, amazing.”

Dr Pasi presented these results—with 1.5 years of follow-up—at the 2017 ASH Annual Meeting (abstract 603*).

One-year results from this phase 1/2 trial were simultaneously published in NEJM. Previous results were reported at the ISTH 2017 Congress.

The trial was sponsored by BioMarin Pharmaceuticals, Inc., the company developing VR.

The trial included 13 patients with previously treated, severe hemophilia A (defined as less than or equal to 1% of FVIII activity levels, expressed as a percentage of normal factor activity in blood).

Seven of the patients received VR at a 6e13 vg/kg dose, and 6 received VR at a 4e13 vg/kg dose.

The data presented at ASH had a cutoff date of November 16, 2017.

4e13 vg/kg-dose group

All 6 patients in the 4e13 vg/kg-dose group had 36 weeks of follow-up. At that point, the median FVIII level for the group was 38%, and the mean was 35% (range, 4-55).

For the 3 patients who had 48 weeks of follow-up, the median and mean FVIII levels were both 49% (range, 38-60).

Before receiving VR, these patients (all 6) had a median annualized bleeding rate (ABR) of 8.0 and a mean ABR of 12.2.

Four weeks after receiving VR, the median ABR was 0.0 and the mean ABR was 0.6.

Before receiving VR, each patient received a median of 155.5 FVIII infusions per year and a mean of 146.5 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean of 2.0 FVIII infusions.

6e13 vg/kg-dose group

All 7 patients in this group had at least 78 weeks of follow-up. At this point, the median FVIII level for the group was 90%, and the mean was 89% (range, 11-179).

One patient received on-demand FVIII treatment while on study and was excluded from the analysis of ABR and FVIII infusions.

The remaining 6 patients, before VR, had a median ABR of 16.5 and a mean ABR of 16.3.

Four weeks after VR infusion, the median ABR was 0.0, and the mean was 0.5.

Before receiving VR, each patient received a median of 138.5 FVIII infusions per year and a mean 136.7 FVIII infusions.

Four weeks after receiving VR, they received a median of 0.0 FVIII infusions and mean 6.1 FVIII infusions.

Five patients had 0 bleeds requiring FVIII infusions and 0 FVIII infusions from week 4 after VR infusion until last follow-up.

“The clinical data, to date, for this investigational gene therapy exceeded our expectations, in terms of increasing FVIII levels and reducing the annualized bleed rate,” Dr Pasi said.

“Many clinical trial participants have seen FVIII levels at or close to normal. With this experimental treatment, we are researching whether it may be possible for hemophilia A patients to reduce or eliminate FVIII treatment over an extended timeline.”

Safety

The safety data included 2 patients who received VR at 6e12 vg/kg and 2e13 vg/kg, respectively, as well as the 13 patients for whom efficacy data were reported at ASH.

None of the patients developed inhibitors to FVIII, and none withdrew from the study.

The most common adverse events (AEs) across all dose cohorts were alanine aminotransferase elevation (n=11, 73%), arthralgia (n=9, 60%), aspartate aminotransferase elevation (n=8, 53%), headache (n=7, 47%), back pain (n=5, 33%), fatigue (n=5, 33%), and upper respiratory tract infection (n=5, 33%).

Serious AEs were reported in 2 patients. One of these events was considered related to VR.

The patient with the VR-related serious AE was hospitalized for observation after developing grade 2 pyrexia with myalgia and headache within 24 hours of receiving VR. The event resolved within 48 hours of treatment with paracetamol.

The other serious AE was attributed to a planned knee surgery to treat hemophilic arthropathy, and it was grade 1 in severity. No complications were reported. 

*Data in the presentation differ from the abstract.

Photo courtesy of Janssen

New research appears to explain why ibrutinib may be less effective in certain patients with chronic lymphocytic leukemia (CLL).

It seems the Bruton’s tyrosine kinase (BTK) inhibitor has a diminished capacity to delocalize and kill tumor cells expressing an adhesive protein called CD49d.

But combining ibrutinib with drugs that block CD49d activation could prevent CLL cells from sheltering in lymphoid organs.

Valter Gattei, MD, of CRO Aviano National Cancer Institute in Aviano, Italy, and his colleagues reported these findings in the Journal of Experimental Medicine.

The team noted that CD49d, the α chain of the CD49d/CD29 integrin heterodimer very late antigen 4 (VLA-4), is expressed in about 40% of CLL cases.

These patients tend to have poorer outcomes than patients who do not express CD49d, but the role of VLA-4 in CLL was unclear.

With this study, researchers found that B-cell receptor (BCR) signaling can activate VLA-4 in CD49d-expressing CLL cells, thereby enhancing the cells’ adhesiveness.

Even though ibrutinib treatment impaired BCR signaling in these cells, it was unable to fully prevent the pathway from activating VLA-4 and enhancing cell adhesion.

The researchers analyzed 3 cohorts of CLL patients and found that patients expressing higher levels of CD49d had reduced responses to ibrutinib.

The BTK inhibitor appeared less able to displace tumor cells from lymph nodes into the blood, resulting in decreased lymph node shrinkage and shorter progression-free survival times.

“Our results suggest that VLA-4-expressing CLL cells residing in the secondary lymphoid organs can receive BCR-mediated stimuli that can activate VLA-4 even in the presence of ibrutinib,” said study author Antonella Zucchetto, ScD, also of CRO Aviano National Cancer Institute.

“This activation leads to enhanced retention of VLA-4-positive CLL cells in tissue sites, thereby affecting patient outcome.”

Fortunately, the researchers found a way around this obstacle. Inhibiting BTK and phosphatidylinositide 3-kinase (PI3K) simultaneously completely blocked VLA-4 activation in CLL cells.

The researchers treated CLL cells with ibrutinib, the PI3K inhibitor idelalisib, or a combination of both.

Neither drug alone was able to fully block anti-IgM-induced VLA-4 activation. However, the team found that simultaneous inhibition of BTK and PI3K “completely abolished the integrin response to BCR triggering.”

The researchers also added idelalisib to ibrutinib-treated CLL cells (collected from patients at day 30 on ibrutinib) and observed a complete upset of anti-IgM–induced VLA-4 activation.

“Our data suggest that evaluation of CD49d expression in patients initiating ibrutinib therapy may identify those cases that would benefit from combination therapy approaches designed to completely block VLA-4 activation and VLA-4-mediated retention of leukemic cells in protective tissue compartments,” Dr Gattei said.

Photo courtesy of Janssen

New research appears to explain why ibrutinib may be less effective in certain patients with chronic lymphocytic leukemia (CLL).

It seems the Bruton’s tyrosine kinase (BTK) inhibitor has a diminished capacity to delocalize and kill tumor cells expressing an adhesive protein called CD49d.

But combining ibrutinib with drugs that block CD49d activation could prevent CLL cells from sheltering in lymphoid organs.

Valter Gattei, MD, of CRO Aviano National Cancer Institute in Aviano, Italy, and his colleagues reported these findings in the Journal of Experimental Medicine.

The team noted that CD49d, the α chain of the CD49d/CD29 integrin heterodimer very late antigen 4 (VLA-4), is expressed in about 40% of CLL cases.

These patients tend to have poorer outcomes than patients who do not express CD49d, but the role of VLA-4 in CLL was unclear.

With this study, researchers found that B-cell receptor (BCR) signaling can activate VLA-4 in CD49d-expressing CLL cells, thereby enhancing the cells’ adhesiveness.

Even though ibrutinib treatment impaired BCR signaling in these cells, it was unable to fully prevent the pathway from activating VLA-4 and enhancing cell adhesion.

The researchers analyzed 3 cohorts of CLL patients and found that patients expressing higher levels of CD49d had reduced responses to ibrutinib.

The BTK inhibitor appeared less able to displace tumor cells from lymph nodes into the blood, resulting in decreased lymph node shrinkage and shorter progression-free survival times.

“Our results suggest that VLA-4-expressing CLL cells residing in the secondary lymphoid organs can receive BCR-mediated stimuli that can activate VLA-4 even in the presence of ibrutinib,” said study author Antonella Zucchetto, ScD, also of CRO Aviano National Cancer Institute.

“This activation leads to enhanced retention of VLA-4-positive CLL cells in tissue sites, thereby affecting patient outcome.”

Fortunately, the researchers found a way around this obstacle. Inhibiting BTK and phosphatidylinositide 3-kinase (PI3K) simultaneously completely blocked VLA-4 activation in CLL cells.

The researchers treated CLL cells with ibrutinib, the PI3K inhibitor idelalisib, or a combination of both.

Neither drug alone was able to fully block anti-IgM-induced VLA-4 activation. However, the team found that simultaneous inhibition of BTK and PI3K “completely abolished the integrin response to BCR triggering.”

The researchers also added idelalisib to ibrutinib-treated CLL cells (collected from patients at day 30 on ibrutinib) and observed a complete upset of anti-IgM–induced VLA-4 activation.

“Our data suggest that evaluation of CD49d expression in patients initiating ibrutinib therapy may identify those cases that would benefit from combination therapy approaches designed to completely block VLA-4 activation and VLA-4-mediated retention of leukemic cells in protective tissue compartments,” Dr Gattei said.

Photo courtesy of Janssen

New research appears to explain why ibrutinib may be less effective in certain patients with chronic lymphocytic leukemia (CLL).

It seems the Bruton’s tyrosine kinase (BTK) inhibitor has a diminished capacity to delocalize and kill tumor cells expressing an adhesive protein called CD49d.

But combining ibrutinib with drugs that block CD49d activation could prevent CLL cells from sheltering in lymphoid organs.

Valter Gattei, MD, of CRO Aviano National Cancer Institute in Aviano, Italy, and his colleagues reported these findings in the Journal of Experimental Medicine.

The team noted that CD49d, the α chain of the CD49d/CD29 integrin heterodimer very late antigen 4 (VLA-4), is expressed in about 40% of CLL cases.

These patients tend to have poorer outcomes than patients who do not express CD49d, but the role of VLA-4 in CLL was unclear.

With this study, researchers found that B-cell receptor (BCR) signaling can activate VLA-4 in CD49d-expressing CLL cells, thereby enhancing the cells’ adhesiveness.

Even though ibrutinib treatment impaired BCR signaling in these cells, it was unable to fully prevent the pathway from activating VLA-4 and enhancing cell adhesion.

The researchers analyzed 3 cohorts of CLL patients and found that patients expressing higher levels of CD49d had reduced responses to ibrutinib.

The BTK inhibitor appeared less able to displace tumor cells from lymph nodes into the blood, resulting in decreased lymph node shrinkage and shorter progression-free survival times.

“Our results suggest that VLA-4-expressing CLL cells residing in the secondary lymphoid organs can receive BCR-mediated stimuli that can activate VLA-4 even in the presence of ibrutinib,” said study author Antonella Zucchetto, ScD, also of CRO Aviano National Cancer Institute.

“This activation leads to enhanced retention of VLA-4-positive CLL cells in tissue sites, thereby affecting patient outcome.”

Fortunately, the researchers found a way around this obstacle. Inhibiting BTK and phosphatidylinositide 3-kinase (PI3K) simultaneously completely blocked VLA-4 activation in CLL cells.

The researchers treated CLL cells with ibrutinib, the PI3K inhibitor idelalisib, or a combination of both.

Neither drug alone was able to fully block anti-IgM-induced VLA-4 activation. However, the team found that simultaneous inhibition of BTK and PI3K “completely abolished the integrin response to BCR triggering.”

The researchers also added idelalisib to ibrutinib-treated CLL cells (collected from patients at day 30 on ibrutinib) and observed a complete upset of anti-IgM–induced VLA-4 activation.

“Our data suggest that evaluation of CD49d expression in patients initiating ibrutinib therapy may identify those cases that would benefit from combination therapy approaches designed to completely block VLA-4 activation and VLA-4-mediated retention of leukemic cells in protective tissue compartments,” Dr Gattei said.

A 26-year-old G1P0 at 40w1d presents in spontaneous labor and is dilated to 4 cm. The patient reached complete cervical dilation after artificial rupture of membranes and oxytocin augmentation. After four hours of pushing, there has been minimal descent of the fetal vertex beyond +1 station with significant caput succedaneum. Her physician decides to proceed with cesarean delivery.^2,3 What antibiotics should be administered prior to incision to reduce postoperative infection?

The CDC reports that nearly 1.3 million cesarean deliveries were performed in the United States in 2015, which represents about a third of all births.⁴ C-section is the most common major surgical procedure performed in this country and is associated with an infection rate five to 10 times that of vaginal delivery.^5,6 Pregnancy-associated infection, particularly during delivery, is a significant risk and the fourth most common cause of maternal death in the United States.⁵

The current standard of care in cesarean delivery is antibiotic prophylaxis (often a first-generation cephalosporin) prior to skin incision.⁷ The majority of c-sections performed are nonelective, and of these, postoperative infections occur in 12% of women who receive standard prophylaxis.^8,9 A small, single-center design trial suggested that azithromycin adjunctive therapy expands antibiotic coverage to Ureaplasma species, resulting in a lower risk for postoperative infection.¹⁰

This study evaluated the use of azithromycin adjunctive therapy, in addition to standard antibiotic prophylaxis, to reduce the risk for postoperative infections in women receiving nonelective c-sections.

STUDY SUMMARY

Reduced infections up to 6 weeks post–c-section

A multicenter, randomized, double-blind trial conducted in 14 hospitals in the United States evaluated the effect of a one-time dose of azithromycin (500 mg IV) on post­cesarean infections. Women with a singleton pregnancy of at least 24 weeks’ gestation were eligible for inclusion if they required nonelective cesarean delivery during labor or at least four hours after membrane rupture. Patients were excluded if they had a known azithromycin allergy, subsequent vaginal delivery, azithromycin use within the week prior to randomization, extensive hepatic or renal dysfunction, a known history of prolonged QT interval, or substantial electrolyte abnormalities. Patients were eligible even if they were receiving other antibiotics for a positive group B Streptococcus screening.¹

All patients (N = 2,013) were treated with standard antibiotic prophylaxis (most often cefazolin), according to individual institution protocols. The women were randomized to receive either an azithromycin 500 mg/250 mL IV infusion (n = 1,019) or an identical placebo IV infusion (n = 994) within one hour of the procedure. The primary outcome was a composite endpoint of endometritis, wound infection, or other infections occurring up to six weeks after the c-section. Secondary outcomes included neonatal death, sepsis, and other neonatal and maternal complications.¹

Patients in the placebo group had a higher rate of smoking during pregnancy; the researchers found no other significant differences.¹

Results. The primary composite outcome occurred less frequently in the azithromycin group than in the placebo group (6.1% vs 12.0%; relative risk [RR], 0.51; number needed to treat [NNT], 17). When the researchers looked at the individual elements of the primary composite outcome, two had significant reductions versus placebo. Endometritis (3.8% vs 6.1%; RR, 0.62; NNT, 43) and wound infections (2.4% vs 6.6%; RR, 0.35; NNT, 24) occurred significantly less frequently, but there was no difference for other infections (0.3% vs 0.6%; RR, 0.49).

Serious maternal adverse events were also lower in the treatment group than in the control group (1.5% vs 2.9%; RR, 0.5; NNT, 71). There was no difference in composite secondary neonatal outcomes, including death and serious complications (14.3% vs 13.6%; RR, 1.05).¹

Fewer infections without more adverse events

This study showed that adding azithromycin to standard antibiotic prophylaxis within one hour of a c-section reduces post–cesarean delivery infection rates without increasing the risk for maternal or neonatal adverse events.

CAVEATS

Caution with prolonged QT

While azithromycin was efficacious and well tolerated in the study, not every patient can take it. Patients with a previous drug reaction or allergy should avoid it, and experts advise prescribing it with caution for patients who have (or are at increased risk for) a prolonged QT interval, including those on other QT-prolonging medications.

Of note, women with scheduled c-sections and those with chorioamnionitis or another infection requiring postpartum antibiotics were excluded from this study. Thus, it is unknown if azithromycin use decreases complications in these patients.

CHALLENGES TO IMPLEMENTATION

Drug availability is key

Nonelective c-sections are performed based on many factors, including a nonreassuring fetal heart rate. In many of these cases, speed of cesarean delivery may mean the difference between positive and negative outcomes. Availability of azithromycin on labor and delivery floors for timely administration within one hour of the procedure is important.

Additionally, azithromycin has known QT prolongation risks.¹¹ While the baseline QT interval is not known for many healthy young women, this should be considered when azithromycin is utilized in combination with other medications that may prolong the QT interval.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[12]:762-764).

A 26-year-old G1P0 at 40w1d presents in spontaneous labor and is dilated to 4 cm. The patient reached complete cervical dilation after artificial rupture of membranes and oxytocin augmentation. After four hours of pushing, there has been minimal descent of the fetal vertex beyond +1 station with significant caput succedaneum. Her physician decides to proceed with cesarean delivery.^2,3 What antibiotics should be administered prior to incision to reduce postoperative infection?

The CDC reports that nearly 1.3 million cesarean deliveries were performed in the United States in 2015, which represents about a third of all births.⁴ C-section is the most common major surgical procedure performed in this country and is associated with an infection rate five to 10 times that of vaginal delivery.^5,6 Pregnancy-associated infection, particularly during delivery, is a significant risk and the fourth most common cause of maternal death in the United States.⁵

The current standard of care in cesarean delivery is antibiotic prophylaxis (often a first-generation cephalosporin) prior to skin incision.⁷ The majority of c-sections performed are nonelective, and of these, postoperative infections occur in 12% of women who receive standard prophylaxis.^8,9 A small, single-center design trial suggested that azithromycin adjunctive therapy expands antibiotic coverage to Ureaplasma species, resulting in a lower risk for postoperative infection.¹⁰

This study evaluated the use of azithromycin adjunctive therapy, in addition to standard antibiotic prophylaxis, to reduce the risk for postoperative infections in women receiving nonelective c-sections.

STUDY SUMMARY

Reduced infections up to 6 weeks post–c-section

A multicenter, randomized, double-blind trial conducted in 14 hospitals in the United States evaluated the effect of a one-time dose of azithromycin (500 mg IV) on post­cesarean infections. Women with a singleton pregnancy of at least 24 weeks’ gestation were eligible for inclusion if they required nonelective cesarean delivery during labor or at least four hours after membrane rupture. Patients were excluded if they had a known azithromycin allergy, subsequent vaginal delivery, azithromycin use within the week prior to randomization, extensive hepatic or renal dysfunction, a known history of prolonged QT interval, or substantial electrolyte abnormalities. Patients were eligible even if they were receiving other antibiotics for a positive group B Streptococcus screening.¹

All patients (N = 2,013) were treated with standard antibiotic prophylaxis (most often cefazolin), according to individual institution protocols. The women were randomized to receive either an azithromycin 500 mg/250 mL IV infusion (n = 1,019) or an identical placebo IV infusion (n = 994) within one hour of the procedure. The primary outcome was a composite endpoint of endometritis, wound infection, or other infections occurring up to six weeks after the c-section. Secondary outcomes included neonatal death, sepsis, and other neonatal and maternal complications.¹

Patients in the placebo group had a higher rate of smoking during pregnancy; the researchers found no other significant differences.¹

Results. The primary composite outcome occurred less frequently in the azithromycin group than in the placebo group (6.1% vs 12.0%; relative risk [RR], 0.51; number needed to treat [NNT], 17). When the researchers looked at the individual elements of the primary composite outcome, two had significant reductions versus placebo. Endometritis (3.8% vs 6.1%; RR, 0.62; NNT, 43) and wound infections (2.4% vs 6.6%; RR, 0.35; NNT, 24) occurred significantly less frequently, but there was no difference for other infections (0.3% vs 0.6%; RR, 0.49).

Serious maternal adverse events were also lower in the treatment group than in the control group (1.5% vs 2.9%; RR, 0.5; NNT, 71). There was no difference in composite secondary neonatal outcomes, including death and serious complications (14.3% vs 13.6%; RR, 1.05).¹

Fewer infections without more adverse events

This study showed that adding azithromycin to standard antibiotic prophylaxis within one hour of a c-section reduces post–cesarean delivery infection rates without increasing the risk for maternal or neonatal adverse events.

CAVEATS

Caution with prolonged QT

While azithromycin was efficacious and well tolerated in the study, not every patient can take it. Patients with a previous drug reaction or allergy should avoid it, and experts advise prescribing it with caution for patients who have (or are at increased risk for) a prolonged QT interval, including those on other QT-prolonging medications.

Of note, women with scheduled c-sections and those with chorioamnionitis or another infection requiring postpartum antibiotics were excluded from this study. Thus, it is unknown if azithromycin use decreases complications in these patients.

CHALLENGES TO IMPLEMENTATION

Drug availability is key

Nonelective c-sections are performed based on many factors, including a nonreassuring fetal heart rate. In many of these cases, speed of cesarean delivery may mean the difference between positive and negative outcomes. Availability of azithromycin on labor and delivery floors for timely administration within one hour of the procedure is important.

Additionally, azithromycin has known QT prolongation risks.¹¹ While the baseline QT interval is not known for many healthy young women, this should be considered when azithromycin is utilized in combination with other medications that may prolong the QT interval.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[12]:762-764).

A 26-year-old G1P0 at 40w1d presents in spontaneous labor and is dilated to 4 cm. The patient reached complete cervical dilation after artificial rupture of membranes and oxytocin augmentation. After four hours of pushing, there has been minimal descent of the fetal vertex beyond +1 station with significant caput succedaneum. Her physician decides to proceed with cesarean delivery.^2,3 What antibiotics should be administered prior to incision to reduce postoperative infection?

The CDC reports that nearly 1.3 million cesarean deliveries were performed in the United States in 2015, which represents about a third of all births.⁴ C-section is the most common major surgical procedure performed in this country and is associated with an infection rate five to 10 times that of vaginal delivery.^5,6 Pregnancy-associated infection, particularly during delivery, is a significant risk and the fourth most common cause of maternal death in the United States.⁵

The current standard of care in cesarean delivery is antibiotic prophylaxis (often a first-generation cephalosporin) prior to skin incision.⁷ The majority of c-sections performed are nonelective, and of these, postoperative infections occur in 12% of women who receive standard prophylaxis.^8,9 A small, single-center design trial suggested that azithromycin adjunctive therapy expands antibiotic coverage to Ureaplasma species, resulting in a lower risk for postoperative infection.¹⁰

This study evaluated the use of azithromycin adjunctive therapy, in addition to standard antibiotic prophylaxis, to reduce the risk for postoperative infections in women receiving nonelective c-sections.

STUDY SUMMARY

Reduced infections up to 6 weeks post–c-section

A multicenter, randomized, double-blind trial conducted in 14 hospitals in the United States evaluated the effect of a one-time dose of azithromycin (500 mg IV) on post­cesarean infections. Women with a singleton pregnancy of at least 24 weeks’ gestation were eligible for inclusion if they required nonelective cesarean delivery during labor or at least four hours after membrane rupture. Patients were excluded if they had a known azithromycin allergy, subsequent vaginal delivery, azithromycin use within the week prior to randomization, extensive hepatic or renal dysfunction, a known history of prolonged QT interval, or substantial electrolyte abnormalities. Patients were eligible even if they were receiving other antibiotics for a positive group B Streptococcus screening.¹

All patients (N = 2,013) were treated with standard antibiotic prophylaxis (most often cefazolin), according to individual institution protocols. The women were randomized to receive either an azithromycin 500 mg/250 mL IV infusion (n = 1,019) or an identical placebo IV infusion (n = 994) within one hour of the procedure. The primary outcome was a composite endpoint of endometritis, wound infection, or other infections occurring up to six weeks after the c-section. Secondary outcomes included neonatal death, sepsis, and other neonatal and maternal complications.¹

Patients in the placebo group had a higher rate of smoking during pregnancy; the researchers found no other significant differences.¹

Results. The primary composite outcome occurred less frequently in the azithromycin group than in the placebo group (6.1% vs 12.0%; relative risk [RR], 0.51; number needed to treat [NNT], 17). When the researchers looked at the individual elements of the primary composite outcome, two had significant reductions versus placebo. Endometritis (3.8% vs 6.1%; RR, 0.62; NNT, 43) and wound infections (2.4% vs 6.6%; RR, 0.35; NNT, 24) occurred significantly less frequently, but there was no difference for other infections (0.3% vs 0.6%; RR, 0.49).

Serious maternal adverse events were also lower in the treatment group than in the control group (1.5% vs 2.9%; RR, 0.5; NNT, 71). There was no difference in composite secondary neonatal outcomes, including death and serious complications (14.3% vs 13.6%; RR, 1.05).¹

Fewer infections without more adverse events

This study showed that adding azithromycin to standard antibiotic prophylaxis within one hour of a c-section reduces post–cesarean delivery infection rates without increasing the risk for maternal or neonatal adverse events.

CAVEATS

Caution with prolonged QT

While azithromycin was efficacious and well tolerated in the study, not every patient can take it. Patients with a previous drug reaction or allergy should avoid it, and experts advise prescribing it with caution for patients who have (or are at increased risk for) a prolonged QT interval, including those on other QT-prolonging medications.

Of note, women with scheduled c-sections and those with chorioamnionitis or another infection requiring postpartum antibiotics were excluded from this study. Thus, it is unknown if azithromycin use decreases complications in these patients.

CHALLENGES TO IMPLEMENTATION

Drug availability is key

Nonelective c-sections are performed based on many factors, including a nonreassuring fetal heart rate. In many of these cases, speed of cesarean delivery may mean the difference between positive and negative outcomes. Availability of azithromycin on labor and delivery floors for timely administration within one hour of the procedure is important.

Additionally, azithromycin has known QT prolongation risks.¹¹ While the baseline QT interval is not known for many healthy young women, this should be considered when azithromycin is utilized in combination with other medications that may prolong the QT interval.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[12]:762-764).