Streptococcus pneumoniae is the most common bacterial cause of pneumonia, sinusitis, and acute otitis media (AOM). It also causes invasive pneumococcal disease (IPD), such as bacteremia and meningitis, and it is the leading cause of vaccine-preventable death in children younger than 5 years of age. Pneumococcal conjugate vaccines (PCVs) are effective in infants and young children against IPD, non-IPD, and the acquisition of vaccine serotype nasopharyngeal carriage (contagion). PCV7 was licensed and introduced in 2000 on a schedule that matched the schedule of other routine infant immunizations of three primary doses at 2, 4, and 6 months, and a booster at 12-15 months. Later in 2010, PCV13 was licensed on that same “3+1” schedule. Different pneumococcal vaccination schedules are recommended across Europe and other countries, after consideration of the epidemiology, disease burden, immunogenicity of the vaccine, its compatibility with other vaccines, and its cost. The World Health Organization recently updated its PCV policy to support the use of three doses on either 3+0 or 2+1 schedules. Most European countries have adopted the 2+1 schedule used for routine infant immunizations.

In light of the escalating costs of providing current vaccines, and the anticipated need for additional vaccines, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) has convened a working group to evaluate the transition from a 3+1 to a 2+1 schedule for PCV administration to infants and children. This is not a trivial decision. In the United States, cost must be considered in the context of an additional focus on non-IPD disease prevention, especially AOM, where serotypes and immune protection levels differ from IPD. A 2+1 schedule may be effective to prevent IPD, compared with a 3+1 schedule, but its impact on non-IPD may be compromised, especially for AOM, for some serotypes of pneumococci, and for control of nasopharyngeal carriage.

Immunogenicity studies show that antibody responses from a vaccine regimen consisting of two doses in the primary series are less immunogenic, compared with those for a three-dose regimen, yet both regimens are effective for the prevention of IPD. Immunogenicity data that support the use of reduced-dose schedules for most, but not all, vaccine serotypes, were based on IPD. The degree to which higher antibody concentrations are important for protecting against nonbacteremic pneumonia, sinusitis, and AOM, and for preventing nasopharyngeal carriage, is not established.

However, clinical outcomes since the introduction of PCVs indicate that the true threshold will vary by serotype and host and disease condition, with higher concentrations required for certain serotypes, in immunologically less mature hosts, and in mucosal infections like nonbacteremic pneumonia, sinusitis, and AOM, compared with IPD. Also, higher IgG levels clearly are important in protecting against nasopharyngeal colonization, thereby conferring herd immunity, prolonging individual protection, and possibly correlating at the individual level with disease protection. Studies that evaluated the correlation of antibody concentration and protection against nasopharyngeal colonization have shown that a greater than 10-fold higher antibody concentration is needed, compared with levels in blood, to protect against IPD. Similarly protection against AOM require higher levels of antibody than are needed to protect against IPD, as evidenced by the lower efficacy of PCVs against AOM, compared with IPD.

Epidemiology and risk factors differ among countries of the world. Therefore, even among developed countries, there is a need for caution in accepting that what works in one country will work as well in another. For example, attendance at day care is the highest risk factor for both IPD and non-IPD. In the United States, we have many types of day care, including relatively large day care centers, and many infants enter day care at 2 months of age. In other developed countries, the size of day care centers is much smaller, and children may not enter day care until 1 or even 2 years of age. Those differences may have implications for protective efficacy with a reduced-dose vaccine schedule.

Siblings under the age of 8 years are also at significant risk. Again, the family size may differ among developed countries. Breastfeeding is protective for pneumococcal infections. Breastfeeding duration may differ among countries. The theme of this concern is apparent: Even evidence of adequate protection with a reduced-dose schedule in Finland, France, Germany, the United Kingdom, or elsewhere should not be interpreted to be completely applicable to the United States.

Whether reduced-dose schedules can provide equivalent protection against vaccine type IPD equivalent to a 3+1 schedule for all serotypes and for non-IPD when introduced into a national immunization program is unclear. Do we have enough data to inform the decision process, and specifically do we have a clear understanding of the full impact of reduced-dose schedules on non-IPD relative to 3+1? How would you vote?

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Pfizer, which makes PCV vaccine, has funded an investigator-initiated grant and a postmarketing study to Dr. Pichichero’s institution, and he is the primary investigator of both grants.

Streptococcus pneumoniae is the most common bacterial cause of pneumonia, sinusitis, and acute otitis media (AOM). It also causes invasive pneumococcal disease (IPD), such as bacteremia and meningitis, and it is the leading cause of vaccine-preventable death in children younger than 5 years of age. Pneumococcal conjugate vaccines (PCVs) are effective in infants and young children against IPD, non-IPD, and the acquisition of vaccine serotype nasopharyngeal carriage (contagion). PCV7 was licensed and introduced in 2000 on a schedule that matched the schedule of other routine infant immunizations of three primary doses at 2, 4, and 6 months, and a booster at 12-15 months. Later in 2010, PCV13 was licensed on that same “3+1” schedule. Different pneumococcal vaccination schedules are recommended across Europe and other countries, after consideration of the epidemiology, disease burden, immunogenicity of the vaccine, its compatibility with other vaccines, and its cost. The World Health Organization recently updated its PCV policy to support the use of three doses on either 3+0 or 2+1 schedules. Most European countries have adopted the 2+1 schedule used for routine infant immunizations.

In light of the escalating costs of providing current vaccines, and the anticipated need for additional vaccines, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) has convened a working group to evaluate the transition from a 3+1 to a 2+1 schedule for PCV administration to infants and children. This is not a trivial decision. In the United States, cost must be considered in the context of an additional focus on non-IPD disease prevention, especially AOM, where serotypes and immune protection levels differ from IPD. A 2+1 schedule may be effective to prevent IPD, compared with a 3+1 schedule, but its impact on non-IPD may be compromised, especially for AOM, for some serotypes of pneumococci, and for control of nasopharyngeal carriage.

Immunogenicity studies show that antibody responses from a vaccine regimen consisting of two doses in the primary series are less immunogenic, compared with those for a three-dose regimen, yet both regimens are effective for the prevention of IPD. Immunogenicity data that support the use of reduced-dose schedules for most, but not all, vaccine serotypes, were based on IPD. The degree to which higher antibody concentrations are important for protecting against nonbacteremic pneumonia, sinusitis, and AOM, and for preventing nasopharyngeal carriage, is not established.

However, clinical outcomes since the introduction of PCVs indicate that the true threshold will vary by serotype and host and disease condition, with higher concentrations required for certain serotypes, in immunologically less mature hosts, and in mucosal infections like nonbacteremic pneumonia, sinusitis, and AOM, compared with IPD. Also, higher IgG levels clearly are important in protecting against nasopharyngeal colonization, thereby conferring herd immunity, prolonging individual protection, and possibly correlating at the individual level with disease protection. Studies that evaluated the correlation of antibody concentration and protection against nasopharyngeal colonization have shown that a greater than 10-fold higher antibody concentration is needed, compared with levels in blood, to protect against IPD. Similarly protection against AOM require higher levels of antibody than are needed to protect against IPD, as evidenced by the lower efficacy of PCVs against AOM, compared with IPD.

Epidemiology and risk factors differ among countries of the world. Therefore, even among developed countries, there is a need for caution in accepting that what works in one country will work as well in another. For example, attendance at day care is the highest risk factor for both IPD and non-IPD. In the United States, we have many types of day care, including relatively large day care centers, and many infants enter day care at 2 months of age. In other developed countries, the size of day care centers is much smaller, and children may not enter day care until 1 or even 2 years of age. Those differences may have implications for protective efficacy with a reduced-dose vaccine schedule.

Siblings under the age of 8 years are also at significant risk. Again, the family size may differ among developed countries. Breastfeeding is protective for pneumococcal infections. Breastfeeding duration may differ among countries. The theme of this concern is apparent: Even evidence of adequate protection with a reduced-dose schedule in Finland, France, Germany, the United Kingdom, or elsewhere should not be interpreted to be completely applicable to the United States.

Whether reduced-dose schedules can provide equivalent protection against vaccine type IPD equivalent to a 3+1 schedule for all serotypes and for non-IPD when introduced into a national immunization program is unclear. Do we have enough data to inform the decision process, and specifically do we have a clear understanding of the full impact of reduced-dose schedules on non-IPD relative to 3+1? How would you vote?

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Pfizer, which makes PCV vaccine, has funded an investigator-initiated grant and a postmarketing study to Dr. Pichichero’s institution, and he is the primary investigator of both grants.

Streptococcus pneumoniae is the most common bacterial cause of pneumonia, sinusitis, and acute otitis media (AOM). It also causes invasive pneumococcal disease (IPD), such as bacteremia and meningitis, and it is the leading cause of vaccine-preventable death in children younger than 5 years of age. Pneumococcal conjugate vaccines (PCVs) are effective in infants and young children against IPD, non-IPD, and the acquisition of vaccine serotype nasopharyngeal carriage (contagion). PCV7 was licensed and introduced in 2000 on a schedule that matched the schedule of other routine infant immunizations of three primary doses at 2, 4, and 6 months, and a booster at 12-15 months. Later in 2010, PCV13 was licensed on that same “3+1” schedule. Different pneumococcal vaccination schedules are recommended across Europe and other countries, after consideration of the epidemiology, disease burden, immunogenicity of the vaccine, its compatibility with other vaccines, and its cost. The World Health Organization recently updated its PCV policy to support the use of three doses on either 3+0 or 2+1 schedules. Most European countries have adopted the 2+1 schedule used for routine infant immunizations.

In light of the escalating costs of providing current vaccines, and the anticipated need for additional vaccines, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) has convened a working group to evaluate the transition from a 3+1 to a 2+1 schedule for PCV administration to infants and children. This is not a trivial decision. In the United States, cost must be considered in the context of an additional focus on non-IPD disease prevention, especially AOM, where serotypes and immune protection levels differ from IPD. A 2+1 schedule may be effective to prevent IPD, compared with a 3+1 schedule, but its impact on non-IPD may be compromised, especially for AOM, for some serotypes of pneumococci, and for control of nasopharyngeal carriage.

Immunogenicity studies show that antibody responses from a vaccine regimen consisting of two doses in the primary series are less immunogenic, compared with those for a three-dose regimen, yet both regimens are effective for the prevention of IPD. Immunogenicity data that support the use of reduced-dose schedules for most, but not all, vaccine serotypes, were based on IPD. The degree to which higher antibody concentrations are important for protecting against nonbacteremic pneumonia, sinusitis, and AOM, and for preventing nasopharyngeal carriage, is not established.

However, clinical outcomes since the introduction of PCVs indicate that the true threshold will vary by serotype and host and disease condition, with higher concentrations required for certain serotypes, in immunologically less mature hosts, and in mucosal infections like nonbacteremic pneumonia, sinusitis, and AOM, compared with IPD. Also, higher IgG levels clearly are important in protecting against nasopharyngeal colonization, thereby conferring herd immunity, prolonging individual protection, and possibly correlating at the individual level with disease protection. Studies that evaluated the correlation of antibody concentration and protection against nasopharyngeal colonization have shown that a greater than 10-fold higher antibody concentration is needed, compared with levels in blood, to protect against IPD. Similarly protection against AOM require higher levels of antibody than are needed to protect against IPD, as evidenced by the lower efficacy of PCVs against AOM, compared with IPD.

Epidemiology and risk factors differ among countries of the world. Therefore, even among developed countries, there is a need for caution in accepting that what works in one country will work as well in another. For example, attendance at day care is the highest risk factor for both IPD and non-IPD. In the United States, we have many types of day care, including relatively large day care centers, and many infants enter day care at 2 months of age. In other developed countries, the size of day care centers is much smaller, and children may not enter day care until 1 or even 2 years of age. Those differences may have implications for protective efficacy with a reduced-dose vaccine schedule.

Siblings under the age of 8 years are also at significant risk. Again, the family size may differ among developed countries. Breastfeeding is protective for pneumococcal infections. Breastfeeding duration may differ among countries. The theme of this concern is apparent: Even evidence of adequate protection with a reduced-dose schedule in Finland, France, Germany, the United Kingdom, or elsewhere should not be interpreted to be completely applicable to the United States.

Whether reduced-dose schedules can provide equivalent protection against vaccine type IPD equivalent to a 3+1 schedule for all serotypes and for non-IPD when introduced into a national immunization program is unclear. Do we have enough data to inform the decision process, and specifically do we have a clear understanding of the full impact of reduced-dose schedules on non-IPD relative to 3+1? How would you vote?

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Pfizer, which makes PCV vaccine, has funded an investigator-initiated grant and a postmarketing study to Dr. Pichichero’s institution, and he is the primary investigator of both grants.

Question: One hour into an Air France international flight out of New York, Dr. Internist responded to a call for emergency medical assistance. A U.S. passenger had briefly passed out but then appeared to recover. Dr. Internist made a tentative diagnosis of a transient ischemic attack, but did not think an immediate divert was necessary. Based on the doctor’s assessment, the pilot continued on the previously scheduled flight path, landing several hours later in Paris. Meanwhile, the passenger’s condition worsened, and he expired shortly after arrival.

Which of the following statements is correct?

A. Under the common law, there is no legal duty to aid a stranger in distress; but under French law, a doctor is legally obligated to provide emergency assistance.

B. The U.S. federal Aviation Medical Assistance Act may immunize the doctor against liability for negligence during a midair medical emergency.

C. A tort action may still lie against the airline, notwithstanding the doctor’s advice not to divert.

D. Expect jurisdictional conflicts in the event there is a lawsuit.

E. All are correct.

Answer: E. Under the common law, there is no legal duty for anyone, even a doctor, to come to the aid of a stranger. However, doctors are generally held to have an ethical duty to offer emergency care. The American Medical Association’s Code of Medical Ethics states: “Physicians are free to choose whom they will serve. The physician should, however, respond to the best of his or her ability in cases of emergency where first aid treatment is essential.”¹

In contrast, Australia and most civil law jurisdictions, e.g., many European countries, impose a legal obligation to render assistance. Under French law, for example, failure to render assistance to a person in urgent need of help can be met with fines of up to 75,000 euros and 5 years imprisonment.

Medical “emergencies” occur in roughly 1 of every 600 flights, which may be an underestimate because of underreporting. The most common medical reasons for aircraft diversion are cardiac, respiratory, and neurologic emergencies. According to a recent review in the New England Journal of Medicine, the decision to divert lies solely with the captain of the aircraft, who must also consider factors such as fuel, costs, the ability to land, and the medical resources available at that airport.² The review also summarizes medical steps to be taken during midair medical emergencies.

Two related laws other than international aviation treaties govern medical liability during commercial flights: the generic “Good Samaritan” statute, which all 50 U.S. states have enacted, and the more specific federal Aviation Medical Assistance Act.

In 1959, California enacted the first Good Samaritan statute, whose intent is to encourage the helping of people in distress. In general, the law protects against liability arising out of nonreimbursed negligent rescue, but it does not affirmatively require doctors to come to the aid of strangers. Vermont, however, is an exception, and imposes a legal duty to assist a victim in need.

Typically, there is legal immunity against ordinary negligence but not gross misconduct, although California appears to excuse even gross negligence so long as the act was done in good faith. In a litigated case, a California court eloquently declared: “The goodness of the Samaritan is a description of the quality of his or her intention, not the quality of the aid delivered.”³

There is no universal definition of gross negligence, but the term frequently is equated with willful, wanton, or reckless conduct. One can think of gross negligence as aggravated negligence, involving more than mere mistake, inadvertence, or inattention, and representing highly unreasonable conduct or an extreme departure from ordinary care where a high degree of danger is apparent.⁴ An example may be an obviously inebriated physician attempting to provide treatment and causing harm to the victim.

However, the Good Samaritan statute, being state based, may not be applicable to scenarios with cross-border jurisdictional issues. The specific law that incorporates Good Samaritan assistance during commercial flights is the federal Aviation Medical Assistance Act (AMAA), which Congress enacted in 1998. In addition to Federal Aviation Administration mandates such as requisite medical supplies on board and training of flight crew, this federal law shields providers who respond to in-flight medical emergencies.

The AMAA covers claims arising from domestic flights and those arising from international flights involving U.S. carriers or residents, but it does not protect a provider who exhibits flagrant disregard for the patient’s health and safety. Liability is generally determined under the law of the country in which the aircraft is registered, but the citizenship status of the parties and where the incident occurs are also relevant.⁵

Under the facts of the hypothetical given above, one can expect jurisdictional conflicts in the event the plaintiff files a lawsuit, because it is unclear whether the AMAA is applicable where a foreign airline is on an international flight over the Atlantic, even one out of New York involving a U.S. citizen.

There does not appear to be an appellate court opinion on physician negligence during an in-flight medical emergency, but there have been lower court decisions and settlements adverse to the airline.⁶

For example, Northwest Airlines reportedly settled out of court following the death of a passenger on a flight from Manila to Tokyo, despite its claim that three doctors on board the aircraft did not feel an emergency landing was warranted. In a similar case, a Miami federal judge ordered Lufthansa German Airlines to pay damages of $2.7 million to a passenger having a heart attack during a 9-hour flight, after the captain heeded the recommendation from a doctor on board against diverting. In neither case were the doctors apparently named as defendants.

In summary, a doctor is ethically obligated to provide medical assistance in a midair emergency situation. It is highly unlikely that any adverse legal repercussion will ensue. Good Samaritan statutes and, more specifically, the AMAA, properly provide immunity against any allegation of ordinary negligence. Finally, one should be mindful of the need for the patient’s consent before examination and treatment, and, as always, keep written notes of what you have done.

References

1. AMA Code of Medical Ethics §8.11, 2012-2013 edition.

2. N Engl J Med. 2015 Sep 3;373(10):939-45.

3. Perkins v. Howard, 232 Cal.App.3d 708 (1991).

4. Prosser and Keeton on Torts, 5th ed. 1984, p. 211-4.

5. Aviation Medical Assistance Act of 1998, Pub L. No. 105-170. Washington, DC.

6. Aviat Space Environ Med. 1997 Dec;68(12):1134-8.

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at siang@hawaii.edu.

Question: One hour into an Air France international flight out of New York, Dr. Internist responded to a call for emergency medical assistance. A U.S. passenger had briefly passed out but then appeared to recover. Dr. Internist made a tentative diagnosis of a transient ischemic attack, but did not think an immediate divert was necessary. Based on the doctor’s assessment, the pilot continued on the previously scheduled flight path, landing several hours later in Paris. Meanwhile, the passenger’s condition worsened, and he expired shortly after arrival.

Which of the following statements is correct?

A. Under the common law, there is no legal duty to aid a stranger in distress; but under French law, a doctor is legally obligated to provide emergency assistance.

B. The U.S. federal Aviation Medical Assistance Act may immunize the doctor against liability for negligence during a midair medical emergency.

C. A tort action may still lie against the airline, notwithstanding the doctor’s advice not to divert.

D. Expect jurisdictional conflicts in the event there is a lawsuit.

E. All are correct.

Answer: E. Under the common law, there is no legal duty for anyone, even a doctor, to come to the aid of a stranger. However, doctors are generally held to have an ethical duty to offer emergency care. The American Medical Association’s Code of Medical Ethics states: “Physicians are free to choose whom they will serve. The physician should, however, respond to the best of his or her ability in cases of emergency where first aid treatment is essential.”¹

In contrast, Australia and most civil law jurisdictions, e.g., many European countries, impose a legal obligation to render assistance. Under French law, for example, failure to render assistance to a person in urgent need of help can be met with fines of up to 75,000 euros and 5 years imprisonment.

Medical “emergencies” occur in roughly 1 of every 600 flights, which may be an underestimate because of underreporting. The most common medical reasons for aircraft diversion are cardiac, respiratory, and neurologic emergencies. According to a recent review in the New England Journal of Medicine, the decision to divert lies solely with the captain of the aircraft, who must also consider factors such as fuel, costs, the ability to land, and the medical resources available at that airport.² The review also summarizes medical steps to be taken during midair medical emergencies.

Two related laws other than international aviation treaties govern medical liability during commercial flights: the generic “Good Samaritan” statute, which all 50 U.S. states have enacted, and the more specific federal Aviation Medical Assistance Act.

In 1959, California enacted the first Good Samaritan statute, whose intent is to encourage the helping of people in distress. In general, the law protects against liability arising out of nonreimbursed negligent rescue, but it does not affirmatively require doctors to come to the aid of strangers. Vermont, however, is an exception, and imposes a legal duty to assist a victim in need.

Typically, there is legal immunity against ordinary negligence but not gross misconduct, although California appears to excuse even gross negligence so long as the act was done in good faith. In a litigated case, a California court eloquently declared: “The goodness of the Samaritan is a description of the quality of his or her intention, not the quality of the aid delivered.”³

There is no universal definition of gross negligence, but the term frequently is equated with willful, wanton, or reckless conduct. One can think of gross negligence as aggravated negligence, involving more than mere mistake, inadvertence, or inattention, and representing highly unreasonable conduct or an extreme departure from ordinary care where a high degree of danger is apparent.⁴ An example may be an obviously inebriated physician attempting to provide treatment and causing harm to the victim.

However, the Good Samaritan statute, being state based, may not be applicable to scenarios with cross-border jurisdictional issues. The specific law that incorporates Good Samaritan assistance during commercial flights is the federal Aviation Medical Assistance Act (AMAA), which Congress enacted in 1998. In addition to Federal Aviation Administration mandates such as requisite medical supplies on board and training of flight crew, this federal law shields providers who respond to in-flight medical emergencies.

The AMAA covers claims arising from domestic flights and those arising from international flights involving U.S. carriers or residents, but it does not protect a provider who exhibits flagrant disregard for the patient’s health and safety. Liability is generally determined under the law of the country in which the aircraft is registered, but the citizenship status of the parties and where the incident occurs are also relevant.⁵

Under the facts of the hypothetical given above, one can expect jurisdictional conflicts in the event the plaintiff files a lawsuit, because it is unclear whether the AMAA is applicable where a foreign airline is on an international flight over the Atlantic, even one out of New York involving a U.S. citizen.

There does not appear to be an appellate court opinion on physician negligence during an in-flight medical emergency, but there have been lower court decisions and settlements adverse to the airline.⁶

For example, Northwest Airlines reportedly settled out of court following the death of a passenger on a flight from Manila to Tokyo, despite its claim that three doctors on board the aircraft did not feel an emergency landing was warranted. In a similar case, a Miami federal judge ordered Lufthansa German Airlines to pay damages of $2.7 million to a passenger having a heart attack during a 9-hour flight, after the captain heeded the recommendation from a doctor on board against diverting. In neither case were the doctors apparently named as defendants.

In summary, a doctor is ethically obligated to provide medical assistance in a midair emergency situation. It is highly unlikely that any adverse legal repercussion will ensue. Good Samaritan statutes and, more specifically, the AMAA, properly provide immunity against any allegation of ordinary negligence. Finally, one should be mindful of the need for the patient’s consent before examination and treatment, and, as always, keep written notes of what you have done.

References

1. AMA Code of Medical Ethics §8.11, 2012-2013 edition.

2. N Engl J Med. 2015 Sep 3;373(10):939-45.

3. Perkins v. Howard, 232 Cal.App.3d 708 (1991).

4. Prosser and Keeton on Torts, 5th ed. 1984, p. 211-4.

5. Aviation Medical Assistance Act of 1998, Pub L. No. 105-170. Washington, DC.

6. Aviat Space Environ Med. 1997 Dec;68(12):1134-8.

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at siang@hawaii.edu.

Question: One hour into an Air France international flight out of New York, Dr. Internist responded to a call for emergency medical assistance. A U.S. passenger had briefly passed out but then appeared to recover. Dr. Internist made a tentative diagnosis of a transient ischemic attack, but did not think an immediate divert was necessary. Based on the doctor’s assessment, the pilot continued on the previously scheduled flight path, landing several hours later in Paris. Meanwhile, the passenger’s condition worsened, and he expired shortly after arrival.

Which of the following statements is correct?

A. Under the common law, there is no legal duty to aid a stranger in distress; but under French law, a doctor is legally obligated to provide emergency assistance.

B. The U.S. federal Aviation Medical Assistance Act may immunize the doctor against liability for negligence during a midair medical emergency.

C. A tort action may still lie against the airline, notwithstanding the doctor’s advice not to divert.

D. Expect jurisdictional conflicts in the event there is a lawsuit.

E. All are correct.

Answer: E. Under the common law, there is no legal duty for anyone, even a doctor, to come to the aid of a stranger. However, doctors are generally held to have an ethical duty to offer emergency care. The American Medical Association’s Code of Medical Ethics states: “Physicians are free to choose whom they will serve. The physician should, however, respond to the best of his or her ability in cases of emergency where first aid treatment is essential.”¹

In contrast, Australia and most civil law jurisdictions, e.g., many European countries, impose a legal obligation to render assistance. Under French law, for example, failure to render assistance to a person in urgent need of help can be met with fines of up to 75,000 euros and 5 years imprisonment.

Medical “emergencies” occur in roughly 1 of every 600 flights, which may be an underestimate because of underreporting. The most common medical reasons for aircraft diversion are cardiac, respiratory, and neurologic emergencies. According to a recent review in the New England Journal of Medicine, the decision to divert lies solely with the captain of the aircraft, who must also consider factors such as fuel, costs, the ability to land, and the medical resources available at that airport.² The review also summarizes medical steps to be taken during midair medical emergencies.

Two related laws other than international aviation treaties govern medical liability during commercial flights: the generic “Good Samaritan” statute, which all 50 U.S. states have enacted, and the more specific federal Aviation Medical Assistance Act.

In 1959, California enacted the first Good Samaritan statute, whose intent is to encourage the helping of people in distress. In general, the law protects against liability arising out of nonreimbursed negligent rescue, but it does not affirmatively require doctors to come to the aid of strangers. Vermont, however, is an exception, and imposes a legal duty to assist a victim in need.

Typically, there is legal immunity against ordinary negligence but not gross misconduct, although California appears to excuse even gross negligence so long as the act was done in good faith. In a litigated case, a California court eloquently declared: “The goodness of the Samaritan is a description of the quality of his or her intention, not the quality of the aid delivered.”³

There is no universal definition of gross negligence, but the term frequently is equated with willful, wanton, or reckless conduct. One can think of gross negligence as aggravated negligence, involving more than mere mistake, inadvertence, or inattention, and representing highly unreasonable conduct or an extreme departure from ordinary care where a high degree of danger is apparent.⁴ An example may be an obviously inebriated physician attempting to provide treatment and causing harm to the victim.

However, the Good Samaritan statute, being state based, may not be applicable to scenarios with cross-border jurisdictional issues. The specific law that incorporates Good Samaritan assistance during commercial flights is the federal Aviation Medical Assistance Act (AMAA), which Congress enacted in 1998. In addition to Federal Aviation Administration mandates such as requisite medical supplies on board and training of flight crew, this federal law shields providers who respond to in-flight medical emergencies.

The AMAA covers claims arising from domestic flights and those arising from international flights involving U.S. carriers or residents, but it does not protect a provider who exhibits flagrant disregard for the patient’s health and safety. Liability is generally determined under the law of the country in which the aircraft is registered, but the citizenship status of the parties and where the incident occurs are also relevant.⁵

Under the facts of the hypothetical given above, one can expect jurisdictional conflicts in the event the plaintiff files a lawsuit, because it is unclear whether the AMAA is applicable where a foreign airline is on an international flight over the Atlantic, even one out of New York involving a U.S. citizen.

There does not appear to be an appellate court opinion on physician negligence during an in-flight medical emergency, but there have been lower court decisions and settlements adverse to the airline.⁶

For example, Northwest Airlines reportedly settled out of court following the death of a passenger on a flight from Manila to Tokyo, despite its claim that three doctors on board the aircraft did not feel an emergency landing was warranted. In a similar case, a Miami federal judge ordered Lufthansa German Airlines to pay damages of $2.7 million to a passenger having a heart attack during a 9-hour flight, after the captain heeded the recommendation from a doctor on board against diverting. In neither case were the doctors apparently named as defendants.

In summary, a doctor is ethically obligated to provide medical assistance in a midair emergency situation. It is highly unlikely that any adverse legal repercussion will ensue. Good Samaritan statutes and, more specifically, the AMAA, properly provide immunity against any allegation of ordinary negligence. Finally, one should be mindful of the need for the patient’s consent before examination and treatment, and, as always, keep written notes of what you have done.

References

1. AMA Code of Medical Ethics §8.11, 2012-2013 edition.

2. N Engl J Med. 2015 Sep 3;373(10):939-45.

3. Perkins v. Howard, 232 Cal.App.3d 708 (1991).

4. Prosser and Keeton on Torts, 5th ed. 1984, p. 211-4.

5. Aviation Medical Assistance Act of 1998, Pub L. No. 105-170. Washington, DC.

6. Aviat Space Environ Med. 1997 Dec;68(12):1134-8.

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at siang@hawaii.edu.

HONOLULU – Early use of a transjugular intrahepatic portosystemic shunt (TIPS) is associated with substantial reductions in mortality, according to an analysis of a national inpatient database.

Based on this study, “early use of TIPS, together with patient and physician education on current guidelines and protocols, should continue to be a priority to improve patient outcomes” in patients with hepatic cirrhosis and risk of recurrent esophageal variceal bleeds, reported Dr. Basile Njei, a gastroenterology fellow at Yale University, New Haven, Conn.

In this study, the Nationwide Inpatient Sample database was queried by ICD-9 codes to identify patients with esophageal variceal bleeding treated between the years 2000 and 2010. The goal was to compare early use of TIPS, defined as TIPS administered within 72 hours of the bleeding, relative to rescue TIPS, defined as TIPS after two or more episodes of bleeding or one bleeding episode followed by another endoscopic intervention, such as balloon tamponade or surgery.

Over the period of study, a Poisson regression analysis used to control for multiple variables associated any TIPS utilization with an inverse association with overall mortality, producing a relative risk of 0.88 (95% confidence interval, 0.83-0.92). In the context of timing of TIPS, in-hospital mortality fell from 5.6% for those who received rescue TIPS to 1.5% in those who underwent early TIPS.

On multivariate analysis, an advantage was observed for early TIPS relative to rescue TIPS for in-hospital mortality (RR, 0.85; P less than .01), in-hospital rebleeding (RR, 0.57; P less than .01), and length of hospital stay (RR, 0.87; P less than .01). Rates of sepsis (RR, 0.83; P = .32) and hepatic encephalopathy (RR, 0.87; P = .22) were not significantly lower in the early TIPS group, but they were also not increased. For early TIPS versus no TIPS, the advantages on multivariate analysis were similar for both in-hospital deaths (RR, 0.87; P less than .01) and in-hospital rebleeding (RR, 0.57; P less than .01), but no advantage was seen for length of stay for TIPS versus no TIPS (RR, 0.99; P = .18).

Overall, there was a steady decline in mortality associated with esophageal variceal bleeding over the period of evaluation, falling incrementally over time from 656 deaths per 100,000 hospitalizations in 2000 to 412 deaths per 100,000 in 2010. This 37.2% reduction was statistically significant (P less than .01). The reduction in mortality was inversely associated with an increasing use of TIPS over the study period.

The data from this analysis are consistent with a multicenter randomized trial conducted several years ago in Europe (N Engl J Med. 2010;362:2370-9). In that study 63 patients with hepatic cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy were randomized to early TIPS or rescue TIPS. At 1 year, 86% of those in the early TIPS group were alive versus 61% (P = .01) of those randomized to receive TIPS as a rescue strategy.

Relative to the previous study, the key finding of this study is that early TIPS “is associated with significant short-term reductions in rebleeding and mortality without a significant increase in encephalopathy in real world U.S. clinical practice,” according to Dr. Njei. It substantiates the European study and encourages a protocol that emphasizes early TIPS, particularly in those with a high risk of repeat esophageal variceal bleeding.

In the discussion that followed the presentation of these results at the annual meeting of the American College of Gastroenterology, the moderator, Dr. Paul Y. Kwo, medical director of liver transplantation, Indiana University, Indianapolis, pointed out, that some of those in the rescue TIPS group might simply have been poor candidates for this intervention. Although he praised the methodology of this study, which won the 2015 ACG Fellows-In-Training Award, he questioned whether rescue TIPS was a last resort salvage therapy in those initially considered poor risks for TIPS. Dr. Njei responded that the multivariate analysis was specifically designed to control for variables such as risk status to diminish this potential bias. Indeed, he said he believes TIPS is underemployed.

“The relatively small percentage of eligible cases receiving early TIPS suggests that there is room for further improvement in the treatment of patients with decompensated cirrhosis and esophageal variceal bleeding,” Dr. Njei concluded.

Dr. Njei reported that he had no relevant financial relationships to disclose.

HONOLULU – Early use of a transjugular intrahepatic portosystemic shunt (TIPS) is associated with substantial reductions in mortality, according to an analysis of a national inpatient database.

Based on this study, “early use of TIPS, together with patient and physician education on current guidelines and protocols, should continue to be a priority to improve patient outcomes” in patients with hepatic cirrhosis and risk of recurrent esophageal variceal bleeds, reported Dr. Basile Njei, a gastroenterology fellow at Yale University, New Haven, Conn.

In this study, the Nationwide Inpatient Sample database was queried by ICD-9 codes to identify patients with esophageal variceal bleeding treated between the years 2000 and 2010. The goal was to compare early use of TIPS, defined as TIPS administered within 72 hours of the bleeding, relative to rescue TIPS, defined as TIPS after two or more episodes of bleeding or one bleeding episode followed by another endoscopic intervention, such as balloon tamponade or surgery.

Over the period of study, a Poisson regression analysis used to control for multiple variables associated any TIPS utilization with an inverse association with overall mortality, producing a relative risk of 0.88 (95% confidence interval, 0.83-0.92). In the context of timing of TIPS, in-hospital mortality fell from 5.6% for those who received rescue TIPS to 1.5% in those who underwent early TIPS.

On multivariate analysis, an advantage was observed for early TIPS relative to rescue TIPS for in-hospital mortality (RR, 0.85; P less than .01), in-hospital rebleeding (RR, 0.57; P less than .01), and length of hospital stay (RR, 0.87; P less than .01). Rates of sepsis (RR, 0.83; P = .32) and hepatic encephalopathy (RR, 0.87; P = .22) were not significantly lower in the early TIPS group, but they were also not increased. For early TIPS versus no TIPS, the advantages on multivariate analysis were similar for both in-hospital deaths (RR, 0.87; P less than .01) and in-hospital rebleeding (RR, 0.57; P less than .01), but no advantage was seen for length of stay for TIPS versus no TIPS (RR, 0.99; P = .18).

Overall, there was a steady decline in mortality associated with esophageal variceal bleeding over the period of evaluation, falling incrementally over time from 656 deaths per 100,000 hospitalizations in 2000 to 412 deaths per 100,000 in 2010. This 37.2% reduction was statistically significant (P less than .01). The reduction in mortality was inversely associated with an increasing use of TIPS over the study period.

The data from this analysis are consistent with a multicenter randomized trial conducted several years ago in Europe (N Engl J Med. 2010;362:2370-9). In that study 63 patients with hepatic cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy were randomized to early TIPS or rescue TIPS. At 1 year, 86% of those in the early TIPS group were alive versus 61% (P = .01) of those randomized to receive TIPS as a rescue strategy.

Relative to the previous study, the key finding of this study is that early TIPS “is associated with significant short-term reductions in rebleeding and mortality without a significant increase in encephalopathy in real world U.S. clinical practice,” according to Dr. Njei. It substantiates the European study and encourages a protocol that emphasizes early TIPS, particularly in those with a high risk of repeat esophageal variceal bleeding.

In the discussion that followed the presentation of these results at the annual meeting of the American College of Gastroenterology, the moderator, Dr. Paul Y. Kwo, medical director of liver transplantation, Indiana University, Indianapolis, pointed out, that some of those in the rescue TIPS group might simply have been poor candidates for this intervention. Although he praised the methodology of this study, which won the 2015 ACG Fellows-In-Training Award, he questioned whether rescue TIPS was a last resort salvage therapy in those initially considered poor risks for TIPS. Dr. Njei responded that the multivariate analysis was specifically designed to control for variables such as risk status to diminish this potential bias. Indeed, he said he believes TIPS is underemployed.

“The relatively small percentage of eligible cases receiving early TIPS suggests that there is room for further improvement in the treatment of patients with decompensated cirrhosis and esophageal variceal bleeding,” Dr. Njei concluded.

Dr. Njei reported that he had no relevant financial relationships to disclose.

HONOLULU – Early use of a transjugular intrahepatic portosystemic shunt (TIPS) is associated with substantial reductions in mortality, according to an analysis of a national inpatient database.

Based on this study, “early use of TIPS, together with patient and physician education on current guidelines and protocols, should continue to be a priority to improve patient outcomes” in patients with hepatic cirrhosis and risk of recurrent esophageal variceal bleeds, reported Dr. Basile Njei, a gastroenterology fellow at Yale University, New Haven, Conn.

In this study, the Nationwide Inpatient Sample database was queried by ICD-9 codes to identify patients with esophageal variceal bleeding treated between the years 2000 and 2010. The goal was to compare early use of TIPS, defined as TIPS administered within 72 hours of the bleeding, relative to rescue TIPS, defined as TIPS after two or more episodes of bleeding or one bleeding episode followed by another endoscopic intervention, such as balloon tamponade or surgery.

Over the period of study, a Poisson regression analysis used to control for multiple variables associated any TIPS utilization with an inverse association with overall mortality, producing a relative risk of 0.88 (95% confidence interval, 0.83-0.92). In the context of timing of TIPS, in-hospital mortality fell from 5.6% for those who received rescue TIPS to 1.5% in those who underwent early TIPS.

On multivariate analysis, an advantage was observed for early TIPS relative to rescue TIPS for in-hospital mortality (RR, 0.85; P less than .01), in-hospital rebleeding (RR, 0.57; P less than .01), and length of hospital stay (RR, 0.87; P less than .01). Rates of sepsis (RR, 0.83; P = .32) and hepatic encephalopathy (RR, 0.87; P = .22) were not significantly lower in the early TIPS group, but they were also not increased. For early TIPS versus no TIPS, the advantages on multivariate analysis were similar for both in-hospital deaths (RR, 0.87; P less than .01) and in-hospital rebleeding (RR, 0.57; P less than .01), but no advantage was seen for length of stay for TIPS versus no TIPS (RR, 0.99; P = .18).

Overall, there was a steady decline in mortality associated with esophageal variceal bleeding over the period of evaluation, falling incrementally over time from 656 deaths per 100,000 hospitalizations in 2000 to 412 deaths per 100,000 in 2010. This 37.2% reduction was statistically significant (P less than .01). The reduction in mortality was inversely associated with an increasing use of TIPS over the study period.

The data from this analysis are consistent with a multicenter randomized trial conducted several years ago in Europe (N Engl J Med. 2010;362:2370-9). In that study 63 patients with hepatic cirrhosis and acute variceal bleeding who had been treated with vasoactive drugs plus endoscopic therapy were randomized to early TIPS or rescue TIPS. At 1 year, 86% of those in the early TIPS group were alive versus 61% (P = .01) of those randomized to receive TIPS as a rescue strategy.

Relative to the previous study, the key finding of this study is that early TIPS “is associated with significant short-term reductions in rebleeding and mortality without a significant increase in encephalopathy in real world U.S. clinical practice,” according to Dr. Njei. It substantiates the European study and encourages a protocol that emphasizes early TIPS, particularly in those with a high risk of repeat esophageal variceal bleeding.

In the discussion that followed the presentation of these results at the annual meeting of the American College of Gastroenterology, the moderator, Dr. Paul Y. Kwo, medical director of liver transplantation, Indiana University, Indianapolis, pointed out, that some of those in the rescue TIPS group might simply have been poor candidates for this intervention. Although he praised the methodology of this study, which won the 2015 ACG Fellows-In-Training Award, he questioned whether rescue TIPS was a last resort salvage therapy in those initially considered poor risks for TIPS. Dr. Njei responded that the multivariate analysis was specifically designed to control for variables such as risk status to diminish this potential bias. Indeed, he said he believes TIPS is underemployed.

“The relatively small percentage of eligible cases receiving early TIPS suggests that there is room for further improvement in the treatment of patients with decompensated cirrhosis and esophageal variceal bleeding,” Dr. Njei concluded.

Dr. Njei reported that he had no relevant financial relationships to disclose.

NEW YORK - Most, but not all, guideline-recommended drugs and their combinations yield modest survival benefits in older adults with multiple chronic medical conditions, researchers report.

"Until there is better evidence in older adults with multiple chronic conditions, clinicians need to take a more thoughtful and nuanced approach to medication prescribing," Dr. Mary E. Tinetti from Yale School of Medicine, New Haven, Connecticut said by email. "This is particularly supported by the fact that outside of perhaps anticoagulation for atrial fibrillation, the magnitude of benefit for most of these medications is quite modest."

Nearly 40% of adults 65 years and older take at least five prescription medications, but the benefits of drugs prescribed for a single condition are difficult to ascertain in the

presence of multiple conditions and drugs.

Dr. Tinetti and colleagues used data from the Medicare Current Beneficiary Survey to estimate the association between nine guideline-recommended and commonly prescribed drugs and death in more than 8,500 Medicare participants (mean age, 77.4 years).

The nine drugs included beta-blockers; calcium channel blockers; clopidogrel; metformin; renin-angiotensin system (RAS) blockers; selective serotonin reuptake inhibitors (SSRIs) and selective serotonin norepinephrine reuptake inhibitors (SNRIs); statins; thiazide diuretics; and warfarin.

The most common medical conditions included hypertension, hyperlipidemia, diabetes, and coronary artery disease, the researchers report in The BMJ, online Oct. 2. More than half of the participants took at least three of the nine study drugs, and the mean number of total drugs was 10.0.

The benefits on survival of beta-blockers, calcium channel blockers, RAS blockers, statins, and warfarin were comparable to those reported in randomized controlled trials, although for beta-blockers and warfarin they varied according to coexisting conditions.

Clopidogrel, metformin, and SSRIs/SNRIs, however, were not associated with survival benefits.

The association between drug use and mortality risk was generally similar across patterns of coexisting conditions, suggesting to the researchers "that benefits often remain despite comorbidity."

"Research focused on identifying the medications that have the greatest benefit (defined by patient's outcomes priority such as improved symptoms, optimal physical or cognitive function, or survival) and least harm for key subpopulations of individuals with varying combinations of coexisting conditions should be a top priority," Dr. Tinetti said. "Ironically, although these are the major users of health care, they have largely been ignored in research."

"Many individuals, although they have many conditions, only one or two are really affecting the outcomes that matter most to them," Dr. Tinetti said. "Therefore, medication regimens can be simplified by eliminating medications for conditions that are not likely to benefit the individuals outcome priority, such as improved symptoms, optimal physical or cognitive function, or simplified treatment regimens."

"We know that about one in five individuals are currently receiving guideline-recommended medications for one condition that may be harming another," Dr. Tinetti concluded. "A careful medication review will review these potential offending medications. Given the marginal benefit of each individual medication, and the importance of avoiding harm, potentially offending medications should be discontinued."

Dr. Una Makris from UT Southwestern Medical Center and Dallas VA Medical Center has reported on high-risk medication use among older veterans with chronic pain. She said by email, "As clinicians we need to understand that not all of the outcomes we measure and not all of the medical conditions a patient has will be perceived as equally important (by the patient), so involving patients in the decision of which medications (even if guideline concordant) to add or remove is integral. How we communicate with and educate our older patients about their chronic conditions and the risks/benefits of each medication is evolving; this often differs between specialty providers and primary care providers."

Dr. Makris added, "This publication should heighten our awareness that patients, especially older adults, often have multiple comorbidities that can be treated with multiple guideline driven therapies and that our goal is really to work with patients to determine which combination of drugs and for which condition optimizes the risks/benefits for that individual."

NEW YORK - Most, but not all, guideline-recommended drugs and their combinations yield modest survival benefits in older adults with multiple chronic medical conditions, researchers report.

"Until there is better evidence in older adults with multiple chronic conditions, clinicians need to take a more thoughtful and nuanced approach to medication prescribing," Dr. Mary E. Tinetti from Yale School of Medicine, New Haven, Connecticut said by email. "This is particularly supported by the fact that outside of perhaps anticoagulation for atrial fibrillation, the magnitude of benefit for most of these medications is quite modest."

Nearly 40% of adults 65 years and older take at least five prescription medications, but the benefits of drugs prescribed for a single condition are difficult to ascertain in the

presence of multiple conditions and drugs.

Dr. Tinetti and colleagues used data from the Medicare Current Beneficiary Survey to estimate the association between nine guideline-recommended and commonly prescribed drugs and death in more than 8,500 Medicare participants (mean age, 77.4 years).

The nine drugs included beta-blockers; calcium channel blockers; clopidogrel; metformin; renin-angiotensin system (RAS) blockers; selective serotonin reuptake inhibitors (SSRIs) and selective serotonin norepinephrine reuptake inhibitors (SNRIs); statins; thiazide diuretics; and warfarin.

The most common medical conditions included hypertension, hyperlipidemia, diabetes, and coronary artery disease, the researchers report in The BMJ, online Oct. 2. More than half of the participants took at least three of the nine study drugs, and the mean number of total drugs was 10.0.

The benefits on survival of beta-blockers, calcium channel blockers, RAS blockers, statins, and warfarin were comparable to those reported in randomized controlled trials, although for beta-blockers and warfarin they varied according to coexisting conditions.

Clopidogrel, metformin, and SSRIs/SNRIs, however, were not associated with survival benefits.

The association between drug use and mortality risk was generally similar across patterns of coexisting conditions, suggesting to the researchers "that benefits often remain despite comorbidity."

"Research focused on identifying the medications that have the greatest benefit (defined by patient's outcomes priority such as improved symptoms, optimal physical or cognitive function, or survival) and least harm for key subpopulations of individuals with varying combinations of coexisting conditions should be a top priority," Dr. Tinetti said. "Ironically, although these are the major users of health care, they have largely been ignored in research."

"Many individuals, although they have many conditions, only one or two are really affecting the outcomes that matter most to them," Dr. Tinetti said. "Therefore, medication regimens can be simplified by eliminating medications for conditions that are not likely to benefit the individuals outcome priority, such as improved symptoms, optimal physical or cognitive function, or simplified treatment regimens."

"We know that about one in five individuals are currently receiving guideline-recommended medications for one condition that may be harming another," Dr. Tinetti concluded. "A careful medication review will review these potential offending medications. Given the marginal benefit of each individual medication, and the importance of avoiding harm, potentially offending medications should be discontinued."

Dr. Una Makris from UT Southwestern Medical Center and Dallas VA Medical Center has reported on high-risk medication use among older veterans with chronic pain. She said by email, "As clinicians we need to understand that not all of the outcomes we measure and not all of the medical conditions a patient has will be perceived as equally important (by the patient), so involving patients in the decision of which medications (even if guideline concordant) to add or remove is integral. How we communicate with and educate our older patients about their chronic conditions and the risks/benefits of each medication is evolving; this often differs between specialty providers and primary care providers."

Dr. Makris added, "This publication should heighten our awareness that patients, especially older adults, often have multiple comorbidities that can be treated with multiple guideline driven therapies and that our goal is really to work with patients to determine which combination of drugs and for which condition optimizes the risks/benefits for that individual."

NEW YORK - Most, but not all, guideline-recommended drugs and their combinations yield modest survival benefits in older adults with multiple chronic medical conditions, researchers report.

"Until there is better evidence in older adults with multiple chronic conditions, clinicians need to take a more thoughtful and nuanced approach to medication prescribing," Dr. Mary E. Tinetti from Yale School of Medicine, New Haven, Connecticut said by email. "This is particularly supported by the fact that outside of perhaps anticoagulation for atrial fibrillation, the magnitude of benefit for most of these medications is quite modest."

Nearly 40% of adults 65 years and older take at least five prescription medications, but the benefits of drugs prescribed for a single condition are difficult to ascertain in the

presence of multiple conditions and drugs.

Dr. Tinetti and colleagues used data from the Medicare Current Beneficiary Survey to estimate the association between nine guideline-recommended and commonly prescribed drugs and death in more than 8,500 Medicare participants (mean age, 77.4 years).

The nine drugs included beta-blockers; calcium channel blockers; clopidogrel; metformin; renin-angiotensin system (RAS) blockers; selective serotonin reuptake inhibitors (SSRIs) and selective serotonin norepinephrine reuptake inhibitors (SNRIs); statins; thiazide diuretics; and warfarin.

The most common medical conditions included hypertension, hyperlipidemia, diabetes, and coronary artery disease, the researchers report in The BMJ, online Oct. 2. More than half of the participants took at least three of the nine study drugs, and the mean number of total drugs was 10.0.

The benefits on survival of beta-blockers, calcium channel blockers, RAS blockers, statins, and warfarin were comparable to those reported in randomized controlled trials, although for beta-blockers and warfarin they varied according to coexisting conditions.

Clopidogrel, metformin, and SSRIs/SNRIs, however, were not associated with survival benefits.

The association between drug use and mortality risk was generally similar across patterns of coexisting conditions, suggesting to the researchers "that benefits often remain despite comorbidity."

"Research focused on identifying the medications that have the greatest benefit (defined by patient's outcomes priority such as improved symptoms, optimal physical or cognitive function, or survival) and least harm for key subpopulations of individuals with varying combinations of coexisting conditions should be a top priority," Dr. Tinetti said. "Ironically, although these are the major users of health care, they have largely been ignored in research."

"Many individuals, although they have many conditions, only one or two are really affecting the outcomes that matter most to them," Dr. Tinetti said. "Therefore, medication regimens can be simplified by eliminating medications for conditions that are not likely to benefit the individuals outcome priority, such as improved symptoms, optimal physical or cognitive function, or simplified treatment regimens."

"We know that about one in five individuals are currently receiving guideline-recommended medications for one condition that may be harming another," Dr. Tinetti concluded. "A careful medication review will review these potential offending medications. Given the marginal benefit of each individual medication, and the importance of avoiding harm, potentially offending medications should be discontinued."

Dr. Una Makris from UT Southwestern Medical Center and Dallas VA Medical Center has reported on high-risk medication use among older veterans with chronic pain. She said by email, "As clinicians we need to understand that not all of the outcomes we measure and not all of the medical conditions a patient has will be perceived as equally important (by the patient), so involving patients in the decision of which medications (even if guideline concordant) to add or remove is integral. How we communicate with and educate our older patients about their chronic conditions and the risks/benefits of each medication is evolving; this often differs between specialty providers and primary care providers."

Dr. Makris added, "This publication should heighten our awareness that patients, especially older adults, often have multiple comorbidities that can be treated with multiple guideline driven therapies and that our goal is really to work with patients to determine which combination of drugs and for which condition optimizes the risks/benefits for that individual."

MONTREAL – A new, next-generation macrolide, solithromycin, showed safety and efficacy as a once-daily oral agent that was noninferior to the comparator oral antibiotic, the fluoroquinolone moxifloxacin, in a phase III trial.

Macrolide resistance among strains of Streptococcus pneumoniae that cause many U.S. cases of severe community-acquired pneumonia has become common, complicating treatment of this common infection with a macrolide, Dr. Carlos M. Barrera explained at the annual meeting of the American College of Chest Physicians.

Mitchel L. Zoler/Frontline Medical News

The SOLITAIRE-ORAL (Efficacy and Safety Study of Oral Solithromycin [CEM-101] Compared to Oral Moxifloxacin in Treatment of Patients With Community-Acquired Bacterial Pneumonia) trial enrolled 860 patients with moderate to moderately severe community-acquired pneumonia.

About half of the patients enrolled in the trial underwent microbiologic assessment of their infecting pathogen, and about 40% of cases in each treatment arm had infections caused by S. pneumoniae. In this subgroup, the 5-day regimen of solithromycin tested in the study succeeded in clearing the infection in 89% of patients, comparable to the 83% success rate achieved with a 7-day course of moxifloxacin (Avelox), said Dr. Barrera, a pulmonologist who practices in Miami.

The study’s primary endpoint for Food and Drug Administration approval of solithromycin was early clinical response, defined as an improvement in at least two listed symptoms at 72 hours after onset of treatment. That endpoint occurred in 78% of patients enrolled in each of the two arms of the study.

The data make solithromycin look like a promising way to once again have a macrolide available for empiric oral treatment of more severe community-acquired pneumonia, pending full peer review of the data, commented Dr. Muthiah P. Muthiah, a pulmonologist at the University of Tennessee Health Science Center in Memphis.

“A couple of decades ago, you could comfortably treat a patient with severe community-acquired pneumonia with a macrolide, but you can’t do that anymore,” Dr. Muthiah said in an interview.

If the newly reported data on oral solithromycin hold up under further review, it would mean that solithromycin was as effective as a potent quinolone, which remains an effective monotherapy for community-acquired pneumonia in patients who do not require treatment in an intensive care unit, Dr. Muthiah noted.

A companion study, SOLITAIRE-IV, is a phase III pivotal trial assessing the safety and efficacy of solithromycin when begun intravenously for treating community-acquired pneumonia, followed by a switch to oral dosing, in comparison with intravenous followed by oral treatment with moxifloxacin.

Once those data are fully collected and analyzed, the company will submit the information from both trials to the FDA, said Dr. David Oldach, chief medical officer for Cempra.

Results from the intravenous trial, reported in a preliminary way by Cempra Oct. 16 in a press release, showed that the solithromycin treatment regimen tested in SOLITAIRE-IV met its noninferiority targets, compared with moxifloxacin. The safety results, however, showed that solithromycin produced a higher number of patients with a liver-enzyme elevation, compared with patients treated with moxifloxacin.

In SOLITAIRE-IV, Cempra reported that grade 3 increase in levels of alanine transaminase (ALT) occurred in 8% of patients on solithromycin and in 3% of patients on moxifloxacin. Grade 4 increases in ALT occurred in less than 1% of patients in both treatment arms.

In the current, orally administered trial, grade 3 ALT increases occurred in 5% of patients treated with solithromycin and in 2% of patients treated with moxifloxacin, Dr. Barrera reported. Grade 4 ALT increases occurred in 0.5% of patients treated with solithromycin and in 1.2% of those treated with moxifloxacin. No patients in either arm developed an elevation of both ALT and bilirubin, and the ALT increases seen were reversible and asymptomatic, Dr. Barrera said.

By other assessments, the safety profiles of solithromycin and moxifloxacin were similar: 7% of patients on solithromycin and 6% on moxifloxacin had a serious adverse event, and 4% of patients in each study arm discontinued treatment because of an adverse event.

SOLITAIRE-ORAL was sponsored by Cempra, the company developing solithromycin. Dr. Barrera has received research funding from Cempra. Dr. Muthiah had no disclosures.

mzoler@frontlinemedcom.com 


On Twitter @mitchelzoler

MONTREAL – A new, next-generation macrolide, solithromycin, showed safety and efficacy as a once-daily oral agent that was noninferior to the comparator oral antibiotic, the fluoroquinolone moxifloxacin, in a phase III trial.

Macrolide resistance among strains of Streptococcus pneumoniae that cause many U.S. cases of severe community-acquired pneumonia has become common, complicating treatment of this common infection with a macrolide, Dr. Carlos M. Barrera explained at the annual meeting of the American College of Chest Physicians.

Mitchel L. Zoler/Frontline Medical News

The SOLITAIRE-ORAL (Efficacy and Safety Study of Oral Solithromycin [CEM-101] Compared to Oral Moxifloxacin in Treatment of Patients With Community-Acquired Bacterial Pneumonia) trial enrolled 860 patients with moderate to moderately severe community-acquired pneumonia.

About half of the patients enrolled in the trial underwent microbiologic assessment of their infecting pathogen, and about 40% of cases in each treatment arm had infections caused by S. pneumoniae. In this subgroup, the 5-day regimen of solithromycin tested in the study succeeded in clearing the infection in 89% of patients, comparable to the 83% success rate achieved with a 7-day course of moxifloxacin (Avelox), said Dr. Barrera, a pulmonologist who practices in Miami.

The study’s primary endpoint for Food and Drug Administration approval of solithromycin was early clinical response, defined as an improvement in at least two listed symptoms at 72 hours after onset of treatment. That endpoint occurred in 78% of patients enrolled in each of the two arms of the study.

The data make solithromycin look like a promising way to once again have a macrolide available for empiric oral treatment of more severe community-acquired pneumonia, pending full peer review of the data, commented Dr. Muthiah P. Muthiah, a pulmonologist at the University of Tennessee Health Science Center in Memphis.

“A couple of decades ago, you could comfortably treat a patient with severe community-acquired pneumonia with a macrolide, but you can’t do that anymore,” Dr. Muthiah said in an interview.

If the newly reported data on oral solithromycin hold up under further review, it would mean that solithromycin was as effective as a potent quinolone, which remains an effective monotherapy for community-acquired pneumonia in patients who do not require treatment in an intensive care unit, Dr. Muthiah noted.

A companion study, SOLITAIRE-IV, is a phase III pivotal trial assessing the safety and efficacy of solithromycin when begun intravenously for treating community-acquired pneumonia, followed by a switch to oral dosing, in comparison with intravenous followed by oral treatment with moxifloxacin.

Once those data are fully collected and analyzed, the company will submit the information from both trials to the FDA, said Dr. David Oldach, chief medical officer for Cempra.

Results from the intravenous trial, reported in a preliminary way by Cempra Oct. 16 in a press release, showed that the solithromycin treatment regimen tested in SOLITAIRE-IV met its noninferiority targets, compared with moxifloxacin. The safety results, however, showed that solithromycin produced a higher number of patients with a liver-enzyme elevation, compared with patients treated with moxifloxacin.

In SOLITAIRE-IV, Cempra reported that grade 3 increase in levels of alanine transaminase (ALT) occurred in 8% of patients on solithromycin and in 3% of patients on moxifloxacin. Grade 4 increases in ALT occurred in less than 1% of patients in both treatment arms.

In the current, orally administered trial, grade 3 ALT increases occurred in 5% of patients treated with solithromycin and in 2% of patients treated with moxifloxacin, Dr. Barrera reported. Grade 4 ALT increases occurred in 0.5% of patients treated with solithromycin and in 1.2% of those treated with moxifloxacin. No patients in either arm developed an elevation of both ALT and bilirubin, and the ALT increases seen were reversible and asymptomatic, Dr. Barrera said.

By other assessments, the safety profiles of solithromycin and moxifloxacin were similar: 7% of patients on solithromycin and 6% on moxifloxacin had a serious adverse event, and 4% of patients in each study arm discontinued treatment because of an adverse event.

SOLITAIRE-ORAL was sponsored by Cempra, the company developing solithromycin. Dr. Barrera has received research funding from Cempra. Dr. Muthiah had no disclosures.

mzoler@frontlinemedcom.com 


On Twitter @mitchelzoler

MONTREAL – A new, next-generation macrolide, solithromycin, showed safety and efficacy as a once-daily oral agent that was noninferior to the comparator oral antibiotic, the fluoroquinolone moxifloxacin, in a phase III trial.

Macrolide resistance among strains of Streptococcus pneumoniae that cause many U.S. cases of severe community-acquired pneumonia has become common, complicating treatment of this common infection with a macrolide, Dr. Carlos M. Barrera explained at the annual meeting of the American College of Chest Physicians.

Mitchel L. Zoler/Frontline Medical News

The SOLITAIRE-ORAL (Efficacy and Safety Study of Oral Solithromycin [CEM-101] Compared to Oral Moxifloxacin in Treatment of Patients With Community-Acquired Bacterial Pneumonia) trial enrolled 860 patients with moderate to moderately severe community-acquired pneumonia.

About half of the patients enrolled in the trial underwent microbiologic assessment of their infecting pathogen, and about 40% of cases in each treatment arm had infections caused by S. pneumoniae. In this subgroup, the 5-day regimen of solithromycin tested in the study succeeded in clearing the infection in 89% of patients, comparable to the 83% success rate achieved with a 7-day course of moxifloxacin (Avelox), said Dr. Barrera, a pulmonologist who practices in Miami.

The study’s primary endpoint for Food and Drug Administration approval of solithromycin was early clinical response, defined as an improvement in at least two listed symptoms at 72 hours after onset of treatment. That endpoint occurred in 78% of patients enrolled in each of the two arms of the study.

The data make solithromycin look like a promising way to once again have a macrolide available for empiric oral treatment of more severe community-acquired pneumonia, pending full peer review of the data, commented Dr. Muthiah P. Muthiah, a pulmonologist at the University of Tennessee Health Science Center in Memphis.

“A couple of decades ago, you could comfortably treat a patient with severe community-acquired pneumonia with a macrolide, but you can’t do that anymore,” Dr. Muthiah said in an interview.

If the newly reported data on oral solithromycin hold up under further review, it would mean that solithromycin was as effective as a potent quinolone, which remains an effective monotherapy for community-acquired pneumonia in patients who do not require treatment in an intensive care unit, Dr. Muthiah noted.

A companion study, SOLITAIRE-IV, is a phase III pivotal trial assessing the safety and efficacy of solithromycin when begun intravenously for treating community-acquired pneumonia, followed by a switch to oral dosing, in comparison with intravenous followed by oral treatment with moxifloxacin.

Once those data are fully collected and analyzed, the company will submit the information from both trials to the FDA, said Dr. David Oldach, chief medical officer for Cempra.

Results from the intravenous trial, reported in a preliminary way by Cempra Oct. 16 in a press release, showed that the solithromycin treatment regimen tested in SOLITAIRE-IV met its noninferiority targets, compared with moxifloxacin. The safety results, however, showed that solithromycin produced a higher number of patients with a liver-enzyme elevation, compared with patients treated with moxifloxacin.

In SOLITAIRE-IV, Cempra reported that grade 3 increase in levels of alanine transaminase (ALT) occurred in 8% of patients on solithromycin and in 3% of patients on moxifloxacin. Grade 4 increases in ALT occurred in less than 1% of patients in both treatment arms.

In the current, orally administered trial, grade 3 ALT increases occurred in 5% of patients treated with solithromycin and in 2% of patients treated with moxifloxacin, Dr. Barrera reported. Grade 4 ALT increases occurred in 0.5% of patients treated with solithromycin and in 1.2% of those treated with moxifloxacin. No patients in either arm developed an elevation of both ALT and bilirubin, and the ALT increases seen were reversible and asymptomatic, Dr. Barrera said.

By other assessments, the safety profiles of solithromycin and moxifloxacin were similar: 7% of patients on solithromycin and 6% on moxifloxacin had a serious adverse event, and 4% of patients in each study arm discontinued treatment because of an adverse event.

SOLITAIRE-ORAL was sponsored by Cempra, the company developing solithromycin. Dr. Barrera has received research funding from Cempra. Dr. Muthiah had no disclosures.

mzoler@frontlinemedcom.com 


On Twitter @mitchelzoler

LONDON – For every 10° C drop in the highest daily air temperature, the risk for ST-elevation myocardial infraction was found to increase by 7% in a Canadian study.

Researchers at the University of Manitoba in Winnipeg performed a retrospective study of all STEMI cases that had occurred in the city during 2009-2014 and linked them to daily air temperatures collected from Environment Canada.

“There is a clear correlation between cold weather and heart attacks,” said Dr. Shuangbo Liu, who presented the findings at the annual congress of the European Society of Cardiology. Previous studies have shown that the incidence of, hospitalization for, and death as a result of, MI are all increased as the weather gets colder. But until now, it wasn’t known what the specific relationship between temperature drops and the rate of STEMI was, she explained.

STEMIs typically occur as a result of acute rupture of an atherosclerotic plaque, but although the risk factors for the development for the plaques have been widely studied, the risk factors for rupture are not so well defined. There is some suggestion that colder weather is linked to factors that might predispose to plaque rupture, such as an increased cardiac workload, higher blood pressure, and an increased procoagulant state.

Winnipeg is one of the coldest large cities in the world in winter, but has more temperate fall and spring seasons with hot and dry summers, and so provided the ideal place to study the effect of environmental temperature on the risk of STEMI, Dr. Liu said.

Over the 6-year retrospective audit period, 1,817 STEMIs were recorded. Only STEMIs that were reported within 12 hours of admission were included in the analyses, with almost all (95%) patients undergoing primary percutaneous coronary intervention.

The highest daily temperature reached was 20° C on 31% of the study days, 0°-20° on 38% of the study days, and less than 0° on 32% of the study days.

The cold – but not warm – weather was associated with the risk of STEMI, with the daily high temperature being the strongest predictor of having a heart attack. On the study days where the highest temperature reached was less than 0°, the STEMI event rate was 0.94 per day. This rate was significantly higher than that when the daily high temperature was above 0°, at a rate of 0.79 per day overall (P less than .001)

STEMI rates on days that were 0°-10°, 10°-20°, 20°-30°, and 30° and above were 0.89, 0.81, 0.74, and 0.61 per day, respectively.

Although any snowfall in the last 2 days was predictive of STEMI on univariate analysis, upping the risk by 20%, it did not remain so after adjustment for temperature.

The daily high temperatures on the 1-2 days preceding STEMI were found to be predictive in univariate analyses, increasing the relative risk by 19%-20% (P less than .001).

Dr. Liu acknowledged the limitations of using retrospective administrative data and that further prospective validation of the results would be needed. However, these data are “thought provoking,” she said, and suggest that increasing public awareness is needed and perhaps health care resources need to be reallocated to help prevent the seasonal surge in STEMI observed in the study.

Dr. Liu reported having no relevant financial disclosures.

LONDON – For every 10° C drop in the highest daily air temperature, the risk for ST-elevation myocardial infraction was found to increase by 7% in a Canadian study.

Researchers at the University of Manitoba in Winnipeg performed a retrospective study of all STEMI cases that had occurred in the city during 2009-2014 and linked them to daily air temperatures collected from Environment Canada.

“There is a clear correlation between cold weather and heart attacks,” said Dr. Shuangbo Liu, who presented the findings at the annual congress of the European Society of Cardiology. Previous studies have shown that the incidence of, hospitalization for, and death as a result of, MI are all increased as the weather gets colder. But until now, it wasn’t known what the specific relationship between temperature drops and the rate of STEMI was, she explained.

STEMIs typically occur as a result of acute rupture of an atherosclerotic plaque, but although the risk factors for the development for the plaques have been widely studied, the risk factors for rupture are not so well defined. There is some suggestion that colder weather is linked to factors that might predispose to plaque rupture, such as an increased cardiac workload, higher blood pressure, and an increased procoagulant state.

Winnipeg is one of the coldest large cities in the world in winter, but has more temperate fall and spring seasons with hot and dry summers, and so provided the ideal place to study the effect of environmental temperature on the risk of STEMI, Dr. Liu said.

Over the 6-year retrospective audit period, 1,817 STEMIs were recorded. Only STEMIs that were reported within 12 hours of admission were included in the analyses, with almost all (95%) patients undergoing primary percutaneous coronary intervention.

The highest daily temperature reached was 20° C on 31% of the study days, 0°-20° on 38% of the study days, and less than 0° on 32% of the study days.

The cold – but not warm – weather was associated with the risk of STEMI, with the daily high temperature being the strongest predictor of having a heart attack. On the study days where the highest temperature reached was less than 0°, the STEMI event rate was 0.94 per day. This rate was significantly higher than that when the daily high temperature was above 0°, at a rate of 0.79 per day overall (P less than .001)

STEMI rates on days that were 0°-10°, 10°-20°, 20°-30°, and 30° and above were 0.89, 0.81, 0.74, and 0.61 per day, respectively.

Although any snowfall in the last 2 days was predictive of STEMI on univariate analysis, upping the risk by 20%, it did not remain so after adjustment for temperature.

The daily high temperatures on the 1-2 days preceding STEMI were found to be predictive in univariate analyses, increasing the relative risk by 19%-20% (P less than .001).

Dr. Liu acknowledged the limitations of using retrospective administrative data and that further prospective validation of the results would be needed. However, these data are “thought provoking,” she said, and suggest that increasing public awareness is needed and perhaps health care resources need to be reallocated to help prevent the seasonal surge in STEMI observed in the study.

Dr. Liu reported having no relevant financial disclosures.

LONDON – For every 10° C drop in the highest daily air temperature, the risk for ST-elevation myocardial infraction was found to increase by 7% in a Canadian study.

Researchers at the University of Manitoba in Winnipeg performed a retrospective study of all STEMI cases that had occurred in the city during 2009-2014 and linked them to daily air temperatures collected from Environment Canada.

“There is a clear correlation between cold weather and heart attacks,” said Dr. Shuangbo Liu, who presented the findings at the annual congress of the European Society of Cardiology. Previous studies have shown that the incidence of, hospitalization for, and death as a result of, MI are all increased as the weather gets colder. But until now, it wasn’t known what the specific relationship between temperature drops and the rate of STEMI was, she explained.

STEMIs typically occur as a result of acute rupture of an atherosclerotic plaque, but although the risk factors for the development for the plaques have been widely studied, the risk factors for rupture are not so well defined. There is some suggestion that colder weather is linked to factors that might predispose to plaque rupture, such as an increased cardiac workload, higher blood pressure, and an increased procoagulant state.

Winnipeg is one of the coldest large cities in the world in winter, but has more temperate fall and spring seasons with hot and dry summers, and so provided the ideal place to study the effect of environmental temperature on the risk of STEMI, Dr. Liu said.

Over the 6-year retrospective audit period, 1,817 STEMIs were recorded. Only STEMIs that were reported within 12 hours of admission were included in the analyses, with almost all (95%) patients undergoing primary percutaneous coronary intervention.

The highest daily temperature reached was 20° C on 31% of the study days, 0°-20° on 38% of the study days, and less than 0° on 32% of the study days.

The cold – but not warm – weather was associated with the risk of STEMI, with the daily high temperature being the strongest predictor of having a heart attack. On the study days where the highest temperature reached was less than 0°, the STEMI event rate was 0.94 per day. This rate was significantly higher than that when the daily high temperature was above 0°, at a rate of 0.79 per day overall (P less than .001)

STEMI rates on days that were 0°-10°, 10°-20°, 20°-30°, and 30° and above were 0.89, 0.81, 0.74, and 0.61 per day, respectively.

Although any snowfall in the last 2 days was predictive of STEMI on univariate analysis, upping the risk by 20%, it did not remain so after adjustment for temperature.

The daily high temperatures on the 1-2 days preceding STEMI were found to be predictive in univariate analyses, increasing the relative risk by 19%-20% (P less than .001).

Dr. Liu acknowledged the limitations of using retrospective administrative data and that further prospective validation of the results would be needed. However, these data are “thought provoking,” she said, and suggest that increasing public awareness is needed and perhaps health care resources need to be reallocated to help prevent the seasonal surge in STEMI observed in the study.

Dr. Liu reported having no relevant financial disclosures.

Patients are often impatient. They want answers.

To some extent, I can’t blame them. When it’s your disease, you want to know what’s going on and what you can do about it. So I try to keep on top of results as they come in and have my staff contact people to relay the news.

The problem is that medicine (like life) does not provide immediate gratification. It takes time to get routine labs back, and some (such as send-outs) can even take a few weeks.

Radiology reports usually have a 24-hour turnaround, and radiologists will call me if they find something urgent. Yet, it’s amazing how many people will call for results before they even leave that facility.

Did it always used to be like this? Were people always this demanding of immediate answers and test results from their doctors?

We live in a world that gets faster and faster, and people get used to things happening quickly. It’s an age of instant gratification, and having to wait for test results seems silly to laypeople. After all, don’t TV medical shows have results coming back quickly, gleaming advanced scanners, and the machine that goes “ping”? So why doesn’t that happen when you visit a doctor in real life?

Of course, I could get the results faster. I could order everything STAT and abuse the privilege ... but crying wolf only works a few times, and then you can’t do it when you really need it. I could call the radiologists for verbal MRI reads ... but then I’m taking their time away from more urgent cases, and other patients with more concerning issues are affected. So I don’t do that routinely, either.

Even people in slow-moving lines of work can have trouble grasping that medicine is the same way. I tell them we’ll call them when we get results, and try to stay on top of things. I admit sometimes things may slip through, and they’re right to call and ask.

Most patients understand this, and are, well, patient. I just wish more were. It would save a lot of time, effort, and frustration for all involved, including them.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Patients are often impatient. They want answers.

To some extent, I can’t blame them. When it’s your disease, you want to know what’s going on and what you can do about it. So I try to keep on top of results as they come in and have my staff contact people to relay the news.

The problem is that medicine (like life) does not provide immediate gratification. It takes time to get routine labs back, and some (such as send-outs) can even take a few weeks.

Radiology reports usually have a 24-hour turnaround, and radiologists will call me if they find something urgent. Yet, it’s amazing how many people will call for results before they even leave that facility.

Did it always used to be like this? Were people always this demanding of immediate answers and test results from their doctors?

We live in a world that gets faster and faster, and people get used to things happening quickly. It’s an age of instant gratification, and having to wait for test results seems silly to laypeople. After all, don’t TV medical shows have results coming back quickly, gleaming advanced scanners, and the machine that goes “ping”? So why doesn’t that happen when you visit a doctor in real life?

Of course, I could get the results faster. I could order everything STAT and abuse the privilege ... but crying wolf only works a few times, and then you can’t do it when you really need it. I could call the radiologists for verbal MRI reads ... but then I’m taking their time away from more urgent cases, and other patients with more concerning issues are affected. So I don’t do that routinely, either.

Even people in slow-moving lines of work can have trouble grasping that medicine is the same way. I tell them we’ll call them when we get results, and try to stay on top of things. I admit sometimes things may slip through, and they’re right to call and ask.

Most patients understand this, and are, well, patient. I just wish more were. It would save a lot of time, effort, and frustration for all involved, including them.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Patients are often impatient. They want answers.

To some extent, I can’t blame them. When it’s your disease, you want to know what’s going on and what you can do about it. So I try to keep on top of results as they come in and have my staff contact people to relay the news.

The problem is that medicine (like life) does not provide immediate gratification. It takes time to get routine labs back, and some (such as send-outs) can even take a few weeks.

Radiology reports usually have a 24-hour turnaround, and radiologists will call me if they find something urgent. Yet, it’s amazing how many people will call for results before they even leave that facility.

Did it always used to be like this? Were people always this demanding of immediate answers and test results from their doctors?

We live in a world that gets faster and faster, and people get used to things happening quickly. It’s an age of instant gratification, and having to wait for test results seems silly to laypeople. After all, don’t TV medical shows have results coming back quickly, gleaming advanced scanners, and the machine that goes “ping”? So why doesn’t that happen when you visit a doctor in real life?

Of course, I could get the results faster. I could order everything STAT and abuse the privilege ... but crying wolf only works a few times, and then you can’t do it when you really need it. I could call the radiologists for verbal MRI reads ... but then I’m taking their time away from more urgent cases, and other patients with more concerning issues are affected. So I don’t do that routinely, either.

Even people in slow-moving lines of work can have trouble grasping that medicine is the same way. I tell them we’ll call them when we get results, and try to stay on top of things. I admit sometimes things may slip through, and they’re right to call and ask.

Most patients understand this, and are, well, patient. I just wish more were. It would save a lot of time, effort, and frustration for all involved, including them.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

CHICAGO – Investigators have come up with a simple way to reduce and maybe even eliminate pull-out pneumothoraces during chest tube removal.

Instead of standard inhale or exhale Valsalva maneuvers, they have their patients blow up a party balloon as the tube is pulled.

Courtesy Dr. Puwadon Thitivaraporn

That produces the same Valsalva effects as the standard maneuvers, but with two significant advantages. First, it’s easy to explain and for patients to understand and do – not much more instruction is required than “blow up the balloon” – and, secondly, the inflating balloon is a visual check to make sure patients are doing the maneuver correctly. “It’s easy. Everyone can do it,” said lead investigator Dr. Puwadon Thitivaraporn, who developed the technique with Dr. Kritaya Kritayakirana and colleagues at King Chulalongkorn Memorial Hospital in Bangkok, Thailand.

To see how well it works, the team randomized 10 women and 38 men about equally to four removal techniques: the standard expire Valsalva, the standard inspire Valsalva, and two balloon maneuvers – blowing the balloon up after a deep breath and blowing it up with residual lung volume after an initial exhalation.

The subjects were trauma patients 15-64 years old, with a mean age of 38 years. Lung injuries, rib fractures, and tube suction were a bit more common in the standard maneuver groups. Patients with tracheotomies, chronic lung disease, and Glasgow Coma Scores below 13 were excluded from the study. Hemopneumothorax was the most common indication for tube placement.

Two patients in each of the standard groups (16%) developed a pull-out pneumothorax within 24 hours of tube removal, confirmed by x-ray. One required chest tube reinsertion, and all four ended up spending extra time in the hospital. Similar problems have been reported in American medicine (J Trauma. 2001 Apr;50[4]:674-7).

Meanwhile, not a single balloon patient had a lung collapse when their tube was pulled.

Because of the small number of subjects, the differences weren’t statistically significant, but they came close in a group comparison of standard patients with balloon patients (P = .11). The investigators estimated they would need almost 600 hundred subjects to reach statistical significance.

Even so, the party balloon technique appears to be “easier and safer” than standard maneuvers, as well as “reproducible and cheap, and it can prevent recurrent pneumothorax. It can be used as an alternative to the classic Valsalva,” said Dr. Thitivaraporn, a cardiothoracic surgery resident at the Bangkok hospital.

The balloon method is being used there now in nontrauma patients, as well, but the standard maneuvers are also being used until the balloon technique shows statistically significant benefits, he said.

With manometry, the team found that a party balloon’s internal pressure builds quickly as it’s inflated from a starting diameter of about 4.5 cm to about 9 cm, peaking at about 60 mm Hg; pressure trails off to about 40 mm Hg as inflation continues past 9 cm.

The investigators have no relevant disclosures.

aotto@frontlinemedcom.com

CHICAGO – Investigators have come up with a simple way to reduce and maybe even eliminate pull-out pneumothoraces during chest tube removal.

Instead of standard inhale or exhale Valsalva maneuvers, they have their patients blow up a party balloon as the tube is pulled.

Courtesy Dr. Puwadon Thitivaraporn

That produces the same Valsalva effects as the standard maneuvers, but with two significant advantages. First, it’s easy to explain and for patients to understand and do – not much more instruction is required than “blow up the balloon” – and, secondly, the inflating balloon is a visual check to make sure patients are doing the maneuver correctly. “It’s easy. Everyone can do it,” said lead investigator Dr. Puwadon Thitivaraporn, who developed the technique with Dr. Kritaya Kritayakirana and colleagues at King Chulalongkorn Memorial Hospital in Bangkok, Thailand.

To see how well it works, the team randomized 10 women and 38 men about equally to four removal techniques: the standard expire Valsalva, the standard inspire Valsalva, and two balloon maneuvers – blowing the balloon up after a deep breath and blowing it up with residual lung volume after an initial exhalation.

The subjects were trauma patients 15-64 years old, with a mean age of 38 years. Lung injuries, rib fractures, and tube suction were a bit more common in the standard maneuver groups. Patients with tracheotomies, chronic lung disease, and Glasgow Coma Scores below 13 were excluded from the study. Hemopneumothorax was the most common indication for tube placement.

Two patients in each of the standard groups (16%) developed a pull-out pneumothorax within 24 hours of tube removal, confirmed by x-ray. One required chest tube reinsertion, and all four ended up spending extra time in the hospital. Similar problems have been reported in American medicine (J Trauma. 2001 Apr;50[4]:674-7).

Meanwhile, not a single balloon patient had a lung collapse when their tube was pulled.

Because of the small number of subjects, the differences weren’t statistically significant, but they came close in a group comparison of standard patients with balloon patients (P = .11). The investigators estimated they would need almost 600 hundred subjects to reach statistical significance.

Even so, the party balloon technique appears to be “easier and safer” than standard maneuvers, as well as “reproducible and cheap, and it can prevent recurrent pneumothorax. It can be used as an alternative to the classic Valsalva,” said Dr. Thitivaraporn, a cardiothoracic surgery resident at the Bangkok hospital.

The balloon method is being used there now in nontrauma patients, as well, but the standard maneuvers are also being used until the balloon technique shows statistically significant benefits, he said.

With manometry, the team found that a party balloon’s internal pressure builds quickly as it’s inflated from a starting diameter of about 4.5 cm to about 9 cm, peaking at about 60 mm Hg; pressure trails off to about 40 mm Hg as inflation continues past 9 cm.

The investigators have no relevant disclosures.

aotto@frontlinemedcom.com

CHICAGO – Investigators have come up with a simple way to reduce and maybe even eliminate pull-out pneumothoraces during chest tube removal.

Instead of standard inhale or exhale Valsalva maneuvers, they have their patients blow up a party balloon as the tube is pulled.

Courtesy Dr. Puwadon Thitivaraporn

That produces the same Valsalva effects as the standard maneuvers, but with two significant advantages. First, it’s easy to explain and for patients to understand and do – not much more instruction is required than “blow up the balloon” – and, secondly, the inflating balloon is a visual check to make sure patients are doing the maneuver correctly. “It’s easy. Everyone can do it,” said lead investigator Dr. Puwadon Thitivaraporn, who developed the technique with Dr. Kritaya Kritayakirana and colleagues at King Chulalongkorn Memorial Hospital in Bangkok, Thailand.

To see how well it works, the team randomized 10 women and 38 men about equally to four removal techniques: the standard expire Valsalva, the standard inspire Valsalva, and two balloon maneuvers – blowing the balloon up after a deep breath and blowing it up with residual lung volume after an initial exhalation.

The subjects were trauma patients 15-64 years old, with a mean age of 38 years. Lung injuries, rib fractures, and tube suction were a bit more common in the standard maneuver groups. Patients with tracheotomies, chronic lung disease, and Glasgow Coma Scores below 13 were excluded from the study. Hemopneumothorax was the most common indication for tube placement.

Two patients in each of the standard groups (16%) developed a pull-out pneumothorax within 24 hours of tube removal, confirmed by x-ray. One required chest tube reinsertion, and all four ended up spending extra time in the hospital. Similar problems have been reported in American medicine (J Trauma. 2001 Apr;50[4]:674-7).

Meanwhile, not a single balloon patient had a lung collapse when their tube was pulled.

Because of the small number of subjects, the differences weren’t statistically significant, but they came close in a group comparison of standard patients with balloon patients (P = .11). The investigators estimated they would need almost 600 hundred subjects to reach statistical significance.

Even so, the party balloon technique appears to be “easier and safer” than standard maneuvers, as well as “reproducible and cheap, and it can prevent recurrent pneumothorax. It can be used as an alternative to the classic Valsalva,” said Dr. Thitivaraporn, a cardiothoracic surgery resident at the Bangkok hospital.

The balloon method is being used there now in nontrauma patients, as well, but the standard maneuvers are also being used until the balloon technique shows statistically significant benefits, he said.

With manometry, the team found that a party balloon’s internal pressure builds quickly as it’s inflated from a starting diameter of about 4.5 cm to about 9 cm, peaking at about 60 mm Hg; pressure trails off to about 40 mm Hg as inflation continues past 9 cm.

The investigators have no relevant disclosures.

aotto@frontlinemedcom.com

HONOLULU – A survey of almost 500 physicians found that primary care physicians (PCPs) are far more concerned about the reported adverse effects of proton pump inhibitors (PPIs) than are gastroenterologists and use them more sparingly. The results of the survey were presented at the 2015 American College of Gastroenterology (ACG) Annual Scientific Meeting and Postgraduate Course.

“We asked physicians about a broad array of adverse effects from long-term use of PPIs and PCPs expressed greater concern for all of them,” reported Dr. Samir Kapadia, division of gastroenterology and hepatology, State University of New York at Stony Brook. “Alternatively, significantly more gastroenterologists responded that they really had no concerns for any of these adverse effects.”

© nebari/Thinkstock

The evidence may be on the side of the gastroenterologists, according to Dr. Kapadia. Although PPIs have been associated with hypomagnesemia, iron deficiency, vitamin B₁₂ deficiency, diarrhea caused by Clostridium difficile infection, and interactions with the platelet inhibitor clopidogrel, Dr. Kapadia noted that few associations have been made on the basis of prospective trials.

“Much of the available literature is observational or based on studies that are heterogeneous and small,” Dr. Kapadia. “Confounding factors in these studies also limit interpretation.”

In this study for which surveys are still being collected, a 19-item questionnaire was distributed to 384 gastroenterologists and 88 PCPs. In addition to demographic information, the surveys were designed to capture opinions about the safety of PPIs as well as elicit information about how these agents are being used in clinical practice.

Of side effects associated with PPIs, significantly more PCPs than gastroenterologists expressed concern about hypomagnesemia (41.7% vs. 6.3%; P less than .001), iron deficiency (33.3% vs. 11.4%; P = .014) and vitamin B₁₂ deficiency (47.6% vs. 17.3%; P = .005). From the other perspective, when asked about their concern for these and other safety issues, the answer was “none of the above” for 26.2% of PCPs and 67.1% of gastroenterologists (P less than .001).

When given specific risk scenarios, PCPs were consistently more prepared to discontinue PPI therapy than were gastroenterologists. For example, in a hypothetical 65-year-old with GERD symptoms expressing concern about risk of hip fracture, 64.5% of PCPs vs. 30.7% of gastroenterologists (P less than .001) responded that they would discontinue the PPI. In a patient of the same age about to start broad-spectrum antibiotics for cellulitis, 16.1% of PCPs, but only 4.3% of gastroenterologists (P = .001) reported that they would discontinue PPIs. Conversely, 68.5% of gastroenterologists vs. 54.2% of PCPs (P = .028) would continue therapy.

For a hypothetical 65-year-old with symptomatic gastroesophageal reflux disease (GERD) initiating clopidogrel, 50% of PCPs vs. 27.6% of gastroenterologists (P = .001) would switch to an H₂-receptor antagonist. Only 27.3% of PCPs vs. 46.4% of gastroenterologists (P = .001) would continue the PPI. When the age of the hypothetical patient is raised to 75 years, PCPs, but not gastroenterologists, were even more likely to discontinue PPI therapy.

Using PPIs appropriately is an important goal, Dr. Kapadia emphasized. However, he suggested that many warnings about the risks of PPIs, including those issued by the Food and Drug Administration, are incompletely substantiated and are not being evaluated with an appropriate attention to benefit-to-risk ratio of a drug that not only controls symptoms but may also reduce risk of GI bleeding. Others share this point of view.

“The pendulum has moved too far in regard to the fear of potential side effects,” agreed Dr. Philip Katz, chairman, division of gastroenterology, Albert Einstein Medical Center, Philadelphia. First author of the 2013 ACG guidelines on GERD, which addresses the safety of PPIs (Am J Gastroenterol. 2013;108:308-28), Dr. Katz said in an interview that the data generated by this survey suggest that PCPs are misinterpreting the relative risks and need to be given more information about indications in which benefits are well established.

Making the same point, Dr. Nicholas J. Shaheen, chief, division of gastroenterology and hepatology, University of North Carolina, Chapel Hill, suggested “This may be a failure on our part [as gastroenterologists] to educate our colleagues about the role of these drugs.”

Dr. Kapadia reported no potential conflicts.

HONOLULU – A survey of almost 500 physicians found that primary care physicians (PCPs) are far more concerned about the reported adverse effects of proton pump inhibitors (PPIs) than are gastroenterologists and use them more sparingly. The results of the survey were presented at the 2015 American College of Gastroenterology (ACG) Annual Scientific Meeting and Postgraduate Course.

“We asked physicians about a broad array of adverse effects from long-term use of PPIs and PCPs expressed greater concern for all of them,” reported Dr. Samir Kapadia, division of gastroenterology and hepatology, State University of New York at Stony Brook. “Alternatively, significantly more gastroenterologists responded that they really had no concerns for any of these adverse effects.”

© nebari/Thinkstock

The evidence may be on the side of the gastroenterologists, according to Dr. Kapadia. Although PPIs have been associated with hypomagnesemia, iron deficiency, vitamin B₁₂ deficiency, diarrhea caused by Clostridium difficile infection, and interactions with the platelet inhibitor clopidogrel, Dr. Kapadia noted that few associations have been made on the basis of prospective trials.

“Much of the available literature is observational or based on studies that are heterogeneous and small,” Dr. Kapadia. “Confounding factors in these studies also limit interpretation.”

In this study for which surveys are still being collected, a 19-item questionnaire was distributed to 384 gastroenterologists and 88 PCPs. In addition to demographic information, the surveys were designed to capture opinions about the safety of PPIs as well as elicit information about how these agents are being used in clinical practice.

Of side effects associated with PPIs, significantly more PCPs than gastroenterologists expressed concern about hypomagnesemia (41.7% vs. 6.3%; P less than .001), iron deficiency (33.3% vs. 11.4%; P = .014) and vitamin B₁₂ deficiency (47.6% vs. 17.3%; P = .005). From the other perspective, when asked about their concern for these and other safety issues, the answer was “none of the above” for 26.2% of PCPs and 67.1% of gastroenterologists (P less than .001).

When given specific risk scenarios, PCPs were consistently more prepared to discontinue PPI therapy than were gastroenterologists. For example, in a hypothetical 65-year-old with GERD symptoms expressing concern about risk of hip fracture, 64.5% of PCPs vs. 30.7% of gastroenterologists (P less than .001) responded that they would discontinue the PPI. In a patient of the same age about to start broad-spectrum antibiotics for cellulitis, 16.1% of PCPs, but only 4.3% of gastroenterologists (P = .001) reported that they would discontinue PPIs. Conversely, 68.5% of gastroenterologists vs. 54.2% of PCPs (P = .028) would continue therapy.

For a hypothetical 65-year-old with symptomatic gastroesophageal reflux disease (GERD) initiating clopidogrel, 50% of PCPs vs. 27.6% of gastroenterologists (P = .001) would switch to an H₂-receptor antagonist. Only 27.3% of PCPs vs. 46.4% of gastroenterologists (P = .001) would continue the PPI. When the age of the hypothetical patient is raised to 75 years, PCPs, but not gastroenterologists, were even more likely to discontinue PPI therapy.

Using PPIs appropriately is an important goal, Dr. Kapadia emphasized. However, he suggested that many warnings about the risks of PPIs, including those issued by the Food and Drug Administration, are incompletely substantiated and are not being evaluated with an appropriate attention to benefit-to-risk ratio of a drug that not only controls symptoms but may also reduce risk of GI bleeding. Others share this point of view.

“The pendulum has moved too far in regard to the fear of potential side effects,” agreed Dr. Philip Katz, chairman, division of gastroenterology, Albert Einstein Medical Center, Philadelphia. First author of the 2013 ACG guidelines on GERD, which addresses the safety of PPIs (Am J Gastroenterol. 2013;108:308-28), Dr. Katz said in an interview that the data generated by this survey suggest that PCPs are misinterpreting the relative risks and need to be given more information about indications in which benefits are well established.

Making the same point, Dr. Nicholas J. Shaheen, chief, division of gastroenterology and hepatology, University of North Carolina, Chapel Hill, suggested “This may be a failure on our part [as gastroenterologists] to educate our colleagues about the role of these drugs.”

Dr. Kapadia reported no potential conflicts.

HONOLULU – A survey of almost 500 physicians found that primary care physicians (PCPs) are far more concerned about the reported adverse effects of proton pump inhibitors (PPIs) than are gastroenterologists and use them more sparingly. The results of the survey were presented at the 2015 American College of Gastroenterology (ACG) Annual Scientific Meeting and Postgraduate Course.

“We asked physicians about a broad array of adverse effects from long-term use of PPIs and PCPs expressed greater concern for all of them,” reported Dr. Samir Kapadia, division of gastroenterology and hepatology, State University of New York at Stony Brook. “Alternatively, significantly more gastroenterologists responded that they really had no concerns for any of these adverse effects.”

© nebari/Thinkstock

The evidence may be on the side of the gastroenterologists, according to Dr. Kapadia. Although PPIs have been associated with hypomagnesemia, iron deficiency, vitamin B₁₂ deficiency, diarrhea caused by Clostridium difficile infection, and interactions with the platelet inhibitor clopidogrel, Dr. Kapadia noted that few associations have been made on the basis of prospective trials.

“Much of the available literature is observational or based on studies that are heterogeneous and small,” Dr. Kapadia. “Confounding factors in these studies also limit interpretation.”

In this study for which surveys are still being collected, a 19-item questionnaire was distributed to 384 gastroenterologists and 88 PCPs. In addition to demographic information, the surveys were designed to capture opinions about the safety of PPIs as well as elicit information about how these agents are being used in clinical practice.

Of side effects associated with PPIs, significantly more PCPs than gastroenterologists expressed concern about hypomagnesemia (41.7% vs. 6.3%; P less than .001), iron deficiency (33.3% vs. 11.4%; P = .014) and vitamin B₁₂ deficiency (47.6% vs. 17.3%; P = .005). From the other perspective, when asked about their concern for these and other safety issues, the answer was “none of the above” for 26.2% of PCPs and 67.1% of gastroenterologists (P less than .001).

When given specific risk scenarios, PCPs were consistently more prepared to discontinue PPI therapy than were gastroenterologists. For example, in a hypothetical 65-year-old with GERD symptoms expressing concern about risk of hip fracture, 64.5% of PCPs vs. 30.7% of gastroenterologists (P less than .001) responded that they would discontinue the PPI. In a patient of the same age about to start broad-spectrum antibiotics for cellulitis, 16.1% of PCPs, but only 4.3% of gastroenterologists (P = .001) reported that they would discontinue PPIs. Conversely, 68.5% of gastroenterologists vs. 54.2% of PCPs (P = .028) would continue therapy.

For a hypothetical 65-year-old with symptomatic gastroesophageal reflux disease (GERD) initiating clopidogrel, 50% of PCPs vs. 27.6% of gastroenterologists (P = .001) would switch to an H₂-receptor antagonist. Only 27.3% of PCPs vs. 46.4% of gastroenterologists (P = .001) would continue the PPI. When the age of the hypothetical patient is raised to 75 years, PCPs, but not gastroenterologists, were even more likely to discontinue PPI therapy.

Using PPIs appropriately is an important goal, Dr. Kapadia emphasized. However, he suggested that many warnings about the risks of PPIs, including those issued by the Food and Drug Administration, are incompletely substantiated and are not being evaluated with an appropriate attention to benefit-to-risk ratio of a drug that not only controls symptoms but may also reduce risk of GI bleeding. Others share this point of view.

“The pendulum has moved too far in regard to the fear of potential side effects,” agreed Dr. Philip Katz, chairman, division of gastroenterology, Albert Einstein Medical Center, Philadelphia. First author of the 2013 ACG guidelines on GERD, which addresses the safety of PPIs (Am J Gastroenterol. 2013;108:308-28), Dr. Katz said in an interview that the data generated by this survey suggest that PCPs are misinterpreting the relative risks and need to be given more information about indications in which benefits are well established.

Making the same point, Dr. Nicholas J. Shaheen, chief, division of gastroenterology and hepatology, University of North Carolina, Chapel Hill, suggested “This may be a failure on our part [as gastroenterologists] to educate our colleagues about the role of these drugs.”

Dr. Kapadia reported no potential conflicts.

Mycosis fungoides

A Notch-related microRNA may be a therapeutic target for mycosis fungoides (MF), according to research published in the Journal of Investigative Dermatology.

The Notch pathway has been implicated in the progression of cutaneous T-cell lymphomas, but the mechanisms driving Notch activation has been unclear.

So investigators studied a series of skin samples from patients with MF in tumor phase, focusing on the Notch pathway.

“The purpose of this project has been to research the state of the Notch pathway in a series of samples from patients with mycosis fungoides and compare the results to a control group to discover if Notch activation in tumors is influenced by epigenetic modifications,” said Fernando Gallardo, MD, of Hospital del Mar Investigacions Mèdiques in Barcelona, Spain.

So he and his colleagues looked at methylation patterns in several components of the Notch pathway and confirmed that Notch1 was activated in samples from patients with MF.

They then identified a microRNA, miR-200C, that was epigenetically repressed in the samples. Further investigation revealed that this repression leads to the activation of the Notch pathway.

“The restoration of miR-200C expression, silenced in the tumor cells, could represent a potential therapeutic target for this subtype of lymphomas,” Dr Gallardo concluded.

Mycosis fungoides

A Notch-related microRNA may be a therapeutic target for mycosis fungoides (MF), according to research published in the Journal of Investigative Dermatology.

The Notch pathway has been implicated in the progression of cutaneous T-cell lymphomas, but the mechanisms driving Notch activation has been unclear.

So investigators studied a series of skin samples from patients with MF in tumor phase, focusing on the Notch pathway.

“The purpose of this project has been to research the state of the Notch pathway in a series of samples from patients with mycosis fungoides and compare the results to a control group to discover if Notch activation in tumors is influenced by epigenetic modifications,” said Fernando Gallardo, MD, of Hospital del Mar Investigacions Mèdiques in Barcelona, Spain.

So he and his colleagues looked at methylation patterns in several components of the Notch pathway and confirmed that Notch1 was activated in samples from patients with MF.

They then identified a microRNA, miR-200C, that was epigenetically repressed in the samples. Further investigation revealed that this repression leads to the activation of the Notch pathway.

“The restoration of miR-200C expression, silenced in the tumor cells, could represent a potential therapeutic target for this subtype of lymphomas,” Dr Gallardo concluded.

Mycosis fungoides

A Notch-related microRNA may be a therapeutic target for mycosis fungoides (MF), according to research published in the Journal of Investigative Dermatology.

The Notch pathway has been implicated in the progression of cutaneous T-cell lymphomas, but the mechanisms driving Notch activation has been unclear.

So investigators studied a series of skin samples from patients with MF in tumor phase, focusing on the Notch pathway.

“The purpose of this project has been to research the state of the Notch pathway in a series of samples from patients with mycosis fungoides and compare the results to a control group to discover if Notch activation in tumors is influenced by epigenetic modifications,” said Fernando Gallardo, MD, of Hospital del Mar Investigacions Mèdiques in Barcelona, Spain.

So he and his colleagues looked at methylation patterns in several components of the Notch pathway and confirmed that Notch1 was activated in samples from patients with MF.

They then identified a microRNA, miR-200C, that was epigenetically repressed in the samples. Further investigation revealed that this repression leads to the activation of the Notch pathway.

“The restoration of miR-200C expression, silenced in the tumor cells, could represent a potential therapeutic target for this subtype of lymphomas,” Dr Gallardo concluded.