NATIONAL HARBOR, MD. – Trial results suggest a personalized vaccination approach is feasible and safe, and the vaccine can produce clinical responses in patients with non–small cell lung cancer (NSCLC).

Jennifer Smith/MDedge News

The neoantigen vaccine produced only grade 1 adverse events, yielded responses in patients with epidermal growth factor receptor (EGFR) mutations, and proved particularly effective in patients who were also receiving an EGFR inhibitor.

“EGFR inhibitors seemed to reduce tumor immunosuppression barriers and may enhance antitumor immune responses before and during immunization, suggesting there may be a potential synergy of EGFR with immunotherapies,” Gregory A. Lizee, PhD, of University of Texas MD Anderson Cancer Center, Houston, said at the annual meeting of the Society for Immunotherapy of Cancer.

The research began with an elderly patient who had heavily pretreated NSCLC (Oncoimmunology. 2016;5[12]:e1238539). Dr. Lizee and colleagues used tumor mutational profiling and human leukocyte antigen (HLA) typing to develop a personalized peptide vaccine for the patient. He received the vaccine along with topical imiquimod and had multiple lung tumor nodules regress. However, the patient also had liver metastasis that remained refractory to treatment, and he ultimately died.

To investigate this treatment approach in a larger group, Dr. Lizee and colleagues began a phase 1b trial of patients with advanced NSCLC (ChiCTR-IIR-16009867). As with the prior patient, the researchers designed personalized peptide vaccines for the trial subjects based on mutational profiling of 508 cancer-associated genes and high-resolution HLA typing. The peptides were selected based on nonsynonymous somatic tumor–associated mutations with variant allele frequency greater than 0.04 and the highest predicted neoantigen peptide binding to each patient’s HLA class I and II molecules. The vaccines targeted up to eight independent somatic mutations (mean, 3.75 mutations).

In all, 31 patients provided lung tumor biopsies and peripheral blood for mutational and HLA analyses. The researchers designed 27 personalized neoantigen vaccines, and 24 patients were ultimately vaccinated. This translates to a vaccination rate of 77%, which suggests this treatment approach is feasible, Dr. Lizee said.

Of the 24 vaccinated patients, 18 had adenocarcinoma, and 6 had squamous cell carcinoma. All patients had received multiple prior therapies, including surgery, chemotherapy, radiation, and EGFR inhibitors.

Each patient was vaccinated with a personalized mixture of short and long neoantigen peptides (mean, 9.4 peptides) dissolved in isotonic saline. Patients received at least 12 weekly immunizations and had topical imiquimod applied over the injection site for costimulation through toll-like receptor 7. The 16 patients with EGFR mutations were given the option of continuing on an EGFR inhibitor, and 9 patients elected to do so.
 

Results

Dr. Lizee said this treatment approach was “very safe,” with only grade 1 treatment-related adverse events. The events were fatigue (n = 2), rash (n = 1), and fever (n = 1).

Seven patients achieved a response after vaccination, and one patient achieved a complete response. All seven responders had EGFR mutations, and four of them were receiving an EGFR inhibitor.

The patients on an EGFR inhibitor had significantly better overall survival than that of EGFR-mutated patients who had stopped taking an EGFR inhibitor – 13.8 months and 7.6 months, respectively (P = .038).

Immune profiling revealed that neoantigen-specific T-cell reactivity was associated with clinical responses. The researchers observed EGFR neoantigen-specific T-cell responses in five responders. In three responders, the strongest response was against a peptide encompassing the L858R driver mutation.

The researchers also found evidence of synergy between EGFR inhibitor therapy and the peptide vaccine. EGFR inhibition caused immunomodulatory pathways in EGFR-mutated cancer cells to favor immune-cell infiltration and HLA-mediated antigen presentation.

“Our mechanistic working model is that, in the circulation, the personalized vaccine increased the T-cell frequency,” Dr. Lizee said. “The EGFR inhibitor increased chemokines and antigen presentation at the tumor site, which then attracted those T cells to migrate to the tumor. Then, recognition of the antigen caused interferon gamma [to increase], which caused, potentially, a feed-forward loop by increasing chemokines and antigen presentation further.”

This research is sponsored by Tianjin Beichen Hospital and funded by Tianjin HengJia Biotechnology Development Co. Ltd. Dr. Lizee disclosed a consulting relationship with Tianjin HengJia Biotechnology Development Co. Ltd.

SOURCE: Lizee G et al. SITC 2019. Abstract O18.

NATIONAL HARBOR, MD. – Trial results suggest a personalized vaccination approach is feasible and safe, and the vaccine can produce clinical responses in patients with non–small cell lung cancer (NSCLC).

Jennifer Smith/MDedge News

The neoantigen vaccine produced only grade 1 adverse events, yielded responses in patients with epidermal growth factor receptor (EGFR) mutations, and proved particularly effective in patients who were also receiving an EGFR inhibitor.

“EGFR inhibitors seemed to reduce tumor immunosuppression barriers and may enhance antitumor immune responses before and during immunization, suggesting there may be a potential synergy of EGFR with immunotherapies,” Gregory A. Lizee, PhD, of University of Texas MD Anderson Cancer Center, Houston, said at the annual meeting of the Society for Immunotherapy of Cancer.

The research began with an elderly patient who had heavily pretreated NSCLC (Oncoimmunology. 2016;5[12]:e1238539). Dr. Lizee and colleagues used tumor mutational profiling and human leukocyte antigen (HLA) typing to develop a personalized peptide vaccine for the patient. He received the vaccine along with topical imiquimod and had multiple lung tumor nodules regress. However, the patient also had liver metastasis that remained refractory to treatment, and he ultimately died.

To investigate this treatment approach in a larger group, Dr. Lizee and colleagues began a phase 1b trial of patients with advanced NSCLC (ChiCTR-IIR-16009867). As with the prior patient, the researchers designed personalized peptide vaccines for the trial subjects based on mutational profiling of 508 cancer-associated genes and high-resolution HLA typing. The peptides were selected based on nonsynonymous somatic tumor–associated mutations with variant allele frequency greater than 0.04 and the highest predicted neoantigen peptide binding to each patient’s HLA class I and II molecules. The vaccines targeted up to eight independent somatic mutations (mean, 3.75 mutations).

In all, 31 patients provided lung tumor biopsies and peripheral blood for mutational and HLA analyses. The researchers designed 27 personalized neoantigen vaccines, and 24 patients were ultimately vaccinated. This translates to a vaccination rate of 77%, which suggests this treatment approach is feasible, Dr. Lizee said.

Of the 24 vaccinated patients, 18 had adenocarcinoma, and 6 had squamous cell carcinoma. All patients had received multiple prior therapies, including surgery, chemotherapy, radiation, and EGFR inhibitors.

Each patient was vaccinated with a personalized mixture of short and long neoantigen peptides (mean, 9.4 peptides) dissolved in isotonic saline. Patients received at least 12 weekly immunizations and had topical imiquimod applied over the injection site for costimulation through toll-like receptor 7. The 16 patients with EGFR mutations were given the option of continuing on an EGFR inhibitor, and 9 patients elected to do so.
 

Results

Dr. Lizee said this treatment approach was “very safe,” with only grade 1 treatment-related adverse events. The events were fatigue (n = 2), rash (n = 1), and fever (n = 1).

Seven patients achieved a response after vaccination, and one patient achieved a complete response. All seven responders had EGFR mutations, and four of them were receiving an EGFR inhibitor.

The patients on an EGFR inhibitor had significantly better overall survival than that of EGFR-mutated patients who had stopped taking an EGFR inhibitor – 13.8 months and 7.6 months, respectively (P = .038).

Immune profiling revealed that neoantigen-specific T-cell reactivity was associated with clinical responses. The researchers observed EGFR neoantigen-specific T-cell responses in five responders. In three responders, the strongest response was against a peptide encompassing the L858R driver mutation.

The researchers also found evidence of synergy between EGFR inhibitor therapy and the peptide vaccine. EGFR inhibition caused immunomodulatory pathways in EGFR-mutated cancer cells to favor immune-cell infiltration and HLA-mediated antigen presentation.

“Our mechanistic working model is that, in the circulation, the personalized vaccine increased the T-cell frequency,” Dr. Lizee said. “The EGFR inhibitor increased chemokines and antigen presentation at the tumor site, which then attracted those T cells to migrate to the tumor. Then, recognition of the antigen caused interferon gamma [to increase], which caused, potentially, a feed-forward loop by increasing chemokines and antigen presentation further.”

This research is sponsored by Tianjin Beichen Hospital and funded by Tianjin HengJia Biotechnology Development Co. Ltd. Dr. Lizee disclosed a consulting relationship with Tianjin HengJia Biotechnology Development Co. Ltd.

SOURCE: Lizee G et al. SITC 2019. Abstract O18.

NATIONAL HARBOR, MD. – Trial results suggest a personalized vaccination approach is feasible and safe, and the vaccine can produce clinical responses in patients with non–small cell lung cancer (NSCLC).

Jennifer Smith/MDedge News

The neoantigen vaccine produced only grade 1 adverse events, yielded responses in patients with epidermal growth factor receptor (EGFR) mutations, and proved particularly effective in patients who were also receiving an EGFR inhibitor.

“EGFR inhibitors seemed to reduce tumor immunosuppression barriers and may enhance antitumor immune responses before and during immunization, suggesting there may be a potential synergy of EGFR with immunotherapies,” Gregory A. Lizee, PhD, of University of Texas MD Anderson Cancer Center, Houston, said at the annual meeting of the Society for Immunotherapy of Cancer.

The research began with an elderly patient who had heavily pretreated NSCLC (Oncoimmunology. 2016;5[12]:e1238539). Dr. Lizee and colleagues used tumor mutational profiling and human leukocyte antigen (HLA) typing to develop a personalized peptide vaccine for the patient. He received the vaccine along with topical imiquimod and had multiple lung tumor nodules regress. However, the patient also had liver metastasis that remained refractory to treatment, and he ultimately died.

To investigate this treatment approach in a larger group, Dr. Lizee and colleagues began a phase 1b trial of patients with advanced NSCLC (ChiCTR-IIR-16009867). As with the prior patient, the researchers designed personalized peptide vaccines for the trial subjects based on mutational profiling of 508 cancer-associated genes and high-resolution HLA typing. The peptides were selected based on nonsynonymous somatic tumor–associated mutations with variant allele frequency greater than 0.04 and the highest predicted neoantigen peptide binding to each patient’s HLA class I and II molecules. The vaccines targeted up to eight independent somatic mutations (mean, 3.75 mutations).

In all, 31 patients provided lung tumor biopsies and peripheral blood for mutational and HLA analyses. The researchers designed 27 personalized neoantigen vaccines, and 24 patients were ultimately vaccinated. This translates to a vaccination rate of 77%, which suggests this treatment approach is feasible, Dr. Lizee said.

Of the 24 vaccinated patients, 18 had adenocarcinoma, and 6 had squamous cell carcinoma. All patients had received multiple prior therapies, including surgery, chemotherapy, radiation, and EGFR inhibitors.

Each patient was vaccinated with a personalized mixture of short and long neoantigen peptides (mean, 9.4 peptides) dissolved in isotonic saline. Patients received at least 12 weekly immunizations and had topical imiquimod applied over the injection site for costimulation through toll-like receptor 7. The 16 patients with EGFR mutations were given the option of continuing on an EGFR inhibitor, and 9 patients elected to do so.
 

Results

Dr. Lizee said this treatment approach was “very safe,” with only grade 1 treatment-related adverse events. The events were fatigue (n = 2), rash (n = 1), and fever (n = 1).

Seven patients achieved a response after vaccination, and one patient achieved a complete response. All seven responders had EGFR mutations, and four of them were receiving an EGFR inhibitor.

The patients on an EGFR inhibitor had significantly better overall survival than that of EGFR-mutated patients who had stopped taking an EGFR inhibitor – 13.8 months and 7.6 months, respectively (P = .038).

Immune profiling revealed that neoantigen-specific T-cell reactivity was associated with clinical responses. The researchers observed EGFR neoantigen-specific T-cell responses in five responders. In three responders, the strongest response was against a peptide encompassing the L858R driver mutation.

The researchers also found evidence of synergy between EGFR inhibitor therapy and the peptide vaccine. EGFR inhibition caused immunomodulatory pathways in EGFR-mutated cancer cells to favor immune-cell infiltration and HLA-mediated antigen presentation.

“Our mechanistic working model is that, in the circulation, the personalized vaccine increased the T-cell frequency,” Dr. Lizee said. “The EGFR inhibitor increased chemokines and antigen presentation at the tumor site, which then attracted those T cells to migrate to the tumor. Then, recognition of the antigen caused interferon gamma [to increase], which caused, potentially, a feed-forward loop by increasing chemokines and antigen presentation further.”

This research is sponsored by Tianjin Beichen Hospital and funded by Tianjin HengJia Biotechnology Development Co. Ltd. Dr. Lizee disclosed a consulting relationship with Tianjin HengJia Biotechnology Development Co. Ltd.

SOURCE: Lizee G et al. SITC 2019. Abstract O18.

“You and I are living in a time when some miracle drugs no longer perform miracles and families are being ripped apart by a microscopic enemy. The time for action is now and we can be part of the solution,” said Robert R. Redfield, MD, director of the Centers for Disease Control and Prevention in his foreword to the new CDC report on antibiotic resistance.

In this update of the previous 2013 report, the CDC details how antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and 35,000 deaths in the United States each year. The current report uses EHRs and other data sources obtained by the CDC for relevant infections extrapolated to develop national disease incidence. The report focuses on “the top 18 pathogens that require attention now,” advises specific steps be taken to address these pathogens, and puts into perspective the future of antibiotic development, their use and abuse, and the continuing threat of antibiotic resistance.

The CDC categorizes these 18 pathogens as either an urgent, serious, or concerning threat.

Urgent Threats

• Carbapenem-resistant Acinetobacter, which cause pneumonia and wound, bloodstream, and urinary tract infections; they tend to affect patients in ICUs. Of particular concern, some Acinetobacter are resistant to nearly all antibiotics, with few new drugs in development (8,500 hospital infections in 2017; 700 deaths).
• Candida auris, a drug-resistant fungus that was first identified in 2009 in Asia and has quickly become a cause of severe infections around the world; it is extremely difficult to eradicate from health care settings. It began spreading in the United States in 2015, with 323 cases reported in 2018 (90% resistant to at least one antifungal, and 30% resistant to at least two antifungals).
• Clostridioides difficile, which can cause life-threatening diarrhea, most often in people who have taken antibiotics for other conditions. It is the most common health care–associated infection, and although decreasing in the health care system, it has not decreased in community settings (223,900 hospital infections in 2017, and 12,800 estimated deaths).
• Carbapenem-resistant Enterobacteriaceae, which most frequently infect patients who require devices such as catheters and those taking long courses of some antibiotics. Of particular concern is the fact that these bacteria contain a transmissible plasmid that can transfer their drug resistance to other pathogens (13,100 hospital infections in 2017, and 1,100 estimated deaths).
• Drug-resistant Neisseria gonorrhoeae, which is a sexually transmitted disease that can result in life-threatening ectopic pregnancy, lead to infertility, and can increase the risk of getting and giving HIV; it can also cause cardiovascular and neurological problems. It is resistant to all but one class of antibiotics, and half of all infections are resistant to at least one antibiotic (550,000 drug-resistant infections yearly).

Serious Threats

• Drug-resistant Campylobacter.
• Drug-resistant Candida.
• Extended spectrum beta-lactamase–producing Enterobacteriaceae.
• Vancomycin-resistant Enterococci.
• Multidrug-resistant Pseudomonas aeruginosa.
• Drug-resistant nontyphoidal Salmonella.
• Drug-resistant Salmonella serotype Typhi.
• Drug-resistant Shigella.
• Methicillin-resistant Staphylococcus aureus (MRSA).
• Drug-resistant Streptococcus pneumoniae.
• Drug-resistant Tuberculosis.

Concerning Threats

These comprise erythromycin-resistant group A Streptococcus and clindamycin-resistant group B Streptococcus.

In addition, the CDC has established a Watch List of three pathogens to be wary of: azole-resistant Aspergillus fumigatus, drug-resistant Mycoplasma genitalium, and drug-resistant Bordetella pertussis.

Because antibiotic resistance is a global phenomenon caused by and affecting everyone, the CDC provided solutions to the problem of antibiotic resistance at every level of society. This “comprehensive and coordinated response implements the U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria” and includes cooperation with the Department of Health and Human Services, Department of Veterans Affairs, Department of Defense, Department of State, and Department of Agriculture, according to the report.

The key components of this response include using data and new technologies to detect and track antibiotic resistance; infection prevention and containment, especially in terms of outbreak response; improving antibiotic use across populations (one successful example being a 16% decrease of outpatient antibiotic prescribing to children during 2011-2017); improvements in the identification and intervention in the environment including water and soil and in sanitation; and a significant investment in vaccines, diagnostics, and novel therapeutics (the CDC provided nearly $110 million to 96 institutions for work in these areas).

The report also details some hope in the development of new antibiotics. As of June 2019, there were 42 new antibiotics in development, including 4 with new drug applications submitted, 17 with the potential to treat serious gram negative bacteria, and 11 that could address the urgent threats of gonorrhea or C. difficile. Overall, a quarter of these new antibiotics represent a novel drug class or use a novel mechanism of action.

Furthermore, 84% of U.S. hospitals report a stewardship program meeting all seven of CDC’s Core Elements of Hospital Antibiotic Stewardship. Proper stewardship is at the core of preventing the development of new antibiotic resistant pathogen strains.

In addition, the CDC noted a 5% overall decline in antibiotic prescribing in outpatient settings during 2011-2016.

“The problem will get worse if we do not act now, but we can make a difference,” according to Dr. Redfield. “Simply, here’s what works. Preventing infections protects everyone. Improving antibiotic use in people and animals slows the threat and helps preserve today’s drugs and those yet to come. Detecting threats and implementing interventions to keep germs from becoming widespread saves lives.”

In response to the release of the report, the AMA issued a supporting statement and cited its collection of educational resources for physicians focused on antibiotic use, resistance, and stewardship.

Similarly, the Society for Healthcare Epidemiology of America (SHEA) stated that hospitals were “a bright spot” in the CDC report and offered tools and resources available to educate and inform health care professionals about best practices in infection prevention and control, as well as antibiotic stewardship.

[email protected]

SOURCE: CDC. Antibiotic Resistance Threats in the United States 2019.

“You and I are living in a time when some miracle drugs no longer perform miracles and families are being ripped apart by a microscopic enemy. The time for action is now and we can be part of the solution,” said Robert R. Redfield, MD, director of the Centers for Disease Control and Prevention in his foreword to the new CDC report on antibiotic resistance.

In this update of the previous 2013 report, the CDC details how antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and 35,000 deaths in the United States each year. The current report uses EHRs and other data sources obtained by the CDC for relevant infections extrapolated to develop national disease incidence. The report focuses on “the top 18 pathogens that require attention now,” advises specific steps be taken to address these pathogens, and puts into perspective the future of antibiotic development, their use and abuse, and the continuing threat of antibiotic resistance.

The CDC categorizes these 18 pathogens as either an urgent, serious, or concerning threat.

Urgent Threats

• Carbapenem-resistant Acinetobacter, which cause pneumonia and wound, bloodstream, and urinary tract infections; they tend to affect patients in ICUs. Of particular concern, some Acinetobacter are resistant to nearly all antibiotics, with few new drugs in development (8,500 hospital infections in 2017; 700 deaths).
• Candida auris, a drug-resistant fungus that was first identified in 2009 in Asia and has quickly become a cause of severe infections around the world; it is extremely difficult to eradicate from health care settings. It began spreading in the United States in 2015, with 323 cases reported in 2018 (90% resistant to at least one antifungal, and 30% resistant to at least two antifungals).
• Clostridioides difficile, which can cause life-threatening diarrhea, most often in people who have taken antibiotics for other conditions. It is the most common health care–associated infection, and although decreasing in the health care system, it has not decreased in community settings (223,900 hospital infections in 2017, and 12,800 estimated deaths).
• Carbapenem-resistant Enterobacteriaceae, which most frequently infect patients who require devices such as catheters and those taking long courses of some antibiotics. Of particular concern is the fact that these bacteria contain a transmissible plasmid that can transfer their drug resistance to other pathogens (13,100 hospital infections in 2017, and 1,100 estimated deaths).
• Drug-resistant Neisseria gonorrhoeae, which is a sexually transmitted disease that can result in life-threatening ectopic pregnancy, lead to infertility, and can increase the risk of getting and giving HIV; it can also cause cardiovascular and neurological problems. It is resistant to all but one class of antibiotics, and half of all infections are resistant to at least one antibiotic (550,000 drug-resistant infections yearly).

Serious Threats

• Drug-resistant Campylobacter.
• Drug-resistant Candida.
• Extended spectrum beta-lactamase–producing Enterobacteriaceae.
• Vancomycin-resistant Enterococci.
• Multidrug-resistant Pseudomonas aeruginosa.
• Drug-resistant nontyphoidal Salmonella.
• Drug-resistant Salmonella serotype Typhi.
• Drug-resistant Shigella.
• Methicillin-resistant Staphylococcus aureus (MRSA).
• Drug-resistant Streptococcus pneumoniae.
• Drug-resistant Tuberculosis.

Concerning Threats

These comprise erythromycin-resistant group A Streptococcus and clindamycin-resistant group B Streptococcus.

In addition, the CDC has established a Watch List of three pathogens to be wary of: azole-resistant Aspergillus fumigatus, drug-resistant Mycoplasma genitalium, and drug-resistant Bordetella pertussis.

Because antibiotic resistance is a global phenomenon caused by and affecting everyone, the CDC provided solutions to the problem of antibiotic resistance at every level of society. This “comprehensive and coordinated response implements the U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria” and includes cooperation with the Department of Health and Human Services, Department of Veterans Affairs, Department of Defense, Department of State, and Department of Agriculture, according to the report.

The key components of this response include using data and new technologies to detect and track antibiotic resistance; infection prevention and containment, especially in terms of outbreak response; improving antibiotic use across populations (one successful example being a 16% decrease of outpatient antibiotic prescribing to children during 2011-2017); improvements in the identification and intervention in the environment including water and soil and in sanitation; and a significant investment in vaccines, diagnostics, and novel therapeutics (the CDC provided nearly $110 million to 96 institutions for work in these areas).

The report also details some hope in the development of new antibiotics. As of June 2019, there were 42 new antibiotics in development, including 4 with new drug applications submitted, 17 with the potential to treat serious gram negative bacteria, and 11 that could address the urgent threats of gonorrhea or C. difficile. Overall, a quarter of these new antibiotics represent a novel drug class or use a novel mechanism of action.

Furthermore, 84% of U.S. hospitals report a stewardship program meeting all seven of CDC’s Core Elements of Hospital Antibiotic Stewardship. Proper stewardship is at the core of preventing the development of new antibiotic resistant pathogen strains.

In addition, the CDC noted a 5% overall decline in antibiotic prescribing in outpatient settings during 2011-2016.

“The problem will get worse if we do not act now, but we can make a difference,” according to Dr. Redfield. “Simply, here’s what works. Preventing infections protects everyone. Improving antibiotic use in people and animals slows the threat and helps preserve today’s drugs and those yet to come. Detecting threats and implementing interventions to keep germs from becoming widespread saves lives.”

In response to the release of the report, the AMA issued a supporting statement and cited its collection of educational resources for physicians focused on antibiotic use, resistance, and stewardship.

Similarly, the Society for Healthcare Epidemiology of America (SHEA) stated that hospitals were “a bright spot” in the CDC report and offered tools and resources available to educate and inform health care professionals about best practices in infection prevention and control, as well as antibiotic stewardship.

[email protected]

SOURCE: CDC. Antibiotic Resistance Threats in the United States 2019.

“You and I are living in a time when some miracle drugs no longer perform miracles and families are being ripped apart by a microscopic enemy. The time for action is now and we can be part of the solution,” said Robert R. Redfield, MD, director of the Centers for Disease Control and Prevention in his foreword to the new CDC report on antibiotic resistance.

In this update of the previous 2013 report, the CDC details how antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and 35,000 deaths in the United States each year. The current report uses EHRs and other data sources obtained by the CDC for relevant infections extrapolated to develop national disease incidence. The report focuses on “the top 18 pathogens that require attention now,” advises specific steps be taken to address these pathogens, and puts into perspective the future of antibiotic development, their use and abuse, and the continuing threat of antibiotic resistance.

The CDC categorizes these 18 pathogens as either an urgent, serious, or concerning threat.

Urgent Threats

• Carbapenem-resistant Acinetobacter, which cause pneumonia and wound, bloodstream, and urinary tract infections; they tend to affect patients in ICUs. Of particular concern, some Acinetobacter are resistant to nearly all antibiotics, with few new drugs in development (8,500 hospital infections in 2017; 700 deaths).
• Candida auris, a drug-resistant fungus that was first identified in 2009 in Asia and has quickly become a cause of severe infections around the world; it is extremely difficult to eradicate from health care settings. It began spreading in the United States in 2015, with 323 cases reported in 2018 (90% resistant to at least one antifungal, and 30% resistant to at least two antifungals).
• Clostridioides difficile, which can cause life-threatening diarrhea, most often in people who have taken antibiotics for other conditions. It is the most common health care–associated infection, and although decreasing in the health care system, it has not decreased in community settings (223,900 hospital infections in 2017, and 12,800 estimated deaths).
• Carbapenem-resistant Enterobacteriaceae, which most frequently infect patients who require devices such as catheters and those taking long courses of some antibiotics. Of particular concern is the fact that these bacteria contain a transmissible plasmid that can transfer their drug resistance to other pathogens (13,100 hospital infections in 2017, and 1,100 estimated deaths).
• Drug-resistant Neisseria gonorrhoeae, which is a sexually transmitted disease that can result in life-threatening ectopic pregnancy, lead to infertility, and can increase the risk of getting and giving HIV; it can also cause cardiovascular and neurological problems. It is resistant to all but one class of antibiotics, and half of all infections are resistant to at least one antibiotic (550,000 drug-resistant infections yearly).

Serious Threats

• Drug-resistant Campylobacter.
• Drug-resistant Candida.
• Extended spectrum beta-lactamase–producing Enterobacteriaceae.
• Vancomycin-resistant Enterococci.
• Multidrug-resistant Pseudomonas aeruginosa.
• Drug-resistant nontyphoidal Salmonella.
• Drug-resistant Salmonella serotype Typhi.
• Drug-resistant Shigella.
• Methicillin-resistant Staphylococcus aureus (MRSA).
• Drug-resistant Streptococcus pneumoniae.
• Drug-resistant Tuberculosis.

Concerning Threats

These comprise erythromycin-resistant group A Streptococcus and clindamycin-resistant group B Streptococcus.

In addition, the CDC has established a Watch List of three pathogens to be wary of: azole-resistant Aspergillus fumigatus, drug-resistant Mycoplasma genitalium, and drug-resistant Bordetella pertussis.

Because antibiotic resistance is a global phenomenon caused by and affecting everyone, the CDC provided solutions to the problem of antibiotic resistance at every level of society. This “comprehensive and coordinated response implements the U.S. National Action Plan for Combating Antibiotic-Resistant Bacteria” and includes cooperation with the Department of Health and Human Services, Department of Veterans Affairs, Department of Defense, Department of State, and Department of Agriculture, according to the report.

The key components of this response include using data and new technologies to detect and track antibiotic resistance; infection prevention and containment, especially in terms of outbreak response; improving antibiotic use across populations (one successful example being a 16% decrease of outpatient antibiotic prescribing to children during 2011-2017); improvements in the identification and intervention in the environment including water and soil and in sanitation; and a significant investment in vaccines, diagnostics, and novel therapeutics (the CDC provided nearly $110 million to 96 institutions for work in these areas).

The report also details some hope in the development of new antibiotics. As of June 2019, there were 42 new antibiotics in development, including 4 with new drug applications submitted, 17 with the potential to treat serious gram negative bacteria, and 11 that could address the urgent threats of gonorrhea or C. difficile. Overall, a quarter of these new antibiotics represent a novel drug class or use a novel mechanism of action.

Furthermore, 84% of U.S. hospitals report a stewardship program meeting all seven of CDC’s Core Elements of Hospital Antibiotic Stewardship. Proper stewardship is at the core of preventing the development of new antibiotic resistant pathogen strains.

In addition, the CDC noted a 5% overall decline in antibiotic prescribing in outpatient settings during 2011-2016.

“The problem will get worse if we do not act now, but we can make a difference,” according to Dr. Redfield. “Simply, here’s what works. Preventing infections protects everyone. Improving antibiotic use in people and animals slows the threat and helps preserve today’s drugs and those yet to come. Detecting threats and implementing interventions to keep germs from becoming widespread saves lives.”

In response to the release of the report, the AMA issued a supporting statement and cited its collection of educational resources for physicians focused on antibiotic use, resistance, and stewardship.

Similarly, the Society for Healthcare Epidemiology of America (SHEA) stated that hospitals were “a bright spot” in the CDC report and offered tools and resources available to educate and inform health care professionals about best practices in infection prevention and control, as well as antibiotic stewardship.

[email protected]

SOURCE: CDC. Antibiotic Resistance Threats in the United States 2019.

NEW ORLEANS – In the opinion of Jason E. Reynolds, MD, PhD,, primary care pediatricians are uniquely qualified to treat adolescents with opioid use disorder (OUD).

Doug Brunk/MDedge News

“One of the real benefits of treatment in primary care is that it removes the stigma so that these patients aren’t isolated into addiction clinics; they’re being treated by providers that they know well and that their family knows well,” Dr. Reynolds, a pediatrician who practices in Wareham, Mass., said at the annual meeting of the American Academy of Pediatrics. “That feels a lot better to them, and I think it makes a statement in the community that these people don’t need to be isolated. Anything we can do to reduce the stigma of opioid use disorder is important. We in primary care are well suited to manage chronic disease over the continuum.”

In 2016, the AAP released a policy statement advocating for pediatricians to consider providing medication-assisted treatment to patients with OUD (Pediatrics. 2016;138[3]e20161893). The statement cited results from a nationally representative sample of 345 addiction treatment programs serving adolescents and adults. It found that fewer than 50% of those programs used medication-assisted treatment (J Addict Med. 2011;5[1]:21-7). “When they looked at patients who actually had opioid dependence, the numbers were even lower,” said Dr. Reynolds, who was not involved with the study. “In fact, 34% of opioid-dependent patients received medication-assisted treatment. When they stratified it by age, the younger you were, the less likely you were to be treated. Only 11.5% of youth under 18 are actually being treated. We know that youth with opioid use disorders have very bad health outcomes over their lifetime. The fact that such few patients receive what is considered to be a gold-standard treatment is really alarming.”

Dr. Reynolds acknowledged that many perceived barriers exist to providing treatment of OUD in pediatric primary care, including the fact that patients with addiction are not easy to treat. “They can be manipulative and can make you feel both sad for them and angry at them within the same visit,” he said. “They also have complex needs. For many of these patients, it’s not just that they use opiates; they have medical problems and psychological diagnoses, and oftentimes they have social issues such as being in foster care. They also may have issues with their parents, employer, or their school, so there are many needs that need to be juggled. That can be overwhelming.”

However, he said that such patients “are actually in our wheelhouse, because as primary care physicians we’re used to coordinating care. These are the perfect patients to have a medical home. We manage chronic disease over the continuum of care. This is a chronic disease, and we have to help patients.”

Another perceived barrier for treating adolescents with OUD relates to reimbursement. While most patients with OUD have insurance, Dr. Reynolds finds that the requirement for prior authorizations can result in delay of treatment and poses an unnecessary burden on care providers. “It’s an administrative task that either the physician or the office staff has to take care of,” he said. “Interestingly, reimbursement ranks as a low concern in studies of buprenorphine providers. That tells me that this is not a major hurdle.”

Pediatricians also cite a lack of knowledge as a reason they’re leery of providing OUD treatment in their office. “They wonder: ‘How do I do this? What’s the right way to do it? Are there best practices?’ ” Dr. Reynolds said. “There’s a feeling that it must be dangerous, the idea that if I don’t do it right I’m going to hurt somebody. The reality is, buprenorphine is no more dangerous than any of the other opiates. Technically, because it’s a partial agonist, it’s probably less dangerous than some of the opiates that we prescribe. It’s no more dangerous than prescribing amitriptyline for chronic pain.”

One key resource, the Providers Clinical Support System (www.pcssnow.org), provides resources for clinicians and family members, education and training, and access to mentoring. Another resource, the American Society of Addiction Medicine (www.asam.org), includes clinical practice guidelines, online courses and training on the treatment of OUD, and sample consent and opioid-withdrawal forms. Dr. Reynolds characterized learning how to treat patients with OUD as no different than learning step therapy for asthma. “Once you look into it, you realize that there’s no sort of magic behind this,” he said. “It’s something that any of us can do. Staff can be trained. There are modules to train your staff into the protocols. Learn the knowledge and put it into action. Have the confidence and the knowledge.”

The Drug Addiction and Treatment Act of 2000 set up the waiver process by which physicians can obtain a waiver from the Drug Enforcement Agency after completing an 8-hour CME course on substance abuse disorder and buprenorphine prescribing. To receive a waiver to practice opioid dependency treatment with approved buprenorphine medications, a clinician must notify the SAMHSA Center for Substance Abuse Treatment of their intent to practice this form of medication-assisted treatment.

Dr. Reynolds acknowledged that not every practice is equipped to provide psychosocial support for complex patients with OUD. “When I first started this in 2017, I wanted to make sure that my patients were in some form of counseling,” he said. “However, the medical literature shows that you can treat OUD without counseling, and some of those patients will be fine, too. There have been reports that just going to Narcotics Anonymous meetings weekly has been shown to improve the effectiveness of medication-assisted treatment.”

For clinicians concerned about having backup when they face challenging cases, data shows that having more than one waivered provider in a practice is associated with completing waiver training. “This makes sense,” Dr. Reynolds said. “We like to be able to discuss our cases with colleagues, but a lot of us don’t want to be on call 365 days a year for our patients. Shared responsibility makes it easier. Access to specialty telemedicine consult has also been identified as a facilitator to physicians prescribing medical-assisted therapy.”

He concluded his presentation by noting that increasing numbers of OUD patients are initiating buprenorphine treatment in the ED. “That takes advantage of the fact that most of these patients present to the emergency room after receiving Narcan for an overdose,” Dr. Reynolds said. “In the emergency room, they’re counseled and instructed on how to start buprenorphine, they’re given the first dose, and they’re told to go home and avoid using any other opiates for 24 hours, start the buprenorphine, and follow up with their primary care doctor or an addiction medicine specialist in 3 days. In my community, this is what our local emergency department is doing for adult patients, except they’re not referring back to primary care. They’re referring to a hospital-based addiction medicine specialist. This is a way to increase access and get people started on buprenorphine treatment.”

Dr. Reynolds reported having no financial disclosures.

[email protected]

NEW ORLEANS – In the opinion of Jason E. Reynolds, MD, PhD,, primary care pediatricians are uniquely qualified to treat adolescents with opioid use disorder (OUD).

Doug Brunk/MDedge News

“One of the real benefits of treatment in primary care is that it removes the stigma so that these patients aren’t isolated into addiction clinics; they’re being treated by providers that they know well and that their family knows well,” Dr. Reynolds, a pediatrician who practices in Wareham, Mass., said at the annual meeting of the American Academy of Pediatrics. “That feels a lot better to them, and I think it makes a statement in the community that these people don’t need to be isolated. Anything we can do to reduce the stigma of opioid use disorder is important. We in primary care are well suited to manage chronic disease over the continuum.”

In 2016, the AAP released a policy statement advocating for pediatricians to consider providing medication-assisted treatment to patients with OUD (Pediatrics. 2016;138[3]e20161893). The statement cited results from a nationally representative sample of 345 addiction treatment programs serving adolescents and adults. It found that fewer than 50% of those programs used medication-assisted treatment (J Addict Med. 2011;5[1]:21-7). “When they looked at patients who actually had opioid dependence, the numbers were even lower,” said Dr. Reynolds, who was not involved with the study. “In fact, 34% of opioid-dependent patients received medication-assisted treatment. When they stratified it by age, the younger you were, the less likely you were to be treated. Only 11.5% of youth under 18 are actually being treated. We know that youth with opioid use disorders have very bad health outcomes over their lifetime. The fact that such few patients receive what is considered to be a gold-standard treatment is really alarming.”

Dr. Reynolds acknowledged that many perceived barriers exist to providing treatment of OUD in pediatric primary care, including the fact that patients with addiction are not easy to treat. “They can be manipulative and can make you feel both sad for them and angry at them within the same visit,” he said. “They also have complex needs. For many of these patients, it’s not just that they use opiates; they have medical problems and psychological diagnoses, and oftentimes they have social issues such as being in foster care. They also may have issues with their parents, employer, or their school, so there are many needs that need to be juggled. That can be overwhelming.”

However, he said that such patients “are actually in our wheelhouse, because as primary care physicians we’re used to coordinating care. These are the perfect patients to have a medical home. We manage chronic disease over the continuum of care. This is a chronic disease, and we have to help patients.”

Another perceived barrier for treating adolescents with OUD relates to reimbursement. While most patients with OUD have insurance, Dr. Reynolds finds that the requirement for prior authorizations can result in delay of treatment and poses an unnecessary burden on care providers. “It’s an administrative task that either the physician or the office staff has to take care of,” he said. “Interestingly, reimbursement ranks as a low concern in studies of buprenorphine providers. That tells me that this is not a major hurdle.”

Pediatricians also cite a lack of knowledge as a reason they’re leery of providing OUD treatment in their office. “They wonder: ‘How do I do this? What’s the right way to do it? Are there best practices?’ ” Dr. Reynolds said. “There’s a feeling that it must be dangerous, the idea that if I don’t do it right I’m going to hurt somebody. The reality is, buprenorphine is no more dangerous than any of the other opiates. Technically, because it’s a partial agonist, it’s probably less dangerous than some of the opiates that we prescribe. It’s no more dangerous than prescribing amitriptyline for chronic pain.”

One key resource, the Providers Clinical Support System (www.pcssnow.org), provides resources for clinicians and family members, education and training, and access to mentoring. Another resource, the American Society of Addiction Medicine (www.asam.org), includes clinical practice guidelines, online courses and training on the treatment of OUD, and sample consent and opioid-withdrawal forms. Dr. Reynolds characterized learning how to treat patients with OUD as no different than learning step therapy for asthma. “Once you look into it, you realize that there’s no sort of magic behind this,” he said. “It’s something that any of us can do. Staff can be trained. There are modules to train your staff into the protocols. Learn the knowledge and put it into action. Have the confidence and the knowledge.”

The Drug Addiction and Treatment Act of 2000 set up the waiver process by which physicians can obtain a waiver from the Drug Enforcement Agency after completing an 8-hour CME course on substance abuse disorder and buprenorphine prescribing. To receive a waiver to practice opioid dependency treatment with approved buprenorphine medications, a clinician must notify the SAMHSA Center for Substance Abuse Treatment of their intent to practice this form of medication-assisted treatment.

Dr. Reynolds acknowledged that not every practice is equipped to provide psychosocial support for complex patients with OUD. “When I first started this in 2017, I wanted to make sure that my patients were in some form of counseling,” he said. “However, the medical literature shows that you can treat OUD without counseling, and some of those patients will be fine, too. There have been reports that just going to Narcotics Anonymous meetings weekly has been shown to improve the effectiveness of medication-assisted treatment.”

For clinicians concerned about having backup when they face challenging cases, data shows that having more than one waivered provider in a practice is associated with completing waiver training. “This makes sense,” Dr. Reynolds said. “We like to be able to discuss our cases with colleagues, but a lot of us don’t want to be on call 365 days a year for our patients. Shared responsibility makes it easier. Access to specialty telemedicine consult has also been identified as a facilitator to physicians prescribing medical-assisted therapy.”

He concluded his presentation by noting that increasing numbers of OUD patients are initiating buprenorphine treatment in the ED. “That takes advantage of the fact that most of these patients present to the emergency room after receiving Narcan for an overdose,” Dr. Reynolds said. “In the emergency room, they’re counseled and instructed on how to start buprenorphine, they’re given the first dose, and they’re told to go home and avoid using any other opiates for 24 hours, start the buprenorphine, and follow up with their primary care doctor or an addiction medicine specialist in 3 days. In my community, this is what our local emergency department is doing for adult patients, except they’re not referring back to primary care. They’re referring to a hospital-based addiction medicine specialist. This is a way to increase access and get people started on buprenorphine treatment.”

Dr. Reynolds reported having no financial disclosures.

[email protected]

NEW ORLEANS – In the opinion of Jason E. Reynolds, MD, PhD,, primary care pediatricians are uniquely qualified to treat adolescents with opioid use disorder (OUD).

Doug Brunk/MDedge News

“One of the real benefits of treatment in primary care is that it removes the stigma so that these patients aren’t isolated into addiction clinics; they’re being treated by providers that they know well and that their family knows well,” Dr. Reynolds, a pediatrician who practices in Wareham, Mass., said at the annual meeting of the American Academy of Pediatrics. “That feels a lot better to them, and I think it makes a statement in the community that these people don’t need to be isolated. Anything we can do to reduce the stigma of opioid use disorder is important. We in primary care are well suited to manage chronic disease over the continuum.”

In 2016, the AAP released a policy statement advocating for pediatricians to consider providing medication-assisted treatment to patients with OUD (Pediatrics. 2016;138[3]e20161893). The statement cited results from a nationally representative sample of 345 addiction treatment programs serving adolescents and adults. It found that fewer than 50% of those programs used medication-assisted treatment (J Addict Med. 2011;5[1]:21-7). “When they looked at patients who actually had opioid dependence, the numbers were even lower,” said Dr. Reynolds, who was not involved with the study. “In fact, 34% of opioid-dependent patients received medication-assisted treatment. When they stratified it by age, the younger you were, the less likely you were to be treated. Only 11.5% of youth under 18 are actually being treated. We know that youth with opioid use disorders have very bad health outcomes over their lifetime. The fact that such few patients receive what is considered to be a gold-standard treatment is really alarming.”

Dr. Reynolds acknowledged that many perceived barriers exist to providing treatment of OUD in pediatric primary care, including the fact that patients with addiction are not easy to treat. “They can be manipulative and can make you feel both sad for them and angry at them within the same visit,” he said. “They also have complex needs. For many of these patients, it’s not just that they use opiates; they have medical problems and psychological diagnoses, and oftentimes they have social issues such as being in foster care. They also may have issues with their parents, employer, or their school, so there are many needs that need to be juggled. That can be overwhelming.”

However, he said that such patients “are actually in our wheelhouse, because as primary care physicians we’re used to coordinating care. These are the perfect patients to have a medical home. We manage chronic disease over the continuum of care. This is a chronic disease, and we have to help patients.”

Another perceived barrier for treating adolescents with OUD relates to reimbursement. While most patients with OUD have insurance, Dr. Reynolds finds that the requirement for prior authorizations can result in delay of treatment and poses an unnecessary burden on care providers. “It’s an administrative task that either the physician or the office staff has to take care of,” he said. “Interestingly, reimbursement ranks as a low concern in studies of buprenorphine providers. That tells me that this is not a major hurdle.”

Pediatricians also cite a lack of knowledge as a reason they’re leery of providing OUD treatment in their office. “They wonder: ‘How do I do this? What’s the right way to do it? Are there best practices?’ ” Dr. Reynolds said. “There’s a feeling that it must be dangerous, the idea that if I don’t do it right I’m going to hurt somebody. The reality is, buprenorphine is no more dangerous than any of the other opiates. Technically, because it’s a partial agonist, it’s probably less dangerous than some of the opiates that we prescribe. It’s no more dangerous than prescribing amitriptyline for chronic pain.”

One key resource, the Providers Clinical Support System (www.pcssnow.org), provides resources for clinicians and family members, education and training, and access to mentoring. Another resource, the American Society of Addiction Medicine (www.asam.org), includes clinical practice guidelines, online courses and training on the treatment of OUD, and sample consent and opioid-withdrawal forms. Dr. Reynolds characterized learning how to treat patients with OUD as no different than learning step therapy for asthma. “Once you look into it, you realize that there’s no sort of magic behind this,” he said. “It’s something that any of us can do. Staff can be trained. There are modules to train your staff into the protocols. Learn the knowledge and put it into action. Have the confidence and the knowledge.”

The Drug Addiction and Treatment Act of 2000 set up the waiver process by which physicians can obtain a waiver from the Drug Enforcement Agency after completing an 8-hour CME course on substance abuse disorder and buprenorphine prescribing. To receive a waiver to practice opioid dependency treatment with approved buprenorphine medications, a clinician must notify the SAMHSA Center for Substance Abuse Treatment of their intent to practice this form of medication-assisted treatment.

Dr. Reynolds acknowledged that not every practice is equipped to provide psychosocial support for complex patients with OUD. “When I first started this in 2017, I wanted to make sure that my patients were in some form of counseling,” he said. “However, the medical literature shows that you can treat OUD without counseling, and some of those patients will be fine, too. There have been reports that just going to Narcotics Anonymous meetings weekly has been shown to improve the effectiveness of medication-assisted treatment.”

For clinicians concerned about having backup when they face challenging cases, data shows that having more than one waivered provider in a practice is associated with completing waiver training. “This makes sense,” Dr. Reynolds said. “We like to be able to discuss our cases with colleagues, but a lot of us don’t want to be on call 365 days a year for our patients. Shared responsibility makes it easier. Access to specialty telemedicine consult has also been identified as a facilitator to physicians prescribing medical-assisted therapy.”

He concluded his presentation by noting that increasing numbers of OUD patients are initiating buprenorphine treatment in the ED. “That takes advantage of the fact that most of these patients present to the emergency room after receiving Narcan for an overdose,” Dr. Reynolds said. “In the emergency room, they’re counseled and instructed on how to start buprenorphine, they’re given the first dose, and they’re told to go home and avoid using any other opiates for 24 hours, start the buprenorphine, and follow up with their primary care doctor or an addiction medicine specialist in 3 days. In my community, this is what our local emergency department is doing for adult patients, except they’re not referring back to primary care. They’re referring to a hospital-based addiction medicine specialist. This is a way to increase access and get people started on buprenorphine treatment.”

Dr. Reynolds reported having no financial disclosures.

[email protected]

VANCOUVER – Two new randomized trials demonstrate that pain following minimally invasive gynecologic surgery can be successfully managed using reduced opioid prescriptions.

Ingram Publishing/Thinkstock

In each case, patients were randomized to receive higher or lower numbers of oxycodone tablets. In both trials, the lower amount was five 5-mg oxycodone tablets. The work should reassure surgeons who wish to change their prescribing patterns, but may worry about patient dissatisfaction, at least in the context of prolapse repair and benign minor gynecologic laparoscopy, which were the focus of the two studies.

The ob.gyn. literature cites rates of 4%-6% of persistent opioid use after surgery on opioid-naive patients, and that’s a risk that needs to be addressed. “If we look at this as a risk factor of our surgical process, this is much higher than any other risk in patients undergoing surgery, and it’s not something we routinely talk to patients about,” Kari Plewniak, MD, an ob.gyn. at Montefiore Medical Center, New York, said during her presentation on pain control during benign gynecologic laparoscopy at the meeting sponsored by AAGL.

The trials provide some welcome guidance. “They provide pretty concrete guidelines with strong evidence of safety, so this is really helpful,” said Sean Dowdy, MD, chair of gynecologic oncology at Mayo Clinic in Rochester, Minn., while speaking as a discussant for the presentations.

Emily Davidson, MD, and associates at the Cleveland Clinic conducted a single-institution, noninferiority trial of standard- versus reduced-prescription opioids in 116 women undergoing prolapse repair. Half were randomized to receive 28 tablets of 5 mg oxycodone (routine arm) and half were prescribed just 5 tablets (reduced arm). All patients also received multimodal pain therapy featuring acetaminophen and ibuprofen. The mean age of patients was 62 years, 91% were white, and 84% were post menopausal. The most common surgery was hysterectomy combined with native tissue repair (60.2%), followed by vaginal colpopexy (15.3%), hysteropexy (15.3%), and sacrocolpopexy (9.3%).

At their postsurgical visit, patients were asked about their satisfaction with their postoperative pain management; 93% in the reduced arm reported that they were very satisfied or somewhat satisfied, as did 93% in the routine arm, which met the standard for noninferiority with a 15% margin. About 15% of patients in the reduced arm used more opioids than originally prescribed, compared with 2% of patients in the routine arm (P less than .01). The reduced arm had an average of 4 unused opioid tablets, compared with 26 in the routine arm. On average, the reduced arm used one tablet, compared with three in the routine arm (P = .03).

The researchers suggested that clinicians should consider prescribing 5-10 tablets for most patients, and all patients should receive multimodal pain management.

The noninferiority nature of the design was welcome, according to Dr. Dowdy. “I think we need to do more noninferiority trial designs because it allows us to make more observations about other parts of the value equation, so if we have two interventions that are equivalent, we can pick the one that has the best patient experience and the lowest cost, so it simplifies a lot of our management.”

The other study, conducted at Montefiore Medical Center, set out to see if a similar regimen of 5 5-mg oxycodone tablets, combined with acetaminophen and ibuprofen, could adequately manage postoperative pain after minor benign gynecologic laparoscopy (excluding hysterectomy), compared with a 10-tablet regimen. All patients received 25 tablets of 600 mg ibuprofen (1 tablet every 6 hours or as needed), plus 50 tablets of 250 mg acetaminophen (1-2 tablets every 6 hours or as needed).

The median number of opioid tablets taken was 2.0 in the 5-tablet group and 2.5 in the 10-tablet group; 32% and 28% took no tablets, and 68% and 65% took three or fewer tablets in the respective groups. The median number of leftover opioid tablets was 3 in the 5-tablet group and 8 in the 10-tablet group, reported Dr. Plewniak.

The studies are a good first step, but more is needed, according to Dr. Dowdy. It’s important to begin looking at more-challenging patient groups, such as those who are not opioid naive, as well as patients taking buprenorphine. “That creates some unique challenges with postoperative pain management,” he said.

Dr. Dowdy, Dr. Davidson, and Dr. Plewniak have no relevant financial disclosures.*

* This article was updated 11/27/2019.

VANCOUVER – Two new randomized trials demonstrate that pain following minimally invasive gynecologic surgery can be successfully managed using reduced opioid prescriptions.

Ingram Publishing/Thinkstock

In each case, patients were randomized to receive higher or lower numbers of oxycodone tablets. In both trials, the lower amount was five 5-mg oxycodone tablets. The work should reassure surgeons who wish to change their prescribing patterns, but may worry about patient dissatisfaction, at least in the context of prolapse repair and benign minor gynecologic laparoscopy, which were the focus of the two studies.

The ob.gyn. literature cites rates of 4%-6% of persistent opioid use after surgery on opioid-naive patients, and that’s a risk that needs to be addressed. “If we look at this as a risk factor of our surgical process, this is much higher than any other risk in patients undergoing surgery, and it’s not something we routinely talk to patients about,” Kari Plewniak, MD, an ob.gyn. at Montefiore Medical Center, New York, said during her presentation on pain control during benign gynecologic laparoscopy at the meeting sponsored by AAGL.

The trials provide some welcome guidance. “They provide pretty concrete guidelines with strong evidence of safety, so this is really helpful,” said Sean Dowdy, MD, chair of gynecologic oncology at Mayo Clinic in Rochester, Minn., while speaking as a discussant for the presentations.

Emily Davidson, MD, and associates at the Cleveland Clinic conducted a single-institution, noninferiority trial of standard- versus reduced-prescription opioids in 116 women undergoing prolapse repair. Half were randomized to receive 28 tablets of 5 mg oxycodone (routine arm) and half were prescribed just 5 tablets (reduced arm). All patients also received multimodal pain therapy featuring acetaminophen and ibuprofen. The mean age of patients was 62 years, 91% were white, and 84% were post menopausal. The most common surgery was hysterectomy combined with native tissue repair (60.2%), followed by vaginal colpopexy (15.3%), hysteropexy (15.3%), and sacrocolpopexy (9.3%).

At their postsurgical visit, patients were asked about their satisfaction with their postoperative pain management; 93% in the reduced arm reported that they were very satisfied or somewhat satisfied, as did 93% in the routine arm, which met the standard for noninferiority with a 15% margin. About 15% of patients in the reduced arm used more opioids than originally prescribed, compared with 2% of patients in the routine arm (P less than .01). The reduced arm had an average of 4 unused opioid tablets, compared with 26 in the routine arm. On average, the reduced arm used one tablet, compared with three in the routine arm (P = .03).

The researchers suggested that clinicians should consider prescribing 5-10 tablets for most patients, and all patients should receive multimodal pain management.

The noninferiority nature of the design was welcome, according to Dr. Dowdy. “I think we need to do more noninferiority trial designs because it allows us to make more observations about other parts of the value equation, so if we have two interventions that are equivalent, we can pick the one that has the best patient experience and the lowest cost, so it simplifies a lot of our management.”

The other study, conducted at Montefiore Medical Center, set out to see if a similar regimen of 5 5-mg oxycodone tablets, combined with acetaminophen and ibuprofen, could adequately manage postoperative pain after minor benign gynecologic laparoscopy (excluding hysterectomy), compared with a 10-tablet regimen. All patients received 25 tablets of 600 mg ibuprofen (1 tablet every 6 hours or as needed), plus 50 tablets of 250 mg acetaminophen (1-2 tablets every 6 hours or as needed).

The median number of opioid tablets taken was 2.0 in the 5-tablet group and 2.5 in the 10-tablet group; 32% and 28% took no tablets, and 68% and 65% took three or fewer tablets in the respective groups. The median number of leftover opioid tablets was 3 in the 5-tablet group and 8 in the 10-tablet group, reported Dr. Plewniak.

The studies are a good first step, but more is needed, according to Dr. Dowdy. It’s important to begin looking at more-challenging patient groups, such as those who are not opioid naive, as well as patients taking buprenorphine. “That creates some unique challenges with postoperative pain management,” he said.

Dr. Dowdy, Dr. Davidson, and Dr. Plewniak have no relevant financial disclosures.*

* This article was updated 11/27/2019.

VANCOUVER – Two new randomized trials demonstrate that pain following minimally invasive gynecologic surgery can be successfully managed using reduced opioid prescriptions.

Ingram Publishing/Thinkstock

In each case, patients were randomized to receive higher or lower numbers of oxycodone tablets. In both trials, the lower amount was five 5-mg oxycodone tablets. The work should reassure surgeons who wish to change their prescribing patterns, but may worry about patient dissatisfaction, at least in the context of prolapse repair and benign minor gynecologic laparoscopy, which were the focus of the two studies.

The ob.gyn. literature cites rates of 4%-6% of persistent opioid use after surgery on opioid-naive patients, and that’s a risk that needs to be addressed. “If we look at this as a risk factor of our surgical process, this is much higher than any other risk in patients undergoing surgery, and it’s not something we routinely talk to patients about,” Kari Plewniak, MD, an ob.gyn. at Montefiore Medical Center, New York, said during her presentation on pain control during benign gynecologic laparoscopy at the meeting sponsored by AAGL.

The trials provide some welcome guidance. “They provide pretty concrete guidelines with strong evidence of safety, so this is really helpful,” said Sean Dowdy, MD, chair of gynecologic oncology at Mayo Clinic in Rochester, Minn., while speaking as a discussant for the presentations.

Emily Davidson, MD, and associates at the Cleveland Clinic conducted a single-institution, noninferiority trial of standard- versus reduced-prescription opioids in 116 women undergoing prolapse repair. Half were randomized to receive 28 tablets of 5 mg oxycodone (routine arm) and half were prescribed just 5 tablets (reduced arm). All patients also received multimodal pain therapy featuring acetaminophen and ibuprofen. The mean age of patients was 62 years, 91% were white, and 84% were post menopausal. The most common surgery was hysterectomy combined with native tissue repair (60.2%), followed by vaginal colpopexy (15.3%), hysteropexy (15.3%), and sacrocolpopexy (9.3%).

At their postsurgical visit, patients were asked about their satisfaction with their postoperative pain management; 93% in the reduced arm reported that they were very satisfied or somewhat satisfied, as did 93% in the routine arm, which met the standard for noninferiority with a 15% margin. About 15% of patients in the reduced arm used more opioids than originally prescribed, compared with 2% of patients in the routine arm (P less than .01). The reduced arm had an average of 4 unused opioid tablets, compared with 26 in the routine arm. On average, the reduced arm used one tablet, compared with three in the routine arm (P = .03).

The researchers suggested that clinicians should consider prescribing 5-10 tablets for most patients, and all patients should receive multimodal pain management.

The noninferiority nature of the design was welcome, according to Dr. Dowdy. “I think we need to do more noninferiority trial designs because it allows us to make more observations about other parts of the value equation, so if we have two interventions that are equivalent, we can pick the one that has the best patient experience and the lowest cost, so it simplifies a lot of our management.”

The other study, conducted at Montefiore Medical Center, set out to see if a similar regimen of 5 5-mg oxycodone tablets, combined with acetaminophen and ibuprofen, could adequately manage postoperative pain after minor benign gynecologic laparoscopy (excluding hysterectomy), compared with a 10-tablet regimen. All patients received 25 tablets of 600 mg ibuprofen (1 tablet every 6 hours or as needed), plus 50 tablets of 250 mg acetaminophen (1-2 tablets every 6 hours or as needed).

The median number of opioid tablets taken was 2.0 in the 5-tablet group and 2.5 in the 10-tablet group; 32% and 28% took no tablets, and 68% and 65% took three or fewer tablets in the respective groups. The median number of leftover opioid tablets was 3 in the 5-tablet group and 8 in the 10-tablet group, reported Dr. Plewniak.

The studies are a good first step, but more is needed, according to Dr. Dowdy. It’s important to begin looking at more-challenging patient groups, such as those who are not opioid naive, as well as patients taking buprenorphine. “That creates some unique challenges with postoperative pain management,” he said.

Dr. Dowdy, Dr. Davidson, and Dr. Plewniak have no relevant financial disclosures.*

* This article was updated 11/27/2019.

Breast cancer survivors may have a lower prevalence of cardiac risk factors at the time of first myocardial infarction and better outcomes compared with those having a first MI from the general population, according to findings from a retrospective study.

In addition, women without breast cancer were younger at the time of first MI compared with survivors, wrote Srikanth Yandrapalli, MD, of New York Medical College, Valhalla, and colleagues. Their report is in the American Journal of Medicine.

The researchers identified 1,644,032 women with a first MI, 56,842 of whom were breast cancer survivors. The team evaluated differences in the prevalence of cardiac risk factors and related outcomes in breast cancer survivors in comparison to the general population.

At baseline, the mean age of subjects with a history of breast cancer was 77 years (range, 11 years), while the mean age of women without breast cancer was 71 years (range, 15 years).

Clinical data were collected from the United States National Inpatient Sample for January 2005 to September 2015. Other outcomes assessed were differences in baseline characteristics and the rate of in-hospital mortality in both groups.

After analysis, the researchers found that breast cancer survivors had a lower prevalence of diabetes mellitus (30.1% vs. 33.1%), obesity (9.4% vs. 13.0%), and smoking (24.1% vs. 27.0%), but higher rates of dyslipidemia (52.7% vs. 48.4%) and hypertension (73.6% vs. 68.1%), compared with women without breast cancer (All P less than .001).

With respect to age, women without breast cancer were 6 years younger than breast cancer survivors at the time of first acute MI (mean age, 71 vs. 77 years; P less than .001).

In addition, the rate of in-hospital mortality was higher in women without breast cancer (7.9%) compared with survivors (7.1%) (P less than .001). After risk adjustment, these results remained unchanged (odds ratio, 0.89; 95% confidence interval, 0.82-0.94).

“Breast cancer survivors in the U.S. are at least 6 years older than the general population of women without breast cancer, and they had a favorable cardiac risk factor profile at the time of first myocardial infarction,” Dr. Yandrapalli and colleagues explained. “The reason for these findings are unclear and hypothesis generating,” they added.

The researchers acknowledged that a key limitation of the study was the retrospective design. As a result, the potential effects of residual confounding should be considered when interpreting the results.

“The favorable impact of health education and participation in cancer survivorship programs on these observed differences in breast cancer survivors should be further explored,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Yandrapalli S et al. Am J Med. 2019 Nov 9. doi: 10.1016/j.amjmed.2019.10.018.

Breast cancer survivors may have a lower prevalence of cardiac risk factors at the time of first myocardial infarction and better outcomes compared with those having a first MI from the general population, according to findings from a retrospective study.

In addition, women without breast cancer were younger at the time of first MI compared with survivors, wrote Srikanth Yandrapalli, MD, of New York Medical College, Valhalla, and colleagues. Their report is in the American Journal of Medicine.

The researchers identified 1,644,032 women with a first MI, 56,842 of whom were breast cancer survivors. The team evaluated differences in the prevalence of cardiac risk factors and related outcomes in breast cancer survivors in comparison to the general population.

At baseline, the mean age of subjects with a history of breast cancer was 77 years (range, 11 years), while the mean age of women without breast cancer was 71 years (range, 15 years).

Clinical data were collected from the United States National Inpatient Sample for January 2005 to September 2015. Other outcomes assessed were differences in baseline characteristics and the rate of in-hospital mortality in both groups.

After analysis, the researchers found that breast cancer survivors had a lower prevalence of diabetes mellitus (30.1% vs. 33.1%), obesity (9.4% vs. 13.0%), and smoking (24.1% vs. 27.0%), but higher rates of dyslipidemia (52.7% vs. 48.4%) and hypertension (73.6% vs. 68.1%), compared with women without breast cancer (All P less than .001).

With respect to age, women without breast cancer were 6 years younger than breast cancer survivors at the time of first acute MI (mean age, 71 vs. 77 years; P less than .001).

In addition, the rate of in-hospital mortality was higher in women without breast cancer (7.9%) compared with survivors (7.1%) (P less than .001). After risk adjustment, these results remained unchanged (odds ratio, 0.89; 95% confidence interval, 0.82-0.94).

“Breast cancer survivors in the U.S. are at least 6 years older than the general population of women without breast cancer, and they had a favorable cardiac risk factor profile at the time of first myocardial infarction,” Dr. Yandrapalli and colleagues explained. “The reason for these findings are unclear and hypothesis generating,” they added.

The researchers acknowledged that a key limitation of the study was the retrospective design. As a result, the potential effects of residual confounding should be considered when interpreting the results.

“The favorable impact of health education and participation in cancer survivorship programs on these observed differences in breast cancer survivors should be further explored,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Yandrapalli S et al. Am J Med. 2019 Nov 9. doi: 10.1016/j.amjmed.2019.10.018.

Breast cancer survivors may have a lower prevalence of cardiac risk factors at the time of first myocardial infarction and better outcomes compared with those having a first MI from the general population, according to findings from a retrospective study.

In addition, women without breast cancer were younger at the time of first MI compared with survivors, wrote Srikanth Yandrapalli, MD, of New York Medical College, Valhalla, and colleagues. Their report is in the American Journal of Medicine.

The researchers identified 1,644,032 women with a first MI, 56,842 of whom were breast cancer survivors. The team evaluated differences in the prevalence of cardiac risk factors and related outcomes in breast cancer survivors in comparison to the general population.

At baseline, the mean age of subjects with a history of breast cancer was 77 years (range, 11 years), while the mean age of women without breast cancer was 71 years (range, 15 years).

Clinical data were collected from the United States National Inpatient Sample for January 2005 to September 2015. Other outcomes assessed were differences in baseline characteristics and the rate of in-hospital mortality in both groups.

After analysis, the researchers found that breast cancer survivors had a lower prevalence of diabetes mellitus (30.1% vs. 33.1%), obesity (9.4% vs. 13.0%), and smoking (24.1% vs. 27.0%), but higher rates of dyslipidemia (52.7% vs. 48.4%) and hypertension (73.6% vs. 68.1%), compared with women without breast cancer (All P less than .001).

With respect to age, women without breast cancer were 6 years younger than breast cancer survivors at the time of first acute MI (mean age, 71 vs. 77 years; P less than .001).

In addition, the rate of in-hospital mortality was higher in women without breast cancer (7.9%) compared with survivors (7.1%) (P less than .001). After risk adjustment, these results remained unchanged (odds ratio, 0.89; 95% confidence interval, 0.82-0.94).

“Breast cancer survivors in the U.S. are at least 6 years older than the general population of women without breast cancer, and they had a favorable cardiac risk factor profile at the time of first myocardial infarction,” Dr. Yandrapalli and colleagues explained. “The reason for these findings are unclear and hypothesis generating,” they added.

The researchers acknowledged that a key limitation of the study was the retrospective design. As a result, the potential effects of residual confounding should be considered when interpreting the results.

“The favorable impact of health education and participation in cancer survivorship programs on these observed differences in breast cancer survivors should be further explored,” they concluded.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Yandrapalli S et al. Am J Med. 2019 Nov 9. doi: 10.1016/j.amjmed.2019.10.018.

The federal health insurance exchange is now through the first 2 weeks of its 2020 open enrollment on the HealthCare.gov platform, and just over 930,000 plans have been selected, the Centers for Medicare & Medicaid Services reported.

The majority of those selections – almost 690,000 – were made by consumers renewing their existing coverage, with the rest coming from new consumers who did not have exchange coverage for 2019, the CMS said in its weekly enrollment snapshot on Nov. 13.

The total number of plans selected through week 2 is down almost 21% from last year, when selections totaled almost 1.18 million. This year, however, week 1 of open enrollment was only 2 days long (Nov. 1-2), versus 3 days (Nov. 1-3) last year, and last year there were 39 states using HealthCare.gov, compared with 38 this year since Nevada now has its own state-based exchange.

The total number of plans selected during a particular reporting period can change later if plans are modified or canceled, CMS noted, and “the weekly snapshot only reports new plan selections and active plan renewals and does not report the number of consumers who have paid premiums to effectuate their enrollment.”

[email protected]

The federal health insurance exchange is now through the first 2 weeks of its 2020 open enrollment on the HealthCare.gov platform, and just over 930,000 plans have been selected, the Centers for Medicare & Medicaid Services reported.

The majority of those selections – almost 690,000 – were made by consumers renewing their existing coverage, with the rest coming from new consumers who did not have exchange coverage for 2019, the CMS said in its weekly enrollment snapshot on Nov. 13.

The total number of plans selected through week 2 is down almost 21% from last year, when selections totaled almost 1.18 million. This year, however, week 1 of open enrollment was only 2 days long (Nov. 1-2), versus 3 days (Nov. 1-3) last year, and last year there were 39 states using HealthCare.gov, compared with 38 this year since Nevada now has its own state-based exchange.

The total number of plans selected during a particular reporting period can change later if plans are modified or canceled, CMS noted, and “the weekly snapshot only reports new plan selections and active plan renewals and does not report the number of consumers who have paid premiums to effectuate their enrollment.”

[email protected]

The federal health insurance exchange is now through the first 2 weeks of its 2020 open enrollment on the HealthCare.gov platform, and just over 930,000 plans have been selected, the Centers for Medicare & Medicaid Services reported.

The majority of those selections – almost 690,000 – were made by consumers renewing their existing coverage, with the rest coming from new consumers who did not have exchange coverage for 2019, the CMS said in its weekly enrollment snapshot on Nov. 13.

The total number of plans selected through week 2 is down almost 21% from last year, when selections totaled almost 1.18 million. This year, however, week 1 of open enrollment was only 2 days long (Nov. 1-2), versus 3 days (Nov. 1-3) last year, and last year there were 39 states using HealthCare.gov, compared with 38 this year since Nevada now has its own state-based exchange.

The total number of plans selected during a particular reporting period can change later if plans are modified or canceled, CMS noted, and “the weekly snapshot only reports new plan selections and active plan renewals and does not report the number of consumers who have paid premiums to effectuate their enrollment.”

[email protected]

VANCOUVER – Follow-up oncologic data from the UTERUS-11 trial shows advantages to surgical staging over clinical staging in stage IIB-IVA cervical cancer, with little apparent risk.

Courtesy Wikimedia Commons/John Hayman/Creative Commons License

Compared with clinical staging using CT, laparoscopic staging led to an improvement in cancer-specific survival, with no delays in treatment or increases in toxicity. It also prompted surgical up-staging and led to treatment changes in 33% of cases. There was no difference in overall survival, but progression-free survival trended towards better outcomes in the surgical-staging group.

The new study presents 5-year follow-up data from patients randomly assigned to surgical (n = 121) or clinical staging (n = 114). The original study, published in 2017 (Oncology. 2017;92[4]:213-20), reported that 33% of surgical-staging patients in the surgical staging were up-staged as a result, compared with 6% who were revealed to have positive paraaortic lymph nodes through a CT-guided core biopsy after suspicious CT results. After a median follow-up of 90 months in both arms, overall survival was similar between the two groups, and progression-free survival trended towards an improvement in the surgical-staging group (P = .088). Cancer-specific survival was better in the surgical-staging arm, compared with clinical staging (P=.028), Audrey Tsunoda, MD, PhD, reported.

Surgical staging didn’t impact the toxicity profile, said Dr. Tsunoda, a surgical oncologist focused in gynecologic cancer surgery who practices at Hospital Erasto Gaertner in Curitiba, Brazil.

The mean time to initiation of chemoradiotherapy following surgery was 14 days (range, 7-21 days) after surgery: 64% had intensity-modulated radiotherapy and 36% had three-dimensional radiotherapy. There were no grade 5 toxicities during chemoradiotherapy and both groups had similar gastrointestinal and genitourinary toxicity profiles. About 97% of the surgical staging procedures were conducted laparoscopically. Two patients had a blood loss of more than 500 cc, and two had a delay to primary chemoradiotherapy (4 days and 5 days). One patient had to be converted to an open approach because of obesity and severe adhesions, and there was no intraoperative mortality.

Previous retrospective studies examining surgical staging in these patients led to confusion and disagreements among guidelines. Surgical staging is clearly associated with increased up-staging, but the oncologic benefit is uncertain. The LiLACS study attempted to address the question with prospective data, but failed to accrue enough patients and was later abandoned. That leaves the UTERUS-11 study, the initial results of which were published in 2017, as the first prospective study to examine the benefit of surgical staging.

The new follow-up results suggest a benefit to surgical staging, but they leave an important question unanswered, according to Lois Ramondetta, MD, professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center, Houston, who served as a discussant at the meeting sponsored by AAGL. “Paraaortic lymph node status does connect to clinical benefit, but the question is really [whether] the removal of the lymph nodes accounts for the benefit, or is the identification of them and the change in treatment plan responsible? [If the latter is the case], a PET scan would have done a better job,” said Dr. Ramondetta. “The question remains unanswered, but I think this was huge progress in trying to answer it. Future studies need to incorporate a PET scan.”

Dr. Tsunoda has received honoraria from AstraZeneca and Roche. Dr. Ramondetta has no relevant financial disclosures.

VANCOUVER – Follow-up oncologic data from the UTERUS-11 trial shows advantages to surgical staging over clinical staging in stage IIB-IVA cervical cancer, with little apparent risk.

Courtesy Wikimedia Commons/John Hayman/Creative Commons License

Compared with clinical staging using CT, laparoscopic staging led to an improvement in cancer-specific survival, with no delays in treatment or increases in toxicity. It also prompted surgical up-staging and led to treatment changes in 33% of cases. There was no difference in overall survival, but progression-free survival trended towards better outcomes in the surgical-staging group.

The new study presents 5-year follow-up data from patients randomly assigned to surgical (n = 121) or clinical staging (n = 114). The original study, published in 2017 (Oncology. 2017;92[4]:213-20), reported that 33% of surgical-staging patients in the surgical staging were up-staged as a result, compared with 6% who were revealed to have positive paraaortic lymph nodes through a CT-guided core biopsy after suspicious CT results. After a median follow-up of 90 months in both arms, overall survival was similar between the two groups, and progression-free survival trended towards an improvement in the surgical-staging group (P = .088). Cancer-specific survival was better in the surgical-staging arm, compared with clinical staging (P=.028), Audrey Tsunoda, MD, PhD, reported.

Surgical staging didn’t impact the toxicity profile, said Dr. Tsunoda, a surgical oncologist focused in gynecologic cancer surgery who practices at Hospital Erasto Gaertner in Curitiba, Brazil.

The mean time to initiation of chemoradiotherapy following surgery was 14 days (range, 7-21 days) after surgery: 64% had intensity-modulated radiotherapy and 36% had three-dimensional radiotherapy. There were no grade 5 toxicities during chemoradiotherapy and both groups had similar gastrointestinal and genitourinary toxicity profiles. About 97% of the surgical staging procedures were conducted laparoscopically. Two patients had a blood loss of more than 500 cc, and two had a delay to primary chemoradiotherapy (4 days and 5 days). One patient had to be converted to an open approach because of obesity and severe adhesions, and there was no intraoperative mortality.

Previous retrospective studies examining surgical staging in these patients led to confusion and disagreements among guidelines. Surgical staging is clearly associated with increased up-staging, but the oncologic benefit is uncertain. The LiLACS study attempted to address the question with prospective data, but failed to accrue enough patients and was later abandoned. That leaves the UTERUS-11 study, the initial results of which were published in 2017, as the first prospective study to examine the benefit of surgical staging.

The new follow-up results suggest a benefit to surgical staging, but they leave an important question unanswered, according to Lois Ramondetta, MD, professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center, Houston, who served as a discussant at the meeting sponsored by AAGL. “Paraaortic lymph node status does connect to clinical benefit, but the question is really [whether] the removal of the lymph nodes accounts for the benefit, or is the identification of them and the change in treatment plan responsible? [If the latter is the case], a PET scan would have done a better job,” said Dr. Ramondetta. “The question remains unanswered, but I think this was huge progress in trying to answer it. Future studies need to incorporate a PET scan.”

Dr. Tsunoda has received honoraria from AstraZeneca and Roche. Dr. Ramondetta has no relevant financial disclosures.

VANCOUVER – Follow-up oncologic data from the UTERUS-11 trial shows advantages to surgical staging over clinical staging in stage IIB-IVA cervical cancer, with little apparent risk.

Courtesy Wikimedia Commons/John Hayman/Creative Commons License

Compared with clinical staging using CT, laparoscopic staging led to an improvement in cancer-specific survival, with no delays in treatment or increases in toxicity. It also prompted surgical up-staging and led to treatment changes in 33% of cases. There was no difference in overall survival, but progression-free survival trended towards better outcomes in the surgical-staging group.

The new study presents 5-year follow-up data from patients randomly assigned to surgical (n = 121) or clinical staging (n = 114). The original study, published in 2017 (Oncology. 2017;92[4]:213-20), reported that 33% of surgical-staging patients in the surgical staging were up-staged as a result, compared with 6% who were revealed to have positive paraaortic lymph nodes through a CT-guided core biopsy after suspicious CT results. After a median follow-up of 90 months in both arms, overall survival was similar between the two groups, and progression-free survival trended towards an improvement in the surgical-staging group (P = .088). Cancer-specific survival was better in the surgical-staging arm, compared with clinical staging (P=.028), Audrey Tsunoda, MD, PhD, reported.

Surgical staging didn’t impact the toxicity profile, said Dr. Tsunoda, a surgical oncologist focused in gynecologic cancer surgery who practices at Hospital Erasto Gaertner in Curitiba, Brazil.

The mean time to initiation of chemoradiotherapy following surgery was 14 days (range, 7-21 days) after surgery: 64% had intensity-modulated radiotherapy and 36% had three-dimensional radiotherapy. There were no grade 5 toxicities during chemoradiotherapy and both groups had similar gastrointestinal and genitourinary toxicity profiles. About 97% of the surgical staging procedures were conducted laparoscopically. Two patients had a blood loss of more than 500 cc, and two had a delay to primary chemoradiotherapy (4 days and 5 days). One patient had to be converted to an open approach because of obesity and severe adhesions, and there was no intraoperative mortality.

Previous retrospective studies examining surgical staging in these patients led to confusion and disagreements among guidelines. Surgical staging is clearly associated with increased up-staging, but the oncologic benefit is uncertain. The LiLACS study attempted to address the question with prospective data, but failed to accrue enough patients and was later abandoned. That leaves the UTERUS-11 study, the initial results of which were published in 2017, as the first prospective study to examine the benefit of surgical staging.

The new follow-up results suggest a benefit to surgical staging, but they leave an important question unanswered, according to Lois Ramondetta, MD, professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center, Houston, who served as a discussant at the meeting sponsored by AAGL. “Paraaortic lymph node status does connect to clinical benefit, but the question is really [whether] the removal of the lymph nodes accounts for the benefit, or is the identification of them and the change in treatment plan responsible? [If the latter is the case], a PET scan would have done a better job,” said Dr. Ramondetta. “The question remains unanswered, but I think this was huge progress in trying to answer it. Future studies need to incorporate a PET scan.”

Dr. Tsunoda has received honoraria from AstraZeneca and Roche. Dr. Ramondetta has no relevant financial disclosures.

Quality improvement (QI) education has become increasingly seen as core content in graduate medical education, said Brian Wong, MD, FRCPC, of the University of Toronto. One of the most common strategies for teaching QI is to have residents participate in a QI project, in which hospitalists often take a leading role.

“Given the investment made and time spent carrying out these projects, it is important to know whether or not the training has led to the desired outcome from both a learning and a project standpoint,” Dr. Wong said, which is why he coauthored a recent editorial on the subject in BMJ Quality and Safety. QI educators have long recognized that it’s difficult to know whether the education was successful.

“For example, if the project was not successful, does it matter if the residents learned key QI principles that they were able to apply to their project work?” Dr. Wong noted. “Our perspective extends this discussion by asking, ‘What does success look like in QI education?’ We argue that rather than focusing on whether the project was successful or not, our real goal should be to create QI educational experiences that will ensure that residents change their behaviors in future practice to embrace QI as an activity that is core to their everyday work.”

Hospitalists have an important role in that. “They can set the stage for learners to recognize just how important it is to incorporate QI into daily work. Through this role modeling, residents who carry out QI projects can see that the lessons learned contribute to lifelong engagement in QI.”

Dr. Wong’s hope is to focus on the type of QI experience that fosters long-term behavior changes.

“We want residents, when they graduate, to embrace QI, to volunteer to participate in organizational initiatives, to welcome practice data and reflect on it for the purposes of continuous improvement, to collaborate interprofessionally to make small iterative changes to the care delivery system to ensure that patients receive the highest quality of care possible,” he said. “My hope is that we can start to think differently about how we measure success in QI education.”

Reference

1. Myers JS, Wong BM. Measuring outcomes in quality improvement education: Success is in the eye of the beholder. BMJ Qual Saf. 2019 Mar 18. doi: 10.1136/bmjqs-2018-008305.

Quality improvement (QI) education has become increasingly seen as core content in graduate medical education, said Brian Wong, MD, FRCPC, of the University of Toronto. One of the most common strategies for teaching QI is to have residents participate in a QI project, in which hospitalists often take a leading role.

“Given the investment made and time spent carrying out these projects, it is important to know whether or not the training has led to the desired outcome from both a learning and a project standpoint,” Dr. Wong said, which is why he coauthored a recent editorial on the subject in BMJ Quality and Safety. QI educators have long recognized that it’s difficult to know whether the education was successful.

“For example, if the project was not successful, does it matter if the residents learned key QI principles that they were able to apply to their project work?” Dr. Wong noted. “Our perspective extends this discussion by asking, ‘What does success look like in QI education?’ We argue that rather than focusing on whether the project was successful or not, our real goal should be to create QI educational experiences that will ensure that residents change their behaviors in future practice to embrace QI as an activity that is core to their everyday work.”

Hospitalists have an important role in that. “They can set the stage for learners to recognize just how important it is to incorporate QI into daily work. Through this role modeling, residents who carry out QI projects can see that the lessons learned contribute to lifelong engagement in QI.”

Dr. Wong’s hope is to focus on the type of QI experience that fosters long-term behavior changes.

“We want residents, when they graduate, to embrace QI, to volunteer to participate in organizational initiatives, to welcome practice data and reflect on it for the purposes of continuous improvement, to collaborate interprofessionally to make small iterative changes to the care delivery system to ensure that patients receive the highest quality of care possible,” he said. “My hope is that we can start to think differently about how we measure success in QI education.”

Reference

1. Myers JS, Wong BM. Measuring outcomes in quality improvement education: Success is in the eye of the beholder. BMJ Qual Saf. 2019 Mar 18. doi: 10.1136/bmjqs-2018-008305.

Quality improvement (QI) education has become increasingly seen as core content in graduate medical education, said Brian Wong, MD, FRCPC, of the University of Toronto. One of the most common strategies for teaching QI is to have residents participate in a QI project, in which hospitalists often take a leading role.

“Given the investment made and time spent carrying out these projects, it is important to know whether or not the training has led to the desired outcome from both a learning and a project standpoint,” Dr. Wong said, which is why he coauthored a recent editorial on the subject in BMJ Quality and Safety. QI educators have long recognized that it’s difficult to know whether the education was successful.

“For example, if the project was not successful, does it matter if the residents learned key QI principles that they were able to apply to their project work?” Dr. Wong noted. “Our perspective extends this discussion by asking, ‘What does success look like in QI education?’ We argue that rather than focusing on whether the project was successful or not, our real goal should be to create QI educational experiences that will ensure that residents change their behaviors in future practice to embrace QI as an activity that is core to their everyday work.”

Hospitalists have an important role in that. “They can set the stage for learners to recognize just how important it is to incorporate QI into daily work. Through this role modeling, residents who carry out QI projects can see that the lessons learned contribute to lifelong engagement in QI.”

Dr. Wong’s hope is to focus on the type of QI experience that fosters long-term behavior changes.

“We want residents, when they graduate, to embrace QI, to volunteer to participate in organizational initiatives, to welcome practice data and reflect on it for the purposes of continuous improvement, to collaborate interprofessionally to make small iterative changes to the care delivery system to ensure that patients receive the highest quality of care possible,” he said. “My hope is that we can start to think differently about how we measure success in QI education.”

Reference

1. Myers JS, Wong BM. Measuring outcomes in quality improvement education: Success is in the eye of the beholder. BMJ Qual Saf. 2019 Mar 18. doi: 10.1136/bmjqs-2018-008305.

Less than a decade ago, the ED at Rady Children’s Hospital in San Diego would see maybe one or two young psychiatric patients per day, said Benjamin Maxwell, MD, the hospital’s interim director of child and adolescent psychiatry.

Fuse/thinkstockphotos.com

Now, it’s not unusual for the ED to see 10 psychiatric patients in a day, and sometimes even 20, said Dr. Maxwell. “What a lot of times is happening now is kids aren’t getting the care they need, until it gets to the point where it is dangerous.”

EDs throughout California are reporting a sharp increase in adolescents and young adults seeking care for a mental health crisis. In 2018, California EDs treated 84,584 young patients aged 13-21 years who had a primary diagnosis involving mental health. That is up from 59,705 in 2012, a 42% increase, according to data provided by the Office of Statewide Health Planning and Development.

By comparison, the number of ED encounters among that age group for all other diagnoses grew by just 4% over the same period. And the number of encounters involving mental health among all other age groups – everyone except adolescents and young adults – rose by about 18%.

The spike in youth mental health visits corresponds with a recent survey that found that members of “Generation Z” – defined in the survey as people born since 1997 – are more likely than other generations to report their mental health as fair or poor. The 2018 polling, done on behalf of the American Psychological Association, also found that members of Generation Z, along with millennials, are more likely to report receiving treatment for mental health issues.

The trend corresponds with another alarming development, as well: a marked increase in suicides among teens and young adults. About 7.5 of every 100,000 young people aged 13-21 in California died by suicide in 2017, up from a rate of 4.9 per 100,000 in 2008, according to the latest figures from the Centers for Disease Control and Prevention. Nationwide, suicides in that age range rose from 7.2 to 11.3 per 100,000 from 2008 to 2017.

Researchers are studying the causes for the surging reports of mental distress among America’s young people. Many recent theories note that the trend parallels the rise of social media, an ever-present window on peer activities that can exacerbate adolescent insecurities and open new avenues of bullying.

“Even though this generation has been raised with social media, youth are feeling more disconnected, judged, bullied, and pressured from their peers,” said Susan Coats, EdD, a school psychologist at Baldwin Park Unified School District near Los Angeles.

“Social media: It’s a blessing and it’s a curse,” Dr. Coats added. “Social media has brought youth together in a forum where maybe they may have felt isolated before, but it also has undermined interpersonal relationships.”

Members of Generation Z also report significant levels of stress about personal debt, housing instability, and hunger, as well as mass shootings and climate change, according to the American Psychological Association survey.

Resources to prevent mental health crisis among youth are often lacking.

“We’re not doing a great job with … catching things before they devolve into broader problems, and we’re not doing a good job with prevention,” said Lishaun Francis, associate director of health collaborations at Children Now, a nonprofit based in Oakland, Calif.

Many California school districts don’t have enough school psychologists and don’t devote enough resources to teaching students how to cope with depression, anxiety, and other mental health issues, said Ms. Coats, who chairs the mental health and crisis consultation committee of the California Association of School Psychologists.

In the broader community, medical providers also are struggling to keep up. “Many times there aren’t psychiatric beds available for kids in our community,” Dr. Maxwell said.

Most of the adolescents who come into the ED at Rady Children’s Hospital during a mental health crisis are considering suicide, have attempted suicide, or have harmed themselves, said Dr. Maxwell, who is also the hospital’s medical director of inpatient psychiatry.

These patients are triaged and quickly seen by a social worker. Often, a behavioral health assistant is assigned to sit with the patients throughout their stay.

“Suicidal patients – we don’t want them to be alone at all in a busy emergency department,” Dr. Maxwell said. “So that’s a major staffing increase.”

Rady Children’s Hospital plans to open a six-bed, 24-hour psychiatric ED in the spring. Improving emergency care will help, Dr. Maxwell said, but a better solution would be to intervene with young people before they need an ED.

“The ED surge probably represents a failure of the system at large,” Dr. Maxwell said. “They’re ending up in the emergency department because they’re not getting the care they need, when they need it.”

Phillip Reese is a data reporting specialist and an assistant professor of journalism at California State University–Sacramento. This Kaiser Health News story first published on California Healthline, a service of the California Health Care Foundation. KHN is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Less than a decade ago, the ED at Rady Children’s Hospital in San Diego would see maybe one or two young psychiatric patients per day, said Benjamin Maxwell, MD, the hospital’s interim director of child and adolescent psychiatry.

Fuse/thinkstockphotos.com

Now, it’s not unusual for the ED to see 10 psychiatric patients in a day, and sometimes even 20, said Dr. Maxwell. “What a lot of times is happening now is kids aren’t getting the care they need, until it gets to the point where it is dangerous.”

EDs throughout California are reporting a sharp increase in adolescents and young adults seeking care for a mental health crisis. In 2018, California EDs treated 84,584 young patients aged 13-21 years who had a primary diagnosis involving mental health. That is up from 59,705 in 2012, a 42% increase, according to data provided by the Office of Statewide Health Planning and Development.

By comparison, the number of ED encounters among that age group for all other diagnoses grew by just 4% over the same period. And the number of encounters involving mental health among all other age groups – everyone except adolescents and young adults – rose by about 18%.

The spike in youth mental health visits corresponds with a recent survey that found that members of “Generation Z” – defined in the survey as people born since 1997 – are more likely than other generations to report their mental health as fair or poor. The 2018 polling, done on behalf of the American Psychological Association, also found that members of Generation Z, along with millennials, are more likely to report receiving treatment for mental health issues.

The trend corresponds with another alarming development, as well: a marked increase in suicides among teens and young adults. About 7.5 of every 100,000 young people aged 13-21 in California died by suicide in 2017, up from a rate of 4.9 per 100,000 in 2008, according to the latest figures from the Centers for Disease Control and Prevention. Nationwide, suicides in that age range rose from 7.2 to 11.3 per 100,000 from 2008 to 2017.

Researchers are studying the causes for the surging reports of mental distress among America’s young people. Many recent theories note that the trend parallels the rise of social media, an ever-present window on peer activities that can exacerbate adolescent insecurities and open new avenues of bullying.

“Even though this generation has been raised with social media, youth are feeling more disconnected, judged, bullied, and pressured from their peers,” said Susan Coats, EdD, a school psychologist at Baldwin Park Unified School District near Los Angeles.

“Social media: It’s a blessing and it’s a curse,” Dr. Coats added. “Social media has brought youth together in a forum where maybe they may have felt isolated before, but it also has undermined interpersonal relationships.”

Members of Generation Z also report significant levels of stress about personal debt, housing instability, and hunger, as well as mass shootings and climate change, according to the American Psychological Association survey.

Resources to prevent mental health crisis among youth are often lacking.

“We’re not doing a great job with … catching things before they devolve into broader problems, and we’re not doing a good job with prevention,” said Lishaun Francis, associate director of health collaborations at Children Now, a nonprofit based in Oakland, Calif.

Many California school districts don’t have enough school psychologists and don’t devote enough resources to teaching students how to cope with depression, anxiety, and other mental health issues, said Ms. Coats, who chairs the mental health and crisis consultation committee of the California Association of School Psychologists.

In the broader community, medical providers also are struggling to keep up. “Many times there aren’t psychiatric beds available for kids in our community,” Dr. Maxwell said.

Most of the adolescents who come into the ED at Rady Children’s Hospital during a mental health crisis are considering suicide, have attempted suicide, or have harmed themselves, said Dr. Maxwell, who is also the hospital’s medical director of inpatient psychiatry.

These patients are triaged and quickly seen by a social worker. Often, a behavioral health assistant is assigned to sit with the patients throughout their stay.

“Suicidal patients – we don’t want them to be alone at all in a busy emergency department,” Dr. Maxwell said. “So that’s a major staffing increase.”

Rady Children’s Hospital plans to open a six-bed, 24-hour psychiatric ED in the spring. Improving emergency care will help, Dr. Maxwell said, but a better solution would be to intervene with young people before they need an ED.

“The ED surge probably represents a failure of the system at large,” Dr. Maxwell said. “They’re ending up in the emergency department because they’re not getting the care they need, when they need it.”

Phillip Reese is a data reporting specialist and an assistant professor of journalism at California State University–Sacramento. This Kaiser Health News story first published on California Healthline, a service of the California Health Care Foundation. KHN is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

Less than a decade ago, the ED at Rady Children’s Hospital in San Diego would see maybe one or two young psychiatric patients per day, said Benjamin Maxwell, MD, the hospital’s interim director of child and adolescent psychiatry.

Fuse/thinkstockphotos.com

Now, it’s not unusual for the ED to see 10 psychiatric patients in a day, and sometimes even 20, said Dr. Maxwell. “What a lot of times is happening now is kids aren’t getting the care they need, until it gets to the point where it is dangerous.”

EDs throughout California are reporting a sharp increase in adolescents and young adults seeking care for a mental health crisis. In 2018, California EDs treated 84,584 young patients aged 13-21 years who had a primary diagnosis involving mental health. That is up from 59,705 in 2012, a 42% increase, according to data provided by the Office of Statewide Health Planning and Development.

By comparison, the number of ED encounters among that age group for all other diagnoses grew by just 4% over the same period. And the number of encounters involving mental health among all other age groups – everyone except adolescents and young adults – rose by about 18%.

The spike in youth mental health visits corresponds with a recent survey that found that members of “Generation Z” – defined in the survey as people born since 1997 – are more likely than other generations to report their mental health as fair or poor. The 2018 polling, done on behalf of the American Psychological Association, also found that members of Generation Z, along with millennials, are more likely to report receiving treatment for mental health issues.

The trend corresponds with another alarming development, as well: a marked increase in suicides among teens and young adults. About 7.5 of every 100,000 young people aged 13-21 in California died by suicide in 2017, up from a rate of 4.9 per 100,000 in 2008, according to the latest figures from the Centers for Disease Control and Prevention. Nationwide, suicides in that age range rose from 7.2 to 11.3 per 100,000 from 2008 to 2017.

Researchers are studying the causes for the surging reports of mental distress among America’s young people. Many recent theories note that the trend parallels the rise of social media, an ever-present window on peer activities that can exacerbate adolescent insecurities and open new avenues of bullying.

“Even though this generation has been raised with social media, youth are feeling more disconnected, judged, bullied, and pressured from their peers,” said Susan Coats, EdD, a school psychologist at Baldwin Park Unified School District near Los Angeles.

“Social media: It’s a blessing and it’s a curse,” Dr. Coats added. “Social media has brought youth together in a forum where maybe they may have felt isolated before, but it also has undermined interpersonal relationships.”

Members of Generation Z also report significant levels of stress about personal debt, housing instability, and hunger, as well as mass shootings and climate change, according to the American Psychological Association survey.

Resources to prevent mental health crisis among youth are often lacking.

“We’re not doing a great job with … catching things before they devolve into broader problems, and we’re not doing a good job with prevention,” said Lishaun Francis, associate director of health collaborations at Children Now, a nonprofit based in Oakland, Calif.

Many California school districts don’t have enough school psychologists and don’t devote enough resources to teaching students how to cope with depression, anxiety, and other mental health issues, said Ms. Coats, who chairs the mental health and crisis consultation committee of the California Association of School Psychologists.

In the broader community, medical providers also are struggling to keep up. “Many times there aren’t psychiatric beds available for kids in our community,” Dr. Maxwell said.

Most of the adolescents who come into the ED at Rady Children’s Hospital during a mental health crisis are considering suicide, have attempted suicide, or have harmed themselves, said Dr. Maxwell, who is also the hospital’s medical director of inpatient psychiatry.

These patients are triaged and quickly seen by a social worker. Often, a behavioral health assistant is assigned to sit with the patients throughout their stay.

“Suicidal patients – we don’t want them to be alone at all in a busy emergency department,” Dr. Maxwell said. “So that’s a major staffing increase.”

Rady Children’s Hospital plans to open a six-bed, 24-hour psychiatric ED in the spring. Improving emergency care will help, Dr. Maxwell said, but a better solution would be to intervene with young people before they need an ED.

“The ED surge probably represents a failure of the system at large,” Dr. Maxwell said. “They’re ending up in the emergency department because they’re not getting the care they need, when they need it.”

Phillip Reese is a data reporting specialist and an assistant professor of journalism at California State University–Sacramento. This Kaiser Health News story first published on California Healthline, a service of the California Health Care Foundation. KHN is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

The FP initially treated the area with topical ketoconazole cream, which stung, but partially improved the patient’s symptoms. Because the rash persisted, the FP performed a punch biopsy, which showed widespread epidermal acantholysis or separation of epidermal cells. This is a hallmark of pemphigus vulgaris and benign familial pemphigus (Hailey-Hailey disease).

Hailey-Hailey disease is an uncommon autosomal dominant inherited blistering disorder that affects connecting proteins in the epidermis, which is why histology overlaps with pemphigus. Symptoms may not present until the second or third decade of life and often occur in flexural or high friction areas, including the axilla and inguinal folds. Any skin injury may trigger a flare, including sunburn, infections, heavy sweating, or friction from clothes. Bacterial overgrowth or colonization can cause a bad odor and social isolation in severe cases.

The differential diagnosis of axillary skin disorders is broad and includes irritant contact dermatitis, contact dermatitis, seborrheic dermatitis, hidradenitis suppurativa, candida intertrigo, and psoriasis. Clinical clues that favor Hailey-Hailey disease include fragile vesicles or pustules at the periphery and small focal erosions. The family history is helpful but not always known.

Some patients require topical therapy sequentially, in combination, or personalized through trial and error that addresses the inflammation, bacterial overgrowth, and fungal disease. Patients also may require long-term doxycycline therapy to suppress flares. Most patients will benefit from at least prn use of topical steroids for inflammation. Addressing sweating with topical aluminum chloride or botulinum injections can be beneficial. Low dose naltrexone, as well as afamelanotide, has shown promise in a few small case series.

The patient in this case improved with topical triamcinolone 0.1% ointment bid and systemic doxycycline 100 mg bid for 2 weeks. However, he continued to require occasional rounds of oral doxycycline with flares.

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Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained).

The FP initially treated the area with topical ketoconazole cream, which stung, but partially improved the patient’s symptoms. Because the rash persisted, the FP performed a punch biopsy, which showed widespread epidermal acantholysis or separation of epidermal cells. This is a hallmark of pemphigus vulgaris and benign familial pemphigus (Hailey-Hailey disease).

Hailey-Hailey disease is an uncommon autosomal dominant inherited blistering disorder that affects connecting proteins in the epidermis, which is why histology overlaps with pemphigus. Symptoms may not present until the second or third decade of life and often occur in flexural or high friction areas, including the axilla and inguinal folds. Any skin injury may trigger a flare, including sunburn, infections, heavy sweating, or friction from clothes. Bacterial overgrowth or colonization can cause a bad odor and social isolation in severe cases.

The differential diagnosis of axillary skin disorders is broad and includes irritant contact dermatitis, contact dermatitis, seborrheic dermatitis, hidradenitis suppurativa, candida intertrigo, and psoriasis. Clinical clues that favor Hailey-Hailey disease include fragile vesicles or pustules at the periphery and small focal erosions. The family history is helpful but not always known.

Some patients require topical therapy sequentially, in combination, or personalized through trial and error that addresses the inflammation, bacterial overgrowth, and fungal disease. Patients also may require long-term doxycycline therapy to suppress flares. Most patients will benefit from at least prn use of topical steroids for inflammation. Addressing sweating with topical aluminum chloride or botulinum injections can be beneficial. Low dose naltrexone, as well as afamelanotide, has shown promise in a few small case series.

The patient in this case improved with topical triamcinolone 0.1% ointment bid and systemic doxycycline 100 mg bid for 2 weeks. However, he continued to require occasional rounds of oral doxycycline with flares.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained).

The FP initially treated the area with topical ketoconazole cream, which stung, but partially improved the patient’s symptoms. Because the rash persisted, the FP performed a punch biopsy, which showed widespread epidermal acantholysis or separation of epidermal cells. This is a hallmark of pemphigus vulgaris and benign familial pemphigus (Hailey-Hailey disease).

Hailey-Hailey disease is an uncommon autosomal dominant inherited blistering disorder that affects connecting proteins in the epidermis, which is why histology overlaps with pemphigus. Symptoms may not present until the second or third decade of life and often occur in flexural or high friction areas, including the axilla and inguinal folds. Any skin injury may trigger a flare, including sunburn, infections, heavy sweating, or friction from clothes. Bacterial overgrowth or colonization can cause a bad odor and social isolation in severe cases.

The differential diagnosis of axillary skin disorders is broad and includes irritant contact dermatitis, contact dermatitis, seborrheic dermatitis, hidradenitis suppurativa, candida intertrigo, and psoriasis. Clinical clues that favor Hailey-Hailey disease include fragile vesicles or pustules at the periphery and small focal erosions. The family history is helpful but not always known.

Some patients require topical therapy sequentially, in combination, or personalized through trial and error that addresses the inflammation, bacterial overgrowth, and fungal disease. Patients also may require long-term doxycycline therapy to suppress flares. Most patients will benefit from at least prn use of topical steroids for inflammation. Addressing sweating with topical aluminum chloride or botulinum injections can be beneficial. Low dose naltrexone, as well as afamelanotide, has shown promise in a few small case series.

The patient in this case improved with topical triamcinolone 0.1% ointment bid and systemic doxycycline 100 mg bid for 2 weeks. However, he continued to require occasional rounds of oral doxycycline with flares.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained).