Fecal microbiota transplantation (FMT) using oral capsules as the delivery method has been shown to be noninferior to delivery using colonoscopy for the treatment of Clostridium difficile infection, but with a significantly lower price tag.

In an unblended noninferiority trial, published in the Nov. 28 issue of JAMA, 116 adults with at least three documented episodes of C. difficile infection were randomized to either 360 mL of fecal slurry delivered to the cecum via colonoscopy or to 40 capsules of processed fecal microbiota swallowed under direct observation.

CDC/Jennifer Hulsey

The AGA Center for Gut Microbiome Research and Education serves as a virtual “home” for AGA activities related to the gut microbiome, including the AGA FMT National Registry, which will assess short- and long-term patient outcomes associated with FMT. Learn more at http://www.gastro.org/about/initiatives/aga-center-for-gut-microbiome-research-education.  

Fecal microbiota transplantation (FMT) using oral capsules as the delivery method has been shown to be noninferior to delivery using colonoscopy for the treatment of Clostridium difficile infection, but with a significantly lower price tag.

In an unblended noninferiority trial, published in the Nov. 28 issue of JAMA, 116 adults with at least three documented episodes of C. difficile infection were randomized to either 360 mL of fecal slurry delivered to the cecum via colonoscopy or to 40 capsules of processed fecal microbiota swallowed under direct observation.

CDC/Jennifer Hulsey

The AGA Center for Gut Microbiome Research and Education serves as a virtual “home” for AGA activities related to the gut microbiome, including the AGA FMT National Registry, which will assess short- and long-term patient outcomes associated with FMT. Learn more at http://www.gastro.org/about/initiatives/aga-center-for-gut-microbiome-research-education.  

Fecal microbiota transplantation (FMT) using oral capsules as the delivery method has been shown to be noninferior to delivery using colonoscopy for the treatment of Clostridium difficile infection, but with a significantly lower price tag.

In an unblended noninferiority trial, published in the Nov. 28 issue of JAMA, 116 adults with at least three documented episodes of C. difficile infection were randomized to either 360 mL of fecal slurry delivered to the cecum via colonoscopy or to 40 capsules of processed fecal microbiota swallowed under direct observation.

CDC/Jennifer Hulsey

The AGA Center for Gut Microbiome Research and Education serves as a virtual “home” for AGA activities related to the gut microbiome, including the AGA FMT National Registry, which will assess short- and long-term patient outcomes associated with FMT. Learn more at http://www.gastro.org/about/initiatives/aga-center-for-gut-microbiome-research-education.  

The Food and Drug Administration has approved trastuzumab-dkst (Ogivri) as a biosimilar to trastuzumab (Herceptin) for the treatment of patients with HER2+ breast or metastatic gastric or gastroesophageal junction adenocarcinoma.

This is the first biosimilar approved in the United States for the treatment of breast cancer or gastric cancer and the second biosimilar approved for the treatment of cancer, the FDA said in a statement.

To prepare for the entry of biosimilars to the market, AGA is taking the lead in educating health-care professionals and patients about biosimilars. Visit www.gastro.org/biosimilars to learn more.

[email protected]

The Food and Drug Administration has approved trastuzumab-dkst (Ogivri) as a biosimilar to trastuzumab (Herceptin) for the treatment of patients with HER2+ breast or metastatic gastric or gastroesophageal junction adenocarcinoma.

This is the first biosimilar approved in the United States for the treatment of breast cancer or gastric cancer and the second biosimilar approved for the treatment of cancer, the FDA said in a statement.

To prepare for the entry of biosimilars to the market, AGA is taking the lead in educating health-care professionals and patients about biosimilars. Visit www.gastro.org/biosimilars to learn more.

[email protected]

The Food and Drug Administration has approved trastuzumab-dkst (Ogivri) as a biosimilar to trastuzumab (Herceptin) for the treatment of patients with HER2+ breast or metastatic gastric or gastroesophageal junction adenocarcinoma.

This is the first biosimilar approved in the United States for the treatment of breast cancer or gastric cancer and the second biosimilar approved for the treatment of cancer, the FDA said in a statement.

To prepare for the entry of biosimilars to the market, AGA is taking the lead in educating health-care professionals and patients about biosimilars. Visit www.gastro.org/biosimilars to learn more.

[email protected]

WASHINGTON – Children with febrile status epilepticus (FSE) may be at risk for memory impairment when abnormal hippocampal development or acute injury is also present, according to research presented at the annual meeting of the American Epilepsy Society.

This analysis of patients enrolled in the FEBSTAT study presents some of the first prospective data available regarding significant risk factors for cognitive dysfunction in children with FSE.

“Overall, children with FSE have generally intact memory function and generally intact IQ,” said Erica Weiss, PhD, a neurology instructor at the Albert Einstein College of Medicine, New York. “However, children with acute T2 [hyperintensities on MRI] and kids who have hippocampal malrotation [HIMAL] tend to have weaker memory scores.”

The investigators conducted a prospective study of 113 children with FSE using data gathered from five medical centers across the United States between June 2003 and March 2010.

Children included in the study were followed with serial MRIs and electroencephalograms for more than 5 years after their having FSE; during this time, their verbal, visual, and screening memory abilities were tested using the Wide Range Assessment of Memory and Learning, Second Edition, (WRAML2) test.

Patients had an average age of 15.5 months at time of FSE. Of the children in the study, 46% were female, and 46% were non-white.

Overall, mean scores at baseline on the WRAML2 were significantly lower for children with acute hippocampal injury shown on T2 hyperintensities or HIMAL than they were for children with a normal MRI scan. On individual memory functions of the WRAML2, mean scores at baseline for children with acute T2 hyperintensities were lower than they were for those with a normal MRI on the verbal index (79 vs. 102.3), visual index (81 vs. 93.7), and screening memory index (76 vs. 97.7). Children with HIMAL at baseline also had lower scores on those indexes (94.9 for verbal memory, 82.5 for visual memory, and 97 for screening memory) than did children with a normal MRI.

The differences were statistically significant for lower verbal memory and screening memory scores in patients with acute T2 hyperintensities and for lower visual memory scores in patients with HIMAL. The differences trended toward statistical significance for lower visual memory scores in children with acute T2 hyperintensities and for lower verbal memory scores in children with focal FSE seizures.

The researchers found no significant differences in memory task performances when stratifying for age at time of FSE, duration of FSE, or patients’ sex, according to Dr. Weiss.

With this initial connection uncovered, Dr. Weiss and her colleagues are looking to dive deeper into different aspects of hippocampal properties and FSE.

“We’re looking into the relationship between hippocampus size and memory performances, as well as continue to track these studies,” Dr. Weiss said in an interview. “Another factor to consider when you talk about memory is attention, and we have looked into it a bit, but we need more information.”

This study was funded by a grant from the National Institute of Neurological Disorders and Stroke. The presenters reported no relevant financial disclosures.

[email protected]

On Twitter @eaztweets

WASHINGTON – Children with febrile status epilepticus (FSE) may be at risk for memory impairment when abnormal hippocampal development or acute injury is also present, according to research presented at the annual meeting of the American Epilepsy Society.

This analysis of patients enrolled in the FEBSTAT study presents some of the first prospective data available regarding significant risk factors for cognitive dysfunction in children with FSE.

“Overall, children with FSE have generally intact memory function and generally intact IQ,” said Erica Weiss, PhD, a neurology instructor at the Albert Einstein College of Medicine, New York. “However, children with acute T2 [hyperintensities on MRI] and kids who have hippocampal malrotation [HIMAL] tend to have weaker memory scores.”

The investigators conducted a prospective study of 113 children with FSE using data gathered from five medical centers across the United States between June 2003 and March 2010.

Children included in the study were followed with serial MRIs and electroencephalograms for more than 5 years after their having FSE; during this time, their verbal, visual, and screening memory abilities were tested using the Wide Range Assessment of Memory and Learning, Second Edition, (WRAML2) test.

Patients had an average age of 15.5 months at time of FSE. Of the children in the study, 46% were female, and 46% were non-white.

Overall, mean scores at baseline on the WRAML2 were significantly lower for children with acute hippocampal injury shown on T2 hyperintensities or HIMAL than they were for children with a normal MRI scan. On individual memory functions of the WRAML2, mean scores at baseline for children with acute T2 hyperintensities were lower than they were for those with a normal MRI on the verbal index (79 vs. 102.3), visual index (81 vs. 93.7), and screening memory index (76 vs. 97.7). Children with HIMAL at baseline also had lower scores on those indexes (94.9 for verbal memory, 82.5 for visual memory, and 97 for screening memory) than did children with a normal MRI.

The differences were statistically significant for lower verbal memory and screening memory scores in patients with acute T2 hyperintensities and for lower visual memory scores in patients with HIMAL. The differences trended toward statistical significance for lower visual memory scores in children with acute T2 hyperintensities and for lower verbal memory scores in children with focal FSE seizures.

The researchers found no significant differences in memory task performances when stratifying for age at time of FSE, duration of FSE, or patients’ sex, according to Dr. Weiss.

With this initial connection uncovered, Dr. Weiss and her colleagues are looking to dive deeper into different aspects of hippocampal properties and FSE.

“We’re looking into the relationship between hippocampus size and memory performances, as well as continue to track these studies,” Dr. Weiss said in an interview. “Another factor to consider when you talk about memory is attention, and we have looked into it a bit, but we need more information.”

This study was funded by a grant from the National Institute of Neurological Disorders and Stroke. The presenters reported no relevant financial disclosures.

[email protected]

On Twitter @eaztweets

WASHINGTON – Children with febrile status epilepticus (FSE) may be at risk for memory impairment when abnormal hippocampal development or acute injury is also present, according to research presented at the annual meeting of the American Epilepsy Society.

This analysis of patients enrolled in the FEBSTAT study presents some of the first prospective data available regarding significant risk factors for cognitive dysfunction in children with FSE.

“Overall, children with FSE have generally intact memory function and generally intact IQ,” said Erica Weiss, PhD, a neurology instructor at the Albert Einstein College of Medicine, New York. “However, children with acute T2 [hyperintensities on MRI] and kids who have hippocampal malrotation [HIMAL] tend to have weaker memory scores.”

The investigators conducted a prospective study of 113 children with FSE using data gathered from five medical centers across the United States between June 2003 and March 2010.

Children included in the study were followed with serial MRIs and electroencephalograms for more than 5 years after their having FSE; during this time, their verbal, visual, and screening memory abilities were tested using the Wide Range Assessment of Memory and Learning, Second Edition, (WRAML2) test.

Patients had an average age of 15.5 months at time of FSE. Of the children in the study, 46% were female, and 46% were non-white.

Overall, mean scores at baseline on the WRAML2 were significantly lower for children with acute hippocampal injury shown on T2 hyperintensities or HIMAL than they were for children with a normal MRI scan. On individual memory functions of the WRAML2, mean scores at baseline for children with acute T2 hyperintensities were lower than they were for those with a normal MRI on the verbal index (79 vs. 102.3), visual index (81 vs. 93.7), and screening memory index (76 vs. 97.7). Children with HIMAL at baseline also had lower scores on those indexes (94.9 for verbal memory, 82.5 for visual memory, and 97 for screening memory) than did children with a normal MRI.

The differences were statistically significant for lower verbal memory and screening memory scores in patients with acute T2 hyperintensities and for lower visual memory scores in patients with HIMAL. The differences trended toward statistical significance for lower visual memory scores in children with acute T2 hyperintensities and for lower verbal memory scores in children with focal FSE seizures.

The researchers found no significant differences in memory task performances when stratifying for age at time of FSE, duration of FSE, or patients’ sex, according to Dr. Weiss.

With this initial connection uncovered, Dr. Weiss and her colleagues are looking to dive deeper into different aspects of hippocampal properties and FSE.

“We’re looking into the relationship between hippocampus size and memory performances, as well as continue to track these studies,” Dr. Weiss said in an interview. “Another factor to consider when you talk about memory is attention, and we have looked into it a bit, but we need more information.”

This study was funded by a grant from the National Institute of Neurological Disorders and Stroke. The presenters reported no relevant financial disclosures.

[email protected]

On Twitter @eaztweets

Biosimilars are primarily as safe as their originators, based on data from a review of current European regulatory documents. The findings were published online in the British Journal of Clinical Pharmacology.

“Biosimilars are officially approved as similar products to a biopharmaceutical originator, which often share the same International Nonproprietary Name,” wrote L.R.A. Lepelaars, MD, of Utrecht University, the Netherlands, and colleagues. However, many clinicians remain cautious about using biosimilars, particularly those in the United States, they noted. The European Medicines Agency (EMA) has filed safety data on biosimilars, but comparative effectiveness studies often are lacking, they wrote.

In this study, the researchers compared data on 25 biologic medicinal products (19 biosimilars and 6 originators). The biosimilars were authorized by the EMA between Jan. 1, 2005 and Oct. 30, 2015 (Br. J. Clin. Pharmacol. 2017 Nov 22; doi: 10.1111/bcp.13454).

Overall, the researchers found 55 general safety concerns, including 22 that were deemed highly clinically relevant. Another 21 were defined as medium, while 12 had low levels of clinical relevance.

Infliximab was the only active substance with more than one difference in safety concerns between the biosimilar and originator; three more general safety concerns (all of medium clinical relevance) were noted for infliximab biosimilars compared with the originator (bowel obstruction, hematologic reactions, and lack of efficacy).

For all other active substances included in the study, one difference or no difference was found in the general safety concerns between the biosimilars and originators, and none of the differences was related to immunogenicity

The researchers assessed the safety of biosimilars by comparing them with European Risk Management Plan or Summary of Product Characteristics.

The findings support the value of biosimilars based on comparable safety profiles, the researchers noted. However, “a direct comparison between biosimilars and related originators through formal postmarketing studies (observational or clinical trials) is mandatory for specific safety and effectiveness issues emerging during the products’ life cycle,” they said.

The researchers had no financial conflicts to disclose.

Biosimilars are primarily as safe as their originators, based on data from a review of current European regulatory documents. The findings were published online in the British Journal of Clinical Pharmacology.

“Biosimilars are officially approved as similar products to a biopharmaceutical originator, which often share the same International Nonproprietary Name,” wrote L.R.A. Lepelaars, MD, of Utrecht University, the Netherlands, and colleagues. However, many clinicians remain cautious about using biosimilars, particularly those in the United States, they noted. The European Medicines Agency (EMA) has filed safety data on biosimilars, but comparative effectiveness studies often are lacking, they wrote.

In this study, the researchers compared data on 25 biologic medicinal products (19 biosimilars and 6 originators). The biosimilars were authorized by the EMA between Jan. 1, 2005 and Oct. 30, 2015 (Br. J. Clin. Pharmacol. 2017 Nov 22; doi: 10.1111/bcp.13454).

Overall, the researchers found 55 general safety concerns, including 22 that were deemed highly clinically relevant. Another 21 were defined as medium, while 12 had low levels of clinical relevance.

Infliximab was the only active substance with more than one difference in safety concerns between the biosimilar and originator; three more general safety concerns (all of medium clinical relevance) were noted for infliximab biosimilars compared with the originator (bowel obstruction, hematologic reactions, and lack of efficacy).

For all other active substances included in the study, one difference or no difference was found in the general safety concerns between the biosimilars and originators, and none of the differences was related to immunogenicity

The researchers assessed the safety of biosimilars by comparing them with European Risk Management Plan or Summary of Product Characteristics.

The findings support the value of biosimilars based on comparable safety profiles, the researchers noted. However, “a direct comparison between biosimilars and related originators through formal postmarketing studies (observational or clinical trials) is mandatory for specific safety and effectiveness issues emerging during the products’ life cycle,” they said.

The researchers had no financial conflicts to disclose.

Biosimilars are primarily as safe as their originators, based on data from a review of current European regulatory documents. The findings were published online in the British Journal of Clinical Pharmacology.

“Biosimilars are officially approved as similar products to a biopharmaceutical originator, which often share the same International Nonproprietary Name,” wrote L.R.A. Lepelaars, MD, of Utrecht University, the Netherlands, and colleagues. However, many clinicians remain cautious about using biosimilars, particularly those in the United States, they noted. The European Medicines Agency (EMA) has filed safety data on biosimilars, but comparative effectiveness studies often are lacking, they wrote.

In this study, the researchers compared data on 25 biologic medicinal products (19 biosimilars and 6 originators). The biosimilars were authorized by the EMA between Jan. 1, 2005 and Oct. 30, 2015 (Br. J. Clin. Pharmacol. 2017 Nov 22; doi: 10.1111/bcp.13454).

Overall, the researchers found 55 general safety concerns, including 22 that were deemed highly clinically relevant. Another 21 were defined as medium, while 12 had low levels of clinical relevance.

Infliximab was the only active substance with more than one difference in safety concerns between the biosimilar and originator; three more general safety concerns (all of medium clinical relevance) were noted for infliximab biosimilars compared with the originator (bowel obstruction, hematologic reactions, and lack of efficacy).

For all other active substances included in the study, one difference or no difference was found in the general safety concerns between the biosimilars and originators, and none of the differences was related to immunogenicity

The researchers assessed the safety of biosimilars by comparing them with European Risk Management Plan or Summary of Product Characteristics.

The findings support the value of biosimilars based on comparable safety profiles, the researchers noted. However, “a direct comparison between biosimilars and related originators through formal postmarketing studies (observational or clinical trials) is mandatory for specific safety and effectiveness issues emerging during the products’ life cycle,” they said.

The researchers had no financial conflicts to disclose.

A lot has happened in oncology since the American Society of Clinical Oncology (ASCO) first issued its guidelines on platelet transfusion for patients with cancer in 2001, noted the authors of the updated recommendations.

“The expense of platelet transfusions, coupled with potential adverse effects such as febrile and allergic reactions, transfusion-related acute lung injury, and bacterial contamination point to the importance of evidence-based transfusion practice,” wrote Charles A Schiffer, MD, of Wayne State Michigan, Detroit, and his colleagues in the updated guidelines.

Many of the original recommendations remain unchanged, but there are updated evidence-based recommendations in five key areas.

For example, regarding platelet transfusion thresholds in the setting of hematologic stem-cell transplantation in adults, the guidelines incorporate evidence from randomized clinical trials showing that among adults who have received autologous hematologic stem-cell transplantation, bleeding rates with decreased use of platelets are similar whether patients are treated prophylactically or at the first sign of bleeding, “and this approach may be used in experienced centers,” wrote Dr. Schiffer and his colleagues (J Clin Oncol. 2017 Nov 28. doi: 10.1200/JCO.2017.76.1734).

The authors caution, however, that the recommendation applies to adults only.

Other updated recommendations include:

• Rhesus D alloimmunization from platelet transfusions to RhD-negative patients can be prevented through either exclusive use of platelet products from RhD-negative donors or immunoprophylaxis. The guidelines note that there is a low rate of RhD alloimmunization in cancer patients in general, but state that prevention may be used in girls and in women of child-bearing age who are being treated with curative intent.

• For patients with acute myeloid leukemia, receiving induction chemotherapy, the use of leukoreduced platelet and red blood cell products can reduce the likelihood that patients will develop alloantibody-mediated refractory reactions to plate transfusions.

“It is therefore appropriate to provide leukoreduced blood products to patients with [acute myeloid leukemia] from the time of diagnosis to ameliorate this important clinical problem,” the investigators wrote.

They noted that leukoreduction to prevent alloimmunization might benefit patients with other leukemia histologies and with other types of cancer who are undergoing chemotherapy, but added that there is a lack of evidence to support this as a recommendation outside of acute myeloid leukemia.

To reduce the risk of bleeding due to thrombocytopenia in patients with solid tumors who are undergoing chemotherapy, the panelists recommend transfusing patients when their platelet levels fall below 10 x 109 per liter. It is appropriate to give platelet transfusions to patients with higher levels when there is active localized bleeding, they stated.

The guideline authors also recommend that when refractoriness to platelet infusions is suspected, clinicians should perform platelet counts from 10 to 60 minutes after the transfusion is completed. A refractoriness determination should be made only after two or more infusions of ABO-compatible units that have been stored for less than 72 hours result in poor increments, they advised.

The guideline development process is supported by ASCO. Dr. Schiffer and six other guideline authors disclosed consulting or advisory roles, research funding, honoraria and/or fees with various pharmaceutical companies or other corporate entities.
 

A lot has happened in oncology since the American Society of Clinical Oncology (ASCO) first issued its guidelines on platelet transfusion for patients with cancer in 2001, noted the authors of the updated recommendations.

“The expense of platelet transfusions, coupled with potential adverse effects such as febrile and allergic reactions, transfusion-related acute lung injury, and bacterial contamination point to the importance of evidence-based transfusion practice,” wrote Charles A Schiffer, MD, of Wayne State Michigan, Detroit, and his colleagues in the updated guidelines.

Many of the original recommendations remain unchanged, but there are updated evidence-based recommendations in five key areas.

For example, regarding platelet transfusion thresholds in the setting of hematologic stem-cell transplantation in adults, the guidelines incorporate evidence from randomized clinical trials showing that among adults who have received autologous hematologic stem-cell transplantation, bleeding rates with decreased use of platelets are similar whether patients are treated prophylactically or at the first sign of bleeding, “and this approach may be used in experienced centers,” wrote Dr. Schiffer and his colleagues (J Clin Oncol. 2017 Nov 28. doi: 10.1200/JCO.2017.76.1734).

The authors caution, however, that the recommendation applies to adults only.

Other updated recommendations include:

• Rhesus D alloimmunization from platelet transfusions to RhD-negative patients can be prevented through either exclusive use of platelet products from RhD-negative donors or immunoprophylaxis. The guidelines note that there is a low rate of RhD alloimmunization in cancer patients in general, but state that prevention may be used in girls and in women of child-bearing age who are being treated with curative intent.

• For patients with acute myeloid leukemia, receiving induction chemotherapy, the use of leukoreduced platelet and red blood cell products can reduce the likelihood that patients will develop alloantibody-mediated refractory reactions to plate transfusions.

“It is therefore appropriate to provide leukoreduced blood products to patients with [acute myeloid leukemia] from the time of diagnosis to ameliorate this important clinical problem,” the investigators wrote.

They noted that leukoreduction to prevent alloimmunization might benefit patients with other leukemia histologies and with other types of cancer who are undergoing chemotherapy, but added that there is a lack of evidence to support this as a recommendation outside of acute myeloid leukemia.

To reduce the risk of bleeding due to thrombocytopenia in patients with solid tumors who are undergoing chemotherapy, the panelists recommend transfusing patients when their platelet levels fall below 10 x 109 per liter. It is appropriate to give platelet transfusions to patients with higher levels when there is active localized bleeding, they stated.

The guideline authors also recommend that when refractoriness to platelet infusions is suspected, clinicians should perform platelet counts from 10 to 60 minutes after the transfusion is completed. A refractoriness determination should be made only after two or more infusions of ABO-compatible units that have been stored for less than 72 hours result in poor increments, they advised.

The guideline development process is supported by ASCO. Dr. Schiffer and six other guideline authors disclosed consulting or advisory roles, research funding, honoraria and/or fees with various pharmaceutical companies or other corporate entities.
 

A lot has happened in oncology since the American Society of Clinical Oncology (ASCO) first issued its guidelines on platelet transfusion for patients with cancer in 2001, noted the authors of the updated recommendations.

“The expense of platelet transfusions, coupled with potential adverse effects such as febrile and allergic reactions, transfusion-related acute lung injury, and bacterial contamination point to the importance of evidence-based transfusion practice,” wrote Charles A Schiffer, MD, of Wayne State Michigan, Detroit, and his colleagues in the updated guidelines.

Many of the original recommendations remain unchanged, but there are updated evidence-based recommendations in five key areas.

For example, regarding platelet transfusion thresholds in the setting of hematologic stem-cell transplantation in adults, the guidelines incorporate evidence from randomized clinical trials showing that among adults who have received autologous hematologic stem-cell transplantation, bleeding rates with decreased use of platelets are similar whether patients are treated prophylactically or at the first sign of bleeding, “and this approach may be used in experienced centers,” wrote Dr. Schiffer and his colleagues (J Clin Oncol. 2017 Nov 28. doi: 10.1200/JCO.2017.76.1734).

The authors caution, however, that the recommendation applies to adults only.

Other updated recommendations include:

• Rhesus D alloimmunization from platelet transfusions to RhD-negative patients can be prevented through either exclusive use of platelet products from RhD-negative donors or immunoprophylaxis. The guidelines note that there is a low rate of RhD alloimmunization in cancer patients in general, but state that prevention may be used in girls and in women of child-bearing age who are being treated with curative intent.

• For patients with acute myeloid leukemia, receiving induction chemotherapy, the use of leukoreduced platelet and red blood cell products can reduce the likelihood that patients will develop alloantibody-mediated refractory reactions to plate transfusions.

“It is therefore appropriate to provide leukoreduced blood products to patients with [acute myeloid leukemia] from the time of diagnosis to ameliorate this important clinical problem,” the investigators wrote.

They noted that leukoreduction to prevent alloimmunization might benefit patients with other leukemia histologies and with other types of cancer who are undergoing chemotherapy, but added that there is a lack of evidence to support this as a recommendation outside of acute myeloid leukemia.

To reduce the risk of bleeding due to thrombocytopenia in patients with solid tumors who are undergoing chemotherapy, the panelists recommend transfusing patients when their platelet levels fall below 10 x 109 per liter. It is appropriate to give platelet transfusions to patients with higher levels when there is active localized bleeding, they stated.

The guideline authors also recommend that when refractoriness to platelet infusions is suspected, clinicians should perform platelet counts from 10 to 60 minutes after the transfusion is completed. A refractoriness determination should be made only after two or more infusions of ABO-compatible units that have been stored for less than 72 hours result in poor increments, they advised.

The guideline development process is supported by ASCO. Dr. Schiffer and six other guideline authors disclosed consulting or advisory roles, research funding, honoraria and/or fees with various pharmaceutical companies or other corporate entities.
 

A 66-year-old man presents with substernal chest pressure and dyspnea that has been present for 45 minutes. He has nausea. Vital signs: blood pressure, 110/60; pulse, 100; oxygen saturation, 92%. Neck: elevated jugular venous pressure. Chest: clear. Cardiac: normal S1 S2, no murmurs. ECG: ST elevation in 2, 3, and aVF leads.

Which of these treatments do you recommend?

A. Morphine, oxygen, nitroglycerin, and aspirin (ASA).

B. Oxygen, morphine, ASA.

C. ASA.

In this patient, I think the correct approach would be to just give aspirin. Nitroglycerin would be problematic, as it appears that this patient might be having a right ventricular infarct, and lowering right-sided filling pressures with nitroglycerin may lead to severe hypotension.

There is controversy over the safety of routine morphine use for patients with chest pain.

Trip J. Meine, MD, and colleagues found that use of morphine either alone or in combination with nitroglycerin for patients presenting with non–ST-elevation acute coronary syndrome (NSTE-ACS) was associated with higher mortality.¹ Cian P. McCarthy, MD, and colleagues found the same results, with morphine use associated with larger infarct size, a longer hospital stay, and a trend toward increased mortality in invasively managed NSTE-ACS patients.² Suzanne de Waha and colleagues found that morphine use in patients with ST-segment elevation MIs had larger infarct size and less reperfusion success, as measured by cardiac MRI.³

Not all recent studies show a detrimental effect of morphine. Etienne Puymirat et al. reviewed in-hospital complications (death, nonfatal re-MI, stroke, stent thrombosis, and bleeding) and 1-year survival according to prehospital morphine use in 2,438 ST-elevation MI (STEMI) patients from the French Registry of Acute ST-elevation and non–ST-elevation Myocardial Infarction (FAST-MI).⁴ They found no increase in in-hospital complications or 1-year mortality.

The practice of using supplemental oxygen to treat all patients with MI became standard nearly a century ago, after oxygen was found in 1900 to relieve angina, and led to clinical improvement in four MI patients in a 1930 case series.^5,6

It was not studied in a controlled trial until 1976, when J.M. Rawles, MD, and colleagues randomized 157 patients with MI to 24 hours of oxygen at 8 L/min or to ambient air. They found no difference in mortality between the groups, but they did find a higher burden of MI in the intervention arm receiving supplemental oxygen, as measured by mean serum aspartate aminotransferase levels.⁷

The topic was not addressed again in a significant randomized trial until this century. Most notably, two recent studies again demonstrated no benefit of supplemental oxygen in normoxemic patients with MI.

In the AVOID trial in 2015, Dion Stub, MD, PhD, and colleagues randomized 441 patients with STEMI to oxygen at 8 L/min – from diagnosis in an ambulance until after cardiac catheterization – or to ambient air. They found no difference in death at 6 months, but did find an increased rate of in-hospital recurrent MIs, with 0.9% of the control group and 5.5% of the oxygen intervention arm suffering recurrence (P = .006).⁸ They also showed a larger area of myocardial infarct in the oxygen group, as measured by peak creatine kinase levels and cardiac MRI at 6 months.

Proposed mechanisms of increased myocardial injury from hyperoxia include increased coronary vascular resistance resulting in decreased myocardial perfusion, and increased reperfusion injury from formation of free radicals.⁹

Dr. Tubbesing is a senior resident in medicine at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Am Heart J. 2005 Jun;149(6):1043-9.

2. J Interv Cardiol. 2017 Nov 22. doi: 10.1111/joic.12464.

3. Clin Res Cardiol. 2015 Sep;104(9):727-34.

4. Eur Heart J. 2016 Apr 1;37(13):1063-71.

5. BMJ. 1900 Dec 1;2(2083):1568.

6. JAMA. 1930 May 3;94(18):1363-5.

7. Br Med J. 1976 May 8;1(6018):1121-3.

8. Circulation. 2015 Jun 16;131(24):2143-50.

9. Cochrane Database Syst Rev. 2016 Dec 19;12:CD007160.

10. N Engl J Med. 2017 Sep 28;377(13):1240-9.

A 66-year-old man presents with substernal chest pressure and dyspnea that has been present for 45 minutes. He has nausea. Vital signs: blood pressure, 110/60; pulse, 100; oxygen saturation, 92%. Neck: elevated jugular venous pressure. Chest: clear. Cardiac: normal S1 S2, no murmurs. ECG: ST elevation in 2, 3, and aVF leads.

Which of these treatments do you recommend?

A. Morphine, oxygen, nitroglycerin, and aspirin (ASA).

B. Oxygen, morphine, ASA.

C. ASA.

In this patient, I think the correct approach would be to just give aspirin. Nitroglycerin would be problematic, as it appears that this patient might be having a right ventricular infarct, and lowering right-sided filling pressures with nitroglycerin may lead to severe hypotension.

There is controversy over the safety of routine morphine use for patients with chest pain.

Trip J. Meine, MD, and colleagues found that use of morphine either alone or in combination with nitroglycerin for patients presenting with non–ST-elevation acute coronary syndrome (NSTE-ACS) was associated with higher mortality.¹ Cian P. McCarthy, MD, and colleagues found the same results, with morphine use associated with larger infarct size, a longer hospital stay, and a trend toward increased mortality in invasively managed NSTE-ACS patients.² Suzanne de Waha and colleagues found that morphine use in patients with ST-segment elevation MIs had larger infarct size and less reperfusion success, as measured by cardiac MRI.³

Not all recent studies show a detrimental effect of morphine. Etienne Puymirat et al. reviewed in-hospital complications (death, nonfatal re-MI, stroke, stent thrombosis, and bleeding) and 1-year survival according to prehospital morphine use in 2,438 ST-elevation MI (STEMI) patients from the French Registry of Acute ST-elevation and non–ST-elevation Myocardial Infarction (FAST-MI).⁴ They found no increase in in-hospital complications or 1-year mortality.

The practice of using supplemental oxygen to treat all patients with MI became standard nearly a century ago, after oxygen was found in 1900 to relieve angina, and led to clinical improvement in four MI patients in a 1930 case series.^5,6

It was not studied in a controlled trial until 1976, when J.M. Rawles, MD, and colleagues randomized 157 patients with MI to 24 hours of oxygen at 8 L/min or to ambient air. They found no difference in mortality between the groups, but they did find a higher burden of MI in the intervention arm receiving supplemental oxygen, as measured by mean serum aspartate aminotransferase levels.⁷

The topic was not addressed again in a significant randomized trial until this century. Most notably, two recent studies again demonstrated no benefit of supplemental oxygen in normoxemic patients with MI.

In the AVOID trial in 2015, Dion Stub, MD, PhD, and colleagues randomized 441 patients with STEMI to oxygen at 8 L/min – from diagnosis in an ambulance until after cardiac catheterization – or to ambient air. They found no difference in death at 6 months, but did find an increased rate of in-hospital recurrent MIs, with 0.9% of the control group and 5.5% of the oxygen intervention arm suffering recurrence (P = .006).⁸ They also showed a larger area of myocardial infarct in the oxygen group, as measured by peak creatine kinase levels and cardiac MRI at 6 months.

Proposed mechanisms of increased myocardial injury from hyperoxia include increased coronary vascular resistance resulting in decreased myocardial perfusion, and increased reperfusion injury from formation of free radicals.⁹

Dr. Tubbesing is a senior resident in medicine at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Am Heart J. 2005 Jun;149(6):1043-9.

2. J Interv Cardiol. 2017 Nov 22. doi: 10.1111/joic.12464.

3. Clin Res Cardiol. 2015 Sep;104(9):727-34.

4. Eur Heart J. 2016 Apr 1;37(13):1063-71.

5. BMJ. 1900 Dec 1;2(2083):1568.

6. JAMA. 1930 May 3;94(18):1363-5.

7. Br Med J. 1976 May 8;1(6018):1121-3.

8. Circulation. 2015 Jun 16;131(24):2143-50.

9. Cochrane Database Syst Rev. 2016 Dec 19;12:CD007160.

10. N Engl J Med. 2017 Sep 28;377(13):1240-9.

A 66-year-old man presents with substernal chest pressure and dyspnea that has been present for 45 minutes. He has nausea. Vital signs: blood pressure, 110/60; pulse, 100; oxygen saturation, 92%. Neck: elevated jugular venous pressure. Chest: clear. Cardiac: normal S1 S2, no murmurs. ECG: ST elevation in 2, 3, and aVF leads.

Which of these treatments do you recommend?

A. Morphine, oxygen, nitroglycerin, and aspirin (ASA).

B. Oxygen, morphine, ASA.

C. ASA.

In this patient, I think the correct approach would be to just give aspirin. Nitroglycerin would be problematic, as it appears that this patient might be having a right ventricular infarct, and lowering right-sided filling pressures with nitroglycerin may lead to severe hypotension.

There is controversy over the safety of routine morphine use for patients with chest pain.

Trip J. Meine, MD, and colleagues found that use of morphine either alone or in combination with nitroglycerin for patients presenting with non–ST-elevation acute coronary syndrome (NSTE-ACS) was associated with higher mortality.¹ Cian P. McCarthy, MD, and colleagues found the same results, with morphine use associated with larger infarct size, a longer hospital stay, and a trend toward increased mortality in invasively managed NSTE-ACS patients.² Suzanne de Waha and colleagues found that morphine use in patients with ST-segment elevation MIs had larger infarct size and less reperfusion success, as measured by cardiac MRI.³

Not all recent studies show a detrimental effect of morphine. Etienne Puymirat et al. reviewed in-hospital complications (death, nonfatal re-MI, stroke, stent thrombosis, and bleeding) and 1-year survival according to prehospital morphine use in 2,438 ST-elevation MI (STEMI) patients from the French Registry of Acute ST-elevation and non–ST-elevation Myocardial Infarction (FAST-MI).⁴ They found no increase in in-hospital complications or 1-year mortality.

The practice of using supplemental oxygen to treat all patients with MI became standard nearly a century ago, after oxygen was found in 1900 to relieve angina, and led to clinical improvement in four MI patients in a 1930 case series.^5,6

It was not studied in a controlled trial until 1976, when J.M. Rawles, MD, and colleagues randomized 157 patients with MI to 24 hours of oxygen at 8 L/min or to ambient air. They found no difference in mortality between the groups, but they did find a higher burden of MI in the intervention arm receiving supplemental oxygen, as measured by mean serum aspartate aminotransferase levels.⁷

The topic was not addressed again in a significant randomized trial until this century. Most notably, two recent studies again demonstrated no benefit of supplemental oxygen in normoxemic patients with MI.

In the AVOID trial in 2015, Dion Stub, MD, PhD, and colleagues randomized 441 patients with STEMI to oxygen at 8 L/min – from diagnosis in an ambulance until after cardiac catheterization – or to ambient air. They found no difference in death at 6 months, but did find an increased rate of in-hospital recurrent MIs, with 0.9% of the control group and 5.5% of the oxygen intervention arm suffering recurrence (P = .006).⁸ They also showed a larger area of myocardial infarct in the oxygen group, as measured by peak creatine kinase levels and cardiac MRI at 6 months.

Proposed mechanisms of increased myocardial injury from hyperoxia include increased coronary vascular resistance resulting in decreased myocardial perfusion, and increased reperfusion injury from formation of free radicals.⁹

Dr. Tubbesing is a senior resident in medicine at the University of Washington, Seattle. Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].

References

1. Am Heart J. 2005 Jun;149(6):1043-9.

2. J Interv Cardiol. 2017 Nov 22. doi: 10.1111/joic.12464.

3. Clin Res Cardiol. 2015 Sep;104(9):727-34.

4. Eur Heart J. 2016 Apr 1;37(13):1063-71.

5. BMJ. 1900 Dec 1;2(2083):1568.

6. JAMA. 1930 May 3;94(18):1363-5.

7. Br Med J. 1976 May 8;1(6018):1121-3.

8. Circulation. 2015 Jun 16;131(24):2143-50.

9. Cochrane Database Syst Rev. 2016 Dec 19;12:CD007160.

10. N Engl J Med. 2017 Sep 28;377(13):1240-9.

The Diagnosis: Epstein-Barr Virus

Physical examination revealed bilateral 1-cm ulcerated lesions on the labia minora with vulvar edema (Figure). She had a palpable liver edge but no splenomegaly, oral ulcers or lesions, conjunctivitis or scleral icterus, or cervical or inguinal lymphadenopathy. A detailed genitourinary examination was performed under anesthesia, but the hymen was not commented on. Inflammatory markers were elevated with a C-reactive protein level of 16.4 mg/L (reference range, 0.08-3.1 mg/mL), erythrocyte sedimentation rate of39 mm/h (reference range, 0-20 mm/h), white blood cell count of 7.1×10⁹/L (reference range, 4.5-11.0×10⁹/L) with 57% neutrophils and 30% lymphocytes, an alanine aminotransferase level of 41 U/L (reference range, 10-40 U/L), and an aspartate aminotransferase level of 126 U/L (reference range, 10-30 U/L). 

Bacterial and fungal cultures of vulvar tissue were negative as well as blood and urine cultures. Serological tests for herpes simplex virus (HSV), syphilis, and cytomegalovirus were negative, and urine testing for gonorrhea and chlamydia were negative. Serologies for Epstein-Barr virus (EBV) all were strongly positive with an EBV viral capsid antigen (VCA) IgM greater than 160 U/mL, early antigen IgG of 68 U/mL, and EBV VCA IgG of 456 U/mL. Two years after the initial presentation, repeat EBV serologies were obtained, showing a strongly positive EBV VCA IgG (>8.0 antibody index; reference range, 0-0.8), and a negative EBV VCA IgM.

Infectious etiologies of genital ulcers in a sexually active female include HSV, syphilis, lymphogranuloma venereum, and chancroid. Herpes simplex virus often is the assumed etiology of genital ulcers, especially in sexually active patients, and misdiagnosis in the setting of negative HSV testing may be high. Less common infectious causes such as mumps and cytomegalovirus also have been reported.^1,2 Lichen planus and lichen sclerosus are noninfectious inflammatory causes, both of which may involve and be limited to the genitals. Autoimmune disorders include Crohn disease and Behçet disease, and vulvar ulcers with an eschar, consistent with aphthous major or complex apotheosis, has been used to describe patients with severe recurrent oral and genital ulcerations without other systemic manifestations of Behçet disease.³

Genital ulcers are an uncommon manifestation of EBV infection. The formation of genital ulcers in EBV infection has been hypothesized to be due to immune complex formation during the acute phase that becomes activated in the vasculature, leading to microthrombosis and eventually necrosis of the tissue.⁴ The mode of transmission for EBV-related acute genital ulcers has been postulated to be hematogenous spread in lymphocytes or EBV shedding in the urine with subsequent transfer to the genital mucosa.⁵

Epstein-Barr virus-related acute genital ulcers are self-limiting. The average healing time for the ulcers is 14 to 18 days.^6,7 Antivirals are ineffective in treating this condition; however, supportive treatment with systemic glucocorticoids for associated swelling and pain medications could be considered. Our patient was treated symptomatically. Two weeks after debridement, granulation tissue was noted at the site and her pain and discomfort had resolved. This case illustrates an uncommon manifestation of EBV in a sexually inactive adolescent and is a reminder for the dermatologist of the diverse spectrum of illness caused by this common virus.

The Diagnosis: Epstein-Barr Virus

Physical examination revealed bilateral 1-cm ulcerated lesions on the labia minora with vulvar edema (Figure). She had a palpable liver edge but no splenomegaly, oral ulcers or lesions, conjunctivitis or scleral icterus, or cervical or inguinal lymphadenopathy. A detailed genitourinary examination was performed under anesthesia, but the hymen was not commented on. Inflammatory markers were elevated with a C-reactive protein level of 16.4 mg/L (reference range, 0.08-3.1 mg/mL), erythrocyte sedimentation rate of39 mm/h (reference range, 0-20 mm/h), white blood cell count of 7.1×10⁹/L (reference range, 4.5-11.0×10⁹/L) with 57% neutrophils and 30% lymphocytes, an alanine aminotransferase level of 41 U/L (reference range, 10-40 U/L), and an aspartate aminotransferase level of 126 U/L (reference range, 10-30 U/L). 

Bacterial and fungal cultures of vulvar tissue were negative as well as blood and urine cultures. Serological tests for herpes simplex virus (HSV), syphilis, and cytomegalovirus were negative, and urine testing for gonorrhea and chlamydia were negative. Serologies for Epstein-Barr virus (EBV) all were strongly positive with an EBV viral capsid antigen (VCA) IgM greater than 160 U/mL, early antigen IgG of 68 U/mL, and EBV VCA IgG of 456 U/mL. Two years after the initial presentation, repeat EBV serologies were obtained, showing a strongly positive EBV VCA IgG (>8.0 antibody index; reference range, 0-0.8), and a negative EBV VCA IgM.

Infectious etiologies of genital ulcers in a sexually active female include HSV, syphilis, lymphogranuloma venereum, and chancroid. Herpes simplex virus often is the assumed etiology of genital ulcers, especially in sexually active patients, and misdiagnosis in the setting of negative HSV testing may be high. Less common infectious causes such as mumps and cytomegalovirus also have been reported.^1,2 Lichen planus and lichen sclerosus are noninfectious inflammatory causes, both of which may involve and be limited to the genitals. Autoimmune disorders include Crohn disease and Behçet disease, and vulvar ulcers with an eschar, consistent with aphthous major or complex apotheosis, has been used to describe patients with severe recurrent oral and genital ulcerations without other systemic manifestations of Behçet disease.³

Genital ulcers are an uncommon manifestation of EBV infection. The formation of genital ulcers in EBV infection has been hypothesized to be due to immune complex formation during the acute phase that becomes activated in the vasculature, leading to microthrombosis and eventually necrosis of the tissue.⁴ The mode of transmission for EBV-related acute genital ulcers has been postulated to be hematogenous spread in lymphocytes or EBV shedding in the urine with subsequent transfer to the genital mucosa.⁵

Epstein-Barr virus-related acute genital ulcers are self-limiting. The average healing time for the ulcers is 14 to 18 days.^6,7 Antivirals are ineffective in treating this condition; however, supportive treatment with systemic glucocorticoids for associated swelling and pain medications could be considered. Our patient was treated symptomatically. Two weeks after debridement, granulation tissue was noted at the site and her pain and discomfort had resolved. This case illustrates an uncommon manifestation of EBV in a sexually inactive adolescent and is a reminder for the dermatologist of the diverse spectrum of illness caused by this common virus.

The Diagnosis: Epstein-Barr Virus

Physical examination revealed bilateral 1-cm ulcerated lesions on the labia minora with vulvar edema (Figure). She had a palpable liver edge but no splenomegaly, oral ulcers or lesions, conjunctivitis or scleral icterus, or cervical or inguinal lymphadenopathy. A detailed genitourinary examination was performed under anesthesia, but the hymen was not commented on. Inflammatory markers were elevated with a C-reactive protein level of 16.4 mg/L (reference range, 0.08-3.1 mg/mL), erythrocyte sedimentation rate of39 mm/h (reference range, 0-20 mm/h), white blood cell count of 7.1×10⁹/L (reference range, 4.5-11.0×10⁹/L) with 57% neutrophils and 30% lymphocytes, an alanine aminotransferase level of 41 U/L (reference range, 10-40 U/L), and an aspartate aminotransferase level of 126 U/L (reference range, 10-30 U/L). 

Bacterial and fungal cultures of vulvar tissue were negative as well as blood and urine cultures. Serological tests for herpes simplex virus (HSV), syphilis, and cytomegalovirus were negative, and urine testing for gonorrhea and chlamydia were negative. Serologies for Epstein-Barr virus (EBV) all were strongly positive with an EBV viral capsid antigen (VCA) IgM greater than 160 U/mL, early antigen IgG of 68 U/mL, and EBV VCA IgG of 456 U/mL. Two years after the initial presentation, repeat EBV serologies were obtained, showing a strongly positive EBV VCA IgG (>8.0 antibody index; reference range, 0-0.8), and a negative EBV VCA IgM.

Infectious etiologies of genital ulcers in a sexually active female include HSV, syphilis, lymphogranuloma venereum, and chancroid. Herpes simplex virus often is the assumed etiology of genital ulcers, especially in sexually active patients, and misdiagnosis in the setting of negative HSV testing may be high. Less common infectious causes such as mumps and cytomegalovirus also have been reported.^1,2 Lichen planus and lichen sclerosus are noninfectious inflammatory causes, both of which may involve and be limited to the genitals. Autoimmune disorders include Crohn disease and Behçet disease, and vulvar ulcers with an eschar, consistent with aphthous major or complex apotheosis, has been used to describe patients with severe recurrent oral and genital ulcerations without other systemic manifestations of Behçet disease.³

Genital ulcers are an uncommon manifestation of EBV infection. The formation of genital ulcers in EBV infection has been hypothesized to be due to immune complex formation during the acute phase that becomes activated in the vasculature, leading to microthrombosis and eventually necrosis of the tissue.⁴ The mode of transmission for EBV-related acute genital ulcers has been postulated to be hematogenous spread in lymphocytes or EBV shedding in the urine with subsequent transfer to the genital mucosa.⁵

Epstein-Barr virus-related acute genital ulcers are self-limiting. The average healing time for the ulcers is 14 to 18 days.^6,7 Antivirals are ineffective in treating this condition; however, supportive treatment with systemic glucocorticoids for associated swelling and pain medications could be considered. Our patient was treated symptomatically. Two weeks after debridement, granulation tissue was noted at the site and her pain and discomfort had resolved. This case illustrates an uncommon manifestation of EBV in a sexually inactive adolescent and is a reminder for the dermatologist of the diverse spectrum of illness caused by this common virus.

Years ago, after the revelation of sexual predations of male members of the U.S. Navy upon their female underlings, the Navy announced a “zero tolerance” policy. I, then the chair of the American Psychiatric Association Committee on Women, was invited to address a meeting of top Naval officers. They seemed dismayed when I told them that zero tolerance was just the beginning. Declarations that certain behaviors are unacceptable are facile, flimsy, and ultimately disingenuous substitutes for the infinitely more difficult task of monitoring and policing forbidden behaviors and protecting potential and actual victims.

The United States, I pointed out, has a zero tolerance policy on murder but still has to maintain a large force of police officers, detectives, judges, and prison guards to enforce that policy. The Navy had to have a similar approach to sexual assaults. Judging from the recent reports of female members of the military, that hasn’t happened.

Clarity in the law

Unwanted physical intrusion by one adult on another is against the law in the United States. Then why do we need laws specifically banning rape? In addition to the fact that rape, unlike any other assault, can result in conception, sexual assault is recognized as a particularly and uniquely evil and damaging invasion and degradation.

Although there are cultural differences about responsibility for rape, and whether marriage obviates a woman’s right to refuse sexual contact, there is little or no dispute about the need to recognize rape as a distinct, degrading, and particularly heinous attack. It is, therefore, no surprise that people who are raped feel soiled, shamed, and degraded. Those feelings are exacerbated by centuries of shifting responsibility for sexual assault, whether forced intercourse or other unwanted sexual behavior, from the perpetrator onto the victim.

The shifting of blame has been rejected in theory, but it very much persists in actuality. Who among us does not wonder how the victim was dressed or why (s)he was on that street, at that party, in that man’s room? Other forms of harassment echo the motivations of rape – to demonstrate the unanswerable power to degrade – and result in similar psychological responses.

The recent media revelations have lumped physical assault together with unwanted touching, sexual acts undergone as a result of psychological coercion, unwanted exposure to perpetrators’ genitalia and masturbation, and offensive sexual requests and comments. All of those acts are wrong, but they are not equivalent. An elderly man in a wheelchair grabbing an adult woman’s buttocks is not in the same category as an adult man sexually assaulting an underage girl.

What is the genesis of all this misbehavior? It’s not just about sex; it’s about sex and power. For many men, bragging about sexual conquests and making derogatory remarks about women’s physical appearance demonstrate machismo – define maleness.

It is not surprising that such comments are called “locker room talk”; sports are macho displays as well. Physically violating sexual boundaries is just the talk put into action. And macho works. Last November, more than 40% of female voters in the United States voted for the candidate who reportedly cheated on at least one of his three wives, bragged about unwanted sexual assault, and has been credibly accused of many other illegal and/or inappropriate behaviors.

Where does it end?

What is going to be the result of all this hullabaloo? The list of convincingly accused perpetrators grows by the day. Sexism and sexual misbehavior are endemic in every sphere of human endeavor, up to and including, of course, the clergy, who are meant to be models and protectors of virtue. The scope of recent revelations may be unusual, but revelations about one sector or another have happened every few years: the military, clergy, Wall Street, Silicon Valley, academia. What would happen if all the sexual misbehavior were to be revealed, and the perpetrators removed from their leadership and management positions? Would we have a film industry, a financial industry, a legislature? I saw a headline somewhere: “He’s always indispensable; you never are.” The argument, or myth, of indispensability is a powerful protection for powerful individuals. The powerful are too powerful to tolerate mass expulsions. Already, Congress has resorted to the time-honored and demonstrably useless response: training. Others among the accused report that they are undergoing treatment of sex addiction, a diagnosis our profession has wisely discarded, and for which there was no effective treatment.

Sex, while not addictive, does have a role in sexual misbehavior. Through the ages, women’s reproductive hormones have been a focus of social and medical attention, as the source of unpleasant behaviors, and, in fact, psychopathology: premenstrual dysphoric disorder, postpartum depression. Little or no attention has been paid to the problematic psychosocial effects of male reproductive hormones. In addition to the offensive behaviors currently in the headlines, there is the behavior of adolescent males. Isn’t reckless driving related to the pubertal influx of testosterone (Neurosci Biobehav Rev. 2006;30[3]:319-45)? This gender discrepancy deserves scientific and social attention.

What can psychiatrists do to help women (and men) who are affected by sexual misbehavior? This is a difficult problem. What would help most victims, of any injustice, most would be to confront those responsible, and see them removed from positions of power and otherwise punished. However, the recent reports of seemingly swift and severe responses are misleading. The responsible journalists who have reported these cases have, in most cases, devoted months to finding victimized women, persuading them to go public, and corroborating their accounts. The perpetrators, even when complaints have been made, have gone unpunished, and often been promoted, for years or even decades. Women who complain often are subject to employer retaliation.

So a treating psychiatrist is left with less-than-satisfactory recommendations and responses. The most important intervention is to identify and counter the patient’s inaccurate and damaging assumptions: that she was responsible, that she should and could have refused to tolerate the misbehavior, that she has been left tainted, impure. Some social groups and families will have reinforced the latter feeling. The remainder of the psychiatric intervention will be focused on the patient’s particular symptoms – of posttraumatic stress, anxiety, or depression – and the relationship between her symptoms, history, and psychodynamics. Group therapy or other support by women who have faced similar abuse may be helpful. I’m afraid that we will continue to have many such patients to treat.

Dr. Stotland, past president of the American Psychiatric Association, is professor of psychiatry, and obstetrics and gynecology, at Rush Medical College, Chicago. She has written numerous articles and books, including “Cutting Edge Medicine: What Psychiatrists Need to Know” (American Psychiatric Association Publishing, 2002).

Years ago, after the revelation of sexual predations of male members of the U.S. Navy upon their female underlings, the Navy announced a “zero tolerance” policy. I, then the chair of the American Psychiatric Association Committee on Women, was invited to address a meeting of top Naval officers. They seemed dismayed when I told them that zero tolerance was just the beginning. Declarations that certain behaviors are unacceptable are facile, flimsy, and ultimately disingenuous substitutes for the infinitely more difficult task of monitoring and policing forbidden behaviors and protecting potential and actual victims.

The United States, I pointed out, has a zero tolerance policy on murder but still has to maintain a large force of police officers, detectives, judges, and prison guards to enforce that policy. The Navy had to have a similar approach to sexual assaults. Judging from the recent reports of female members of the military, that hasn’t happened.

Clarity in the law

Unwanted physical intrusion by one adult on another is against the law in the United States. Then why do we need laws specifically banning rape? In addition to the fact that rape, unlike any other assault, can result in conception, sexual assault is recognized as a particularly and uniquely evil and damaging invasion and degradation.

Although there are cultural differences about responsibility for rape, and whether marriage obviates a woman’s right to refuse sexual contact, there is little or no dispute about the need to recognize rape as a distinct, degrading, and particularly heinous attack. It is, therefore, no surprise that people who are raped feel soiled, shamed, and degraded. Those feelings are exacerbated by centuries of shifting responsibility for sexual assault, whether forced intercourse or other unwanted sexual behavior, from the perpetrator onto the victim.

The shifting of blame has been rejected in theory, but it very much persists in actuality. Who among us does not wonder how the victim was dressed or why (s)he was on that street, at that party, in that man’s room? Other forms of harassment echo the motivations of rape – to demonstrate the unanswerable power to degrade – and result in similar psychological responses.

The recent media revelations have lumped physical assault together with unwanted touching, sexual acts undergone as a result of psychological coercion, unwanted exposure to perpetrators’ genitalia and masturbation, and offensive sexual requests and comments. All of those acts are wrong, but they are not equivalent. An elderly man in a wheelchair grabbing an adult woman’s buttocks is not in the same category as an adult man sexually assaulting an underage girl.

What is the genesis of all this misbehavior? It’s not just about sex; it’s about sex and power. For many men, bragging about sexual conquests and making derogatory remarks about women’s physical appearance demonstrate machismo – define maleness.

It is not surprising that such comments are called “locker room talk”; sports are macho displays as well. Physically violating sexual boundaries is just the talk put into action. And macho works. Last November, more than 40% of female voters in the United States voted for the candidate who reportedly cheated on at least one of his three wives, bragged about unwanted sexual assault, and has been credibly accused of many other illegal and/or inappropriate behaviors.

Where does it end?

What is going to be the result of all this hullabaloo? The list of convincingly accused perpetrators grows by the day. Sexism and sexual misbehavior are endemic in every sphere of human endeavor, up to and including, of course, the clergy, who are meant to be models and protectors of virtue. The scope of recent revelations may be unusual, but revelations about one sector or another have happened every few years: the military, clergy, Wall Street, Silicon Valley, academia. What would happen if all the sexual misbehavior were to be revealed, and the perpetrators removed from their leadership and management positions? Would we have a film industry, a financial industry, a legislature? I saw a headline somewhere: “He’s always indispensable; you never are.” The argument, or myth, of indispensability is a powerful protection for powerful individuals. The powerful are too powerful to tolerate mass expulsions. Already, Congress has resorted to the time-honored and demonstrably useless response: training. Others among the accused report that they are undergoing treatment of sex addiction, a diagnosis our profession has wisely discarded, and for which there was no effective treatment.

Sex, while not addictive, does have a role in sexual misbehavior. Through the ages, women’s reproductive hormones have been a focus of social and medical attention, as the source of unpleasant behaviors, and, in fact, psychopathology: premenstrual dysphoric disorder, postpartum depression. Little or no attention has been paid to the problematic psychosocial effects of male reproductive hormones. In addition to the offensive behaviors currently in the headlines, there is the behavior of adolescent males. Isn’t reckless driving related to the pubertal influx of testosterone (Neurosci Biobehav Rev. 2006;30[3]:319-45)? This gender discrepancy deserves scientific and social attention.

What can psychiatrists do to help women (and men) who are affected by sexual misbehavior? This is a difficult problem. What would help most victims, of any injustice, most would be to confront those responsible, and see them removed from positions of power and otherwise punished. However, the recent reports of seemingly swift and severe responses are misleading. The responsible journalists who have reported these cases have, in most cases, devoted months to finding victimized women, persuading them to go public, and corroborating their accounts. The perpetrators, even when complaints have been made, have gone unpunished, and often been promoted, for years or even decades. Women who complain often are subject to employer retaliation.

So a treating psychiatrist is left with less-than-satisfactory recommendations and responses. The most important intervention is to identify and counter the patient’s inaccurate and damaging assumptions: that she was responsible, that she should and could have refused to tolerate the misbehavior, that she has been left tainted, impure. Some social groups and families will have reinforced the latter feeling. The remainder of the psychiatric intervention will be focused on the patient’s particular symptoms – of posttraumatic stress, anxiety, or depression – and the relationship between her symptoms, history, and psychodynamics. Group therapy or other support by women who have faced similar abuse may be helpful. I’m afraid that we will continue to have many such patients to treat.

Dr. Stotland, past president of the American Psychiatric Association, is professor of psychiatry, and obstetrics and gynecology, at Rush Medical College, Chicago. She has written numerous articles and books, including “Cutting Edge Medicine: What Psychiatrists Need to Know” (American Psychiatric Association Publishing, 2002).

Years ago, after the revelation of sexual predations of male members of the U.S. Navy upon their female underlings, the Navy announced a “zero tolerance” policy. I, then the chair of the American Psychiatric Association Committee on Women, was invited to address a meeting of top Naval officers. They seemed dismayed when I told them that zero tolerance was just the beginning. Declarations that certain behaviors are unacceptable are facile, flimsy, and ultimately disingenuous substitutes for the infinitely more difficult task of monitoring and policing forbidden behaviors and protecting potential and actual victims.

The United States, I pointed out, has a zero tolerance policy on murder but still has to maintain a large force of police officers, detectives, judges, and prison guards to enforce that policy. The Navy had to have a similar approach to sexual assaults. Judging from the recent reports of female members of the military, that hasn’t happened.

Clarity in the law

Unwanted physical intrusion by one adult on another is against the law in the United States. Then why do we need laws specifically banning rape? In addition to the fact that rape, unlike any other assault, can result in conception, sexual assault is recognized as a particularly and uniquely evil and damaging invasion and degradation.

Although there are cultural differences about responsibility for rape, and whether marriage obviates a woman’s right to refuse sexual contact, there is little or no dispute about the need to recognize rape as a distinct, degrading, and particularly heinous attack. It is, therefore, no surprise that people who are raped feel soiled, shamed, and degraded. Those feelings are exacerbated by centuries of shifting responsibility for sexual assault, whether forced intercourse or other unwanted sexual behavior, from the perpetrator onto the victim.

The shifting of blame has been rejected in theory, but it very much persists in actuality. Who among us does not wonder how the victim was dressed or why (s)he was on that street, at that party, in that man’s room? Other forms of harassment echo the motivations of rape – to demonstrate the unanswerable power to degrade – and result in similar psychological responses.

The recent media revelations have lumped physical assault together with unwanted touching, sexual acts undergone as a result of psychological coercion, unwanted exposure to perpetrators’ genitalia and masturbation, and offensive sexual requests and comments. All of those acts are wrong, but they are not equivalent. An elderly man in a wheelchair grabbing an adult woman’s buttocks is not in the same category as an adult man sexually assaulting an underage girl.

What is the genesis of all this misbehavior? It’s not just about sex; it’s about sex and power. For many men, bragging about sexual conquests and making derogatory remarks about women’s physical appearance demonstrate machismo – define maleness.

It is not surprising that such comments are called “locker room talk”; sports are macho displays as well. Physically violating sexual boundaries is just the talk put into action. And macho works. Last November, more than 40% of female voters in the United States voted for the candidate who reportedly cheated on at least one of his three wives, bragged about unwanted sexual assault, and has been credibly accused of many other illegal and/or inappropriate behaviors.

Where does it end?

What is going to be the result of all this hullabaloo? The list of convincingly accused perpetrators grows by the day. Sexism and sexual misbehavior are endemic in every sphere of human endeavor, up to and including, of course, the clergy, who are meant to be models and protectors of virtue. The scope of recent revelations may be unusual, but revelations about one sector or another have happened every few years: the military, clergy, Wall Street, Silicon Valley, academia. What would happen if all the sexual misbehavior were to be revealed, and the perpetrators removed from their leadership and management positions? Would we have a film industry, a financial industry, a legislature? I saw a headline somewhere: “He’s always indispensable; you never are.” The argument, or myth, of indispensability is a powerful protection for powerful individuals. The powerful are too powerful to tolerate mass expulsions. Already, Congress has resorted to the time-honored and demonstrably useless response: training. Others among the accused report that they are undergoing treatment of sex addiction, a diagnosis our profession has wisely discarded, and for which there was no effective treatment.

Sex, while not addictive, does have a role in sexual misbehavior. Through the ages, women’s reproductive hormones have been a focus of social and medical attention, as the source of unpleasant behaviors, and, in fact, psychopathology: premenstrual dysphoric disorder, postpartum depression. Little or no attention has been paid to the problematic psychosocial effects of male reproductive hormones. In addition to the offensive behaviors currently in the headlines, there is the behavior of adolescent males. Isn’t reckless driving related to the pubertal influx of testosterone (Neurosci Biobehav Rev. 2006;30[3]:319-45)? This gender discrepancy deserves scientific and social attention.

What can psychiatrists do to help women (and men) who are affected by sexual misbehavior? This is a difficult problem. What would help most victims, of any injustice, most would be to confront those responsible, and see them removed from positions of power and otherwise punished. However, the recent reports of seemingly swift and severe responses are misleading. The responsible journalists who have reported these cases have, in most cases, devoted months to finding victimized women, persuading them to go public, and corroborating their accounts. The perpetrators, even when complaints have been made, have gone unpunished, and often been promoted, for years or even decades. Women who complain often are subject to employer retaliation.

So a treating psychiatrist is left with less-than-satisfactory recommendations and responses. The most important intervention is to identify and counter the patient’s inaccurate and damaging assumptions: that she was responsible, that she should and could have refused to tolerate the misbehavior, that she has been left tainted, impure. Some social groups and families will have reinforced the latter feeling. The remainder of the psychiatric intervention will be focused on the patient’s particular symptoms – of posttraumatic stress, anxiety, or depression – and the relationship between her symptoms, history, and psychodynamics. Group therapy or other support by women who have faced similar abuse may be helpful. I’m afraid that we will continue to have many such patients to treat.

Dr. Stotland, past president of the American Psychiatric Association, is professor of psychiatry, and obstetrics and gynecology, at Rush Medical College, Chicago. She has written numerous articles and books, including “Cutting Edge Medicine: What Psychiatrists Need to Know” (American Psychiatric Association Publishing, 2002).

BOSTON – Changes in the retina seem to mirror changes that begin to reshape the brain in preclinical Alzheimer’s disease.

Manifested as a reduction in volume in the retinal nerve fiber layer, these changes appear to track the aggregation of beta amyloid brain plaques well before cognitive problems arise – and can be easily measured with a piece of equipment already in many optometry offices, Peter J. Snyder, PhD, said at the Clinical Trials in Alzheimer’s Disease conference.

Courtesy Dr. Peter Synder

[email protected]

On Twitter @Alz_Gal

BOSTON – Changes in the retina seem to mirror changes that begin to reshape the brain in preclinical Alzheimer’s disease.

Manifested as a reduction in volume in the retinal nerve fiber layer, these changes appear to track the aggregation of beta amyloid brain plaques well before cognitive problems arise – and can be easily measured with a piece of equipment already in many optometry offices, Peter J. Snyder, PhD, said at the Clinical Trials in Alzheimer’s Disease conference.

Courtesy Dr. Peter Synder

[email protected]

On Twitter @Alz_Gal

BOSTON – Changes in the retina seem to mirror changes that begin to reshape the brain in preclinical Alzheimer’s disease.

Manifested as a reduction in volume in the retinal nerve fiber layer, these changes appear to track the aggregation of beta amyloid brain plaques well before cognitive problems arise – and can be easily measured with a piece of equipment already in many optometry offices, Peter J. Snyder, PhD, said at the Clinical Trials in Alzheimer’s Disease conference.

Courtesy Dr. Peter Synder

[email protected]

On Twitter @Alz_Gal

During your career, you serve as staff member and leader to many different professional groups. Some are collaborative, collegial, and supportive. Others are competitive, antagonistic, or even combative. What are the benefits and downsides of each of these cultures and what can you do, as a hospitalist leader, to influence the character of your workplace?

• Unity of mission – In Boston, that was to “save lives,” and it motivated and activated the whole of the response.
• Generosity of spirit and action – Across the community, people were eager to assist in the response.
• Everyone stayed in their own lanes of responsibility and helped others succeed in theirs – There were law enforcement, medical, and resilience activities and the theme across the leaders was “how can I help make you a success?”
• No ego and no blame – There was a level of emotional intelligence and maturity among the leaders.
• A foundation of trusting relations – These leaders had known one another for years and, though the decisions were tough, they were confident in the motives and actions of the others.

While the discovery emerged from our crisis research, the findings equally apply to other, more routine work and interactions. Conduct your own assessment. Have you worked in groups in which these principles of swarm leadership characterized the experience? People were focused on a shared mission: They were available to assist one another; accomplished their work in ways that were respectful and supportive of their different responsibilities; did not claim undue credit or swipe at each another; and knew one another well enough to trust the others’ actions and motives.

The flip side of this continuum of collaboration and competition we term “suspicion leadership.” This is characterized by selfish ambitions; narcissistic actions; grabs for authority and resources; credit taking for the good and accusations for the bad; and an environment of mistrust and back stabbing.

Leaders influence the tone and tenor of their own group’s interactions as well as interactions among different working groups. As role models, if they articulate and demonstrate a mission that others can rally around, they forge that critical unity of mission. By contrast, suspicion leaders make it clear that “it is all about me and my priorities.” There is much work to be done, and swarm leaders ensure that people have the resources, autonomy, and support necessary to get the job done. On the other end, the work environment is burdened by the uncertainties about who does what and who is responsible. Swarm leaders are focused on “we” and suspicion leaders are caught up on “me.” There is no trust when people are suspicious of one another. Much can be accomplished when people believe in themselves, their colleagues, and the reasons that bring them together.

As a hospitalist leader, you influence where on this continuum your group will lie. It is your choice to be a role model for the principles of swarm, encouraging the same among others. When those principles become the beacons by which you work and relate, you will find an environment that inspires people to be and to do their best.

In the next column, how to build trust within your teams.

Dr. Marcus is director, Program on Health Care Negotiation and Conflict Resolution, at the Harvard T.H. Chan School of Public Health, in Boston.

During your career, you serve as staff member and leader to many different professional groups. Some are collaborative, collegial, and supportive. Others are competitive, antagonistic, or even combative. What are the benefits and downsides of each of these cultures and what can you do, as a hospitalist leader, to influence the character of your workplace?

• Unity of mission – In Boston, that was to “save lives,” and it motivated and activated the whole of the response.
• Generosity of spirit and action – Across the community, people were eager to assist in the response.
• Everyone stayed in their own lanes of responsibility and helped others succeed in theirs – There were law enforcement, medical, and resilience activities and the theme across the leaders was “how can I help make you a success?”
• No ego and no blame – There was a level of emotional intelligence and maturity among the leaders.
• A foundation of trusting relations – These leaders had known one another for years and, though the decisions were tough, they were confident in the motives and actions of the others.

While the discovery emerged from our crisis research, the findings equally apply to other, more routine work and interactions. Conduct your own assessment. Have you worked in groups in which these principles of swarm leadership characterized the experience? People were focused on a shared mission: They were available to assist one another; accomplished their work in ways that were respectful and supportive of their different responsibilities; did not claim undue credit or swipe at each another; and knew one another well enough to trust the others’ actions and motives.

The flip side of this continuum of collaboration and competition we term “suspicion leadership.” This is characterized by selfish ambitions; narcissistic actions; grabs for authority and resources; credit taking for the good and accusations for the bad; and an environment of mistrust and back stabbing.

Leaders influence the tone and tenor of their own group’s interactions as well as interactions among different working groups. As role models, if they articulate and demonstrate a mission that others can rally around, they forge that critical unity of mission. By contrast, suspicion leaders make it clear that “it is all about me and my priorities.” There is much work to be done, and swarm leaders ensure that people have the resources, autonomy, and support necessary to get the job done. On the other end, the work environment is burdened by the uncertainties about who does what and who is responsible. Swarm leaders are focused on “we” and suspicion leaders are caught up on “me.” There is no trust when people are suspicious of one another. Much can be accomplished when people believe in themselves, their colleagues, and the reasons that bring them together.

As a hospitalist leader, you influence where on this continuum your group will lie. It is your choice to be a role model for the principles of swarm, encouraging the same among others. When those principles become the beacons by which you work and relate, you will find an environment that inspires people to be and to do their best.

In the next column, how to build trust within your teams.

Dr. Marcus is director, Program on Health Care Negotiation and Conflict Resolution, at the Harvard T.H. Chan School of Public Health, in Boston.

During your career, you serve as staff member and leader to many different professional groups. Some are collaborative, collegial, and supportive. Others are competitive, antagonistic, or even combative. What are the benefits and downsides of each of these cultures and what can you do, as a hospitalist leader, to influence the character of your workplace?

• Unity of mission – In Boston, that was to “save lives,” and it motivated and activated the whole of the response.
• Generosity of spirit and action – Across the community, people were eager to assist in the response.
• Everyone stayed in their own lanes of responsibility and helped others succeed in theirs – There were law enforcement, medical, and resilience activities and the theme across the leaders was “how can I help make you a success?”
• No ego and no blame – There was a level of emotional intelligence and maturity among the leaders.
• A foundation of trusting relations – These leaders had known one another for years and, though the decisions were tough, they were confident in the motives and actions of the others.

While the discovery emerged from our crisis research, the findings equally apply to other, more routine work and interactions. Conduct your own assessment. Have you worked in groups in which these principles of swarm leadership characterized the experience? People were focused on a shared mission: They were available to assist one another; accomplished their work in ways that were respectful and supportive of their different responsibilities; did not claim undue credit or swipe at each another; and knew one another well enough to trust the others’ actions and motives.

The flip side of this continuum of collaboration and competition we term “suspicion leadership.” This is characterized by selfish ambitions; narcissistic actions; grabs for authority and resources; credit taking for the good and accusations for the bad; and an environment of mistrust and back stabbing.

Leaders influence the tone and tenor of their own group’s interactions as well as interactions among different working groups. As role models, if they articulate and demonstrate a mission that others can rally around, they forge that critical unity of mission. By contrast, suspicion leaders make it clear that “it is all about me and my priorities.” There is much work to be done, and swarm leaders ensure that people have the resources, autonomy, and support necessary to get the job done. On the other end, the work environment is burdened by the uncertainties about who does what and who is responsible. Swarm leaders are focused on “we” and suspicion leaders are caught up on “me.” There is no trust when people are suspicious of one another. Much can be accomplished when people believe in themselves, their colleagues, and the reasons that bring them together.

As a hospitalist leader, you influence where on this continuum your group will lie. It is your choice to be a role model for the principles of swarm, encouraging the same among others. When those principles become the beacons by which you work and relate, you will find an environment that inspires people to be and to do their best.

In the next column, how to build trust within your teams.

Dr. Marcus is director, Program on Health Care Negotiation and Conflict Resolution, at the Harvard T.H. Chan School of Public Health, in Boston.