Legislation requiring doctors to tell their patients that a medication abortion can be reversed is cropping up across the country.

Already in 2017, Colorado, Georgia, Indiana, Idaho, and North Carolina have introduced versions of the so-called abortion reversal legislation. In March, Utah became the latest state to pass a law addressing discontinuation of a medication abortion. Arkansas, South Dakota, and Arizona have similar laws on the books, but a court challenge ultimately led Arizona to amend its law, significantly toning down the language on reversal.

Courtesy Dr. Daniel Grossman

[email protected]

On Twitter @legal_med

Legislation requiring doctors to tell their patients that a medication abortion can be reversed is cropping up across the country.

Already in 2017, Colorado, Georgia, Indiana, Idaho, and North Carolina have introduced versions of the so-called abortion reversal legislation. In March, Utah became the latest state to pass a law addressing discontinuation of a medication abortion. Arkansas, South Dakota, and Arizona have similar laws on the books, but a court challenge ultimately led Arizona to amend its law, significantly toning down the language on reversal.

Courtesy Dr. Daniel Grossman

[email protected]

On Twitter @legal_med

Legislation requiring doctors to tell their patients that a medication abortion can be reversed is cropping up across the country.

Already in 2017, Colorado, Georgia, Indiana, Idaho, and North Carolina have introduced versions of the so-called abortion reversal legislation. In March, Utah became the latest state to pass a law addressing discontinuation of a medication abortion. Arkansas, South Dakota, and Arizona have similar laws on the books, but a court challenge ultimately led Arizona to amend its law, significantly toning down the language on reversal.

Courtesy Dr. Daniel Grossman

[email protected]

On Twitter @legal_med

Clozapine is an atypical antipsychotic that is usually reserved for use in patients with treatment-resistant schizophrenia or schizoaffective disorder with suicidality. Due to the risk of severe neutropenia, clozapine is available only through a restricted Clozapine Risk Evaluation and Mitigation Strategy (REMS) Program, which requires provider certification, patient enrollment and adherence with absolute neutrophil count (ANC) testing and monitoring, and dispensing pharmacy certification.¹ In addition, clozapine (Clozaril) prescribing information contains a boxed warning for potentially fatal cardiomyopathy. One recently published study from Australia demonstrated a 4.65% incidence of cardiomyopathy in patients started on clozapine, which is much higher than the incidence provided by national drug surveillance programs.^2-4 An increased awareness is needed among health care professionals, including physicians, pharmacists, and nurses, about this serious fatal condition.

Clozapine-induced cardiomyopathy is a diagnosis of exclusion that requires the absence of other etiologies of cardiac dysfunction (ie, coronary artery disease, hypertension, valvular disease, congenital heart disease, etc). Diagnosing a clozapine-related cardiomyopathy may be a long and laborious task. Patients with cardiomyopathy may present with many nonspecific signs and symptoms, such as fatigue, dyspnea, edema, and/or nausea and vomiting, which are present in other diseases; therefore, multiple encounters and lab tests may be needed until a cardiac source is implicated. The exact mechanism is unknown; however, Chow and colleagues believe that clozapine is a direct toxin of the myocardium.^5-7

Case Presentation

A 30-year-old woman with a history of asthma, hypothyroidism (euthyroid with supplementation), posttraumatic stress disorder, and schizoaffective disorder was started on clozapine due to major depression and increased suicidal ideation despite previous treatment with several other antipsychotic agents. Clozapine was gradually titrated to a dose of 150 mg twice a day during an inpatient psychiatric admission. Prior to starting clozapine, this patient had been admitted to the psychiatry unit 11 times within the prior 2 years. After initiating and titrating clozapine over 4 months, her psychiatric symptoms markedly improved.

More than 4 years after the initiation of clozapine and after various treatments for multiple symptoms (Sidebar), the patient was diagnosed with heart failure (HF) with a reduced ejection fraction (EF) of 10% to 15%. She was referred to the cardiology HF clinic. Her dose of clozapine 150 mg at bedtime was discontinued after a discussion with psychiatry. She had a negative workup for other HF etiologies and was started on HF medications that included carvedilol, losartan, and spironolactone. After discontinuation of clozapine, her psychiatric symptoms worsened, and she was admitted to the psychiatry unit twice within a year. Two months after clozapine was discontinued, a repeat echocardiogram (ECHO) was obtained and was essentially unchanged. A chest X-ray (CXR) obtained 4 months after clozapine discontinuation demonstrated a normalized cardio-mediastinal silhouette. A third ECHO was ordered during her second psychiatric admission, which was 11 months after clozapine discontinuation; this revealed an improved left ventricular EF (LVEF) of 30% to 35% and resolution of left ventricular (LV) dilation.

This patient’s clinical course led to an extensive chart review that investigated whether there may have been earlier signs and symptoms of HF or cardiomyopathy. It was discovered that the initial HF signs and symptoms were likely present for about 1 year before the diagnosis was made and after having been on clozapine for about 40 months (Patient’s ECHO before and after clozapine discontinuation, click here for additional ECHO perspectives ).

Discussion

In retrospect, this patient likely had HF for many months prior to the official diagnosis; however, given this patient’s young age, prior history of asthma, respiratory disorders, underlying severe psychiatric disease, and confounding symptoms, it is easy to understand why the diagnosis was initially overlooked and delayed.

This patient did not have significant lower extremity edema, but she reported nausea, vomiting, and weight loss. Typical patients with HF exhibit edema and weight gain unless they experience cardiac cachexia. It is not clear whether this patient had a coexisting gastrointestinal (GI) disorder or whether the GI symptoms were secondary to cardiac cachexia. Additionally, weight gain and metabolic syndrome have been documented with clozapine therapy.

It is interesting that a repeat ECHO within 2 months of clozapine discontinuation did not show an improvement, whereas a CXR at 4 months showed a normal cardiac silhouette, and an ECHO at 11 months showed an improvement in EF and normalization of LV size while on appropriate HF medications. It would have been interesting if an ECHO had been completed at 4 months to correspond with the time when the CXR normalized.

There does not seem to be a high level of awareness regarding this potentially fatal diagnosis of cardiomyopathy related to the use of clozapine. A recent review of clozapine-induced cardiomyopathy by Alawami and colleagues revealed characteristics, including median age of diagnosis of 33.5 years, a mean daily dose of 360 mg (range 125-700 mg/d), average time of therapy until the development of symptoms 14.4 months (range between 3 weeks and 4 years), and the presence of ventricular dilation in 39%.⁸ The most common symptoms on clinical presentation were shortness of breath (60%), palpitations (36%), cough (16%), fatigue (16%), and chest pain (8%).⁸

It is interesting that edema was not present in the patients studied in their review; this difference from the usual presentation of severe HF may lower clinical suspicion and makes diagnosing this type of cardiomyopathy more difficult. Alawami also noted that patients with an LVEF < 25% at the time of diagnosis tended to have a poorer prognosis with the highest risk of mortality and limited recovery. Fortunately, in this case, the patient’s LVEF improved significantly, and it will be interesting to continue to monitor the patient for further improvement.

As a result of this case, the authors have performed a chart review on all patients prescribed clozapine at VA Loma Linda Healthcare System. Additionally, this case supports the implementation of better cardiomyopathy monitoring of all clozapine patients. It may be recommended to obtain a baseline CXR in all patients starting clozapine, conduct monthly cardiomyopathy symptom screening that coincides with ANC monitoring, and perform an ECHO immediately on any clinical suspicion of cardiomyopathy.

Conclusion

Better awareness and regular screening for signs and symptoms of HF may help prevent a delay in diagnosing a rare but serious and potentially fatal condition associated with clozapine. Chest X-rays demonstrating cardiomegaly can be helpful when the early diagnosis of HF is suspected and may be the first diagnostic imaging test to normalize after clozapine discontinuation.

Since clozapine is a REMS medication and all patients are scheduled for regular ANC follow-up, it would seem prudent that patients also should be screened for signs and symptoms of HF, including the new onset or worsening of baseline shortness of breath, palpitations, cough, fatigue, chest pain, edema, gastroparesis, and perhaps extreme weight loss. Once a physician suspects HF, an ECHO should be obtained immediately.

In addition to the clozapine boxed warning for cardiomyopathy, it would be helpful if the clozapine patient counseling information section had a specific warning that advises patients to contact their clinician if they develop the signs and symptoms of HF.

Clozapine is an atypical antipsychotic that is usually reserved for use in patients with treatment-resistant schizophrenia or schizoaffective disorder with suicidality. Due to the risk of severe neutropenia, clozapine is available only through a restricted Clozapine Risk Evaluation and Mitigation Strategy (REMS) Program, which requires provider certification, patient enrollment and adherence with absolute neutrophil count (ANC) testing and monitoring, and dispensing pharmacy certification.¹ In addition, clozapine (Clozaril) prescribing information contains a boxed warning for potentially fatal cardiomyopathy. One recently published study from Australia demonstrated a 4.65% incidence of cardiomyopathy in patients started on clozapine, which is much higher than the incidence provided by national drug surveillance programs.^2-4 An increased awareness is needed among health care professionals, including physicians, pharmacists, and nurses, about this serious fatal condition.

Clozapine-induced cardiomyopathy is a diagnosis of exclusion that requires the absence of other etiologies of cardiac dysfunction (ie, coronary artery disease, hypertension, valvular disease, congenital heart disease, etc). Diagnosing a clozapine-related cardiomyopathy may be a long and laborious task. Patients with cardiomyopathy may present with many nonspecific signs and symptoms, such as fatigue, dyspnea, edema, and/or nausea and vomiting, which are present in other diseases; therefore, multiple encounters and lab tests may be needed until a cardiac source is implicated. The exact mechanism is unknown; however, Chow and colleagues believe that clozapine is a direct toxin of the myocardium.^5-7

Case Presentation

A 30-year-old woman with a history of asthma, hypothyroidism (euthyroid with supplementation), posttraumatic stress disorder, and schizoaffective disorder was started on clozapine due to major depression and increased suicidal ideation despite previous treatment with several other antipsychotic agents. Clozapine was gradually titrated to a dose of 150 mg twice a day during an inpatient psychiatric admission. Prior to starting clozapine, this patient had been admitted to the psychiatry unit 11 times within the prior 2 years. After initiating and titrating clozapine over 4 months, her psychiatric symptoms markedly improved.

More than 4 years after the initiation of clozapine and after various treatments for multiple symptoms (Sidebar), the patient was diagnosed with heart failure (HF) with a reduced ejection fraction (EF) of 10% to 15%. She was referred to the cardiology HF clinic. Her dose of clozapine 150 mg at bedtime was discontinued after a discussion with psychiatry. She had a negative workup for other HF etiologies and was started on HF medications that included carvedilol, losartan, and spironolactone. After discontinuation of clozapine, her psychiatric symptoms worsened, and she was admitted to the psychiatry unit twice within a year. Two months after clozapine was discontinued, a repeat echocardiogram (ECHO) was obtained and was essentially unchanged. A chest X-ray (CXR) obtained 4 months after clozapine discontinuation demonstrated a normalized cardio-mediastinal silhouette. A third ECHO was ordered during her second psychiatric admission, which was 11 months after clozapine discontinuation; this revealed an improved left ventricular EF (LVEF) of 30% to 35% and resolution of left ventricular (LV) dilation.

This patient’s clinical course led to an extensive chart review that investigated whether there may have been earlier signs and symptoms of HF or cardiomyopathy. It was discovered that the initial HF signs and symptoms were likely present for about 1 year before the diagnosis was made and after having been on clozapine for about 40 months (Patient’s ECHO before and after clozapine discontinuation, click here for additional ECHO perspectives ).

Discussion

In retrospect, this patient likely had HF for many months prior to the official diagnosis; however, given this patient’s young age, prior history of asthma, respiratory disorders, underlying severe psychiatric disease, and confounding symptoms, it is easy to understand why the diagnosis was initially overlooked and delayed.

This patient did not have significant lower extremity edema, but she reported nausea, vomiting, and weight loss. Typical patients with HF exhibit edema and weight gain unless they experience cardiac cachexia. It is not clear whether this patient had a coexisting gastrointestinal (GI) disorder or whether the GI symptoms were secondary to cardiac cachexia. Additionally, weight gain and metabolic syndrome have been documented with clozapine therapy.

It is interesting that a repeat ECHO within 2 months of clozapine discontinuation did not show an improvement, whereas a CXR at 4 months showed a normal cardiac silhouette, and an ECHO at 11 months showed an improvement in EF and normalization of LV size while on appropriate HF medications. It would have been interesting if an ECHO had been completed at 4 months to correspond with the time when the CXR normalized.

There does not seem to be a high level of awareness regarding this potentially fatal diagnosis of cardiomyopathy related to the use of clozapine. A recent review of clozapine-induced cardiomyopathy by Alawami and colleagues revealed characteristics, including median age of diagnosis of 33.5 years, a mean daily dose of 360 mg (range 125-700 mg/d), average time of therapy until the development of symptoms 14.4 months (range between 3 weeks and 4 years), and the presence of ventricular dilation in 39%.⁸ The most common symptoms on clinical presentation were shortness of breath (60%), palpitations (36%), cough (16%), fatigue (16%), and chest pain (8%).⁸

It is interesting that edema was not present in the patients studied in their review; this difference from the usual presentation of severe HF may lower clinical suspicion and makes diagnosing this type of cardiomyopathy more difficult. Alawami also noted that patients with an LVEF < 25% at the time of diagnosis tended to have a poorer prognosis with the highest risk of mortality and limited recovery. Fortunately, in this case, the patient’s LVEF improved significantly, and it will be interesting to continue to monitor the patient for further improvement.

As a result of this case, the authors have performed a chart review on all patients prescribed clozapine at VA Loma Linda Healthcare System. Additionally, this case supports the implementation of better cardiomyopathy monitoring of all clozapine patients. It may be recommended to obtain a baseline CXR in all patients starting clozapine, conduct monthly cardiomyopathy symptom screening that coincides with ANC monitoring, and perform an ECHO immediately on any clinical suspicion of cardiomyopathy.

Conclusion

Better awareness and regular screening for signs and symptoms of HF may help prevent a delay in diagnosing a rare but serious and potentially fatal condition associated with clozapine. Chest X-rays demonstrating cardiomegaly can be helpful when the early diagnosis of HF is suspected and may be the first diagnostic imaging test to normalize after clozapine discontinuation.

Since clozapine is a REMS medication and all patients are scheduled for regular ANC follow-up, it would seem prudent that patients also should be screened for signs and symptoms of HF, including the new onset or worsening of baseline shortness of breath, palpitations, cough, fatigue, chest pain, edema, gastroparesis, and perhaps extreme weight loss. Once a physician suspects HF, an ECHO should be obtained immediately.

In addition to the clozapine boxed warning for cardiomyopathy, it would be helpful if the clozapine patient counseling information section had a specific warning that advises patients to contact their clinician if they develop the signs and symptoms of HF.

Clozapine is an atypical antipsychotic that is usually reserved for use in patients with treatment-resistant schizophrenia or schizoaffective disorder with suicidality. Due to the risk of severe neutropenia, clozapine is available only through a restricted Clozapine Risk Evaluation and Mitigation Strategy (REMS) Program, which requires provider certification, patient enrollment and adherence with absolute neutrophil count (ANC) testing and monitoring, and dispensing pharmacy certification.¹ In addition, clozapine (Clozaril) prescribing information contains a boxed warning for potentially fatal cardiomyopathy. One recently published study from Australia demonstrated a 4.65% incidence of cardiomyopathy in patients started on clozapine, which is much higher than the incidence provided by national drug surveillance programs.^2-4 An increased awareness is needed among health care professionals, including physicians, pharmacists, and nurses, about this serious fatal condition.

Clozapine-induced cardiomyopathy is a diagnosis of exclusion that requires the absence of other etiologies of cardiac dysfunction (ie, coronary artery disease, hypertension, valvular disease, congenital heart disease, etc). Diagnosing a clozapine-related cardiomyopathy may be a long and laborious task. Patients with cardiomyopathy may present with many nonspecific signs and symptoms, such as fatigue, dyspnea, edema, and/or nausea and vomiting, which are present in other diseases; therefore, multiple encounters and lab tests may be needed until a cardiac source is implicated. The exact mechanism is unknown; however, Chow and colleagues believe that clozapine is a direct toxin of the myocardium.^5-7

Case Presentation

A 30-year-old woman with a history of asthma, hypothyroidism (euthyroid with supplementation), posttraumatic stress disorder, and schizoaffective disorder was started on clozapine due to major depression and increased suicidal ideation despite previous treatment with several other antipsychotic agents. Clozapine was gradually titrated to a dose of 150 mg twice a day during an inpatient psychiatric admission. Prior to starting clozapine, this patient had been admitted to the psychiatry unit 11 times within the prior 2 years. After initiating and titrating clozapine over 4 months, her psychiatric symptoms markedly improved.

More than 4 years after the initiation of clozapine and after various treatments for multiple symptoms (Sidebar), the patient was diagnosed with heart failure (HF) with a reduced ejection fraction (EF) of 10% to 15%. She was referred to the cardiology HF clinic. Her dose of clozapine 150 mg at bedtime was discontinued after a discussion with psychiatry. She had a negative workup for other HF etiologies and was started on HF medications that included carvedilol, losartan, and spironolactone. After discontinuation of clozapine, her psychiatric symptoms worsened, and she was admitted to the psychiatry unit twice within a year. Two months after clozapine was discontinued, a repeat echocardiogram (ECHO) was obtained and was essentially unchanged. A chest X-ray (CXR) obtained 4 months after clozapine discontinuation demonstrated a normalized cardio-mediastinal silhouette. A third ECHO was ordered during her second psychiatric admission, which was 11 months after clozapine discontinuation; this revealed an improved left ventricular EF (LVEF) of 30% to 35% and resolution of left ventricular (LV) dilation.

This patient’s clinical course led to an extensive chart review that investigated whether there may have been earlier signs and symptoms of HF or cardiomyopathy. It was discovered that the initial HF signs and symptoms were likely present for about 1 year before the diagnosis was made and after having been on clozapine for about 40 months (Patient’s ECHO before and after clozapine discontinuation, click here for additional ECHO perspectives ).

Discussion

In retrospect, this patient likely had HF for many months prior to the official diagnosis; however, given this patient’s young age, prior history of asthma, respiratory disorders, underlying severe psychiatric disease, and confounding symptoms, it is easy to understand why the diagnosis was initially overlooked and delayed.

This patient did not have significant lower extremity edema, but she reported nausea, vomiting, and weight loss. Typical patients with HF exhibit edema and weight gain unless they experience cardiac cachexia. It is not clear whether this patient had a coexisting gastrointestinal (GI) disorder or whether the GI symptoms were secondary to cardiac cachexia. Additionally, weight gain and metabolic syndrome have been documented with clozapine therapy.

It is interesting that a repeat ECHO within 2 months of clozapine discontinuation did not show an improvement, whereas a CXR at 4 months showed a normal cardiac silhouette, and an ECHO at 11 months showed an improvement in EF and normalization of LV size while on appropriate HF medications. It would have been interesting if an ECHO had been completed at 4 months to correspond with the time when the CXR normalized.

There does not seem to be a high level of awareness regarding this potentially fatal diagnosis of cardiomyopathy related to the use of clozapine. A recent review of clozapine-induced cardiomyopathy by Alawami and colleagues revealed characteristics, including median age of diagnosis of 33.5 years, a mean daily dose of 360 mg (range 125-700 mg/d), average time of therapy until the development of symptoms 14.4 months (range between 3 weeks and 4 years), and the presence of ventricular dilation in 39%.⁸ The most common symptoms on clinical presentation were shortness of breath (60%), palpitations (36%), cough (16%), fatigue (16%), and chest pain (8%).⁸

It is interesting that edema was not present in the patients studied in their review; this difference from the usual presentation of severe HF may lower clinical suspicion and makes diagnosing this type of cardiomyopathy more difficult. Alawami also noted that patients with an LVEF < 25% at the time of diagnosis tended to have a poorer prognosis with the highest risk of mortality and limited recovery. Fortunately, in this case, the patient’s LVEF improved significantly, and it will be interesting to continue to monitor the patient for further improvement.

As a result of this case, the authors have performed a chart review on all patients prescribed clozapine at VA Loma Linda Healthcare System. Additionally, this case supports the implementation of better cardiomyopathy monitoring of all clozapine patients. It may be recommended to obtain a baseline CXR in all patients starting clozapine, conduct monthly cardiomyopathy symptom screening that coincides with ANC monitoring, and perform an ECHO immediately on any clinical suspicion of cardiomyopathy.

Conclusion

Better awareness and regular screening for signs and symptoms of HF may help prevent a delay in diagnosing a rare but serious and potentially fatal condition associated with clozapine. Chest X-rays demonstrating cardiomegaly can be helpful when the early diagnosis of HF is suspected and may be the first diagnostic imaging test to normalize after clozapine discontinuation.

Since clozapine is a REMS medication and all patients are scheduled for regular ANC follow-up, it would seem prudent that patients also should be screened for signs and symptoms of HF, including the new onset or worsening of baseline shortness of breath, palpitations, cough, fatigue, chest pain, edema, gastroparesis, and perhaps extreme weight loss. Once a physician suspects HF, an ECHO should be obtained immediately.

In addition to the clozapine boxed warning for cardiomyopathy, it would be helpful if the clozapine patient counseling information section had a specific warning that advises patients to contact their clinician if they develop the signs and symptoms of HF.

Photo by Rhoda Baer

Second cancers take a greater toll on patients under the age of 40, according to research published in JAMA Oncology.

Researchers studied 14 types of cancer occurring in more than 1 million patients.

For nearly all of the cancers studied, 5-year survival rates were much higher if the cancer occurred as a first malignancy rather than a second cancer.

These survival differences were more pronounced in pediatric patients and adolescents and young adults (AYAs) than they were in patients age 40 and older.

Researchers hope these findings will help guide clinicians in providing age-specific recommendations on cancer prevention, screening, treatment, and survivorship, especially among the AYA population.

“Although the increased incidence of second cancers is well known among cancer survivors, less is known about outcomes of these cancers or the influence of age,” said Theresa Keegan, PhD, of the UC Davis Comprehensive Cancer Center in Sacramento, California.

With this in mind, Dr Keegan and her colleagues analyzed data on patients diagnosed with either a single cancer or a first and second malignancy during 1992 through 2008. The researchers used Surveillance, Epidemiology and End Results program data collected from 13 cancer registries.

The team collected data on the 14 most common cancer types that affect AYAs: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), soft tissue sarcoma, and bone sarcoma, as well as female breast, thyroid, testicular, colorectal, central nervous system, cervical, and ovarian cancers.

There were a total of 15,954 pediatric patients (younger than 15 years at diagnosis), 125,750 AYAs (ages 15 to 39), and 878,370 older adult patients (age 40 and older).

Survival rates

For pediatric patients, the 5-year relative survival was 80% for a first cancer and 47% for a second primary malignancy.

For AYAs, the 5-year relative survival was 81% for a first cancer and 60% for a second primary malignancy.

For older adults, the 5-year relative survival was 70% for a first cancer and 61% for a second primary malignancy.

When the researchers looked at 5-year survival by age and individual cancer types, they found striking differences depending on whether it was a first or second malignancy in all but 2 of the 14 cancer types, testicular cancer and melanoma.

“For almost every type of cancer, the AYA population did worse with a secondary cancer,” said study author Melanie Goldfarb, MD, of John Wayne Cancer Institute at Providence Saint John’s Health Center in Santa Monica, California.

“What struck us was that the second cancer caused such an increased risk of death.”

Lymphomas

For pediatric patients with HL, the 5-year relative survival was 95% when patients had HL as a first cancer. There were no data on HL as a second primary malignancy.

For AYAs, the 5-year relative survival was 93% when patients had HL as a first cancer and 72% when they had HL as a second primary malignancy.

For older adults, the 5-year relative survival was 69% when patients had HL as a first cancer and 54% when they had HL as a second primary malignancy.

For pediatric patients with NHL, the 5-year relative survival was 84% when patients had NHL as a first cancer and 63% when they had NHL as a second primary malignancy.

For AYAs, the 5-year relative survival was 64% when patients had NHL as a first cancer and 22% when they had NHL as a second primary malignancy.

For older adults, the 5-year relative survival was 57% when patients had NHL as a first cancer and 54% when they had NHL as a second primary malignancy.

Leukemias

For pediatric patients with ALL, the 5-year relative survival was 87% when patients had ALL as a first cancer and 63% when they had ALL as a second primary malignancy.

For AYAs, the 5-year relative survival was 48% when patients had ALL as a first cancer and 26% when they had ALL as a second primary malignancy.

For older adults, the 5-year relative survival was 17% when patients had ALL as a first cancer and 11% when they had ALL as a second primary malignancy.

For pediatric patients with AML, the 5-year relative survival was 57% when patients had AML as a first cancer and 29% when they had AML as a second primary malignancy.

For AYAs, the 5-year relative survival was 46% when patients had AML as a first cancer and 23% when they had AML as a second primary malignancy.

For older adults, the 5-year relative survival was 12% when patients had AML as a first cancer and 10% when they had AML as a second primary malignancy.

Why younger patients tend to fare worse after a second cancer than older patients is not fully understood or specifically addressed in the current study, the researchers noted.

Now, the team plans to examine how the time between getting a first and second cancer affects survival and whether the type of treatment for the first cancer influences the outcome of a second cancer.

Photo by Rhoda Baer

Second cancers take a greater toll on patients under the age of 40, according to research published in JAMA Oncology.

Researchers studied 14 types of cancer occurring in more than 1 million patients.

For nearly all of the cancers studied, 5-year survival rates were much higher if the cancer occurred as a first malignancy rather than a second cancer.

These survival differences were more pronounced in pediatric patients and adolescents and young adults (AYAs) than they were in patients age 40 and older.

Researchers hope these findings will help guide clinicians in providing age-specific recommendations on cancer prevention, screening, treatment, and survivorship, especially among the AYA population.

“Although the increased incidence of second cancers is well known among cancer survivors, less is known about outcomes of these cancers or the influence of age,” said Theresa Keegan, PhD, of the UC Davis Comprehensive Cancer Center in Sacramento, California.

With this in mind, Dr Keegan and her colleagues analyzed data on patients diagnosed with either a single cancer or a first and second malignancy during 1992 through 2008. The researchers used Surveillance, Epidemiology and End Results program data collected from 13 cancer registries.

The team collected data on the 14 most common cancer types that affect AYAs: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), soft tissue sarcoma, and bone sarcoma, as well as female breast, thyroid, testicular, colorectal, central nervous system, cervical, and ovarian cancers.

There were a total of 15,954 pediatric patients (younger than 15 years at diagnosis), 125,750 AYAs (ages 15 to 39), and 878,370 older adult patients (age 40 and older).

Survival rates

For pediatric patients, the 5-year relative survival was 80% for a first cancer and 47% for a second primary malignancy.

For AYAs, the 5-year relative survival was 81% for a first cancer and 60% for a second primary malignancy.

For older adults, the 5-year relative survival was 70% for a first cancer and 61% for a second primary malignancy.

When the researchers looked at 5-year survival by age and individual cancer types, they found striking differences depending on whether it was a first or second malignancy in all but 2 of the 14 cancer types, testicular cancer and melanoma.

“For almost every type of cancer, the AYA population did worse with a secondary cancer,” said study author Melanie Goldfarb, MD, of John Wayne Cancer Institute at Providence Saint John’s Health Center in Santa Monica, California.

“What struck us was that the second cancer caused such an increased risk of death.”

Lymphomas

For pediatric patients with HL, the 5-year relative survival was 95% when patients had HL as a first cancer. There were no data on HL as a second primary malignancy.

For AYAs, the 5-year relative survival was 93% when patients had HL as a first cancer and 72% when they had HL as a second primary malignancy.

For older adults, the 5-year relative survival was 69% when patients had HL as a first cancer and 54% when they had HL as a second primary malignancy.

For pediatric patients with NHL, the 5-year relative survival was 84% when patients had NHL as a first cancer and 63% when they had NHL as a second primary malignancy.

For AYAs, the 5-year relative survival was 64% when patients had NHL as a first cancer and 22% when they had NHL as a second primary malignancy.

For older adults, the 5-year relative survival was 57% when patients had NHL as a first cancer and 54% when they had NHL as a second primary malignancy.

Leukemias

For pediatric patients with ALL, the 5-year relative survival was 87% when patients had ALL as a first cancer and 63% when they had ALL as a second primary malignancy.

For AYAs, the 5-year relative survival was 48% when patients had ALL as a first cancer and 26% when they had ALL as a second primary malignancy.

For older adults, the 5-year relative survival was 17% when patients had ALL as a first cancer and 11% when they had ALL as a second primary malignancy.

For pediatric patients with AML, the 5-year relative survival was 57% when patients had AML as a first cancer and 29% when they had AML as a second primary malignancy.

For AYAs, the 5-year relative survival was 46% when patients had AML as a first cancer and 23% when they had AML as a second primary malignancy.

For older adults, the 5-year relative survival was 12% when patients had AML as a first cancer and 10% when they had AML as a second primary malignancy.

Why younger patients tend to fare worse after a second cancer than older patients is not fully understood or specifically addressed in the current study, the researchers noted.

Now, the team plans to examine how the time between getting a first and second cancer affects survival and whether the type of treatment for the first cancer influences the outcome of a second cancer.

Photo by Rhoda Baer

Second cancers take a greater toll on patients under the age of 40, according to research published in JAMA Oncology.

Researchers studied 14 types of cancer occurring in more than 1 million patients.

For nearly all of the cancers studied, 5-year survival rates were much higher if the cancer occurred as a first malignancy rather than a second cancer.

These survival differences were more pronounced in pediatric patients and adolescents and young adults (AYAs) than they were in patients age 40 and older.

Researchers hope these findings will help guide clinicians in providing age-specific recommendations on cancer prevention, screening, treatment, and survivorship, especially among the AYA population.

“Although the increased incidence of second cancers is well known among cancer survivors, less is known about outcomes of these cancers or the influence of age,” said Theresa Keegan, PhD, of the UC Davis Comprehensive Cancer Center in Sacramento, California.

With this in mind, Dr Keegan and her colleagues analyzed data on patients diagnosed with either a single cancer or a first and second malignancy during 1992 through 2008. The researchers used Surveillance, Epidemiology and End Results program data collected from 13 cancer registries.

The team collected data on the 14 most common cancer types that affect AYAs: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), soft tissue sarcoma, and bone sarcoma, as well as female breast, thyroid, testicular, colorectal, central nervous system, cervical, and ovarian cancers.

There were a total of 15,954 pediatric patients (younger than 15 years at diagnosis), 125,750 AYAs (ages 15 to 39), and 878,370 older adult patients (age 40 and older).

Survival rates

For pediatric patients, the 5-year relative survival was 80% for a first cancer and 47% for a second primary malignancy.

For AYAs, the 5-year relative survival was 81% for a first cancer and 60% for a second primary malignancy.

For older adults, the 5-year relative survival was 70% for a first cancer and 61% for a second primary malignancy.

When the researchers looked at 5-year survival by age and individual cancer types, they found striking differences depending on whether it was a first or second malignancy in all but 2 of the 14 cancer types, testicular cancer and melanoma.

“For almost every type of cancer, the AYA population did worse with a secondary cancer,” said study author Melanie Goldfarb, MD, of John Wayne Cancer Institute at Providence Saint John’s Health Center in Santa Monica, California.

“What struck us was that the second cancer caused such an increased risk of death.”

Lymphomas

For pediatric patients with HL, the 5-year relative survival was 95% when patients had HL as a first cancer. There were no data on HL as a second primary malignancy.

For AYAs, the 5-year relative survival was 93% when patients had HL as a first cancer and 72% when they had HL as a second primary malignancy.

For older adults, the 5-year relative survival was 69% when patients had HL as a first cancer and 54% when they had HL as a second primary malignancy.

For pediatric patients with NHL, the 5-year relative survival was 84% when patients had NHL as a first cancer and 63% when they had NHL as a second primary malignancy.

For AYAs, the 5-year relative survival was 64% when patients had NHL as a first cancer and 22% when they had NHL as a second primary malignancy.

For older adults, the 5-year relative survival was 57% when patients had NHL as a first cancer and 54% when they had NHL as a second primary malignancy.

Leukemias

For pediatric patients with ALL, the 5-year relative survival was 87% when patients had ALL as a first cancer and 63% when they had ALL as a second primary malignancy.

For AYAs, the 5-year relative survival was 48% when patients had ALL as a first cancer and 26% when they had ALL as a second primary malignancy.

For older adults, the 5-year relative survival was 17% when patients had ALL as a first cancer and 11% when they had ALL as a second primary malignancy.

For pediatric patients with AML, the 5-year relative survival was 57% when patients had AML as a first cancer and 29% when they had AML as a second primary malignancy.

For AYAs, the 5-year relative survival was 46% when patients had AML as a first cancer and 23% when they had AML as a second primary malignancy.

For older adults, the 5-year relative survival was 12% when patients had AML as a first cancer and 10% when they had AML as a second primary malignancy.

Why younger patients tend to fare worse after a second cancer than older patients is not fully understood or specifically addressed in the current study, the researchers noted.

Now, the team plans to examine how the time between getting a first and second cancer affects survival and whether the type of treatment for the first cancer influences the outcome of a second cancer.

Photo courtesy of NHS

The expanded umbilical cord blood (UCB) product NiCord can provide benefits over standard UCB transplant, according to research published in Biology of Blood and Marrow Transplantation.

NiCord is a stand-alone graft derived from a single UCB unit that has been expanded in culture and enriched with stem and progenitor cells.

The study showed that patients transplanted with NiCord had shorter time to engraftment, a lower risk of infection, and shorter hospital stays than patients who received standard UCB transplants.

On the other hand, there was no significant difference between the transplant groups when it came to grade 2-4 acute graft-versus-host disease (GVHD), relapse, or survival within 100 days of transplant.

“Our results indicate that rapid hematopoietic recovery from Gamida Cell’s NiCord transplantation approach is associated with clinical benefit,” said study author Mitchell Horwitz, MD, of Duke University School of Medicine in Durham, North Carolina.

Dr Horwitz receives research support from Gamida Cell Ltd., makers of NiCord.

Patient characteristics

The researchers compared 18 consecutive NiCord-transplanted patients and 86 consecutive patients who received standard UCB transplants. All of the patients received total body irradiation-based myeloablative conditioning.

In both arms, most patients received a double transplant. In the NiCord arm, 61.1% of patients (n=11) received NiCord along with a second unmanipulated UCB unit. In the standard UCB arm, 95.3% of patients (n=82) received a double UCB transplant.

Patients in the NiCord arm were older than patients in the standard UCB arm, with median ages of 45.5 (range, 42-57) and 37.5 (range, 28-51), respectively.

Most patients in both arms had acute leukemia or myelodysplastic syndromes (about 89%), although roughly 11% had lymphoid malignancies.

There were no significant differences between the arms when it came to patient sex, pre-transplant weight, cytomegalovirus serostatus, and Karnofsky Performance Status.

Results

The median time to neutrophil engraftment was 12.5 days (range, 10-18) in the NiCord arm and 27 days (range, 23-28) in the standard UCB arm (P<0.001).

All of the patients studied had at least 1 infection of any severity. However, patients in the NiCord arm had a significantly lower risk of infection than patients in the standard UCB arm.

In an analysis adjusted for age, disease stage, and grade 2-4 acute GVHD, the risk ratios (RRs) for NiCord versus standard UCB transplant were as follows:

• Total infection—RR=0.72, P=0.03
• Grade 2-3 infection—RR=0.38, P=0.001
• Bacterial infection—RR=0.42, P=0.008
• Grade 2-3 bacterial infection—RR=0.23, P=0.006.

Patients in the NiCord arm spent a mean of 72.4 days out of the hospital in the first 100 days after transplant, compared to 48.6 days for the standard UCB arm (P=0.001).

After the researchers adjusted for age and Karnofsky Performance Status, patients in the NiCord arm had a mean of 20.2 more days out of the hospital than their peers who received standard UCB (P=0.005).

The incidence of grade 2-4 acute GHVD was 55.6% in the NiCord arm and 41.9% in the standard UCB arm (P=0.31). The rate of second transplant was 5.6% and 11.6%, respectively (P=0.68).

The rate of relapse was 0% in the NiCord arm and 7% in the standard UCB arm (P=0.59). And the rate of death was 5.6% and 16.3%, respectively (P=0.46).

Photo courtesy of NHS

The expanded umbilical cord blood (UCB) product NiCord can provide benefits over standard UCB transplant, according to research published in Biology of Blood and Marrow Transplantation.

NiCord is a stand-alone graft derived from a single UCB unit that has been expanded in culture and enriched with stem and progenitor cells.

The study showed that patients transplanted with NiCord had shorter time to engraftment, a lower risk of infection, and shorter hospital stays than patients who received standard UCB transplants.

On the other hand, there was no significant difference between the transplant groups when it came to grade 2-4 acute graft-versus-host disease (GVHD), relapse, or survival within 100 days of transplant.

“Our results indicate that rapid hematopoietic recovery from Gamida Cell’s NiCord transplantation approach is associated with clinical benefit,” said study author Mitchell Horwitz, MD, of Duke University School of Medicine in Durham, North Carolina.

Dr Horwitz receives research support from Gamida Cell Ltd., makers of NiCord.

Patient characteristics

The researchers compared 18 consecutive NiCord-transplanted patients and 86 consecutive patients who received standard UCB transplants. All of the patients received total body irradiation-based myeloablative conditioning.

In both arms, most patients received a double transplant. In the NiCord arm, 61.1% of patients (n=11) received NiCord along with a second unmanipulated UCB unit. In the standard UCB arm, 95.3% of patients (n=82) received a double UCB transplant.

Patients in the NiCord arm were older than patients in the standard UCB arm, with median ages of 45.5 (range, 42-57) and 37.5 (range, 28-51), respectively.

Most patients in both arms had acute leukemia or myelodysplastic syndromes (about 89%), although roughly 11% had lymphoid malignancies.

There were no significant differences between the arms when it came to patient sex, pre-transplant weight, cytomegalovirus serostatus, and Karnofsky Performance Status.

Results

The median time to neutrophil engraftment was 12.5 days (range, 10-18) in the NiCord arm and 27 days (range, 23-28) in the standard UCB arm (P<0.001).

All of the patients studied had at least 1 infection of any severity. However, patients in the NiCord arm had a significantly lower risk of infection than patients in the standard UCB arm.

In an analysis adjusted for age, disease stage, and grade 2-4 acute GVHD, the risk ratios (RRs) for NiCord versus standard UCB transplant were as follows:

• Total infection—RR=0.72, P=0.03
• Grade 2-3 infection—RR=0.38, P=0.001
• Bacterial infection—RR=0.42, P=0.008
• Grade 2-3 bacterial infection—RR=0.23, P=0.006.

Patients in the NiCord arm spent a mean of 72.4 days out of the hospital in the first 100 days after transplant, compared to 48.6 days for the standard UCB arm (P=0.001).

After the researchers adjusted for age and Karnofsky Performance Status, patients in the NiCord arm had a mean of 20.2 more days out of the hospital than their peers who received standard UCB (P=0.005).

The incidence of grade 2-4 acute GHVD was 55.6% in the NiCord arm and 41.9% in the standard UCB arm (P=0.31). The rate of second transplant was 5.6% and 11.6%, respectively (P=0.68).

The rate of relapse was 0% in the NiCord arm and 7% in the standard UCB arm (P=0.59). And the rate of death was 5.6% and 16.3%, respectively (P=0.46).

Photo courtesy of NHS

The expanded umbilical cord blood (UCB) product NiCord can provide benefits over standard UCB transplant, according to research published in Biology of Blood and Marrow Transplantation.

NiCord is a stand-alone graft derived from a single UCB unit that has been expanded in culture and enriched with stem and progenitor cells.

The study showed that patients transplanted with NiCord had shorter time to engraftment, a lower risk of infection, and shorter hospital stays than patients who received standard UCB transplants.

On the other hand, there was no significant difference between the transplant groups when it came to grade 2-4 acute graft-versus-host disease (GVHD), relapse, or survival within 100 days of transplant.

“Our results indicate that rapid hematopoietic recovery from Gamida Cell’s NiCord transplantation approach is associated with clinical benefit,” said study author Mitchell Horwitz, MD, of Duke University School of Medicine in Durham, North Carolina.

Dr Horwitz receives research support from Gamida Cell Ltd., makers of NiCord.

Patient characteristics

The researchers compared 18 consecutive NiCord-transplanted patients and 86 consecutive patients who received standard UCB transplants. All of the patients received total body irradiation-based myeloablative conditioning.

In both arms, most patients received a double transplant. In the NiCord arm, 61.1% of patients (n=11) received NiCord along with a second unmanipulated UCB unit. In the standard UCB arm, 95.3% of patients (n=82) received a double UCB transplant.

Patients in the NiCord arm were older than patients in the standard UCB arm, with median ages of 45.5 (range, 42-57) and 37.5 (range, 28-51), respectively.

Most patients in both arms had acute leukemia or myelodysplastic syndromes (about 89%), although roughly 11% had lymphoid malignancies.

There were no significant differences between the arms when it came to patient sex, pre-transplant weight, cytomegalovirus serostatus, and Karnofsky Performance Status.

Results

The median time to neutrophil engraftment was 12.5 days (range, 10-18) in the NiCord arm and 27 days (range, 23-28) in the standard UCB arm (P<0.001).

All of the patients studied had at least 1 infection of any severity. However, patients in the NiCord arm had a significantly lower risk of infection than patients in the standard UCB arm.

In an analysis adjusted for age, disease stage, and grade 2-4 acute GVHD, the risk ratios (RRs) for NiCord versus standard UCB transplant were as follows:

• Total infection—RR=0.72, P=0.03
• Grade 2-3 infection—RR=0.38, P=0.001
• Bacterial infection—RR=0.42, P=0.008
• Grade 2-3 bacterial infection—RR=0.23, P=0.006.

Patients in the NiCord arm spent a mean of 72.4 days out of the hospital in the first 100 days after transplant, compared to 48.6 days for the standard UCB arm (P=0.001).

After the researchers adjusted for age and Karnofsky Performance Status, patients in the NiCord arm had a mean of 20.2 more days out of the hospital than their peers who received standard UCB (P=0.005).

The incidence of grade 2-4 acute GHVD was 55.6% in the NiCord arm and 41.9% in the standard UCB arm (P=0.31). The rate of second transplant was 5.6% and 11.6%, respectively (P=0.68).

The rate of relapse was 0% in the NiCord arm and 7% in the standard UCB arm (P=0.59). And the rate of death was 5.6% and 16.3%, respectively (P=0.46).

Antihemophilic factor

The Australian Therapeutic Goods Administration (TGA) has approved use of lonoctocog alfa (AFSTYLA®), a recombinant single-chain coagulation factor VIII (FVIII) therapy, in patients with hemophilia A.

The product is indicated for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for control and prevention of bleeding episodes, and for perioperative management.

Lonoctocog alfa is designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

The TGA’s approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically in these trials, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12.

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August 2016. Results from the trial of children were published in the Journal of Thrombosis and Haemostasis in March 2017.

Antihemophilic factor

The Australian Therapeutic Goods Administration (TGA) has approved use of lonoctocog alfa (AFSTYLA®), a recombinant single-chain coagulation factor VIII (FVIII) therapy, in patients with hemophilia A.

The product is indicated for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for control and prevention of bleeding episodes, and for perioperative management.

Lonoctocog alfa is designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

The TGA’s approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically in these trials, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12.

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August 2016. Results from the trial of children were published in the Journal of Thrombosis and Haemostasis in March 2017.

Antihemophilic factor

The Australian Therapeutic Goods Administration (TGA) has approved use of lonoctocog alfa (AFSTYLA®), a recombinant single-chain coagulation factor VIII (FVIII) therapy, in patients with hemophilia A.

The product is indicated for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes, for control and prevention of bleeding episodes, and for perioperative management.

Lonoctocog alfa is designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

The TGA’s approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically in these trials, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12.

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August 2016. Results from the trial of children were published in the Journal of Thrombosis and Haemostasis in March 2017.

Children’s Research Hospital

Malaria parasites change the properties of red blood cells (RBCs) in a way that helps the parasites achieve cell entry, according to research published in PNAS.

Researchers found that Plasmodium parasites, upon binding to the surface of RBCs, cause the cell membranes to become more pliable, making it easier for the parasites to push inside the cells.

This suggests that differences in RBC stiffness, due to age or increased cholesterol content, could influence the parasites’ ability to invade.

“We have discovered that red cell entry is not just down to the ability of the parasite itself but that parasite-initiated changes to the red blood cells appear to contribute to the process of invasion,” said study author Marion Koch, a PhD student at Imperial College London in the UK.

“This could also mean that naturally more flexible cells would be easier for parasites to invade, which raises some interesting questions. Are parasites choosy about which cells to invade, picking the most deformable? Is susceptibility to malaria modified by fat or cholesterol content, or the age of circulating red blood cells?”

In the PNAS paper, the researchers noted that erythrocyte-binding antigen 175 (EBA175), a protein that’s required for entry in most parasite strains, binds to glycophorin A (GPA) on the RBC surface. However, the function of this binding interaction was unknown.

The team took a closer look at the interaction using real-time deformability cytometry and flicker spectroscopy.

They filmed 1000 RBCs per second passing through a narrow channel. Using this approach, the researchers were able to determine cell deformability by measuring how elongated the cells became during transit through the channel.

The team then measured where this deformation came from. They measured how much the RBCs deviate from their normally circular shape as their membranes naturally fluctuate or flicker.

The researchers found that EBA175 binding to GPA leads to an increase in the cytoskeletal tension of the RBC and a reduction in the bending modulus of the cell’s membrane. (The bending modulus is a measure of how much energy it takes to bend the cell membrane.)

The team then showed that the reduction in the bending modulus was “directly correlated with parasite invasion efficiency.”

The researchers said these results suggest the parasite primes the RBC surface through its binding antigens, altering the cell and reducing a barrier to invasion.

“This suggests we should be investigating not just parasite biology, but also how the body’s own red blood cells respond,” said study author Jake Baum, PhD, of Imperial College London.

“There are therapies developed for diseases like HIV that strengthen the body’s responses in addition to tackling the ‘invader.’ It’s not impossible to imagine something similar for malaria; for example, looking at a host-directed drug target and not just the parasite.”

Children’s Research Hospital

Malaria parasites change the properties of red blood cells (RBCs) in a way that helps the parasites achieve cell entry, according to research published in PNAS.

Researchers found that Plasmodium parasites, upon binding to the surface of RBCs, cause the cell membranes to become more pliable, making it easier for the parasites to push inside the cells.

This suggests that differences in RBC stiffness, due to age or increased cholesterol content, could influence the parasites’ ability to invade.

“We have discovered that red cell entry is not just down to the ability of the parasite itself but that parasite-initiated changes to the red blood cells appear to contribute to the process of invasion,” said study author Marion Koch, a PhD student at Imperial College London in the UK.

“This could also mean that naturally more flexible cells would be easier for parasites to invade, which raises some interesting questions. Are parasites choosy about which cells to invade, picking the most deformable? Is susceptibility to malaria modified by fat or cholesterol content, or the age of circulating red blood cells?”

In the PNAS paper, the researchers noted that erythrocyte-binding antigen 175 (EBA175), a protein that’s required for entry in most parasite strains, binds to glycophorin A (GPA) on the RBC surface. However, the function of this binding interaction was unknown.

The team took a closer look at the interaction using real-time deformability cytometry and flicker spectroscopy.

They filmed 1000 RBCs per second passing through a narrow channel. Using this approach, the researchers were able to determine cell deformability by measuring how elongated the cells became during transit through the channel.

The team then measured where this deformation came from. They measured how much the RBCs deviate from their normally circular shape as their membranes naturally fluctuate or flicker.

The researchers found that EBA175 binding to GPA leads to an increase in the cytoskeletal tension of the RBC and a reduction in the bending modulus of the cell’s membrane. (The bending modulus is a measure of how much energy it takes to bend the cell membrane.)

The team then showed that the reduction in the bending modulus was “directly correlated with parasite invasion efficiency.”

The researchers said these results suggest the parasite primes the RBC surface through its binding antigens, altering the cell and reducing a barrier to invasion.

“This suggests we should be investigating not just parasite biology, but also how the body’s own red blood cells respond,” said study author Jake Baum, PhD, of Imperial College London.

“There are therapies developed for diseases like HIV that strengthen the body’s responses in addition to tackling the ‘invader.’ It’s not impossible to imagine something similar for malaria; for example, looking at a host-directed drug target and not just the parasite.”

Children’s Research Hospital

Malaria parasites change the properties of red blood cells (RBCs) in a way that helps the parasites achieve cell entry, according to research published in PNAS.

Researchers found that Plasmodium parasites, upon binding to the surface of RBCs, cause the cell membranes to become more pliable, making it easier for the parasites to push inside the cells.

This suggests that differences in RBC stiffness, due to age or increased cholesterol content, could influence the parasites’ ability to invade.

“We have discovered that red cell entry is not just down to the ability of the parasite itself but that parasite-initiated changes to the red blood cells appear to contribute to the process of invasion,” said study author Marion Koch, a PhD student at Imperial College London in the UK.

“This could also mean that naturally more flexible cells would be easier for parasites to invade, which raises some interesting questions. Are parasites choosy about which cells to invade, picking the most deformable? Is susceptibility to malaria modified by fat or cholesterol content, or the age of circulating red blood cells?”

In the PNAS paper, the researchers noted that erythrocyte-binding antigen 175 (EBA175), a protein that’s required for entry in most parasite strains, binds to glycophorin A (GPA) on the RBC surface. However, the function of this binding interaction was unknown.

The team took a closer look at the interaction using real-time deformability cytometry and flicker spectroscopy.

They filmed 1000 RBCs per second passing through a narrow channel. Using this approach, the researchers were able to determine cell deformability by measuring how elongated the cells became during transit through the channel.

The team then measured where this deformation came from. They measured how much the RBCs deviate from their normally circular shape as their membranes naturally fluctuate or flicker.

The researchers found that EBA175 binding to GPA leads to an increase in the cytoskeletal tension of the RBC and a reduction in the bending modulus of the cell’s membrane. (The bending modulus is a measure of how much energy it takes to bend the cell membrane.)

The team then showed that the reduction in the bending modulus was “directly correlated with parasite invasion efficiency.”

The researchers said these results suggest the parasite primes the RBC surface through its binding antigens, altering the cell and reducing a barrier to invasion.

“This suggests we should be investigating not just parasite biology, but also how the body’s own red blood cells respond,” said study author Jake Baum, PhD, of Imperial College London.

“There are therapies developed for diseases like HIV that strengthen the body’s responses in addition to tackling the ‘invader.’ It’s not impossible to imagine something similar for malaria; for example, looking at a host-directed drug target and not just the parasite.”

Is HCAHPS Hurting Our Patients?

Speakers: Suparna Dutta, MD, MS, MPH, and John Biebelhausen, MD, MBA

Explore the unintended consequences of assessing patient satisfaction and labeling pain as “the fifth vital sign” in the midst of a national opioid epidemic. The Hospital Consumer Assessment of Healthcare Providers and Systems, which was developed by the Centers for Medicare & Medicaid Services to assess the inpatient experience and impacts hospital reimbursement, includes directed questions about pain management.

Join us as we review the background of HCAHPS, its potential unintended impacts over the years, as well as current and future efforts of SHM toward improving health policy in this domain.

Hello, My Name Is POCUS (Point-of-Care Ultrasound)

Speaker: Nilam Soni, MD, MS, FHM

Point-of-care ultrasound is being used by more hospitalists to perform bedside diagnostics and to guide invasive procedures. However, most practicing hospitalists completed their training before point-of-care ultrasound education was common in medical school and residency curricula. This interactive session will:

• Explain what point-of-care ultrasonography is and how hospitalists are currently using it.
• Highlight some of the unique point-of-care ultrasound activities at HM17.
• Describe the launch of a new point-of-care ultrasound certification program offered by SHM & ACCP.

The Best-Kept Secrets from the State of Hospital Medicine Report

Speaker: Johnbuck Creamer, MD, SFHM

The State of Hospital Medicine Report is powered by SHM’s biannual survey that recently captured data from nearly 600 HM groups, augmented by additional hospitalist data licensed from MGMA. We’ll explore trends and difference among groups, including:

• Compensation per wRVU and use of nocturnists are increasing.
• Turnover rates are decreasing.
• Compensation for quality performance varies greatly among academic, nonacademic, and pediatric practice groups.
• NP/PA utilization rates are very different between East and West U.S. regions.
• Family Practice presence is increasing in adult-only practice groups.
• Academic groups are falling further behind in CPT coding levels.

We Need to Talk: Opioid-Related Respiratory Failure & Death

Speaker: Thomas Frederickson, MD, SFHM

Discussion topics:

• The opioid epidemic – not just an outpatient issue.
• How opioids can cause respiratory arrest and death, and why current screening and monitoring strategies can fail.
• What works – examples of successful strategies that have been implemented and have saved lives.

PediBOOST^®: Kids Need Better Care Transitions, Too!

Speaker: James O’Callaghan, MD, SFHM

PediBOOST is a pediatric-specific adaption of the SHM Project BOOST^® (Better Outcomes by Optimizing Safe Transitions) quality initiative. The goal is to improve poor discharge processes (demonstrated by low patient satisfaction and worse clinical outcomes, not just higher hospital readmission rates).

It considers unique problems for hospitalized children, including:

• Medication issues – palatability and adherence concerns, need for compounding.
• Equipment issues – portability use for home and school.
• Education issues – engagement of patient, as developmentally appropriate, along with training of all providers who might care for the patient (parents, teachers).

How Hospitalists Really Feel about EMRs

Speaker: Rupesh Prasad, MD, MPH, SFHM

Electronic medical record use has tremendously increased in the last few years.

• What are the potential benefits of use – have they been realized?
• What do the hospitalists think:
• How have EMRs impacted patient safety?
• How have EMRs impacted patient face to face time?
• What are hospitalists’ frustrations about EMRs?

Improve Your Interactions with the 5 Rs of Cultural Humility

Speaker: O’Neil Pyke, MD, SFHM

As the proverbial stranger at the bedside, HM providers are tasked with a very challenging proposition: meet a new patient in their most vulnerable state and quickly establish effective lines of communication and trust and provide patient-centric care, ultimately yielding a satisfied patient (and family) irrespective of the clinical outcome. With increased focus on patient experience and satisfaction, it is imperative that hospitals and health systems equip all hospitalists with the tools needed to deliver culturally competent care to all patients served.

The goal of the 5 Rs is to equip HM providers with tangible resources and easy to understand reminders that focus on encouraging awareness and, ultimately, deliver culturally “humble” care to all patients (and family members).

• Respect: Hospitalists will treat every person with the utmost respect and strive to preserve patient dignity.
• Regard: Hospitalists will hold every person in their highest regard and not allow unconscious biases to manifest, exercising utmost sensitivity to anticipated differences in beliefs, value systems, and preferences.
• Relevance: Hospitalists will expect cultural humility to be relevant and apply this practice to every encounter.
• Reflection: Hospitalists will approach every encounter with humility and understanding that there is always something to learn from everyone.
• Resiliency: In order to provide better care for hospitalized patients, hospitalists will embody the practice of cultural humility to enhance personal resiliency and compassion for all.

It’s Critical: Hospitalists in the ICU

Speaker: Joseph Sweigart, MD

We hope to:

• Describe formation of purpose of the critical care task force within the Education Committee.
• Discuss the creation and execution of the SHM critical care survey.
• Present selected results including:
• Introduce strategies to address the practice gaps identified including:

Palliative Care in Hospital Medicine: Figuring Out What Matters Most

Speaker: Rab Razzak, MBBS, MD

We aim to:

• Discuss the overall definition of palliative care. It is for all seriously ill patients and focuses on human-centered care and quality of life, best provided early in an illness.
• Idea of primary palliative care and role of hospitalists. Most palliative care is provided by frontline clinicians, and hospitalists are optimally positioned to support seriously ill patients and their families. It is crucial for HM to involve palliative care specialists when needed.
• Effective communication about serious illness – words that work and how to operationalize human-centered care while honestly discussing serious illness.
  

Is HCAHPS Hurting Our Patients?

Speakers: Suparna Dutta, MD, MS, MPH, and John Biebelhausen, MD, MBA

Explore the unintended consequences of assessing patient satisfaction and labeling pain as “the fifth vital sign” in the midst of a national opioid epidemic. The Hospital Consumer Assessment of Healthcare Providers and Systems, which was developed by the Centers for Medicare & Medicaid Services to assess the inpatient experience and impacts hospital reimbursement, includes directed questions about pain management.

Join us as we review the background of HCAHPS, its potential unintended impacts over the years, as well as current and future efforts of SHM toward improving health policy in this domain.

Hello, My Name Is POCUS (Point-of-Care Ultrasound)

Speaker: Nilam Soni, MD, MS, FHM

Point-of-care ultrasound is being used by more hospitalists to perform bedside diagnostics and to guide invasive procedures. However, most practicing hospitalists completed their training before point-of-care ultrasound education was common in medical school and residency curricula. This interactive session will:

• Explain what point-of-care ultrasonography is and how hospitalists are currently using it.
• Highlight some of the unique point-of-care ultrasound activities at HM17.
• Describe the launch of a new point-of-care ultrasound certification program offered by SHM & ACCP.

The Best-Kept Secrets from the State of Hospital Medicine Report

Speaker: Johnbuck Creamer, MD, SFHM

The State of Hospital Medicine Report is powered by SHM’s biannual survey that recently captured data from nearly 600 HM groups, augmented by additional hospitalist data licensed from MGMA. We’ll explore trends and difference among groups, including:

• Compensation per wRVU and use of nocturnists are increasing.
• Turnover rates are decreasing.
• Compensation for quality performance varies greatly among academic, nonacademic, and pediatric practice groups.
• NP/PA utilization rates are very different between East and West U.S. regions.
• Family Practice presence is increasing in adult-only practice groups.
• Academic groups are falling further behind in CPT coding levels.

We Need to Talk: Opioid-Related Respiratory Failure & Death

Speaker: Thomas Frederickson, MD, SFHM

Discussion topics:

• The opioid epidemic – not just an outpatient issue.
• How opioids can cause respiratory arrest and death, and why current screening and monitoring strategies can fail.
• What works – examples of successful strategies that have been implemented and have saved lives.

PediBOOST^®: Kids Need Better Care Transitions, Too!

Speaker: James O’Callaghan, MD, SFHM

PediBOOST is a pediatric-specific adaption of the SHM Project BOOST^® (Better Outcomes by Optimizing Safe Transitions) quality initiative. The goal is to improve poor discharge processes (demonstrated by low patient satisfaction and worse clinical outcomes, not just higher hospital readmission rates).

It considers unique problems for hospitalized children, including:

• Medication issues – palatability and adherence concerns, need for compounding.
• Equipment issues – portability use for home and school.
• Education issues – engagement of patient, as developmentally appropriate, along with training of all providers who might care for the patient (parents, teachers).

How Hospitalists Really Feel about EMRs

Speaker: Rupesh Prasad, MD, MPH, SFHM

Electronic medical record use has tremendously increased in the last few years.

• What are the potential benefits of use – have they been realized?
• What do the hospitalists think:
• How have EMRs impacted patient safety?
• How have EMRs impacted patient face to face time?
• What are hospitalists’ frustrations about EMRs?

Improve Your Interactions with the 5 Rs of Cultural Humility

Speaker: O’Neil Pyke, MD, SFHM

As the proverbial stranger at the bedside, HM providers are tasked with a very challenging proposition: meet a new patient in their most vulnerable state and quickly establish effective lines of communication and trust and provide patient-centric care, ultimately yielding a satisfied patient (and family) irrespective of the clinical outcome. With increased focus on patient experience and satisfaction, it is imperative that hospitals and health systems equip all hospitalists with the tools needed to deliver culturally competent care to all patients served.

The goal of the 5 Rs is to equip HM providers with tangible resources and easy to understand reminders that focus on encouraging awareness and, ultimately, deliver culturally “humble” care to all patients (and family members).

• Respect: Hospitalists will treat every person with the utmost respect and strive to preserve patient dignity.
• Regard: Hospitalists will hold every person in their highest regard and not allow unconscious biases to manifest, exercising utmost sensitivity to anticipated differences in beliefs, value systems, and preferences.
• Relevance: Hospitalists will expect cultural humility to be relevant and apply this practice to every encounter.
• Reflection: Hospitalists will approach every encounter with humility and understanding that there is always something to learn from everyone.
• Resiliency: In order to provide better care for hospitalized patients, hospitalists will embody the practice of cultural humility to enhance personal resiliency and compassion for all.

It’s Critical: Hospitalists in the ICU

Speaker: Joseph Sweigart, MD

We hope to:

• Describe formation of purpose of the critical care task force within the Education Committee.
• Discuss the creation and execution of the SHM critical care survey.
• Present selected results including:
• Introduce strategies to address the practice gaps identified including:

Palliative Care in Hospital Medicine: Figuring Out What Matters Most

Speaker: Rab Razzak, MBBS, MD

We aim to:

• Discuss the overall definition of palliative care. It is for all seriously ill patients and focuses on human-centered care and quality of life, best provided early in an illness.
• Idea of primary palliative care and role of hospitalists. Most palliative care is provided by frontline clinicians, and hospitalists are optimally positioned to support seriously ill patients and their families. It is crucial for HM to involve palliative care specialists when needed.
• Effective communication about serious illness – words that work and how to operationalize human-centered care while honestly discussing serious illness.
  

Is HCAHPS Hurting Our Patients?

Speakers: Suparna Dutta, MD, MS, MPH, and John Biebelhausen, MD, MBA

Explore the unintended consequences of assessing patient satisfaction and labeling pain as “the fifth vital sign” in the midst of a national opioid epidemic. The Hospital Consumer Assessment of Healthcare Providers and Systems, which was developed by the Centers for Medicare & Medicaid Services to assess the inpatient experience and impacts hospital reimbursement, includes directed questions about pain management.

Join us as we review the background of HCAHPS, its potential unintended impacts over the years, as well as current and future efforts of SHM toward improving health policy in this domain.

Hello, My Name Is POCUS (Point-of-Care Ultrasound)

Speaker: Nilam Soni, MD, MS, FHM

Point-of-care ultrasound is being used by more hospitalists to perform bedside diagnostics and to guide invasive procedures. However, most practicing hospitalists completed their training before point-of-care ultrasound education was common in medical school and residency curricula. This interactive session will:

• Explain what point-of-care ultrasonography is and how hospitalists are currently using it.
• Highlight some of the unique point-of-care ultrasound activities at HM17.
• Describe the launch of a new point-of-care ultrasound certification program offered by SHM & ACCP.

The Best-Kept Secrets from the State of Hospital Medicine Report

Speaker: Johnbuck Creamer, MD, SFHM

The State of Hospital Medicine Report is powered by SHM’s biannual survey that recently captured data from nearly 600 HM groups, augmented by additional hospitalist data licensed from MGMA. We’ll explore trends and difference among groups, including:

• Compensation per wRVU and use of nocturnists are increasing.
• Turnover rates are decreasing.
• Compensation for quality performance varies greatly among academic, nonacademic, and pediatric practice groups.
• NP/PA utilization rates are very different between East and West U.S. regions.
• Family Practice presence is increasing in adult-only practice groups.
• Academic groups are falling further behind in CPT coding levels.

We Need to Talk: Opioid-Related Respiratory Failure & Death

Speaker: Thomas Frederickson, MD, SFHM

Discussion topics:

• The opioid epidemic – not just an outpatient issue.
• How opioids can cause respiratory arrest and death, and why current screening and monitoring strategies can fail.
• What works – examples of successful strategies that have been implemented and have saved lives.

PediBOOST^®: Kids Need Better Care Transitions, Too!

Speaker: James O’Callaghan, MD, SFHM

PediBOOST is a pediatric-specific adaption of the SHM Project BOOST^® (Better Outcomes by Optimizing Safe Transitions) quality initiative. The goal is to improve poor discharge processes (demonstrated by low patient satisfaction and worse clinical outcomes, not just higher hospital readmission rates).

It considers unique problems for hospitalized children, including:

• Medication issues – palatability and adherence concerns, need for compounding.
• Equipment issues – portability use for home and school.
• Education issues – engagement of patient, as developmentally appropriate, along with training of all providers who might care for the patient (parents, teachers).

How Hospitalists Really Feel about EMRs

Speaker: Rupesh Prasad, MD, MPH, SFHM

Electronic medical record use has tremendously increased in the last few years.

• What are the potential benefits of use – have they been realized?
• What do the hospitalists think:
• How have EMRs impacted patient safety?
• How have EMRs impacted patient face to face time?
• What are hospitalists’ frustrations about EMRs?

Improve Your Interactions with the 5 Rs of Cultural Humility

Speaker: O’Neil Pyke, MD, SFHM

As the proverbial stranger at the bedside, HM providers are tasked with a very challenging proposition: meet a new patient in their most vulnerable state and quickly establish effective lines of communication and trust and provide patient-centric care, ultimately yielding a satisfied patient (and family) irrespective of the clinical outcome. With increased focus on patient experience and satisfaction, it is imperative that hospitals and health systems equip all hospitalists with the tools needed to deliver culturally competent care to all patients served.

The goal of the 5 Rs is to equip HM providers with tangible resources and easy to understand reminders that focus on encouraging awareness and, ultimately, deliver culturally “humble” care to all patients (and family members).

• Respect: Hospitalists will treat every person with the utmost respect and strive to preserve patient dignity.
• Regard: Hospitalists will hold every person in their highest regard and not allow unconscious biases to manifest, exercising utmost sensitivity to anticipated differences in beliefs, value systems, and preferences.
• Relevance: Hospitalists will expect cultural humility to be relevant and apply this practice to every encounter.
• Reflection: Hospitalists will approach every encounter with humility and understanding that there is always something to learn from everyone.
• Resiliency: In order to provide better care for hospitalized patients, hospitalists will embody the practice of cultural humility to enhance personal resiliency and compassion for all.

It’s Critical: Hospitalists in the ICU

Speaker: Joseph Sweigart, MD

We hope to:

• Describe formation of purpose of the critical care task force within the Education Committee.
• Discuss the creation and execution of the SHM critical care survey.
• Present selected results including:
• Introduce strategies to address the practice gaps identified including:

Palliative Care in Hospital Medicine: Figuring Out What Matters Most

Speaker: Rab Razzak, MBBS, MD

We aim to:

• Discuss the overall definition of palliative care. It is for all seriously ill patients and focuses on human-centered care and quality of life, best provided early in an illness.
• Idea of primary palliative care and role of hospitalists. Most palliative care is provided by frontline clinicians, and hospitalists are optimally positioned to support seriously ill patients and their families. It is crucial for HM to involve palliative care specialists when needed.
• Effective communication about serious illness – words that work and how to operationalize human-centered care while honestly discussing serious illness.
  

Infective endocarditis (IE) is a devastating complication of heart valve disease that, left untreated, can be fatal. Management requires a multidisciplinary approach, and many of the respective medical societies that represent the participating specialties have developed guidelines. Now, the American Association for Thoracic Surgery has published “Consensus Guidelines for the Surgical Treatment of Infective Endocarditis” to guide thoracic and cardiovascular surgeons in making decisions of when to operate in cases of IE (J Thorac Cardiovasc Surg. 2017 Jan 24. doi: 10.1016/j.jtcvs.2016.09.093).

• Repair when possible for patients with NVE (COR I, LOE B).
• When replacement is indicated, the surgeon should base valve choice on normal criteria – age, life expectancy, comorbidities, and expected compliance with anticoagulation (COR I, LOE B).
• Avoid use of mechanical valves in patients with intracranial bleeding or who have had a major stroke (COR IIA, LOE C).
• In patients with invasive disease and deconstruction, reconstruction should depend on the involved valve, severity of destruction, and available options for cardiac reconstruction (COR I, LOE B).

The AATS guidelines also challenge conventional thinking on the practice of soaking a gel-impregnated graft with antimicrobials targeting a specific organism. “We found no evidence to support this practice,” Dr. Pettersson and his coauthors said (COR IIB, LOE B). They came to the same conclusion with regard to the use of local antimicrobials or antiseptics during irrigation after debridement and local injection of antimicrobials around the infected area (COR I, LOE C).

The guidelines provide direction on a host of other surgical issues in IE: use of aortic valve grafts; when to remove or replace noninfected grafts; when to remove pacemakers; the role of drainage; postoperative management; follow-up; and additional screening. They also shed insight into what the guideline authors call “residual controversies,” including surgery for injection drug users (use “all available resources and options for drug rehabilitation”) and dialysis patients (“it is reasonable to offer surgery when the additional burden of comorbidities is not overwhelming”). They also acknowledge seven different scenarios that lack clear evidence for intervention but require the surgeon to determine the need for surgery, ranging from timing of surgery for IE in patients with neurologic complications to how to treat patients with functional valve issues after being cured of IE.

The guideline writers acknowledged that institutional funds supported the work. Dr. Pettersson had no financial relationships to disclose.

*Correction 5/172017: It was incorrectly stated that these complications were not addressed in the guidelines due to lack of evidence

Infective endocarditis (IE) is a devastating complication of heart valve disease that, left untreated, can be fatal. Management requires a multidisciplinary approach, and many of the respective medical societies that represent the participating specialties have developed guidelines. Now, the American Association for Thoracic Surgery has published “Consensus Guidelines for the Surgical Treatment of Infective Endocarditis” to guide thoracic and cardiovascular surgeons in making decisions of when to operate in cases of IE (J Thorac Cardiovasc Surg. 2017 Jan 24. doi: 10.1016/j.jtcvs.2016.09.093).

• Repair when possible for patients with NVE (COR I, LOE B).
• When replacement is indicated, the surgeon should base valve choice on normal criteria – age, life expectancy, comorbidities, and expected compliance with anticoagulation (COR I, LOE B).
• Avoid use of mechanical valves in patients with intracranial bleeding or who have had a major stroke (COR IIA, LOE C).
• In patients with invasive disease and deconstruction, reconstruction should depend on the involved valve, severity of destruction, and available options for cardiac reconstruction (COR I, LOE B).

The AATS guidelines also challenge conventional thinking on the practice of soaking a gel-impregnated graft with antimicrobials targeting a specific organism. “We found no evidence to support this practice,” Dr. Pettersson and his coauthors said (COR IIB, LOE B). They came to the same conclusion with regard to the use of local antimicrobials or antiseptics during irrigation after debridement and local injection of antimicrobials around the infected area (COR I, LOE C).

The guidelines provide direction on a host of other surgical issues in IE: use of aortic valve grafts; when to remove or replace noninfected grafts; when to remove pacemakers; the role of drainage; postoperative management; follow-up; and additional screening. They also shed insight into what the guideline authors call “residual controversies,” including surgery for injection drug users (use “all available resources and options for drug rehabilitation”) and dialysis patients (“it is reasonable to offer surgery when the additional burden of comorbidities is not overwhelming”). They also acknowledge seven different scenarios that lack clear evidence for intervention but require the surgeon to determine the need for surgery, ranging from timing of surgery for IE in patients with neurologic complications to how to treat patients with functional valve issues after being cured of IE.

The guideline writers acknowledged that institutional funds supported the work. Dr. Pettersson had no financial relationships to disclose.

*Correction 5/172017: It was incorrectly stated that these complications were not addressed in the guidelines due to lack of evidence

Infective endocarditis (IE) is a devastating complication of heart valve disease that, left untreated, can be fatal. Management requires a multidisciplinary approach, and many of the respective medical societies that represent the participating specialties have developed guidelines. Now, the American Association for Thoracic Surgery has published “Consensus Guidelines for the Surgical Treatment of Infective Endocarditis” to guide thoracic and cardiovascular surgeons in making decisions of when to operate in cases of IE (J Thorac Cardiovasc Surg. 2017 Jan 24. doi: 10.1016/j.jtcvs.2016.09.093).

• Repair when possible for patients with NVE (COR I, LOE B).
• When replacement is indicated, the surgeon should base valve choice on normal criteria – age, life expectancy, comorbidities, and expected compliance with anticoagulation (COR I, LOE B).
• Avoid use of mechanical valves in patients with intracranial bleeding or who have had a major stroke (COR IIA, LOE C).
• In patients with invasive disease and deconstruction, reconstruction should depend on the involved valve, severity of destruction, and available options for cardiac reconstruction (COR I, LOE B).

The AATS guidelines also challenge conventional thinking on the practice of soaking a gel-impregnated graft with antimicrobials targeting a specific organism. “We found no evidence to support this practice,” Dr. Pettersson and his coauthors said (COR IIB, LOE B). They came to the same conclusion with regard to the use of local antimicrobials or antiseptics during irrigation after debridement and local injection of antimicrobials around the infected area (COR I, LOE C).

The guidelines provide direction on a host of other surgical issues in IE: use of aortic valve grafts; when to remove or replace noninfected grafts; when to remove pacemakers; the role of drainage; postoperative management; follow-up; and additional screening. They also shed insight into what the guideline authors call “residual controversies,” including surgery for injection drug users (use “all available resources and options for drug rehabilitation”) and dialysis patients (“it is reasonable to offer surgery when the additional burden of comorbidities is not overwhelming”). They also acknowledge seven different scenarios that lack clear evidence for intervention but require the surgeon to determine the need for surgery, ranging from timing of surgery for IE in patients with neurologic complications to how to treat patients with functional valve issues after being cured of IE.

The guideline writers acknowledged that institutional funds supported the work. Dr. Pettersson had no financial relationships to disclose.

*Correction 5/172017: It was incorrectly stated that these complications were not addressed in the guidelines due to lack of evidence

The Food and Drug Administration is restricting the use of two opiates – codeine and tramadol – in children, and also warns they are potentially dangerous to infants of breastfeeding women.

Codeine is approved to treat pain and cough; tramadol is approved to treat pain.

“We understand that there are limited options when it comes to treating pain or cough in children, and that these changes may raise some questions for health care providers and parents. However, please know that our decision today was made based on the latest evidence and with this goal in mind: keeping our kids safe,” Douglas Throckmorton, MD, the deputy center director for regulatory programs at the FDA Center for Drug Evaluation and Research, said in a statement.

In the current safety statement, the FDA said it will require additional labeling changes, including contraindications for use of codeine or tramadol in all children younger than 12 years of age and a new contraindication for tramadol in children younger than 18 years being treated for pain after tonsillectomy and/or adenoidectomy, warnings about their use in children 12-18 years of age with certain medical conditions, and a stronger warning recommending against their use in nursing mothers.

Single-ingredient codeine and all tramadol-containing products are FDA-approved only for use in adults, the agency noted.

The agency cited particular concerns over those who are “ultra-rapid metabolizers” of substrates of the cytochrome P450 isoenzyme 2D6 (CYP2D6) genotype. These people more quickly convert codeine into potentially dangerously high levels of morphine, which can lead to fatal respiratory depression.

Supporting the restrictions and warning were data on 64 cases of respiratory depression that occurred worldwide between 1969 and 2015, when a codeine-based medicine was used in children younger than 18 years. Twenty-four of these children died.

The most frequently cited medicines in the cases were acetaminophen with codeine and promethazine with codeine with or without phenylephrine, either given to soothe postoperative pain, general pain, sore or strep throat pain, or cough and cold.

Ten of the 64 cases implicated the CYP2D6 genotype. Seven of the patients were “ultrarapid metabolizers,” five of whom died.

Data cited on tramadol included nine worldwide cases of tramadol-related respiratory depression occurring between 1969 and 2016, resulting in the deaths of three children, all under the age of 6 years, and all of whom were taking the drug for postoperative pain or fever.

All but one case of respiratory depression occurred within the first 24 hours of taking the drug. One of the patients was genotyped for CYP2D6, and found to have three functional alleles consistent with ultrarapid metabolism.

Mothers who are ultrarapid metabolizers of codeine can have high levels of morphine in their breast milk that are dangerous to their breastfed infants, whereas there is less of a threat posed by women with normal codeine metabolism because the amount of codeine secreted into the breast milk is low and dose dependent.

The FDA stated that data reveal numerous reports of respiratory depression and at least one death in infants of breastfeeding mothers taking these medicines, particularly mothers with the CYP2D6 genotype. Although there are FDA-cleared tests for ultrarapid metabolism, they are not commonly used.

The agency stated that breastfeeding women taking any opioid pain medicine, including codeine or tramadol should contact their health care provider if they notice the infant is sleeping more than 4 hours at a time, or if the infant is having difficulty breastfeeding or seems limp.

Clinicians are urged to report side effects that occur while using codeine or tramadol to the FDA’s MedWatch Adverse Event Reporting program.

[email protected]

On Twitter @whitneymcknight

The Food and Drug Administration is restricting the use of two opiates – codeine and tramadol – in children, and also warns they are potentially dangerous to infants of breastfeeding women.

Codeine is approved to treat pain and cough; tramadol is approved to treat pain.

“We understand that there are limited options when it comes to treating pain or cough in children, and that these changes may raise some questions for health care providers and parents. However, please know that our decision today was made based on the latest evidence and with this goal in mind: keeping our kids safe,” Douglas Throckmorton, MD, the deputy center director for regulatory programs at the FDA Center for Drug Evaluation and Research, said in a statement.

In the current safety statement, the FDA said it will require additional labeling changes, including contraindications for use of codeine or tramadol in all children younger than 12 years of age and a new contraindication for tramadol in children younger than 18 years being treated for pain after tonsillectomy and/or adenoidectomy, warnings about their use in children 12-18 years of age with certain medical conditions, and a stronger warning recommending against their use in nursing mothers.

Single-ingredient codeine and all tramadol-containing products are FDA-approved only for use in adults, the agency noted.

The agency cited particular concerns over those who are “ultra-rapid metabolizers” of substrates of the cytochrome P450 isoenzyme 2D6 (CYP2D6) genotype. These people more quickly convert codeine into potentially dangerously high levels of morphine, which can lead to fatal respiratory depression.

Supporting the restrictions and warning were data on 64 cases of respiratory depression that occurred worldwide between 1969 and 2015, when a codeine-based medicine was used in children younger than 18 years. Twenty-four of these children died.

The most frequently cited medicines in the cases were acetaminophen with codeine and promethazine with codeine with or without phenylephrine, either given to soothe postoperative pain, general pain, sore or strep throat pain, or cough and cold.

Ten of the 64 cases implicated the CYP2D6 genotype. Seven of the patients were “ultrarapid metabolizers,” five of whom died.

Data cited on tramadol included nine worldwide cases of tramadol-related respiratory depression occurring between 1969 and 2016, resulting in the deaths of three children, all under the age of 6 years, and all of whom were taking the drug for postoperative pain or fever.

All but one case of respiratory depression occurred within the first 24 hours of taking the drug. One of the patients was genotyped for CYP2D6, and found to have three functional alleles consistent with ultrarapid metabolism.

Mothers who are ultrarapid metabolizers of codeine can have high levels of morphine in their breast milk that are dangerous to their breastfed infants, whereas there is less of a threat posed by women with normal codeine metabolism because the amount of codeine secreted into the breast milk is low and dose dependent.

The FDA stated that data reveal numerous reports of respiratory depression and at least one death in infants of breastfeeding mothers taking these medicines, particularly mothers with the CYP2D6 genotype. Although there are FDA-cleared tests for ultrarapid metabolism, they are not commonly used.

The agency stated that breastfeeding women taking any opioid pain medicine, including codeine or tramadol should contact their health care provider if they notice the infant is sleeping more than 4 hours at a time, or if the infant is having difficulty breastfeeding or seems limp.

Clinicians are urged to report side effects that occur while using codeine or tramadol to the FDA’s MedWatch Adverse Event Reporting program.

[email protected]

On Twitter @whitneymcknight

The Food and Drug Administration is restricting the use of two opiates – codeine and tramadol – in children, and also warns they are potentially dangerous to infants of breastfeeding women.

Codeine is approved to treat pain and cough; tramadol is approved to treat pain.

“We understand that there are limited options when it comes to treating pain or cough in children, and that these changes may raise some questions for health care providers and parents. However, please know that our decision today was made based on the latest evidence and with this goal in mind: keeping our kids safe,” Douglas Throckmorton, MD, the deputy center director for regulatory programs at the FDA Center for Drug Evaluation and Research, said in a statement.

In the current safety statement, the FDA said it will require additional labeling changes, including contraindications for use of codeine or tramadol in all children younger than 12 years of age and a new contraindication for tramadol in children younger than 18 years being treated for pain after tonsillectomy and/or adenoidectomy, warnings about their use in children 12-18 years of age with certain medical conditions, and a stronger warning recommending against their use in nursing mothers.

Single-ingredient codeine and all tramadol-containing products are FDA-approved only for use in adults, the agency noted.

The agency cited particular concerns over those who are “ultra-rapid metabolizers” of substrates of the cytochrome P450 isoenzyme 2D6 (CYP2D6) genotype. These people more quickly convert codeine into potentially dangerously high levels of morphine, which can lead to fatal respiratory depression.

Supporting the restrictions and warning were data on 64 cases of respiratory depression that occurred worldwide between 1969 and 2015, when a codeine-based medicine was used in children younger than 18 years. Twenty-four of these children died.

The most frequently cited medicines in the cases were acetaminophen with codeine and promethazine with codeine with or without phenylephrine, either given to soothe postoperative pain, general pain, sore or strep throat pain, or cough and cold.

Ten of the 64 cases implicated the CYP2D6 genotype. Seven of the patients were “ultrarapid metabolizers,” five of whom died.

Data cited on tramadol included nine worldwide cases of tramadol-related respiratory depression occurring between 1969 and 2016, resulting in the deaths of three children, all under the age of 6 years, and all of whom were taking the drug for postoperative pain or fever.

All but one case of respiratory depression occurred within the first 24 hours of taking the drug. One of the patients was genotyped for CYP2D6, and found to have three functional alleles consistent with ultrarapid metabolism.

Mothers who are ultrarapid metabolizers of codeine can have high levels of morphine in their breast milk that are dangerous to their breastfed infants, whereas there is less of a threat posed by women with normal codeine metabolism because the amount of codeine secreted into the breast milk is low and dose dependent.

The FDA stated that data reveal numerous reports of respiratory depression and at least one death in infants of breastfeeding mothers taking these medicines, particularly mothers with the CYP2D6 genotype. Although there are FDA-cleared tests for ultrarapid metabolism, they are not commonly used.

The agency stated that breastfeeding women taking any opioid pain medicine, including codeine or tramadol should contact their health care provider if they notice the infant is sleeping more than 4 hours at a time, or if the infant is having difficulty breastfeeding or seems limp.

Clinicians are urged to report side effects that occur while using codeine or tramadol to the FDA’s MedWatch Adverse Event Reporting program.

[email protected]

On Twitter @whitneymcknight

In patients with inflammatory bowel disease and spondyloarthritis (IBD-SpA), dactylitis, enthesitis, and anterior uveitis (AU) are significantly less frequent than in patients with other types of SpA, according to Fabrizio Cantini, MD, and his associates.

In a 12-month, case-control study, 88 patients with IBD-SpA, 29 with ulcerative colitis (UC), and 59 with Crohn’s disease (CD) were examined along with the 176 patients with SpA in the control group. Results showed a significantly lower occurrence of dactylitis in case patients, with 4 episodes (4.5%) in IBD-SpA patients and 30 (17.4%) in controls (P = .008). The comparison of the frequency of dactylitis in patients with UC-SpA and in patients with CD-SpA found no significant differences between the two (3.4% and 5.08%, respectively; P = .843). Enthesitis was significantly lower in IBD-SpA, occurring in 16 out of 88 patients (18.1%), compared with in 78 out of 176 controls (44.3%; P less than .001). AU was also recorded in 3 (3.4%) of the patients with IBD-SpA and in 26 controls (14.7%; P = .010), and B27 positivity was recorded in 10 (11.3%) of patients with IBD-SpA and in 70 (39.8%) of patients with SpA (P less than .001).

There was a significantly lower occurrence of dactylitis reported in IBD-SpA patients without psoriasis (1 case in 74 patients; P = .001) compared with the control group, while dactylitis occurrence was not significantly different in 3 out of 14 patients (21.4%) with coexistent psoriasis (P = .960). Enthesitis was significantly higher in 14 IBD-SpA patients with associated psoriasis (50%), compared with the remaining 74 cases (12.1%; P = .003). It was noted that enthesitis occurrence was not different in patients with UC and in those with CD (P = .103).

“The results of our case-control study show that dactylitis, enthesitis, and AU are significantly less frequent in IBD-SpA, compared with other types of SpA,” researchers concluded. “Owing to the frequent association of psoriasis with IBD, and especially with CD, the coexistence of skin disease should be taken into account when evaluating the prevalence of dactylitis and enthesitis in patients with IBD-SpA.”

Find the full study in the Journal of Rheumatology (doi: 10.3899/jrheum.161518).

[email protected]

In patients with inflammatory bowel disease and spondyloarthritis (IBD-SpA), dactylitis, enthesitis, and anterior uveitis (AU) are significantly less frequent than in patients with other types of SpA, according to Fabrizio Cantini, MD, and his associates.

In a 12-month, case-control study, 88 patients with IBD-SpA, 29 with ulcerative colitis (UC), and 59 with Crohn’s disease (CD) were examined along with the 176 patients with SpA in the control group. Results showed a significantly lower occurrence of dactylitis in case patients, with 4 episodes (4.5%) in IBD-SpA patients and 30 (17.4%) in controls (P = .008). The comparison of the frequency of dactylitis in patients with UC-SpA and in patients with CD-SpA found no significant differences between the two (3.4% and 5.08%, respectively; P = .843). Enthesitis was significantly lower in IBD-SpA, occurring in 16 out of 88 patients (18.1%), compared with in 78 out of 176 controls (44.3%; P less than .001). AU was also recorded in 3 (3.4%) of the patients with IBD-SpA and in 26 controls (14.7%; P = .010), and B27 positivity was recorded in 10 (11.3%) of patients with IBD-SpA and in 70 (39.8%) of patients with SpA (P less than .001).

There was a significantly lower occurrence of dactylitis reported in IBD-SpA patients without psoriasis (1 case in 74 patients; P = .001) compared with the control group, while dactylitis occurrence was not significantly different in 3 out of 14 patients (21.4%) with coexistent psoriasis (P = .960). Enthesitis was significantly higher in 14 IBD-SpA patients with associated psoriasis (50%), compared with the remaining 74 cases (12.1%; P = .003). It was noted that enthesitis occurrence was not different in patients with UC and in those with CD (P = .103).

“The results of our case-control study show that dactylitis, enthesitis, and AU are significantly less frequent in IBD-SpA, compared with other types of SpA,” researchers concluded. “Owing to the frequent association of psoriasis with IBD, and especially with CD, the coexistence of skin disease should be taken into account when evaluating the prevalence of dactylitis and enthesitis in patients with IBD-SpA.”

Find the full study in the Journal of Rheumatology (doi: 10.3899/jrheum.161518).

[email protected]

In patients with inflammatory bowel disease and spondyloarthritis (IBD-SpA), dactylitis, enthesitis, and anterior uveitis (AU) are significantly less frequent than in patients with other types of SpA, according to Fabrizio Cantini, MD, and his associates.

In a 12-month, case-control study, 88 patients with IBD-SpA, 29 with ulcerative colitis (UC), and 59 with Crohn’s disease (CD) were examined along with the 176 patients with SpA in the control group. Results showed a significantly lower occurrence of dactylitis in case patients, with 4 episodes (4.5%) in IBD-SpA patients and 30 (17.4%) in controls (P = .008). The comparison of the frequency of dactylitis in patients with UC-SpA and in patients with CD-SpA found no significant differences between the two (3.4% and 5.08%, respectively; P = .843). Enthesitis was significantly lower in IBD-SpA, occurring in 16 out of 88 patients (18.1%), compared with in 78 out of 176 controls (44.3%; P less than .001). AU was also recorded in 3 (3.4%) of the patients with IBD-SpA and in 26 controls (14.7%; P = .010), and B27 positivity was recorded in 10 (11.3%) of patients with IBD-SpA and in 70 (39.8%) of patients with SpA (P less than .001).

There was a significantly lower occurrence of dactylitis reported in IBD-SpA patients without psoriasis (1 case in 74 patients; P = .001) compared with the control group, while dactylitis occurrence was not significantly different in 3 out of 14 patients (21.4%) with coexistent psoriasis (P = .960). Enthesitis was significantly higher in 14 IBD-SpA patients with associated psoriasis (50%), compared with the remaining 74 cases (12.1%; P = .003). It was noted that enthesitis occurrence was not different in patients with UC and in those with CD (P = .103).

“The results of our case-control study show that dactylitis, enthesitis, and AU are significantly less frequent in IBD-SpA, compared with other types of SpA,” researchers concluded. “Owing to the frequent association of psoriasis with IBD, and especially with CD, the coexistence of skin disease should be taken into account when evaluating the prevalence of dactylitis and enthesitis in patients with IBD-SpA.”

Find the full study in the Journal of Rheumatology (doi: 10.3899/jrheum.161518).

[email protected]