Facilities that performed outpatient colonoscopies varied significantly in terms of subsequent unplanned hospital visits, even after patient-level risk factors were adjusted for, according to a Medicare claims analysis reported in the January issue of Gastroenterology.

This first-in-kind quality measure will help “make transparent the full range of adverse events requiring hospital care that patients experience post-[colonoscopy], inform patient choice, create incentives for improved care, and assist providers’ quality improvement efforts, wrote Dr. Isuru Ranasinghe of Yale–New Haven (Conn.) Hospital and his associates. Preventing unplanned hospitals visits after colonoscopy could also help improve patient outcomes and cut health care costs, they added.

© HUNG KUO CHUN/Thinkstock

More than 90% of colonoscopies occur in outpatient settings, where it is difficult to follow-up and track serious adverse events such as colonic perforation or gastrointestinal bleeding. Furthermore, there are no publicly available quality reports of providers or facilities that perform outpatient colonoscopies. To help fill that gap, the researchers tracked unplanned hospital visits within 7 days after colonoscopy as part of an outpatient quality initiative by the Centers for Medicare & Medicaid Services. The analysis included 20% of Medicare outpatient colonoscopy claims in 2010, which amounted to 331,880 colonoscopies performed at 8,140 facilities (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.09.009]).

In 2010, there were 16.3 unplanned hospital visits for every 1,000 Medicare claims for outpatient colonoscopies, which equated to 27,000 such visits nationwide, the investigators said. Patients who were older than 85 years were significantly more likely to have an unplanned hospital visit than were patients aged 65-69 years (odds ratio, 1.87; 95% confidence interval, 1.54-2.28). The other most significant predictors included having an electrolyte or acid/base imbalance (OR, 1.43) or a psychiatric disorder (OR, 1.34). After adjusting for these factors, unplanned admission rates varied significantly among facilities in all four states with available data, including New York, California, Florida, and Nebraska, the researchers said.

These findings might not apply to patients who are too young to be enrolled in Medicare, which “is important, as most colonoscopies are performed among patients aged less than 65 years, although older patients are more likely to suffer adverse events,” Dr. Ranasinghe and his associates noted. The study also did not assess deaths, the one-third of GI bleeding events that occur more than a week after colonoscopy, or the various factors that might affect quality of care, such as type of anesthesia, polypectomy technique, and access to follow-up care. “The goal of the measure is to reveal the opportunity for improvement, and to prompt facilities to examine their practices in depth to identify ways to lower hospital visit rates to the level achieved by the best providers,” the researchers emphasized.

The work was supported by the Centers for Medicare & Medicaid Services, the National Health and Medical Research Council, the National Heart Foundation of Australia, the National Institute on Aging, the American Federation for Aging Research. Dr. Ranasinghe and nine coinvestigators reported working under contract with CMS to develop and maintain performance measures. Three coinvestigators reported financial relationships with AbbVie, qMed, Pentax, Olympus, Myriad Genetics, UnitedHealth, Medtronic, and Johnson & Johnson.

Source: American Gastroenterological Association

Facilities that performed outpatient colonoscopies varied significantly in terms of subsequent unplanned hospital visits, even after patient-level risk factors were adjusted for, according to a Medicare claims analysis reported in the January issue of Gastroenterology.

This first-in-kind quality measure will help “make transparent the full range of adverse events requiring hospital care that patients experience post-[colonoscopy], inform patient choice, create incentives for improved care, and assist providers’ quality improvement efforts, wrote Dr. Isuru Ranasinghe of Yale–New Haven (Conn.) Hospital and his associates. Preventing unplanned hospitals visits after colonoscopy could also help improve patient outcomes and cut health care costs, they added.

© HUNG KUO CHUN/Thinkstock

More than 90% of colonoscopies occur in outpatient settings, where it is difficult to follow-up and track serious adverse events such as colonic perforation or gastrointestinal bleeding. Furthermore, there are no publicly available quality reports of providers or facilities that perform outpatient colonoscopies. To help fill that gap, the researchers tracked unplanned hospital visits within 7 days after colonoscopy as part of an outpatient quality initiative by the Centers for Medicare & Medicaid Services. The analysis included 20% of Medicare outpatient colonoscopy claims in 2010, which amounted to 331,880 colonoscopies performed at 8,140 facilities (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.09.009]).

In 2010, there were 16.3 unplanned hospital visits for every 1,000 Medicare claims for outpatient colonoscopies, which equated to 27,000 such visits nationwide, the investigators said. Patients who were older than 85 years were significantly more likely to have an unplanned hospital visit than were patients aged 65-69 years (odds ratio, 1.87; 95% confidence interval, 1.54-2.28). The other most significant predictors included having an electrolyte or acid/base imbalance (OR, 1.43) or a psychiatric disorder (OR, 1.34). After adjusting for these factors, unplanned admission rates varied significantly among facilities in all four states with available data, including New York, California, Florida, and Nebraska, the researchers said.

These findings might not apply to patients who are too young to be enrolled in Medicare, which “is important, as most colonoscopies are performed among patients aged less than 65 years, although older patients are more likely to suffer adverse events,” Dr. Ranasinghe and his associates noted. The study also did not assess deaths, the one-third of GI bleeding events that occur more than a week after colonoscopy, or the various factors that might affect quality of care, such as type of anesthesia, polypectomy technique, and access to follow-up care. “The goal of the measure is to reveal the opportunity for improvement, and to prompt facilities to examine their practices in depth to identify ways to lower hospital visit rates to the level achieved by the best providers,” the researchers emphasized.

The work was supported by the Centers for Medicare & Medicaid Services, the National Health and Medical Research Council, the National Heart Foundation of Australia, the National Institute on Aging, the American Federation for Aging Research. Dr. Ranasinghe and nine coinvestigators reported working under contract with CMS to develop and maintain performance measures. Three coinvestigators reported financial relationships with AbbVie, qMed, Pentax, Olympus, Myriad Genetics, UnitedHealth, Medtronic, and Johnson & Johnson.

Source: American Gastroenterological Association

Facilities that performed outpatient colonoscopies varied significantly in terms of subsequent unplanned hospital visits, even after patient-level risk factors were adjusted for, according to a Medicare claims analysis reported in the January issue of Gastroenterology.

This first-in-kind quality measure will help “make transparent the full range of adverse events requiring hospital care that patients experience post-[colonoscopy], inform patient choice, create incentives for improved care, and assist providers’ quality improvement efforts, wrote Dr. Isuru Ranasinghe of Yale–New Haven (Conn.) Hospital and his associates. Preventing unplanned hospitals visits after colonoscopy could also help improve patient outcomes and cut health care costs, they added.

© HUNG KUO CHUN/Thinkstock

More than 90% of colonoscopies occur in outpatient settings, where it is difficult to follow-up and track serious adverse events such as colonic perforation or gastrointestinal bleeding. Furthermore, there are no publicly available quality reports of providers or facilities that perform outpatient colonoscopies. To help fill that gap, the researchers tracked unplanned hospital visits within 7 days after colonoscopy as part of an outpatient quality initiative by the Centers for Medicare & Medicaid Services. The analysis included 20% of Medicare outpatient colonoscopy claims in 2010, which amounted to 331,880 colonoscopies performed at 8,140 facilities (Gastroenterology 2015 [doi: 10.1053/j.gastro.2015.09.009]).

In 2010, there were 16.3 unplanned hospital visits for every 1,000 Medicare claims for outpatient colonoscopies, which equated to 27,000 such visits nationwide, the investigators said. Patients who were older than 85 years were significantly more likely to have an unplanned hospital visit than were patients aged 65-69 years (odds ratio, 1.87; 95% confidence interval, 1.54-2.28). The other most significant predictors included having an electrolyte or acid/base imbalance (OR, 1.43) or a psychiatric disorder (OR, 1.34). After adjusting for these factors, unplanned admission rates varied significantly among facilities in all four states with available data, including New York, California, Florida, and Nebraska, the researchers said.

These findings might not apply to patients who are too young to be enrolled in Medicare, which “is important, as most colonoscopies are performed among patients aged less than 65 years, although older patients are more likely to suffer adverse events,” Dr. Ranasinghe and his associates noted. The study also did not assess deaths, the one-third of GI bleeding events that occur more than a week after colonoscopy, or the various factors that might affect quality of care, such as type of anesthesia, polypectomy technique, and access to follow-up care. “The goal of the measure is to reveal the opportunity for improvement, and to prompt facilities to examine their practices in depth to identify ways to lower hospital visit rates to the level achieved by the best providers,” the researchers emphasized.

The work was supported by the Centers for Medicare & Medicaid Services, the National Health and Medical Research Council, the National Heart Foundation of Australia, the National Institute on Aging, the American Federation for Aging Research. Dr. Ranasinghe and nine coinvestigators reported working under contract with CMS to develop and maintain performance measures. Three coinvestigators reported financial relationships with AbbVie, qMed, Pentax, Olympus, Myriad Genetics, UnitedHealth, Medtronic, and Johnson & Johnson.

Source: American Gastroenterological Association

Allergic Reaction Versus Anaphylaxis

A 34-year-old woman presented to ED with complaints of an allergic reaction, the onset of which began approximately 1 hour prior. The patient did not know what might have caused her symptoms. She complained of hives and itching all over; she denied difficulty swallowing, wheezing, and shortness of breath. Her medical history was unremarkable. She was on no medications, and she denied any alcohol or tobacco use. She had no known medication or food allergies.

Physical examination revealed a woman in mild discomfort, secondary to generalized itching. Her vital signs, including pulse oximetry, were normal. There was no swelling of the face, lips, or oropharynx. The lungs were clear to auscultation bilaterally. The heart and abdominal examinations were normal. Examination of the skin revealed diffuse urticaria without petechiae or purpura.

The emergency physician (EP) ordered 125 mg of methylprednisolone sodium succinate and 25 mg of diphenhydramine intravenously (IV). After approximately 1 hour, the hives and itching decreased and the patient felt improved. She was diagnosed with an allergic reaction and discharged home with a prescription for diphenhydramine and a methylprednisolone dose pack.

The following day, the patient collapsed at home and emergency medical services was called. Unfortunately, the patient could not be resuscitated and was pronounced dead at the scene. An autopsy revealed the patient had died from anaphylaxis and laryngeal edema, with an extremely elevated tryptase level of 200 ng/mL (normal, <11.5 ng/mL).

The patient’s family sued the EP for failure to diagnose and treat anaphylaxis, failure to treat with epinephrine, and failure to admit the patient to the hospital. The defense claimed the patient did not present with anaphylaxis, but rather simply a worsening of the hives and angioedema, and that the treatment provided was appropriate. The jury found in favor of the defendants.

Discussion

It does not appear the patient presented with anaphylaxis on the first visit, but may have had it on the second visit. In 2004, the National Institutes of Allergy and Infectious Disease (NIAID) panel and the Food Allergy and Anaphylaxis Network (FAAN) developed criteria for the diagnosis of anaphylaxis.¹ According to the criteria, anaphylaxis is likely when any one of the following three criteria are present: (1) acute onset of symptoms involving the skin or mucosa (eg, pruritus, hives, angioedema), and either respiratory compromise (eg, dyspnea, wheezing, stridor, hypoxia) or hypotension/end-organ dysfunction (eg, syncope, incontinence); (2) two or more symptoms (eg, respiratory compromise, hypotension/end-organ dysfunction, persistent gastrointestinal [GI] symptoms such as vomiting, diarrhea, or crampy abdominal pain) that occur rapidly after exposure involving the skin or mucosa; or (3) hypotension from a known allergen to the patient. The accuracy of these criteria has been retrospectively evaluated in an ED study, and found to have a 97% sensitivity and an 82% specificity.² The negative predictive value was good at 98%, but the positive predictive value was only 69%.²

When a patient presents with minimal or subtle symptoms, anaphylaxis can be a very difficult diagnosis to make in the ED early on in the process. While no EP will miss the diagnosis in a patient with hives, hypotension, and wheezing, it can be easy to miss when the predominant symptoms are GI, such as nausea, vomiting, or diarrhea. In addition, the differential diagnosis for the presentation of anaphylaxis in the ED can be extremely broad and include vasovagal reaction, asthma attack, myocardial infarction, gastroenteritis, panic attack, or airway obstruction.

Due to the nature of emergency medicine, EPs must consider multiple etiologies before determining an evaluation and management plan. While recognizing there are limitations to the NIAID/FAAN criteria, EPs should be aware of them. We are very good at treating these types of symptoms with antihistamines and steroids; however, we frequently fail to give epinephrine when indicated. It is important to remember that epinephrine is the first-line treatment for anaphylaxis—not corticosteroids or antihistamines.³

Reasons for not administering epinephrine are multiple. First, as discussed above, if the diagnosis of anaphylaxis is not considered, the EP is not going to administer the drug of choice. Secondly, EPs have been taught to have a healthy respect for epinephrine and its effects, especially in older patients. Due to this cautious approach, epinephrine is frequently not given to patients with mild symptoms or to those who present early in the course of disease.

Emergency physicians have experience giving epinephrine subcutaneously, but not nearly as much with the intramuscular (IM) route. This is important, because an IM injection in the anterolateral thigh is the recommended location for the treatment of anaphylaxis. The dose should be weight based (0.01 mg/kg) to a maximum of 0.5 mg. This dose can be given every 5 to 15 minutes as necessary to control symptoms.³ The dosing is important to remember, since many EDs stock only autoinjectable epinephrine devices for use in anaphylaxis. These autoinjectors only contain 0.3 mg of epinephrine, so some patients may be underdosed if used.

In the management of allergic reactions and anaphylaxis, EPs frequently administer antihistamines and corticosteroids. While there is no direct evidence to support their use in the management of anaphylaxis, theoretical benefits do exist.³ This, combined with the excellent medication safety profile and lack of serious side effects, make these two medication classes appropriate for use in the ED.

Allergic Reaction Versus Anaphylaxis

A 34-year-old woman presented to ED with complaints of an allergic reaction, the onset of which began approximately 1 hour prior. The patient did not know what might have caused her symptoms. She complained of hives and itching all over; she denied difficulty swallowing, wheezing, and shortness of breath. Her medical history was unremarkable. She was on no medications, and she denied any alcohol or tobacco use. She had no known medication or food allergies.

Physical examination revealed a woman in mild discomfort, secondary to generalized itching. Her vital signs, including pulse oximetry, were normal. There was no swelling of the face, lips, or oropharynx. The lungs were clear to auscultation bilaterally. The heart and abdominal examinations were normal. Examination of the skin revealed diffuse urticaria without petechiae or purpura.

The emergency physician (EP) ordered 125 mg of methylprednisolone sodium succinate and 25 mg of diphenhydramine intravenously (IV). After approximately 1 hour, the hives and itching decreased and the patient felt improved. She was diagnosed with an allergic reaction and discharged home with a prescription for diphenhydramine and a methylprednisolone dose pack.

The following day, the patient collapsed at home and emergency medical services was called. Unfortunately, the patient could not be resuscitated and was pronounced dead at the scene. An autopsy revealed the patient had died from anaphylaxis and laryngeal edema, with an extremely elevated tryptase level of 200 ng/mL (normal, <11.5 ng/mL).

The patient’s family sued the EP for failure to diagnose and treat anaphylaxis, failure to treat with epinephrine, and failure to admit the patient to the hospital. The defense claimed the patient did not present with anaphylaxis, but rather simply a worsening of the hives and angioedema, and that the treatment provided was appropriate. The jury found in favor of the defendants.

Discussion

It does not appear the patient presented with anaphylaxis on the first visit, but may have had it on the second visit. In 2004, the National Institutes of Allergy and Infectious Disease (NIAID) panel and the Food Allergy and Anaphylaxis Network (FAAN) developed criteria for the diagnosis of anaphylaxis.¹ According to the criteria, anaphylaxis is likely when any one of the following three criteria are present: (1) acute onset of symptoms involving the skin or mucosa (eg, pruritus, hives, angioedema), and either respiratory compromise (eg, dyspnea, wheezing, stridor, hypoxia) or hypotension/end-organ dysfunction (eg, syncope, incontinence); (2) two or more symptoms (eg, respiratory compromise, hypotension/end-organ dysfunction, persistent gastrointestinal [GI] symptoms such as vomiting, diarrhea, or crampy abdominal pain) that occur rapidly after exposure involving the skin or mucosa; or (3) hypotension from a known allergen to the patient. The accuracy of these criteria has been retrospectively evaluated in an ED study, and found to have a 97% sensitivity and an 82% specificity.² The negative predictive value was good at 98%, but the positive predictive value was only 69%.²

When a patient presents with minimal or subtle symptoms, anaphylaxis can be a very difficult diagnosis to make in the ED early on in the process. While no EP will miss the diagnosis in a patient with hives, hypotension, and wheezing, it can be easy to miss when the predominant symptoms are GI, such as nausea, vomiting, or diarrhea. In addition, the differential diagnosis for the presentation of anaphylaxis in the ED can be extremely broad and include vasovagal reaction, asthma attack, myocardial infarction, gastroenteritis, panic attack, or airway obstruction.

Due to the nature of emergency medicine, EPs must consider multiple etiologies before determining an evaluation and management plan. While recognizing there are limitations to the NIAID/FAAN criteria, EPs should be aware of them. We are very good at treating these types of symptoms with antihistamines and steroids; however, we frequently fail to give epinephrine when indicated. It is important to remember that epinephrine is the first-line treatment for anaphylaxis—not corticosteroids or antihistamines.³

Reasons for not administering epinephrine are multiple. First, as discussed above, if the diagnosis of anaphylaxis is not considered, the EP is not going to administer the drug of choice. Secondly, EPs have been taught to have a healthy respect for epinephrine and its effects, especially in older patients. Due to this cautious approach, epinephrine is frequently not given to patients with mild symptoms or to those who present early in the course of disease.

Emergency physicians have experience giving epinephrine subcutaneously, but not nearly as much with the intramuscular (IM) route. This is important, because an IM injection in the anterolateral thigh is the recommended location for the treatment of anaphylaxis. The dose should be weight based (0.01 mg/kg) to a maximum of 0.5 mg. This dose can be given every 5 to 15 minutes as necessary to control symptoms.³ The dosing is important to remember, since many EDs stock only autoinjectable epinephrine devices for use in anaphylaxis. These autoinjectors only contain 0.3 mg of epinephrine, so some patients may be underdosed if used.

In the management of allergic reactions and anaphylaxis, EPs frequently administer antihistamines and corticosteroids. While there is no direct evidence to support their use in the management of anaphylaxis, theoretical benefits do exist.³ This, combined with the excellent medication safety profile and lack of serious side effects, make these two medication classes appropriate for use in the ED.

Allergic Reaction Versus Anaphylaxis

A 34-year-old woman presented to ED with complaints of an allergic reaction, the onset of which began approximately 1 hour prior. The patient did not know what might have caused her symptoms. She complained of hives and itching all over; she denied difficulty swallowing, wheezing, and shortness of breath. Her medical history was unremarkable. She was on no medications, and she denied any alcohol or tobacco use. She had no known medication or food allergies.

Physical examination revealed a woman in mild discomfort, secondary to generalized itching. Her vital signs, including pulse oximetry, were normal. There was no swelling of the face, lips, or oropharynx. The lungs were clear to auscultation bilaterally. The heart and abdominal examinations were normal. Examination of the skin revealed diffuse urticaria without petechiae or purpura.

The emergency physician (EP) ordered 125 mg of methylprednisolone sodium succinate and 25 mg of diphenhydramine intravenously (IV). After approximately 1 hour, the hives and itching decreased and the patient felt improved. She was diagnosed with an allergic reaction and discharged home with a prescription for diphenhydramine and a methylprednisolone dose pack.

The following day, the patient collapsed at home and emergency medical services was called. Unfortunately, the patient could not be resuscitated and was pronounced dead at the scene. An autopsy revealed the patient had died from anaphylaxis and laryngeal edema, with an extremely elevated tryptase level of 200 ng/mL (normal, <11.5 ng/mL).

The patient’s family sued the EP for failure to diagnose and treat anaphylaxis, failure to treat with epinephrine, and failure to admit the patient to the hospital. The defense claimed the patient did not present with anaphylaxis, but rather simply a worsening of the hives and angioedema, and that the treatment provided was appropriate. The jury found in favor of the defendants.

Discussion

It does not appear the patient presented with anaphylaxis on the first visit, but may have had it on the second visit. In 2004, the National Institutes of Allergy and Infectious Disease (NIAID) panel and the Food Allergy and Anaphylaxis Network (FAAN) developed criteria for the diagnosis of anaphylaxis.¹ According to the criteria, anaphylaxis is likely when any one of the following three criteria are present: (1) acute onset of symptoms involving the skin or mucosa (eg, pruritus, hives, angioedema), and either respiratory compromise (eg, dyspnea, wheezing, stridor, hypoxia) or hypotension/end-organ dysfunction (eg, syncope, incontinence); (2) two or more symptoms (eg, respiratory compromise, hypotension/end-organ dysfunction, persistent gastrointestinal [GI] symptoms such as vomiting, diarrhea, or crampy abdominal pain) that occur rapidly after exposure involving the skin or mucosa; or (3) hypotension from a known allergen to the patient. The accuracy of these criteria has been retrospectively evaluated in an ED study, and found to have a 97% sensitivity and an 82% specificity.² The negative predictive value was good at 98%, but the positive predictive value was only 69%.²

When a patient presents with minimal or subtle symptoms, anaphylaxis can be a very difficult diagnosis to make in the ED early on in the process. While no EP will miss the diagnosis in a patient with hives, hypotension, and wheezing, it can be easy to miss when the predominant symptoms are GI, such as nausea, vomiting, or diarrhea. In addition, the differential diagnosis for the presentation of anaphylaxis in the ED can be extremely broad and include vasovagal reaction, asthma attack, myocardial infarction, gastroenteritis, panic attack, or airway obstruction.

Due to the nature of emergency medicine, EPs must consider multiple etiologies before determining an evaluation and management plan. While recognizing there are limitations to the NIAID/FAAN criteria, EPs should be aware of them. We are very good at treating these types of symptoms with antihistamines and steroids; however, we frequently fail to give epinephrine when indicated. It is important to remember that epinephrine is the first-line treatment for anaphylaxis—not corticosteroids or antihistamines.³

Reasons for not administering epinephrine are multiple. First, as discussed above, if the diagnosis of anaphylaxis is not considered, the EP is not going to administer the drug of choice. Secondly, EPs have been taught to have a healthy respect for epinephrine and its effects, especially in older patients. Due to this cautious approach, epinephrine is frequently not given to patients with mild symptoms or to those who present early in the course of disease.

Emergency physicians have experience giving epinephrine subcutaneously, but not nearly as much with the intramuscular (IM) route. This is important, because an IM injection in the anterolateral thigh is the recommended location for the treatment of anaphylaxis. The dose should be weight based (0.01 mg/kg) to a maximum of 0.5 mg. This dose can be given every 5 to 15 minutes as necessary to control symptoms.³ The dosing is important to remember, since many EDs stock only autoinjectable epinephrine devices for use in anaphylaxis. These autoinjectors only contain 0.3 mg of epinephrine, so some patients may be underdosed if used.

In the management of allergic reactions and anaphylaxis, EPs frequently administer antihistamines and corticosteroids. While there is no direct evidence to support their use in the management of anaphylaxis, theoretical benefits do exist.³ This, combined with the excellent medication safety profile and lack of serious side effects, make these two medication classes appropriate for use in the ED.

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One of the challenges a new academic hospitalist faces is trying to become a valued member of the teaching faculty. You are intent on becoming that next great attending you have always aspired to be; however, no one has clearly guided you on making this transition. In our experience, a handful of common teaching pitfalls frequently unravel the best efforts of young hospitalists. Below, you will find five strategies to take your teaching to the next level.

1. Don’t Try to Be Attending AND Resident.

Being a hospitalist attending is distinctly different than being a resident. It certainly is not being a “super-resident,” PGY-4, or PGY-17 for the team. When challenged with a new role and greater responsibility, it is natural to default to a more comfortable position (i.e., the hands-on mindset of the resident), but by doing so, you encroach on the work of the actual resident on your team. Adult learning theory teaches that it is responsibility that is the cornerstone of adult motivation. Trainees must have a chance to perform the work expected of their position without interference.

Let the resident be the resident. To reach this goal, set clear expectations and discuss the expectations up front. Make sure that you draw a sharp line between where the responsibility of the resident ends and yours begins. Have your resident help set her own expectations for the team, as well. This empowers the resident and also gives you insight into her view of the team dynamics. Your expectations should vary with the ability of the learner and the time of year. For example, the degree of autonomy that you may give a second-year resident in July is much less than what you might give a ready-to-graduate, third-year resident in June.

If granting autonomy makes you uncomfortable, observe your trainees from a distance for your own reassurance. Read the electronic medical record in depth; follow up on orders after attending rounds. If you don’t like a treatment decision, step in without inducing undue shame. After all, this is why residents are still in training, and it gives you the chance to demonstrate how to turn good care into great care.

2. Make Sure You Get to Know Your Trainees

Getting to know your trainees seems so simple that it often gets overlooked. Yet this may be the way your teaching and role modeling make their greatest impact. For adults to thrive in a learning environment, inclusion is key. There is no better way to feel included than to feel known. Inclusion allows learners to feel comfortable with being vulnerable by answering questions, asking questions, interacting, and participating in a meaningful manner on rounds. Consider your own behavior: How comfortable are you asking a question among a large audience of strangers versus asking the same question in a small group of friends? Inclusion will affect behavior.

Engage in “biographic rounds” near the start of your time together. As the attending, set the example by telling your trainees about yourself. Let them know where you are from, where you trained, what led you to choose hospital medicine, and some details about what you do in your spare time. Personal information will help break down the artificial walls that separate attendings from trainees.

Allow every member of your team to tell his or her story. It may not seem like much to you, but the effect on learners has been well established. If you invest in them, they will invest in the team.

3. Make Time to Observe Your Learners

You are responsible for evaluation and feedback of all your learners. Many factors contribute to poor feedback, but one of the most important is that new attendings often do not make a conscious effort to observe their learners. These attendings struggle to give meaningful feedback.

Take time and take notes:

• Take the time to watch your resident respond when the student is presenting her patient.
• Take time to allow the resident or intern to conduct bedside rounds on his patient.
• Take time to stop by on call to watch a student, intern, or resident take a history and perform a physical exam.

Even if you are unable to observe the whole encounter, there is little that gives you as much insight into your trainees as seeing them perform even part of a history and physical exam on a new patient. With time, a series of small observations will add up to a large number of specific comments.

Take notes on your trainees’ actions as you might do for your patients. This way, you have a record of what they did well and what needs work. Specific feedback will show that you paid attention and took the time to care about them as you would your patients.

4. Don’t Keep Your Thoughts to Yourself

Your job is akin to that of a syndicated columnist who is paid to give an informed narrative on the facts of the day. You must explain how the facts actually matter to patient care.

Think out loud. Explain your thoughts as much as possible. Do not assume that even your most senior trainees understand why you recommend a certain test or treatment. It is like algebra, where the teacher would never accept your answer unless you showed your work. For the sake of your learners, you must always “show your thinking.” They will learn as much from your clinical reasoning as they can from any canned talk on a subject.

5. Explicitly Plan Time for Teaching

“Thinking out loud” is a great way to teach, but a prepared talk can go into more depth on a topic. Yet how to find the time? The demands of a busy clinical service can overwhelm the best of intentions. Preparation is key. Good teaching does not happen by chance.

Set aside time for formal teaching outside of rounds. Be explicit as to when this will happen. Tell your team a day before, so they can prepare themselves or clear their time.

Have a handful of “canned” talks that you can give on topics related to common situations encountered in the hospital. They need not last more than 10 minutes. Always leave time for questions, and do your best to make them interactive. Even on a busy service, 10-15 minutes is reasonable for a brief, focused teaching session.

In Sum

Being an academic hospitalist with teaching responsibilities is highly rewarding. But becoming that next “great attending” requires an ongoing commitment to acquiring and developing your teaching skills.

Consider attending the SHM annual meeting or the Academic Hospitalist Academy to gain further knowledge on how to enhance your teaching career. In the meantime, try and practice some of the above tips—your learners may thank you. TH

Dr. Burger is associate program director of internal medicine residency in the Department of Medicine at Mount Sinai Beth Israel and assistant professor of medicine at Icahn School of Medicine at Mount Sinai, both in New York City. Dr. Miller is chief of the division of general internal medicine, associate chair of education, and associate professor in the Department of Internal Medicine at Saint Louis University.

One of the challenges a new academic hospitalist faces is trying to become a valued member of the teaching faculty. You are intent on becoming that next great attending you have always aspired to be; however, no one has clearly guided you on making this transition. In our experience, a handful of common teaching pitfalls frequently unravel the best efforts of young hospitalists. Below, you will find five strategies to take your teaching to the next level.

1. Don’t Try to Be Attending AND Resident.

Being a hospitalist attending is distinctly different than being a resident. It certainly is not being a “super-resident,” PGY-4, or PGY-17 for the team. When challenged with a new role and greater responsibility, it is natural to default to a more comfortable position (i.e., the hands-on mindset of the resident), but by doing so, you encroach on the work of the actual resident on your team. Adult learning theory teaches that it is responsibility that is the cornerstone of adult motivation. Trainees must have a chance to perform the work expected of their position without interference.

Let the resident be the resident. To reach this goal, set clear expectations and discuss the expectations up front. Make sure that you draw a sharp line between where the responsibility of the resident ends and yours begins. Have your resident help set her own expectations for the team, as well. This empowers the resident and also gives you insight into her view of the team dynamics. Your expectations should vary with the ability of the learner and the time of year. For example, the degree of autonomy that you may give a second-year resident in July is much less than what you might give a ready-to-graduate, third-year resident in June.

If granting autonomy makes you uncomfortable, observe your trainees from a distance for your own reassurance. Read the electronic medical record in depth; follow up on orders after attending rounds. If you don’t like a treatment decision, step in without inducing undue shame. After all, this is why residents are still in training, and it gives you the chance to demonstrate how to turn good care into great care.

2. Make Sure You Get to Know Your Trainees

Getting to know your trainees seems so simple that it often gets overlooked. Yet this may be the way your teaching and role modeling make their greatest impact. For adults to thrive in a learning environment, inclusion is key. There is no better way to feel included than to feel known. Inclusion allows learners to feel comfortable with being vulnerable by answering questions, asking questions, interacting, and participating in a meaningful manner on rounds. Consider your own behavior: How comfortable are you asking a question among a large audience of strangers versus asking the same question in a small group of friends? Inclusion will affect behavior.

Engage in “biographic rounds” near the start of your time together. As the attending, set the example by telling your trainees about yourself. Let them know where you are from, where you trained, what led you to choose hospital medicine, and some details about what you do in your spare time. Personal information will help break down the artificial walls that separate attendings from trainees.

Allow every member of your team to tell his or her story. It may not seem like much to you, but the effect on learners has been well established. If you invest in them, they will invest in the team.

3. Make Time to Observe Your Learners

You are responsible for evaluation and feedback of all your learners. Many factors contribute to poor feedback, but one of the most important is that new attendings often do not make a conscious effort to observe their learners. These attendings struggle to give meaningful feedback.

Take time and take notes:

• Take the time to watch your resident respond when the student is presenting her patient.
• Take time to allow the resident or intern to conduct bedside rounds on his patient.
• Take time to stop by on call to watch a student, intern, or resident take a history and perform a physical exam.

Even if you are unable to observe the whole encounter, there is little that gives you as much insight into your trainees as seeing them perform even part of a history and physical exam on a new patient. With time, a series of small observations will add up to a large number of specific comments.

Take notes on your trainees’ actions as you might do for your patients. This way, you have a record of what they did well and what needs work. Specific feedback will show that you paid attention and took the time to care about them as you would your patients.

4. Don’t Keep Your Thoughts to Yourself

Your job is akin to that of a syndicated columnist who is paid to give an informed narrative on the facts of the day. You must explain how the facts actually matter to patient care.

Think out loud. Explain your thoughts as much as possible. Do not assume that even your most senior trainees understand why you recommend a certain test or treatment. It is like algebra, where the teacher would never accept your answer unless you showed your work. For the sake of your learners, you must always “show your thinking.” They will learn as much from your clinical reasoning as they can from any canned talk on a subject.

5. Explicitly Plan Time for Teaching

“Thinking out loud” is a great way to teach, but a prepared talk can go into more depth on a topic. Yet how to find the time? The demands of a busy clinical service can overwhelm the best of intentions. Preparation is key. Good teaching does not happen by chance.

Set aside time for formal teaching outside of rounds. Be explicit as to when this will happen. Tell your team a day before, so they can prepare themselves or clear their time.

Have a handful of “canned” talks that you can give on topics related to common situations encountered in the hospital. They need not last more than 10 minutes. Always leave time for questions, and do your best to make them interactive. Even on a busy service, 10-15 minutes is reasonable for a brief, focused teaching session.

In Sum

Being an academic hospitalist with teaching responsibilities is highly rewarding. But becoming that next “great attending” requires an ongoing commitment to acquiring and developing your teaching skills.

Consider attending the SHM annual meeting or the Academic Hospitalist Academy to gain further knowledge on how to enhance your teaching career. In the meantime, try and practice some of the above tips—your learners may thank you. TH

Dr. Burger is associate program director of internal medicine residency in the Department of Medicine at Mount Sinai Beth Israel and assistant professor of medicine at Icahn School of Medicine at Mount Sinai, both in New York City. Dr. Miller is chief of the division of general internal medicine, associate chair of education, and associate professor in the Department of Internal Medicine at Saint Louis University.

One of the challenges a new academic hospitalist faces is trying to become a valued member of the teaching faculty. You are intent on becoming that next great attending you have always aspired to be; however, no one has clearly guided you on making this transition. In our experience, a handful of common teaching pitfalls frequently unravel the best efforts of young hospitalists. Below, you will find five strategies to take your teaching to the next level.

1. Don’t Try to Be Attending AND Resident.

Being a hospitalist attending is distinctly different than being a resident. It certainly is not being a “super-resident,” PGY-4, or PGY-17 for the team. When challenged with a new role and greater responsibility, it is natural to default to a more comfortable position (i.e., the hands-on mindset of the resident), but by doing so, you encroach on the work of the actual resident on your team. Adult learning theory teaches that it is responsibility that is the cornerstone of adult motivation. Trainees must have a chance to perform the work expected of their position without interference.

Let the resident be the resident. To reach this goal, set clear expectations and discuss the expectations up front. Make sure that you draw a sharp line between where the responsibility of the resident ends and yours begins. Have your resident help set her own expectations for the team, as well. This empowers the resident and also gives you insight into her view of the team dynamics. Your expectations should vary with the ability of the learner and the time of year. For example, the degree of autonomy that you may give a second-year resident in July is much less than what you might give a ready-to-graduate, third-year resident in June.

If granting autonomy makes you uncomfortable, observe your trainees from a distance for your own reassurance. Read the electronic medical record in depth; follow up on orders after attending rounds. If you don’t like a treatment decision, step in without inducing undue shame. After all, this is why residents are still in training, and it gives you the chance to demonstrate how to turn good care into great care.

2. Make Sure You Get to Know Your Trainees

Getting to know your trainees seems so simple that it often gets overlooked. Yet this may be the way your teaching and role modeling make their greatest impact. For adults to thrive in a learning environment, inclusion is key. There is no better way to feel included than to feel known. Inclusion allows learners to feel comfortable with being vulnerable by answering questions, asking questions, interacting, and participating in a meaningful manner on rounds. Consider your own behavior: How comfortable are you asking a question among a large audience of strangers versus asking the same question in a small group of friends? Inclusion will affect behavior.

Engage in “biographic rounds” near the start of your time together. As the attending, set the example by telling your trainees about yourself. Let them know where you are from, where you trained, what led you to choose hospital medicine, and some details about what you do in your spare time. Personal information will help break down the artificial walls that separate attendings from trainees.

Allow every member of your team to tell his or her story. It may not seem like much to you, but the effect on learners has been well established. If you invest in them, they will invest in the team.

3. Make Time to Observe Your Learners

You are responsible for evaluation and feedback of all your learners. Many factors contribute to poor feedback, but one of the most important is that new attendings often do not make a conscious effort to observe their learners. These attendings struggle to give meaningful feedback.

Take time and take notes:

• Take the time to watch your resident respond when the student is presenting her patient.
• Take time to allow the resident or intern to conduct bedside rounds on his patient.
• Take time to stop by on call to watch a student, intern, or resident take a history and perform a physical exam.

Even if you are unable to observe the whole encounter, there is little that gives you as much insight into your trainees as seeing them perform even part of a history and physical exam on a new patient. With time, a series of small observations will add up to a large number of specific comments.

Take notes on your trainees’ actions as you might do for your patients. This way, you have a record of what they did well and what needs work. Specific feedback will show that you paid attention and took the time to care about them as you would your patients.

4. Don’t Keep Your Thoughts to Yourself

Your job is akin to that of a syndicated columnist who is paid to give an informed narrative on the facts of the day. You must explain how the facts actually matter to patient care.

Think out loud. Explain your thoughts as much as possible. Do not assume that even your most senior trainees understand why you recommend a certain test or treatment. It is like algebra, where the teacher would never accept your answer unless you showed your work. For the sake of your learners, you must always “show your thinking.” They will learn as much from your clinical reasoning as they can from any canned talk on a subject.

5. Explicitly Plan Time for Teaching

“Thinking out loud” is a great way to teach, but a prepared talk can go into more depth on a topic. Yet how to find the time? The demands of a busy clinical service can overwhelm the best of intentions. Preparation is key. Good teaching does not happen by chance.

Set aside time for formal teaching outside of rounds. Be explicit as to when this will happen. Tell your team a day before, so they can prepare themselves or clear their time.

Have a handful of “canned” talks that you can give on topics related to common situations encountered in the hospital. They need not last more than 10 minutes. Always leave time for questions, and do your best to make them interactive. Even on a busy service, 10-15 minutes is reasonable for a brief, focused teaching session.

In Sum

Being an academic hospitalist with teaching responsibilities is highly rewarding. But becoming that next “great attending” requires an ongoing commitment to acquiring and developing your teaching skills.

Consider attending the SHM annual meeting or the Academic Hospitalist Academy to gain further knowledge on how to enhance your teaching career. In the meantime, try and practice some of the above tips—your learners may thank you. TH

Dr. Burger is associate program director of internal medicine residency in the Department of Medicine at Mount Sinai Beth Israel and assistant professor of medicine at Icahn School of Medicine at Mount Sinai, both in New York City. Dr. Miller is chief of the division of general internal medicine, associate chair of education, and associate professor in the Department of Internal Medicine at Saint Louis University.

 

 

Micrograph showing DLBCL

 

ORLANDO, FL—Updated results of a phase 1 study suggest the EZH2 inhibitor tazemetostat (EPZ-6438) can produce durable responses in patients with advanced non-Hodgkin lymphoma (NHL).

The drug has demonstrated activity against diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL).

The overall response rate among NHL patients in this study was 56%, and 1 patient has maintained a response for more than 21 months.

In addition, the drug’s safety profile is “still acceptable,” according to Vincent Ribrag, MD, of Institut Gustave Roussy in Villejuif, France.

Dr Ribrag presented the results of this study at the 2015 ASH Annual Meeting (abstract 473*). The research, which was previously presented at the 13th International Conference on Malignant Lymphoma, was sponsored by Epizyme, Inc., the company developing tazemetostat.

The trial has enrolled 58 patients, 21 with relapsed or refractory B-cell NHL and 37 with advanced solid tumors. The NHL cohort includes 5 patients with germinal center B-cell (GCB) DLBCL, 6 cases of non-GCB DLBCL, 3 DLBCL cases of an undetermined subtype, 6 patients with FL, and 1 case of MZL.

At baseline, the NHL patients had a median age of 63 (range, 24-84) and were heavily pretreated. Eighty-five percent of patients had received 3 or more prior therapies, and 33% had received 5 or more. Thirty-eight percent of patients had undergone an autologous transplant, and 57% had received radiotherapy.

The patients received tazemetostat twice daily at a range of doses. For the dose-escalation portion of the trial, they received 100 mg, 200 mg, 400 mg, 800 mg, or 1600 mg. For the dose-expansion phase, they received 800 mg or 1600 mg.

The researchers are now conducting a drug-drug interaction substudy in which patients receive 800 mg of tazemetostat twice daily and a food-effect substudy in which patients receive the drug at 400 mg twice daily.

Dr Ribrag said the recommended phase 2 dose of tazemetostat is 800 mg twice daily.

Safety

At the data cutoff point (November 7, 2015), 55 patients—20 with NHL and 35 with solid tumors—were evaluable for safety.

Treatment-related adverse events in these patients included asthenia (n=13), nausea (n=8), thrombocytopenia (n=7), dysgeusia (n=5), vomiting (n=5), dry skin (n=4), decreased appetite (n=4), diarrhea (n=4), muscle spasms (n=3), neutropenia (n=3), anemia (n=3), night sweats (n=3), hypertension (n=2), constipation (n=2), peripheral edema (n=2), hypophosphatemia (n=1), anxiety (n=1), depression (n=1), abdominal pain (n=1), and hepatocellular injury (n=1).

There were 4 grade 3 or higher adverse events that were considered treatment-related, including nausea, hypertension, neutropenia, and hepatocellular injury.

Efficacy

Sixteen of the NHL patients were evaluable for efficacy. Nine patients responded to treatment, 2 with complete responses (CRs) and 7 with partial responses (PRs).

Five of the 10 DLBCL patients responded, 4 with PRs and 1 with a CR. Three of the 5 FL patients responded, 2 with PRs and 1 with a CR. The patient with MZL achieved a PR.

Four responders remain on study—2 with DLBCL and 2 with FL.

One DLBCL patient with an EZH2 mutation (Y646H) had relapsed after or was refractory to 6 previous treatment regimens. This patient achieved a PR after 16 weeks of tazemetostat. The patient is still in PR at week 44 and remains on study.

Based on these results, Epizyme is currently enrolling patients in a phase 2 study of tazemetostat monotherapy. The trial is open to patients with DLBCL or FL in France, Australia, and the UK.

*Data in the abstract differ from the presentation.

 

 

Micrograph showing DLBCL

 

ORLANDO, FL—Updated results of a phase 1 study suggest the EZH2 inhibitor tazemetostat (EPZ-6438) can produce durable responses in patients with advanced non-Hodgkin lymphoma (NHL).

The drug has demonstrated activity against diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL).

The overall response rate among NHL patients in this study was 56%, and 1 patient has maintained a response for more than 21 months.

In addition, the drug’s safety profile is “still acceptable,” according to Vincent Ribrag, MD, of Institut Gustave Roussy in Villejuif, France.

Dr Ribrag presented the results of this study at the 2015 ASH Annual Meeting (abstract 473*). The research, which was previously presented at the 13th International Conference on Malignant Lymphoma, was sponsored by Epizyme, Inc., the company developing tazemetostat.

The trial has enrolled 58 patients, 21 with relapsed or refractory B-cell NHL and 37 with advanced solid tumors. The NHL cohort includes 5 patients with germinal center B-cell (GCB) DLBCL, 6 cases of non-GCB DLBCL, 3 DLBCL cases of an undetermined subtype, 6 patients with FL, and 1 case of MZL.

At baseline, the NHL patients had a median age of 63 (range, 24-84) and were heavily pretreated. Eighty-five percent of patients had received 3 or more prior therapies, and 33% had received 5 or more. Thirty-eight percent of patients had undergone an autologous transplant, and 57% had received radiotherapy.

The patients received tazemetostat twice daily at a range of doses. For the dose-escalation portion of the trial, they received 100 mg, 200 mg, 400 mg, 800 mg, or 1600 mg. For the dose-expansion phase, they received 800 mg or 1600 mg.

The researchers are now conducting a drug-drug interaction substudy in which patients receive 800 mg of tazemetostat twice daily and a food-effect substudy in which patients receive the drug at 400 mg twice daily.

Dr Ribrag said the recommended phase 2 dose of tazemetostat is 800 mg twice daily.

Safety

At the data cutoff point (November 7, 2015), 55 patients—20 with NHL and 35 with solid tumors—were evaluable for safety.

Treatment-related adverse events in these patients included asthenia (n=13), nausea (n=8), thrombocytopenia (n=7), dysgeusia (n=5), vomiting (n=5), dry skin (n=4), decreased appetite (n=4), diarrhea (n=4), muscle spasms (n=3), neutropenia (n=3), anemia (n=3), night sweats (n=3), hypertension (n=2), constipation (n=2), peripheral edema (n=2), hypophosphatemia (n=1), anxiety (n=1), depression (n=1), abdominal pain (n=1), and hepatocellular injury (n=1).

There were 4 grade 3 or higher adverse events that were considered treatment-related, including nausea, hypertension, neutropenia, and hepatocellular injury.

Efficacy

Sixteen of the NHL patients were evaluable for efficacy. Nine patients responded to treatment, 2 with complete responses (CRs) and 7 with partial responses (PRs).

Five of the 10 DLBCL patients responded, 4 with PRs and 1 with a CR. Three of the 5 FL patients responded, 2 with PRs and 1 with a CR. The patient with MZL achieved a PR.

Four responders remain on study—2 with DLBCL and 2 with FL.

One DLBCL patient with an EZH2 mutation (Y646H) had relapsed after or was refractory to 6 previous treatment regimens. This patient achieved a PR after 16 weeks of tazemetostat. The patient is still in PR at week 44 and remains on study.

Based on these results, Epizyme is currently enrolling patients in a phase 2 study of tazemetostat monotherapy. The trial is open to patients with DLBCL or FL in France, Australia, and the UK.

*Data in the abstract differ from the presentation.

 

 

Micrograph showing DLBCL

 

ORLANDO, FL—Updated results of a phase 1 study suggest the EZH2 inhibitor tazemetostat (EPZ-6438) can produce durable responses in patients with advanced non-Hodgkin lymphoma (NHL).

The drug has demonstrated activity against diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL).

The overall response rate among NHL patients in this study was 56%, and 1 patient has maintained a response for more than 21 months.

In addition, the drug’s safety profile is “still acceptable,” according to Vincent Ribrag, MD, of Institut Gustave Roussy in Villejuif, France.

Dr Ribrag presented the results of this study at the 2015 ASH Annual Meeting (abstract 473*). The research, which was previously presented at the 13th International Conference on Malignant Lymphoma, was sponsored by Epizyme, Inc., the company developing tazemetostat.

The trial has enrolled 58 patients, 21 with relapsed or refractory B-cell NHL and 37 with advanced solid tumors. The NHL cohort includes 5 patients with germinal center B-cell (GCB) DLBCL, 6 cases of non-GCB DLBCL, 3 DLBCL cases of an undetermined subtype, 6 patients with FL, and 1 case of MZL.

At baseline, the NHL patients had a median age of 63 (range, 24-84) and were heavily pretreated. Eighty-five percent of patients had received 3 or more prior therapies, and 33% had received 5 or more. Thirty-eight percent of patients had undergone an autologous transplant, and 57% had received radiotherapy.

The patients received tazemetostat twice daily at a range of doses. For the dose-escalation portion of the trial, they received 100 mg, 200 mg, 400 mg, 800 mg, or 1600 mg. For the dose-expansion phase, they received 800 mg or 1600 mg.

The researchers are now conducting a drug-drug interaction substudy in which patients receive 800 mg of tazemetostat twice daily and a food-effect substudy in which patients receive the drug at 400 mg twice daily.

Dr Ribrag said the recommended phase 2 dose of tazemetostat is 800 mg twice daily.

Safety

At the data cutoff point (November 7, 2015), 55 patients—20 with NHL and 35 with solid tumors—were evaluable for safety.

Treatment-related adverse events in these patients included asthenia (n=13), nausea (n=8), thrombocytopenia (n=7), dysgeusia (n=5), vomiting (n=5), dry skin (n=4), decreased appetite (n=4), diarrhea (n=4), muscle spasms (n=3), neutropenia (n=3), anemia (n=3), night sweats (n=3), hypertension (n=2), constipation (n=2), peripheral edema (n=2), hypophosphatemia (n=1), anxiety (n=1), depression (n=1), abdominal pain (n=1), and hepatocellular injury (n=1).

There were 4 grade 3 or higher adverse events that were considered treatment-related, including nausea, hypertension, neutropenia, and hepatocellular injury.

Efficacy

Sixteen of the NHL patients were evaluable for efficacy. Nine patients responded to treatment, 2 with complete responses (CRs) and 7 with partial responses (PRs).

Five of the 10 DLBCL patients responded, 4 with PRs and 1 with a CR. Three of the 5 FL patients responded, 2 with PRs and 1 with a CR. The patient with MZL achieved a PR.

Four responders remain on study—2 with DLBCL and 2 with FL.

One DLBCL patient with an EZH2 mutation (Y646H) had relapsed after or was refractory to 6 previous treatment regimens. This patient achieved a PR after 16 weeks of tazemetostat. The patient is still in PR at week 44 and remains on study.

Based on these results, Epizyme is currently enrolling patients in a phase 2 study of tazemetostat monotherapy. The trial is open to patients with DLBCL or FL in France, Australia, and the UK.

*Data in the abstract differ from the presentation.

Micrograph showing PMF

ORLANDO, FL—Having a higher grade of bone marrow (BM) fibrosis may confer inferior overall survival (OS) in patients with primary myelofibrosis (PMF), according to a retrospective study.

Investigators found that having a fibrosis grade of 2 or higher at diagnosis was associated with “unique clinical and molecular variables” that suggested a more aggressive disease phenotype.

And the median OS was significantly shorter in patients with higher grades of fibrosis.

However, when the investigators divided patients according to their International Prognostic Scoring System (IPSS) risk group, having a fibrosis grade of 2 or higher was only significantly associated with reduced OS among patients in the low-risk or intermediate-1-risk categories.

Paola Guglielmelli, MD, PhD, of the University of Florence in Italy, presented these findings at the 2015 ASH Annual Meeting (abstract 351*).

Dr Guglielmelli noted that the prognostic significance of BM fibrosis grade in PMF has been debated. So she and her colleagues set out to analyze the prognostic impact of fibrosis in 540 PMF patients from 6 Italian centers belonging to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative).

BM biopsies were obtained at diagnosis and evaluated by local pathologists according to 2008 World Health Organization criteria. The European consensus scoring system was used to grade fibrosis on a scale of MF-0 to MF-3.

Fifty patients were classified as MF-0 (9.3%), 180 were MF-1 (33.3%), 196 were MF-2 (36.3%), and 114 were MF-3 (21.1%).

Patients in the MF-2 and MF-3 groups were significantly more likely to have constitutional symptoms (P<0.0001), splenomegaly ≥10 cm from left costal margin (P<0.0001), a peripheral blast count ≥1% (P<0.0001), a greater risk of anemia (P<0.0001) or thrombocytopenia (P=0.001), and belong to the intermediate-2 or high-risk IPSS categories (P<0.0001).

In addition, patients in the MF-2 and MF-3 groups were significantly more likely to qualify as high-molecular-risk (HMR), which was defined as having at least 1 mutation in ASXL1, EZH2, SRSF2, or IDH1/2 (P<0.0001). The frequency of HMR patients increased progressively according to fibrosis grade: MF-0 (16%), MF-1 (25.6%), MF-2 (33.7%), and MF-3 (44.7%).

Patients with 2 or more HMR mutated genes were preferentially MF-2 or MF-3. None of the MF-0 patients fell into this category, compared to 4.4% for MF-1, 10.2% for MF-2, and 10.5% for MF-3 (P<0.0001).

Survival

The median OS was significantly shorter in patients with higher BM fibrosis grades (P<0.0001). The median OS was 7.2 years in the MF-3 group (hazard ratio [HR]=8.7), 6.7 years in the MF-2 group (HR=7.3), 14.7 years in the MF-1 group (HR=3.9), and not reached in the MF-0 group (reference).

In multivariable analysis, having a BM fibrosis grade of 2 or greater was significantly associated with reduced OS (HR=3.8, P=0.01).

Other variables significantly associated with reduced OS were being in the intermediate-1 (HR=2.9, P<0.0001), intermedicate-2 (HR=10.0, P<0.0001), or high-risk IPSS categories (HR=9.7, P<0.0001); having CALR type 2 mutation (HR=3.4, P=0.010), JAK2/MPL mutation (HR=2.4, P=0.003), or being triple-negative (HR=4.5, P<0.0001); being classified as HMR (HR=2.4, P<0.0001); and having 2 or more HMR mutations (HR=4.3, P=0.009).

Dr Guglielmelli and her colleagues also assessed the impact of BM fibrosis grade according to IPSS risk score.

They found that, for patients in the low/intermediate-1-risk categories, the median OS was not reached in the MF-0 group, was 22.8 years in the MF-1 group (HR=3.9), and was 15.4 years in the MF-2 and -3 groups combined (HR=7.4, P=0.001).

In the intermediate-2/high-risk categories, the median OS was 11 years for the MF-0 group, 3.6 years for the MF-1 group (HR=2.2), and 3.6 years in the MF-2 and -3 groups (HR=2.7, P=0.28).

Dr Guglielmelli therefore concluded that BM fibrosis grade might help refine prognostic stratification for PMF patients in the lower-risk IPSS categories. However, she noted that this study had limitations, and the results should be confirmed with prospective research.

*Data in the abstract differ from the presentation.

Micrograph showing PMF

ORLANDO, FL—Having a higher grade of bone marrow (BM) fibrosis may confer inferior overall survival (OS) in patients with primary myelofibrosis (PMF), according to a retrospective study.

Investigators found that having a fibrosis grade of 2 or higher at diagnosis was associated with “unique clinical and molecular variables” that suggested a more aggressive disease phenotype.

And the median OS was significantly shorter in patients with higher grades of fibrosis.

However, when the investigators divided patients according to their International Prognostic Scoring System (IPSS) risk group, having a fibrosis grade of 2 or higher was only significantly associated with reduced OS among patients in the low-risk or intermediate-1-risk categories.

Paola Guglielmelli, MD, PhD, of the University of Florence in Italy, presented these findings at the 2015 ASH Annual Meeting (abstract 351*).

Dr Guglielmelli noted that the prognostic significance of BM fibrosis grade in PMF has been debated. So she and her colleagues set out to analyze the prognostic impact of fibrosis in 540 PMF patients from 6 Italian centers belonging to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative).

BM biopsies were obtained at diagnosis and evaluated by local pathologists according to 2008 World Health Organization criteria. The European consensus scoring system was used to grade fibrosis on a scale of MF-0 to MF-3.

Fifty patients were classified as MF-0 (9.3%), 180 were MF-1 (33.3%), 196 were MF-2 (36.3%), and 114 were MF-3 (21.1%).

Patients in the MF-2 and MF-3 groups were significantly more likely to have constitutional symptoms (P<0.0001), splenomegaly ≥10 cm from left costal margin (P<0.0001), a peripheral blast count ≥1% (P<0.0001), a greater risk of anemia (P<0.0001) or thrombocytopenia (P=0.001), and belong to the intermediate-2 or high-risk IPSS categories (P<0.0001).

In addition, patients in the MF-2 and MF-3 groups were significantly more likely to qualify as high-molecular-risk (HMR), which was defined as having at least 1 mutation in ASXL1, EZH2, SRSF2, or IDH1/2 (P<0.0001). The frequency of HMR patients increased progressively according to fibrosis grade: MF-0 (16%), MF-1 (25.6%), MF-2 (33.7%), and MF-3 (44.7%).

Patients with 2 or more HMR mutated genes were preferentially MF-2 or MF-3. None of the MF-0 patients fell into this category, compared to 4.4% for MF-1, 10.2% for MF-2, and 10.5% for MF-3 (P<0.0001).

Survival

The median OS was significantly shorter in patients with higher BM fibrosis grades (P<0.0001). The median OS was 7.2 years in the MF-3 group (hazard ratio [HR]=8.7), 6.7 years in the MF-2 group (HR=7.3), 14.7 years in the MF-1 group (HR=3.9), and not reached in the MF-0 group (reference).

In multivariable analysis, having a BM fibrosis grade of 2 or greater was significantly associated with reduced OS (HR=3.8, P=0.01).

Other variables significantly associated with reduced OS were being in the intermediate-1 (HR=2.9, P<0.0001), intermedicate-2 (HR=10.0, P<0.0001), or high-risk IPSS categories (HR=9.7, P<0.0001); having CALR type 2 mutation (HR=3.4, P=0.010), JAK2/MPL mutation (HR=2.4, P=0.003), or being triple-negative (HR=4.5, P<0.0001); being classified as HMR (HR=2.4, P<0.0001); and having 2 or more HMR mutations (HR=4.3, P=0.009).

Dr Guglielmelli and her colleagues also assessed the impact of BM fibrosis grade according to IPSS risk score.

They found that, for patients in the low/intermediate-1-risk categories, the median OS was not reached in the MF-0 group, was 22.8 years in the MF-1 group (HR=3.9), and was 15.4 years in the MF-2 and -3 groups combined (HR=7.4, P=0.001).

In the intermediate-2/high-risk categories, the median OS was 11 years for the MF-0 group, 3.6 years for the MF-1 group (HR=2.2), and 3.6 years in the MF-2 and -3 groups (HR=2.7, P=0.28).

Dr Guglielmelli therefore concluded that BM fibrosis grade might help refine prognostic stratification for PMF patients in the lower-risk IPSS categories. However, she noted that this study had limitations, and the results should be confirmed with prospective research.

*Data in the abstract differ from the presentation.

Micrograph showing PMF

ORLANDO, FL—Having a higher grade of bone marrow (BM) fibrosis may confer inferior overall survival (OS) in patients with primary myelofibrosis (PMF), according to a retrospective study.

Investigators found that having a fibrosis grade of 2 or higher at diagnosis was associated with “unique clinical and molecular variables” that suggested a more aggressive disease phenotype.

And the median OS was significantly shorter in patients with higher grades of fibrosis.

However, when the investigators divided patients according to their International Prognostic Scoring System (IPSS) risk group, having a fibrosis grade of 2 or higher was only significantly associated with reduced OS among patients in the low-risk or intermediate-1-risk categories.

Paola Guglielmelli, MD, PhD, of the University of Florence in Italy, presented these findings at the 2015 ASH Annual Meeting (abstract 351*).

Dr Guglielmelli noted that the prognostic significance of BM fibrosis grade in PMF has been debated. So she and her colleagues set out to analyze the prognostic impact of fibrosis in 540 PMF patients from 6 Italian centers belonging to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative).

BM biopsies were obtained at diagnosis and evaluated by local pathologists according to 2008 World Health Organization criteria. The European consensus scoring system was used to grade fibrosis on a scale of MF-0 to MF-3.

Fifty patients were classified as MF-0 (9.3%), 180 were MF-1 (33.3%), 196 were MF-2 (36.3%), and 114 were MF-3 (21.1%).

Patients in the MF-2 and MF-3 groups were significantly more likely to have constitutional symptoms (P<0.0001), splenomegaly ≥10 cm from left costal margin (P<0.0001), a peripheral blast count ≥1% (P<0.0001), a greater risk of anemia (P<0.0001) or thrombocytopenia (P=0.001), and belong to the intermediate-2 or high-risk IPSS categories (P<0.0001).

In addition, patients in the MF-2 and MF-3 groups were significantly more likely to qualify as high-molecular-risk (HMR), which was defined as having at least 1 mutation in ASXL1, EZH2, SRSF2, or IDH1/2 (P<0.0001). The frequency of HMR patients increased progressively according to fibrosis grade: MF-0 (16%), MF-1 (25.6%), MF-2 (33.7%), and MF-3 (44.7%).

Patients with 2 or more HMR mutated genes were preferentially MF-2 or MF-3. None of the MF-0 patients fell into this category, compared to 4.4% for MF-1, 10.2% for MF-2, and 10.5% for MF-3 (P<0.0001).

Survival

The median OS was significantly shorter in patients with higher BM fibrosis grades (P<0.0001). The median OS was 7.2 years in the MF-3 group (hazard ratio [HR]=8.7), 6.7 years in the MF-2 group (HR=7.3), 14.7 years in the MF-1 group (HR=3.9), and not reached in the MF-0 group (reference).

In multivariable analysis, having a BM fibrosis grade of 2 or greater was significantly associated with reduced OS (HR=3.8, P=0.01).

Other variables significantly associated with reduced OS were being in the intermediate-1 (HR=2.9, P<0.0001), intermedicate-2 (HR=10.0, P<0.0001), or high-risk IPSS categories (HR=9.7, P<0.0001); having CALR type 2 mutation (HR=3.4, P=0.010), JAK2/MPL mutation (HR=2.4, P=0.003), or being triple-negative (HR=4.5, P<0.0001); being classified as HMR (HR=2.4, P<0.0001); and having 2 or more HMR mutations (HR=4.3, P=0.009).

Dr Guglielmelli and her colleagues also assessed the impact of BM fibrosis grade according to IPSS risk score.

They found that, for patients in the low/intermediate-1-risk categories, the median OS was not reached in the MF-0 group, was 22.8 years in the MF-1 group (HR=3.9), and was 15.4 years in the MF-2 and -3 groups combined (HR=7.4, P=0.001).

In the intermediate-2/high-risk categories, the median OS was 11 years for the MF-0 group, 3.6 years for the MF-1 group (HR=2.2), and 3.6 years in the MF-2 and -3 groups (HR=2.7, P=0.28).

Dr Guglielmelli therefore concluded that BM fibrosis grade might help refine prognostic stratification for PMF patients in the lower-risk IPSS categories. However, she noted that this study had limitations, and the results should be confirmed with prospective research.

*Data in the abstract differ from the presentation.

Jinghui Zhang, PhD, (left)

and Xin Zhou, PhD

Photo by Peter Barta/St. Jude

Children’s Research Hospital

Researchers say they have developed a tool that may advance our understanding of the mutations that drive pediatric cancers.

The tool, called ProteinPaint, is a web application that allows the user to visualize genetic lesions and RNA expression in pediatric cancers.

ProteinPaint’s infographics let users see all mutations in individual genes and their corresponding proteins, including detailed information about mutation type, frequency in cancer subtype, and location in the protein domain.

That information provides clues about how a change might contribute to cancer’s start, progression, or relapse.

Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and her colleagues described ProteinPaint in a letter to Nature Genetics.

ProteinPaint currently integrates information from 5 studies, but Dr Zhang and her colleagues said the data will be updated as new studies are published.

ProteinPaint now includes information on almost 27,500 mutations discovered in more than 1000 pediatric patients with 21 cancer subtypes. The application also includes RNA-sequencing data from 928 pediatric tumors belonging to 36 different subtypes.

Xin Zhou, PhD, also of St. Jude, developed ProteinPaint’s infographics to display the genomic information in an interactive format. A click of the mouse gives users additional details about the mutations listed, including the pediatric cancer subtype where the change has been validated and a link to the publication.

“ProteinPaint’s focus on pediatric cancer and presentation of mutations at the gene level complements existing cancer genome data portals,” Dr Zhang said. “For St. Jude, the application is the foundation for developing a global reference database for information about pediatric cancer.”

Dr Zhou added that the ProteinPaint software has the potential to help researchers studying other disorders, including sickle cell disease, that involve a mutation that affects protein function.

ProteinPaint is available at no cost to academic researchers who are free to use the tool to analyze their own data. The application also lets researchers compare information about pediatric and adult cancer genomes by providing a parallel view of data from COSMIC, the world’s largest database of somatic mutations, primarily from adult cancer.

ProteinPaint has already been used to study the role played by germline mutations in pediatric cancers. That research was published in NEJM in November.

More information about ProteinPaint is available on the St. Jude PeCan Data Portal.

Jinghui Zhang, PhD, (left)

and Xin Zhou, PhD

Photo by Peter Barta/St. Jude

Children’s Research Hospital

Researchers say they have developed a tool that may advance our understanding of the mutations that drive pediatric cancers.

The tool, called ProteinPaint, is a web application that allows the user to visualize genetic lesions and RNA expression in pediatric cancers.

ProteinPaint’s infographics let users see all mutations in individual genes and their corresponding proteins, including detailed information about mutation type, frequency in cancer subtype, and location in the protein domain.

That information provides clues about how a change might contribute to cancer’s start, progression, or relapse.

Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and her colleagues described ProteinPaint in a letter to Nature Genetics.

ProteinPaint currently integrates information from 5 studies, but Dr Zhang and her colleagues said the data will be updated as new studies are published.

ProteinPaint now includes information on almost 27,500 mutations discovered in more than 1000 pediatric patients with 21 cancer subtypes. The application also includes RNA-sequencing data from 928 pediatric tumors belonging to 36 different subtypes.

Xin Zhou, PhD, also of St. Jude, developed ProteinPaint’s infographics to display the genomic information in an interactive format. A click of the mouse gives users additional details about the mutations listed, including the pediatric cancer subtype where the change has been validated and a link to the publication.

“ProteinPaint’s focus on pediatric cancer and presentation of mutations at the gene level complements existing cancer genome data portals,” Dr Zhang said. “For St. Jude, the application is the foundation for developing a global reference database for information about pediatric cancer.”

Dr Zhou added that the ProteinPaint software has the potential to help researchers studying other disorders, including sickle cell disease, that involve a mutation that affects protein function.

ProteinPaint is available at no cost to academic researchers who are free to use the tool to analyze their own data. The application also lets researchers compare information about pediatric and adult cancer genomes by providing a parallel view of data from COSMIC, the world’s largest database of somatic mutations, primarily from adult cancer.

ProteinPaint has already been used to study the role played by germline mutations in pediatric cancers. That research was published in NEJM in November.

More information about ProteinPaint is available on the St. Jude PeCan Data Portal.

Jinghui Zhang, PhD, (left)

and Xin Zhou, PhD

Photo by Peter Barta/St. Jude

Children’s Research Hospital

Researchers say they have developed a tool that may advance our understanding of the mutations that drive pediatric cancers.

The tool, called ProteinPaint, is a web application that allows the user to visualize genetic lesions and RNA expression in pediatric cancers.

ProteinPaint’s infographics let users see all mutations in individual genes and their corresponding proteins, including detailed information about mutation type, frequency in cancer subtype, and location in the protein domain.

That information provides clues about how a change might contribute to cancer’s start, progression, or relapse.

Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and her colleagues described ProteinPaint in a letter to Nature Genetics.

ProteinPaint currently integrates information from 5 studies, but Dr Zhang and her colleagues said the data will be updated as new studies are published.

ProteinPaint now includes information on almost 27,500 mutations discovered in more than 1000 pediatric patients with 21 cancer subtypes. The application also includes RNA-sequencing data from 928 pediatric tumors belonging to 36 different subtypes.

Xin Zhou, PhD, also of St. Jude, developed ProteinPaint’s infographics to display the genomic information in an interactive format. A click of the mouse gives users additional details about the mutations listed, including the pediatric cancer subtype where the change has been validated and a link to the publication.

“ProteinPaint’s focus on pediatric cancer and presentation of mutations at the gene level complements existing cancer genome data portals,” Dr Zhang said. “For St. Jude, the application is the foundation for developing a global reference database for information about pediatric cancer.”

Dr Zhou added that the ProteinPaint software has the potential to help researchers studying other disorders, including sickle cell disease, that involve a mutation that affects protein function.

ProteinPaint is available at no cost to academic researchers who are free to use the tool to analyze their own data. The application also lets researchers compare information about pediatric and adult cancer genomes by providing a parallel view of data from COSMIC, the world’s largest database of somatic mutations, primarily from adult cancer.

ProteinPaint has already been used to study the role played by germline mutations in pediatric cancers. That research was published in NEJM in November.

More information about ProteinPaint is available on the St. Jude PeCan Data Portal.

Researcher on a computer

Photo by Darren Baker

A computer model that employs techniques used to analyze social networks could aid the development of new cancer treatments, according to researchers.

The model analyzes the unique behaviors of cancer-causing proteins, spotting what makes them different from normal proteins and mapping out molecular targets for drugs that could potentially be developed to treat cancers.

The researchers described this model in PLOS Computational Biology.

Bissan Al-Lazikani, PhD, of The Institute of Cancer Research in London, UK, and her colleagues compared proteins to members of an enormous social network, mapping the ways they interact. This allowed the team to predict which proteins might be most effectively targeted with drugs.

Cancer-causing proteins that have already been successfully targeted tended to have particular “social” characteristics that differed from non-cancer proteins. “Hub-like” proteins that were shown to “communicate” with lots of other proteins were more likely to cause cancers.

The researchers said this suggests that previously unexplored cancer proteins with similar characteristics could make good drug targets.

“Our study is the first to identify the rules of social behavior of cancer proteins and use it to predict new targets for potential cancer drugs,” Dr Al-Lazikani said.

“It shows that cancer drug targets behave very differently from normal proteins and often have a complex web of social interactions. Finding new targets is one of the most important steps in drug discovery, but it can be a lengthy, expensive process.”

“The map that we’ve made will help researchers design better new drugs, more quickly, saving time and money. It also sheds light on how resistance to treatments may occur and, in just a few years, could help doctors choose the best drug combinations to suit individual patients.”

All of the researchers’ target predictions are available on the canSAR website. The underlying data and tools are also available on the site.

Researcher on a computer

Photo by Darren Baker

A computer model that employs techniques used to analyze social networks could aid the development of new cancer treatments, according to researchers.

The model analyzes the unique behaviors of cancer-causing proteins, spotting what makes them different from normal proteins and mapping out molecular targets for drugs that could potentially be developed to treat cancers.

The researchers described this model in PLOS Computational Biology.

Bissan Al-Lazikani, PhD, of The Institute of Cancer Research in London, UK, and her colleagues compared proteins to members of an enormous social network, mapping the ways they interact. This allowed the team to predict which proteins might be most effectively targeted with drugs.

Cancer-causing proteins that have already been successfully targeted tended to have particular “social” characteristics that differed from non-cancer proteins. “Hub-like” proteins that were shown to “communicate” with lots of other proteins were more likely to cause cancers.

The researchers said this suggests that previously unexplored cancer proteins with similar characteristics could make good drug targets.

“Our study is the first to identify the rules of social behavior of cancer proteins and use it to predict new targets for potential cancer drugs,” Dr Al-Lazikani said.

“It shows that cancer drug targets behave very differently from normal proteins and often have a complex web of social interactions. Finding new targets is one of the most important steps in drug discovery, but it can be a lengthy, expensive process.”

“The map that we’ve made will help researchers design better new drugs, more quickly, saving time and money. It also sheds light on how resistance to treatments may occur and, in just a few years, could help doctors choose the best drug combinations to suit individual patients.”

All of the researchers’ target predictions are available on the canSAR website. The underlying data and tools are also available on the site.

Researcher on a computer

Photo by Darren Baker

A computer model that employs techniques used to analyze social networks could aid the development of new cancer treatments, according to researchers.

The model analyzes the unique behaviors of cancer-causing proteins, spotting what makes them different from normal proteins and mapping out molecular targets for drugs that could potentially be developed to treat cancers.

The researchers described this model in PLOS Computational Biology.

Bissan Al-Lazikani, PhD, of The Institute of Cancer Research in London, UK, and her colleagues compared proteins to members of an enormous social network, mapping the ways they interact. This allowed the team to predict which proteins might be most effectively targeted with drugs.

Cancer-causing proteins that have already been successfully targeted tended to have particular “social” characteristics that differed from non-cancer proteins. “Hub-like” proteins that were shown to “communicate” with lots of other proteins were more likely to cause cancers.

The researchers said this suggests that previously unexplored cancer proteins with similar characteristics could make good drug targets.

“Our study is the first to identify the rules of social behavior of cancer proteins and use it to predict new targets for potential cancer drugs,” Dr Al-Lazikani said.

“It shows that cancer drug targets behave very differently from normal proteins and often have a complex web of social interactions. Finding new targets is one of the most important steps in drug discovery, but it can be a lengthy, expensive process.”

“The map that we’ve made will help researchers design better new drugs, more quickly, saving time and money. It also sheds light on how resistance to treatments may occur and, in just a few years, could help doctors choose the best drug combinations to suit individual patients.”

All of the researchers’ target predictions are available on the canSAR website. The underlying data and tools are also available on the site.