At a recent surgical Morbidity and Mortality Conference, we discussed a tragic case of an elderly gentleman who had been explored for a gastric outlet obstruction. He was found to have a widely metastatic malignancy of unknown primary that was clearly unresectable. Biopsies were taken, a bypass was performed to alleviate the obstruction, and the patient was closed. The surgeon subsequently discussed the findings with the patient and his family. They were understandably upset after getting the news, but plans were made for follow-up and possible treatment when the final pathology was back. During several days in the hospital, the patient seemed to be in good spirits and was seen regularly, encouraging his family not to worry. However, on the day of discharge, the patient went home and committed suicide.

This case raised a series of important questions at the Morbidity and Mortality (M&M) Conference. Had the patient shown signs of depression? Should he have been evaluated by psychiatry? Did the surgical team miss any signs of his impending actions? In the tradition of M&M Conferences, the discussion focused on the question, "What would you have done differently?"

One issue repeatedly raised in the discussions at conference given the patient’s response was whether he should have been told his diagnosis. Such a consideration is a radical idea today when no physician would argue against telling a patient a diagnosis of cancer. But this consensus of full disclosure is relatively new in the medical profession. In 1961, 88% of physicians surveyed at Michael Reese Hospital in Chicago stated that their general policy was not to disclose a cancer diagnosis to the patient (JAMA 1961;175:1120-8). Certainly, this view among physicians has changed dramatically in recent decades. By 1979, the same survey at the same hospital revealed that 98% of physicians said that they tell patients that when the diagnosis is cancer (JAMA 1979;241:897-900).

In the medical profession, a diagnosis is no longer seen as information that can be withheld from a patient. The idea of respecting the patient as a person means that the patient must have the information necessary to make decisions about his or her future.

In this context, the recent New York Times article entitled "When Doctors Need to Lie" (Feb. 22, 2014) is provocative. Dr. Sandeep Jauhar suggests that sometimes there are situations in which doctors need to exercise a form of paternalism and lie to patients for their own benefit. Dr. Jauhar described a case in which he informed the family of a young patient of the true diagnosis, but only gradually and gently told the young man of his true condition.

Informing the elderly gentleman of his diagnosis may well have triggered his suicide. If the patient had not known that he had unresectable cancer, he could well still be alive. Nevertheless, no one at the M&M conference thought that lying about the diagnosis could be justified. Knowing the diagnosis is the fundamental basis for a patient to project a future existence. The ability to make the best medical and nonmedical decisions is dependent on having valid information. Without truthful information, the decisions made are uninformed and no better than guesses. It is not the physician’s role to guess the reaction of a patient to a diagnosis or project a future circumstance that may result from the patient learning the truth.

While the outcome of the transmission of knowledge to the patient may at times be unfortunate, the ethical implications of not telling patients the truth are potentially even more unfortunate. How can a surgeon establish a relationship of trust while also lying to a patient or withholding important information? Even though the choice made by this particular patient was tragic, to have lied to him is contrary to the physician’s role. Truth is the basis of trust, and trust in turn must be the basis of the relationship between doctor and patient.

Dr. Angelos is an ACS Fellow; the Linda Kohler Anderson Professor of Surgery and Surgical Ethics; chief, endocrine surgery; and associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago.

At a recent surgical Morbidity and Mortality Conference, we discussed a tragic case of an elderly gentleman who had been explored for a gastric outlet obstruction. He was found to have a widely metastatic malignancy of unknown primary that was clearly unresectable. Biopsies were taken, a bypass was performed to alleviate the obstruction, and the patient was closed. The surgeon subsequently discussed the findings with the patient and his family. They were understandably upset after getting the news, but plans were made for follow-up and possible treatment when the final pathology was back. During several days in the hospital, the patient seemed to be in good spirits and was seen regularly, encouraging his family not to worry. However, on the day of discharge, the patient went home and committed suicide.

This case raised a series of important questions at the Morbidity and Mortality (M&M) Conference. Had the patient shown signs of depression? Should he have been evaluated by psychiatry? Did the surgical team miss any signs of his impending actions? In the tradition of M&M Conferences, the discussion focused on the question, "What would you have done differently?"

One issue repeatedly raised in the discussions at conference given the patient’s response was whether he should have been told his diagnosis. Such a consideration is a radical idea today when no physician would argue against telling a patient a diagnosis of cancer. But this consensus of full disclosure is relatively new in the medical profession. In 1961, 88% of physicians surveyed at Michael Reese Hospital in Chicago stated that their general policy was not to disclose a cancer diagnosis to the patient (JAMA 1961;175:1120-8). Certainly, this view among physicians has changed dramatically in recent decades. By 1979, the same survey at the same hospital revealed that 98% of physicians said that they tell patients that when the diagnosis is cancer (JAMA 1979;241:897-900).

In the medical profession, a diagnosis is no longer seen as information that can be withheld from a patient. The idea of respecting the patient as a person means that the patient must have the information necessary to make decisions about his or her future.

In this context, the recent New York Times article entitled "When Doctors Need to Lie" (Feb. 22, 2014) is provocative. Dr. Sandeep Jauhar suggests that sometimes there are situations in which doctors need to exercise a form of paternalism and lie to patients for their own benefit. Dr. Jauhar described a case in which he informed the family of a young patient of the true diagnosis, but only gradually and gently told the young man of his true condition.

Informing the elderly gentleman of his diagnosis may well have triggered his suicide. If the patient had not known that he had unresectable cancer, he could well still be alive. Nevertheless, no one at the M&M conference thought that lying about the diagnosis could be justified. Knowing the diagnosis is the fundamental basis for a patient to project a future existence. The ability to make the best medical and nonmedical decisions is dependent on having valid information. Without truthful information, the decisions made are uninformed and no better than guesses. It is not the physician’s role to guess the reaction of a patient to a diagnosis or project a future circumstance that may result from the patient learning the truth.

While the outcome of the transmission of knowledge to the patient may at times be unfortunate, the ethical implications of not telling patients the truth are potentially even more unfortunate. How can a surgeon establish a relationship of trust while also lying to a patient or withholding important information? Even though the choice made by this particular patient was tragic, to have lied to him is contrary to the physician’s role. Truth is the basis of trust, and trust in turn must be the basis of the relationship between doctor and patient.

Dr. Angelos is an ACS Fellow; the Linda Kohler Anderson Professor of Surgery and Surgical Ethics; chief, endocrine surgery; and associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago.

At a recent surgical Morbidity and Mortality Conference, we discussed a tragic case of an elderly gentleman who had been explored for a gastric outlet obstruction. He was found to have a widely metastatic malignancy of unknown primary that was clearly unresectable. Biopsies were taken, a bypass was performed to alleviate the obstruction, and the patient was closed. The surgeon subsequently discussed the findings with the patient and his family. They were understandably upset after getting the news, but plans were made for follow-up and possible treatment when the final pathology was back. During several days in the hospital, the patient seemed to be in good spirits and was seen regularly, encouraging his family not to worry. However, on the day of discharge, the patient went home and committed suicide.

This case raised a series of important questions at the Morbidity and Mortality (M&M) Conference. Had the patient shown signs of depression? Should he have been evaluated by psychiatry? Did the surgical team miss any signs of his impending actions? In the tradition of M&M Conferences, the discussion focused on the question, "What would you have done differently?"

One issue repeatedly raised in the discussions at conference given the patient’s response was whether he should have been told his diagnosis. Such a consideration is a radical idea today when no physician would argue against telling a patient a diagnosis of cancer. But this consensus of full disclosure is relatively new in the medical profession. In 1961, 88% of physicians surveyed at Michael Reese Hospital in Chicago stated that their general policy was not to disclose a cancer diagnosis to the patient (JAMA 1961;175:1120-8). Certainly, this view among physicians has changed dramatically in recent decades. By 1979, the same survey at the same hospital revealed that 98% of physicians said that they tell patients that when the diagnosis is cancer (JAMA 1979;241:897-900).

In the medical profession, a diagnosis is no longer seen as information that can be withheld from a patient. The idea of respecting the patient as a person means that the patient must have the information necessary to make decisions about his or her future.

In this context, the recent New York Times article entitled "When Doctors Need to Lie" (Feb. 22, 2014) is provocative. Dr. Sandeep Jauhar suggests that sometimes there are situations in which doctors need to exercise a form of paternalism and lie to patients for their own benefit. Dr. Jauhar described a case in which he informed the family of a young patient of the true diagnosis, but only gradually and gently told the young man of his true condition.

Informing the elderly gentleman of his diagnosis may well have triggered his suicide. If the patient had not known that he had unresectable cancer, he could well still be alive. Nevertheless, no one at the M&M conference thought that lying about the diagnosis could be justified. Knowing the diagnosis is the fundamental basis for a patient to project a future existence. The ability to make the best medical and nonmedical decisions is dependent on having valid information. Without truthful information, the decisions made are uninformed and no better than guesses. It is not the physician’s role to guess the reaction of a patient to a diagnosis or project a future circumstance that may result from the patient learning the truth.

While the outcome of the transmission of knowledge to the patient may at times be unfortunate, the ethical implications of not telling patients the truth are potentially even more unfortunate. How can a surgeon establish a relationship of trust while also lying to a patient or withholding important information? Even though the choice made by this particular patient was tragic, to have lied to him is contrary to the physician’s role. Truth is the basis of trust, and trust in turn must be the basis of the relationship between doctor and patient.

Dr. Angelos is an ACS Fellow; the Linda Kohler Anderson Professor of Surgery and Surgical Ethics; chief, endocrine surgery; and associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago.

Obesity rates in the United States have skyrocketed over the last 30 years, with rates for adults having doubled and rates for children tripled from 1980 to 2010. Approximately one-third of the U.S adult population is obese; that’s 72 million people. The consequences of obesity include an increased risk for stroke, hypertension, type 2 diabetes, liver and gallbladder disease, orthopedic complications, mental health conditions, cancers, elevated lipids, obstructive sleep apnea (OSA), and reproductive complications such as infertility.

There is now solid evidence that we can intervene to help patient lose weight and decrease the complications that result from obesity. To this end, the American Association of Clinical Endocrinology (AACE) has issued recommendations giving guidance for clinicians about how to approach this issue. Intensive approaches to lifestyle modification with diet and exercise can help patients lose 7% or more of their body weight and have been show to decrease progression from prediabetes to diabetes. Two new medications, lorcaserin and phentermine/topiramate ER, have received Food and Drug Administration approval over the past 2 years as an adjunct to diet for weight loss. Bariatric surgery has emerged as a safe and effective method of weight loss as well.

The AACE guidelines focus on a "complications-centric model" as opposed to a body mass index–driven approach. The guidelines recommend treating obesity to decrease the risk of developing adverse metabolic consequences such as diabetes and metabolic syndrome, and to decrease disability from mechanical comorbidities such as osteoarthritis and obstructive sleep apnea. The AACE guidelines place obese patients into two categories: those that have obesity-related comorbidities and those that do not. The guidelines recommend a graded approach to treatment. All overweight and obese patients should receive therapeutic lifestyle counseling focusing on diet and exercise. Medical or surgical treatment is then recommended for the patients who stand to benefit the most, those with obesity-related comorbidities and those with more severe obesity who have not been able to lose weight using lifestyle modification alone.

In the initial evaluation of overweight and obese patients, the patients should be assessed for cardiometabolic and mechanical complications of obesity, as well as the severity of those complications in order to determine the level of treatment that is appropriate. Patients with obesity-related comorbidities are classified into two groups. The first group includes those with insulin resistance and/or cardiovascular consequences. For this group, evaluation should include waist circumference, fasting, and 2-hour glucose tolerance testing, and lipids, blood pressure, and liver function testing. The second group is composed of people with mechanical consequences including OSA, stress incontinence, orthopedic complications, and chronic pulmonary diseases.

It is important to determine target goals for weight loss to improve mechanical and cardiometabolic complications. Weight loss of 5% or more is enough to affect improvement in metabolic parameters such as glucose and lipids, decrease progression to diabetes, and improve mechanical complications such as knee and hip pain in osteoarthritis. The next step in the approach to treatment is to determine the type and intensity. Therapeutic lifestyle changes (TLC) are important for all patients with diabetes and prediabetes, regardless of risk factors. TLC recommendations include smoking cessation, physical activity, weight management, and healthy eating. Exercise is recommended 5 days/week for more than 30 minutes of moderate intensity activity, to achieve a more than 60% age-related heart rate. The diet recommended reduced saturated fat to less than 7% of calories, reduced cholesterol intake to 200 mg/day, increased fiber to 10-25 g/day, increased plant sterols/stanol esters to 2 g/day, caloric restriction, reduced simple carbohydrates and sugars, increased intake of unsaturated fats, elimination of trans fats, increased marine-based omega-3 ethyl esters, and restriction of alcohol to 20-30 g/day.

For patients with comorbidities and with a BMI of 27 kg/m² or more, consideration should be given to weight-loss medication in addition to lifestyle intervention. The currently approved medications for long-term weight loss include lorcaserin and phentermine/topiramate ER. In the FDA registration studies, the lorcaserin group had an average weight loss of 5.8% after 1 year vs. 2.2% in the placebo group. Phentermine/topiramate ER had an average weight loss of 10% at 1 year vs. 1.2% in the placebo group. These medications are FDA approved as adjuncts to lifestyle modification for the treatment of overweight patients with a BMI greater than 27 kg/m² with comorbidities and for obese patients with a BMI greater than 30 kg/m² regardless of comorbidities. Both medications improve blood pressure, triglycerides, and insulin sensitivity and prevent the progression to diabetes in patients with diabetes. Bariatric surgery should be considered for those with a BMI of 35 kg/m² or morewith comorbidities, especially if they have failed using other methods.

Once goals are reached, reassess the patient to evaluate for more interventions, if needed. If the targets for improvement in complications were not reached, then the weight loss therapy should become more intense.

Bottom line

The AACE recommendations recognize obesity as a disease and have formulated guidelines using a "complications-centric model." Patients should be assessed for obesity and related complications. Lifestyle counseling should be provided for all overweight and obese individuals, with the addition of weight loss medications for individuals with a BMI of 27 kg/m² or more who have obesity-related comorbidities, and the consideration of bariatric surgery for those with a BMI of 35 kg/m² or more with comorbidities.

Reference

American Association of Clinical Endocrinologists’ Comprehensive Diabetes Management Algorithm 2013 Consensus Statement. Published May/June 2013, Endocrine Practice, Vol. 19 (Suppl. 2).

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. Dr. McDonald is a second-year resident in the Family Medicine Residency Program at Abington Memorial Hospital.

[email protected]

Obesity rates in the United States have skyrocketed over the last 30 years, with rates for adults having doubled and rates for children tripled from 1980 to 2010. Approximately one-third of the U.S adult population is obese; that’s 72 million people. The consequences of obesity include an increased risk for stroke, hypertension, type 2 diabetes, liver and gallbladder disease, orthopedic complications, mental health conditions, cancers, elevated lipids, obstructive sleep apnea (OSA), and reproductive complications such as infertility.

There is now solid evidence that we can intervene to help patient lose weight and decrease the complications that result from obesity. To this end, the American Association of Clinical Endocrinology (AACE) has issued recommendations giving guidance for clinicians about how to approach this issue. Intensive approaches to lifestyle modification with diet and exercise can help patients lose 7% or more of their body weight and have been show to decrease progression from prediabetes to diabetes. Two new medications, lorcaserin and phentermine/topiramate ER, have received Food and Drug Administration approval over the past 2 years as an adjunct to diet for weight loss. Bariatric surgery has emerged as a safe and effective method of weight loss as well.

The AACE guidelines focus on a "complications-centric model" as opposed to a body mass index–driven approach. The guidelines recommend treating obesity to decrease the risk of developing adverse metabolic consequences such as diabetes and metabolic syndrome, and to decrease disability from mechanical comorbidities such as osteoarthritis and obstructive sleep apnea. The AACE guidelines place obese patients into two categories: those that have obesity-related comorbidities and those that do not. The guidelines recommend a graded approach to treatment. All overweight and obese patients should receive therapeutic lifestyle counseling focusing on diet and exercise. Medical or surgical treatment is then recommended for the patients who stand to benefit the most, those with obesity-related comorbidities and those with more severe obesity who have not been able to lose weight using lifestyle modification alone.

In the initial evaluation of overweight and obese patients, the patients should be assessed for cardiometabolic and mechanical complications of obesity, as well as the severity of those complications in order to determine the level of treatment that is appropriate. Patients with obesity-related comorbidities are classified into two groups. The first group includes those with insulin resistance and/or cardiovascular consequences. For this group, evaluation should include waist circumference, fasting, and 2-hour glucose tolerance testing, and lipids, blood pressure, and liver function testing. The second group is composed of people with mechanical consequences including OSA, stress incontinence, orthopedic complications, and chronic pulmonary diseases.

It is important to determine target goals for weight loss to improve mechanical and cardiometabolic complications. Weight loss of 5% or more is enough to affect improvement in metabolic parameters such as glucose and lipids, decrease progression to diabetes, and improve mechanical complications such as knee and hip pain in osteoarthritis. The next step in the approach to treatment is to determine the type and intensity. Therapeutic lifestyle changes (TLC) are important for all patients with diabetes and prediabetes, regardless of risk factors. TLC recommendations include smoking cessation, physical activity, weight management, and healthy eating. Exercise is recommended 5 days/week for more than 30 minutes of moderate intensity activity, to achieve a more than 60% age-related heart rate. The diet recommended reduced saturated fat to less than 7% of calories, reduced cholesterol intake to 200 mg/day, increased fiber to 10-25 g/day, increased plant sterols/stanol esters to 2 g/day, caloric restriction, reduced simple carbohydrates and sugars, increased intake of unsaturated fats, elimination of trans fats, increased marine-based omega-3 ethyl esters, and restriction of alcohol to 20-30 g/day.

For patients with comorbidities and with a BMI of 27 kg/m² or more, consideration should be given to weight-loss medication in addition to lifestyle intervention. The currently approved medications for long-term weight loss include lorcaserin and phentermine/topiramate ER. In the FDA registration studies, the lorcaserin group had an average weight loss of 5.8% after 1 year vs. 2.2% in the placebo group. Phentermine/topiramate ER had an average weight loss of 10% at 1 year vs. 1.2% in the placebo group. These medications are FDA approved as adjuncts to lifestyle modification for the treatment of overweight patients with a BMI greater than 27 kg/m² with comorbidities and for obese patients with a BMI greater than 30 kg/m² regardless of comorbidities. Both medications improve blood pressure, triglycerides, and insulin sensitivity and prevent the progression to diabetes in patients with diabetes. Bariatric surgery should be considered for those with a BMI of 35 kg/m² or morewith comorbidities, especially if they have failed using other methods.

Once goals are reached, reassess the patient to evaluate for more interventions, if needed. If the targets for improvement in complications were not reached, then the weight loss therapy should become more intense.

Bottom line

The AACE recommendations recognize obesity as a disease and have formulated guidelines using a "complications-centric model." Patients should be assessed for obesity and related complications. Lifestyle counseling should be provided for all overweight and obese individuals, with the addition of weight loss medications for individuals with a BMI of 27 kg/m² or more who have obesity-related comorbidities, and the consideration of bariatric surgery for those with a BMI of 35 kg/m² or more with comorbidities.

Reference

American Association of Clinical Endocrinologists’ Comprehensive Diabetes Management Algorithm 2013 Consensus Statement. Published May/June 2013, Endocrine Practice, Vol. 19 (Suppl. 2).

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. Dr. McDonald is a second-year resident in the Family Medicine Residency Program at Abington Memorial Hospital.

[email protected]

Obesity rates in the United States have skyrocketed over the last 30 years, with rates for adults having doubled and rates for children tripled from 1980 to 2010. Approximately one-third of the U.S adult population is obese; that’s 72 million people. The consequences of obesity include an increased risk for stroke, hypertension, type 2 diabetes, liver and gallbladder disease, orthopedic complications, mental health conditions, cancers, elevated lipids, obstructive sleep apnea (OSA), and reproductive complications such as infertility.

There is now solid evidence that we can intervene to help patient lose weight and decrease the complications that result from obesity. To this end, the American Association of Clinical Endocrinology (AACE) has issued recommendations giving guidance for clinicians about how to approach this issue. Intensive approaches to lifestyle modification with diet and exercise can help patients lose 7% or more of their body weight and have been show to decrease progression from prediabetes to diabetes. Two new medications, lorcaserin and phentermine/topiramate ER, have received Food and Drug Administration approval over the past 2 years as an adjunct to diet for weight loss. Bariatric surgery has emerged as a safe and effective method of weight loss as well.

The AACE guidelines focus on a "complications-centric model" as opposed to a body mass index–driven approach. The guidelines recommend treating obesity to decrease the risk of developing adverse metabolic consequences such as diabetes and metabolic syndrome, and to decrease disability from mechanical comorbidities such as osteoarthritis and obstructive sleep apnea. The AACE guidelines place obese patients into two categories: those that have obesity-related comorbidities and those that do not. The guidelines recommend a graded approach to treatment. All overweight and obese patients should receive therapeutic lifestyle counseling focusing on diet and exercise. Medical or surgical treatment is then recommended for the patients who stand to benefit the most, those with obesity-related comorbidities and those with more severe obesity who have not been able to lose weight using lifestyle modification alone.

In the initial evaluation of overweight and obese patients, the patients should be assessed for cardiometabolic and mechanical complications of obesity, as well as the severity of those complications in order to determine the level of treatment that is appropriate. Patients with obesity-related comorbidities are classified into two groups. The first group includes those with insulin resistance and/or cardiovascular consequences. For this group, evaluation should include waist circumference, fasting, and 2-hour glucose tolerance testing, and lipids, blood pressure, and liver function testing. The second group is composed of people with mechanical consequences including OSA, stress incontinence, orthopedic complications, and chronic pulmonary diseases.

It is important to determine target goals for weight loss to improve mechanical and cardiometabolic complications. Weight loss of 5% or more is enough to affect improvement in metabolic parameters such as glucose and lipids, decrease progression to diabetes, and improve mechanical complications such as knee and hip pain in osteoarthritis. The next step in the approach to treatment is to determine the type and intensity. Therapeutic lifestyle changes (TLC) are important for all patients with diabetes and prediabetes, regardless of risk factors. TLC recommendations include smoking cessation, physical activity, weight management, and healthy eating. Exercise is recommended 5 days/week for more than 30 minutes of moderate intensity activity, to achieve a more than 60% age-related heart rate. The diet recommended reduced saturated fat to less than 7% of calories, reduced cholesterol intake to 200 mg/day, increased fiber to 10-25 g/day, increased plant sterols/stanol esters to 2 g/day, caloric restriction, reduced simple carbohydrates and sugars, increased intake of unsaturated fats, elimination of trans fats, increased marine-based omega-3 ethyl esters, and restriction of alcohol to 20-30 g/day.

For patients with comorbidities and with a BMI of 27 kg/m² or more, consideration should be given to weight-loss medication in addition to lifestyle intervention. The currently approved medications for long-term weight loss include lorcaserin and phentermine/topiramate ER. In the FDA registration studies, the lorcaserin group had an average weight loss of 5.8% after 1 year vs. 2.2% in the placebo group. Phentermine/topiramate ER had an average weight loss of 10% at 1 year vs. 1.2% in the placebo group. These medications are FDA approved as adjuncts to lifestyle modification for the treatment of overweight patients with a BMI greater than 27 kg/m² with comorbidities and for obese patients with a BMI greater than 30 kg/m² regardless of comorbidities. Both medications improve blood pressure, triglycerides, and insulin sensitivity and prevent the progression to diabetes in patients with diabetes. Bariatric surgery should be considered for those with a BMI of 35 kg/m² or morewith comorbidities, especially if they have failed using other methods.

Once goals are reached, reassess the patient to evaluate for more interventions, if needed. If the targets for improvement in complications were not reached, then the weight loss therapy should become more intense.

Bottom line

The AACE recommendations recognize obesity as a disease and have formulated guidelines using a "complications-centric model." Patients should be assessed for obesity and related complications. Lifestyle counseling should be provided for all overweight and obese individuals, with the addition of weight loss medications for individuals with a BMI of 27 kg/m² or more who have obesity-related comorbidities, and the consideration of bariatric surgery for those with a BMI of 35 kg/m² or more with comorbidities.

Reference

American Association of Clinical Endocrinologists’ Comprehensive Diabetes Management Algorithm 2013 Consensus Statement. Published May/June 2013, Endocrine Practice, Vol. 19 (Suppl. 2).

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. Dr. McDonald is a second-year resident in the Family Medicine Residency Program at Abington Memorial Hospital.

[email protected]

The prevailing view among many psy­chiatrists and mental health profession­als is that borderline personality disorder (BPD) is a “psychological” condition. BPD often is conceptualized as a behav­ioral consequence of childhood trauma; treatment approaches have emphasized intensive psychotherapeutic modali­ties, less so biologic interventions. You might not be aware that a large body of research over the past decade provides strong evidence that BPD is a neuro­biological illness—a finding that would drastically alter how the disorder should be conceptualized and managed.

Neuropathology underpins the personality disorder
Foremost, BPD must be regarded as a serious, disabling brain disorder, not simply an aberration of personality. In DSM-5, symptoms of BPD are listed as: feelings of abandonment; unstable and intense interpersonal relationships; un­stable sense of self; impulsivity; suicidal or self-mutilating behavior; affective in­stability (dysphoria, irritability, anxiety); chronic feelings of emptiness; intense anger episodes; and transient paranoid or dissociative symptoms. Clearly, these clusters of psychopathological and be­havioral symptoms reflect a pervasive brain disorder associated with abnormal neurobiology and neural circuitry that might, at times, stubbornly defy thera­peutic intervention.

No wonder that 42 published stud­ies report that, compared with healthy controls, people who have BPD display extensive cortical and subcortical abnor­malities in brain structure and function.¹ These anomalous patterns have been detected across all 4 available neuroim­aging techniques.

Magnetic resonance imaging. MRI studies have revealed the following abnormalities in BPD:
   • hypoplasia of the hippocampus, caudate, and dorsolateral prefrontal cortex
   • variations in the CA1 region of the hippocampus and subiculum
   • smaller-than-normal orbitofrontal cortex (by 24%, compared with healthy controls) and the mid-temporal and left cingulate gyrii (by 26%)
   • larger-than-normal volume of the right inferior parietal cortex and the right parahippocampal gyrus
   • loss of gray matter in the frontal, temporal, and parietal cortices
   • an enlarged third cerebral ventricle
   • in women, reduced size of the me­dial temporal lobe and amygdala
   • in men, a decreased concentra­tion of gray matter in the anterior cingulate
   • reversal of normal right-greater-than-left asymmetry of the orbitofron­tal cortex gray matter, reflecting loss of gray matter on the right side
   • a lower concentration of gray mat­ter in the rostral/subgenual anterior cin­gulate cortex
   • a  smaller frontal lobe.

In an analysis of MRI studies,2 cor­relation was found between structural brain abnormalities and specific symp­toms of BPD, such as impulsivity, sui­cidality, and aggression. These findings might someday guide personalized in­terventions—for example, using neuro­stimulation techniques such as repetitive transcranial magnetic stimulation and deep brain stimulation—to modulate the activity of a given region of the brain (depending on which symptom is most prominent or disabling).
 

Magnetic resonance spectroscopy. In BPD, MRS studies reveal:
   • compared with controls, a higher glutamate level in the anterior cingulate cortex
   • reduced levels of N-acetyl aspar­tate (NAA; found in neurons) and cre­atinine in the left amygdala
   • a reduction (on average, 19%) in the NAA concentration in the dorsolat­eral prefrontal cortex.

Functional magnetic resonance im­aging. From fMRI studies, there is evi­dence in BPD of:
   • greater activation of the amygdala and prolonged return to baseline
   • increased functional connectiv­ity in the left frontopolar cortex and left insula
   • decreased connectivity in the left cuneus and left inferior parietal and the right middle temporal lobes
   • marked frontal hypometabolism
   • hypermetabolism in the motor cor­tex, medial and anterior cingulate, and occipital and temporal poles
   • lower connectivity between the amygdala during a neutral stimulus
   • higher connectivity between the amygdala during fear stimulus
   • higher connectivity between the amygdala during fear stimulus
   • deactivation of the opioid system in the left nucleus accumbens, hypothal­amus, and hippocampus
   • hyperactivation of the left medial prefrontal cortex during social exclusion
   • more mistakes made in differenti­ating an emotional and a neutral facial expression.
 

Diffusion tensor imaging. DTI white-matter integrity studies of BPD show:
   • a bilateral decrease in fractional an­isotropy (FA) in frontal, uncinated, and occipitalfrontal fasciculi
   • a decrease in FA in the genu and rostrum of the corpus callosum
   • a decrease in inter-hemispheric connectivity between right and left ante­rior cigulate cortices.

Genetic Studies
There is substantial scientific evidence that BPD is highly heritable—a finding that suggests that brain abnormalities of this disorder are a consequence of genes involved in brain development (similar to what is known about schizophrenia, bipolar disorder, and autism).

A systematic review of the heritabil­ity of BPD examined 59 published stud­ies that were categorized into 12 family studies, 18 twin studies, 24 association studies, and 5 gene-environment inter­action studies.3 The authors concluded that BPD has a strong genetic compo­nent, although there also is evidence of gene-environment (G.E) interactions (ie, how nature and nurture influence each other).

The G.E interaction model appears to be consistent with the theory that ex­pression of plasticity genes is modified by childhood experiences and environ­ment, such as physical or sexual abuse. Some studies have found evidence of hypermethylation in BPD, which can ex­ert epigenetic effects. Childhood abuse might, therefore, disrupt certain neuro­plasticity genes, culminating in morpho­logical, neurochemical, metabolic, and white-matter aberrations—leading to pathological behavioral patterns identi­fied as BPD.
 

The neuropsychiatric basis of BPD must guide treatment
There is no such thing as a purely psycho­logical disorder: Invariably, it is an abnor­mality of brain circuits that disrupts normal development of emotions, thought, behavior, and social cognition. BPD is an exemplar of such neuropsychiatric illness, and treat­ment should support psychotherapeutic ap­proaches to mend the mind at the same time it moves aggressively to repair the brain.

The prevailing view among many psy­chiatrists and mental health profession­als is that borderline personality disorder (BPD) is a “psychological” condition. BPD often is conceptualized as a behav­ioral consequence of childhood trauma; treatment approaches have emphasized intensive psychotherapeutic modali­ties, less so biologic interventions. You might not be aware that a large body of research over the past decade provides strong evidence that BPD is a neuro­biological illness—a finding that would drastically alter how the disorder should be conceptualized and managed.

Neuropathology underpins the personality disorder
Foremost, BPD must be regarded as a serious, disabling brain disorder, not simply an aberration of personality. In DSM-5, symptoms of BPD are listed as: feelings of abandonment; unstable and intense interpersonal relationships; un­stable sense of self; impulsivity; suicidal or self-mutilating behavior; affective in­stability (dysphoria, irritability, anxiety); chronic feelings of emptiness; intense anger episodes; and transient paranoid or dissociative symptoms. Clearly, these clusters of psychopathological and be­havioral symptoms reflect a pervasive brain disorder associated with abnormal neurobiology and neural circuitry that might, at times, stubbornly defy thera­peutic intervention.

No wonder that 42 published stud­ies report that, compared with healthy controls, people who have BPD display extensive cortical and subcortical abnor­malities in brain structure and function.¹ These anomalous patterns have been detected across all 4 available neuroim­aging techniques.

Magnetic resonance imaging. MRI studies have revealed the following abnormalities in BPD:
   • hypoplasia of the hippocampus, caudate, and dorsolateral prefrontal cortex
   • variations in the CA1 region of the hippocampus and subiculum
   • smaller-than-normal orbitofrontal cortex (by 24%, compared with healthy controls) and the mid-temporal and left cingulate gyrii (by 26%)
   • larger-than-normal volume of the right inferior parietal cortex and the right parahippocampal gyrus
   • loss of gray matter in the frontal, temporal, and parietal cortices
   • an enlarged third cerebral ventricle
   • in women, reduced size of the me­dial temporal lobe and amygdala
   • in men, a decreased concentra­tion of gray matter in the anterior cingulate
   • reversal of normal right-greater-than-left asymmetry of the orbitofron­tal cortex gray matter, reflecting loss of gray matter on the right side
   • a lower concentration of gray mat­ter in the rostral/subgenual anterior cin­gulate cortex
   • a  smaller frontal lobe.

In an analysis of MRI studies,2 cor­relation was found between structural brain abnormalities and specific symp­toms of BPD, such as impulsivity, sui­cidality, and aggression. These findings might someday guide personalized in­terventions—for example, using neuro­stimulation techniques such as repetitive transcranial magnetic stimulation and deep brain stimulation—to modulate the activity of a given region of the brain (depending on which symptom is most prominent or disabling).
 

Magnetic resonance spectroscopy. In BPD, MRS studies reveal:
   • compared with controls, a higher glutamate level in the anterior cingulate cortex
   • reduced levels of N-acetyl aspar­tate (NAA; found in neurons) and cre­atinine in the left amygdala
   • a reduction (on average, 19%) in the NAA concentration in the dorsolat­eral prefrontal cortex.

Functional magnetic resonance im­aging. From fMRI studies, there is evi­dence in BPD of:
   • greater activation of the amygdala and prolonged return to baseline
   • increased functional connectiv­ity in the left frontopolar cortex and left insula
   • decreased connectivity in the left cuneus and left inferior parietal and the right middle temporal lobes
   • marked frontal hypometabolism
   • hypermetabolism in the motor cor­tex, medial and anterior cingulate, and occipital and temporal poles
   • lower connectivity between the amygdala during a neutral stimulus
   • higher connectivity between the amygdala during fear stimulus
   • higher connectivity between the amygdala during fear stimulus
   • deactivation of the opioid system in the left nucleus accumbens, hypothal­amus, and hippocampus
   • hyperactivation of the left medial prefrontal cortex during social exclusion
   • more mistakes made in differenti­ating an emotional and a neutral facial expression.
 

Diffusion tensor imaging. DTI white-matter integrity studies of BPD show:
   • a bilateral decrease in fractional an­isotropy (FA) in frontal, uncinated, and occipitalfrontal fasciculi
   • a decrease in FA in the genu and rostrum of the corpus callosum
   • a decrease in inter-hemispheric connectivity between right and left ante­rior cigulate cortices.

Genetic Studies
There is substantial scientific evidence that BPD is highly heritable—a finding that suggests that brain abnormalities of this disorder are a consequence of genes involved in brain development (similar to what is known about schizophrenia, bipolar disorder, and autism).

A systematic review of the heritabil­ity of BPD examined 59 published stud­ies that were categorized into 12 family studies, 18 twin studies, 24 association studies, and 5 gene-environment inter­action studies.3 The authors concluded that BPD has a strong genetic compo­nent, although there also is evidence of gene-environment (G.E) interactions (ie, how nature and nurture influence each other).

The G.E interaction model appears to be consistent with the theory that ex­pression of plasticity genes is modified by childhood experiences and environ­ment, such as physical or sexual abuse. Some studies have found evidence of hypermethylation in BPD, which can ex­ert epigenetic effects. Childhood abuse might, therefore, disrupt certain neuro­plasticity genes, culminating in morpho­logical, neurochemical, metabolic, and white-matter aberrations—leading to pathological behavioral patterns identi­fied as BPD.
 

The neuropsychiatric basis of BPD must guide treatment
There is no such thing as a purely psycho­logical disorder: Invariably, it is an abnor­mality of brain circuits that disrupts normal development of emotions, thought, behavior, and social cognition. BPD is an exemplar of such neuropsychiatric illness, and treat­ment should support psychotherapeutic ap­proaches to mend the mind at the same time it moves aggressively to repair the brain.

The prevailing view among many psy­chiatrists and mental health profession­als is that borderline personality disorder (BPD) is a “psychological” condition. BPD often is conceptualized as a behav­ioral consequence of childhood trauma; treatment approaches have emphasized intensive psychotherapeutic modali­ties, less so biologic interventions. You might not be aware that a large body of research over the past decade provides strong evidence that BPD is a neuro­biological illness—a finding that would drastically alter how the disorder should be conceptualized and managed.

Neuropathology underpins the personality disorder
Foremost, BPD must be regarded as a serious, disabling brain disorder, not simply an aberration of personality. In DSM-5, symptoms of BPD are listed as: feelings of abandonment; unstable and intense interpersonal relationships; un­stable sense of self; impulsivity; suicidal or self-mutilating behavior; affective in­stability (dysphoria, irritability, anxiety); chronic feelings of emptiness; intense anger episodes; and transient paranoid or dissociative symptoms. Clearly, these clusters of psychopathological and be­havioral symptoms reflect a pervasive brain disorder associated with abnormal neurobiology and neural circuitry that might, at times, stubbornly defy thera­peutic intervention.

No wonder that 42 published stud­ies report that, compared with healthy controls, people who have BPD display extensive cortical and subcortical abnor­malities in brain structure and function.¹ These anomalous patterns have been detected across all 4 available neuroim­aging techniques.

Magnetic resonance imaging. MRI studies have revealed the following abnormalities in BPD:
   • hypoplasia of the hippocampus, caudate, and dorsolateral prefrontal cortex
   • variations in the CA1 region of the hippocampus and subiculum
   • smaller-than-normal orbitofrontal cortex (by 24%, compared with healthy controls) and the mid-temporal and left cingulate gyrii (by 26%)
   • larger-than-normal volume of the right inferior parietal cortex and the right parahippocampal gyrus
   • loss of gray matter in the frontal, temporal, and parietal cortices
   • an enlarged third cerebral ventricle
   • in women, reduced size of the me­dial temporal lobe and amygdala
   • in men, a decreased concentra­tion of gray matter in the anterior cingulate
   • reversal of normal right-greater-than-left asymmetry of the orbitofron­tal cortex gray matter, reflecting loss of gray matter on the right side
   • a lower concentration of gray mat­ter in the rostral/subgenual anterior cin­gulate cortex
   • a  smaller frontal lobe.

In an analysis of MRI studies,2 cor­relation was found between structural brain abnormalities and specific symp­toms of BPD, such as impulsivity, sui­cidality, and aggression. These findings might someday guide personalized in­terventions—for example, using neuro­stimulation techniques such as repetitive transcranial magnetic stimulation and deep brain stimulation—to modulate the activity of a given region of the brain (depending on which symptom is most prominent or disabling).
 

Magnetic resonance spectroscopy. In BPD, MRS studies reveal:
   • compared with controls, a higher glutamate level in the anterior cingulate cortex
   • reduced levels of N-acetyl aspar­tate (NAA; found in neurons) and cre­atinine in the left amygdala
   • a reduction (on average, 19%) in the NAA concentration in the dorsolat­eral prefrontal cortex.

Functional magnetic resonance im­aging. From fMRI studies, there is evi­dence in BPD of:
   • greater activation of the amygdala and prolonged return to baseline
   • increased functional connectiv­ity in the left frontopolar cortex and left insula
   • decreased connectivity in the left cuneus and left inferior parietal and the right middle temporal lobes
   • marked frontal hypometabolism
   • hypermetabolism in the motor cor­tex, medial and anterior cingulate, and occipital and temporal poles
   • lower connectivity between the amygdala during a neutral stimulus
   • higher connectivity between the amygdala during fear stimulus
   • higher connectivity between the amygdala during fear stimulus
   • deactivation of the opioid system in the left nucleus accumbens, hypothal­amus, and hippocampus
   • hyperactivation of the left medial prefrontal cortex during social exclusion
   • more mistakes made in differenti­ating an emotional and a neutral facial expression.
 

Diffusion tensor imaging. DTI white-matter integrity studies of BPD show:
   • a bilateral decrease in fractional an­isotropy (FA) in frontal, uncinated, and occipitalfrontal fasciculi
   • a decrease in FA in the genu and rostrum of the corpus callosum
   • a decrease in inter-hemispheric connectivity between right and left ante­rior cigulate cortices.

Genetic Studies
There is substantial scientific evidence that BPD is highly heritable—a finding that suggests that brain abnormalities of this disorder are a consequence of genes involved in brain development (similar to what is known about schizophrenia, bipolar disorder, and autism).

A systematic review of the heritabil­ity of BPD examined 59 published stud­ies that were categorized into 12 family studies, 18 twin studies, 24 association studies, and 5 gene-environment inter­action studies.3 The authors concluded that BPD has a strong genetic compo­nent, although there also is evidence of gene-environment (G.E) interactions (ie, how nature and nurture influence each other).

The G.E interaction model appears to be consistent with the theory that ex­pression of plasticity genes is modified by childhood experiences and environ­ment, such as physical or sexual abuse. Some studies have found evidence of hypermethylation in BPD, which can ex­ert epigenetic effects. Childhood abuse might, therefore, disrupt certain neuro­plasticity genes, culminating in morpho­logical, neurochemical, metabolic, and white-matter aberrations—leading to pathological behavioral patterns identi­fied as BPD.
 

The neuropsychiatric basis of BPD must guide treatment
There is no such thing as a purely psycho­logical disorder: Invariably, it is an abnor­mality of brain circuits that disrupts normal development of emotions, thought, behavior, and social cognition. BPD is an exemplar of such neuropsychiatric illness, and treat­ment should support psychotherapeutic ap­proaches to mend the mind at the same time it moves aggressively to repair the brain.

Doctor and patient

Credit: CDC

SAN DIEGO—Watching videos through special glasses can calm patients undergoing a biopsy or other minimally invasive treatment, according to research presented at the Society of Interventional Radiology’s 39th Annual Scientific Meeting.

Researchers have explored strategies other than medication to reduce anxiety in these patients, including having patients listen to music or undergo hypnosis. But these methods have had modest benefits.

“Our study—the first of its kind for interventional radiology treatments—puts a spin on using modern technology to provide a safe, potentially cost-effective strategy of reducing anxiety, which can help and improve patient care,” said David L. Waldman, MD, PhD, of the University of Rochester Medical Center in New York.

“Whether they were watching a children’s movie or a nature show, patients wearing video glasses were successful at tuning out their surroundings. It’s an effective distraction technique that helps focus the individual’s attention away from the treatment.”

The study involved 49 patients (33 men and 16 women, ages 18-87) who were undergoing an outpatient interventional radiology treatment, such as a biopsy or placement of a catheter in the arm or chest to receive medication for treating cancer or infection.

Twenty-five of the patients donned video glasses prior to undergoing the treatment, and 24 did not. The video viewers chose from 20 videos, none of which were violent.

All of the patients filled out a standard 20-question test called the State-Trait Anxiety Inventory Form Y before and after the procedure to assess their level of anxiety.

Patients who wore the video glasses were 18.1% less anxious after the treatment than they were before, while those who didn’t wear video glasses were 7.5% less anxious afterward.

And the presence of the video glasses did not bother either the patient or the doctor, Dr Waldman said.

The glasses had no significant effect on blood pressure, heart rate, respiratory rate, pain, procedure time, or the amount of sedation or pain medication used.

“Patients told us the video glasses really helped calm them down and took their mind off the treatment, and we now offer video glasses to help distract patients from medical treatment going on mere inches away,” Dr Waldman said. “It is really comforting for patients, especially the ones who tend to be more nervous.

Dr Waldman and his colleagues presented these results at the meeting as abstract 126.

Doctor and patient

Credit: CDC

SAN DIEGO—Watching videos through special glasses can calm patients undergoing a biopsy or other minimally invasive treatment, according to research presented at the Society of Interventional Radiology’s 39th Annual Scientific Meeting.

Researchers have explored strategies other than medication to reduce anxiety in these patients, including having patients listen to music or undergo hypnosis. But these methods have had modest benefits.

“Our study—the first of its kind for interventional radiology treatments—puts a spin on using modern technology to provide a safe, potentially cost-effective strategy of reducing anxiety, which can help and improve patient care,” said David L. Waldman, MD, PhD, of the University of Rochester Medical Center in New York.

“Whether they were watching a children’s movie or a nature show, patients wearing video glasses were successful at tuning out their surroundings. It’s an effective distraction technique that helps focus the individual’s attention away from the treatment.”

The study involved 49 patients (33 men and 16 women, ages 18-87) who were undergoing an outpatient interventional radiology treatment, such as a biopsy or placement of a catheter in the arm or chest to receive medication for treating cancer or infection.

Twenty-five of the patients donned video glasses prior to undergoing the treatment, and 24 did not. The video viewers chose from 20 videos, none of which were violent.

All of the patients filled out a standard 20-question test called the State-Trait Anxiety Inventory Form Y before and after the procedure to assess their level of anxiety.

Patients who wore the video glasses were 18.1% less anxious after the treatment than they were before, while those who didn’t wear video glasses were 7.5% less anxious afterward.

And the presence of the video glasses did not bother either the patient or the doctor, Dr Waldman said.

The glasses had no significant effect on blood pressure, heart rate, respiratory rate, pain, procedure time, or the amount of sedation or pain medication used.

“Patients told us the video glasses really helped calm them down and took their mind off the treatment, and we now offer video glasses to help distract patients from medical treatment going on mere inches away,” Dr Waldman said. “It is really comforting for patients, especially the ones who tend to be more nervous.

Dr Waldman and his colleagues presented these results at the meeting as abstract 126.

Doctor and patient

Credit: CDC

SAN DIEGO—Watching videos through special glasses can calm patients undergoing a biopsy or other minimally invasive treatment, according to research presented at the Society of Interventional Radiology’s 39th Annual Scientific Meeting.

Researchers have explored strategies other than medication to reduce anxiety in these patients, including having patients listen to music or undergo hypnosis. But these methods have had modest benefits.

“Our study—the first of its kind for interventional radiology treatments—puts a spin on using modern technology to provide a safe, potentially cost-effective strategy of reducing anxiety, which can help and improve patient care,” said David L. Waldman, MD, PhD, of the University of Rochester Medical Center in New York.

“Whether they were watching a children’s movie or a nature show, patients wearing video glasses were successful at tuning out their surroundings. It’s an effective distraction technique that helps focus the individual’s attention away from the treatment.”

The study involved 49 patients (33 men and 16 women, ages 18-87) who were undergoing an outpatient interventional radiology treatment, such as a biopsy or placement of a catheter in the arm or chest to receive medication for treating cancer or infection.

Twenty-five of the patients donned video glasses prior to undergoing the treatment, and 24 did not. The video viewers chose from 20 videos, none of which were violent.

All of the patients filled out a standard 20-question test called the State-Trait Anxiety Inventory Form Y before and after the procedure to assess their level of anxiety.

Patients who wore the video glasses were 18.1% less anxious after the treatment than they were before, while those who didn’t wear video glasses were 7.5% less anxious afterward.

And the presence of the video glasses did not bother either the patient or the doctor, Dr Waldman said.

The glasses had no significant effect on blood pressure, heart rate, respiratory rate, pain, procedure time, or the amount of sedation or pain medication used.

“Patients told us the video glasses really helped calm them down and took their mind off the treatment, and we now offer video glasses to help distract patients from medical treatment going on mere inches away,” Dr Waldman said. “It is really comforting for patients, especially the ones who tend to be more nervous.

Dr Waldman and his colleagues presented these results at the meeting as abstract 126.

 

 

Micrograph showing FL

 

Single-agent treatment with the HDAC inhibitor vorinostat can be effective in certain patients with indolent non-Hodgkin lymphoma (NHL), according to research published in the British Journal of Haematology.

In the phase 2 study, vorinostat prompted a 49% overall response rate among 39 patients with relapsed or refractory follicular lymphoma (FL).

However, none of the 4 patients with previously treated mantle cell lymphoma (MCL) achieved a response.

Michinori Ogura, MD, PhD, of Nagoya Daini Red Cross Hospital in Japan, and his colleagues set out to analyze the effects of vorinostat in 56 patients with indolent NHL. Six patients were excluded from the final analysis, as their diseases could not be classified.

Thirty-nine patients had FL, 4 had extranodal marginal zone lymphoma (MZL) of MALT type, 4 had MCL, 2 had small B-cell lymphoma not otherwise specified (NOS), and 1 had small lymphocytic lymphoma.

The median age was 60 years (range, 33-75), and the median number of prior therapies was 2 (range, 1-4). These therapies included rituximab (n=40), alkylating agents (n=7), purine analogs (n=5), and radioimmunotherapy (n=3).

The patients received vorinostat for a median of 8 months. The planned dosage was 200 mg twice daily for 14 consecutive days in a 21-day cycle.

At the first data cutoff point (1 year from the last patient’s enrollment), 18 patients remained on treatment. Thirty-eight had discontinued due to disease progression (n=25), drug-related adverse events (n=9), or withdrawn consent (n=4).

The overall response rate was 49% among FL patients. Ten percent (n=4) achieved a complete response, 8% (n=3) achieved an unconfirmed complete response, and 31% (n=12) achieved a partial response.

None of the patients with MCL responded, but 3 of the 7 (43%) patients with other indolent NHLs achieved a response.

That included 2 patients with small B-cell lymphoma NOS and 1 with extranodal MZL of MALT type. One of the patients with small B-cell lymphoma NOS achieved a complete response.

Approximately 81% of all 56 patients remained alive at 2 years after the last patients had enrolled (the second data cutoff point).

At that point, the median overall survival had not been reached. And the median progression-free survival was 26 months among the FL patients who responded.

There were no treatment-related deaths. The most common drug-related events (in all 56 patients) were thrombocytopenia (93%), diarrhea (68%), neutropenia (68%), decreased appetite (63%), nausea (61%), leukopenia (55%), and fatigue (52%).

Eighty percent of patients (n=45) experienced grade 3/4 adverse events, the most common of which were thrombocytopenia (23% grade 3; 25% grade 4) and neutropenia (36% grade 3; 5% grade 4).

However, all of the patients with thrombocytopenia or neutropenia recovered after they received adequate supportive care and their vorinostat dose was reduced or treatment was interrupted or discontinued.

Taking these results together, the researchers concluded that vorinostat offers sustained antitumor activity and has an acceptable safety profile for patients with relapsed or refractory FL. The team noted, however, that because this was a single-arm study with limited data, a comparative study is needed.

 

 

Micrograph showing FL

 

Single-agent treatment with the HDAC inhibitor vorinostat can be effective in certain patients with indolent non-Hodgkin lymphoma (NHL), according to research published in the British Journal of Haematology.

In the phase 2 study, vorinostat prompted a 49% overall response rate among 39 patients with relapsed or refractory follicular lymphoma (FL).

However, none of the 4 patients with previously treated mantle cell lymphoma (MCL) achieved a response.

Michinori Ogura, MD, PhD, of Nagoya Daini Red Cross Hospital in Japan, and his colleagues set out to analyze the effects of vorinostat in 56 patients with indolent NHL. Six patients were excluded from the final analysis, as their diseases could not be classified.

Thirty-nine patients had FL, 4 had extranodal marginal zone lymphoma (MZL) of MALT type, 4 had MCL, 2 had small B-cell lymphoma not otherwise specified (NOS), and 1 had small lymphocytic lymphoma.

The median age was 60 years (range, 33-75), and the median number of prior therapies was 2 (range, 1-4). These therapies included rituximab (n=40), alkylating agents (n=7), purine analogs (n=5), and radioimmunotherapy (n=3).

The patients received vorinostat for a median of 8 months. The planned dosage was 200 mg twice daily for 14 consecutive days in a 21-day cycle.

At the first data cutoff point (1 year from the last patient’s enrollment), 18 patients remained on treatment. Thirty-eight had discontinued due to disease progression (n=25), drug-related adverse events (n=9), or withdrawn consent (n=4).

The overall response rate was 49% among FL patients. Ten percent (n=4) achieved a complete response, 8% (n=3) achieved an unconfirmed complete response, and 31% (n=12) achieved a partial response.

None of the patients with MCL responded, but 3 of the 7 (43%) patients with other indolent NHLs achieved a response.

That included 2 patients with small B-cell lymphoma NOS and 1 with extranodal MZL of MALT type. One of the patients with small B-cell lymphoma NOS achieved a complete response.

Approximately 81% of all 56 patients remained alive at 2 years after the last patients had enrolled (the second data cutoff point).

At that point, the median overall survival had not been reached. And the median progression-free survival was 26 months among the FL patients who responded.

There were no treatment-related deaths. The most common drug-related events (in all 56 patients) were thrombocytopenia (93%), diarrhea (68%), neutropenia (68%), decreased appetite (63%), nausea (61%), leukopenia (55%), and fatigue (52%).

Eighty percent of patients (n=45) experienced grade 3/4 adverse events, the most common of which were thrombocytopenia (23% grade 3; 25% grade 4) and neutropenia (36% grade 3; 5% grade 4).

However, all of the patients with thrombocytopenia or neutropenia recovered after they received adequate supportive care and their vorinostat dose was reduced or treatment was interrupted or discontinued.

Taking these results together, the researchers concluded that vorinostat offers sustained antitumor activity and has an acceptable safety profile for patients with relapsed or refractory FL. The team noted, however, that because this was a single-arm study with limited data, a comparative study is needed.

 

 

Micrograph showing FL

 

Single-agent treatment with the HDAC inhibitor vorinostat can be effective in certain patients with indolent non-Hodgkin lymphoma (NHL), according to research published in the British Journal of Haematology.

In the phase 2 study, vorinostat prompted a 49% overall response rate among 39 patients with relapsed or refractory follicular lymphoma (FL).

However, none of the 4 patients with previously treated mantle cell lymphoma (MCL) achieved a response.

Michinori Ogura, MD, PhD, of Nagoya Daini Red Cross Hospital in Japan, and his colleagues set out to analyze the effects of vorinostat in 56 patients with indolent NHL. Six patients were excluded from the final analysis, as their diseases could not be classified.

Thirty-nine patients had FL, 4 had extranodal marginal zone lymphoma (MZL) of MALT type, 4 had MCL, 2 had small B-cell lymphoma not otherwise specified (NOS), and 1 had small lymphocytic lymphoma.

The median age was 60 years (range, 33-75), and the median number of prior therapies was 2 (range, 1-4). These therapies included rituximab (n=40), alkylating agents (n=7), purine analogs (n=5), and radioimmunotherapy (n=3).

The patients received vorinostat for a median of 8 months. The planned dosage was 200 mg twice daily for 14 consecutive days in a 21-day cycle.

At the first data cutoff point (1 year from the last patient’s enrollment), 18 patients remained on treatment. Thirty-eight had discontinued due to disease progression (n=25), drug-related adverse events (n=9), or withdrawn consent (n=4).

The overall response rate was 49% among FL patients. Ten percent (n=4) achieved a complete response, 8% (n=3) achieved an unconfirmed complete response, and 31% (n=12) achieved a partial response.

None of the patients with MCL responded, but 3 of the 7 (43%) patients with other indolent NHLs achieved a response.

That included 2 patients with small B-cell lymphoma NOS and 1 with extranodal MZL of MALT type. One of the patients with small B-cell lymphoma NOS achieved a complete response.

Approximately 81% of all 56 patients remained alive at 2 years after the last patients had enrolled (the second data cutoff point).

At that point, the median overall survival had not been reached. And the median progression-free survival was 26 months among the FL patients who responded.

There were no treatment-related deaths. The most common drug-related events (in all 56 patients) were thrombocytopenia (93%), diarrhea (68%), neutropenia (68%), decreased appetite (63%), nausea (61%), leukopenia (55%), and fatigue (52%).

Eighty percent of patients (n=45) experienced grade 3/4 adverse events, the most common of which were thrombocytopenia (23% grade 3; 25% grade 4) and neutropenia (36% grade 3; 5% grade 4).

However, all of the patients with thrombocytopenia or neutropenia recovered after they received adequate supportive care and their vorinostat dose was reduced or treatment was interrupted or discontinued.

Taking these results together, the researchers concluded that vorinostat offers sustained antitumor activity and has an acceptable safety profile for patients with relapsed or refractory FL. The team noted, however, that because this was a single-arm study with limited data, a comparative study is needed.

Micrograph showing cutaneous

diffuse large B-cell lymphoma

Credit: Leszek Woźniak

& Krzysztof W. Zieliński

An immunotherapeutic agent can confer clinical benefit in patients with relapsed cutaneous B-cell lymphoma (CBCL), results of a small phase 2 study suggest.

The therapy, TG1042, is human adenovirus type 5 engineered to express interferon-gamma.

Repeat injections of TG1042 elicited responses in 11 of 12 evaluable patients, with complete responses in 7.

All 13 of the patients enrolled on the study experienced an adverse event that may have been related to TG1042, but most were grade 1 or 2 in severity.

“Intralesional TG1042 therapy is well-tolerated and results in lasting tumor regressions,” said study author Reinhard Dummer, MD, of the University of Zurich in Switzerland.

He and his colleagues reported these results in PLOS ONE. The study was sponsored by Transgene SA, makers of TG1042.

The trial consisted of 13 patients with primary CBCL, including primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle center B-cell lymphoma, primary cutaneous diffuse large B-cell lymphoma other than leg type, and T-cell/histiocyte-rich B-cell lymphoma.

Patients were required to have either relapsed or active disease after at least 1 first-line treatment.

The patients received intralesional injections of TG1042 at 5 x 10¹⁰ viral particles per lesion. They could receive injections in up to 6 lesions, which were treated simultaneously on days 1, 8, and 15 of a 4-week cycle.

Patients did not receive treatment during the fourth week. At the end of the cycle, the researchers evaluated tumors for response.

If patients’ disease did not progress, they could receive an additional cycle, up to a maximum of 4. If patients responded to treatment and their lesions disappeared, they were eligible to receive a second series of injections in untreated lesions.

Of the 13 patients treated, 12 were evaluable for response. Eleven of the patients (85%) achieved an objective response—7 complete responses and 4 partial responses. One patient had stable disease.

All reviewed skin biopsies showed that lesions improved after treatment, with a decrease of the lymphoid infiltrate.

The median time to first objective response was 3.2 months (rage, 1-17.5 months). Among complete responders, the median time to response was 4.3 months (range, 1.4-17.5 months).

The median time to progression was 23.5 months (range, 6.5-26.4+ months).

All 13 patients were included in the safety evaluation, and all experienced 1 or more adverse events that were considered possibly or probably related to the treatment.

One patient discontinued treatment due to influenza-like illness, pyrexia, headache, and skin blisters that were possibly related to TG1042.

Another patient had grade 3 increased lipase, but this was thought to be unrelated to TG1042. And it resolved without treatment.

All other adverse events were grade 1 or 2 in nature. They included fatigue, headache, pyrexia, chills, influenza-like illness, injection site irritation, injection site erythema, and injection site pain.

All of these reactions resolved after treatment discontinuation.

Micrograph showing cutaneous

diffuse large B-cell lymphoma

Credit: Leszek Woźniak

& Krzysztof W. Zieliński

An immunotherapeutic agent can confer clinical benefit in patients with relapsed cutaneous B-cell lymphoma (CBCL), results of a small phase 2 study suggest.

The therapy, TG1042, is human adenovirus type 5 engineered to express interferon-gamma.

Repeat injections of TG1042 elicited responses in 11 of 12 evaluable patients, with complete responses in 7.

All 13 of the patients enrolled on the study experienced an adverse event that may have been related to TG1042, but most were grade 1 or 2 in severity.

“Intralesional TG1042 therapy is well-tolerated and results in lasting tumor regressions,” said study author Reinhard Dummer, MD, of the University of Zurich in Switzerland.

He and his colleagues reported these results in PLOS ONE. The study was sponsored by Transgene SA, makers of TG1042.

The trial consisted of 13 patients with primary CBCL, including primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle center B-cell lymphoma, primary cutaneous diffuse large B-cell lymphoma other than leg type, and T-cell/histiocyte-rich B-cell lymphoma.

Patients were required to have either relapsed or active disease after at least 1 first-line treatment.

The patients received intralesional injections of TG1042 at 5 x 10¹⁰ viral particles per lesion. They could receive injections in up to 6 lesions, which were treated simultaneously on days 1, 8, and 15 of a 4-week cycle.

Patients did not receive treatment during the fourth week. At the end of the cycle, the researchers evaluated tumors for response.

If patients’ disease did not progress, they could receive an additional cycle, up to a maximum of 4. If patients responded to treatment and their lesions disappeared, they were eligible to receive a second series of injections in untreated lesions.

Of the 13 patients treated, 12 were evaluable for response. Eleven of the patients (85%) achieved an objective response—7 complete responses and 4 partial responses. One patient had stable disease.

All reviewed skin biopsies showed that lesions improved after treatment, with a decrease of the lymphoid infiltrate.

The median time to first objective response was 3.2 months (rage, 1-17.5 months). Among complete responders, the median time to response was 4.3 months (range, 1.4-17.5 months).

The median time to progression was 23.5 months (range, 6.5-26.4+ months).

All 13 patients were included in the safety evaluation, and all experienced 1 or more adverse events that were considered possibly or probably related to the treatment.

One patient discontinued treatment due to influenza-like illness, pyrexia, headache, and skin blisters that were possibly related to TG1042.

Another patient had grade 3 increased lipase, but this was thought to be unrelated to TG1042. And it resolved without treatment.

All other adverse events were grade 1 or 2 in nature. They included fatigue, headache, pyrexia, chills, influenza-like illness, injection site irritation, injection site erythema, and injection site pain.

All of these reactions resolved after treatment discontinuation.

Micrograph showing cutaneous

diffuse large B-cell lymphoma

Credit: Leszek Woźniak

& Krzysztof W. Zieliński

An immunotherapeutic agent can confer clinical benefit in patients with relapsed cutaneous B-cell lymphoma (CBCL), results of a small phase 2 study suggest.

The therapy, TG1042, is human adenovirus type 5 engineered to express interferon-gamma.

Repeat injections of TG1042 elicited responses in 11 of 12 evaluable patients, with complete responses in 7.

All 13 of the patients enrolled on the study experienced an adverse event that may have been related to TG1042, but most were grade 1 or 2 in severity.

“Intralesional TG1042 therapy is well-tolerated and results in lasting tumor regressions,” said study author Reinhard Dummer, MD, of the University of Zurich in Switzerland.

He and his colleagues reported these results in PLOS ONE. The study was sponsored by Transgene SA, makers of TG1042.

The trial consisted of 13 patients with primary CBCL, including primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle center B-cell lymphoma, primary cutaneous diffuse large B-cell lymphoma other than leg type, and T-cell/histiocyte-rich B-cell lymphoma.

Patients were required to have either relapsed or active disease after at least 1 first-line treatment.

The patients received intralesional injections of TG1042 at 5 x 10¹⁰ viral particles per lesion. They could receive injections in up to 6 lesions, which were treated simultaneously on days 1, 8, and 15 of a 4-week cycle.

Patients did not receive treatment during the fourth week. At the end of the cycle, the researchers evaluated tumors for response.

If patients’ disease did not progress, they could receive an additional cycle, up to a maximum of 4. If patients responded to treatment and their lesions disappeared, they were eligible to receive a second series of injections in untreated lesions.

Of the 13 patients treated, 12 were evaluable for response. Eleven of the patients (85%) achieved an objective response—7 complete responses and 4 partial responses. One patient had stable disease.

All reviewed skin biopsies showed that lesions improved after treatment, with a decrease of the lymphoid infiltrate.

The median time to first objective response was 3.2 months (rage, 1-17.5 months). Among complete responders, the median time to response was 4.3 months (range, 1.4-17.5 months).

The median time to progression was 23.5 months (range, 6.5-26.4+ months).

All 13 patients were included in the safety evaluation, and all experienced 1 or more adverse events that were considered possibly or probably related to the treatment.

One patient discontinued treatment due to influenza-like illness, pyrexia, headache, and skin blisters that were possibly related to TG1042.

Another patient had grade 3 increased lipase, but this was thought to be unrelated to TG1042. And it resolved without treatment.

All other adverse events were grade 1 or 2 in nature. They included fatigue, headache, pyrexia, chills, influenza-like illness, injection site irritation, injection site erythema, and injection site pain.

All of these reactions resolved after treatment discontinuation.

Artificial blood vessels

on a microfluidic chip

Credit: Rob Felt

New research suggests a microfluidic device could help physicians choose the appropriate antiplatelet therapy for patients in need of thromboprophylaxis.

Study investigators ran patient blood samples through the microfluidic device to compare the effects of 3 antiplatelet agents—aspirin, eptifibatide, and heparin—on occlusion times and thrombus detachment.

They found that shear rates had a significant impact on treatment effects.

Although aspirin was effective at low shear rates, it proved largely ineffective at high shear rates, even with increasing doses. And the same was true of heparin.

Eptifibatide was affected by shear rates but still lengthened occlusion times and decreased the risk of thrombus detachment. At higher doses, the drug could prevent occlusion regardless of shear rate.

Melissa Li, PhD, of the University of Washington in Seattle, and her colleagues reported these results in PLOS ONE.

“Doctors have many drug options, and it is difficult for them to determine how well each of those options is going to work for a patient,” Dr Li said. “This study is the first time that a prototype benchtop diagnostic device has tried to address this problem using varying shear rates and patient dosing and tried to make it more personalized.”

The researchers used the microfluidic device to measure occlusion times and thrombus detachment for a range of shear rates (500, 1500, 4000, and 10000 s^-1) and drug concentrations (0-2.4 μM for eptifibatide, 0-2 mM for aspirin, and 3.5-40 units/L for heparin).

The team took blood samples from healthy patients, added the drugs to the samples, and ran them through the device. The device has 4 channels that mimic the coronary arteries, which allowed the investigators to study clotting under a variety of conditions.

Results showed that eptifibatide lengthened occlusion time, but the time decreased as shear rates increased. Increasing doses of the drug reduced the risk of occlusion, however. At doses greater than 1.2 μM, eptifibatide prevented occlusion at all shear rates.

Aspirin was unable to fully prevent occlusive thrombosis at high shear rates (4000 and 10000 s^-1), even at doses of 2 mM, which is 20 times the recommended daily oral dose.

However, the drug did prevent nearly all occlusive thromboses at low shear rates (500 and 1500 s^-1), even at the lowest doses tested. The researchers said they observed identical trends in aspirin and heparin.

When they controlled for shear rate, dosage, and inter-subject variability, the investigators found that occlusion rates were significantly different with the 3 therapies.

Compared to samples treated with eptifibatide, those treated with aspirin had a 4-fold greater risk of occlusion, and those treated with heparin had a 9-fold greater risk. An untreated sample had 14 times the risk of occlusion as an eptifibatide-treated sample.

The researchers also assessed the risk of thrombus detachment and found that eptifibatide lowered the risk, while aspirin raised it. Compared to no therapy, the odds ratios were 0.72 for eptifibatide and 4.48 for aspirin.

Dr Li said this evidence suggests that aspirin can prevent thrombosis in some patients but may not be effective in others, particularly those with atherosclerosis. The team’s device could one day help physicians identify which patients can benefit from aspirin and which cannot, although more testing is needed.

“This finding is something that’s been echoed in the literature by physicians who would find that a number of patients who would take aspirin were not receiving any clinical benefit,” Dr Li said. “What we showed is a good explanation for the conditions under which aspirin resistance occurs and one that matches up with what other people have found.”

On the other hand, as eptifibatide could prevent thrombosis across all shear rates, this research suggests the drug (and other GPIIb/IIIa inhibitors) could be effective for patients whether or not they had atherosclerosis. Dr Li noted that clinical evidence supports this finding.

Artificial blood vessels

on a microfluidic chip

Credit: Rob Felt

New research suggests a microfluidic device could help physicians choose the appropriate antiplatelet therapy for patients in need of thromboprophylaxis.

Study investigators ran patient blood samples through the microfluidic device to compare the effects of 3 antiplatelet agents—aspirin, eptifibatide, and heparin—on occlusion times and thrombus detachment.

They found that shear rates had a significant impact on treatment effects.

Although aspirin was effective at low shear rates, it proved largely ineffective at high shear rates, even with increasing doses. And the same was true of heparin.

Eptifibatide was affected by shear rates but still lengthened occlusion times and decreased the risk of thrombus detachment. At higher doses, the drug could prevent occlusion regardless of shear rate.

Melissa Li, PhD, of the University of Washington in Seattle, and her colleagues reported these results in PLOS ONE.

“Doctors have many drug options, and it is difficult for them to determine how well each of those options is going to work for a patient,” Dr Li said. “This study is the first time that a prototype benchtop diagnostic device has tried to address this problem using varying shear rates and patient dosing and tried to make it more personalized.”

The researchers used the microfluidic device to measure occlusion times and thrombus detachment for a range of shear rates (500, 1500, 4000, and 10000 s^-1) and drug concentrations (0-2.4 μM for eptifibatide, 0-2 mM for aspirin, and 3.5-40 units/L for heparin).

The team took blood samples from healthy patients, added the drugs to the samples, and ran them through the device. The device has 4 channels that mimic the coronary arteries, which allowed the investigators to study clotting under a variety of conditions.

Results showed that eptifibatide lengthened occlusion time, but the time decreased as shear rates increased. Increasing doses of the drug reduced the risk of occlusion, however. At doses greater than 1.2 μM, eptifibatide prevented occlusion at all shear rates.

Aspirin was unable to fully prevent occlusive thrombosis at high shear rates (4000 and 10000 s^-1), even at doses of 2 mM, which is 20 times the recommended daily oral dose.

However, the drug did prevent nearly all occlusive thromboses at low shear rates (500 and 1500 s^-1), even at the lowest doses tested. The researchers said they observed identical trends in aspirin and heparin.

When they controlled for shear rate, dosage, and inter-subject variability, the investigators found that occlusion rates were significantly different with the 3 therapies.

Compared to samples treated with eptifibatide, those treated with aspirin had a 4-fold greater risk of occlusion, and those treated with heparin had a 9-fold greater risk. An untreated sample had 14 times the risk of occlusion as an eptifibatide-treated sample.

The researchers also assessed the risk of thrombus detachment and found that eptifibatide lowered the risk, while aspirin raised it. Compared to no therapy, the odds ratios were 0.72 for eptifibatide and 4.48 for aspirin.

Dr Li said this evidence suggests that aspirin can prevent thrombosis in some patients but may not be effective in others, particularly those with atherosclerosis. The team’s device could one day help physicians identify which patients can benefit from aspirin and which cannot, although more testing is needed.

“This finding is something that’s been echoed in the literature by physicians who would find that a number of patients who would take aspirin were not receiving any clinical benefit,” Dr Li said. “What we showed is a good explanation for the conditions under which aspirin resistance occurs and one that matches up with what other people have found.”

On the other hand, as eptifibatide could prevent thrombosis across all shear rates, this research suggests the drug (and other GPIIb/IIIa inhibitors) could be effective for patients whether or not they had atherosclerosis. Dr Li noted that clinical evidence supports this finding.

Artificial blood vessels

on a microfluidic chip

Credit: Rob Felt

New research suggests a microfluidic device could help physicians choose the appropriate antiplatelet therapy for patients in need of thromboprophylaxis.

Study investigators ran patient blood samples through the microfluidic device to compare the effects of 3 antiplatelet agents—aspirin, eptifibatide, and heparin—on occlusion times and thrombus detachment.

They found that shear rates had a significant impact on treatment effects.

Although aspirin was effective at low shear rates, it proved largely ineffective at high shear rates, even with increasing doses. And the same was true of heparin.

Eptifibatide was affected by shear rates but still lengthened occlusion times and decreased the risk of thrombus detachment. At higher doses, the drug could prevent occlusion regardless of shear rate.

Melissa Li, PhD, of the University of Washington in Seattle, and her colleagues reported these results in PLOS ONE.

“Doctors have many drug options, and it is difficult for them to determine how well each of those options is going to work for a patient,” Dr Li said. “This study is the first time that a prototype benchtop diagnostic device has tried to address this problem using varying shear rates and patient dosing and tried to make it more personalized.”

The researchers used the microfluidic device to measure occlusion times and thrombus detachment for a range of shear rates (500, 1500, 4000, and 10000 s^-1) and drug concentrations (0-2.4 μM for eptifibatide, 0-2 mM for aspirin, and 3.5-40 units/L for heparin).

The team took blood samples from healthy patients, added the drugs to the samples, and ran them through the device. The device has 4 channels that mimic the coronary arteries, which allowed the investigators to study clotting under a variety of conditions.

Results showed that eptifibatide lengthened occlusion time, but the time decreased as shear rates increased. Increasing doses of the drug reduced the risk of occlusion, however. At doses greater than 1.2 μM, eptifibatide prevented occlusion at all shear rates.

Aspirin was unable to fully prevent occlusive thrombosis at high shear rates (4000 and 10000 s^-1), even at doses of 2 mM, which is 20 times the recommended daily oral dose.

However, the drug did prevent nearly all occlusive thromboses at low shear rates (500 and 1500 s^-1), even at the lowest doses tested. The researchers said they observed identical trends in aspirin and heparin.

When they controlled for shear rate, dosage, and inter-subject variability, the investigators found that occlusion rates were significantly different with the 3 therapies.

Compared to samples treated with eptifibatide, those treated with aspirin had a 4-fold greater risk of occlusion, and those treated with heparin had a 9-fold greater risk. An untreated sample had 14 times the risk of occlusion as an eptifibatide-treated sample.

The researchers also assessed the risk of thrombus detachment and found that eptifibatide lowered the risk, while aspirin raised it. Compared to no therapy, the odds ratios were 0.72 for eptifibatide and 4.48 for aspirin.

Dr Li said this evidence suggests that aspirin can prevent thrombosis in some patients but may not be effective in others, particularly those with atherosclerosis. The team’s device could one day help physicians identify which patients can benefit from aspirin and which cannot, although more testing is needed.

“This finding is something that’s been echoed in the literature by physicians who would find that a number of patients who would take aspirin were not receiving any clinical benefit,” Dr Li said. “What we showed is a good explanation for the conditions under which aspirin resistance occurs and one that matches up with what other people have found.”

On the other hand, as eptifibatide could prevent thrombosis across all shear rates, this research suggests the drug (and other GPIIb/IIIa inhibitors) could be effective for patients whether or not they had atherosclerosis. Dr Li noted that clinical evidence supports this finding.

Presenters: Dahlia Rizk, Alfred Burger, Reza Samad, Beth Israel Medical Center, New York City

Summary: Disasters can happen anywhere. The team at Beth Israel Medical Center shared their experience with disaster pre-planning and also with severe storm effects of Hurricane Sandy in lower Manhattan in New York City in 2012.

Disaster pre-planning is a very helpful tool. Beth Israel Medical Center (BIMC) had regular leadership planning meetings and mock disaster situations in advance of Hurricane Sandy. Their overall disaster plan included triage of existing patients to a lower acuity setting or discharge. Planning for staff needs, including places to stay if they cannot safely travel home, is part of the disaster plan.

Hurricane Sandy was a disaster in multiple areas including power loss, closure of other healthcare facilities, trauma, infrastructure impairment, and flooding. Some patients were trapped at home. Many ambulatory centers were closed including dialysis units. Hospitals only had partial power because they were working on emergency generators. Infrastructure was not functioning properly. Cell towers and paging system were not functioning.

BIMC received a surge of patients after the storm because of decreased access to medical care in the storm area. One way they dealt with the surge was opening new patient units on two revamped substance abuse units.

There were many lessons learned. A command center for internal communication is required. Communication with outside entities is also important.

Surge planning is also a key consideration. Making bed space, alternative use of staff, patient supplies, staff supplies, staff quarters are all aspects of planning. Disposition enhancement is important for patient care. Social workers and nursing home collaboration are needed. Human resources is needed for short and long term surge staffing. Relationships with other institutions and staffing companies can assist with staffing needs.

Key Takeaways:

• Disasters happen and are often unpredictable.
• Preparation is essential.
• Leadership among staff is crucial.
• Teamwork is a must and will get the organization through a disaster.

Dr. Hale is a pediatric hospitalist at the Floating Hospital for Children at Tufts Medical Center in Boston, and a member of Team Hospitalist.

Presenters: Dahlia Rizk, Alfred Burger, Reza Samad, Beth Israel Medical Center, New York City

Summary: Disasters can happen anywhere. The team at Beth Israel Medical Center shared their experience with disaster pre-planning and also with severe storm effects of Hurricane Sandy in lower Manhattan in New York City in 2012.

Disaster pre-planning is a very helpful tool. Beth Israel Medical Center (BIMC) had regular leadership planning meetings and mock disaster situations in advance of Hurricane Sandy. Their overall disaster plan included triage of existing patients to a lower acuity setting or discharge. Planning for staff needs, including places to stay if they cannot safely travel home, is part of the disaster plan.

Hurricane Sandy was a disaster in multiple areas including power loss, closure of other healthcare facilities, trauma, infrastructure impairment, and flooding. Some patients were trapped at home. Many ambulatory centers were closed including dialysis units. Hospitals only had partial power because they were working on emergency generators. Infrastructure was not functioning properly. Cell towers and paging system were not functioning.

BIMC received a surge of patients after the storm because of decreased access to medical care in the storm area. One way they dealt with the surge was opening new patient units on two revamped substance abuse units.

There were many lessons learned. A command center for internal communication is required. Communication with outside entities is also important.

Surge planning is also a key consideration. Making bed space, alternative use of staff, patient supplies, staff supplies, staff quarters are all aspects of planning. Disposition enhancement is important for patient care. Social workers and nursing home collaboration are needed. Human resources is needed for short and long term surge staffing. Relationships with other institutions and staffing companies can assist with staffing needs.

Key Takeaways:

• Disasters happen and are often unpredictable.
• Preparation is essential.
• Leadership among staff is crucial.
• Teamwork is a must and will get the organization through a disaster.

Dr. Hale is a pediatric hospitalist at the Floating Hospital for Children at Tufts Medical Center in Boston, and a member of Team Hospitalist.

Presenters: Dahlia Rizk, Alfred Burger, Reza Samad, Beth Israel Medical Center, New York City

Summary: Disasters can happen anywhere. The team at Beth Israel Medical Center shared their experience with disaster pre-planning and also with severe storm effects of Hurricane Sandy in lower Manhattan in New York City in 2012.

Disaster pre-planning is a very helpful tool. Beth Israel Medical Center (BIMC) had regular leadership planning meetings and mock disaster situations in advance of Hurricane Sandy. Their overall disaster plan included triage of existing patients to a lower acuity setting or discharge. Planning for staff needs, including places to stay if they cannot safely travel home, is part of the disaster plan.

Hurricane Sandy was a disaster in multiple areas including power loss, closure of other healthcare facilities, trauma, infrastructure impairment, and flooding. Some patients were trapped at home. Many ambulatory centers were closed including dialysis units. Hospitals only had partial power because they were working on emergency generators. Infrastructure was not functioning properly. Cell towers and paging system were not functioning.

BIMC received a surge of patients after the storm because of decreased access to medical care in the storm area. One way they dealt with the surge was opening new patient units on two revamped substance abuse units.

There were many lessons learned. A command center for internal communication is required. Communication with outside entities is also important.

Surge planning is also a key consideration. Making bed space, alternative use of staff, patient supplies, staff supplies, staff quarters are all aspects of planning. Disposition enhancement is important for patient care. Social workers and nursing home collaboration are needed. Human resources is needed for short and long term surge staffing. Relationships with other institutions and staffing companies can assist with staffing needs.

Key Takeaways:

• Disasters happen and are often unpredictable.
• Preparation is essential.
• Leadership among staff is crucial.
• Teamwork is a must and will get the organization through a disaster.

Dr. Hale is a pediatric hospitalist at the Floating Hospital for Children at Tufts Medical Center in Boston, and a member of Team Hospitalist.

Presenter: Shawn Ralston, MD, Children’s Hospital at Dartmouth and Giesel School of Medicine, Hanover, NH

As the evidence comes in, the use of HFNC in patients with bronchiolitis is likely to be an innovation in pediatric hospital medicine,” said Dr. Ralston, with a potentially large impact on the healthcare of hospitalized children in the U.S.

Key Takeaways

Dr. Ralson provided a succinct overview of the literature surrounding the use of HFNC in patients with bronchiolitis:

• Over the past 10 years, the incidence rates of bronchiolitis hospitalizations have declined in all age groups, but during the same time period in-hospital use of mechanical ventilation, and therefore hospital charges per case, have increased.
• Surprisingly, the definition of high-flow nasal cannula (HFNC) is not uniform among institutions. Most would agree that it is a heated circuit of humidified oxygen at flow rates that exceed a patient’s respiratory demand.
• The goal of the nasal cannula in HFNC is to occupy at least 50% of the nares. If correctly sized, this will provide end-expiratory pressures that reduce the subjective work of breathing in infants.
• Can we predict the non-responders to HFNC? Failure to decrease respiratory rate (RR) at onset of therapy was associated with intubation, or failure of successful use of HFNC.
• One needs to be aware of potential biases when evaluating the literature on the use of HFNC in bronchiolitis. Seasonal disease variation, secular trends in ICU and/or ED training, and QI culture in hospital such as guidelines and protocols may all potentially impact study results.

James O’Callaghan is a Clinical Assistant Professor of Pediatrics at the University of Washington and a member of Team Hospitalist.

Presenter: Shawn Ralston, MD, Children’s Hospital at Dartmouth and Giesel School of Medicine, Hanover, NH

As the evidence comes in, the use of HFNC in patients with bronchiolitis is likely to be an innovation in pediatric hospital medicine,” said Dr. Ralston, with a potentially large impact on the healthcare of hospitalized children in the U.S.

Key Takeaways

Dr. Ralson provided a succinct overview of the literature surrounding the use of HFNC in patients with bronchiolitis:

• Over the past 10 years, the incidence rates of bronchiolitis hospitalizations have declined in all age groups, but during the same time period in-hospital use of mechanical ventilation, and therefore hospital charges per case, have increased.
• Surprisingly, the definition of high-flow nasal cannula (HFNC) is not uniform among institutions. Most would agree that it is a heated circuit of humidified oxygen at flow rates that exceed a patient’s respiratory demand.
• The goal of the nasal cannula in HFNC is to occupy at least 50% of the nares. If correctly sized, this will provide end-expiratory pressures that reduce the subjective work of breathing in infants.
• Can we predict the non-responders to HFNC? Failure to decrease respiratory rate (RR) at onset of therapy was associated with intubation, or failure of successful use of HFNC.
• One needs to be aware of potential biases when evaluating the literature on the use of HFNC in bronchiolitis. Seasonal disease variation, secular trends in ICU and/or ED training, and QI culture in hospital such as guidelines and protocols may all potentially impact study results.

James O’Callaghan is a Clinical Assistant Professor of Pediatrics at the University of Washington and a member of Team Hospitalist.

Presenter: Shawn Ralston, MD, Children’s Hospital at Dartmouth and Giesel School of Medicine, Hanover, NH

As the evidence comes in, the use of HFNC in patients with bronchiolitis is likely to be an innovation in pediatric hospital medicine,” said Dr. Ralston, with a potentially large impact on the healthcare of hospitalized children in the U.S.

Key Takeaways

Dr. Ralson provided a succinct overview of the literature surrounding the use of HFNC in patients with bronchiolitis:

• Over the past 10 years, the incidence rates of bronchiolitis hospitalizations have declined in all age groups, but during the same time period in-hospital use of mechanical ventilation, and therefore hospital charges per case, have increased.
• Surprisingly, the definition of high-flow nasal cannula (HFNC) is not uniform among institutions. Most would agree that it is a heated circuit of humidified oxygen at flow rates that exceed a patient’s respiratory demand.
• The goal of the nasal cannula in HFNC is to occupy at least 50% of the nares. If correctly sized, this will provide end-expiratory pressures that reduce the subjective work of breathing in infants.
• Can we predict the non-responders to HFNC? Failure to decrease respiratory rate (RR) at onset of therapy was associated with intubation, or failure of successful use of HFNC.
• One needs to be aware of potential biases when evaluating the literature on the use of HFNC in bronchiolitis. Seasonal disease variation, secular trends in ICU and/or ED training, and QI culture in hospital such as guidelines and protocols may all potentially impact study results.

James O’Callaghan is a Clinical Assistant Professor of Pediatrics at the University of Washington and a member of Team Hospitalist.

LAS VEGAS—Hospitalist Michael Hoftiezer, MD, has been to pre-courses at annual meetings before HM14, but yesterday’s lineup offered a new option: “Cardiology: What Hospitalists Need to Know as Front-Line Providers.”

The eight-hour seminar was one of three new pre-courses at SHM’s annual meeting, along with “Efficient High-Value Evidence-Based Medicine for the Practicing Hospitalist” and “NP/PA Playbook for Hospital Medicine.” The offerings drew hundreds of hospitalists to the unofficial first day of HM14 at Mandalay Bay Resort and Casino.

“It’s nice to have an extra day of learning,” says Dr. Hoftiezer, who practices at Holy Family Memorial Medical Center in Manitowoc, Wis. And “it’s concentrated on one subject. It’s a good overview of a single subject, rather than bouncing around different things.” Course director Matthews Chacko, MD, of Johns Hopkins Hospital in Baltimore, says the time is right for hospitalists to devote a full-day pre-course focused on cardiology. “Cardiovascular disease is the most common reason we die,” he says.

“It’s something hospital-based practitioners see often. Providing a comprehensive but yet simplified overview of the way to manage some of these diseases with talks given by some of the leading experts in the field seemed very appropriate for this meeting.”

The course covered such topics as arrhythmia, heart failure, peripheral artery disease, and unstable myocardial infarction. Dr. Hoftiezer says he gleaned tips he can take back to his hospital—including the mechanisms of atrial fibrillation and when to measure rhythm versus rate—and that’s what made the pre-course valuable.

“The more relevant, the better,” he adds. “My favorite lectures are the ones that change something I do.”

LAS VEGAS—Hospitalist Michael Hoftiezer, MD, has been to pre-courses at annual meetings before HM14, but yesterday’s lineup offered a new option: “Cardiology: What Hospitalists Need to Know as Front-Line Providers.”

The eight-hour seminar was one of three new pre-courses at SHM’s annual meeting, along with “Efficient High-Value Evidence-Based Medicine for the Practicing Hospitalist” and “NP/PA Playbook for Hospital Medicine.” The offerings drew hundreds of hospitalists to the unofficial first day of HM14 at Mandalay Bay Resort and Casino.

“It’s nice to have an extra day of learning,” says Dr. Hoftiezer, who practices at Holy Family Memorial Medical Center in Manitowoc, Wis. And “it’s concentrated on one subject. It’s a good overview of a single subject, rather than bouncing around different things.” Course director Matthews Chacko, MD, of Johns Hopkins Hospital in Baltimore, says the time is right for hospitalists to devote a full-day pre-course focused on cardiology. “Cardiovascular disease is the most common reason we die,” he says.

“It’s something hospital-based practitioners see often. Providing a comprehensive but yet simplified overview of the way to manage some of these diseases with talks given by some of the leading experts in the field seemed very appropriate for this meeting.”

The course covered such topics as arrhythmia, heart failure, peripheral artery disease, and unstable myocardial infarction. Dr. Hoftiezer says he gleaned tips he can take back to his hospital—including the mechanisms of atrial fibrillation and when to measure rhythm versus rate—and that’s what made the pre-course valuable.

“The more relevant, the better,” he adds. “My favorite lectures are the ones that change something I do.”

LAS VEGAS—Hospitalist Michael Hoftiezer, MD, has been to pre-courses at annual meetings before HM14, but yesterday’s lineup offered a new option: “Cardiology: What Hospitalists Need to Know as Front-Line Providers.”

The eight-hour seminar was one of three new pre-courses at SHM’s annual meeting, along with “Efficient High-Value Evidence-Based Medicine for the Practicing Hospitalist” and “NP/PA Playbook for Hospital Medicine.” The offerings drew hundreds of hospitalists to the unofficial first day of HM14 at Mandalay Bay Resort and Casino.

“It’s nice to have an extra day of learning,” says Dr. Hoftiezer, who practices at Holy Family Memorial Medical Center in Manitowoc, Wis. And “it’s concentrated on one subject. It’s a good overview of a single subject, rather than bouncing around different things.” Course director Matthews Chacko, MD, of Johns Hopkins Hospital in Baltimore, says the time is right for hospitalists to devote a full-day pre-course focused on cardiology. “Cardiovascular disease is the most common reason we die,” he says.

“It’s something hospital-based practitioners see often. Providing a comprehensive but yet simplified overview of the way to manage some of these diseases with talks given by some of the leading experts in the field seemed very appropriate for this meeting.”

The course covered such topics as arrhythmia, heart failure, peripheral artery disease, and unstable myocardial infarction. Dr. Hoftiezer says he gleaned tips he can take back to his hospital—including the mechanisms of atrial fibrillation and when to measure rhythm versus rate—and that’s what made the pre-course valuable.

“The more relevant, the better,” he adds. “My favorite lectures are the ones that change something I do.”