As a pediatrician, you are on the front line of acne treatment for neonates, children, and adolescents. Acne is a very common condition that will affect 80% of your patients at some point in their lives. It can be easy to diagnose, but acne is often difficult to evaluate and manage. Presentations vary from mild to severe, and you’re likely to see a wide range of acne severity as you treat babies, children, and adolescents through office consultations and regular wellness checks.

Minimal intervention is reasonable for children with mild, comedonal acne. Most are unaware and unconcerned about their acne. It is important to stress they should avoid aggressive facial scrubbing and "popping zits." A discussion of acne physiology that dispels common myths – for example, that junk foods and poor hygiene cause acne in children and adolescents – also is useful.

Early intervention is essential to successful management. Prompt initiation of acne therapy can prevent sequelae that, if left untreated, can include significant scarring and emotional distress for your patients.

Refer your patient to a dermatologic surgeon early if the child’s acne is recalcitrant to treatment or shows early signs of scarring. Dermatologic surgeons understand the science behind healthy skin and can help your patients with the special needs of skin through every stage of life.

The differential diagnosis for acneiform eruptions varies by age. Neonatal acne (or neonatal cephalic pustulosis, as it is sometimes called) can affect about one in five babies. It is usually self-limited and requires no treatment, although topical ketoconazole can be prescribed if the parents are concerned or the presentation is extensive.

Infantile acne is less common. This occurs between the ages of 6 months and 1 year. Typical lesions include comedones or more inflammatory lesions. Benzoyl peroxide products and/or topical retinoids can be used to treat infantile acne if it is comedonal.

Acne that appears at age 1-7 years is very rare. Toddlers and children with this early childhood acne also should be evaluated further and/or referred to a specialist. A careful history and physical examination are warranted. Measure height and weight, and plot them on the growth chart. Also look for signs of virilization or precocious sexual development.

An abnormal blood pressure can point to congenital adrenal hyperplasia in the neonatal period. Rule out hyperandrogenism, particularly with severe or persistent infantile acne or sudden onset childhood acne. Refer patients to an endocrinologist if you are uncertain, or if any of the following screening tests are abnormal: bone age, serum DHEA (dehydroepiandrosterone), and free testosterone levels. (Total testosterone can be checked if the free testosterone test is unavailable.) Also consider serologic measures of follicle stimulating hormone, luteinizing hormone, prolactin, and 17 alpha-hydroxyprogesterone.

Performance of an exhaustive search for hyperandrogenism in your office is unnecessary in the majority of neonates, infants, children, and adolescents. It is important to know when these screening tests should be ordered and when to refer to a specialist for further evaluation and/or management.

Prepubertal or adolescent acne can occur earlier than parents might expect (at around 8 years of age), and can be the first sign of pubertal maturation. Distinguish comedonal from inflammatory acne to determine appropriate therapy.

Treatment with topical retinoids is the best for comedonal acne. Take the time to educate parents and the child on proper application of a topical retinoid. Instruct them to apply a pea-sized amount to dry skin every other night (or even every third night) for the first 2-4 weeks. This initial small dose can be titrated up gradually over time to minimize adverse effects. Improper use can lead to significant irritation and dryness, and contribute to the lack of treatment compliance.

As with any disease process, patient education is extremely important and can have a great impact on outcomes. Extensively counsel patients and parents on therapy options, and stress the importance of compliance with your recommended treatment regimen.

If the child has inflammatory acne lesions, a combination of benzoyl peroxide and topical antibiotic therapy (erythromycin or clindamycin) is more effective than either agent alone. With more severe acne, oral antibiotics may be warranted. Keep in mind that the tetracycline family of antibiotics can interfere with bone and teeth development, and is contraindicated in children younger than 8 years. Treatment with erythromycin or with Mutual Pharmaceutical’s Bactrim (a combination of sulfamethoxazole and trimethoprim) is appropriate for this age group. For older children with fully developed teeth, oral tetracycline, minocycline, and doxycycline are often the antibiotics of choice.

Infants, children, or adolescents with severe, recalcitrant, or scarring acne should be referred to a specialist for more aggressive intervention. For adolescents with nodulocystic acne (severe acne characterized by inflammation, nodular breakouts, and cysts), early intervention with systemic therapies, including isotretinoin, is important to prevent scarring. Also refer patients to dermatologic surgeons for further evaluation and management if their acne causes them psychological distress, whether or not their clinical presentation is severe.

Dr. Sikora is a private practice dermatologist in Chestnut Hill, Mass., and a member of many professional organizations, including the American Society for Dermatologic Surgery (www.ASDS.net) and the American Academy of Dermatology. Dr. Sikora said she had no relevant financial disclosures.

As a pediatrician, you are on the front line of acne treatment for neonates, children, and adolescents. Acne is a very common condition that will affect 80% of your patients at some point in their lives. It can be easy to diagnose, but acne is often difficult to evaluate and manage. Presentations vary from mild to severe, and you’re likely to see a wide range of acne severity as you treat babies, children, and adolescents through office consultations and regular wellness checks.

Minimal intervention is reasonable for children with mild, comedonal acne. Most are unaware and unconcerned about their acne. It is important to stress they should avoid aggressive facial scrubbing and "popping zits." A discussion of acne physiology that dispels common myths – for example, that junk foods and poor hygiene cause acne in children and adolescents – also is useful.

Early intervention is essential to successful management. Prompt initiation of acne therapy can prevent sequelae that, if left untreated, can include significant scarring and emotional distress for your patients.

Refer your patient to a dermatologic surgeon early if the child’s acne is recalcitrant to treatment or shows early signs of scarring. Dermatologic surgeons understand the science behind healthy skin and can help your patients with the special needs of skin through every stage of life.

The differential diagnosis for acneiform eruptions varies by age. Neonatal acne (or neonatal cephalic pustulosis, as it is sometimes called) can affect about one in five babies. It is usually self-limited and requires no treatment, although topical ketoconazole can be prescribed if the parents are concerned or the presentation is extensive.

Infantile acne is less common. This occurs between the ages of 6 months and 1 year. Typical lesions include comedones or more inflammatory lesions. Benzoyl peroxide products and/or topical retinoids can be used to treat infantile acne if it is comedonal.

Acne that appears at age 1-7 years is very rare. Toddlers and children with this early childhood acne also should be evaluated further and/or referred to a specialist. A careful history and physical examination are warranted. Measure height and weight, and plot them on the growth chart. Also look for signs of virilization or precocious sexual development.

An abnormal blood pressure can point to congenital adrenal hyperplasia in the neonatal period. Rule out hyperandrogenism, particularly with severe or persistent infantile acne or sudden onset childhood acne. Refer patients to an endocrinologist if you are uncertain, or if any of the following screening tests are abnormal: bone age, serum DHEA (dehydroepiandrosterone), and free testosterone levels. (Total testosterone can be checked if the free testosterone test is unavailable.) Also consider serologic measures of follicle stimulating hormone, luteinizing hormone, prolactin, and 17 alpha-hydroxyprogesterone.

Performance of an exhaustive search for hyperandrogenism in your office is unnecessary in the majority of neonates, infants, children, and adolescents. It is important to know when these screening tests should be ordered and when to refer to a specialist for further evaluation and/or management.

Prepubertal or adolescent acne can occur earlier than parents might expect (at around 8 years of age), and can be the first sign of pubertal maturation. Distinguish comedonal from inflammatory acne to determine appropriate therapy.

Treatment with topical retinoids is the best for comedonal acne. Take the time to educate parents and the child on proper application of a topical retinoid. Instruct them to apply a pea-sized amount to dry skin every other night (or even every third night) for the first 2-4 weeks. This initial small dose can be titrated up gradually over time to minimize adverse effects. Improper use can lead to significant irritation and dryness, and contribute to the lack of treatment compliance.

As with any disease process, patient education is extremely important and can have a great impact on outcomes. Extensively counsel patients and parents on therapy options, and stress the importance of compliance with your recommended treatment regimen.

If the child has inflammatory acne lesions, a combination of benzoyl peroxide and topical antibiotic therapy (erythromycin or clindamycin) is more effective than either agent alone. With more severe acne, oral antibiotics may be warranted. Keep in mind that the tetracycline family of antibiotics can interfere with bone and teeth development, and is contraindicated in children younger than 8 years. Treatment with erythromycin or with Mutual Pharmaceutical’s Bactrim (a combination of sulfamethoxazole and trimethoprim) is appropriate for this age group. For older children with fully developed teeth, oral tetracycline, minocycline, and doxycycline are often the antibiotics of choice.

Infants, children, or adolescents with severe, recalcitrant, or scarring acne should be referred to a specialist for more aggressive intervention. For adolescents with nodulocystic acne (severe acne characterized by inflammation, nodular breakouts, and cysts), early intervention with systemic therapies, including isotretinoin, is important to prevent scarring. Also refer patients to dermatologic surgeons for further evaluation and management if their acne causes them psychological distress, whether or not their clinical presentation is severe.

Dr. Sikora is a private practice dermatologist in Chestnut Hill, Mass., and a member of many professional organizations, including the American Society for Dermatologic Surgery (www.ASDS.net) and the American Academy of Dermatology. Dr. Sikora said she had no relevant financial disclosures.

As a pediatrician, you are on the front line of acne treatment for neonates, children, and adolescents. Acne is a very common condition that will affect 80% of your patients at some point in their lives. It can be easy to diagnose, but acne is often difficult to evaluate and manage. Presentations vary from mild to severe, and you’re likely to see a wide range of acne severity as you treat babies, children, and adolescents through office consultations and regular wellness checks.

Minimal intervention is reasonable for children with mild, comedonal acne. Most are unaware and unconcerned about their acne. It is important to stress they should avoid aggressive facial scrubbing and "popping zits." A discussion of acne physiology that dispels common myths – for example, that junk foods and poor hygiene cause acne in children and adolescents – also is useful.

Early intervention is essential to successful management. Prompt initiation of acne therapy can prevent sequelae that, if left untreated, can include significant scarring and emotional distress for your patients.

Refer your patient to a dermatologic surgeon early if the child’s acne is recalcitrant to treatment or shows early signs of scarring. Dermatologic surgeons understand the science behind healthy skin and can help your patients with the special needs of skin through every stage of life.

The differential diagnosis for acneiform eruptions varies by age. Neonatal acne (or neonatal cephalic pustulosis, as it is sometimes called) can affect about one in five babies. It is usually self-limited and requires no treatment, although topical ketoconazole can be prescribed if the parents are concerned or the presentation is extensive.

Infantile acne is less common. This occurs between the ages of 6 months and 1 year. Typical lesions include comedones or more inflammatory lesions. Benzoyl peroxide products and/or topical retinoids can be used to treat infantile acne if it is comedonal.

Acne that appears at age 1-7 years is very rare. Toddlers and children with this early childhood acne also should be evaluated further and/or referred to a specialist. A careful history and physical examination are warranted. Measure height and weight, and plot them on the growth chart. Also look for signs of virilization or precocious sexual development.

An abnormal blood pressure can point to congenital adrenal hyperplasia in the neonatal period. Rule out hyperandrogenism, particularly with severe or persistent infantile acne or sudden onset childhood acne. Refer patients to an endocrinologist if you are uncertain, or if any of the following screening tests are abnormal: bone age, serum DHEA (dehydroepiandrosterone), and free testosterone levels. (Total testosterone can be checked if the free testosterone test is unavailable.) Also consider serologic measures of follicle stimulating hormone, luteinizing hormone, prolactin, and 17 alpha-hydroxyprogesterone.

Performance of an exhaustive search for hyperandrogenism in your office is unnecessary in the majority of neonates, infants, children, and adolescents. It is important to know when these screening tests should be ordered and when to refer to a specialist for further evaluation and/or management.

Prepubertal or adolescent acne can occur earlier than parents might expect (at around 8 years of age), and can be the first sign of pubertal maturation. Distinguish comedonal from inflammatory acne to determine appropriate therapy.

Treatment with topical retinoids is the best for comedonal acne. Take the time to educate parents and the child on proper application of a topical retinoid. Instruct them to apply a pea-sized amount to dry skin every other night (or even every third night) for the first 2-4 weeks. This initial small dose can be titrated up gradually over time to minimize adverse effects. Improper use can lead to significant irritation and dryness, and contribute to the lack of treatment compliance.

As with any disease process, patient education is extremely important and can have a great impact on outcomes. Extensively counsel patients and parents on therapy options, and stress the importance of compliance with your recommended treatment regimen.

If the child has inflammatory acne lesions, a combination of benzoyl peroxide and topical antibiotic therapy (erythromycin or clindamycin) is more effective than either agent alone. With more severe acne, oral antibiotics may be warranted. Keep in mind that the tetracycline family of antibiotics can interfere with bone and teeth development, and is contraindicated in children younger than 8 years. Treatment with erythromycin or with Mutual Pharmaceutical’s Bactrim (a combination of sulfamethoxazole and trimethoprim) is appropriate for this age group. For older children with fully developed teeth, oral tetracycline, minocycline, and doxycycline are often the antibiotics of choice.

Infants, children, or adolescents with severe, recalcitrant, or scarring acne should be referred to a specialist for more aggressive intervention. For adolescents with nodulocystic acne (severe acne characterized by inflammation, nodular breakouts, and cysts), early intervention with systemic therapies, including isotretinoin, is important to prevent scarring. Also refer patients to dermatologic surgeons for further evaluation and management if their acne causes them psychological distress, whether or not their clinical presentation is severe.

Dr. Sikora is a private practice dermatologist in Chestnut Hill, Mass., and a member of many professional organizations, including the American Society for Dermatologic Surgery (www.ASDS.net) and the American Academy of Dermatology. Dr. Sikora said she had no relevant financial disclosures.

Hospitalists unfamiliar with palliative care might think that older patients are the ones generating higher costs per day and longer length of stay (LOS). But new research from a fellow hospitalist suggests that's not the case.

A report in this month's Journal of Hospital Medicine found that patients 65 years and older had a significantly lower cost per day ($811; P=0.02) and LOS (-1.8 days; P=0.003) for each decade increase in age (J Hosp Med. 2011;6(6):338-343). The data also show patients on surgical specialty services generate higher costs and higher LOS, a likely nod to the complexity of cases that land on those services, says University of Colorado Denver hospitalist Jean Youngwerth, MD.

"We were anticipating more from the start that patients who were older were going to have higher costs per day and LOS," says Dr. Youngwerth, who also serves as associate program director for the Colorado Palliative Medicine Fellowship and Director of the University of Colorado Hospital Palliative Care Consult Service. "A lot of times, it is younger patients who are the sickest of the sick.

"People will go full force on them and they won't necessarily have a lot of the conversations they'd be having with older patients. The assumption is 'They're young, they shouldn't be dying' … even though they're a very sick person."

Dr. Youngwerth says hospitalists working without the aid of institutional support can still make palliative-care discussions a priority.

"You don't need a specialist for that," she adds, "[for] sitting down and setting goals of care, learning about the person, and then making sure that we're matching what their goals and values are to their plan of care."

Hospitalists unfamiliar with palliative care might think that older patients are the ones generating higher costs per day and longer length of stay (LOS). But new research from a fellow hospitalist suggests that's not the case.

A report in this month's Journal of Hospital Medicine found that patients 65 years and older had a significantly lower cost per day ($811; P=0.02) and LOS (-1.8 days; P=0.003) for each decade increase in age (J Hosp Med. 2011;6(6):338-343). The data also show patients on surgical specialty services generate higher costs and higher LOS, a likely nod to the complexity of cases that land on those services, says University of Colorado Denver hospitalist Jean Youngwerth, MD.

"We were anticipating more from the start that patients who were older were going to have higher costs per day and LOS," says Dr. Youngwerth, who also serves as associate program director for the Colorado Palliative Medicine Fellowship and Director of the University of Colorado Hospital Palliative Care Consult Service. "A lot of times, it is younger patients who are the sickest of the sick.

"People will go full force on them and they won't necessarily have a lot of the conversations they'd be having with older patients. The assumption is 'They're young, they shouldn't be dying' … even though they're a very sick person."

Dr. Youngwerth says hospitalists working without the aid of institutional support can still make palliative-care discussions a priority.

"You don't need a specialist for that," she adds, "[for] sitting down and setting goals of care, learning about the person, and then making sure that we're matching what their goals and values are to their plan of care."

Hospitalists unfamiliar with palliative care might think that older patients are the ones generating higher costs per day and longer length of stay (LOS). But new research from a fellow hospitalist suggests that's not the case.

A report in this month's Journal of Hospital Medicine found that patients 65 years and older had a significantly lower cost per day ($811; P=0.02) and LOS (-1.8 days; P=0.003) for each decade increase in age (J Hosp Med. 2011;6(6):338-343). The data also show patients on surgical specialty services generate higher costs and higher LOS, a likely nod to the complexity of cases that land on those services, says University of Colorado Denver hospitalist Jean Youngwerth, MD.

"We were anticipating more from the start that patients who were older were going to have higher costs per day and LOS," says Dr. Youngwerth, who also serves as associate program director for the Colorado Palliative Medicine Fellowship and Director of the University of Colorado Hospital Palliative Care Consult Service. "A lot of times, it is younger patients who are the sickest of the sick.

"People will go full force on them and they won't necessarily have a lot of the conversations they'd be having with older patients. The assumption is 'They're young, they shouldn't be dying' … even though they're a very sick person."

Dr. Youngwerth says hospitalists working without the aid of institutional support can still make palliative-care discussions a priority.

"You don't need a specialist for that," she adds, "[for] sitting down and setting goals of care, learning about the person, and then making sure that we're matching what their goals and values are to their plan of care."

Clinical question: Is decreased nursing staffing and increased patient turnover across various inpatient adult hospital units associated with higher patient mortality?

Background: Studies that have shown an association between lower nurse staffing and higher inpatient mortality have been limited by methodological issues. These limitations include the use of hospital-level administrative data that do not fully capture actual staffing levels and the lack of control for expected nursing requirements for patients.

Study design: Retrospective observational study.

Setting: Forty-three hospital units on both medical and surgical services at a single institution.

Synopsis: The authors examined whether patients who were cared for during shifts that had nursing staffing that was eight hours or more below the staffing target had a higher-than-expected mortality compared with predicted mortality, based on risk-adjusted DRG-related mortality. They also assessed if increased patient turnover during a patient-care shift was associated with a higher-than-expected mortality.

The authors analyzed mortality outcomes of 197,961 patients who were cared for across 176,696 staffed unit-shifts. The risk of death increased with the number of shifts a patient was cared for when the nursing staffing was eight hours below target, with a hazard ratio per below-target shift of 1.02 (95% CI: 1.01 to 1.03). There was also an association between a higher mortality and a greater number of high-turnover shifts, with a hazard ratio of 1.04 (95% CI 1.02 to 1.03).

Bottom line: Patients cared for during shifts with below-target levels of nurse staffing and during shifts with increased patient turnover had an increased mortality.

Citation: Needleman J, Buerhaus P, Pankratz S, Leibson CL, Stevens SR, Harris M. Nurse staffing and inpatient hospital mortality. N Engl J Med. 2011;364(11):1037-1045.

For more physician reviews of HM-related literature, visit our website.

Clinical question: Is decreased nursing staffing and increased patient turnover across various inpatient adult hospital units associated with higher patient mortality?

Background: Studies that have shown an association between lower nurse staffing and higher inpatient mortality have been limited by methodological issues. These limitations include the use of hospital-level administrative data that do not fully capture actual staffing levels and the lack of control for expected nursing requirements for patients.

Study design: Retrospective observational study.

Setting: Forty-three hospital units on both medical and surgical services at a single institution.

Synopsis: The authors examined whether patients who were cared for during shifts that had nursing staffing that was eight hours or more below the staffing target had a higher-than-expected mortality compared with predicted mortality, based on risk-adjusted DRG-related mortality. They also assessed if increased patient turnover during a patient-care shift was associated with a higher-than-expected mortality.

The authors analyzed mortality outcomes of 197,961 patients who were cared for across 176,696 staffed unit-shifts. The risk of death increased with the number of shifts a patient was cared for when the nursing staffing was eight hours below target, with a hazard ratio per below-target shift of 1.02 (95% CI: 1.01 to 1.03). There was also an association between a higher mortality and a greater number of high-turnover shifts, with a hazard ratio of 1.04 (95% CI 1.02 to 1.03).

Bottom line: Patients cared for during shifts with below-target levels of nurse staffing and during shifts with increased patient turnover had an increased mortality.

Citation: Needleman J, Buerhaus P, Pankratz S, Leibson CL, Stevens SR, Harris M. Nurse staffing and inpatient hospital mortality. N Engl J Med. 2011;364(11):1037-1045.

For more physician reviews of HM-related literature, visit our website.

Clinical question: Is decreased nursing staffing and increased patient turnover across various inpatient adult hospital units associated with higher patient mortality?

Background: Studies that have shown an association between lower nurse staffing and higher inpatient mortality have been limited by methodological issues. These limitations include the use of hospital-level administrative data that do not fully capture actual staffing levels and the lack of control for expected nursing requirements for patients.

Study design: Retrospective observational study.

Setting: Forty-three hospital units on both medical and surgical services at a single institution.

Synopsis: The authors examined whether patients who were cared for during shifts that had nursing staffing that was eight hours or more below the staffing target had a higher-than-expected mortality compared with predicted mortality, based on risk-adjusted DRG-related mortality. They also assessed if increased patient turnover during a patient-care shift was associated with a higher-than-expected mortality.

The authors analyzed mortality outcomes of 197,961 patients who were cared for across 176,696 staffed unit-shifts. The risk of death increased with the number of shifts a patient was cared for when the nursing staffing was eight hours below target, with a hazard ratio per below-target shift of 1.02 (95% CI: 1.01 to 1.03). There was also an association between a higher mortality and a greater number of high-turnover shifts, with a hazard ratio of 1.04 (95% CI 1.02 to 1.03).

Bottom line: Patients cared for during shifts with below-target levels of nurse staffing and during shifts with increased patient turnover had an increased mortality.

Citation: Needleman J, Buerhaus P, Pankratz S, Leibson CL, Stevens SR, Harris M. Nurse staffing and inpatient hospital mortality. N Engl J Med. 2011;364(11):1037-1045.

For more physician reviews of HM-related literature, visit our website.

AMSTERDAM – An experimental combination of PET scanning and a positron-emitting form of erlotinib appeared to work as a noninvasive way of identifying patients with advanced non–small cell lung cancer tumors that have the right genotype to receive erlotinib therapy.

"[¹¹C]erlotinib PET shows promise as a noninvasive, in vivo means of selecting patients who may benefit from thymidine kinase inhibitor therapy," Dr. Idris Bahce said, reporting on a pilot study of 10 patients. Erlotinib (Tarceva) is from the thymidine kinase inhibitor drug class.

In his study, uptake of ¹¹C-labeled erlotinib was significantly linked to the patients’ having an activating mutation in their epidermal growth factor receptor (EGFR) gene, specifically an exon 19 deletion.

Patients positive for erlotinib uptake on the PET scan also showed a tendency for better clinical responses to a therapeutic erlotinib regimen, reported Dr. Bahce, a pulmonologist at VU University, Amsterdam, during the World Conference on Lung Cancer.

Until now, the only way to identify advanced non–small cell lung cancer (NSCLC) tumors that are candidates for treatment with a tyrosine kinase inhibitor has been to biopsy the tumor and run an in vitro genetic analysis on the tumor cells. That can be challenging in some patients, such as when the tumor is not easy to biopsy, a limited amount of tissue is available, or the tumor is genetically heterogeneous. To get a reliable result from biopsy and testing, at least 30% of the specimen must contain malignant cells, Dr. Bahce said at the conference, sponsored by the International Association for the Study of Lung Cancer.

"It is a very early study, but ... it’s important because personalized treatment [for cancer] has gone to the next level, where we use new agents and match them to the right patients by doing biopsies," commented Dr. Roy S. Herbst, chief of medical oncology at the Yale Cancer Center in New Haven. "The PET method also allows physicians to assess the volume of cancer carrying the EGFR mutation following treatment, a way to track treatment efficacy," said Dr. Herbst in an interview.

"Instead of getting tissue at one point in time, you can image more frequently. It’s a way to track the course of treatment noninvasively," and in real time, he said.

He also predicted that the [¹¹C]erlotinib PET test will become commercialized, although currently Dr. Bahce’s studies do not have any commercial funding.

"This is a proof of concept study," commented Dr. Luis Paz-Ares, chief of medical oncology at University Hospital Virgin del Rocio in Seville, Spain. "We need to define the positive predictive value and the negative predictive value" of the test, he added. The long-term future of a test like this may also be limited because future testing will probably need to look at multiple biomarkers, Dr. Paz-Ares said.

The study enrolled five patients with advanced NSCLC who had exon 19 deletion EGFR mutations, and five advanced NSCLC patients with wild-type EGFR genes. Each patient underwent a pair of [¹¹C]erlotinib PET scans, each preceded by a [¹⁵O]water PET scan to assess blood perfusion of the tumors. A 4-hour interval separated the two sets of scans.

The scan results showed that the volume of distribution of the tagged erlotinib in the patients with EGFR mutations ran about 50% higher than in the patients with wild-type tumors, a difference that was significant (P = .03).

Clinically, two of the five wild-type patients had nonetheless received erlotinib treatment prior to testing, and neither patient responded, with both showing progressive disease.

Three of the five patients with an EGFR mutation began receiving erlotinib treatment after testing and responded. In one of these patients, the tumor remained in check for 13 months. In a second patient, the tumor began to progress after 17 months of no progression on treatment. In the third patient, the tumor began to progress again after about 4 weeks of no progression on erlotinib treatment, Dr. Bahce said. A fourth patient went on erlotinib treatment before testing, and did not respond and continued to have progressive disease.

The two patient subgroups showed no difference in blood perfusion into the tumors, or in EGFR expression in cell membranes.

Dr. Bahce said he had no disclosures.

AMSTERDAM – An experimental combination of PET scanning and a positron-emitting form of erlotinib appeared to work as a noninvasive way of identifying patients with advanced non–small cell lung cancer tumors that have the right genotype to receive erlotinib therapy.

"[¹¹C]erlotinib PET shows promise as a noninvasive, in vivo means of selecting patients who may benefit from thymidine kinase inhibitor therapy," Dr. Idris Bahce said, reporting on a pilot study of 10 patients. Erlotinib (Tarceva) is from the thymidine kinase inhibitor drug class.

In his study, uptake of ¹¹C-labeled erlotinib was significantly linked to the patients’ having an activating mutation in their epidermal growth factor receptor (EGFR) gene, specifically an exon 19 deletion.

Patients positive for erlotinib uptake on the PET scan also showed a tendency for better clinical responses to a therapeutic erlotinib regimen, reported Dr. Bahce, a pulmonologist at VU University, Amsterdam, during the World Conference on Lung Cancer.

Until now, the only way to identify advanced non–small cell lung cancer (NSCLC) tumors that are candidates for treatment with a tyrosine kinase inhibitor has been to biopsy the tumor and run an in vitro genetic analysis on the tumor cells. That can be challenging in some patients, such as when the tumor is not easy to biopsy, a limited amount of tissue is available, or the tumor is genetically heterogeneous. To get a reliable result from biopsy and testing, at least 30% of the specimen must contain malignant cells, Dr. Bahce said at the conference, sponsored by the International Association for the Study of Lung Cancer.

"It is a very early study, but ... it’s important because personalized treatment [for cancer] has gone to the next level, where we use new agents and match them to the right patients by doing biopsies," commented Dr. Roy S. Herbst, chief of medical oncology at the Yale Cancer Center in New Haven. "The PET method also allows physicians to assess the volume of cancer carrying the EGFR mutation following treatment, a way to track treatment efficacy," said Dr. Herbst in an interview.

"Instead of getting tissue at one point in time, you can image more frequently. It’s a way to track the course of treatment noninvasively," and in real time, he said.

He also predicted that the [¹¹C]erlotinib PET test will become commercialized, although currently Dr. Bahce’s studies do not have any commercial funding.

"This is a proof of concept study," commented Dr. Luis Paz-Ares, chief of medical oncology at University Hospital Virgin del Rocio in Seville, Spain. "We need to define the positive predictive value and the negative predictive value" of the test, he added. The long-term future of a test like this may also be limited because future testing will probably need to look at multiple biomarkers, Dr. Paz-Ares said.

The study enrolled five patients with advanced NSCLC who had exon 19 deletion EGFR mutations, and five advanced NSCLC patients with wild-type EGFR genes. Each patient underwent a pair of [¹¹C]erlotinib PET scans, each preceded by a [¹⁵O]water PET scan to assess blood perfusion of the tumors. A 4-hour interval separated the two sets of scans.

The scan results showed that the volume of distribution of the tagged erlotinib in the patients with EGFR mutations ran about 50% higher than in the patients with wild-type tumors, a difference that was significant (P = .03).

Clinically, two of the five wild-type patients had nonetheless received erlotinib treatment prior to testing, and neither patient responded, with both showing progressive disease.

Three of the five patients with an EGFR mutation began receiving erlotinib treatment after testing and responded. In one of these patients, the tumor remained in check for 13 months. In a second patient, the tumor began to progress after 17 months of no progression on treatment. In the third patient, the tumor began to progress again after about 4 weeks of no progression on erlotinib treatment, Dr. Bahce said. A fourth patient went on erlotinib treatment before testing, and did not respond and continued to have progressive disease.

The two patient subgroups showed no difference in blood perfusion into the tumors, or in EGFR expression in cell membranes.

Dr. Bahce said he had no disclosures.

AMSTERDAM – An experimental combination of PET scanning and a positron-emitting form of erlotinib appeared to work as a noninvasive way of identifying patients with advanced non–small cell lung cancer tumors that have the right genotype to receive erlotinib therapy.

"[¹¹C]erlotinib PET shows promise as a noninvasive, in vivo means of selecting patients who may benefit from thymidine kinase inhibitor therapy," Dr. Idris Bahce said, reporting on a pilot study of 10 patients. Erlotinib (Tarceva) is from the thymidine kinase inhibitor drug class.

In his study, uptake of ¹¹C-labeled erlotinib was significantly linked to the patients’ having an activating mutation in their epidermal growth factor receptor (EGFR) gene, specifically an exon 19 deletion.

Patients positive for erlotinib uptake on the PET scan also showed a tendency for better clinical responses to a therapeutic erlotinib regimen, reported Dr. Bahce, a pulmonologist at VU University, Amsterdam, during the World Conference on Lung Cancer.

Until now, the only way to identify advanced non–small cell lung cancer (NSCLC) tumors that are candidates for treatment with a tyrosine kinase inhibitor has been to biopsy the tumor and run an in vitro genetic analysis on the tumor cells. That can be challenging in some patients, such as when the tumor is not easy to biopsy, a limited amount of tissue is available, or the tumor is genetically heterogeneous. To get a reliable result from biopsy and testing, at least 30% of the specimen must contain malignant cells, Dr. Bahce said at the conference, sponsored by the International Association for the Study of Lung Cancer.

"It is a very early study, but ... it’s important because personalized treatment [for cancer] has gone to the next level, where we use new agents and match them to the right patients by doing biopsies," commented Dr. Roy S. Herbst, chief of medical oncology at the Yale Cancer Center in New Haven. "The PET method also allows physicians to assess the volume of cancer carrying the EGFR mutation following treatment, a way to track treatment efficacy," said Dr. Herbst in an interview.

"Instead of getting tissue at one point in time, you can image more frequently. It’s a way to track the course of treatment noninvasively," and in real time, he said.

He also predicted that the [¹¹C]erlotinib PET test will become commercialized, although currently Dr. Bahce’s studies do not have any commercial funding.

"This is a proof of concept study," commented Dr. Luis Paz-Ares, chief of medical oncology at University Hospital Virgin del Rocio in Seville, Spain. "We need to define the positive predictive value and the negative predictive value" of the test, he added. The long-term future of a test like this may also be limited because future testing will probably need to look at multiple biomarkers, Dr. Paz-Ares said.

The study enrolled five patients with advanced NSCLC who had exon 19 deletion EGFR mutations, and five advanced NSCLC patients with wild-type EGFR genes. Each patient underwent a pair of [¹¹C]erlotinib PET scans, each preceded by a [¹⁵O]water PET scan to assess blood perfusion of the tumors. A 4-hour interval separated the two sets of scans.

The scan results showed that the volume of distribution of the tagged erlotinib in the patients with EGFR mutations ran about 50% higher than in the patients with wild-type tumors, a difference that was significant (P = .03).

Clinically, two of the five wild-type patients had nonetheless received erlotinib treatment prior to testing, and neither patient responded, with both showing progressive disease.

Three of the five patients with an EGFR mutation began receiving erlotinib treatment after testing and responded. In one of these patients, the tumor remained in check for 13 months. In a second patient, the tumor began to progress after 17 months of no progression on treatment. In the third patient, the tumor began to progress again after about 4 weeks of no progression on erlotinib treatment, Dr. Bahce said. A fourth patient went on erlotinib treatment before testing, and did not respond and continued to have progressive disease.

The two patient subgroups showed no difference in blood perfusion into the tumors, or in EGFR expression in cell membranes.

Dr. Bahce said he had no disclosures.

A large, multicenter, randomized study of 14, 264 patients at risk for stroke with nonvalvular atrial fibrillation (AF) found the factor Xa inhibitor rivaroxaban to be noninferior to warfarin for preventing stroke or systemic embolism.

The ROCKET AF investigators, who reported the results online August 10 in The New England Journal of Medicine, detected no significant difference between rivaroxaban and warfarin in the rates of major or nonmajor clinically relevant bleeding.

Investigators at 1178 study sites in 45 countries randomly assigned the patients to receive either fixed-dose rivaroxaban at 20 mg daily or adjusted-dose warfarin to a target of INR 2.0 – 3.0. Patients with a creatinine clearance of 30-49 mL/minute received a rivaroxaban dose of 15 mg daily.

Patients in both arms of the intent-to-treat population were a median age of 73 years and about 40% were women. The patients had considerable rates of coexisting conditions, including 90.5% with hypertension, 62.5% with heart failure, and 54.8% who had had a previous stroke, embolism, or transient ischemic attack.

After a median treatment duration of 590 days, the primary efficacy analysis showed188 patients (1.7% per year) in the rivaroxaban group had a stroke or systemic embolism, compared with 241 patients (2.2% per year) in the warfarin group (P<0.001 for noninferiority).

Rates of major bleeding were similar in the 2 groups—3.6% with rivaroxaban and 3.4% with warfarin (P=0.58). Major and clinically relevant nonmajor bleeding occurred in 1475 (14.9%) rivaroxaban-treated patients and 1449 (14.5%) warfarin-treated patients (P=0.44). Intracranial and fatal bleeding occurred less often in the rivaroxaban group.

The investigators noted that the warfarin-treated patients were in therapeutic range a mean of 55% of the time. However, the efficacy of rivaroxaban was as favorable in those centers with the best INR control as it was in those with inferior control.

Lead author Manesh R. Patel, MD, of Duke University School of Medicine in North Carolina, said, “Warfarin has been a standard treatment for decades, but requires a rigorous monitoring schedule to ensure therapeutic dosing levels, and is subject to the potential of food and drug interactions that present treatment obstacles for patients and doctors alike.”

He indicated that the result of the trial “have convincingly shown rivaroxaban to be an alternative to warfarin in treating patients with atrial fibrillation, and importantly, with no increase in bleeding.”

The study was funded by Johnson & Johnson and Bayer.

ROCKET AF stands for Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonist for Prevention of Stroke and Embolism Trial in Atrial Fibrillation.

A large, multicenter, randomized study of 14, 264 patients at risk for stroke with nonvalvular atrial fibrillation (AF) found the factor Xa inhibitor rivaroxaban to be noninferior to warfarin for preventing stroke or systemic embolism.

The ROCKET AF investigators, who reported the results online August 10 in The New England Journal of Medicine, detected no significant difference between rivaroxaban and warfarin in the rates of major or nonmajor clinically relevant bleeding.

Investigators at 1178 study sites in 45 countries randomly assigned the patients to receive either fixed-dose rivaroxaban at 20 mg daily or adjusted-dose warfarin to a target of INR 2.0 – 3.0. Patients with a creatinine clearance of 30-49 mL/minute received a rivaroxaban dose of 15 mg daily.

Patients in both arms of the intent-to-treat population were a median age of 73 years and about 40% were women. The patients had considerable rates of coexisting conditions, including 90.5% with hypertension, 62.5% with heart failure, and 54.8% who had had a previous stroke, embolism, or transient ischemic attack.

After a median treatment duration of 590 days, the primary efficacy analysis showed188 patients (1.7% per year) in the rivaroxaban group had a stroke or systemic embolism, compared with 241 patients (2.2% per year) in the warfarin group (P<0.001 for noninferiority).

Rates of major bleeding were similar in the 2 groups—3.6% with rivaroxaban and 3.4% with warfarin (P=0.58). Major and clinically relevant nonmajor bleeding occurred in 1475 (14.9%) rivaroxaban-treated patients and 1449 (14.5%) warfarin-treated patients (P=0.44). Intracranial and fatal bleeding occurred less often in the rivaroxaban group.

The investigators noted that the warfarin-treated patients were in therapeutic range a mean of 55% of the time. However, the efficacy of rivaroxaban was as favorable in those centers with the best INR control as it was in those with inferior control.

Lead author Manesh R. Patel, MD, of Duke University School of Medicine in North Carolina, said, “Warfarin has been a standard treatment for decades, but requires a rigorous monitoring schedule to ensure therapeutic dosing levels, and is subject to the potential of food and drug interactions that present treatment obstacles for patients and doctors alike.”

He indicated that the result of the trial “have convincingly shown rivaroxaban to be an alternative to warfarin in treating patients with atrial fibrillation, and importantly, with no increase in bleeding.”

The study was funded by Johnson & Johnson and Bayer.

ROCKET AF stands for Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonist for Prevention of Stroke and Embolism Trial in Atrial Fibrillation.

A large, multicenter, randomized study of 14, 264 patients at risk for stroke with nonvalvular atrial fibrillation (AF) found the factor Xa inhibitor rivaroxaban to be noninferior to warfarin for preventing stroke or systemic embolism.

The ROCKET AF investigators, who reported the results online August 10 in The New England Journal of Medicine, detected no significant difference between rivaroxaban and warfarin in the rates of major or nonmajor clinically relevant bleeding.

Investigators at 1178 study sites in 45 countries randomly assigned the patients to receive either fixed-dose rivaroxaban at 20 mg daily or adjusted-dose warfarin to a target of INR 2.0 – 3.0. Patients with a creatinine clearance of 30-49 mL/minute received a rivaroxaban dose of 15 mg daily.

Patients in both arms of the intent-to-treat population were a median age of 73 years and about 40% were women. The patients had considerable rates of coexisting conditions, including 90.5% with hypertension, 62.5% with heart failure, and 54.8% who had had a previous stroke, embolism, or transient ischemic attack.

After a median treatment duration of 590 days, the primary efficacy analysis showed188 patients (1.7% per year) in the rivaroxaban group had a stroke or systemic embolism, compared with 241 patients (2.2% per year) in the warfarin group (P<0.001 for noninferiority).

Rates of major bleeding were similar in the 2 groups—3.6% with rivaroxaban and 3.4% with warfarin (P=0.58). Major and clinically relevant nonmajor bleeding occurred in 1475 (14.9%) rivaroxaban-treated patients and 1449 (14.5%) warfarin-treated patients (P=0.44). Intracranial and fatal bleeding occurred less often in the rivaroxaban group.

The investigators noted that the warfarin-treated patients were in therapeutic range a mean of 55% of the time. However, the efficacy of rivaroxaban was as favorable in those centers with the best INR control as it was in those with inferior control.

Lead author Manesh R. Patel, MD, of Duke University School of Medicine in North Carolina, said, “Warfarin has been a standard treatment for decades, but requires a rigorous monitoring schedule to ensure therapeutic dosing levels, and is subject to the potential of food and drug interactions that present treatment obstacles for patients and doctors alike.”

He indicated that the result of the trial “have convincingly shown rivaroxaban to be an alternative to warfarin in treating patients with atrial fibrillation, and importantly, with no increase in bleeding.”

The study was funded by Johnson & Johnson and Bayer.

ROCKET AF stands for Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonist for Prevention of Stroke and Embolism Trial in Atrial Fibrillation.

That the largest-ever study of glucose control in U.S. hospitals found roughly 1 in 3 patients are hyperglycemic (<180 mg/dL) during their hospital stay is no surprise to hospitalist Cheryl O'Malley, MD, FACP, program director of internal medicine at the Banner Good Samaritan Medical Center, Phoenix.

The data (PDF), based on point-of-care bedside glucose tests at 575 hospitals, showed hyperglycemia in 32.2% of ICU patients and 32% in non-ICU patients. Dr. O'Malley says the findings are further evidence that HM leaders have a duty to focus on glycemic control because so many of their patients are hyperglycemic.

Dr. O'Malley does her part as a mentor for SHM's Glycemic Control Mentored Initiative (GCMI) program, which recently expanded to a second cohort of 96 sites. The mentoring program has branched out to include nurses, physician assistants, and even two leading endocrinologists as mentors: Emory University School of Medicine's Guillermo Umpierrez, MD, FACP, FACE, and HealthPartners' John MacIndoe, MD.

SHM also has launched a microsite, dubbed eQUIPS (Electronic Quality Improvement Programs), which gives HM groups not involved in the mentoring program access to data analysis, benchmarking tools, and other services.

Kendall M. Rogers, MD, CPE, FACP, SFHM, associate professor of medicine and hospital medicine division chief at the University of New Mexico Health Sciences Center's Department of Internal Medicine, says SHM has always wanted to broaden the program to as many hospitals and physicians as possible to battle glycemic-control issues. And bringing in nationally respected endocrinologists as mentors furthers the goal to build "teams of experts within local hospitals."

"Hospitalists, endocrinologists, and other specialists have to work together," Dr. O'Malley adds. "The volume of work is just too much for any one group to bear."

That the largest-ever study of glucose control in U.S. hospitals found roughly 1 in 3 patients are hyperglycemic (<180 mg/dL) during their hospital stay is no surprise to hospitalist Cheryl O'Malley, MD, FACP, program director of internal medicine at the Banner Good Samaritan Medical Center, Phoenix.

The data (PDF), based on point-of-care bedside glucose tests at 575 hospitals, showed hyperglycemia in 32.2% of ICU patients and 32% in non-ICU patients. Dr. O'Malley says the findings are further evidence that HM leaders have a duty to focus on glycemic control because so many of their patients are hyperglycemic.

Dr. O'Malley does her part as a mentor for SHM's Glycemic Control Mentored Initiative (GCMI) program, which recently expanded to a second cohort of 96 sites. The mentoring program has branched out to include nurses, physician assistants, and even two leading endocrinologists as mentors: Emory University School of Medicine's Guillermo Umpierrez, MD, FACP, FACE, and HealthPartners' John MacIndoe, MD.

SHM also has launched a microsite, dubbed eQUIPS (Electronic Quality Improvement Programs), which gives HM groups not involved in the mentoring program access to data analysis, benchmarking tools, and other services.

Kendall M. Rogers, MD, CPE, FACP, SFHM, associate professor of medicine and hospital medicine division chief at the University of New Mexico Health Sciences Center's Department of Internal Medicine, says SHM has always wanted to broaden the program to as many hospitals and physicians as possible to battle glycemic-control issues. And bringing in nationally respected endocrinologists as mentors furthers the goal to build "teams of experts within local hospitals."

"Hospitalists, endocrinologists, and other specialists have to work together," Dr. O'Malley adds. "The volume of work is just too much for any one group to bear."

That the largest-ever study of glucose control in U.S. hospitals found roughly 1 in 3 patients are hyperglycemic (<180 mg/dL) during their hospital stay is no surprise to hospitalist Cheryl O'Malley, MD, FACP, program director of internal medicine at the Banner Good Samaritan Medical Center, Phoenix.

The data (PDF), based on point-of-care bedside glucose tests at 575 hospitals, showed hyperglycemia in 32.2% of ICU patients and 32% in non-ICU patients. Dr. O'Malley says the findings are further evidence that HM leaders have a duty to focus on glycemic control because so many of their patients are hyperglycemic.

Dr. O'Malley does her part as a mentor for SHM's Glycemic Control Mentored Initiative (GCMI) program, which recently expanded to a second cohort of 96 sites. The mentoring program has branched out to include nurses, physician assistants, and even two leading endocrinologists as mentors: Emory University School of Medicine's Guillermo Umpierrez, MD, FACP, FACE, and HealthPartners' John MacIndoe, MD.

SHM also has launched a microsite, dubbed eQUIPS (Electronic Quality Improvement Programs), which gives HM groups not involved in the mentoring program access to data analysis, benchmarking tools, and other services.

Kendall M. Rogers, MD, CPE, FACP, SFHM, associate professor of medicine and hospital medicine division chief at the University of New Mexico Health Sciences Center's Department of Internal Medicine, says SHM has always wanted to broaden the program to as many hospitals and physicians as possible to battle glycemic-control issues. And bringing in nationally respected endocrinologists as mentors furthers the goal to build "teams of experts within local hospitals."

"Hospitalists, endocrinologists, and other specialists have to work together," Dr. O'Malley adds. "The volume of work is just too much for any one group to bear."

A recent study in the Journal of Hospital Medicine concluded that by rescheduling fewer than 10 elective admissions per week from a weekday to a weekend, hospitals can reduce overcrowding. The report should encourage hospitalists to reconsider their own scheduling strategies, the lead author says.

"If they notice that on certain days their unit or their hospital is very crowded and on other days it's less so, it may be worth working with their organization's quality and safety or operational leadership to learn more about those patterns and see if they can improve on them," says Evan S. Fieldston, MD, MBA, MSHP, pediatric hospitalist at the Children's Hospital of Philadelphia.

The study examined 2007 daily inpatient census data from 39 tertiary-care children's hospitals. The average weekday occupancy ranged from 70.9% to 108.1%, while the average weekend occupancy ranged from 65.7% to 94.9%. After rescheduling, or "smoothing," elective admissions from days with "thresholds of high occupancy," defined as >85% occupancy, to less busy days, 39,607 patients were removed from exposure to occupancy levels greater than 95%.

Eugene Litvak, MD, president and CEO of the nonprofit Institute for Healthcare Optimization and adjunct professor of operations management at the Harvard School of Public Health in Boston, says the issue goes beyond U.S. hospitals. Dr. Litvak says he's discussed overcrowding with more than 100 hospitals in Europe, Japan, Australia, and the U.S. "In talking with their leadership in healthcare, I saw the same problem," he says.

The solution, Dr. Litvak suggests, lies with queueing theory, a mathematical formula that addresses random demand for a fixed capacity. Based on average census data, hospitals can apply queueing theory to determine how many beds and staff they need for ED admissions throughout a typical week.

A recent study in the Journal of Hospital Medicine concluded that by rescheduling fewer than 10 elective admissions per week from a weekday to a weekend, hospitals can reduce overcrowding. The report should encourage hospitalists to reconsider their own scheduling strategies, the lead author says.

"If they notice that on certain days their unit or their hospital is very crowded and on other days it's less so, it may be worth working with their organization's quality and safety or operational leadership to learn more about those patterns and see if they can improve on them," says Evan S. Fieldston, MD, MBA, MSHP, pediatric hospitalist at the Children's Hospital of Philadelphia.

The study examined 2007 daily inpatient census data from 39 tertiary-care children's hospitals. The average weekday occupancy ranged from 70.9% to 108.1%, while the average weekend occupancy ranged from 65.7% to 94.9%. After rescheduling, or "smoothing," elective admissions from days with "thresholds of high occupancy," defined as >85% occupancy, to less busy days, 39,607 patients were removed from exposure to occupancy levels greater than 95%.

Eugene Litvak, MD, president and CEO of the nonprofit Institute for Healthcare Optimization and adjunct professor of operations management at the Harvard School of Public Health in Boston, says the issue goes beyond U.S. hospitals. Dr. Litvak says he's discussed overcrowding with more than 100 hospitals in Europe, Japan, Australia, and the U.S. "In talking with their leadership in healthcare, I saw the same problem," he says.

The solution, Dr. Litvak suggests, lies with queueing theory, a mathematical formula that addresses random demand for a fixed capacity. Based on average census data, hospitals can apply queueing theory to determine how many beds and staff they need for ED admissions throughout a typical week.

A recent study in the Journal of Hospital Medicine concluded that by rescheduling fewer than 10 elective admissions per week from a weekday to a weekend, hospitals can reduce overcrowding. The report should encourage hospitalists to reconsider their own scheduling strategies, the lead author says.

"If they notice that on certain days their unit or their hospital is very crowded and on other days it's less so, it may be worth working with their organization's quality and safety or operational leadership to learn more about those patterns and see if they can improve on them," says Evan S. Fieldston, MD, MBA, MSHP, pediatric hospitalist at the Children's Hospital of Philadelphia.

The study examined 2007 daily inpatient census data from 39 tertiary-care children's hospitals. The average weekday occupancy ranged from 70.9% to 108.1%, while the average weekend occupancy ranged from 65.7% to 94.9%. After rescheduling, or "smoothing," elective admissions from days with "thresholds of high occupancy," defined as >85% occupancy, to less busy days, 39,607 patients were removed from exposure to occupancy levels greater than 95%.

Eugene Litvak, MD, president and CEO of the nonprofit Institute for Healthcare Optimization and adjunct professor of operations management at the Harvard School of Public Health in Boston, says the issue goes beyond U.S. hospitals. Dr. Litvak says he's discussed overcrowding with more than 100 hospitals in Europe, Japan, Australia, and the U.S. "In talking with their leadership in healthcare, I saw the same problem," he says.

The solution, Dr. Litvak suggests, lies with queueing theory, a mathematical formula that addresses random demand for a fixed capacity. Based on average census data, hospitals can apply queueing theory to determine how many beds and staff they need for ED admissions throughout a typical week.

Gene therapy with a lentiviral vector expressing a chimeric antigen receptor with specificity for CD19 (CART19) has induced complete remission in 3 patients with chronic lymphocytic leukemia (CLL), according to research published simultaneously in the August 10 issues of The New England Journal of Medicine and Science Translational Medicine.

The research team, from the University of Pennsylvania, reported that the reinfused, modified T cells expanded to more than 1000 times the initial engraftment level. The patients’ remission was ongoing at 10 months after treatment.

The investigators believe the big difference between this genetically modified T cell and previous ones that had disappointing clinical activity is the addition of the CD137 (4-1BB) costimulatory signaling domain that significantly increases antitumor activity.

The team, led by Carl June, MD, described in the NEJM article the T-cell treatment of one of the patients with advanced, p53-deficient CLL.

A half year prior to enrolling in the trial, the 64-year-old patient’s T cells were collected and frozen. Before reinfusing the T cells into the patient, the investigators thawed the cells and transduced them with lentivirus expressing CD19-specific chimeric antigen receptor.

Four days prior to reinfusion, the patient received chemotherapy with pentostatin and cyclophosphamide to deplete his lymphocytes. After 3 days of chemotherapy, his bone marrow was hypercellular with approximately 40% involvement by CLL.

After 4 days of chemotherapy, the patient received an infusion of T cells, of which 5% were transduced, totaling 1.42 x 10⁷ transduced cells, split into 3 consecutive daily infusions.

Two weeks after the infusion, the patient experienced chills, fever, and fatigue, which intensified over the subsequent days. He was diagnosed with tumor lysis syndrome on day 22 after infusion. On day 23 after the CART19-cell infusion, the patient had no evidence of CLL in the bone marrow, and by day 28, his adenopathy was not palpable.

In addition to tumor lysis syndrome, the only other grade 3/4 toxicity observed was lymphopenia.

The investigators did not expect that such a low dose of chimeric antigen receptor T cells would result in a clinically evident antitumor response. The dose was several orders of magnitude lower than that used in previous studies of modified T cells.

They speculated that the course of chemotherapy administered to the patient prior to the CART19-cell infusion may have been responsible for the increased engraftment and for “potentiating the ability of chimeric antigen receptor T cells to kill stressed tumor cells that would otherwise survive the chemotherapy.”

The researchers conclude that continued study of CD19-redirected T cells is warranted and plan to test the approach in other CD19-positive tumors, including non-Hodgkin lymphoma and acute lymphocytic leukemia.

Gene therapy with a lentiviral vector expressing a chimeric antigen receptor with specificity for CD19 (CART19) has induced complete remission in 3 patients with chronic lymphocytic leukemia (CLL), according to research published simultaneously in the August 10 issues of The New England Journal of Medicine and Science Translational Medicine.

The research team, from the University of Pennsylvania, reported that the reinfused, modified T cells expanded to more than 1000 times the initial engraftment level. The patients’ remission was ongoing at 10 months after treatment.

The investigators believe the big difference between this genetically modified T cell and previous ones that had disappointing clinical activity is the addition of the CD137 (4-1BB) costimulatory signaling domain that significantly increases antitumor activity.

The team, led by Carl June, MD, described in the NEJM article the T-cell treatment of one of the patients with advanced, p53-deficient CLL.

A half year prior to enrolling in the trial, the 64-year-old patient’s T cells were collected and frozen. Before reinfusing the T cells into the patient, the investigators thawed the cells and transduced them with lentivirus expressing CD19-specific chimeric antigen receptor.

Four days prior to reinfusion, the patient received chemotherapy with pentostatin and cyclophosphamide to deplete his lymphocytes. After 3 days of chemotherapy, his bone marrow was hypercellular with approximately 40% involvement by CLL.

After 4 days of chemotherapy, the patient received an infusion of T cells, of which 5% were transduced, totaling 1.42 x 10⁷ transduced cells, split into 3 consecutive daily infusions.

Two weeks after the infusion, the patient experienced chills, fever, and fatigue, which intensified over the subsequent days. He was diagnosed with tumor lysis syndrome on day 22 after infusion. On day 23 after the CART19-cell infusion, the patient had no evidence of CLL in the bone marrow, and by day 28, his adenopathy was not palpable.

In addition to tumor lysis syndrome, the only other grade 3/4 toxicity observed was lymphopenia.

The investigators did not expect that such a low dose of chimeric antigen receptor T cells would result in a clinically evident antitumor response. The dose was several orders of magnitude lower than that used in previous studies of modified T cells.

They speculated that the course of chemotherapy administered to the patient prior to the CART19-cell infusion may have been responsible for the increased engraftment and for “potentiating the ability of chimeric antigen receptor T cells to kill stressed tumor cells that would otherwise survive the chemotherapy.”

The researchers conclude that continued study of CD19-redirected T cells is warranted and plan to test the approach in other CD19-positive tumors, including non-Hodgkin lymphoma and acute lymphocytic leukemia.

Gene therapy with a lentiviral vector expressing a chimeric antigen receptor with specificity for CD19 (CART19) has induced complete remission in 3 patients with chronic lymphocytic leukemia (CLL), according to research published simultaneously in the August 10 issues of The New England Journal of Medicine and Science Translational Medicine.

The research team, from the University of Pennsylvania, reported that the reinfused, modified T cells expanded to more than 1000 times the initial engraftment level. The patients’ remission was ongoing at 10 months after treatment.

The investigators believe the big difference between this genetically modified T cell and previous ones that had disappointing clinical activity is the addition of the CD137 (4-1BB) costimulatory signaling domain that significantly increases antitumor activity.

The team, led by Carl June, MD, described in the NEJM article the T-cell treatment of one of the patients with advanced, p53-deficient CLL.

A half year prior to enrolling in the trial, the 64-year-old patient’s T cells were collected and frozen. Before reinfusing the T cells into the patient, the investigators thawed the cells and transduced them with lentivirus expressing CD19-specific chimeric antigen receptor.

Four days prior to reinfusion, the patient received chemotherapy with pentostatin and cyclophosphamide to deplete his lymphocytes. After 3 days of chemotherapy, his bone marrow was hypercellular with approximately 40% involvement by CLL.

After 4 days of chemotherapy, the patient received an infusion of T cells, of which 5% were transduced, totaling 1.42 x 10⁷ transduced cells, split into 3 consecutive daily infusions.

Two weeks after the infusion, the patient experienced chills, fever, and fatigue, which intensified over the subsequent days. He was diagnosed with tumor lysis syndrome on day 22 after infusion. On day 23 after the CART19-cell infusion, the patient had no evidence of CLL in the bone marrow, and by day 28, his adenopathy was not palpable.

In addition to tumor lysis syndrome, the only other grade 3/4 toxicity observed was lymphopenia.

The investigators did not expect that such a low dose of chimeric antigen receptor T cells would result in a clinically evident antitumor response. The dose was several orders of magnitude lower than that used in previous studies of modified T cells.

They speculated that the course of chemotherapy administered to the patient prior to the CART19-cell infusion may have been responsible for the increased engraftment and for “potentiating the ability of chimeric antigen receptor T cells to kill stressed tumor cells that would otherwise survive the chemotherapy.”

The researchers conclude that continued study of CD19-redirected T cells is warranted and plan to test the approach in other CD19-positive tumors, including non-Hodgkin lymphoma and acute lymphocytic leukemia.

“Enter The Neurohospitalist” might sound like a medical spoof of a Bruce Lee movie, but it’s really a subspecialty’s announcement that it’s here to stay.

The clever moniker was the name of a plenary session at the 8th New York Symposium on Neurological Emergencies & Neurological Care, sponsored by Columbia University’s Center for Continuing Medical Education. The two-hour presentation on neurology’s take on HM was a new feature for the annual meeting, and to presenter David Likosky, MD, SFHM, hospitalist and stroke program director at Evergreen Hospital Medical Center in Kirkland, Wash., it was the latest sign that the field of HM is cementing its future.

“The neurohospitalist world right now is where the hospital medicine world was, say, ten, fifteen years ago,” says Dr. Likosky, who is board-certified in both neurology and internal medicine.

Multiple fields have adopted the HM model, to the point that SHM is holding its first national specialty hospitalist meeting, Focused Practice in Hospital Medicine, on Nov. 4 in Las Vegas. The meeting is designed to help promote networking of people interested in the hospitalist model in various specialties, as well as to help identify issues related to those specialties. Click here for more information and registration.

But even within the growth of speciality hospitalist models, neurology might be the cohort embracing it the fastest. Dr. Likosky estimates there are 500 neurohospitalists practicing nationwide. The Neurohospitalist Society held its first meeting earlier this year, and the field’s first textbook, which he is contributing to, is set for release in November. The Academy of Neurology has a dedicated neurohospitalist section. And the subspecialty even has its own quarterly journal, The Neurohospitalist.

There is now a critical mass of neurohospitalists. There’s also an increasing recognition by the neurointensivists that someone has to help them take care of these patients, either before they get to the unit or when they come out of the unit.

—David Likosky, MD, SFHM, hospitalist, stroke program director, Evergreen Hospital Medical Center, Kirkland, Wash.

“There is now a critical mass of neurohospitalists,” Dr. Likosky says. “There’s also an increasing recognition by the neurointensivists that someone has to help them take care of these patients, either before they get to the unit or when they come out of the unit. … Most hospitals don’t have neurointensivists, but they have very ill neurology patients. That’s another niche for neurohospitalists. All specialties of intensivists are looking for help with these patients.”

Another panelist at the four-day Manhattan conference, William D. Freeman, MD, assistant professor of neurology at the Mayo Clinic in Jacksonville, Fla., says the continued success of the field will be judged on data. He says three areas of potential “low-hanging fruit” to focus on are:

• Increased use of intravenous tissue plasminogen activators (tPA). The FDA-approved “clot-busting therapy” has been shown to reverse the effects of ischemic stroke if given within a time-sensitive window of therapeutic opportunity.
• Reduced length of stay for stroke patients. Adherence to best practices, Dr. Freeman says, will most effectively reduce patient stays and will be the ones that also demonstrate quality and patient-safety attributes.
• Focus on stroke patient metrics. Administrators often focus on quality measures that are easily identifiable; Dr. Likosky says new programs have to be able to show they can meet those thresholds.

“Hospital administrators are new to the concept of a neurohospitalist,” Dr. Likosky adds. “It’s easier in that they get the hospitalist model because that’s been around for so long, but figuring out the expense of a neurohospitalist program, how that functionally works, are there enough volumes, are all questions that are being asked.”

Still, Drs. Freeman and Likosky agree that the advantages of the subspecialty—everything from physicians’ quality of life to newly satisfied specialists in other departments (who will have a quicker neuro consult available)—mean the nascent specialty can continue to grow in numbers and influence.

“The future is bright for neurohospitalists,” Dr. Freeman says.

Richard Quinn is a freelance writer based in New Jersey.

“Enter The Neurohospitalist” might sound like a medical spoof of a Bruce Lee movie, but it’s really a subspecialty’s announcement that it’s here to stay.

The clever moniker was the name of a plenary session at the 8th New York Symposium on Neurological Emergencies & Neurological Care, sponsored by Columbia University’s Center for Continuing Medical Education. The two-hour presentation on neurology’s take on HM was a new feature for the annual meeting, and to presenter David Likosky, MD, SFHM, hospitalist and stroke program director at Evergreen Hospital Medical Center in Kirkland, Wash., it was the latest sign that the field of HM is cementing its future.

“The neurohospitalist world right now is where the hospital medicine world was, say, ten, fifteen years ago,” says Dr. Likosky, who is board-certified in both neurology and internal medicine.

Multiple fields have adopted the HM model, to the point that SHM is holding its first national specialty hospitalist meeting, Focused Practice in Hospital Medicine, on Nov. 4 in Las Vegas. The meeting is designed to help promote networking of people interested in the hospitalist model in various specialties, as well as to help identify issues related to those specialties. Click here for more information and registration.

But even within the growth of speciality hospitalist models, neurology might be the cohort embracing it the fastest. Dr. Likosky estimates there are 500 neurohospitalists practicing nationwide. The Neurohospitalist Society held its first meeting earlier this year, and the field’s first textbook, which he is contributing to, is set for release in November. The Academy of Neurology has a dedicated neurohospitalist section. And the subspecialty even has its own quarterly journal, The Neurohospitalist.

There is now a critical mass of neurohospitalists. There’s also an increasing recognition by the neurointensivists that someone has to help them take care of these patients, either before they get to the unit or when they come out of the unit.

—David Likosky, MD, SFHM, hospitalist, stroke program director, Evergreen Hospital Medical Center, Kirkland, Wash.

“There is now a critical mass of neurohospitalists,” Dr. Likosky says. “There’s also an increasing recognition by the neurointensivists that someone has to help them take care of these patients, either before they get to the unit or when they come out of the unit. … Most hospitals don’t have neurointensivists, but they have very ill neurology patients. That’s another niche for neurohospitalists. All specialties of intensivists are looking for help with these patients.”

Another panelist at the four-day Manhattan conference, William D. Freeman, MD, assistant professor of neurology at the Mayo Clinic in Jacksonville, Fla., says the continued success of the field will be judged on data. He says three areas of potential “low-hanging fruit” to focus on are:

• Increased use of intravenous tissue plasminogen activators (tPA). The FDA-approved “clot-busting therapy” has been shown to reverse the effects of ischemic stroke if given within a time-sensitive window of therapeutic opportunity.
• Reduced length of stay for stroke patients. Adherence to best practices, Dr. Freeman says, will most effectively reduce patient stays and will be the ones that also demonstrate quality and patient-safety attributes.
• Focus on stroke patient metrics. Administrators often focus on quality measures that are easily identifiable; Dr. Likosky says new programs have to be able to show they can meet those thresholds.

“Hospital administrators are new to the concept of a neurohospitalist,” Dr. Likosky adds. “It’s easier in that they get the hospitalist model because that’s been around for so long, but figuring out the expense of a neurohospitalist program, how that functionally works, are there enough volumes, are all questions that are being asked.”

Still, Drs. Freeman and Likosky agree that the advantages of the subspecialty—everything from physicians’ quality of life to newly satisfied specialists in other departments (who will have a quicker neuro consult available)—mean the nascent specialty can continue to grow in numbers and influence.

“The future is bright for neurohospitalists,” Dr. Freeman says.

Richard Quinn is a freelance writer based in New Jersey.

“Enter The Neurohospitalist” might sound like a medical spoof of a Bruce Lee movie, but it’s really a subspecialty’s announcement that it’s here to stay.

The clever moniker was the name of a plenary session at the 8th New York Symposium on Neurological Emergencies & Neurological Care, sponsored by Columbia University’s Center for Continuing Medical Education. The two-hour presentation on neurology’s take on HM was a new feature for the annual meeting, and to presenter David Likosky, MD, SFHM, hospitalist and stroke program director at Evergreen Hospital Medical Center in Kirkland, Wash., it was the latest sign that the field of HM is cementing its future.

“The neurohospitalist world right now is where the hospital medicine world was, say, ten, fifteen years ago,” says Dr. Likosky, who is board-certified in both neurology and internal medicine.

Multiple fields have adopted the HM model, to the point that SHM is holding its first national specialty hospitalist meeting, Focused Practice in Hospital Medicine, on Nov. 4 in Las Vegas. The meeting is designed to help promote networking of people interested in the hospitalist model in various specialties, as well as to help identify issues related to those specialties. Click here for more information and registration.

But even within the growth of speciality hospitalist models, neurology might be the cohort embracing it the fastest. Dr. Likosky estimates there are 500 neurohospitalists practicing nationwide. The Neurohospitalist Society held its first meeting earlier this year, and the field’s first textbook, which he is contributing to, is set for release in November. The Academy of Neurology has a dedicated neurohospitalist section. And the subspecialty even has its own quarterly journal, The Neurohospitalist.

There is now a critical mass of neurohospitalists. There’s also an increasing recognition by the neurointensivists that someone has to help them take care of these patients, either before they get to the unit or when they come out of the unit.

—David Likosky, MD, SFHM, hospitalist, stroke program director, Evergreen Hospital Medical Center, Kirkland, Wash.

“There is now a critical mass of neurohospitalists,” Dr. Likosky says. “There’s also an increasing recognition by the neurointensivists that someone has to help them take care of these patients, either before they get to the unit or when they come out of the unit. … Most hospitals don’t have neurointensivists, but they have very ill neurology patients. That’s another niche for neurohospitalists. All specialties of intensivists are looking for help with these patients.”

Another panelist at the four-day Manhattan conference, William D. Freeman, MD, assistant professor of neurology at the Mayo Clinic in Jacksonville, Fla., says the continued success of the field will be judged on data. He says three areas of potential “low-hanging fruit” to focus on are:

• Increased use of intravenous tissue plasminogen activators (tPA). The FDA-approved “clot-busting therapy” has been shown to reverse the effects of ischemic stroke if given within a time-sensitive window of therapeutic opportunity.
• Reduced length of stay for stroke patients. Adherence to best practices, Dr. Freeman says, will most effectively reduce patient stays and will be the ones that also demonstrate quality and patient-safety attributes.
• Focus on stroke patient metrics. Administrators often focus on quality measures that are easily identifiable; Dr. Likosky says new programs have to be able to show they can meet those thresholds.

“Hospital administrators are new to the concept of a neurohospitalist,” Dr. Likosky adds. “It’s easier in that they get the hospitalist model because that’s been around for so long, but figuring out the expense of a neurohospitalist program, how that functionally works, are there enough volumes, are all questions that are being asked.”

Still, Drs. Freeman and Likosky agree that the advantages of the subspecialty—everything from physicians’ quality of life to newly satisfied specialists in other departments (who will have a quicker neuro consult available)—mean the nascent specialty can continue to grow in numbers and influence.

“The future is bright for neurohospitalists,” Dr. Freeman says.

Richard Quinn is a freelance writer based in New Jersey.