Progressive multifocal
leukoencephalopathy

Two additional cases of progressive multifocal leukoencephalopathy (PML) have been reported with the lymphoma drug brentuximab vedotin (Adcetris), according to the US Food and Drug Administration (FDA).

So the agency has added a new boxed warning to the drug’s label highlighting the risk of PML. At the time of brentuximab vedotin’s approval in August 2011, only 1 case of PML was described in the warnings and precautions section of the label.

The label change also includes a contraindication warning against the use of brentuximab vedotin with bleomycin, as the combination appears to increase the risk of pulmonary toxicity.

Diagnosing PML

The FDA says healthcare professionals should consider a possible diagnosis of PML in any patient who is receiving or has received brentuximab vedotin and who presents with new signs or symptoms of central nervous system abnormalities.

Healthcare professionals should also instruct patients to report changes in mood or usual behavior, confusion, problems thinking, loss of memory, changes in walking or talking, decreased strength or weakness on one side of the body, or changes in vision.

Evaluation of PML may include consultation with a neurologist, a brain MRI, lumbar puncture with analysis of cerebrospinal fluid by polymerase chain reaction for John Cunningham (JC) virus, and/or a brain biopsy.

Healthcare professionals should hold brentuximab vedotin dosing for any suspected case of PML and discontinue brentuximab vedotin dosing if PML is confirmed.

PML case reports

To date, 3 patients have developed PML while receiving treatment with brentuximab vedotin.

A 48-year-old man with Hodgkin lymphoma (HL) was diagnosed with PML after receiving the drug. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

After the third dose of brentuximab vedotin, the patient presented with left-sided weakness and slurred speech. Cerebrospinal fluid was positive for JC virus. The patient’s condition deteriorated rapidly, resulting in death within 4 weeks of symptom onset.

A 50-year-old man with HL was also diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents, targeted radiation therapy, and autologous stem cell transplant.

After 8 cycles of brentuximab vedotin, this patient presented to the local emergency room with complaints of changes in speech, difficulty writing with his right hand, and right lower extremity weakness. In addition, he had poor coordination, poor balance, and left-sided sensory deficits.

Although MRI results were inconclusive and cerebrospinal fluid analyses were negative for JC virus early in the course of the neurologic work-up, an immunostain of a spinal cord lesion biopsy was positive for JC virus.

The patient’s neurological condition continues to worsen. Most recently, he lost motor function of his lower extremities and deep tendon reflexes of his legs. He also has tremulousness of his hands and hypoactive arm reflexes.

Lastly, a 38-year-old female patient with a history of stage 4 cutaneous anaplastic large cell lymphoma was diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

Prior to treatment with brentuximab vedotin, a baseline neurological examination was normal. After the second dose, the patient complained of the inability to read, inability to find words to express herself, memory lapses, and slight loss of balance.

A brain MRI revealed a demyelinating process, and a brain biopsy was positive for JC virus. The patient’s treatment with brentuximab vedotin was discontinued.

Pulmonary toxicity risk

In addition to the risk of PML, research has revealed that brentuximab vedotin can confer a risk of pulmonary toxicity when combined with bleomycin.

A clinical trial compared the combination of brentuximab vedotin plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to combination brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD) as front-line therapy for HL.

An excessive number of patients in the brentuximab vedotin plus ABVD treatment group experienced noninfectious pulmonary toxicity. The frequency of pulmonary toxicity in this group was approximately 40%, compared to a frequency of 10% to 25% previously observed with bleomycin-based regimens not containing brentuximab vedotin.

Researchers observed no pulmonary toxicity in the brentuximab vedotin plus AVD treatment group.

Progressive multifocal
leukoencephalopathy

Two additional cases of progressive multifocal leukoencephalopathy (PML) have been reported with the lymphoma drug brentuximab vedotin (Adcetris), according to the US Food and Drug Administration (FDA).

So the agency has added a new boxed warning to the drug’s label highlighting the risk of PML. At the time of brentuximab vedotin’s approval in August 2011, only 1 case of PML was described in the warnings and precautions section of the label.

The label change also includes a contraindication warning against the use of brentuximab vedotin with bleomycin, as the combination appears to increase the risk of pulmonary toxicity.

Diagnosing PML

The FDA says healthcare professionals should consider a possible diagnosis of PML in any patient who is receiving or has received brentuximab vedotin and who presents with new signs or symptoms of central nervous system abnormalities.

Healthcare professionals should also instruct patients to report changes in mood or usual behavior, confusion, problems thinking, loss of memory, changes in walking or talking, decreased strength or weakness on one side of the body, or changes in vision.

Evaluation of PML may include consultation with a neurologist, a brain MRI, lumbar puncture with analysis of cerebrospinal fluid by polymerase chain reaction for John Cunningham (JC) virus, and/or a brain biopsy.

Healthcare professionals should hold brentuximab vedotin dosing for any suspected case of PML and discontinue brentuximab vedotin dosing if PML is confirmed.

PML case reports

To date, 3 patients have developed PML while receiving treatment with brentuximab vedotin.

A 48-year-old man with Hodgkin lymphoma (HL) was diagnosed with PML after receiving the drug. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

After the third dose of brentuximab vedotin, the patient presented with left-sided weakness and slurred speech. Cerebrospinal fluid was positive for JC virus. The patient’s condition deteriorated rapidly, resulting in death within 4 weeks of symptom onset.

A 50-year-old man with HL was also diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents, targeted radiation therapy, and autologous stem cell transplant.

After 8 cycles of brentuximab vedotin, this patient presented to the local emergency room with complaints of changes in speech, difficulty writing with his right hand, and right lower extremity weakness. In addition, he had poor coordination, poor balance, and left-sided sensory deficits.

Although MRI results were inconclusive and cerebrospinal fluid analyses were negative for JC virus early in the course of the neurologic work-up, an immunostain of a spinal cord lesion biopsy was positive for JC virus.

The patient’s neurological condition continues to worsen. Most recently, he lost motor function of his lower extremities and deep tendon reflexes of his legs. He also has tremulousness of his hands and hypoactive arm reflexes.

Lastly, a 38-year-old female patient with a history of stage 4 cutaneous anaplastic large cell lymphoma was diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

Prior to treatment with brentuximab vedotin, a baseline neurological examination was normal. After the second dose, the patient complained of the inability to read, inability to find words to express herself, memory lapses, and slight loss of balance.

A brain MRI revealed a demyelinating process, and a brain biopsy was positive for JC virus. The patient’s treatment with brentuximab vedotin was discontinued.

Pulmonary toxicity risk

In addition to the risk of PML, research has revealed that brentuximab vedotin can confer a risk of pulmonary toxicity when combined with bleomycin.

A clinical trial compared the combination of brentuximab vedotin plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to combination brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD) as front-line therapy for HL.

An excessive number of patients in the brentuximab vedotin plus ABVD treatment group experienced noninfectious pulmonary toxicity. The frequency of pulmonary toxicity in this group was approximately 40%, compared to a frequency of 10% to 25% previously observed with bleomycin-based regimens not containing brentuximab vedotin.

Researchers observed no pulmonary toxicity in the brentuximab vedotin plus AVD treatment group.

Progressive multifocal
leukoencephalopathy

Two additional cases of progressive multifocal leukoencephalopathy (PML) have been reported with the lymphoma drug brentuximab vedotin (Adcetris), according to the US Food and Drug Administration (FDA).

So the agency has added a new boxed warning to the drug’s label highlighting the risk of PML. At the time of brentuximab vedotin’s approval in August 2011, only 1 case of PML was described in the warnings and precautions section of the label.

The label change also includes a contraindication warning against the use of brentuximab vedotin with bleomycin, as the combination appears to increase the risk of pulmonary toxicity.

Diagnosing PML

The FDA says healthcare professionals should consider a possible diagnosis of PML in any patient who is receiving or has received brentuximab vedotin and who presents with new signs or symptoms of central nervous system abnormalities.

Healthcare professionals should also instruct patients to report changes in mood or usual behavior, confusion, problems thinking, loss of memory, changes in walking or talking, decreased strength or weakness on one side of the body, or changes in vision.

Evaluation of PML may include consultation with a neurologist, a brain MRI, lumbar puncture with analysis of cerebrospinal fluid by polymerase chain reaction for John Cunningham (JC) virus, and/or a brain biopsy.

Healthcare professionals should hold brentuximab vedotin dosing for any suspected case of PML and discontinue brentuximab vedotin dosing if PML is confirmed.

PML case reports

To date, 3 patients have developed PML while receiving treatment with brentuximab vedotin.

A 48-year-old man with Hodgkin lymphoma (HL) was diagnosed with PML after receiving the drug. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

After the third dose of brentuximab vedotin, the patient presented with left-sided weakness and slurred speech. Cerebrospinal fluid was positive for JC virus. The patient’s condition deteriorated rapidly, resulting in death within 4 weeks of symptom onset.

A 50-year-old man with HL was also diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents, targeted radiation therapy, and autologous stem cell transplant.

After 8 cycles of brentuximab vedotin, this patient presented to the local emergency room with complaints of changes in speech, difficulty writing with his right hand, and right lower extremity weakness. In addition, he had poor coordination, poor balance, and left-sided sensory deficits.

Although MRI results were inconclusive and cerebrospinal fluid analyses were negative for JC virus early in the course of the neurologic work-up, an immunostain of a spinal cord lesion biopsy was positive for JC virus.

The patient’s neurological condition continues to worsen. Most recently, he lost motor function of his lower extremities and deep tendon reflexes of his legs. He also has tremulousness of his hands and hypoactive arm reflexes.

Lastly, a 38-year-old female patient with a history of stage 4 cutaneous anaplastic large cell lymphoma was diagnosed with PML after receiving brentuximab vedotin. The patient’s medical history included prior treatment with multiple chemotherapeutic agents and targeted radiation therapy.

Prior to treatment with brentuximab vedotin, a baseline neurological examination was normal. After the second dose, the patient complained of the inability to read, inability to find words to express herself, memory lapses, and slight loss of balance.

A brain MRI revealed a demyelinating process, and a brain biopsy was positive for JC virus. The patient’s treatment with brentuximab vedotin was discontinued.

Pulmonary toxicity risk

In addition to the risk of PML, research has revealed that brentuximab vedotin can confer a risk of pulmonary toxicity when combined with bleomycin.

A clinical trial compared the combination of brentuximab vedotin plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to combination brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (AVD) as front-line therapy for HL.

An excessive number of patients in the brentuximab vedotin plus ABVD treatment group experienced noninfectious pulmonary toxicity. The frequency of pulmonary toxicity in this group was approximately 40%, compared to a frequency of 10% to 25% previously observed with bleomycin-based regimens not containing brentuximab vedotin.

Researchers observed no pulmonary toxicity in the brentuximab vedotin plus AVD treatment group.

Hospitalizations for drowning dropped 51% between 1993 and 2008, according to the results of a study based on data from the Nationwide Inpatient Sample.

The number of hospitalizations fell from an estimated 3,623 in 1993 to 1,781 in 2008. During the same period, the estimated annual incidence rate of pediatric hospitalizations associated with drowning declined 57% – from 4.9 to 2.1 per 100,000, according to findings published online Jan. 16 in Pediatrics (2012;129:1-7).

"Our study provides national estimates of pediatric drowning hospitalizations that can be used as benchmarks to inform drowning prevention efforts and to help target interventions to high-risk areas. Given the significant burden of drowning in both real and human costs, additional monitoring of pediatric drowning is needed," wrote Stephen M. Bowman, Ph.D., of the center for injury research and policy at Johns Hopkins University in Baltimore, and his coinvestigators.

"This is an important finding that provides some evidence of a true decrease in drowning incidents."

The researchers used administrative discharge data from the 1993 to 2008 Nationwide Inpatient Sample (NIS). The NIS is created from state inpatient databases provided by public/private statewide data organizations from participating states. The NIS is the largest, longitudinal, all-payer inpatient care database in the United States, with an average of 8 million hospitalizations from approximately 1,000 hospitals each year, the researchers noted. The NIS approximates a 20% stratified random sample of all short-term U.S. community hospitals.

Eligibility for this study was limited to children and adolescents who were aged 0-19 years at admission and who were hospitalized with a primary or secondary ICD-9-CM diagnosis code for drowning injury. Patients who died while hospitalized were included.

The circumstances of drowning were determined based on the external cause of injury code when possible. The circumstances of drowning injury were categorized into five groups: recreational swimming and diving, drowning in bathtubs, other drowning activities, all other codes, and missing. For the incidence rate calculations, the investigators used U.S. Census estimates for the national civilian population at midyears during this time interval. External cause of injury codes were missing for up to 55% of hospitalizations before 1997. For this reason, the investigators compared 2-year aggregate data for the years 1998-1999 and 2007-2008 to evaluate changes in drowning mechanism and intent over time.

Drowning characteristics typically differ by age and sex. Young children (less than 4 years of age) have the greatest mortality rate from drowning and are more likely to drown while bathing or falling into water, the authors noted. Older children are more likely to drown while swimming in open water. In addition, males are four to six times more likely than females to experience a drowning injury, because of factors such as overestimation of swimming ability and greater use of alcohol by adolescent males, Dr. Bowman and his associates said.

The hospitalization rates declined significantly for all ages and for both sexes. However, the rate for males remained greater at each point in time. The total annual hospital days also declined from an estimated 14,570 days in 1993 to approximately 6,295 days in 2008. However no trend in mean hospital length of stay was observed.

"Consistent with decreases in pediatric drowning mortality, we observed a significant decline in the rate of pediatric drowning hospitalizations, primarily because of decreases in the South and West. This is an important finding that provides some evidence of a true decrease in drowning incidents, rather than a possible shift from fatal out-of-hospital drowning to nonfatal in-hospital cases," Dr. Bowman and his associates wrote. Hospitalization rates decreased significantly across all geographic regions of the United States, although the greatest decline in drowning hospitalization rates occurred in the South. The overall drowning rate fell from 7.5 hospitalizations per 100,000 in 1993-1994 to 3.5 per 100,000 in 2007-2008 in this region.

"Between 1998-1999 and 2007-2008, we observed a significant change in drowning hospitalization rates for selected ages and mechanisms," they wrote. Overall, there was a significant decline (40%) in bathtub-related drowning hospitalizations in children aged 0-4 years. Drowning hospitalizations due to swimming and diving decreased by nearly half in older children aged 10-14 years.

"Reductions in bathtub drowning hospitalizations among the youngest children may reflect a response to targeted injury prevention efforts that have been aimed at parents and caregivers of young children, encouraging increased vigilance in supervision.

"Interestingly, we did observe a decrease in the rate of in-hospital deaths over the 14-year period, although the in-hospital case fatality did not change significantly," the researchers noted. In-hospital mortality declined 42% from an estimated 359 deaths in 1993 to 207 deaths in 2008. "Although improvements in treatment might be having an impact on survival, it is not clear from these data what level of neurologic functioning survivors may have. An alternate explanation is that better decision making in the prehospital period may be resulting in more pronouncement of death in the field for unsurvivable cases."

The study was funded by the National Institutes of Health. Dr. Bowman and his associates reported that they have no relevant financial disclosures.

Hospitalizations for drowning dropped 51% between 1993 and 2008, according to the results of a study based on data from the Nationwide Inpatient Sample.

The number of hospitalizations fell from an estimated 3,623 in 1993 to 1,781 in 2008. During the same period, the estimated annual incidence rate of pediatric hospitalizations associated with drowning declined 57% – from 4.9 to 2.1 per 100,000, according to findings published online Jan. 16 in Pediatrics (2012;129:1-7).

"Our study provides national estimates of pediatric drowning hospitalizations that can be used as benchmarks to inform drowning prevention efforts and to help target interventions to high-risk areas. Given the significant burden of drowning in both real and human costs, additional monitoring of pediatric drowning is needed," wrote Stephen M. Bowman, Ph.D., of the center for injury research and policy at Johns Hopkins University in Baltimore, and his coinvestigators.

"This is an important finding that provides some evidence of a true decrease in drowning incidents."

The researchers used administrative discharge data from the 1993 to 2008 Nationwide Inpatient Sample (NIS). The NIS is created from state inpatient databases provided by public/private statewide data organizations from participating states. The NIS is the largest, longitudinal, all-payer inpatient care database in the United States, with an average of 8 million hospitalizations from approximately 1,000 hospitals each year, the researchers noted. The NIS approximates a 20% stratified random sample of all short-term U.S. community hospitals.

Eligibility for this study was limited to children and adolescents who were aged 0-19 years at admission and who were hospitalized with a primary or secondary ICD-9-CM diagnosis code for drowning injury. Patients who died while hospitalized were included.

The circumstances of drowning were determined based on the external cause of injury code when possible. The circumstances of drowning injury were categorized into five groups: recreational swimming and diving, drowning in bathtubs, other drowning activities, all other codes, and missing. For the incidence rate calculations, the investigators used U.S. Census estimates for the national civilian population at midyears during this time interval. External cause of injury codes were missing for up to 55% of hospitalizations before 1997. For this reason, the investigators compared 2-year aggregate data for the years 1998-1999 and 2007-2008 to evaluate changes in drowning mechanism and intent over time.

Drowning characteristics typically differ by age and sex. Young children (less than 4 years of age) have the greatest mortality rate from drowning and are more likely to drown while bathing or falling into water, the authors noted. Older children are more likely to drown while swimming in open water. In addition, males are four to six times more likely than females to experience a drowning injury, because of factors such as overestimation of swimming ability and greater use of alcohol by adolescent males, Dr. Bowman and his associates said.

The hospitalization rates declined significantly for all ages and for both sexes. However, the rate for males remained greater at each point in time. The total annual hospital days also declined from an estimated 14,570 days in 1993 to approximately 6,295 days in 2008. However no trend in mean hospital length of stay was observed.

"Consistent with decreases in pediatric drowning mortality, we observed a significant decline in the rate of pediatric drowning hospitalizations, primarily because of decreases in the South and West. This is an important finding that provides some evidence of a true decrease in drowning incidents, rather than a possible shift from fatal out-of-hospital drowning to nonfatal in-hospital cases," Dr. Bowman and his associates wrote. Hospitalization rates decreased significantly across all geographic regions of the United States, although the greatest decline in drowning hospitalization rates occurred in the South. The overall drowning rate fell from 7.5 hospitalizations per 100,000 in 1993-1994 to 3.5 per 100,000 in 2007-2008 in this region.

"Between 1998-1999 and 2007-2008, we observed a significant change in drowning hospitalization rates for selected ages and mechanisms," they wrote. Overall, there was a significant decline (40%) in bathtub-related drowning hospitalizations in children aged 0-4 years. Drowning hospitalizations due to swimming and diving decreased by nearly half in older children aged 10-14 years.

"Reductions in bathtub drowning hospitalizations among the youngest children may reflect a response to targeted injury prevention efforts that have been aimed at parents and caregivers of young children, encouraging increased vigilance in supervision.

"Interestingly, we did observe a decrease in the rate of in-hospital deaths over the 14-year period, although the in-hospital case fatality did not change significantly," the researchers noted. In-hospital mortality declined 42% from an estimated 359 deaths in 1993 to 207 deaths in 2008. "Although improvements in treatment might be having an impact on survival, it is not clear from these data what level of neurologic functioning survivors may have. An alternate explanation is that better decision making in the prehospital period may be resulting in more pronouncement of death in the field for unsurvivable cases."

The study was funded by the National Institutes of Health. Dr. Bowman and his associates reported that they have no relevant financial disclosures.

Hospitalizations for drowning dropped 51% between 1993 and 2008, according to the results of a study based on data from the Nationwide Inpatient Sample.

The number of hospitalizations fell from an estimated 3,623 in 1993 to 1,781 in 2008. During the same period, the estimated annual incidence rate of pediatric hospitalizations associated with drowning declined 57% – from 4.9 to 2.1 per 100,000, according to findings published online Jan. 16 in Pediatrics (2012;129:1-7).

"Our study provides national estimates of pediatric drowning hospitalizations that can be used as benchmarks to inform drowning prevention efforts and to help target interventions to high-risk areas. Given the significant burden of drowning in both real and human costs, additional monitoring of pediatric drowning is needed," wrote Stephen M. Bowman, Ph.D., of the center for injury research and policy at Johns Hopkins University in Baltimore, and his coinvestigators.

"This is an important finding that provides some evidence of a true decrease in drowning incidents."

The researchers used administrative discharge data from the 1993 to 2008 Nationwide Inpatient Sample (NIS). The NIS is created from state inpatient databases provided by public/private statewide data organizations from participating states. The NIS is the largest, longitudinal, all-payer inpatient care database in the United States, with an average of 8 million hospitalizations from approximately 1,000 hospitals each year, the researchers noted. The NIS approximates a 20% stratified random sample of all short-term U.S. community hospitals.

Eligibility for this study was limited to children and adolescents who were aged 0-19 years at admission and who were hospitalized with a primary or secondary ICD-9-CM diagnosis code for drowning injury. Patients who died while hospitalized were included.

The circumstances of drowning were determined based on the external cause of injury code when possible. The circumstances of drowning injury were categorized into five groups: recreational swimming and diving, drowning in bathtubs, other drowning activities, all other codes, and missing. For the incidence rate calculations, the investigators used U.S. Census estimates for the national civilian population at midyears during this time interval. External cause of injury codes were missing for up to 55% of hospitalizations before 1997. For this reason, the investigators compared 2-year aggregate data for the years 1998-1999 and 2007-2008 to evaluate changes in drowning mechanism and intent over time.

Drowning characteristics typically differ by age and sex. Young children (less than 4 years of age) have the greatest mortality rate from drowning and are more likely to drown while bathing or falling into water, the authors noted. Older children are more likely to drown while swimming in open water. In addition, males are four to six times more likely than females to experience a drowning injury, because of factors such as overestimation of swimming ability and greater use of alcohol by adolescent males, Dr. Bowman and his associates said.

The hospitalization rates declined significantly for all ages and for both sexes. However, the rate for males remained greater at each point in time. The total annual hospital days also declined from an estimated 14,570 days in 1993 to approximately 6,295 days in 2008. However no trend in mean hospital length of stay was observed.

"Consistent with decreases in pediatric drowning mortality, we observed a significant decline in the rate of pediatric drowning hospitalizations, primarily because of decreases in the South and West. This is an important finding that provides some evidence of a true decrease in drowning incidents, rather than a possible shift from fatal out-of-hospital drowning to nonfatal in-hospital cases," Dr. Bowman and his associates wrote. Hospitalization rates decreased significantly across all geographic regions of the United States, although the greatest decline in drowning hospitalization rates occurred in the South. The overall drowning rate fell from 7.5 hospitalizations per 100,000 in 1993-1994 to 3.5 per 100,000 in 2007-2008 in this region.

"Between 1998-1999 and 2007-2008, we observed a significant change in drowning hospitalization rates for selected ages and mechanisms," they wrote. Overall, there was a significant decline (40%) in bathtub-related drowning hospitalizations in children aged 0-4 years. Drowning hospitalizations due to swimming and diving decreased by nearly half in older children aged 10-14 years.

"Reductions in bathtub drowning hospitalizations among the youngest children may reflect a response to targeted injury prevention efforts that have been aimed at parents and caregivers of young children, encouraging increased vigilance in supervision.

"Interestingly, we did observe a decrease in the rate of in-hospital deaths over the 14-year period, although the in-hospital case fatality did not change significantly," the researchers noted. In-hospital mortality declined 42% from an estimated 359 deaths in 1993 to 207 deaths in 2008. "Although improvements in treatment might be having an impact on survival, it is not clear from these data what level of neurologic functioning survivors may have. An alternate explanation is that better decision making in the prehospital period may be resulting in more pronouncement of death in the field for unsurvivable cases."

The study was funded by the National Institutes of Health. Dr. Bowman and his associates reported that they have no relevant financial disclosures.

Background Little is known about the impact of myelodysplastic syndromes (MDS) on the quality of life (QoL) of those living with the disease. 

Objectives To explore the impact of MDS on the quality of life of those living with the disease.

Methods Seventy patients with MDS participated in five focus groups conducted throughout the United States. Transcripts from recordings of focus group sessions were coded and emerging themes identified using thematic analysis.

Results Findings revealed a multifaceted description of how MDS affects QoL. MDS was found to cause a substantial and sustained decrease in ability to function. QoL was adversely affected by work expended on managing the disease. The emotional impact was often viewed as more problematic than the physical impact; emotional reactions included shock, anger, depression, and anxiety. In contrast, spiritual well-being was often enhanced, with a renewed appreciation for life, relationships, and faith.

Limitations The method of subject recruitment may have limited participation to individuals who are more proactive in obtaining information about their illness. The focus groups convened only once, thus purposive sampling and repeated assessments were not possible.

Conclusions MDS has a substantial, often negative impact on patients' lives and clinicians should be cognizant of this impact. Attention must be directed at providing more comprehensive support for the patient throughout the illness trajectory.

Click on the PDF icon at the top of this introduction to read the full article.

Background Little is known about the impact of myelodysplastic syndromes (MDS) on the quality of life (QoL) of those living with the disease. 

Objectives To explore the impact of MDS on the quality of life of those living with the disease.

Methods Seventy patients with MDS participated in five focus groups conducted throughout the United States. Transcripts from recordings of focus group sessions were coded and emerging themes identified using thematic analysis.

Results Findings revealed a multifaceted description of how MDS affects QoL. MDS was found to cause a substantial and sustained decrease in ability to function. QoL was adversely affected by work expended on managing the disease. The emotional impact was often viewed as more problematic than the physical impact; emotional reactions included shock, anger, depression, and anxiety. In contrast, spiritual well-being was often enhanced, with a renewed appreciation for life, relationships, and faith.

Limitations The method of subject recruitment may have limited participation to individuals who are more proactive in obtaining information about their illness. The focus groups convened only once, thus purposive sampling and repeated assessments were not possible.

Conclusions MDS has a substantial, often negative impact on patients' lives and clinicians should be cognizant of this impact. Attention must be directed at providing more comprehensive support for the patient throughout the illness trajectory.

Click on the PDF icon at the top of this introduction to read the full article.

Background Little is known about the impact of myelodysplastic syndromes (MDS) on the quality of life (QoL) of those living with the disease. 

Objectives To explore the impact of MDS on the quality of life of those living with the disease.

Methods Seventy patients with MDS participated in five focus groups conducted throughout the United States. Transcripts from recordings of focus group sessions were coded and emerging themes identified using thematic analysis.

Results Findings revealed a multifaceted description of how MDS affects QoL. MDS was found to cause a substantial and sustained decrease in ability to function. QoL was adversely affected by work expended on managing the disease. The emotional impact was often viewed as more problematic than the physical impact; emotional reactions included shock, anger, depression, and anxiety. In contrast, spiritual well-being was often enhanced, with a renewed appreciation for life, relationships, and faith.

Limitations The method of subject recruitment may have limited participation to individuals who are more proactive in obtaining information about their illness. The focus groups convened only once, thus purposive sampling and repeated assessments were not possible.

Conclusions MDS has a substantial, often negative impact on patients' lives and clinicians should be cognizant of this impact. Attention must be directed at providing more comprehensive support for the patient throughout the illness trajectory.

Click on the PDF icon at the top of this introduction to read the full article.

Determinants of Physical Activity in Palliative Cancer Patients: An Application of the Theory of Planned Behavior

• Sonya S. Lowe, MD, MSc
  
  ^,

  

  ,
• Sharon M. Watanabe, MD,
• Vickie E. Baracos, PhD,
• Kerry S. Courneya, PhD

• Department of Symptom Control and Palliative Care, The Division of Palliative Care Medicine, Department of Oncology, and the Faculty of Physical Education and Recreation, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada

• Received 23 March 2011. Accepted 29 July 2011. Available online 12 October 2011.

• http://dx.doi.org/10.1016/j.suponc.2011.07.005, How to Cite or Link Using DOI

• Permissions & Reprints

Determinants of Physical Activity in Palliative Cancer Patients: An Application of the Theory of Planned Behavior

• Sonya S. Lowe, MD, MSc
  
  ^,

  

  ,
• Sharon M. Watanabe, MD,
• Vickie E. Baracos, PhD,
• Kerry S. Courneya, PhD

• Department of Symptom Control and Palliative Care, The Division of Palliative Care Medicine, Department of Oncology, and the Faculty of Physical Education and Recreation, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada

• Received 23 March 2011. Accepted 29 July 2011. Available online 12 October 2011.

• http://dx.doi.org/10.1016/j.suponc.2011.07.005, How to Cite or Link Using DOI

• Permissions & Reprints

Determinants of Physical Activity in Palliative Cancer Patients: An Application of the Theory of Planned Behavior

• Sonya S. Lowe, MD, MSc
  
  ^,

  

  ,
• Sharon M. Watanabe, MD,
• Vickie E. Baracos, PhD,
• Kerry S. Courneya, PhD

• Department of Symptom Control and Palliative Care, The Division of Palliative Care Medicine, Department of Oncology, and the Faculty of Physical Education and Recreation, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada

• Received 23 March 2011. Accepted 29 July 2011. Available online 12 October 2011.

• http://dx.doi.org/10.1016/j.suponc.2011.07.005, How to Cite or Link Using DOI

• Permissions & Reprints

Managing Side Effects of Tyrosine Kinase Inhibitor Therapy to Optimize Adherence in Patients with Chronic Myeloid Leukemia: The Role of the Midlevel Practitioner

• Megan Cornelison, MS, PA-C ,
• Elias J. Jabbour, MD ,
• Mary Alma Welch, MS, PA-C^,

  

• Received 2 May 2011. Accepted 5 August 2011. Available online 11 January 2012.

• http://dx.doi.org/10.1016/j.suponc.2011.08.001

• Permissions & Reprints

  ABSTRACT

  In the last decade, the development of imatinib, a tyrosine kinase inhibitor, has brought about unprecedented change in the way newly diagnosed, chronic-phase chronic myeloid leukemia patients are treated. Two next-generation tyrosine kinase inhibitors, nilotinib and dasatinib, were initially indicated for imatinib-resistant or imatinib-intolerant chronic myeloid leukemia patients and recently received approval from the Food and Drug Administration for treatment of newly diagnosed, chronic-phase chronic myeloid leukemia patients. In comparison with the previous standards of care, benefits with these three tyrosine kinase inhibitors have included more rapid response rates, increased survival, and fewer side effects. The improved long-term outcomes have altered the approach to management of chronic myeloid leukemia from a progressive fatal disease with a poor prognosis to a chronic condition similar to diabetes or hypertension. Prolonged survival increases the need for patient education, support, monitoring, and assistance with adverse event management. Even low-grade side effects can adversely affect patients' quality of life and, therefore, require prompt attention to prevent long-term complications or suboptimal outcomes. New evidence has indicated that patient adherence to tyrosine kinase inhibitor therapy is essential to successful treatment. Midlevel practitioners can help to optimize outcomes by educating patients regarding the importance of adherence, performing regular monitoring, helping patients to understand their test results, and aggressively managing treatment-related side effects.

Managing Side Effects of Tyrosine Kinase Inhibitor Therapy to Optimize Adherence in Patients with Chronic Myeloid Leukemia: The Role of the Midlevel Practitioner

• Megan Cornelison, MS, PA-C ,
• Elias J. Jabbour, MD ,
• Mary Alma Welch, MS, PA-C^,

  

• Received 2 May 2011. Accepted 5 August 2011. Available online 11 January 2012.

• http://dx.doi.org/10.1016/j.suponc.2011.08.001

• Permissions & Reprints

  ABSTRACT

  In the last decade, the development of imatinib, a tyrosine kinase inhibitor, has brought about unprecedented change in the way newly diagnosed, chronic-phase chronic myeloid leukemia patients are treated. Two next-generation tyrosine kinase inhibitors, nilotinib and dasatinib, were initially indicated for imatinib-resistant or imatinib-intolerant chronic myeloid leukemia patients and recently received approval from the Food and Drug Administration for treatment of newly diagnosed, chronic-phase chronic myeloid leukemia patients. In comparison with the previous standards of care, benefits with these three tyrosine kinase inhibitors have included more rapid response rates, increased survival, and fewer side effects. The improved long-term outcomes have altered the approach to management of chronic myeloid leukemia from a progressive fatal disease with a poor prognosis to a chronic condition similar to diabetes or hypertension. Prolonged survival increases the need for patient education, support, monitoring, and assistance with adverse event management. Even low-grade side effects can adversely affect patients' quality of life and, therefore, require prompt attention to prevent long-term complications or suboptimal outcomes. New evidence has indicated that patient adherence to tyrosine kinase inhibitor therapy is essential to successful treatment. Midlevel practitioners can help to optimize outcomes by educating patients regarding the importance of adherence, performing regular monitoring, helping patients to understand their test results, and aggressively managing treatment-related side effects.

Managing Side Effects of Tyrosine Kinase Inhibitor Therapy to Optimize Adherence in Patients with Chronic Myeloid Leukemia: The Role of the Midlevel Practitioner

• Megan Cornelison, MS, PA-C ,
• Elias J. Jabbour, MD ,
• Mary Alma Welch, MS, PA-C^,

  

• Received 2 May 2011. Accepted 5 August 2011. Available online 11 January 2012.

• http://dx.doi.org/10.1016/j.suponc.2011.08.001

• Permissions & Reprints

  ABSTRACT

  In the last decade, the development of imatinib, a tyrosine kinase inhibitor, has brought about unprecedented change in the way newly diagnosed, chronic-phase chronic myeloid leukemia patients are treated. Two next-generation tyrosine kinase inhibitors, nilotinib and dasatinib, were initially indicated for imatinib-resistant or imatinib-intolerant chronic myeloid leukemia patients and recently received approval from the Food and Drug Administration for treatment of newly diagnosed, chronic-phase chronic myeloid leukemia patients. In comparison with the previous standards of care, benefits with these three tyrosine kinase inhibitors have included more rapid response rates, increased survival, and fewer side effects. The improved long-term outcomes have altered the approach to management of chronic myeloid leukemia from a progressive fatal disease with a poor prognosis to a chronic condition similar to diabetes or hypertension. Prolonged survival increases the need for patient education, support, monitoring, and assistance with adverse event management. Even low-grade side effects can adversely affect patients' quality of life and, therefore, require prompt attention to prevent long-term complications or suboptimal outcomes. New evidence has indicated that patient adherence to tyrosine kinase inhibitor therapy is essential to successful treatment. Midlevel practitioners can help to optimize outcomes by educating patients regarding the importance of adherence, performing regular monitoring, helping patients to understand their test results, and aggressively managing treatment-related side effects.

SAN DIEGO – Despite growing use of chemotherapy in elderly patients with acute myeloid leukemia, more than half still did not receive any chemotherapy between 1997 and 2007, according to an analysis of 6,888 cases in a large national database.

Median survival was significantly longer in patients who received chemotherapy than in those given best supportive care only, Yanni F. Yu reported at the annual meeting of the American Society of Hematology. In all, 56% of elderly acute myeloid leukemia (AML) patients did not receive chemotherapy, however, and median survival as well as chemotherapy use declined with advancing age.

"Older patient with AML generally have a poor outcome," said Ms. Yu, manager of health economics and outcomes research at Boehringer Ingelheim Pharmaceuticals. "If they are not eligible for intensive chemotherapy, the median survival is usually less than 3 months," she noted.

Previous studies in the elderly AML population showed that the percentage of chemotherapy treatment increased from 29% in 1991 to 38% in 1999, Ms. Yu said. To determine more current treatment trends in this patient population, she and her associates evaluated data from Medicare patients aged 65 years and older who had a new AML diagnosis between Jan. 1, 1997, and Dec. 31, 2007, recorded in the Surveillance, Epidemiology, and End Results (SEER) cancer registry.

The analysis was limited to fee-for-service Medicare patients who had at least 6 months of pre-AML Medicare Part A and B benefit coverage. The researchers excluded patients who had evidence of another tumor in the SEER registry before the first AML diagnosis and those who had a diagnosis of a solid tumor within 6 months pre-AML in Medicare claims.

Eligible patients were followed from initial AML diagnosis until their date of death or the end of the observation period, which was Dec. 31, 2009.

The researchers evaluated the type of care received, chemotherapy treatment patterns, and mortality and patient survival separately for AML cases diagnosed in three time frames: 1997-1999, 2000-2003, and 2004-2007. They performed multivariate logistic regression to assess predictors of receipt of chemotherapy, including patient demographics, comorbidities, and year of AML diagnosis.

A total of 6,888 patients met the study criteria. Their mean age was 78 years, 48% were women, 88% were white, and 43% received chemotherapy at any point after diagnosis. The use of chemotherapy increased slightly over time, from 40.7% in 1999-2000 to 42.3% in 2000-2003 and 46% in 2004-2007.

More than half of patients (56%) received only best supportive care post diagnosis, although the percentage decreased slightly over time. Among patients receiving best supportive care, rates of hospice care increased from 30.3% in 1997-1999 to 36.4% in 2000-2003 and 42.3% in 2004-2007.

Among patients who received chemotherapy, the use of antibiotics increased substantially over the three time periods (11.1%, 14%, and 29.6%, respectively), as did the use of antifungals (1.3%, 3.1%, and 12.4%), indicating more patients were in need of prophylaxis or treatment for chemotherapy-related infections.

Older AML patients received strikingly less chemotherapy with advancing age. For example, 66.3% of patients aged 65-74 years received chemotherapy, compared with 39.2% of those aged 75-84 years and 14.8% of those aged 85 years and older. The proportions of patients receiving antibiotics and antifungals also decreased with advancing age.

Regression analysis showed a similar association between age and chemotherapy, revealing that the strongest predictor of not receiving chemotherapy was older age, with an odds ratio of 0.12 for being aged 85 years or more and an OR of 0.42 for being aged 75-84 years.

The overall 30-day mortality rate was 20.5%, and the 60-day mortality rate was 42.8%. Median survival among all patients was 2.6 months, and it decreased with advancing age from 4.5 months to 2.4 months to 1.6 months for those aged 65-74 years, 75-84 years, and 85 years and older, respectively.

Furthermore, although nearly all patients had died during follow-up, median survival was much longer in patients receiving chemotherapy than in those receiving best supportive care only. This was true across all age groups, with 8.0 vs. 1.5 months reported in those aged 65-74 years, 5.3 vs. 1.7 months in those 75-84 years, and 3.8 vs. 1.4 months in those 85 years and older.

Ms. Yu acknowledged certain limitations of the study, including the fact that results may not be applicable to younger patients or to those covered by a managed care Medicaid plan.

In addition, "Medicare Part D information was not included since information on prescription claims was available only after 2007," she said. "Also, no information was available on the chemotherapy agents or the doses received in the inpatient or outpatient settings. Patient performance status was also unavailable."

She said that further studies are warranted "to investigate the potential benefit of chemotherapy treatment for elderly patients with AML."

The study was sponsored by Boehringer Ingelheim Pharmaceuticals. Ms. Yu disclosed that she is a full-time employee of the company.

SAN DIEGO – Despite growing use of chemotherapy in elderly patients with acute myeloid leukemia, more than half still did not receive any chemotherapy between 1997 and 2007, according to an analysis of 6,888 cases in a large national database.

Median survival was significantly longer in patients who received chemotherapy than in those given best supportive care only, Yanni F. Yu reported at the annual meeting of the American Society of Hematology. In all, 56% of elderly acute myeloid leukemia (AML) patients did not receive chemotherapy, however, and median survival as well as chemotherapy use declined with advancing age.

"Older patient with AML generally have a poor outcome," said Ms. Yu, manager of health economics and outcomes research at Boehringer Ingelheim Pharmaceuticals. "If they are not eligible for intensive chemotherapy, the median survival is usually less than 3 months," she noted.

Previous studies in the elderly AML population showed that the percentage of chemotherapy treatment increased from 29% in 1991 to 38% in 1999, Ms. Yu said. To determine more current treatment trends in this patient population, she and her associates evaluated data from Medicare patients aged 65 years and older who had a new AML diagnosis between Jan. 1, 1997, and Dec. 31, 2007, recorded in the Surveillance, Epidemiology, and End Results (SEER) cancer registry.

The analysis was limited to fee-for-service Medicare patients who had at least 6 months of pre-AML Medicare Part A and B benefit coverage. The researchers excluded patients who had evidence of another tumor in the SEER registry before the first AML diagnosis and those who had a diagnosis of a solid tumor within 6 months pre-AML in Medicare claims.

Eligible patients were followed from initial AML diagnosis until their date of death or the end of the observation period, which was Dec. 31, 2009.

The researchers evaluated the type of care received, chemotherapy treatment patterns, and mortality and patient survival separately for AML cases diagnosed in three time frames: 1997-1999, 2000-2003, and 2004-2007. They performed multivariate logistic regression to assess predictors of receipt of chemotherapy, including patient demographics, comorbidities, and year of AML diagnosis.

A total of 6,888 patients met the study criteria. Their mean age was 78 years, 48% were women, 88% were white, and 43% received chemotherapy at any point after diagnosis. The use of chemotherapy increased slightly over time, from 40.7% in 1999-2000 to 42.3% in 2000-2003 and 46% in 2004-2007.

More than half of patients (56%) received only best supportive care post diagnosis, although the percentage decreased slightly over time. Among patients receiving best supportive care, rates of hospice care increased from 30.3% in 1997-1999 to 36.4% in 2000-2003 and 42.3% in 2004-2007.

Among patients who received chemotherapy, the use of antibiotics increased substantially over the three time periods (11.1%, 14%, and 29.6%, respectively), as did the use of antifungals (1.3%, 3.1%, and 12.4%), indicating more patients were in need of prophylaxis or treatment for chemotherapy-related infections.

Older AML patients received strikingly less chemotherapy with advancing age. For example, 66.3% of patients aged 65-74 years received chemotherapy, compared with 39.2% of those aged 75-84 years and 14.8% of those aged 85 years and older. The proportions of patients receiving antibiotics and antifungals also decreased with advancing age.

Regression analysis showed a similar association between age and chemotherapy, revealing that the strongest predictor of not receiving chemotherapy was older age, with an odds ratio of 0.12 for being aged 85 years or more and an OR of 0.42 for being aged 75-84 years.

The overall 30-day mortality rate was 20.5%, and the 60-day mortality rate was 42.8%. Median survival among all patients was 2.6 months, and it decreased with advancing age from 4.5 months to 2.4 months to 1.6 months for those aged 65-74 years, 75-84 years, and 85 years and older, respectively.

Furthermore, although nearly all patients had died during follow-up, median survival was much longer in patients receiving chemotherapy than in those receiving best supportive care only. This was true across all age groups, with 8.0 vs. 1.5 months reported in those aged 65-74 years, 5.3 vs. 1.7 months in those 75-84 years, and 3.8 vs. 1.4 months in those 85 years and older.

Ms. Yu acknowledged certain limitations of the study, including the fact that results may not be applicable to younger patients or to those covered by a managed care Medicaid plan.

In addition, "Medicare Part D information was not included since information on prescription claims was available only after 2007," she said. "Also, no information was available on the chemotherapy agents or the doses received in the inpatient or outpatient settings. Patient performance status was also unavailable."

She said that further studies are warranted "to investigate the potential benefit of chemotherapy treatment for elderly patients with AML."

The study was sponsored by Boehringer Ingelheim Pharmaceuticals. Ms. Yu disclosed that she is a full-time employee of the company.

SAN DIEGO – Despite growing use of chemotherapy in elderly patients with acute myeloid leukemia, more than half still did not receive any chemotherapy between 1997 and 2007, according to an analysis of 6,888 cases in a large national database.

Median survival was significantly longer in patients who received chemotherapy than in those given best supportive care only, Yanni F. Yu reported at the annual meeting of the American Society of Hematology. In all, 56% of elderly acute myeloid leukemia (AML) patients did not receive chemotherapy, however, and median survival as well as chemotherapy use declined with advancing age.

"Older patient with AML generally have a poor outcome," said Ms. Yu, manager of health economics and outcomes research at Boehringer Ingelheim Pharmaceuticals. "If they are not eligible for intensive chemotherapy, the median survival is usually less than 3 months," she noted.

Previous studies in the elderly AML population showed that the percentage of chemotherapy treatment increased from 29% in 1991 to 38% in 1999, Ms. Yu said. To determine more current treatment trends in this patient population, she and her associates evaluated data from Medicare patients aged 65 years and older who had a new AML diagnosis between Jan. 1, 1997, and Dec. 31, 2007, recorded in the Surveillance, Epidemiology, and End Results (SEER) cancer registry.

The analysis was limited to fee-for-service Medicare patients who had at least 6 months of pre-AML Medicare Part A and B benefit coverage. The researchers excluded patients who had evidence of another tumor in the SEER registry before the first AML diagnosis and those who had a diagnosis of a solid tumor within 6 months pre-AML in Medicare claims.

Eligible patients were followed from initial AML diagnosis until their date of death or the end of the observation period, which was Dec. 31, 2009.

The researchers evaluated the type of care received, chemotherapy treatment patterns, and mortality and patient survival separately for AML cases diagnosed in three time frames: 1997-1999, 2000-2003, and 2004-2007. They performed multivariate logistic regression to assess predictors of receipt of chemotherapy, including patient demographics, comorbidities, and year of AML diagnosis.

A total of 6,888 patients met the study criteria. Their mean age was 78 years, 48% were women, 88% were white, and 43% received chemotherapy at any point after diagnosis. The use of chemotherapy increased slightly over time, from 40.7% in 1999-2000 to 42.3% in 2000-2003 and 46% in 2004-2007.

More than half of patients (56%) received only best supportive care post diagnosis, although the percentage decreased slightly over time. Among patients receiving best supportive care, rates of hospice care increased from 30.3% in 1997-1999 to 36.4% in 2000-2003 and 42.3% in 2004-2007.

Among patients who received chemotherapy, the use of antibiotics increased substantially over the three time periods (11.1%, 14%, and 29.6%, respectively), as did the use of antifungals (1.3%, 3.1%, and 12.4%), indicating more patients were in need of prophylaxis or treatment for chemotherapy-related infections.

Older AML patients received strikingly less chemotherapy with advancing age. For example, 66.3% of patients aged 65-74 years received chemotherapy, compared with 39.2% of those aged 75-84 years and 14.8% of those aged 85 years and older. The proportions of patients receiving antibiotics and antifungals also decreased with advancing age.

Regression analysis showed a similar association between age and chemotherapy, revealing that the strongest predictor of not receiving chemotherapy was older age, with an odds ratio of 0.12 for being aged 85 years or more and an OR of 0.42 for being aged 75-84 years.

The overall 30-day mortality rate was 20.5%, and the 60-day mortality rate was 42.8%. Median survival among all patients was 2.6 months, and it decreased with advancing age from 4.5 months to 2.4 months to 1.6 months for those aged 65-74 years, 75-84 years, and 85 years and older, respectively.

Furthermore, although nearly all patients had died during follow-up, median survival was much longer in patients receiving chemotherapy than in those receiving best supportive care only. This was true across all age groups, with 8.0 vs. 1.5 months reported in those aged 65-74 years, 5.3 vs. 1.7 months in those 75-84 years, and 3.8 vs. 1.4 months in those 85 years and older.

Ms. Yu acknowledged certain limitations of the study, including the fact that results may not be applicable to younger patients or to those covered by a managed care Medicaid plan.

In addition, "Medicare Part D information was not included since information on prescription claims was available only after 2007," she said. "Also, no information was available on the chemotherapy agents or the doses received in the inpatient or outpatient settings. Patient performance status was also unavailable."

She said that further studies are warranted "to investigate the potential benefit of chemotherapy treatment for elderly patients with AML."

The study was sponsored by Boehringer Ingelheim Pharmaceuticals. Ms. Yu disclosed that she is a full-time employee of the company.

While researchers and policymakers are making progress in finding ways to prevent and diagnose diabetes, physicians can take small steps every day in their offices to help their patients. A diabetes-themed event, held by journal Health Affairs, focused on some of the recent findings, and we spoke with a few of the leaders in the field, including the U.S. Surgeon General, Dr. Regina Benjamin.

While researchers and policymakers are making progress in finding ways to prevent and diagnose diabetes, physicians can take small steps every day in their offices to help their patients. A diabetes-themed event, held by journal Health Affairs, focused on some of the recent findings, and we spoke with a few of the leaders in the field, including the U.S. Surgeon General, Dr. Regina Benjamin.

While researchers and policymakers are making progress in finding ways to prevent and diagnose diabetes, physicians can take small steps every day in their offices to help their patients. A diabetes-themed event, held by journal Health Affairs, focused on some of the recent findings, and we spoke with a few of the leaders in the field, including the U.S. Surgeon General, Dr. Regina Benjamin.

SAN DIEGO – Novel genetic alterations have been identified in a new subtype of high-risk B-cell acute lymphoblastic leukemia that could be effectively targeted with existing therapies.

The subtype, termed Ph-like ALL, was first identified by the Children’s Oncology Group in 2009 (N. Engl. J. Med. 2009;360:470-80), and accounts for up to 15% of pediatric acute lymphoblastic leukemia (ALL) cases.

"Until this study, the genetic basis of Ph-like ALL was unknown," said Kathryn G. Roberts, Ph.D., lead author of the cooperative research study.

Ph-like ALL is associated with alteration of lymphoid transcription factors, most commonly IKZF1, and has a gene expression profile similar to that of Philadelphia chromosome–positive (Ph+) ALL. Ph+ ALL accounts for just 5% of pediatric ALL cases, but because it is driven by the oncogenic tyrosine kinase, BCR-ABL1, it can be effectively treated with available tyrosine kinase inhibitors such as imatinib (Gleevec).

Ph-like ALL, however, is BCR-ABL negative, so patients with this poor-outcome subtype are currently treated with conventional chemotherapy. Higher doses and intensified regimens are limited by toxicity.

Screening ALL patients at the time of diagnosis could identify those with Ph-like ALL, and determine who may benefit from more-aggressive treatment with targeted therapies, said Dr. Roberts, a postdoctoral pathology fellow at St. Jude Children’s Research Hospital in Memphis, Tenn.

In an effort to better understand the genetic basis of Ph-like ALL, the investigators used next-generation genome sequencing and other techniques to analyze the transcriptome or RNA sequence of 12 patients with Ph-like ALL. Strikingly, 11 of the 12 cases harbored alterations disrupting kinase and cytokine receptor signaling, which provides a treatable target with current drugs, she said. The alterations included novel rearrangements, structural variations, and sequence mutations.

Specifically, the spectrum of alterations included NUP214-ABL1 or RANBP2-ABL1 rearrangements, immunoglobulin heavy chain rearrangements involving the cytokine receptor genes CRLF2 and EPOR, and in-frame fusions of EBF1-PDGFRB (platelet-derived growth factor receptor beta), BCR-JAK2 or STRN3-JAK2. In addition, activating mutations within IL7R, and loss of function SH2B3 deletions were also identified.

Importantly, laboratory studies showed that patient samples harboring the ABL1 rearrangement were sensitive to the tyrosine kinase inhibitors imatinib, dasatinib (Sprycel), and XL228, whereas the JAK2-rearranged samples were sensitive to the JAK2 inhibitors XL019 and ruxolitinib (Jakafi), which was recently approved for the treatment of myelofibrosis. Furthermore, mouse cells harboring the EBF1-PDGFRB fusion responded to imatinib, dasatinib, and dovitinib, a specific PDGFRB/FGFR (fibroblast growth factor receptor) inhibitor, Dr. Roberts reported.

The group also screened 231 additional high-risk ALL patients (aged 1 year 2 months to 17 years 6 months) and found that the genetic alterations were present in 40 cases (17%), suggesting that these genetic lesions are "hallmarks of this subtype of ALL," she said.

Dr. Martin Tallman, chief of the leukemia service at Memorial Sloan-Kettering Cancer Center in New York, told reporters at a press briefing that the study could potentially change the standard of care, and "provides further evidence that we’re able to target specific leukemias with specific, directed therapy rather than continuing to give relatively indiscriminate chemotherapy."

The diversity of lesions in Ph-like ALL suggests that screening methods to identify patients at diagnosis may be more attractive than transcriptome sequencing, Dr. Roberts noted. Phosphoflow cytometric signaling analysis can be used to detect activation of pathways common to the novel genetic lesions and to identify patients who will most likely respond to targeted therapy. Gene expression profiling is also being investigated as a complimentary approach to identify Ph-like ALL patients.

St. Jude is currently not screening its ALL patients for Ph-like ALL, but the researchers hope to be able to start treating children who have ALL based on their genetic alterations in the next 12 months, she said in an interview.

The researchers are also currently establishing Ph-like ALL animal models and plan to broaden the scope of their testing to include young adolescents and adults. The current study earned the outstanding abstract achievement award for a postdoctoral fellow at the meeting.

Dr. Roberts reported no conflicts of interest. A coauthor, Dr. Steve Hunger, reported that his children own stock in Bristol-Myers Squibb and that he is a member of an entity’s board of directors or advisory committee.

SAN DIEGO – Novel genetic alterations have been identified in a new subtype of high-risk B-cell acute lymphoblastic leukemia that could be effectively targeted with existing therapies.

The subtype, termed Ph-like ALL, was first identified by the Children’s Oncology Group in 2009 (N. Engl. J. Med. 2009;360:470-80), and accounts for up to 15% of pediatric acute lymphoblastic leukemia (ALL) cases.

"Until this study, the genetic basis of Ph-like ALL was unknown," said Kathryn G. Roberts, Ph.D., lead author of the cooperative research study.

Ph-like ALL is associated with alteration of lymphoid transcription factors, most commonly IKZF1, and has a gene expression profile similar to that of Philadelphia chromosome–positive (Ph+) ALL. Ph+ ALL accounts for just 5% of pediatric ALL cases, but because it is driven by the oncogenic tyrosine kinase, BCR-ABL1, it can be effectively treated with available tyrosine kinase inhibitors such as imatinib (Gleevec).

Ph-like ALL, however, is BCR-ABL negative, so patients with this poor-outcome subtype are currently treated with conventional chemotherapy. Higher doses and intensified regimens are limited by toxicity.

Screening ALL patients at the time of diagnosis could identify those with Ph-like ALL, and determine who may benefit from more-aggressive treatment with targeted therapies, said Dr. Roberts, a postdoctoral pathology fellow at St. Jude Children’s Research Hospital in Memphis, Tenn.

In an effort to better understand the genetic basis of Ph-like ALL, the investigators used next-generation genome sequencing and other techniques to analyze the transcriptome or RNA sequence of 12 patients with Ph-like ALL. Strikingly, 11 of the 12 cases harbored alterations disrupting kinase and cytokine receptor signaling, which provides a treatable target with current drugs, she said. The alterations included novel rearrangements, structural variations, and sequence mutations.

Specifically, the spectrum of alterations included NUP214-ABL1 or RANBP2-ABL1 rearrangements, immunoglobulin heavy chain rearrangements involving the cytokine receptor genes CRLF2 and EPOR, and in-frame fusions of EBF1-PDGFRB (platelet-derived growth factor receptor beta), BCR-JAK2 or STRN3-JAK2. In addition, activating mutations within IL7R, and loss of function SH2B3 deletions were also identified.

Importantly, laboratory studies showed that patient samples harboring the ABL1 rearrangement were sensitive to the tyrosine kinase inhibitors imatinib, dasatinib (Sprycel), and XL228, whereas the JAK2-rearranged samples were sensitive to the JAK2 inhibitors XL019 and ruxolitinib (Jakafi), which was recently approved for the treatment of myelofibrosis. Furthermore, mouse cells harboring the EBF1-PDGFRB fusion responded to imatinib, dasatinib, and dovitinib, a specific PDGFRB/FGFR (fibroblast growth factor receptor) inhibitor, Dr. Roberts reported.

The group also screened 231 additional high-risk ALL patients (aged 1 year 2 months to 17 years 6 months) and found that the genetic alterations were present in 40 cases (17%), suggesting that these genetic lesions are "hallmarks of this subtype of ALL," she said.

Dr. Martin Tallman, chief of the leukemia service at Memorial Sloan-Kettering Cancer Center in New York, told reporters at a press briefing that the study could potentially change the standard of care, and "provides further evidence that we’re able to target specific leukemias with specific, directed therapy rather than continuing to give relatively indiscriminate chemotherapy."

The diversity of lesions in Ph-like ALL suggests that screening methods to identify patients at diagnosis may be more attractive than transcriptome sequencing, Dr. Roberts noted. Phosphoflow cytometric signaling analysis can be used to detect activation of pathways common to the novel genetic lesions and to identify patients who will most likely respond to targeted therapy. Gene expression profiling is also being investigated as a complimentary approach to identify Ph-like ALL patients.

St. Jude is currently not screening its ALL patients for Ph-like ALL, but the researchers hope to be able to start treating children who have ALL based on their genetic alterations in the next 12 months, she said in an interview.

The researchers are also currently establishing Ph-like ALL animal models and plan to broaden the scope of their testing to include young adolescents and adults. The current study earned the outstanding abstract achievement award for a postdoctoral fellow at the meeting.

Dr. Roberts reported no conflicts of interest. A coauthor, Dr. Steve Hunger, reported that his children own stock in Bristol-Myers Squibb and that he is a member of an entity’s board of directors or advisory committee.

SAN DIEGO – Novel genetic alterations have been identified in a new subtype of high-risk B-cell acute lymphoblastic leukemia that could be effectively targeted with existing therapies.

The subtype, termed Ph-like ALL, was first identified by the Children’s Oncology Group in 2009 (N. Engl. J. Med. 2009;360:470-80), and accounts for up to 15% of pediatric acute lymphoblastic leukemia (ALL) cases.

"Until this study, the genetic basis of Ph-like ALL was unknown," said Kathryn G. Roberts, Ph.D., lead author of the cooperative research study.

Ph-like ALL is associated with alteration of lymphoid transcription factors, most commonly IKZF1, and has a gene expression profile similar to that of Philadelphia chromosome–positive (Ph+) ALL. Ph+ ALL accounts for just 5% of pediatric ALL cases, but because it is driven by the oncogenic tyrosine kinase, BCR-ABL1, it can be effectively treated with available tyrosine kinase inhibitors such as imatinib (Gleevec).

Ph-like ALL, however, is BCR-ABL negative, so patients with this poor-outcome subtype are currently treated with conventional chemotherapy. Higher doses and intensified regimens are limited by toxicity.

Screening ALL patients at the time of diagnosis could identify those with Ph-like ALL, and determine who may benefit from more-aggressive treatment with targeted therapies, said Dr. Roberts, a postdoctoral pathology fellow at St. Jude Children’s Research Hospital in Memphis, Tenn.

In an effort to better understand the genetic basis of Ph-like ALL, the investigators used next-generation genome sequencing and other techniques to analyze the transcriptome or RNA sequence of 12 patients with Ph-like ALL. Strikingly, 11 of the 12 cases harbored alterations disrupting kinase and cytokine receptor signaling, which provides a treatable target with current drugs, she said. The alterations included novel rearrangements, structural variations, and sequence mutations.

Specifically, the spectrum of alterations included NUP214-ABL1 or RANBP2-ABL1 rearrangements, immunoglobulin heavy chain rearrangements involving the cytokine receptor genes CRLF2 and EPOR, and in-frame fusions of EBF1-PDGFRB (platelet-derived growth factor receptor beta), BCR-JAK2 or STRN3-JAK2. In addition, activating mutations within IL7R, and loss of function SH2B3 deletions were also identified.

Importantly, laboratory studies showed that patient samples harboring the ABL1 rearrangement were sensitive to the tyrosine kinase inhibitors imatinib, dasatinib (Sprycel), and XL228, whereas the JAK2-rearranged samples were sensitive to the JAK2 inhibitors XL019 and ruxolitinib (Jakafi), which was recently approved for the treatment of myelofibrosis. Furthermore, mouse cells harboring the EBF1-PDGFRB fusion responded to imatinib, dasatinib, and dovitinib, a specific PDGFRB/FGFR (fibroblast growth factor receptor) inhibitor, Dr. Roberts reported.

The group also screened 231 additional high-risk ALL patients (aged 1 year 2 months to 17 years 6 months) and found that the genetic alterations were present in 40 cases (17%), suggesting that these genetic lesions are "hallmarks of this subtype of ALL," she said.

Dr. Martin Tallman, chief of the leukemia service at Memorial Sloan-Kettering Cancer Center in New York, told reporters at a press briefing that the study could potentially change the standard of care, and "provides further evidence that we’re able to target specific leukemias with specific, directed therapy rather than continuing to give relatively indiscriminate chemotherapy."

The diversity of lesions in Ph-like ALL suggests that screening methods to identify patients at diagnosis may be more attractive than transcriptome sequencing, Dr. Roberts noted. Phosphoflow cytometric signaling analysis can be used to detect activation of pathways common to the novel genetic lesions and to identify patients who will most likely respond to targeted therapy. Gene expression profiling is also being investigated as a complimentary approach to identify Ph-like ALL patients.

St. Jude is currently not screening its ALL patients for Ph-like ALL, but the researchers hope to be able to start treating children who have ALL based on their genetic alterations in the next 12 months, she said in an interview.

The researchers are also currently establishing Ph-like ALL animal models and plan to broaden the scope of their testing to include young adolescents and adults. The current study earned the outstanding abstract achievement award for a postdoctoral fellow at the meeting.

Dr. Roberts reported no conflicts of interest. A coauthor, Dr. Steve Hunger, reported that his children own stock in Bristol-Myers Squibb and that he is a member of an entity’s board of directors or advisory committee.

Hospitalists should consider the arena of antimicrobial stewardship one of the newest frontiers of clinical efficiency and cost savings, according to the author of a study in a supplement to this month's Journal of Hospital Medicine.

David Rosenberg, MD, MPH, FACP, SFHM, of the Department of Medicine, Section of Hospital Medicine at North Shore University Hospital in Manhasset, N.Y., says that changing the mindset on antibiotic resistance might seem like a daunting task, but it dovetails neatly with HM's current focus on quality and safety, particularly when it can help reduce length of stay (LOS).

"Think different about antibiotics and build that into your practice," he says.

The supplement highlights four related papers tackling the issues of appropriate initiation and selection of antibiotics, antimicrobial de-escalation strategies, duration and cessation of treatment, and Dr. Rosenberg's paper, "The Emerging Role of Hospitalists." The research includes an online CME component.

Dr. Rosenberg writes that hospitalists "are positioned as excellent champions of the principles and practices of antimicrobial stewardship." That means revamping the use of antibiotics both for individual patients and on an institutional level. That leadership means accepting that "culture change is slow" and physicians often feel "trapped" in letting an antibiotic treatment run its course rather than reassessing midstream.

Still, Dr. Rosenberg says, national guidelines on antibiotic overuse are likely to be developed in the coming years, and hospitalists would do well to get ahead of that curve.

"We're talking about the optimal treatment of patients we are already taking care of," he says. "Stewardship is a natural step forward."

Hospitalists should consider the arena of antimicrobial stewardship one of the newest frontiers of clinical efficiency and cost savings, according to the author of a study in a supplement to this month's Journal of Hospital Medicine.

David Rosenberg, MD, MPH, FACP, SFHM, of the Department of Medicine, Section of Hospital Medicine at North Shore University Hospital in Manhasset, N.Y., says that changing the mindset on antibiotic resistance might seem like a daunting task, but it dovetails neatly with HM's current focus on quality and safety, particularly when it can help reduce length of stay (LOS).

"Think different about antibiotics and build that into your practice," he says.

The supplement highlights four related papers tackling the issues of appropriate initiation and selection of antibiotics, antimicrobial de-escalation strategies, duration and cessation of treatment, and Dr. Rosenberg's paper, "The Emerging Role of Hospitalists." The research includes an online CME component.

Dr. Rosenberg writes that hospitalists "are positioned as excellent champions of the principles and practices of antimicrobial stewardship." That means revamping the use of antibiotics both for individual patients and on an institutional level. That leadership means accepting that "culture change is slow" and physicians often feel "trapped" in letting an antibiotic treatment run its course rather than reassessing midstream.

Still, Dr. Rosenberg says, national guidelines on antibiotic overuse are likely to be developed in the coming years, and hospitalists would do well to get ahead of that curve.

"We're talking about the optimal treatment of patients we are already taking care of," he says. "Stewardship is a natural step forward."

Hospitalists should consider the arena of antimicrobial stewardship one of the newest frontiers of clinical efficiency and cost savings, according to the author of a study in a supplement to this month's Journal of Hospital Medicine.

David Rosenberg, MD, MPH, FACP, SFHM, of the Department of Medicine, Section of Hospital Medicine at North Shore University Hospital in Manhasset, N.Y., says that changing the mindset on antibiotic resistance might seem like a daunting task, but it dovetails neatly with HM's current focus on quality and safety, particularly when it can help reduce length of stay (LOS).

"Think different about antibiotics and build that into your practice," he says.

The supplement highlights four related papers tackling the issues of appropriate initiation and selection of antibiotics, antimicrobial de-escalation strategies, duration and cessation of treatment, and Dr. Rosenberg's paper, "The Emerging Role of Hospitalists." The research includes an online CME component.

Dr. Rosenberg writes that hospitalists "are positioned as excellent champions of the principles and practices of antimicrobial stewardship." That means revamping the use of antibiotics both for individual patients and on an institutional level. That leadership means accepting that "culture change is slow" and physicians often feel "trapped" in letting an antibiotic treatment run its course rather than reassessing midstream.

Still, Dr. Rosenberg says, national guidelines on antibiotic overuse are likely to be developed in the coming years, and hospitalists would do well to get ahead of that curve.

"We're talking about the optimal treatment of patients we are already taking care of," he says. "Stewardship is a natural step forward."

Clinical question: What is the association between time to clinical stability (TCS) and post-discharge death or readmission in patients hospitalized with community-acquired pneumonia (CAP)?

Background: In patients with CAP, inflammatory response during hospitalization might be associated with adverse outcomes after discharge. Studies have not evaluated if time to clinical stability, a reflection of inflammatory response, can be used to identify patients at high risk of adverse outcomes after discharge.

Study design: Retrospective cohort study.

Setting: Veterans Hospital, Louisville, Ky.

Synopsis: Of 464 hospitalized patients with CAP, those with TCS >3 days had a higher rate of readmission or death within 30 days after discharge compared with those who had a TCS =3 days (26% versus 15%; OR 1.98; 95% CI, 1.19-3.3; P=0.008). Longer TCS during hospitalization was associated with a significantly increased risk of adverse outcomes (adjusted OR 1.06, 1.54, 2.40, 10.53 if TCS was reached at days 2, 3, 4, 5 versus Day 1, respectively). The authors proposed that patients with delays in reaching clinical stability should receive a special discharge management approach to decrease the risk of morbidity and mortality after discharge; this may include close observation, home visits, and a follow-up clinic appointment within 10 days.

As a retrospective cohort study, unaccounted-for confounders might exist between TCS and adverse outcomes. The small sample size precluded development of a fully predictive model. Additionally, the population studied was elderly men in a single hospital, which might limit generalizability.

Bottom line: Hospitalized patients with community-acquired pneumonia whose time to clinical stability was greater than three days had a higher risk of readmission or death within 30 days after discharge.

Citation: Aliberti S, Peyrani P, Filardo G, et al. Association between time to clinical stability and outcomes after discharge in hospitalized patients with community-acquired pneumonia. Chest. 2011;140:482-488.

For more physician reviews of HM-relevant research, visit our website.

Clinical question: What is the association between time to clinical stability (TCS) and post-discharge death or readmission in patients hospitalized with community-acquired pneumonia (CAP)?

Background: In patients with CAP, inflammatory response during hospitalization might be associated with adverse outcomes after discharge. Studies have not evaluated if time to clinical stability, a reflection of inflammatory response, can be used to identify patients at high risk of adverse outcomes after discharge.

Study design: Retrospective cohort study.

Setting: Veterans Hospital, Louisville, Ky.

Synopsis: Of 464 hospitalized patients with CAP, those with TCS >3 days had a higher rate of readmission or death within 30 days after discharge compared with those who had a TCS =3 days (26% versus 15%; OR 1.98; 95% CI, 1.19-3.3; P=0.008). Longer TCS during hospitalization was associated with a significantly increased risk of adverse outcomes (adjusted OR 1.06, 1.54, 2.40, 10.53 if TCS was reached at days 2, 3, 4, 5 versus Day 1, respectively). The authors proposed that patients with delays in reaching clinical stability should receive a special discharge management approach to decrease the risk of morbidity and mortality after discharge; this may include close observation, home visits, and a follow-up clinic appointment within 10 days.

As a retrospective cohort study, unaccounted-for confounders might exist between TCS and adverse outcomes. The small sample size precluded development of a fully predictive model. Additionally, the population studied was elderly men in a single hospital, which might limit generalizability.

Bottom line: Hospitalized patients with community-acquired pneumonia whose time to clinical stability was greater than three days had a higher risk of readmission or death within 30 days after discharge.

Citation: Aliberti S, Peyrani P, Filardo G, et al. Association between time to clinical stability and outcomes after discharge in hospitalized patients with community-acquired pneumonia. Chest. 2011;140:482-488.

For more physician reviews of HM-relevant research, visit our website.

Clinical question: What is the association between time to clinical stability (TCS) and post-discharge death or readmission in patients hospitalized with community-acquired pneumonia (CAP)?

Background: In patients with CAP, inflammatory response during hospitalization might be associated with adverse outcomes after discharge. Studies have not evaluated if time to clinical stability, a reflection of inflammatory response, can be used to identify patients at high risk of adverse outcomes after discharge.

Study design: Retrospective cohort study.

Setting: Veterans Hospital, Louisville, Ky.

Synopsis: Of 464 hospitalized patients with CAP, those with TCS >3 days had a higher rate of readmission or death within 30 days after discharge compared with those who had a TCS =3 days (26% versus 15%; OR 1.98; 95% CI, 1.19-3.3; P=0.008). Longer TCS during hospitalization was associated with a significantly increased risk of adverse outcomes (adjusted OR 1.06, 1.54, 2.40, 10.53 if TCS was reached at days 2, 3, 4, 5 versus Day 1, respectively). The authors proposed that patients with delays in reaching clinical stability should receive a special discharge management approach to decrease the risk of morbidity and mortality after discharge; this may include close observation, home visits, and a follow-up clinic appointment within 10 days.

As a retrospective cohort study, unaccounted-for confounders might exist between TCS and adverse outcomes. The small sample size precluded development of a fully predictive model. Additionally, the population studied was elderly men in a single hospital, which might limit generalizability.

Bottom line: Hospitalized patients with community-acquired pneumonia whose time to clinical stability was greater than three days had a higher risk of readmission or death within 30 days after discharge.

Citation: Aliberti S, Peyrani P, Filardo G, et al. Association between time to clinical stability and outcomes after discharge in hospitalized patients with community-acquired pneumonia. Chest. 2011;140:482-488.

For more physician reviews of HM-relevant research, visit our website.