The Centers for Disease Control and Prevention offers a helpful patient handout about hepatitis C. “Hepatitis C: Information on testing and diagnosis,” which is available at http://www.cdc.gov/hepatitis/HCV/PDFs/HepCTesting-Diagnosis.pdf, explains how hepatitis C is spread, who should get tested for it, why it is important to get tested, and how test results are interpreted.

The Centers for Disease Control and Prevention offers a helpful patient handout about hepatitis C. “Hepatitis C: Information on testing and diagnosis,” which is available at http://www.cdc.gov/hepatitis/HCV/PDFs/HepCTesting-Diagnosis.pdf, explains how hepatitis C is spread, who should get tested for it, why it is important to get tested, and how test results are interpreted.

The Centers for Disease Control and Prevention offers a helpful patient handout about hepatitis C. “Hepatitis C: Information on testing and diagnosis,” which is available at http://www.cdc.gov/hepatitis/HCV/PDFs/HepCTesting-Diagnosis.pdf, explains how hepatitis C is spread, who should get tested for it, why it is important to get tested, and how test results are interpreted.

Chronic disease burden increases the risk of mild cognitive impairment (MCI), but certain lifestyle factors reduce the risk of MCI in people ages 85 and older, according to a study published online ahead of print April 8 in Neurology. Participants in the population-based prospective study were evaluated at baseline and at 15 monthly intervals to determine incident MCI. At baseline, lifestyle factors in midlife and late life were assessed, and vascular and comorbid conditions were abstracted from participants’ medical records. The risk of MCI was increased for participants with APOE ε4 allele or current depressive symptoms. The risk of MCI was reduced for participants who reported engagement in artistic, craft, and social activities in both midlife and late life, and those who reported the use of a computer in late life.

A new blood test may identify biomarkers for Parkinson’s disease more accurately than before, according to a study published online ahead of print March 18 in Movement Disorders. Researchers used a digital gene expression platform to quantify 175 mRNA markers with low coefficients of variation. They compared whole-blood transcript levels in mouse models overexpressing wild-type LRRK2, overexpressing G2019S LRRK2, lacking LRRK2, and wild-type controls. The investigators then studied a cohort of 34 symptomatic patients with Parkinson’s disease and 32 asymptomatic controls. The expression profiles distinguished the four mouse groups with different genetic backgrounds. Significant differences in blood transcript levels were found between individuals differing in LRRK2 genotype and between patients with Parkinson’s disease and controls. Thus, whole-blood mRNA signatures may correlate with LRRK2 genotype and Parkinson’s disease state.

There is a relationship between Alzheimer’s disease-related white matter alterations and impaired cognitive-motor control, according to a study published January 1 in Journal of Alzheimer’s Disease. Using diffusion-weighted MRI, researchers examined changes in white matter integrity associated with normal aging and increased Alzheimer’s disease risk, and assessed the relationship between these white matter alterations and cognitive-motor performance. The investigators found significant age-related declines in white matter integrity, which were more widespread in patients at high risk of Alzheimer’s disease, compared with those at low risk. Furthermore, an analysis of mean diffusivity measures within isolated white matter clusters revealed a stepwise decline in white matter integrity across young, low Alzheimer’s disease risk, and high Alzheimer’s disease risk groups. Investigators also observed that lower white matter integrity was associated with poorer cognitive-motor performance.

Researchers have developed mild cognitive impairment (MCI) risk scores using variables that are easily assessable in the clinical setting and that may be useful in routine patient care, according to a study published April 7 in Neurology. Investigators randomly selected people between ages 70 and 89 on October 1, 2004, for a population-based sample in a longitudinal cohort study. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychologic measures and were classified as cognitively normal, having MCI, or having dementia. Of 1,449 cognitively normal participants, 401 developed MCI. Both men and women in the highest versus lowest sex-specific quartiles of the augmented model’s risk scores had an approximately sevenfold higher risk of developing MCI. The presence of APOE ε4 carrier status improved the model.

The progression of dysfunctional tau protein may be the primary cause of cognitive decline and memory loss in Alzheimer’s disease, according to a study published online ahead of print March 23 in Brain. Researchers evaluated the correspondence of Thal amyloid phase to Braak tangle stage and ante mortem clinical characteristics in a large autopsy cohort. In the brain bank cohort of patients with a high likelihood of Alzheimer’s disease, samples with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE ε4 positive. Regression modeling in these samples with Alzheimer’s disease showed that Braak tangle stage, but not Thal amyloid phase, predicted age at onset, disease duration, and final Mini-Mental State Examination score.

A panel of blood biomarkers distinguishes accurately between patients with isolated concussion and uninjured individuals within the first eight hours after an accident, according to a study published online ahead of print in March 20 in Journal of Neurotrauma. Adult patients were enrolled in a study within 24 hours of concussion. Controls included uninjured people and patients with orthopedic injury. The investigators identified copeptin, galectin 3, matrix metalloproteinase 9, and occludin as biomarkers of concussion. A 3.4-fold decrease in plasma concentration of copeptin was found in patients with mild traumatic brain injury (mTBI) within eight hours after accident, compared with uninjured controls. Plasma levels of all biomarkers but copeptin increased by 3.6 to 4.5 times during the same time postinjury. The levels of at least two biomarkers were altered beyond their cutoff values in 90% of patients with mTBI.

Exploding head syndrome is relatively common in younger individuals, according to a study published online ahead of print March 13 in Journal of Sleep Research. Researchers assessed 211 undergraduate students for exploding head syndrome and isolated sleep paralysis using semistructured diagnostic interviews. A total of 18% of the sample population had exploding head syndrome during their lifetimes, and 16.60% of the population had recurrent cases of the syndrome. Exploding head syndrome affected both genders at equal rates, and investigators found it in 36.89% of participants who had been diagnosed with isolated sleep paralysis. Furthermore, exploding head syndrome episodes were accompanied by clinically significant levels of fear. For a minority of participants (2.80%), the fear was associated with clinically significant distress or impairment.

A distinctive pattern of abnormal protein deposits in the brain could help identify athletes with brain disorders, according to a study published online ahead of print April 6 in Proceedings of the National Academy of Science. Investigators used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in 14 retired professional football players with suspected chronic traumatic encephalopathy and compared results with those of 28 cognitively intact controls and 24 patients with Alzheimer’s dementia. The [F-18]FDDNP PET imaging results in retired players suggested the presence of the neuropathologic patterns consistent with models of concussion in which brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical regions that support mood, emotions, and behavior. The pattern was distinct from that observed in Alzheimer’s disease.

A blood test could help identify women with fragile X syndrome who are at risk of dysexecutive and social anxiety symptoms, according to a study published online ahead of print March 25 in Neurology. Thirty-five women with FMR1 premutation between ages 22 and 55 and 35 age- and IQ-matched controls completed a range of executive function tests and self-reported symptoms of psychiatric disorders. The researchers found that FMR1 intron 1 methylation levels could help dichotomize women with the premutation into categories of greater and lesser risk. FMR1 intron 1 methylation and activation ratio were significantly correlated with the likelihood of probable dysexecutive or psychiatric symptoms. The significant relationships between methylation and social anxiety were mediated by executive function performance, but only in women with the premutation.

Targeted temperature management at 33 °C or 36 °C helps maintain good quality of life in patients with cardiac arrest, according to a study published online ahead of print April 6 in JAMA Neurology. Investigators studied 939 unconscious adults with cardiac arrest at 36 intensive care units. Patients were assigned to temperature management at 33 °C or 36 °C for 36 hours. Cognitive function was measured by Mini-Mental State Examination (MMSE). The median MMSE score was 14 for patients assigned to 33 °C and 17 for patients assigned to 36 °C. Approximately 19% of the 33 °C group and 18% of the 36 °C group reported needing help with everyday activities, and 66.5% in the 33 °C group versus 61.8% in the 36 °C group reported making a complete mental recovery.

Biracial population eligibility for r-tPA is similar by gender, according to a study published in the March issue of Stroke. The study included 1,837 patients with ischemic stroke who were age 18 or older and presented to 16 emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association and European Cooperative Acute Stroke Study III guidelines. The mean age was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex, and adjusting the data for age did not alter this result. More women than men had severe hypertension, and the investigators found no gender differences in blood pressure treatment rates among patients with severe hypertension. More women were older than 80 and had an NIH Stroke Scale score greater than 25.

The brains of patients with traumatic brain injury (TBI) may appear to be older than their chronological age, according to a study published in the April issue of Annals of Neurology. A predictive model of normal aging was defined using machine learning in 1,537 healthy individuals, based on MRI-derived estimates of gray matter and white matter. Investigators used this aging model to estimate brain age for 99 patients with TBI and 113 healthy controls. Brains with TBI were estimated to be older, with a mean predicted age difference between chronological and estimated brain age of 4.66 years for gray matter and 5.97 years for white matter. The predicted age difference correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase.

A combination of mental practice and physical therapy may help stroke survivors regain the strength of their motor behaviors, according to a study published March 30 in Frontiers in Human Neuroscience. The researchers recorded fMRI signals from 17 young healthy controls and 13 older stroke survivors. Participants with stroke underwent mental practice or both mental practice and physical therapy within 14 to 51 days following stroke. Investigators discovered that network activity was in the frequency range of 0.06 to 0.08 Hz for all brain regions studied and for controls and participants with stroke. Information flow between brain regions was reduced significantly for stroke survivors. The flow did not increase significantly after mental practice alone, but the flow among the regions during mental practice and physical therapy increased significantly.

—Kimberly Williams

Chronic disease burden increases the risk of mild cognitive impairment (MCI), but certain lifestyle factors reduce the risk of MCI in people ages 85 and older, according to a study published online ahead of print April 8 in Neurology. Participants in the population-based prospective study were evaluated at baseline and at 15 monthly intervals to determine incident MCI. At baseline, lifestyle factors in midlife and late life were assessed, and vascular and comorbid conditions were abstracted from participants’ medical records. The risk of MCI was increased for participants with APOE ε4 allele or current depressive symptoms. The risk of MCI was reduced for participants who reported engagement in artistic, craft, and social activities in both midlife and late life, and those who reported the use of a computer in late life.

A new blood test may identify biomarkers for Parkinson’s disease more accurately than before, according to a study published online ahead of print March 18 in Movement Disorders. Researchers used a digital gene expression platform to quantify 175 mRNA markers with low coefficients of variation. They compared whole-blood transcript levels in mouse models overexpressing wild-type LRRK2, overexpressing G2019S LRRK2, lacking LRRK2, and wild-type controls. The investigators then studied a cohort of 34 symptomatic patients with Parkinson’s disease and 32 asymptomatic controls. The expression profiles distinguished the four mouse groups with different genetic backgrounds. Significant differences in blood transcript levels were found between individuals differing in LRRK2 genotype and between patients with Parkinson’s disease and controls. Thus, whole-blood mRNA signatures may correlate with LRRK2 genotype and Parkinson’s disease state.

There is a relationship between Alzheimer’s disease-related white matter alterations and impaired cognitive-motor control, according to a study published January 1 in Journal of Alzheimer’s Disease. Using diffusion-weighted MRI, researchers examined changes in white matter integrity associated with normal aging and increased Alzheimer’s disease risk, and assessed the relationship between these white matter alterations and cognitive-motor performance. The investigators found significant age-related declines in white matter integrity, which were more widespread in patients at high risk of Alzheimer’s disease, compared with those at low risk. Furthermore, an analysis of mean diffusivity measures within isolated white matter clusters revealed a stepwise decline in white matter integrity across young, low Alzheimer’s disease risk, and high Alzheimer’s disease risk groups. Investigators also observed that lower white matter integrity was associated with poorer cognitive-motor performance.

Researchers have developed mild cognitive impairment (MCI) risk scores using variables that are easily assessable in the clinical setting and that may be useful in routine patient care, according to a study published April 7 in Neurology. Investigators randomly selected people between ages 70 and 89 on October 1, 2004, for a population-based sample in a longitudinal cohort study. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychologic measures and were classified as cognitively normal, having MCI, or having dementia. Of 1,449 cognitively normal participants, 401 developed MCI. Both men and women in the highest versus lowest sex-specific quartiles of the augmented model’s risk scores had an approximately sevenfold higher risk of developing MCI. The presence of APOE ε4 carrier status improved the model.

The progression of dysfunctional tau protein may be the primary cause of cognitive decline and memory loss in Alzheimer’s disease, according to a study published online ahead of print March 23 in Brain. Researchers evaluated the correspondence of Thal amyloid phase to Braak tangle stage and ante mortem clinical characteristics in a large autopsy cohort. In the brain bank cohort of patients with a high likelihood of Alzheimer’s disease, samples with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE ε4 positive. Regression modeling in these samples with Alzheimer’s disease showed that Braak tangle stage, but not Thal amyloid phase, predicted age at onset, disease duration, and final Mini-Mental State Examination score.

A panel of blood biomarkers distinguishes accurately between patients with isolated concussion and uninjured individuals within the first eight hours after an accident, according to a study published online ahead of print in March 20 in Journal of Neurotrauma. Adult patients were enrolled in a study within 24 hours of concussion. Controls included uninjured people and patients with orthopedic injury. The investigators identified copeptin, galectin 3, matrix metalloproteinase 9, and occludin as biomarkers of concussion. A 3.4-fold decrease in plasma concentration of copeptin was found in patients with mild traumatic brain injury (mTBI) within eight hours after accident, compared with uninjured controls. Plasma levels of all biomarkers but copeptin increased by 3.6 to 4.5 times during the same time postinjury. The levels of at least two biomarkers were altered beyond their cutoff values in 90% of patients with mTBI.

Exploding head syndrome is relatively common in younger individuals, according to a study published online ahead of print March 13 in Journal of Sleep Research. Researchers assessed 211 undergraduate students for exploding head syndrome and isolated sleep paralysis using semistructured diagnostic interviews. A total of 18% of the sample population had exploding head syndrome during their lifetimes, and 16.60% of the population had recurrent cases of the syndrome. Exploding head syndrome affected both genders at equal rates, and investigators found it in 36.89% of participants who had been diagnosed with isolated sleep paralysis. Furthermore, exploding head syndrome episodes were accompanied by clinically significant levels of fear. For a minority of participants (2.80%), the fear was associated with clinically significant distress or impairment.

A distinctive pattern of abnormal protein deposits in the brain could help identify athletes with brain disorders, according to a study published online ahead of print April 6 in Proceedings of the National Academy of Science. Investigators used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in 14 retired professional football players with suspected chronic traumatic encephalopathy and compared results with those of 28 cognitively intact controls and 24 patients with Alzheimer’s dementia. The [F-18]FDDNP PET imaging results in retired players suggested the presence of the neuropathologic patterns consistent with models of concussion in which brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical regions that support mood, emotions, and behavior. The pattern was distinct from that observed in Alzheimer’s disease.

A blood test could help identify women with fragile X syndrome who are at risk of dysexecutive and social anxiety symptoms, according to a study published online ahead of print March 25 in Neurology. Thirty-five women with FMR1 premutation between ages 22 and 55 and 35 age- and IQ-matched controls completed a range of executive function tests and self-reported symptoms of psychiatric disorders. The researchers found that FMR1 intron 1 methylation levels could help dichotomize women with the premutation into categories of greater and lesser risk. FMR1 intron 1 methylation and activation ratio were significantly correlated with the likelihood of probable dysexecutive or psychiatric symptoms. The significant relationships between methylation and social anxiety were mediated by executive function performance, but only in women with the premutation.

Targeted temperature management at 33 °C or 36 °C helps maintain good quality of life in patients with cardiac arrest, according to a study published online ahead of print April 6 in JAMA Neurology. Investigators studied 939 unconscious adults with cardiac arrest at 36 intensive care units. Patients were assigned to temperature management at 33 °C or 36 °C for 36 hours. Cognitive function was measured by Mini-Mental State Examination (MMSE). The median MMSE score was 14 for patients assigned to 33 °C and 17 for patients assigned to 36 °C. Approximately 19% of the 33 °C group and 18% of the 36 °C group reported needing help with everyday activities, and 66.5% in the 33 °C group versus 61.8% in the 36 °C group reported making a complete mental recovery.

Biracial population eligibility for r-tPA is similar by gender, according to a study published in the March issue of Stroke. The study included 1,837 patients with ischemic stroke who were age 18 or older and presented to 16 emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association and European Cooperative Acute Stroke Study III guidelines. The mean age was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex, and adjusting the data for age did not alter this result. More women than men had severe hypertension, and the investigators found no gender differences in blood pressure treatment rates among patients with severe hypertension. More women were older than 80 and had an NIH Stroke Scale score greater than 25.

The brains of patients with traumatic brain injury (TBI) may appear to be older than their chronological age, according to a study published in the April issue of Annals of Neurology. A predictive model of normal aging was defined using machine learning in 1,537 healthy individuals, based on MRI-derived estimates of gray matter and white matter. Investigators used this aging model to estimate brain age for 99 patients with TBI and 113 healthy controls. Brains with TBI were estimated to be older, with a mean predicted age difference between chronological and estimated brain age of 4.66 years for gray matter and 5.97 years for white matter. The predicted age difference correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase.

A combination of mental practice and physical therapy may help stroke survivors regain the strength of their motor behaviors, according to a study published March 30 in Frontiers in Human Neuroscience. The researchers recorded fMRI signals from 17 young healthy controls and 13 older stroke survivors. Participants with stroke underwent mental practice or both mental practice and physical therapy within 14 to 51 days following stroke. Investigators discovered that network activity was in the frequency range of 0.06 to 0.08 Hz for all brain regions studied and for controls and participants with stroke. Information flow between brain regions was reduced significantly for stroke survivors. The flow did not increase significantly after mental practice alone, but the flow among the regions during mental practice and physical therapy increased significantly.

—Kimberly Williams

Chronic disease burden increases the risk of mild cognitive impairment (MCI), but certain lifestyle factors reduce the risk of MCI in people ages 85 and older, according to a study published online ahead of print April 8 in Neurology. Participants in the population-based prospective study were evaluated at baseline and at 15 monthly intervals to determine incident MCI. At baseline, lifestyle factors in midlife and late life were assessed, and vascular and comorbid conditions were abstracted from participants’ medical records. The risk of MCI was increased for participants with APOE ε4 allele or current depressive symptoms. The risk of MCI was reduced for participants who reported engagement in artistic, craft, and social activities in both midlife and late life, and those who reported the use of a computer in late life.

A new blood test may identify biomarkers for Parkinson’s disease more accurately than before, according to a study published online ahead of print March 18 in Movement Disorders. Researchers used a digital gene expression platform to quantify 175 mRNA markers with low coefficients of variation. They compared whole-blood transcript levels in mouse models overexpressing wild-type LRRK2, overexpressing G2019S LRRK2, lacking LRRK2, and wild-type controls. The investigators then studied a cohort of 34 symptomatic patients with Parkinson’s disease and 32 asymptomatic controls. The expression profiles distinguished the four mouse groups with different genetic backgrounds. Significant differences in blood transcript levels were found between individuals differing in LRRK2 genotype and between patients with Parkinson’s disease and controls. Thus, whole-blood mRNA signatures may correlate with LRRK2 genotype and Parkinson’s disease state.

There is a relationship between Alzheimer’s disease-related white matter alterations and impaired cognitive-motor control, according to a study published January 1 in Journal of Alzheimer’s Disease. Using diffusion-weighted MRI, researchers examined changes in white matter integrity associated with normal aging and increased Alzheimer’s disease risk, and assessed the relationship between these white matter alterations and cognitive-motor performance. The investigators found significant age-related declines in white matter integrity, which were more widespread in patients at high risk of Alzheimer’s disease, compared with those at low risk. Furthermore, an analysis of mean diffusivity measures within isolated white matter clusters revealed a stepwise decline in white matter integrity across young, low Alzheimer’s disease risk, and high Alzheimer’s disease risk groups. Investigators also observed that lower white matter integrity was associated with poorer cognitive-motor performance.

Researchers have developed mild cognitive impairment (MCI) risk scores using variables that are easily assessable in the clinical setting and that may be useful in routine patient care, according to a study published April 7 in Neurology. Investigators randomly selected people between ages 70 and 89 on October 1, 2004, for a population-based sample in a longitudinal cohort study. At baseline and subsequent visits, participants were evaluated for demographic, clinical, and neuropsychologic measures and were classified as cognitively normal, having MCI, or having dementia. Of 1,449 cognitively normal participants, 401 developed MCI. Both men and women in the highest versus lowest sex-specific quartiles of the augmented model’s risk scores had an approximately sevenfold higher risk of developing MCI. The presence of APOE ε4 carrier status improved the model.

The progression of dysfunctional tau protein may be the primary cause of cognitive decline and memory loss in Alzheimer’s disease, according to a study published online ahead of print March 23 in Brain. Researchers evaluated the correspondence of Thal amyloid phase to Braak tangle stage and ante mortem clinical characteristics in a large autopsy cohort. In the brain bank cohort of patients with a high likelihood of Alzheimer’s disease, samples with lower Thal amyloid phases were older at death, had a lower Braak tangle stage, and were less frequently APOE ε4 positive. Regression modeling in these samples with Alzheimer’s disease showed that Braak tangle stage, but not Thal amyloid phase, predicted age at onset, disease duration, and final Mini-Mental State Examination score.

A panel of blood biomarkers distinguishes accurately between patients with isolated concussion and uninjured individuals within the first eight hours after an accident, according to a study published online ahead of print in March 20 in Journal of Neurotrauma. Adult patients were enrolled in a study within 24 hours of concussion. Controls included uninjured people and patients with orthopedic injury. The investigators identified copeptin, galectin 3, matrix metalloproteinase 9, and occludin as biomarkers of concussion. A 3.4-fold decrease in plasma concentration of copeptin was found in patients with mild traumatic brain injury (mTBI) within eight hours after accident, compared with uninjured controls. Plasma levels of all biomarkers but copeptin increased by 3.6 to 4.5 times during the same time postinjury. The levels of at least two biomarkers were altered beyond their cutoff values in 90% of patients with mTBI.

Exploding head syndrome is relatively common in younger individuals, according to a study published online ahead of print March 13 in Journal of Sleep Research. Researchers assessed 211 undergraduate students for exploding head syndrome and isolated sleep paralysis using semistructured diagnostic interviews. A total of 18% of the sample population had exploding head syndrome during their lifetimes, and 16.60% of the population had recurrent cases of the syndrome. Exploding head syndrome affected both genders at equal rates, and investigators found it in 36.89% of participants who had been diagnosed with isolated sleep paralysis. Furthermore, exploding head syndrome episodes were accompanied by clinically significant levels of fear. For a minority of participants (2.80%), the fear was associated with clinically significant distress or impairment.

A distinctive pattern of abnormal protein deposits in the brain could help identify athletes with brain disorders, according to a study published online ahead of print April 6 in Proceedings of the National Academy of Science. Investigators used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in 14 retired professional football players with suspected chronic traumatic encephalopathy and compared results with those of 28 cognitively intact controls and 24 patients with Alzheimer’s dementia. The [F-18]FDDNP PET imaging results in retired players suggested the presence of the neuropathologic patterns consistent with models of concussion in which brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical regions that support mood, emotions, and behavior. The pattern was distinct from that observed in Alzheimer’s disease.

A blood test could help identify women with fragile X syndrome who are at risk of dysexecutive and social anxiety symptoms, according to a study published online ahead of print March 25 in Neurology. Thirty-five women with FMR1 premutation between ages 22 and 55 and 35 age- and IQ-matched controls completed a range of executive function tests and self-reported symptoms of psychiatric disorders. The researchers found that FMR1 intron 1 methylation levels could help dichotomize women with the premutation into categories of greater and lesser risk. FMR1 intron 1 methylation and activation ratio were significantly correlated with the likelihood of probable dysexecutive or psychiatric symptoms. The significant relationships between methylation and social anxiety were mediated by executive function performance, but only in women with the premutation.

Targeted temperature management at 33 °C or 36 °C helps maintain good quality of life in patients with cardiac arrest, according to a study published online ahead of print April 6 in JAMA Neurology. Investigators studied 939 unconscious adults with cardiac arrest at 36 intensive care units. Patients were assigned to temperature management at 33 °C or 36 °C for 36 hours. Cognitive function was measured by Mini-Mental State Examination (MMSE). The median MMSE score was 14 for patients assigned to 33 °C and 17 for patients assigned to 36 °C. Approximately 19% of the 33 °C group and 18% of the 36 °C group reported needing help with everyday activities, and 66.5% in the 33 °C group versus 61.8% in the 36 °C group reported making a complete mental recovery.

Biracial population eligibility for r-tPA is similar by gender, according to a study published in the March issue of Stroke. The study included 1,837 patients with ischemic stroke who were age 18 or older and presented to 16 emergency departments in 2005. Eligibility for r-tPA and individual exclusion criteria were determined using 2013 American Heart Association and European Cooperative Acute Stroke Study III guidelines. The mean age was 72.2 for women and 66.1 for men. Eligibility for r-tPA was similar by sex, and adjusting the data for age did not alter this result. More women than men had severe hypertension, and the investigators found no gender differences in blood pressure treatment rates among patients with severe hypertension. More women were older than 80 and had an NIH Stroke Scale score greater than 25.

The brains of patients with traumatic brain injury (TBI) may appear to be older than their chronological age, according to a study published in the April issue of Annals of Neurology. A predictive model of normal aging was defined using machine learning in 1,537 healthy individuals, based on MRI-derived estimates of gray matter and white matter. Investigators used this aging model to estimate brain age for 99 patients with TBI and 113 healthy controls. Brains with TBI were estimated to be older, with a mean predicted age difference between chronological and estimated brain age of 4.66 years for gray matter and 5.97 years for white matter. The predicted age difference correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase.

A combination of mental practice and physical therapy may help stroke survivors regain the strength of their motor behaviors, according to a study published March 30 in Frontiers in Human Neuroscience. The researchers recorded fMRI signals from 17 young healthy controls and 13 older stroke survivors. Participants with stroke underwent mental practice or both mental practice and physical therapy within 14 to 51 days following stroke. Investigators discovered that network activity was in the frequency range of 0.06 to 0.08 Hz for all brain regions studied and for controls and participants with stroke. Information flow between brain regions was reduced significantly for stroke survivors. The flow did not increase significantly after mental practice alone, but the flow among the regions during mental practice and physical therapy increased significantly.

—Kimberly Williams

The first year of residency came faster than I had expected and concluded just as quickly. At times, it felt like medical school, with different rotations, adjusting to newly formed teams, dealing with the pressures of getting the right diagnosis and treatment, managing the unrelenting speed of rounds, and trying to make a difference for the better. I must be honest – there were times when I was counting down the days for the rotation to end so that I could begin focusing and working directly in the mental health field.

Now, in my second year, the pace has improved, and the rotations resemble the work and patient population that I chose during the match process. Nonetheless, I am thankful for the time spent and the knowledge gained during my intern year, because it is only now that I understand the true value of my first-year experiences and the need to continue getting a well-rounded medical education for the benefit of my patients.

During my second year of residency, I have come across multiple instances of health disparities for people with mental illness. While working in several inpatient units, I have witnessed delayed time of visit from medical/surgical or ob.gyn. consults, shorter evaluation times from visiting consulting personnel, and postponed follow-up appointments for general medical conditions. I remember one occasion when a patient with urinary incontinence waited 3 days until internal medicine completed its consult. These experiences remind me of the conversations I had in medical school. Some of my colleagues would say, “Psychiatric patients are difficult.” Others were honest in admitting that they were scared to even enter a psychiatric inpatient unit.

Medical comorbidities common

During one 24-hour shift, I was paged to the inpatient unit. A new admission from that afternoon was complaining of “toe pain.”

The patient had been admitted for suicidal ideation and alcohol withdrawal. He reported tripping over a concrete step 2 weeks prior to admission. Under examination, he had an open laceration with purulent, foul-smelling discharge, erythema, and edema around the wound. The patient had signs of cellulitis, had a possible fracture of the phalanx, and was at risk for osteomyelitis.

He had been medically cleared at another facility prior to his admission, where he also had complained of toe pain. At that time, however, he was told, “You are not here for that,” and the extremity was not examined during the medical clearance. I ordered a referral, imaging was completed, and antibiotic treatment was started for his infection. Unfortunately, this is not an incidental or isolated case; situations similar to this one have become more frequent than we would like for those with mental illness.

Often, psychiatric patients are overlooked and undertreated. We frequently are the only physicians who evaluate the patient and help improve their quality of life. After reviewing the literature, I found countless studies concluding that patients who have a psychiatric diagnosis often have increased medical comorbidity and even increased mortality. A review and meta-analysis published earlier this year suggested that “people with mental disorders often do not receive preventive services, such as immunizations, cancer screenings, and tobacco counseling, and often receive a lower quality of care for medical conditions” (JAMA Psychiatry 2015;72:334-41). The researchers also found that “mortality was significantly higher among people with mental disorders than among the comparison population.”

Focusing on mind, body

I knew I wanted to be a psychiatrist since my early years in training. Initially, I was drawn toward psychology, in which I completed a bachelor’s degree, but my world turned around after a conversation with the father of a high school classmate. He told me: “I commend you on your decision to want to help people; however, I would like to give you food for thought. If your goal is to be of service to your patients and provide care, it would be to their benefit to address not only the mind but also the body” (which, coincidentally, is the theme of this year’s American Psychiatric Association meeting in Toronto.)

At that time, I was weighing becoming a clinician versus a physician; after all, both have instrumental roles in treatment. Yet, those words resonate now in my life for a new reason, namely, that my duty as an advocate for mental health is not only to treat psychiatric disorders but also to work toward treating general medical conditions.

I have been fortunate to cross paths with mentors who helped strengthen my commitment to well-rounded care and a multidisciplinary approach for the mentally ill. I am thankful to have worked with Dr. Jill Williams, who stressed the need to treat tobacco dependence, and Dr. Anthony Tobia, who emphasized the need to rule out substance- and medication-induced disorders prior to treatment. I have had the pleasure of working with many other attending psychiatrists who not only focused on psychiatric symptoms and diagnosis but stressed the need to address the medical care of our patients.

If I can understand my patients by learning about human behavior, conditioning, defense mechanisms, and interpersonal relationships and also focus on pathophysiology, comorbid conditions, differential diagnosis, and exacerbating medical conditions, I will be able to give them the best medical care possible.

Dr. Poulsen, a second-year psychiatry resident at the Robert Wood Johnson Medical School, Piscataway, N.J., is interested in cultural psychiatry and advocacy, and in pursuing a fellowship in child and adolescent psychiatry. After obtaining a bachelor of science degree at the University of Florida, Gainesville, he earned a medical degree at the University of Puerto Rico. He is currently serving in multiple leadership positions, including vice president of the New Jersey Psychiatric Association (NJPA) Residents Chapter and NJPA chapter advocacy coordinator. In addition, he has been selected as resident-fellow representative of the APA’s Area 3.

The first year of residency came faster than I had expected and concluded just as quickly. At times, it felt like medical school, with different rotations, adjusting to newly formed teams, dealing with the pressures of getting the right diagnosis and treatment, managing the unrelenting speed of rounds, and trying to make a difference for the better. I must be honest – there were times when I was counting down the days for the rotation to end so that I could begin focusing and working directly in the mental health field.

Now, in my second year, the pace has improved, and the rotations resemble the work and patient population that I chose during the match process. Nonetheless, I am thankful for the time spent and the knowledge gained during my intern year, because it is only now that I understand the true value of my first-year experiences and the need to continue getting a well-rounded medical education for the benefit of my patients.

During my second year of residency, I have come across multiple instances of health disparities for people with mental illness. While working in several inpatient units, I have witnessed delayed time of visit from medical/surgical or ob.gyn. consults, shorter evaluation times from visiting consulting personnel, and postponed follow-up appointments for general medical conditions. I remember one occasion when a patient with urinary incontinence waited 3 days until internal medicine completed its consult. These experiences remind me of the conversations I had in medical school. Some of my colleagues would say, “Psychiatric patients are difficult.” Others were honest in admitting that they were scared to even enter a psychiatric inpatient unit.

Medical comorbidities common

During one 24-hour shift, I was paged to the inpatient unit. A new admission from that afternoon was complaining of “toe pain.”

The patient had been admitted for suicidal ideation and alcohol withdrawal. He reported tripping over a concrete step 2 weeks prior to admission. Under examination, he had an open laceration with purulent, foul-smelling discharge, erythema, and edema around the wound. The patient had signs of cellulitis, had a possible fracture of the phalanx, and was at risk for osteomyelitis.

He had been medically cleared at another facility prior to his admission, where he also had complained of toe pain. At that time, however, he was told, “You are not here for that,” and the extremity was not examined during the medical clearance. I ordered a referral, imaging was completed, and antibiotic treatment was started for his infection. Unfortunately, this is not an incidental or isolated case; situations similar to this one have become more frequent than we would like for those with mental illness.

Often, psychiatric patients are overlooked and undertreated. We frequently are the only physicians who evaluate the patient and help improve their quality of life. After reviewing the literature, I found countless studies concluding that patients who have a psychiatric diagnosis often have increased medical comorbidity and even increased mortality. A review and meta-analysis published earlier this year suggested that “people with mental disorders often do not receive preventive services, such as immunizations, cancer screenings, and tobacco counseling, and often receive a lower quality of care for medical conditions” (JAMA Psychiatry 2015;72:334-41). The researchers also found that “mortality was significantly higher among people with mental disorders than among the comparison population.”

Focusing on mind, body

I knew I wanted to be a psychiatrist since my early years in training. Initially, I was drawn toward psychology, in which I completed a bachelor’s degree, but my world turned around after a conversation with the father of a high school classmate. He told me: “I commend you on your decision to want to help people; however, I would like to give you food for thought. If your goal is to be of service to your patients and provide care, it would be to their benefit to address not only the mind but also the body” (which, coincidentally, is the theme of this year’s American Psychiatric Association meeting in Toronto.)

At that time, I was weighing becoming a clinician versus a physician; after all, both have instrumental roles in treatment. Yet, those words resonate now in my life for a new reason, namely, that my duty as an advocate for mental health is not only to treat psychiatric disorders but also to work toward treating general medical conditions.

I have been fortunate to cross paths with mentors who helped strengthen my commitment to well-rounded care and a multidisciplinary approach for the mentally ill. I am thankful to have worked with Dr. Jill Williams, who stressed the need to treat tobacco dependence, and Dr. Anthony Tobia, who emphasized the need to rule out substance- and medication-induced disorders prior to treatment. I have had the pleasure of working with many other attending psychiatrists who not only focused on psychiatric symptoms and diagnosis but stressed the need to address the medical care of our patients.

If I can understand my patients by learning about human behavior, conditioning, defense mechanisms, and interpersonal relationships and also focus on pathophysiology, comorbid conditions, differential diagnosis, and exacerbating medical conditions, I will be able to give them the best medical care possible.

Dr. Poulsen, a second-year psychiatry resident at the Robert Wood Johnson Medical School, Piscataway, N.J., is interested in cultural psychiatry and advocacy, and in pursuing a fellowship in child and adolescent psychiatry. After obtaining a bachelor of science degree at the University of Florida, Gainesville, he earned a medical degree at the University of Puerto Rico. He is currently serving in multiple leadership positions, including vice president of the New Jersey Psychiatric Association (NJPA) Residents Chapter and NJPA chapter advocacy coordinator. In addition, he has been selected as resident-fellow representative of the APA’s Area 3.

The first year of residency came faster than I had expected and concluded just as quickly. At times, it felt like medical school, with different rotations, adjusting to newly formed teams, dealing with the pressures of getting the right diagnosis and treatment, managing the unrelenting speed of rounds, and trying to make a difference for the better. I must be honest – there were times when I was counting down the days for the rotation to end so that I could begin focusing and working directly in the mental health field.

Now, in my second year, the pace has improved, and the rotations resemble the work and patient population that I chose during the match process. Nonetheless, I am thankful for the time spent and the knowledge gained during my intern year, because it is only now that I understand the true value of my first-year experiences and the need to continue getting a well-rounded medical education for the benefit of my patients.

During my second year of residency, I have come across multiple instances of health disparities for people with mental illness. While working in several inpatient units, I have witnessed delayed time of visit from medical/surgical or ob.gyn. consults, shorter evaluation times from visiting consulting personnel, and postponed follow-up appointments for general medical conditions. I remember one occasion when a patient with urinary incontinence waited 3 days until internal medicine completed its consult. These experiences remind me of the conversations I had in medical school. Some of my colleagues would say, “Psychiatric patients are difficult.” Others were honest in admitting that they were scared to even enter a psychiatric inpatient unit.

Medical comorbidities common

During one 24-hour shift, I was paged to the inpatient unit. A new admission from that afternoon was complaining of “toe pain.”

The patient had been admitted for suicidal ideation and alcohol withdrawal. He reported tripping over a concrete step 2 weeks prior to admission. Under examination, he had an open laceration with purulent, foul-smelling discharge, erythema, and edema around the wound. The patient had signs of cellulitis, had a possible fracture of the phalanx, and was at risk for osteomyelitis.

He had been medically cleared at another facility prior to his admission, where he also had complained of toe pain. At that time, however, he was told, “You are not here for that,” and the extremity was not examined during the medical clearance. I ordered a referral, imaging was completed, and antibiotic treatment was started for his infection. Unfortunately, this is not an incidental or isolated case; situations similar to this one have become more frequent than we would like for those with mental illness.

Often, psychiatric patients are overlooked and undertreated. We frequently are the only physicians who evaluate the patient and help improve their quality of life. After reviewing the literature, I found countless studies concluding that patients who have a psychiatric diagnosis often have increased medical comorbidity and even increased mortality. A review and meta-analysis published earlier this year suggested that “people with mental disorders often do not receive preventive services, such as immunizations, cancer screenings, and tobacco counseling, and often receive a lower quality of care for medical conditions” (JAMA Psychiatry 2015;72:334-41). The researchers also found that “mortality was significantly higher among people with mental disorders than among the comparison population.”

Focusing on mind, body

I knew I wanted to be a psychiatrist since my early years in training. Initially, I was drawn toward psychology, in which I completed a bachelor’s degree, but my world turned around after a conversation with the father of a high school classmate. He told me: “I commend you on your decision to want to help people; however, I would like to give you food for thought. If your goal is to be of service to your patients and provide care, it would be to their benefit to address not only the mind but also the body” (which, coincidentally, is the theme of this year’s American Psychiatric Association meeting in Toronto.)

At that time, I was weighing becoming a clinician versus a physician; after all, both have instrumental roles in treatment. Yet, those words resonate now in my life for a new reason, namely, that my duty as an advocate for mental health is not only to treat psychiatric disorders but also to work toward treating general medical conditions.

I have been fortunate to cross paths with mentors who helped strengthen my commitment to well-rounded care and a multidisciplinary approach for the mentally ill. I am thankful to have worked with Dr. Jill Williams, who stressed the need to treat tobacco dependence, and Dr. Anthony Tobia, who emphasized the need to rule out substance- and medication-induced disorders prior to treatment. I have had the pleasure of working with many other attending psychiatrists who not only focused on psychiatric symptoms and diagnosis but stressed the need to address the medical care of our patients.

If I can understand my patients by learning about human behavior, conditioning, defense mechanisms, and interpersonal relationships and also focus on pathophysiology, comorbid conditions, differential diagnosis, and exacerbating medical conditions, I will be able to give them the best medical care possible.

Dr. Poulsen, a second-year psychiatry resident at the Robert Wood Johnson Medical School, Piscataway, N.J., is interested in cultural psychiatry and advocacy, and in pursuing a fellowship in child and adolescent psychiatry. After obtaining a bachelor of science degree at the University of Florida, Gainesville, he earned a medical degree at the University of Puerto Rico. He is currently serving in multiple leadership positions, including vice president of the New Jersey Psychiatric Association (NJPA) Residents Chapter and NJPA chapter advocacy coordinator. In addition, he has been selected as resident-fellow representative of the APA’s Area 3.

AACR Annual Meeting 2015

PHILADELPHIA—Two multikinase inhibitors (MKIs) can treat chronic myeloid leukemia (CML) that is resistant to other inhibitors, according to preclinical research.

A series of in vitro experiments showed that the MKIs, sorafenib and axitinib, can overcome treatment resistance mediated by hyperactivation of the Src kinase Lyn, overexpression of the docking protein Gab2, and the presence of the Bcr-Abl T315I mutation.

Sebastian Halbach, of the University of Freiburg in Germany, and his colleagues presented these findings in a poster at the AACR Annual Meeting 2015 (abstract 2708).

Mechanisms of resistance

Halbach noted that CML is driven by the hyperactive fusion kinase Bcr-Abl, which builds up its own signaling network with various proteins, such as Gab2 and Lyn.

Resistance to tyrosine kinase inhibitors (TKIs) and MKIs can be caused by mutations in the Bcr-Abl oncogene, such as T315I, or by aberrant activity of components of the Bcr-Abl signaling network.

“We have previously shown in our lab that overexpression of the docking protein Gab2 . . . confers resistance against imatinib and dasatinib,” Halbach said. “And another mechanism of resistance is hyperactivation of the Src kinase Lyn.”

For the current study, Halbach and his colleagues investigated the role of Lyn by introducing imatinib, dasatinib, or DMSO to K562 cells (blast-phase CML), Lyn-transformed K562 cells, and Lyn-Y508F-transformed K562 cells.

They also compared imatinib and DMSO in Ba/F3 cells (a murine pro-B cell line), Lyn-transformed Ba/F3 cells, and Lyn-Y508F-transformed Ba/F3 cells.

The results of these experiments showed that hyperactive Lyn confers resistance to imatinib but not dasatinib.

“That’s not that surprising because dasatinib is a multikinase inhibitor which targets Src kinases,” Halbach noted. “Therefore, the hyperactivity of Lyn is directly targeted.”

Identifying new drugs

Having established that TKI and MKI resistance in CML can be mediated by Lyn and Gab2, as well as T315I, Halbach and his colleagues wanted to find drugs that would overcome this problem. They screened a panel of inhibitors and identified sorafenib and axitinib.

The researchers first evaluated the effects of sorafenib and axitinib against the T315I mutation. They tested the 2 MKIs—as well as imatinib, dasatinib, nilotinib, ponatinib, and DMSO—in the KBM5 cell line (blast-phase CML) and the KBM5-T315I cell line (imatinib-resistant CML).

Sorafenib and axitinib killed KBM5-T315I cells more effectively than any of the other inhibitors. The 2 MKIs also decreased the metabolic activity of T315I-positive cells more effectively than imatinib, dasatinib, or nilotinib, but not ponatinib, which produced similar results.

Next, Halbach and his colleagues tested sorafenib, axitinib, and the aforementioned inhibitors in K562 cells overexpressing Gab2. Overexpression of Gab2 conferred resistance to imatinib, dasatinib, nilotinib, and ponatinib, but not sorafenib and axitinib.

Both sorafenib and axitinib decreased the metabolic activity of Gab2-overexpressing cells more effectively than any of the other inhibitors.

Lastly, the researchers tested all of the inhibitors in Lyn-transformed K562 cells, Lyn-Y508F-transformed K562 cells, and K562 cells. They found that sorafenib and axitinib both overcame Lyn-Y508F-mediated resistance.

Sorafenib and axitinib killed K562 cells and Lyn-transformed K562 cells more effectively than any of the other inhibitors. The 2 MKIs also killed Lyn-Y508F-transformed K562 cells more effectively than imatinib and nilotinib, but not ponatinib or dasatinib.

Sorafenib decreased the metabolic activity of Lyn-Y508F-transformed K562 cells more effectively than all of the other inhibitors. But axitinib only proved more effective than imatinib in this regard.

Halbach said he hopes sorafenib and axitinib can one day serve as alternatives to ponatinib for CML patients, especially those with T315I mutations or high Gab2 levels.

For now, his team’s next step is to further analyze the influence of axitinib and sorafenib on the Bcr-Abl—Gab2 signaling complex.

AACR Annual Meeting 2015

PHILADELPHIA—Two multikinase inhibitors (MKIs) can treat chronic myeloid leukemia (CML) that is resistant to other inhibitors, according to preclinical research.

A series of in vitro experiments showed that the MKIs, sorafenib and axitinib, can overcome treatment resistance mediated by hyperactivation of the Src kinase Lyn, overexpression of the docking protein Gab2, and the presence of the Bcr-Abl T315I mutation.

Sebastian Halbach, of the University of Freiburg in Germany, and his colleagues presented these findings in a poster at the AACR Annual Meeting 2015 (abstract 2708).

Mechanisms of resistance

Halbach noted that CML is driven by the hyperactive fusion kinase Bcr-Abl, which builds up its own signaling network with various proteins, such as Gab2 and Lyn.

Resistance to tyrosine kinase inhibitors (TKIs) and MKIs can be caused by mutations in the Bcr-Abl oncogene, such as T315I, or by aberrant activity of components of the Bcr-Abl signaling network.

“We have previously shown in our lab that overexpression of the docking protein Gab2 . . . confers resistance against imatinib and dasatinib,” Halbach said. “And another mechanism of resistance is hyperactivation of the Src kinase Lyn.”

For the current study, Halbach and his colleagues investigated the role of Lyn by introducing imatinib, dasatinib, or DMSO to K562 cells (blast-phase CML), Lyn-transformed K562 cells, and Lyn-Y508F-transformed K562 cells.

They also compared imatinib and DMSO in Ba/F3 cells (a murine pro-B cell line), Lyn-transformed Ba/F3 cells, and Lyn-Y508F-transformed Ba/F3 cells.

The results of these experiments showed that hyperactive Lyn confers resistance to imatinib but not dasatinib.

“That’s not that surprising because dasatinib is a multikinase inhibitor which targets Src kinases,” Halbach noted. “Therefore, the hyperactivity of Lyn is directly targeted.”

Identifying new drugs

Having established that TKI and MKI resistance in CML can be mediated by Lyn and Gab2, as well as T315I, Halbach and his colleagues wanted to find drugs that would overcome this problem. They screened a panel of inhibitors and identified sorafenib and axitinib.

The researchers first evaluated the effects of sorafenib and axitinib against the T315I mutation. They tested the 2 MKIs—as well as imatinib, dasatinib, nilotinib, ponatinib, and DMSO—in the KBM5 cell line (blast-phase CML) and the KBM5-T315I cell line (imatinib-resistant CML).

Sorafenib and axitinib killed KBM5-T315I cells more effectively than any of the other inhibitors. The 2 MKIs also decreased the metabolic activity of T315I-positive cells more effectively than imatinib, dasatinib, or nilotinib, but not ponatinib, which produced similar results.

Next, Halbach and his colleagues tested sorafenib, axitinib, and the aforementioned inhibitors in K562 cells overexpressing Gab2. Overexpression of Gab2 conferred resistance to imatinib, dasatinib, nilotinib, and ponatinib, but not sorafenib and axitinib.

Both sorafenib and axitinib decreased the metabolic activity of Gab2-overexpressing cells more effectively than any of the other inhibitors.

Lastly, the researchers tested all of the inhibitors in Lyn-transformed K562 cells, Lyn-Y508F-transformed K562 cells, and K562 cells. They found that sorafenib and axitinib both overcame Lyn-Y508F-mediated resistance.

Sorafenib and axitinib killed K562 cells and Lyn-transformed K562 cells more effectively than any of the other inhibitors. The 2 MKIs also killed Lyn-Y508F-transformed K562 cells more effectively than imatinib and nilotinib, but not ponatinib or dasatinib.

Sorafenib decreased the metabolic activity of Lyn-Y508F-transformed K562 cells more effectively than all of the other inhibitors. But axitinib only proved more effective than imatinib in this regard.

Halbach said he hopes sorafenib and axitinib can one day serve as alternatives to ponatinib for CML patients, especially those with T315I mutations or high Gab2 levels.

For now, his team’s next step is to further analyze the influence of axitinib and sorafenib on the Bcr-Abl—Gab2 signaling complex.

AACR Annual Meeting 2015

PHILADELPHIA—Two multikinase inhibitors (MKIs) can treat chronic myeloid leukemia (CML) that is resistant to other inhibitors, according to preclinical research.

A series of in vitro experiments showed that the MKIs, sorafenib and axitinib, can overcome treatment resistance mediated by hyperactivation of the Src kinase Lyn, overexpression of the docking protein Gab2, and the presence of the Bcr-Abl T315I mutation.

Sebastian Halbach, of the University of Freiburg in Germany, and his colleagues presented these findings in a poster at the AACR Annual Meeting 2015 (abstract 2708).

Mechanisms of resistance

Halbach noted that CML is driven by the hyperactive fusion kinase Bcr-Abl, which builds up its own signaling network with various proteins, such as Gab2 and Lyn.

Resistance to tyrosine kinase inhibitors (TKIs) and MKIs can be caused by mutations in the Bcr-Abl oncogene, such as T315I, or by aberrant activity of components of the Bcr-Abl signaling network.

“We have previously shown in our lab that overexpression of the docking protein Gab2 . . . confers resistance against imatinib and dasatinib,” Halbach said. “And another mechanism of resistance is hyperactivation of the Src kinase Lyn.”

For the current study, Halbach and his colleagues investigated the role of Lyn by introducing imatinib, dasatinib, or DMSO to K562 cells (blast-phase CML), Lyn-transformed K562 cells, and Lyn-Y508F-transformed K562 cells.

They also compared imatinib and DMSO in Ba/F3 cells (a murine pro-B cell line), Lyn-transformed Ba/F3 cells, and Lyn-Y508F-transformed Ba/F3 cells.

The results of these experiments showed that hyperactive Lyn confers resistance to imatinib but not dasatinib.

“That’s not that surprising because dasatinib is a multikinase inhibitor which targets Src kinases,” Halbach noted. “Therefore, the hyperactivity of Lyn is directly targeted.”

Identifying new drugs

Having established that TKI and MKI resistance in CML can be mediated by Lyn and Gab2, as well as T315I, Halbach and his colleagues wanted to find drugs that would overcome this problem. They screened a panel of inhibitors and identified sorafenib and axitinib.

The researchers first evaluated the effects of sorafenib and axitinib against the T315I mutation. They tested the 2 MKIs—as well as imatinib, dasatinib, nilotinib, ponatinib, and DMSO—in the KBM5 cell line (blast-phase CML) and the KBM5-T315I cell line (imatinib-resistant CML).

Sorafenib and axitinib killed KBM5-T315I cells more effectively than any of the other inhibitors. The 2 MKIs also decreased the metabolic activity of T315I-positive cells more effectively than imatinib, dasatinib, or nilotinib, but not ponatinib, which produced similar results.

Next, Halbach and his colleagues tested sorafenib, axitinib, and the aforementioned inhibitors in K562 cells overexpressing Gab2. Overexpression of Gab2 conferred resistance to imatinib, dasatinib, nilotinib, and ponatinib, but not sorafenib and axitinib.

Both sorafenib and axitinib decreased the metabolic activity of Gab2-overexpressing cells more effectively than any of the other inhibitors.

Lastly, the researchers tested all of the inhibitors in Lyn-transformed K562 cells, Lyn-Y508F-transformed K562 cells, and K562 cells. They found that sorafenib and axitinib both overcame Lyn-Y508F-mediated resistance.

Sorafenib and axitinib killed K562 cells and Lyn-transformed K562 cells more effectively than any of the other inhibitors. The 2 MKIs also killed Lyn-Y508F-transformed K562 cells more effectively than imatinib and nilotinib, but not ponatinib or dasatinib.

Sorafenib decreased the metabolic activity of Lyn-Y508F-transformed K562 cells more effectively than all of the other inhibitors. But axitinib only proved more effective than imatinib in this regard.

Halbach said he hopes sorafenib and axitinib can one day serve as alternatives to ponatinib for CML patients, especially those with T315I mutations or high Gab2 levels.

For now, his team’s next step is to further analyze the influence of axitinib and sorafenib on the Bcr-Abl—Gab2 signaling complex.

Inferior vena cava filter

Photo from Business Wire

Retrievable inferior vena cava filters do not reduce the risk of recurrent pulmonary embolism (PE) or death in patients with PE, according to a study

published in JAMA.

The study showed no significant difference in outcomes between patients who received anticoagulation in conjunction with an inferior vena cava

filter and patients who received anticoagulant therapy alone.

Studies have shown an increase in the placement of inferior vena cava filters over the past few decades. However, a lack of reliable data on the use of these filters has meant the benefit-risk ratio of using them in patients at risk of recurrent venous thromboembolism (VTE) is uncertain.

To gain more insight, Patrick Mismetti, MD, PhD, of the Centre Hospitalier Universitaire de Saint-Etienne in France, and his colleagues conducted a prospective study.

They enrolled hospitalized patients with acute, symptomatic PE associated with lower-limb vein thrombosis who had at least 1 criterion for severity. Patients were randomized to receive anticoagulation and a retrievable inferior vena cava filter (n=200) or anticoagulation alone (n=199).

The follow-up period was 6 months. Patients received full-dose anticoagulation for at least 6 months, and filter retrieval was planned at 3 months from placement.

Filters were successfully inserted in 193 patients. Filter retrieval was successful in 153 of the 164 patients in whom retrieval was attempted.

In the anticoagulant-only group, 6 patients ultimately received a filter, 4 because they were undergoing surgery and needed to stop anticoagulation, and 2 because of bleeding complications.

By 3 months, 6 patients (3.0%) had recurrent PE in the filter group, as did 3 patients (1.5%) in the anticoagulant-only group (P=0.50). All episodes in the filter group and 2 in the anticoagulant group were fatal.

The researchers observed 1 additional PE recurrence in each treatment group between 3 and 6 months (P=0.54). And 3 patients developed filter thrombosis.

At 3 months, there was no significant difference between the 2 treatment groups with regard to recurrent deep vein thrombosis (P>0.99), recurrent VTE (P=0.36), major bleeding (P=0.63), or death from any cause (P=0.55).

At 6 months, there was no significant difference between the treatment groups with regard to recurrent deep vein thrombosis (P>0.99), recurrent VTE (P=0.59), major bleeding (P=0.69), or death from any cause (P=0.29).

The main cause of death in both treatment groups was cancer.

The researchers noted that the availability of retrievable inferior vena cava filters has probably contributed to their increased use for managing acute VTE, including their use in addition to full-dose anticoagulant therapy in patients with PE, a large clot burden, a poor cardiopulmonary reserve, or a suspected increased risk for recurrence, as advocated by several guidelines.

However, the team said the results of this study do not support the use of these filters in patients who can be treated with anticoagulation.

Inferior vena cava filter

Photo from Business Wire

Retrievable inferior vena cava filters do not reduce the risk of recurrent pulmonary embolism (PE) or death in patients with PE, according to a study

published in JAMA.

The study showed no significant difference in outcomes between patients who received anticoagulation in conjunction with an inferior vena cava

filter and patients who received anticoagulant therapy alone.

Studies have shown an increase in the placement of inferior vena cava filters over the past few decades. However, a lack of reliable data on the use of these filters has meant the benefit-risk ratio of using them in patients at risk of recurrent venous thromboembolism (VTE) is uncertain.

To gain more insight, Patrick Mismetti, MD, PhD, of the Centre Hospitalier Universitaire de Saint-Etienne in France, and his colleagues conducted a prospective study.

They enrolled hospitalized patients with acute, symptomatic PE associated with lower-limb vein thrombosis who had at least 1 criterion for severity. Patients were randomized to receive anticoagulation and a retrievable inferior vena cava filter (n=200) or anticoagulation alone (n=199).

The follow-up period was 6 months. Patients received full-dose anticoagulation for at least 6 months, and filter retrieval was planned at 3 months from placement.

Filters were successfully inserted in 193 patients. Filter retrieval was successful in 153 of the 164 patients in whom retrieval was attempted.

In the anticoagulant-only group, 6 patients ultimately received a filter, 4 because they were undergoing surgery and needed to stop anticoagulation, and 2 because of bleeding complications.

By 3 months, 6 patients (3.0%) had recurrent PE in the filter group, as did 3 patients (1.5%) in the anticoagulant-only group (P=0.50). All episodes in the filter group and 2 in the anticoagulant group were fatal.

The researchers observed 1 additional PE recurrence in each treatment group between 3 and 6 months (P=0.54). And 3 patients developed filter thrombosis.

At 3 months, there was no significant difference between the 2 treatment groups with regard to recurrent deep vein thrombosis (P>0.99), recurrent VTE (P=0.36), major bleeding (P=0.63), or death from any cause (P=0.55).

At 6 months, there was no significant difference between the treatment groups with regard to recurrent deep vein thrombosis (P>0.99), recurrent VTE (P=0.59), major bleeding (P=0.69), or death from any cause (P=0.29).

The main cause of death in both treatment groups was cancer.

The researchers noted that the availability of retrievable inferior vena cava filters has probably contributed to their increased use for managing acute VTE, including their use in addition to full-dose anticoagulant therapy in patients with PE, a large clot burden, a poor cardiopulmonary reserve, or a suspected increased risk for recurrence, as advocated by several guidelines.

However, the team said the results of this study do not support the use of these filters in patients who can be treated with anticoagulation.

Inferior vena cava filter

Photo from Business Wire

Retrievable inferior vena cava filters do not reduce the risk of recurrent pulmonary embolism (PE) or death in patients with PE, according to a study

published in JAMA.

The study showed no significant difference in outcomes between patients who received anticoagulation in conjunction with an inferior vena cava

filter and patients who received anticoagulant therapy alone.

Studies have shown an increase in the placement of inferior vena cava filters over the past few decades. However, a lack of reliable data on the use of these filters has meant the benefit-risk ratio of using them in patients at risk of recurrent venous thromboembolism (VTE) is uncertain.

To gain more insight, Patrick Mismetti, MD, PhD, of the Centre Hospitalier Universitaire de Saint-Etienne in France, and his colleagues conducted a prospective study.

They enrolled hospitalized patients with acute, symptomatic PE associated with lower-limb vein thrombosis who had at least 1 criterion for severity. Patients were randomized to receive anticoagulation and a retrievable inferior vena cava filter (n=200) or anticoagulation alone (n=199).

The follow-up period was 6 months. Patients received full-dose anticoagulation for at least 6 months, and filter retrieval was planned at 3 months from placement.

Filters were successfully inserted in 193 patients. Filter retrieval was successful in 153 of the 164 patients in whom retrieval was attempted.

In the anticoagulant-only group, 6 patients ultimately received a filter, 4 because they were undergoing surgery and needed to stop anticoagulation, and 2 because of bleeding complications.

By 3 months, 6 patients (3.0%) had recurrent PE in the filter group, as did 3 patients (1.5%) in the anticoagulant-only group (P=0.50). All episodes in the filter group and 2 in the anticoagulant group were fatal.

The researchers observed 1 additional PE recurrence in each treatment group between 3 and 6 months (P=0.54). And 3 patients developed filter thrombosis.

At 3 months, there was no significant difference between the 2 treatment groups with regard to recurrent deep vein thrombosis (P>0.99), recurrent VTE (P=0.36), major bleeding (P=0.63), or death from any cause (P=0.55).

At 6 months, there was no significant difference between the treatment groups with regard to recurrent deep vein thrombosis (P>0.99), recurrent VTE (P=0.59), major bleeding (P=0.69), or death from any cause (P=0.29).

The main cause of death in both treatment groups was cancer.

The researchers noted that the availability of retrievable inferior vena cava filters has probably contributed to their increased use for managing acute VTE, including their use in addition to full-dose anticoagulant therapy in patients with PE, a large clot burden, a poor cardiopulmonary reserve, or a suspected increased risk for recurrence, as advocated by several guidelines.

However, the team said the results of this study do not support the use of these filters in patients who can be treated with anticoagulation.

Malaria parasite infecting

a red blood cell

Photo courtesy of St. Jude

Children’s Research Hospital

Researchers say they have pinpointed one of the mechanisms responsible for the progression of malaria.

Computer modeling showed that the nanoscale knobs that form at the membrane of infected red blood cells cause the cell stiffening that is, in part, responsible for the reduced blood flow that can turn malaria deadly.

Subra Suresh, ScD, of Carnegie Mellon University in Pittsburgh, Pennsylvania, and his colleagues reported this finding in PNAS.

“Many of malaria’s symptoms are the result of impeded blood flow, which is directly tied to structural changes in infected red blood cells,” Dr Suresh said.

When a red blood cell is infected with malaria, the parasite releases proteins that interact with the cell membrane. The cell membrane undergoes a series of changes that result in stiffness and stickiness.

While researchers are fairly certain that the stickiness is caused by nanoscale knobs that protrude from the cell membrane, they were uncertain as to what caused the stiffness.

They hypothesized that the parasite protein/cell membrane interaction caused spectrin, a cytoskeletal protein that provides a scaffold for the cell membrane, to rearrange its networked structure to be more rigid.

However, the complexity of the cell membrane made it difficult for researchers to study and prove this hypothesis experimentally.

To visualize what happens at the cell membrane during malarial infection, Dr Suresh and his colleagues turned to a computer simulation technique called coarse-grained molecular dynamics (CGMD). CGMD has proven valuable for studying what happens at the cell membrane because it represents the membrane’s complex proteins and lipids with larger, simplified components rather than atom by atom.

Doing this requires less computing time and power than standard atomistic models, which allows scientists to run simulations for longer periods of time while still accurately recreating the behavior of the cell membrane.

Typically, researchers introduce different variables into the simulation and observe how the membrane reacts. In the current study, the researchers seeded the model membrane with proteins released by the malaria parasite Plasmodium falciparum.

From their simulation, the researchers found that the stiffening of the red blood cell membrane had little to do with the remodeling of spectrin.

Instead, the nanoscale knobs that cause the red blood cells to stick to the vein’s walls also cause the membrane to stiffen through a number of different mechanisms, including composite strengthening, strain hardening, and density-dependent vertical coupling effects.

According to the researchers, the discovery of this mechanism could provide a promising target for new antimalarial therapies.

Malaria parasite infecting

a red blood cell

Photo courtesy of St. Jude

Children’s Research Hospital

Researchers say they have pinpointed one of the mechanisms responsible for the progression of malaria.

Computer modeling showed that the nanoscale knobs that form at the membrane of infected red blood cells cause the cell stiffening that is, in part, responsible for the reduced blood flow that can turn malaria deadly.

Subra Suresh, ScD, of Carnegie Mellon University in Pittsburgh, Pennsylvania, and his colleagues reported this finding in PNAS.

“Many of malaria’s symptoms are the result of impeded blood flow, which is directly tied to structural changes in infected red blood cells,” Dr Suresh said.

When a red blood cell is infected with malaria, the parasite releases proteins that interact with the cell membrane. The cell membrane undergoes a series of changes that result in stiffness and stickiness.

While researchers are fairly certain that the stickiness is caused by nanoscale knobs that protrude from the cell membrane, they were uncertain as to what caused the stiffness.

They hypothesized that the parasite protein/cell membrane interaction caused spectrin, a cytoskeletal protein that provides a scaffold for the cell membrane, to rearrange its networked structure to be more rigid.

However, the complexity of the cell membrane made it difficult for researchers to study and prove this hypothesis experimentally.

To visualize what happens at the cell membrane during malarial infection, Dr Suresh and his colleagues turned to a computer simulation technique called coarse-grained molecular dynamics (CGMD). CGMD has proven valuable for studying what happens at the cell membrane because it represents the membrane’s complex proteins and lipids with larger, simplified components rather than atom by atom.

Doing this requires less computing time and power than standard atomistic models, which allows scientists to run simulations for longer periods of time while still accurately recreating the behavior of the cell membrane.

Typically, researchers introduce different variables into the simulation and observe how the membrane reacts. In the current study, the researchers seeded the model membrane with proteins released by the malaria parasite Plasmodium falciparum.

From their simulation, the researchers found that the stiffening of the red blood cell membrane had little to do with the remodeling of spectrin.

Instead, the nanoscale knobs that cause the red blood cells to stick to the vein’s walls also cause the membrane to stiffen through a number of different mechanisms, including composite strengthening, strain hardening, and density-dependent vertical coupling effects.

According to the researchers, the discovery of this mechanism could provide a promising target for new antimalarial therapies.

Malaria parasite infecting

a red blood cell

Photo courtesy of St. Jude

Children’s Research Hospital

Researchers say they have pinpointed one of the mechanisms responsible for the progression of malaria.

Computer modeling showed that the nanoscale knobs that form at the membrane of infected red blood cells cause the cell stiffening that is, in part, responsible for the reduced blood flow that can turn malaria deadly.

Subra Suresh, ScD, of Carnegie Mellon University in Pittsburgh, Pennsylvania, and his colleagues reported this finding in PNAS.

“Many of malaria’s symptoms are the result of impeded blood flow, which is directly tied to structural changes in infected red blood cells,” Dr Suresh said.

When a red blood cell is infected with malaria, the parasite releases proteins that interact with the cell membrane. The cell membrane undergoes a series of changes that result in stiffness and stickiness.

While researchers are fairly certain that the stickiness is caused by nanoscale knobs that protrude from the cell membrane, they were uncertain as to what caused the stiffness.

They hypothesized that the parasite protein/cell membrane interaction caused spectrin, a cytoskeletal protein that provides a scaffold for the cell membrane, to rearrange its networked structure to be more rigid.

However, the complexity of the cell membrane made it difficult for researchers to study and prove this hypothesis experimentally.

To visualize what happens at the cell membrane during malarial infection, Dr Suresh and his colleagues turned to a computer simulation technique called coarse-grained molecular dynamics (CGMD). CGMD has proven valuable for studying what happens at the cell membrane because it represents the membrane’s complex proteins and lipids with larger, simplified components rather than atom by atom.

Doing this requires less computing time and power than standard atomistic models, which allows scientists to run simulations for longer periods of time while still accurately recreating the behavior of the cell membrane.

Typically, researchers introduce different variables into the simulation and observe how the membrane reacts. In the current study, the researchers seeded the model membrane with proteins released by the malaria parasite Plasmodium falciparum.

From their simulation, the researchers found that the stiffening of the red blood cell membrane had little to do with the remodeling of spectrin.

Instead, the nanoscale knobs that cause the red blood cells to stick to the vein’s walls also cause the membrane to stiffen through a number of different mechanisms, including composite strengthening, strain hardening, and density-dependent vertical coupling effects.

According to the researchers, the discovery of this mechanism could provide a promising target for new antimalarial therapies.

Hydroxyurea

Photo by Zak Hubbard

Results of a retrospective study reinforce the idea that hydroxyurea (HU) is underused in US patients with sickle cell anemia (SCA).

Researchers analyzed data from an insurance claims database and identified 570 patients with probable SCA who were available for follow-up and likely would have benefitted from receiving HU.

Less than a quarter of those patients actually received the drug within a year of their third visit to a hospital seeking treatment for pain crises.

The researchers noted that these data may not be representative of the US population because the analysis does not include uninsured patients or publicly insured patients.

Nicolas Stettler, MD, of the Lewin Group in Falls Church, Virginia, and his colleagues conducted this research and reported the results in a letter to JAMA.

The researchers noted that the 2014 National Heart, Lung, and Blood Institute guidelines recommend using HU to treat all adults with SCA who experience 3 or more moderate-to-severe pain crises within a year. This is a “strong” recommendation based on high-quality evidence reviewed in 2008.

Despite this recommendation, it is thought that HU is underused, although the extent of its use has been unclear.

With that in mind, Dr Stettler and his colleagues examined the use of HU when indicated for SCA in the Optum Normative Health Informatics database. This database is a nationwide sample of commercial health and pharmacy claims from more than 36 million residents in all 50 states and Washington, DC.

The researchers identified adults ages 18 and older with 1 or more inpatient or outpatient claims for SCA between January 2009 and June 2013.

The team selected patients when they had 3 or more hospitalizations, emergency department visits, or both within 12 months that included 1 of the 5 most frequent diagnosis codes used for patients with SCA and pain crises.

Treatment was defined as filling 1 or more HU prescriptions during the 3, 6, or 12 months of continued enrollment following the third episode.

Of the enrolled population (n=26,631,901), the researchers identified 2086 adults with probable SCA. Of these patients, 677 had at least 3 pain-related hospitalizations or emergency department visits within 12 months, and 570 had at least 3 months of coverage after the third episode.

Among those 570 patients, 86 (15%) were treated with HU within 3 months of their third encounter. The percentage of treated patients increased slightly to 18% at 6 months and to 23% at 12 months.

The researchers noted that there are several barriers to HU treatment, including fear of adverse events, lack of clinician training, and failure to engage in shared decision-making.

The team also pointed out that their data do not include the uninsured or publicly insured population, which may have more limited access to healthcare or awareness of treatment options than the patients studied. So these findings may not be representative of the entire US population with SCA and may be a conservative estimate of the HU treatment gap.

To address this gap, it may be necessary to enhance patient outreach and clinician training and develop healthcare quality measures aimed at increasing the use of HU for all patients who would benefit, the researchers said.

Hydroxyurea

Photo by Zak Hubbard

Results of a retrospective study reinforce the idea that hydroxyurea (HU) is underused in US patients with sickle cell anemia (SCA).

Researchers analyzed data from an insurance claims database and identified 570 patients with probable SCA who were available for follow-up and likely would have benefitted from receiving HU.

Less than a quarter of those patients actually received the drug within a year of their third visit to a hospital seeking treatment for pain crises.

The researchers noted that these data may not be representative of the US population because the analysis does not include uninsured patients or publicly insured patients.

Nicolas Stettler, MD, of the Lewin Group in Falls Church, Virginia, and his colleagues conducted this research and reported the results in a letter to JAMA.

The researchers noted that the 2014 National Heart, Lung, and Blood Institute guidelines recommend using HU to treat all adults with SCA who experience 3 or more moderate-to-severe pain crises within a year. This is a “strong” recommendation based on high-quality evidence reviewed in 2008.

Despite this recommendation, it is thought that HU is underused, although the extent of its use has been unclear.

With that in mind, Dr Stettler and his colleagues examined the use of HU when indicated for SCA in the Optum Normative Health Informatics database. This database is a nationwide sample of commercial health and pharmacy claims from more than 36 million residents in all 50 states and Washington, DC.

The researchers identified adults ages 18 and older with 1 or more inpatient or outpatient claims for SCA between January 2009 and June 2013.

The team selected patients when they had 3 or more hospitalizations, emergency department visits, or both within 12 months that included 1 of the 5 most frequent diagnosis codes used for patients with SCA and pain crises.

Treatment was defined as filling 1 or more HU prescriptions during the 3, 6, or 12 months of continued enrollment following the third episode.

Of the enrolled population (n=26,631,901), the researchers identified 2086 adults with probable SCA. Of these patients, 677 had at least 3 pain-related hospitalizations or emergency department visits within 12 months, and 570 had at least 3 months of coverage after the third episode.

Among those 570 patients, 86 (15%) were treated with HU within 3 months of their third encounter. The percentage of treated patients increased slightly to 18% at 6 months and to 23% at 12 months.

The researchers noted that there are several barriers to HU treatment, including fear of adverse events, lack of clinician training, and failure to engage in shared decision-making.

The team also pointed out that their data do not include the uninsured or publicly insured population, which may have more limited access to healthcare or awareness of treatment options than the patients studied. So these findings may not be representative of the entire US population with SCA and may be a conservative estimate of the HU treatment gap.

To address this gap, it may be necessary to enhance patient outreach and clinician training and develop healthcare quality measures aimed at increasing the use of HU for all patients who would benefit, the researchers said.

Hydroxyurea

Photo by Zak Hubbard

Results of a retrospective study reinforce the idea that hydroxyurea (HU) is underused in US patients with sickle cell anemia (SCA).

Researchers analyzed data from an insurance claims database and identified 570 patients with probable SCA who were available for follow-up and likely would have benefitted from receiving HU.

Less than a quarter of those patients actually received the drug within a year of their third visit to a hospital seeking treatment for pain crises.

The researchers noted that these data may not be representative of the US population because the analysis does not include uninsured patients or publicly insured patients.

Nicolas Stettler, MD, of the Lewin Group in Falls Church, Virginia, and his colleagues conducted this research and reported the results in a letter to JAMA.

The researchers noted that the 2014 National Heart, Lung, and Blood Institute guidelines recommend using HU to treat all adults with SCA who experience 3 or more moderate-to-severe pain crises within a year. This is a “strong” recommendation based on high-quality evidence reviewed in 2008.

Despite this recommendation, it is thought that HU is underused, although the extent of its use has been unclear.

With that in mind, Dr Stettler and his colleagues examined the use of HU when indicated for SCA in the Optum Normative Health Informatics database. This database is a nationwide sample of commercial health and pharmacy claims from more than 36 million residents in all 50 states and Washington, DC.

The researchers identified adults ages 18 and older with 1 or more inpatient or outpatient claims for SCA between January 2009 and June 2013.

The team selected patients when they had 3 or more hospitalizations, emergency department visits, or both within 12 months that included 1 of the 5 most frequent diagnosis codes used for patients with SCA and pain crises.

Treatment was defined as filling 1 or more HU prescriptions during the 3, 6, or 12 months of continued enrollment following the third episode.

Of the enrolled population (n=26,631,901), the researchers identified 2086 adults with probable SCA. Of these patients, 677 had at least 3 pain-related hospitalizations or emergency department visits within 12 months, and 570 had at least 3 months of coverage after the third episode.

Among those 570 patients, 86 (15%) were treated with HU within 3 months of their third encounter. The percentage of treated patients increased slightly to 18% at 6 months and to 23% at 12 months.

The researchers noted that there are several barriers to HU treatment, including fear of adverse events, lack of clinician training, and failure to engage in shared decision-making.

The team also pointed out that their data do not include the uninsured or publicly insured population, which may have more limited access to healthcare or awareness of treatment options than the patients studied. So these findings may not be representative of the entire US population with SCA and may be a conservative estimate of the HU treatment gap.

To address this gap, it may be necessary to enhance patient outreach and clinician training and develop healthcare quality measures aimed at increasing the use of HU for all patients who would benefit, the researchers said.

Implanting a retrievable filter in the inferior vena cava did not reduce the rate of recurrent pulmonary embolism or mortality in high-risk patients, according to a report published online April 28 in JAMA.

In recent years, there has been a sharp increase in the use of these devices as an add-on to anticoagulant therapy among patients hospitalized for acute PE associated with lower-limb deep or superficial vein thrombosis. Several clinical guidelines advocate this strategy, though others do not, citing the paucity of reliable data concerning both risks and benefits.

The findings in this study “do not support the use of this type of filter in patients who can be treated with anticoagulation alone,” and clinical guidelines recommending this approach should be reexamined, Dr. Patrick Mismetti of the University Hospital of Saint-Etienne, France, and his associates said.

They performed a randomized, open-label clinical study at 17 French medical centers to compare anticoagulation alone against anticoagulation plus implanting a filter to be retrieved 3 months later.

The study participants were 399 adults enrolled during a 6-year period who were deemed at high risk for recurrent PE because of advanced age, active cancer, chronic cardiac or respiratory insufficiency, ischemic stroke with leg paralysis, DVT that was bilateral or affected the iliocaval segment, or signs of right ventricular dysfunction or myocardial injury.

The primary efficacy outcome, recurrent PE within 3 months of hospitalization, developed in 6 of 200 patients assigned to receive an implantable filter (3%) and 3 of the 199 assigned to the control group (1.5%). All but one of these episodes of recurrent PE were fatal. One additional PE developed in each study group between 3 and 6 months. There were no differences between patients who received an inferior vena cava filter and those who did not in the incidence of DVT, major bleeding, or death from any cause at 3 or 6 months, the investigators said (JAMA 2015 April 28 [doi:10.1001/jama.2015.3780]).

Besides failing to prevent recurrent PE, the filter implantation caused access site hematomas in five patients, and the filter itself caused thrombosis formation in three. One patient developed cardiac arrest during the procedure. In addition, retrieval of the device failed in 11 patients because of mechanical problems.

Implanting a retrievable filter in the inferior vena cava did not reduce the rate of recurrent pulmonary embolism or mortality in high-risk patients, according to a report published online April 28 in JAMA.

In recent years, there has been a sharp increase in the use of these devices as an add-on to anticoagulant therapy among patients hospitalized for acute PE associated with lower-limb deep or superficial vein thrombosis. Several clinical guidelines advocate this strategy, though others do not, citing the paucity of reliable data concerning both risks and benefits.

The findings in this study “do not support the use of this type of filter in patients who can be treated with anticoagulation alone,” and clinical guidelines recommending this approach should be reexamined, Dr. Patrick Mismetti of the University Hospital of Saint-Etienne, France, and his associates said.

They performed a randomized, open-label clinical study at 17 French medical centers to compare anticoagulation alone against anticoagulation plus implanting a filter to be retrieved 3 months later.

The study participants were 399 adults enrolled during a 6-year period who were deemed at high risk for recurrent PE because of advanced age, active cancer, chronic cardiac or respiratory insufficiency, ischemic stroke with leg paralysis, DVT that was bilateral or affected the iliocaval segment, or signs of right ventricular dysfunction or myocardial injury.

The primary efficacy outcome, recurrent PE within 3 months of hospitalization, developed in 6 of 200 patients assigned to receive an implantable filter (3%) and 3 of the 199 assigned to the control group (1.5%). All but one of these episodes of recurrent PE were fatal. One additional PE developed in each study group between 3 and 6 months. There were no differences between patients who received an inferior vena cava filter and those who did not in the incidence of DVT, major bleeding, or death from any cause at 3 or 6 months, the investigators said (JAMA 2015 April 28 [doi:10.1001/jama.2015.3780]).

Besides failing to prevent recurrent PE, the filter implantation caused access site hematomas in five patients, and the filter itself caused thrombosis formation in three. One patient developed cardiac arrest during the procedure. In addition, retrieval of the device failed in 11 patients because of mechanical problems.

Implanting a retrievable filter in the inferior vena cava did not reduce the rate of recurrent pulmonary embolism or mortality in high-risk patients, according to a report published online April 28 in JAMA.

In recent years, there has been a sharp increase in the use of these devices as an add-on to anticoagulant therapy among patients hospitalized for acute PE associated with lower-limb deep or superficial vein thrombosis. Several clinical guidelines advocate this strategy, though others do not, citing the paucity of reliable data concerning both risks and benefits.

The findings in this study “do not support the use of this type of filter in patients who can be treated with anticoagulation alone,” and clinical guidelines recommending this approach should be reexamined, Dr. Patrick Mismetti of the University Hospital of Saint-Etienne, France, and his associates said.

They performed a randomized, open-label clinical study at 17 French medical centers to compare anticoagulation alone against anticoagulation plus implanting a filter to be retrieved 3 months later.

The study participants were 399 adults enrolled during a 6-year period who were deemed at high risk for recurrent PE because of advanced age, active cancer, chronic cardiac or respiratory insufficiency, ischemic stroke with leg paralysis, DVT that was bilateral or affected the iliocaval segment, or signs of right ventricular dysfunction or myocardial injury.

The primary efficacy outcome, recurrent PE within 3 months of hospitalization, developed in 6 of 200 patients assigned to receive an implantable filter (3%) and 3 of the 199 assigned to the control group (1.5%). All but one of these episodes of recurrent PE were fatal. One additional PE developed in each study group between 3 and 6 months. There were no differences between patients who received an inferior vena cava filter and those who did not in the incidence of DVT, major bleeding, or death from any cause at 3 or 6 months, the investigators said (JAMA 2015 April 28 [doi:10.1001/jama.2015.3780]).

Besides failing to prevent recurrent PE, the filter implantation caused access site hematomas in five patients, and the filter itself caused thrombosis formation in three. One patient developed cardiac arrest during the procedure. In addition, retrieval of the device failed in 11 patients because of mechanical problems.

KISSIMMEE, FLA. – Reflective confocal microscopic imaging successfully guided carbon dioxide laser ablation of basal cell carcinomas, and imaging results fully matched those from Mohs histology, a small study found.

“Our results suggest that reflective confocal microscopy can accurately guide carbon dioxide laser ablation of superficial and early nodular basal cell carcinomas,” said Dr. Brian Hibler of Memorial Sloan Kettering Cancer Center in New York. The technique provides a real-time, noninvasive way to delineate the tumor area before ablation and to check for residual tumor between passes with the laser, he said at the annual meeting of the American Society for Laser Medicine and surgery.

While conventional and Mohs microscopic surgeries remain the gold standard for removing basal carcinomas (BCC), surgery is not an option for some patients because of tumor location, comorbidities, or personal preferences, Dr. Hibler noted. Past studies have reported good clinical and cosmetic outcomes with laser ablation of BCCs, but use of the modality has been limited because there was no way to assess response without excision or biopsies. Reflective confocal microscopy (RCM) uses a low-powered laser system that provides cellular-level imaging and can distinguish BCCs, he said.

Dr. Hibler and his colleagues performed baseline RCM of eight BCCs (three on the trunk, three on the extremities, and two on the head and neck) from seven patients aged 29-83 years. Two patients were men and five were women. The patients then underwent carbon dioxide laser ablation with a wavelength of 10,600 nm, pulse duration of 750 microseconds, and fluence of 7.5 J/cm², using a square pattern and density of 30%. If RCM revealed residual BCC, the researchers repeated the process up to two more times, for a maximum of three passes. They then removed the entire lesion using Mohs micrographic surgery, performing vertical histologic sectioning of the tissue.

Reflective confocal microscopy generated reliable cellular-level images in real time on the tumor surface and up to 150 mcm deep, Dr. Hibler reported. Tissue from BCCs appears as dense nodular areas with adjacent spaces and red blood cell trafficking, he noted. Microscopy results were consistent with Mohs histology findings in all eight cases, including six in which the tumor was completely removed and two with residual tumor. One of these two cases was the only infiltrative BCC in the series, while the other might have been tissue artifact, Dr. Hibler said.

Patients experienced no adverse effects from the interventions, Dr. Hibler reported. “Future studies are planned are planned without Mohs, so we can use reflective confocal microscopy to longitudinally monitor for recurrence,” he added.

The study won an award at the meeting.

Dr. Hibler reported no funding sources and made no disclosures.

KISSIMMEE, FLA. – Reflective confocal microscopic imaging successfully guided carbon dioxide laser ablation of basal cell carcinomas, and imaging results fully matched those from Mohs histology, a small study found.

“Our results suggest that reflective confocal microscopy can accurately guide carbon dioxide laser ablation of superficial and early nodular basal cell carcinomas,” said Dr. Brian Hibler of Memorial Sloan Kettering Cancer Center in New York. The technique provides a real-time, noninvasive way to delineate the tumor area before ablation and to check for residual tumor between passes with the laser, he said at the annual meeting of the American Society for Laser Medicine and surgery.

While conventional and Mohs microscopic surgeries remain the gold standard for removing basal carcinomas (BCC), surgery is not an option for some patients because of tumor location, comorbidities, or personal preferences, Dr. Hibler noted. Past studies have reported good clinical and cosmetic outcomes with laser ablation of BCCs, but use of the modality has been limited because there was no way to assess response without excision or biopsies. Reflective confocal microscopy (RCM) uses a low-powered laser system that provides cellular-level imaging and can distinguish BCCs, he said.

Dr. Hibler and his colleagues performed baseline RCM of eight BCCs (three on the trunk, three on the extremities, and two on the head and neck) from seven patients aged 29-83 years. Two patients were men and five were women. The patients then underwent carbon dioxide laser ablation with a wavelength of 10,600 nm, pulse duration of 750 microseconds, and fluence of 7.5 J/cm², using a square pattern and density of 30%. If RCM revealed residual BCC, the researchers repeated the process up to two more times, for a maximum of three passes. They then removed the entire lesion using Mohs micrographic surgery, performing vertical histologic sectioning of the tissue.

Reflective confocal microscopy generated reliable cellular-level images in real time on the tumor surface and up to 150 mcm deep, Dr. Hibler reported. Tissue from BCCs appears as dense nodular areas with adjacent spaces and red blood cell trafficking, he noted. Microscopy results were consistent with Mohs histology findings in all eight cases, including six in which the tumor was completely removed and two with residual tumor. One of these two cases was the only infiltrative BCC in the series, while the other might have been tissue artifact, Dr. Hibler said.

Patients experienced no adverse effects from the interventions, Dr. Hibler reported. “Future studies are planned are planned without Mohs, so we can use reflective confocal microscopy to longitudinally monitor for recurrence,” he added.

The study won an award at the meeting.

Dr. Hibler reported no funding sources and made no disclosures.

KISSIMMEE, FLA. – Reflective confocal microscopic imaging successfully guided carbon dioxide laser ablation of basal cell carcinomas, and imaging results fully matched those from Mohs histology, a small study found.

“Our results suggest that reflective confocal microscopy can accurately guide carbon dioxide laser ablation of superficial and early nodular basal cell carcinomas,” said Dr. Brian Hibler of Memorial Sloan Kettering Cancer Center in New York. The technique provides a real-time, noninvasive way to delineate the tumor area before ablation and to check for residual tumor between passes with the laser, he said at the annual meeting of the American Society for Laser Medicine and surgery.

While conventional and Mohs microscopic surgeries remain the gold standard for removing basal carcinomas (BCC), surgery is not an option for some patients because of tumor location, comorbidities, or personal preferences, Dr. Hibler noted. Past studies have reported good clinical and cosmetic outcomes with laser ablation of BCCs, but use of the modality has been limited because there was no way to assess response without excision or biopsies. Reflective confocal microscopy (RCM) uses a low-powered laser system that provides cellular-level imaging and can distinguish BCCs, he said.

Dr. Hibler and his colleagues performed baseline RCM of eight BCCs (three on the trunk, three on the extremities, and two on the head and neck) from seven patients aged 29-83 years. Two patients were men and five were women. The patients then underwent carbon dioxide laser ablation with a wavelength of 10,600 nm, pulse duration of 750 microseconds, and fluence of 7.5 J/cm², using a square pattern and density of 30%. If RCM revealed residual BCC, the researchers repeated the process up to two more times, for a maximum of three passes. They then removed the entire lesion using Mohs micrographic surgery, performing vertical histologic sectioning of the tissue.

Reflective confocal microscopy generated reliable cellular-level images in real time on the tumor surface and up to 150 mcm deep, Dr. Hibler reported. Tissue from BCCs appears as dense nodular areas with adjacent spaces and red blood cell trafficking, he noted. Microscopy results were consistent with Mohs histology findings in all eight cases, including six in which the tumor was completely removed and two with residual tumor. One of these two cases was the only infiltrative BCC in the series, while the other might have been tissue artifact, Dr. Hibler said.

Patients experienced no adverse effects from the interventions, Dr. Hibler reported. “Future studies are planned are planned without Mohs, so we can use reflective confocal microscopy to longitudinally monitor for recurrence,” he added.

The study won an award at the meeting.

Dr. Hibler reported no funding sources and made no disclosures.

ORLANDO – Hormonal add-back therapy using combination norethindrone acetate and conjugated equine estrogens was effective and better than norethindrone acetate plus placebo for preserving bone health and improving quality of life in adolescents receiving treatment with gonadotropin-releasing hormone agonists (GnRH-A) for endometriosis in a randomized, double-blind, placebo-controlled study.

Of 51 adolescents aged 15-22 years who were initiating GnRH-A therapy for endometriosis, 25 were randomized to receive add-back therapy with 5 mg daily oral norethindrone acetate (NA) plus 0.625 mg oral daily conjugated equine estrogens (CEE), and 26 were randomized to receive NA plus placebo; 18 and 16, respectively, completed the study.

Those in the combination-therapy group experienced significant increases over 12 months in both total body bone mineral content (BMC) and bone mineral density (BMD), compared with those who received NA plus placebo. BMC increased by nearly 40 g/unit scanned in the combination-therapy group, compared with about 12 g in the NA plus placebo group, and BMD increased more than 0.01 g/cm², compared with no change in the NA plus placebo group, Dr. Amy D. DiVasta reported at the North American Society for Pediatric and Adolescent Gynecology annual meeting.

No losses of total hip or lumbar spine BMC or BMD occurred, said Dr. DiVasta of Boston Children’s Hospital.

Further, lean mass increased in the combination-therapy group at 12 months – by about 1.4 kg, compared with no change in the placebo group. No differences were seen between the groups in change in fat mass.

As for quality of life measures, overall physical health scores at baseline were significantly below the U.S. mean in both groups, and overall mental health scores were above the U.S. mean in both groups. Both groups improved over time on both measures; the increase in the Physical Component Summary scale scores on the SF-36 (Short Form 36 Health Survey) was significantly greater with combination-therapy group (increase from about 40 to 50 out of 100 ), compared with NA plus placebo (increase from about 40 to 45), but the increases on the Mental Component Summary scale scores were not statistically significant in either group, or between the groups.

The study subjects, who were treated for 12 months between 2008 and 2012, were at least 2 years post menarche at baseline and had a surgical diagnosis of endometriosis. The two treatment groups were similar with respect to baseline characteristics, including age, BMD Z score, and disease severity. No significant side effects were observed in either the combination or NA plus placebo group, Dr. DiVasta said, noting that laboratory tests included liver function tests and lipid levels.

Areal BMD, BMC, and body composition were measured by dual-energy X-ray absorptiometry (DXA) at baseline, 6 months, and 12 months. Anthropometrics, quality of life measures, and laboratory studies were conducted at 1, 3, 6, and 12 months.

GnRH-A are commonly utilized for endometriosis patients who fail primary therapy, such as NSAIDs or combined oral contraceptives, but long-term use is associated with deleterious effects on bone mineralization; adults have been shown to lose 5%-8% of BMD after 3-6 months of treatment, Dr. DiVasta noted.

Hormonal add-back therapy is a promising adjunct to counteract these effects and could be an important tool for protecting adolescents, who are at the greatest risk for the deleterious effects of GnRH-A therapy, she said.

In the current study, hormonal add-back did successfully protect bone health and improve quality of life for adolescents with endometriosis who were treated with 12 months of GnRH-A. Combination therapy with NA and CEE appears to be more effective for increasing total body BMC and BMD, lean mass, and physical health-related quality of life, as compared with NA monotherapy, she said.

The findings are limited by the inclusion of only skeletally mature young women, as the results may not be generalizable to growing girls. Also, DXA measures provide two-dimensional measures of bone mineral density, and do not yield information regarding skeletal strength or bone microarchitecture, she noted.

“Given the prevalence of endometriosis, our data suggest norethindrone plus estrogens to be a useful adjunctive therapy to prevent bone loss in these young women while they receive appropriate medical treatment for their underlying disease,” she concluded, noting that future work will explore the effects of add-back on the peripheral skeleton and bone strength.

This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the McCarthy Family Foundation, Thrasher Research Fund, and Boston Children’s Hospital department of medicine. Medications were provided by Abbott, Duramed Pharmaceuticals, and Wyeth Pharmaceuticals. Dr. DiVasta reported having no relevant financial disclosures.

[email protected]

ORLANDO – Hormonal add-back therapy using combination norethindrone acetate and conjugated equine estrogens was effective and better than norethindrone acetate plus placebo for preserving bone health and improving quality of life in adolescents receiving treatment with gonadotropin-releasing hormone agonists (GnRH-A) for endometriosis in a randomized, double-blind, placebo-controlled study.

Of 51 adolescents aged 15-22 years who were initiating GnRH-A therapy for endometriosis, 25 were randomized to receive add-back therapy with 5 mg daily oral norethindrone acetate (NA) plus 0.625 mg oral daily conjugated equine estrogens (CEE), and 26 were randomized to receive NA plus placebo; 18 and 16, respectively, completed the study.

Those in the combination-therapy group experienced significant increases over 12 months in both total body bone mineral content (BMC) and bone mineral density (BMD), compared with those who received NA plus placebo. BMC increased by nearly 40 g/unit scanned in the combination-therapy group, compared with about 12 g in the NA plus placebo group, and BMD increased more than 0.01 g/cm², compared with no change in the NA plus placebo group, Dr. Amy D. DiVasta reported at the North American Society for Pediatric and Adolescent Gynecology annual meeting.

No losses of total hip or lumbar spine BMC or BMD occurred, said Dr. DiVasta of Boston Children’s Hospital.

Further, lean mass increased in the combination-therapy group at 12 months – by about 1.4 kg, compared with no change in the placebo group. No differences were seen between the groups in change in fat mass.

As for quality of life measures, overall physical health scores at baseline were significantly below the U.S. mean in both groups, and overall mental health scores were above the U.S. mean in both groups. Both groups improved over time on both measures; the increase in the Physical Component Summary scale scores on the SF-36 (Short Form 36 Health Survey) was significantly greater with combination-therapy group (increase from about 40 to 50 out of 100 ), compared with NA plus placebo (increase from about 40 to 45), but the increases on the Mental Component Summary scale scores were not statistically significant in either group, or between the groups.

The study subjects, who were treated for 12 months between 2008 and 2012, were at least 2 years post menarche at baseline and had a surgical diagnosis of endometriosis. The two treatment groups were similar with respect to baseline characteristics, including age, BMD Z score, and disease severity. No significant side effects were observed in either the combination or NA plus placebo group, Dr. DiVasta said, noting that laboratory tests included liver function tests and lipid levels.

Areal BMD, BMC, and body composition were measured by dual-energy X-ray absorptiometry (DXA) at baseline, 6 months, and 12 months. Anthropometrics, quality of life measures, and laboratory studies were conducted at 1, 3, 6, and 12 months.

GnRH-A are commonly utilized for endometriosis patients who fail primary therapy, such as NSAIDs or combined oral contraceptives, but long-term use is associated with deleterious effects on bone mineralization; adults have been shown to lose 5%-8% of BMD after 3-6 months of treatment, Dr. DiVasta noted.

Hormonal add-back therapy is a promising adjunct to counteract these effects and could be an important tool for protecting adolescents, who are at the greatest risk for the deleterious effects of GnRH-A therapy, she said.

In the current study, hormonal add-back did successfully protect bone health and improve quality of life for adolescents with endometriosis who were treated with 12 months of GnRH-A. Combination therapy with NA and CEE appears to be more effective for increasing total body BMC and BMD, lean mass, and physical health-related quality of life, as compared with NA monotherapy, she said.

The findings are limited by the inclusion of only skeletally mature young women, as the results may not be generalizable to growing girls. Also, DXA measures provide two-dimensional measures of bone mineral density, and do not yield information regarding skeletal strength or bone microarchitecture, she noted.

“Given the prevalence of endometriosis, our data suggest norethindrone plus estrogens to be a useful adjunctive therapy to prevent bone loss in these young women while they receive appropriate medical treatment for their underlying disease,” she concluded, noting that future work will explore the effects of add-back on the peripheral skeleton and bone strength.

This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the McCarthy Family Foundation, Thrasher Research Fund, and Boston Children’s Hospital department of medicine. Medications were provided by Abbott, Duramed Pharmaceuticals, and Wyeth Pharmaceuticals. Dr. DiVasta reported having no relevant financial disclosures.

[email protected]

ORLANDO – Hormonal add-back therapy using combination norethindrone acetate and conjugated equine estrogens was effective and better than norethindrone acetate plus placebo for preserving bone health and improving quality of life in adolescents receiving treatment with gonadotropin-releasing hormone agonists (GnRH-A) for endometriosis in a randomized, double-blind, placebo-controlled study.

Of 51 adolescents aged 15-22 years who were initiating GnRH-A therapy for endometriosis, 25 were randomized to receive add-back therapy with 5 mg daily oral norethindrone acetate (NA) plus 0.625 mg oral daily conjugated equine estrogens (CEE), and 26 were randomized to receive NA plus placebo; 18 and 16, respectively, completed the study.

Those in the combination-therapy group experienced significant increases over 12 months in both total body bone mineral content (BMC) and bone mineral density (BMD), compared with those who received NA plus placebo. BMC increased by nearly 40 g/unit scanned in the combination-therapy group, compared with about 12 g in the NA plus placebo group, and BMD increased more than 0.01 g/cm², compared with no change in the NA plus placebo group, Dr. Amy D. DiVasta reported at the North American Society for Pediatric and Adolescent Gynecology annual meeting.

No losses of total hip or lumbar spine BMC or BMD occurred, said Dr. DiVasta of Boston Children’s Hospital.

Further, lean mass increased in the combination-therapy group at 12 months – by about 1.4 kg, compared with no change in the placebo group. No differences were seen between the groups in change in fat mass.

As for quality of life measures, overall physical health scores at baseline were significantly below the U.S. mean in both groups, and overall mental health scores were above the U.S. mean in both groups. Both groups improved over time on both measures; the increase in the Physical Component Summary scale scores on the SF-36 (Short Form 36 Health Survey) was significantly greater with combination-therapy group (increase from about 40 to 50 out of 100 ), compared with NA plus placebo (increase from about 40 to 45), but the increases on the Mental Component Summary scale scores were not statistically significant in either group, or between the groups.

The study subjects, who were treated for 12 months between 2008 and 2012, were at least 2 years post menarche at baseline and had a surgical diagnosis of endometriosis. The two treatment groups were similar with respect to baseline characteristics, including age, BMD Z score, and disease severity. No significant side effects were observed in either the combination or NA plus placebo group, Dr. DiVasta said, noting that laboratory tests included liver function tests and lipid levels.

Areal BMD, BMC, and body composition were measured by dual-energy X-ray absorptiometry (DXA) at baseline, 6 months, and 12 months. Anthropometrics, quality of life measures, and laboratory studies were conducted at 1, 3, 6, and 12 months.

GnRH-A are commonly utilized for endometriosis patients who fail primary therapy, such as NSAIDs or combined oral contraceptives, but long-term use is associated with deleterious effects on bone mineralization; adults have been shown to lose 5%-8% of BMD after 3-6 months of treatment, Dr. DiVasta noted.

Hormonal add-back therapy is a promising adjunct to counteract these effects and could be an important tool for protecting adolescents, who are at the greatest risk for the deleterious effects of GnRH-A therapy, she said.

In the current study, hormonal add-back did successfully protect bone health and improve quality of life for adolescents with endometriosis who were treated with 12 months of GnRH-A. Combination therapy with NA and CEE appears to be more effective for increasing total body BMC and BMD, lean mass, and physical health-related quality of life, as compared with NA monotherapy, she said.

The findings are limited by the inclusion of only skeletally mature young women, as the results may not be generalizable to growing girls. Also, DXA measures provide two-dimensional measures of bone mineral density, and do not yield information regarding skeletal strength or bone microarchitecture, she noted.

“Given the prevalence of endometriosis, our data suggest norethindrone plus estrogens to be a useful adjunctive therapy to prevent bone loss in these young women while they receive appropriate medical treatment for their underlying disease,” she concluded, noting that future work will explore the effects of add-back on the peripheral skeleton and bone strength.

This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the McCarthy Family Foundation, Thrasher Research Fund, and Boston Children’s Hospital department of medicine. Medications were provided by Abbott, Duramed Pharmaceuticals, and Wyeth Pharmaceuticals. Dr. DiVasta reported having no relevant financial disclosures.

[email protected]