Spending on care of hospitalized patients is expected to pass $1 trillion in 2015, a new high. Thomas Selden, PhD, of the Agency for Healthcare Research and Quality recently asked where that money is likely to go. The answer: private insurers.

Dr. Selden and his colleagues report in Health Affairs this month that in 2012, private insurers’ payment rates for inpatient hospital stays were approximately 75% greater than Medicare’s payment rates, a sharp increase from the differential of approximately 10% percent during the period of 1996 to 2001. “We need to understand who’s paying what,” Dr. Selden says. “It’s the first step to a better understanding of public policy.”

The report found that “the predicted percentage difference between the rates of private insurers and those of Medicare has increased substantially over time.” In 1996, private insurers paid 106.1% of Medicare payment rates, a payment rate difference of 6.1% (95% CI: -3.2, 15.5). The difference climbed to 64.1% (95% CI: 48.3, 80.0) in 2011 and 75.3% (95% CI: 52.0, 98.6) in 2012. Medicaid payment rates averaged approximately 90% of Medicare payment rates throughout the study period.

Dr. Selden is hopeful that stakeholders will use the data his team collected to determine the impetus for the widening gap. He also plans to research whether payment differences affect quality metrics.

“Anytime you’re talking about a trillion dollars, it’s really important when a payment difference opens up of this magnitude,” he adds. “The difference is real … what the policy implications are is for the policy makers to decide.” TH

Visit our website for more information on healthcare payment models.

Spending on care of hospitalized patients is expected to pass $1 trillion in 2015, a new high. Thomas Selden, PhD, of the Agency for Healthcare Research and Quality recently asked where that money is likely to go. The answer: private insurers.

Dr. Selden and his colleagues report in Health Affairs this month that in 2012, private insurers’ payment rates for inpatient hospital stays were approximately 75% greater than Medicare’s payment rates, a sharp increase from the differential of approximately 10% percent during the period of 1996 to 2001. “We need to understand who’s paying what,” Dr. Selden says. “It’s the first step to a better understanding of public policy.”

The report found that “the predicted percentage difference between the rates of private insurers and those of Medicare has increased substantially over time.” In 1996, private insurers paid 106.1% of Medicare payment rates, a payment rate difference of 6.1% (95% CI: -3.2, 15.5). The difference climbed to 64.1% (95% CI: 48.3, 80.0) in 2011 and 75.3% (95% CI: 52.0, 98.6) in 2012. Medicaid payment rates averaged approximately 90% of Medicare payment rates throughout the study period.

Dr. Selden is hopeful that stakeholders will use the data his team collected to determine the impetus for the widening gap. He also plans to research whether payment differences affect quality metrics.

“Anytime you’re talking about a trillion dollars, it’s really important when a payment difference opens up of this magnitude,” he adds. “The difference is real … what the policy implications are is for the policy makers to decide.” TH

Visit our website for more information on healthcare payment models.

Spending on care of hospitalized patients is expected to pass $1 trillion in 2015, a new high. Thomas Selden, PhD, of the Agency for Healthcare Research and Quality recently asked where that money is likely to go. The answer: private insurers.

Dr. Selden and his colleagues report in Health Affairs this month that in 2012, private insurers’ payment rates for inpatient hospital stays were approximately 75% greater than Medicare’s payment rates, a sharp increase from the differential of approximately 10% percent during the period of 1996 to 2001. “We need to understand who’s paying what,” Dr. Selden says. “It’s the first step to a better understanding of public policy.”

The report found that “the predicted percentage difference between the rates of private insurers and those of Medicare has increased substantially over time.” In 1996, private insurers paid 106.1% of Medicare payment rates, a payment rate difference of 6.1% (95% CI: -3.2, 15.5). The difference climbed to 64.1% (95% CI: 48.3, 80.0) in 2011 and 75.3% (95% CI: 52.0, 98.6) in 2012. Medicaid payment rates averaged approximately 90% of Medicare payment rates throughout the study period.

Dr. Selden is hopeful that stakeholders will use the data his team collected to determine the impetus for the widening gap. He also plans to research whether payment differences affect quality metrics.

“Anytime you’re talking about a trillion dollars, it’s really important when a payment difference opens up of this magnitude,” he adds. “The difference is real … what the policy implications are is for the policy makers to decide.” TH

Visit our website for more information on healthcare payment models.

Suicide attempts and recurrent suicide attempts are associated with subsequent epilepsy, suggesting a common underlying biology, according to a study published online ahead of print December 9 in JAMA Psychiatry. The population-based retrospective cohort study in the United Kingdom included patients with incident epilepsy and control patients without a history of epilepsy. For 14,059 patients who later had an onset of epilepsy, versus 56,184 control patients, the risk for a first suicide attempt during the time period before the case patients received a diagnosis of epilepsy was increased 2.9-fold. For 278 case patients who later had an onset of epilepsy, versus 434 control patients, the risk for a recurrent suicide attempt up to and including the day that epilepsy was diagnosed was increased 1.8-fold.

Asthma is associated with an increased risk of new-onset chronic migraine one year later among individuals with episodic migraine, and the highest risk is among people with the greatest number of respiratory symptoms, according to a study published online ahead of print November 19 in Headache. Using the European Community Respiratory Health Survey, researchers defined asthma as a binary variable based on an empirical cut score and developed a Respiratory Symptom Severity Score based on the number of positive responses. This study included 4,446 individuals with episodic migraine in 2008, of whom 17% had asthma. In 2009, new-onset chronic migraine developed in 2.9% of the 2008 episodic migraine cohort, including 5.4% of the asthma subgroup and 2.5% of the non-asthma subgroup.

Vagus nerve stimulation (VNS) paired with rehabilitation is feasible and safe, according to a study published online ahead of print December 8 in Stroke. Twenty-one participants with ischemic stroke more than six months earlier and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three two-hour sessions per week for six weeks. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five patients had minor adverse device effects, including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different between groups. In the per-protocol analysis, researchers found a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score between groups.

The Chikungunya virus is a significant cause of CNS disease, according to a study published online ahead of print November 25 in Neurology. During the La Réunion outbreak between September 2005 and June 2006, 57 patients were diagnosed with Chikungunya virus-associated CNS disease, including 24 with Chikungunya virus-associated encephalitis (which corresponded to a cumulative incidence rate of 8.6 per 100,000 people). Patients with encephalitis were observed at both extremes of age categories. The cumulative incidence rates per 100,000 persons were 187 and 37 in patients younger than 1 and patients older than 65, respectively. The case-fatality rate of Chikungunya virus-associated encephalitis was 16.6%, and the proportion of children discharged with persistent disabilities was estimated at between 30% and 45%. Beyond the neonatal period, the clinical presentation and outcomes were less severe in infants than in adults.

Acute stroke is preventable to some extent in most patients, according to a study published online ahead of print December 7 in JAMA Neurology. Researchers evaluated the medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012. Mean patient age was 67.2. Seventy-one patients (25.9%) had scores of 4 or greater on a 10-point scale, indicating that the stroke was highly preventable. Severity of stroke was not related to preventability of stroke. However, 29.6% of patients whose stroke was highly preventable were treated with IV or intra-arterial acute stroke therapy. These treatments were provided for 19.4% of patients with scores of 0, and 14% of patients with scores of 1 to 3.

Alpha-blocker therapy is associated with an increased risk of ischemic stroke during the early initiation period, especially among patients who are not taking other antihypertensive agents, according to a study published online ahead of print December 7 in Canadian Medical Association Journal. Researchers identified 7,502 men ages 50 and older as of 2007 who were incident users of alpha-blockers and who had a diagnosis of ischemic stroke during the study period, which lasted from 2007 to 2009. Investigators examined the incidence of stroke during risk periods before and after alpha-blocker prescription. Compared with the risk in the unexposed period, the risk of ischemic stroke was increased within 21 days after alpha-blocker initiation among all patients in the study population and among patients without concomitant prescriptions.

In patients with mild Alzheimer’s disease, moderate alcohol consumption (ie, two to three units per day) is associated with a significantly lower mortality over a period of 36 months, according to a study published December 11 in BMJ Open. Investigators examined data collected as part of the Danish Alzheimer’s Intervention Study (DAISY). Information about current daily alcohol consumption was obtained from 321 study participants. In all, 8% abstained from drinking alcohol, 71% drank alcohol occasionally, 17% had two to three units per day, and 4% had more than three units per day. Mortality was not significantly different in abstinent patients or in patients with an alcohol consumption of more than three units per day, compared with patients drinking one or less than one unit per day.

Stress is a potentially remediable risk factor for amnestic mild cognitive impairment (aMCI), according to a study published online ahead of print December 10 in Alzheimer Disease & Associated Disorders. The Perceived Stress Scale (PSS) was administered annually in the Einstein Aging Study to participants age 70 and older who were free of aMCI and dementia at baseline PSS administration and who had at least one subsequent annual follow-up. Cox hazard models were used to examine time to aMCI onset, adjusting for covariates. High levels of perceived stress were associated with a 30% greater risk of incident aMCI, independent of covariates. Overall, understanding the effect that perceived stress has on cognition may lead to intervention strategies that prevent the onset of aMCI and Alzheimer’s-related dementia, said the investigators.

Heptachlor epoxide, a pesticide, is associated with higher risk for signs of Parkinson’s disease, according to a study published online ahead of print December 9 in Neurology. For the study, 449 Japanese-American men with an average age of 54 were followed for more than 30 years and until death in the Honolulu-Asia Aging Study. Tests determined whether participants had lost brain cells in the substantia nigra. In 116 brains, researchers also measured the amount of heptachlor epoxide residue, which was present at high levels in Hawaii’s milk in the early 1980s. Nonsmokers who drank more than two cups of milk per day had 40% fewer brain cells in the substantia nigra than people who drank less than two cups of milk per day.

An in vivo florbetapir PET study confirms previous postmortem evidence showing an association between Alzheimer’s disease pathology and gait speed, and provides additional evidence on potential regional effects of brain β-amyloid on motor function, according to data published online ahead of print December 7 in Neurology. Cross-sectional associations between brain β-amyloid, as measured with [¹⁸F]florbetapir PET, and gait speed were examined in 128 elderly participants. Researchers found a significant association between β-amyloid in the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate and slow gait speed. A multivariate model emphasized the posterior putamen and the precuneus. The β-amyloid burden explained as much as 9% of the variance in gait speed and significantly improved regression models that contained demographic variables, BMI, and APOE status.

Blast-related injury and loss of consciousness are common in traumatic brain injury (TBI) that is sustained while in the military, according to a study published online ahead of print December 15 in Radiology. Study participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI. MRIs were performed at 3 T, primarily with three-dimensional volume imaging at voxels smaller than 1 mm³. In all, 84.2% of participants reported one or more blast-related incidents, and 63.0% reported loss of consciousness at the time of injury. White matter T2-weighted hyperintense areas were the most common pathologic finding and were observed in 51.8% of TBI participants.

Researchers have created a transgenic mouse models of familial amyotrophic lateral sclerosis (ALS), according to research published in the December 2 issue of Neuron. To investigate the pathologic role of C9ORF72 in ALS and frontotemporal dementia (FTD), researchers generated a line of mice carrying a bacterial artificial chromosome containing exons one to six of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. The mice showed no overt behavioral phenotype, but recapitulated distinctive histopathologic features of C9ORF72 ALS/FTD, including sense and antisense intranuclear RNA foci and poly(glycine-proline) dipeptide repeat proteins. Using an artificial microRNA that targets human C9ORF72 in cultures of primary cortical neurons from the C9BAC mice, investigators attenuated expression of the C9BAC transgene and the poly(GP) dipeptides.

Oxidative stress may underlie most of the migraine triggers encountered in clinical practice, according to a study published online ahead of print December 7 in Headache. Investigators searched the literature for studies of common migraine triggers published between 1990 and 2014. The reference lists of the resulting articles were examined for further relevant studies. In all cases except pericranial pain, common migraine triggers are capable of generating oxidative stress. Mechanisms include a high rate of energy production by the mitochondria, toxicity or altered membrane properties of the mitochondria, calcium overload and excitotoxicity, neuroinflammation and activation of microglia, and activation of neuronal nicotinamide adenine dinucleotide phosphate oxidase. For some triggers, oxidants also arise as a byproduct of monoamine oxidase or cytochrome P450 processing, or from uncoupling of nitric oxide synthase.

—Kimberly Williams

Suicide attempts and recurrent suicide attempts are associated with subsequent epilepsy, suggesting a common underlying biology, according to a study published online ahead of print December 9 in JAMA Psychiatry. The population-based retrospective cohort study in the United Kingdom included patients with incident epilepsy and control patients without a history of epilepsy. For 14,059 patients who later had an onset of epilepsy, versus 56,184 control patients, the risk for a first suicide attempt during the time period before the case patients received a diagnosis of epilepsy was increased 2.9-fold. For 278 case patients who later had an onset of epilepsy, versus 434 control patients, the risk for a recurrent suicide attempt up to and including the day that epilepsy was diagnosed was increased 1.8-fold.

Asthma is associated with an increased risk of new-onset chronic migraine one year later among individuals with episodic migraine, and the highest risk is among people with the greatest number of respiratory symptoms, according to a study published online ahead of print November 19 in Headache. Using the European Community Respiratory Health Survey, researchers defined asthma as a binary variable based on an empirical cut score and developed a Respiratory Symptom Severity Score based on the number of positive responses. This study included 4,446 individuals with episodic migraine in 2008, of whom 17% had asthma. In 2009, new-onset chronic migraine developed in 2.9% of the 2008 episodic migraine cohort, including 5.4% of the asthma subgroup and 2.5% of the non-asthma subgroup.

Vagus nerve stimulation (VNS) paired with rehabilitation is feasible and safe, according to a study published online ahead of print December 8 in Stroke. Twenty-one participants with ischemic stroke more than six months earlier and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three two-hour sessions per week for six weeks. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five patients had minor adverse device effects, including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different between groups. In the per-protocol analysis, researchers found a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score between groups.

The Chikungunya virus is a significant cause of CNS disease, according to a study published online ahead of print November 25 in Neurology. During the La Réunion outbreak between September 2005 and June 2006, 57 patients were diagnosed with Chikungunya virus-associated CNS disease, including 24 with Chikungunya virus-associated encephalitis (which corresponded to a cumulative incidence rate of 8.6 per 100,000 people). Patients with encephalitis were observed at both extremes of age categories. The cumulative incidence rates per 100,000 persons were 187 and 37 in patients younger than 1 and patients older than 65, respectively. The case-fatality rate of Chikungunya virus-associated encephalitis was 16.6%, and the proportion of children discharged with persistent disabilities was estimated at between 30% and 45%. Beyond the neonatal period, the clinical presentation and outcomes were less severe in infants than in adults.

Acute stroke is preventable to some extent in most patients, according to a study published online ahead of print December 7 in JAMA Neurology. Researchers evaluated the medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012. Mean patient age was 67.2. Seventy-one patients (25.9%) had scores of 4 or greater on a 10-point scale, indicating that the stroke was highly preventable. Severity of stroke was not related to preventability of stroke. However, 29.6% of patients whose stroke was highly preventable were treated with IV or intra-arterial acute stroke therapy. These treatments were provided for 19.4% of patients with scores of 0, and 14% of patients with scores of 1 to 3.

Alpha-blocker therapy is associated with an increased risk of ischemic stroke during the early initiation period, especially among patients who are not taking other antihypertensive agents, according to a study published online ahead of print December 7 in Canadian Medical Association Journal. Researchers identified 7,502 men ages 50 and older as of 2007 who were incident users of alpha-blockers and who had a diagnosis of ischemic stroke during the study period, which lasted from 2007 to 2009. Investigators examined the incidence of stroke during risk periods before and after alpha-blocker prescription. Compared with the risk in the unexposed period, the risk of ischemic stroke was increased within 21 days after alpha-blocker initiation among all patients in the study population and among patients without concomitant prescriptions.

In patients with mild Alzheimer’s disease, moderate alcohol consumption (ie, two to three units per day) is associated with a significantly lower mortality over a period of 36 months, according to a study published December 11 in BMJ Open. Investigators examined data collected as part of the Danish Alzheimer’s Intervention Study (DAISY). Information about current daily alcohol consumption was obtained from 321 study participants. In all, 8% abstained from drinking alcohol, 71% drank alcohol occasionally, 17% had two to three units per day, and 4% had more than three units per day. Mortality was not significantly different in abstinent patients or in patients with an alcohol consumption of more than three units per day, compared with patients drinking one or less than one unit per day.

Stress is a potentially remediable risk factor for amnestic mild cognitive impairment (aMCI), according to a study published online ahead of print December 10 in Alzheimer Disease & Associated Disorders. The Perceived Stress Scale (PSS) was administered annually in the Einstein Aging Study to participants age 70 and older who were free of aMCI and dementia at baseline PSS administration and who had at least one subsequent annual follow-up. Cox hazard models were used to examine time to aMCI onset, adjusting for covariates. High levels of perceived stress were associated with a 30% greater risk of incident aMCI, independent of covariates. Overall, understanding the effect that perceived stress has on cognition may lead to intervention strategies that prevent the onset of aMCI and Alzheimer’s-related dementia, said the investigators.

Heptachlor epoxide, a pesticide, is associated with higher risk for signs of Parkinson’s disease, according to a study published online ahead of print December 9 in Neurology. For the study, 449 Japanese-American men with an average age of 54 were followed for more than 30 years and until death in the Honolulu-Asia Aging Study. Tests determined whether participants had lost brain cells in the substantia nigra. In 116 brains, researchers also measured the amount of heptachlor epoxide residue, which was present at high levels in Hawaii’s milk in the early 1980s. Nonsmokers who drank more than two cups of milk per day had 40% fewer brain cells in the substantia nigra than people who drank less than two cups of milk per day.

An in vivo florbetapir PET study confirms previous postmortem evidence showing an association between Alzheimer’s disease pathology and gait speed, and provides additional evidence on potential regional effects of brain β-amyloid on motor function, according to data published online ahead of print December 7 in Neurology. Cross-sectional associations between brain β-amyloid, as measured with [¹⁸F]florbetapir PET, and gait speed were examined in 128 elderly participants. Researchers found a significant association between β-amyloid in the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate and slow gait speed. A multivariate model emphasized the posterior putamen and the precuneus. The β-amyloid burden explained as much as 9% of the variance in gait speed and significantly improved regression models that contained demographic variables, BMI, and APOE status.

Blast-related injury and loss of consciousness are common in traumatic brain injury (TBI) that is sustained while in the military, according to a study published online ahead of print December 15 in Radiology. Study participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI. MRIs were performed at 3 T, primarily with three-dimensional volume imaging at voxels smaller than 1 mm³. In all, 84.2% of participants reported one or more blast-related incidents, and 63.0% reported loss of consciousness at the time of injury. White matter T2-weighted hyperintense areas were the most common pathologic finding and were observed in 51.8% of TBI participants.

Researchers have created a transgenic mouse models of familial amyotrophic lateral sclerosis (ALS), according to research published in the December 2 issue of Neuron. To investigate the pathologic role of C9ORF72 in ALS and frontotemporal dementia (FTD), researchers generated a line of mice carrying a bacterial artificial chromosome containing exons one to six of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. The mice showed no overt behavioral phenotype, but recapitulated distinctive histopathologic features of C9ORF72 ALS/FTD, including sense and antisense intranuclear RNA foci and poly(glycine-proline) dipeptide repeat proteins. Using an artificial microRNA that targets human C9ORF72 in cultures of primary cortical neurons from the C9BAC mice, investigators attenuated expression of the C9BAC transgene and the poly(GP) dipeptides.

Oxidative stress may underlie most of the migraine triggers encountered in clinical practice, according to a study published online ahead of print December 7 in Headache. Investigators searched the literature for studies of common migraine triggers published between 1990 and 2014. The reference lists of the resulting articles were examined for further relevant studies. In all cases except pericranial pain, common migraine triggers are capable of generating oxidative stress. Mechanisms include a high rate of energy production by the mitochondria, toxicity or altered membrane properties of the mitochondria, calcium overload and excitotoxicity, neuroinflammation and activation of microglia, and activation of neuronal nicotinamide adenine dinucleotide phosphate oxidase. For some triggers, oxidants also arise as a byproduct of monoamine oxidase or cytochrome P450 processing, or from uncoupling of nitric oxide synthase.

—Kimberly Williams

Suicide attempts and recurrent suicide attempts are associated with subsequent epilepsy, suggesting a common underlying biology, according to a study published online ahead of print December 9 in JAMA Psychiatry. The population-based retrospective cohort study in the United Kingdom included patients with incident epilepsy and control patients without a history of epilepsy. For 14,059 patients who later had an onset of epilepsy, versus 56,184 control patients, the risk for a first suicide attempt during the time period before the case patients received a diagnosis of epilepsy was increased 2.9-fold. For 278 case patients who later had an onset of epilepsy, versus 434 control patients, the risk for a recurrent suicide attempt up to and including the day that epilepsy was diagnosed was increased 1.8-fold.

Asthma is associated with an increased risk of new-onset chronic migraine one year later among individuals with episodic migraine, and the highest risk is among people with the greatest number of respiratory symptoms, according to a study published online ahead of print November 19 in Headache. Using the European Community Respiratory Health Survey, researchers defined asthma as a binary variable based on an empirical cut score and developed a Respiratory Symptom Severity Score based on the number of positive responses. This study included 4,446 individuals with episodic migraine in 2008, of whom 17% had asthma. In 2009, new-onset chronic migraine developed in 2.9% of the 2008 episodic migraine cohort, including 5.4% of the asthma subgroup and 2.5% of the non-asthma subgroup.

Vagus nerve stimulation (VNS) paired with rehabilitation is feasible and safe, according to a study published online ahead of print December 8 in Stroke. Twenty-one participants with ischemic stroke more than six months earlier and moderate to severe upper-limb impairment were randomized to VNS plus rehabilitation or rehabilitation alone. Rehabilitation consisted of three two-hour sessions per week for six weeks. There were no serious adverse device effects. One patient had transient vocal cord palsy and dysphagia after implantation. Five patients had minor adverse device effects, including nausea and taste disturbance on the evening of therapy. In the intention-to-treat analysis, the change in Fugl-Meyer Assessment-Upper Extremity scores was not significantly different between groups. In the per-protocol analysis, researchers found a significant difference in change in Fugl-Meyer Assessment-Upper Extremity score between groups.

The Chikungunya virus is a significant cause of CNS disease, according to a study published online ahead of print November 25 in Neurology. During the La Réunion outbreak between September 2005 and June 2006, 57 patients were diagnosed with Chikungunya virus-associated CNS disease, including 24 with Chikungunya virus-associated encephalitis (which corresponded to a cumulative incidence rate of 8.6 per 100,000 people). Patients with encephalitis were observed at both extremes of age categories. The cumulative incidence rates per 100,000 persons were 187 and 37 in patients younger than 1 and patients older than 65, respectively. The case-fatality rate of Chikungunya virus-associated encephalitis was 16.6%, and the proportion of children discharged with persistent disabilities was estimated at between 30% and 45%. Beyond the neonatal period, the clinical presentation and outcomes were less severe in infants than in adults.

Acute stroke is preventable to some extent in most patients, according to a study published online ahead of print December 7 in JAMA Neurology. Researchers evaluated the medical records of 274 consecutive patients discharged with a diagnosis of ischemic stroke between December 2, 2010, and June 11, 2012. Mean patient age was 67.2. Seventy-one patients (25.9%) had scores of 4 or greater on a 10-point scale, indicating that the stroke was highly preventable. Severity of stroke was not related to preventability of stroke. However, 29.6% of patients whose stroke was highly preventable were treated with IV or intra-arterial acute stroke therapy. These treatments were provided for 19.4% of patients with scores of 0, and 14% of patients with scores of 1 to 3.

Alpha-blocker therapy is associated with an increased risk of ischemic stroke during the early initiation period, especially among patients who are not taking other antihypertensive agents, according to a study published online ahead of print December 7 in Canadian Medical Association Journal. Researchers identified 7,502 men ages 50 and older as of 2007 who were incident users of alpha-blockers and who had a diagnosis of ischemic stroke during the study period, which lasted from 2007 to 2009. Investigators examined the incidence of stroke during risk periods before and after alpha-blocker prescription. Compared with the risk in the unexposed period, the risk of ischemic stroke was increased within 21 days after alpha-blocker initiation among all patients in the study population and among patients without concomitant prescriptions.

In patients with mild Alzheimer’s disease, moderate alcohol consumption (ie, two to three units per day) is associated with a significantly lower mortality over a period of 36 months, according to a study published December 11 in BMJ Open. Investigators examined data collected as part of the Danish Alzheimer’s Intervention Study (DAISY). Information about current daily alcohol consumption was obtained from 321 study participants. In all, 8% abstained from drinking alcohol, 71% drank alcohol occasionally, 17% had two to three units per day, and 4% had more than three units per day. Mortality was not significantly different in abstinent patients or in patients with an alcohol consumption of more than three units per day, compared with patients drinking one or less than one unit per day.

Stress is a potentially remediable risk factor for amnestic mild cognitive impairment (aMCI), according to a study published online ahead of print December 10 in Alzheimer Disease & Associated Disorders. The Perceived Stress Scale (PSS) was administered annually in the Einstein Aging Study to participants age 70 and older who were free of aMCI and dementia at baseline PSS administration and who had at least one subsequent annual follow-up. Cox hazard models were used to examine time to aMCI onset, adjusting for covariates. High levels of perceived stress were associated with a 30% greater risk of incident aMCI, independent of covariates. Overall, understanding the effect that perceived stress has on cognition may lead to intervention strategies that prevent the onset of aMCI and Alzheimer’s-related dementia, said the investigators.

Heptachlor epoxide, a pesticide, is associated with higher risk for signs of Parkinson’s disease, according to a study published online ahead of print December 9 in Neurology. For the study, 449 Japanese-American men with an average age of 54 were followed for more than 30 years and until death in the Honolulu-Asia Aging Study. Tests determined whether participants had lost brain cells in the substantia nigra. In 116 brains, researchers also measured the amount of heptachlor epoxide residue, which was present at high levels in Hawaii’s milk in the early 1980s. Nonsmokers who drank more than two cups of milk per day had 40% fewer brain cells in the substantia nigra than people who drank less than two cups of milk per day.

An in vivo florbetapir PET study confirms previous postmortem evidence showing an association between Alzheimer’s disease pathology and gait speed, and provides additional evidence on potential regional effects of brain β-amyloid on motor function, according to data published online ahead of print December 7 in Neurology. Cross-sectional associations between brain β-amyloid, as measured with [¹⁸F]florbetapir PET, and gait speed were examined in 128 elderly participants. Researchers found a significant association between β-amyloid in the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate and slow gait speed. A multivariate model emphasized the posterior putamen and the precuneus. The β-amyloid burden explained as much as 9% of the variance in gait speed and significantly improved regression models that contained demographic variables, BMI, and APOE status.

Blast-related injury and loss of consciousness are common in traumatic brain injury (TBI) that is sustained while in the military, according to a study published online ahead of print December 15 in Radiology. Study participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI. MRIs were performed at 3 T, primarily with three-dimensional volume imaging at voxels smaller than 1 mm³. In all, 84.2% of participants reported one or more blast-related incidents, and 63.0% reported loss of consciousness at the time of injury. White matter T2-weighted hyperintense areas were the most common pathologic finding and were observed in 51.8% of TBI participants.

Researchers have created a transgenic mouse models of familial amyotrophic lateral sclerosis (ALS), according to research published in the December 2 issue of Neuron. To investigate the pathologic role of C9ORF72 in ALS and frontotemporal dementia (FTD), researchers generated a line of mice carrying a bacterial artificial chromosome containing exons one to six of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. The mice showed no overt behavioral phenotype, but recapitulated distinctive histopathologic features of C9ORF72 ALS/FTD, including sense and antisense intranuclear RNA foci and poly(glycine-proline) dipeptide repeat proteins. Using an artificial microRNA that targets human C9ORF72 in cultures of primary cortical neurons from the C9BAC mice, investigators attenuated expression of the C9BAC transgene and the poly(GP) dipeptides.

Oxidative stress may underlie most of the migraine triggers encountered in clinical practice, according to a study published online ahead of print December 7 in Headache. Investigators searched the literature for studies of common migraine triggers published between 1990 and 2014. The reference lists of the resulting articles were examined for further relevant studies. In all cases except pericranial pain, common migraine triggers are capable of generating oxidative stress. Mechanisms include a high rate of energy production by the mitochondria, toxicity or altered membrane properties of the mitochondria, calcium overload and excitotoxicity, neuroinflammation and activation of microglia, and activation of neuronal nicotinamide adenine dinucleotide phosphate oxidase. For some triggers, oxidants also arise as a byproduct of monoamine oxidase or cytochrome P450 processing, or from uncoupling of nitric oxide synthase.

—Kimberly Williams

Almost all patients who had nonfatal overdoses while taking long-term opioids for noncancer pain continued to receive opioid prescriptions, usually from the same physicians, in a nationwide cohort study published online Dec. 28 in Annals of Internal Medicine.

Clinical guidelines specify that adverse events related to the misuse of opioids are clear indications to discontinue long-term opioid therapy. But patterns of prescribing after opioid overdoses are not monitored. To examine prescribing trends following nonfatal opioid overdoses, researchers analyzed information in a database of inpatient, outpatient, and pharmacy claims from a large U.S. health insurer covering all 50 states.

They focused on 2,848 insured adults enrolled in 2000-2012 who received hospital or ED treatment for a prescription opioid overdose and were followed in the database for a median of 15 months. The prescribed drugs included codeine, dihydrocodeine, meperidine, morphine, oxycodone, hydrocodone, hydromorphone, fentanyl, oxymorphone, propoxyphene, methadone, tramadol, and levorphanol, said Dr. Marc R. Larochelle of Boston Medical Center and his associates.

©PhotoDisk

A total of 2,597 of these patients (91%) continued to receive opioid prescriptions after their overdose. The primary prescriber was the same person before and after the overdose in 1,198 cases (61%). Two hundred twelve of these patients (7%) had another opioid overdose during follow-up. The likelihood of a second overdose was much higher for patients taking the highest doses of opioids (100 mg or more morphine-equivalent dosage per day), with hazard ratios of 1.13 for patients taking low doses of opioids, 1.89 for those taking mid-range doses, and 2.57 for those taking high doses.

“We could not determine the reason for the treatment patterns after the overdose; however, some prescribers may have been unaware that the opioid overdose had occurred” because there are no procedures in place to ensure provider notification in such cases. Newly introduced prescription monitoring programs may facilitate such communication, but a more rigorous approach would mandate that all overdoses be reported to public health departments, which would then notify providers and pharmacies, and perhaps secure patient referral to substance abuse treatment programs, the investigators said (Ann Intern Med. 2015 Dec 28. doi: 10.7326/M15-0038). It is possible that some overdoses stemmed from therapeutic error rather than opioid misuse, and that providers felt the risk-benefit ratio justified continued opioid treatment. But it also is likely that many providers simply did not have the knowledge and skills to identify and treat opioid misuse, they added.

“Simply eliminating opioid prescribing for patients who had an overdose is not sufficient. … because some [patients] may turn to diverted or illicit opioids. Rather, efforts to identify and treat substance use disorders in these patients are needed,” Dr. Larochelle and his associates said.

Overall, the study findings indicate that nonfatal overdoses provide a meaningful opportunity to improve the safety of opioid prescribing, but that most prescribers at present are missing this opportunity.

Almost all patients who had nonfatal overdoses while taking long-term opioids for noncancer pain continued to receive opioid prescriptions, usually from the same physicians, in a nationwide cohort study published online Dec. 28 in Annals of Internal Medicine.

Clinical guidelines specify that adverse events related to the misuse of opioids are clear indications to discontinue long-term opioid therapy. But patterns of prescribing after opioid overdoses are not monitored. To examine prescribing trends following nonfatal opioid overdoses, researchers analyzed information in a database of inpatient, outpatient, and pharmacy claims from a large U.S. health insurer covering all 50 states.

They focused on 2,848 insured adults enrolled in 2000-2012 who received hospital or ED treatment for a prescription opioid overdose and were followed in the database for a median of 15 months. The prescribed drugs included codeine, dihydrocodeine, meperidine, morphine, oxycodone, hydrocodone, hydromorphone, fentanyl, oxymorphone, propoxyphene, methadone, tramadol, and levorphanol, said Dr. Marc R. Larochelle of Boston Medical Center and his associates.

©PhotoDisk

A total of 2,597 of these patients (91%) continued to receive opioid prescriptions after their overdose. The primary prescriber was the same person before and after the overdose in 1,198 cases (61%). Two hundred twelve of these patients (7%) had another opioid overdose during follow-up. The likelihood of a second overdose was much higher for patients taking the highest doses of opioids (100 mg or more morphine-equivalent dosage per day), with hazard ratios of 1.13 for patients taking low doses of opioids, 1.89 for those taking mid-range doses, and 2.57 for those taking high doses.

“We could not determine the reason for the treatment patterns after the overdose; however, some prescribers may have been unaware that the opioid overdose had occurred” because there are no procedures in place to ensure provider notification in such cases. Newly introduced prescription monitoring programs may facilitate such communication, but a more rigorous approach would mandate that all overdoses be reported to public health departments, which would then notify providers and pharmacies, and perhaps secure patient referral to substance abuse treatment programs, the investigators said (Ann Intern Med. 2015 Dec 28. doi: 10.7326/M15-0038). It is possible that some overdoses stemmed from therapeutic error rather than opioid misuse, and that providers felt the risk-benefit ratio justified continued opioid treatment. But it also is likely that many providers simply did not have the knowledge and skills to identify and treat opioid misuse, they added.

“Simply eliminating opioid prescribing for patients who had an overdose is not sufficient. … because some [patients] may turn to diverted or illicit opioids. Rather, efforts to identify and treat substance use disorders in these patients are needed,” Dr. Larochelle and his associates said.

Overall, the study findings indicate that nonfatal overdoses provide a meaningful opportunity to improve the safety of opioid prescribing, but that most prescribers at present are missing this opportunity.

Almost all patients who had nonfatal overdoses while taking long-term opioids for noncancer pain continued to receive opioid prescriptions, usually from the same physicians, in a nationwide cohort study published online Dec. 28 in Annals of Internal Medicine.

Clinical guidelines specify that adverse events related to the misuse of opioids are clear indications to discontinue long-term opioid therapy. But patterns of prescribing after opioid overdoses are not monitored. To examine prescribing trends following nonfatal opioid overdoses, researchers analyzed information in a database of inpatient, outpatient, and pharmacy claims from a large U.S. health insurer covering all 50 states.

They focused on 2,848 insured adults enrolled in 2000-2012 who received hospital or ED treatment for a prescription opioid overdose and were followed in the database for a median of 15 months. The prescribed drugs included codeine, dihydrocodeine, meperidine, morphine, oxycodone, hydrocodone, hydromorphone, fentanyl, oxymorphone, propoxyphene, methadone, tramadol, and levorphanol, said Dr. Marc R. Larochelle of Boston Medical Center and his associates.

©PhotoDisk

A total of 2,597 of these patients (91%) continued to receive opioid prescriptions after their overdose. The primary prescriber was the same person before and after the overdose in 1,198 cases (61%). Two hundred twelve of these patients (7%) had another opioid overdose during follow-up. The likelihood of a second overdose was much higher for patients taking the highest doses of opioids (100 mg or more morphine-equivalent dosage per day), with hazard ratios of 1.13 for patients taking low doses of opioids, 1.89 for those taking mid-range doses, and 2.57 for those taking high doses.

“We could not determine the reason for the treatment patterns after the overdose; however, some prescribers may have been unaware that the opioid overdose had occurred” because there are no procedures in place to ensure provider notification in such cases. Newly introduced prescription monitoring programs may facilitate such communication, but a more rigorous approach would mandate that all overdoses be reported to public health departments, which would then notify providers and pharmacies, and perhaps secure patient referral to substance abuse treatment programs, the investigators said (Ann Intern Med. 2015 Dec 28. doi: 10.7326/M15-0038). It is possible that some overdoses stemmed from therapeutic error rather than opioid misuse, and that providers felt the risk-benefit ratio justified continued opioid treatment. But it also is likely that many providers simply did not have the knowledge and skills to identify and treat opioid misuse, they added.

“Simply eliminating opioid prescribing for patients who had an overdose is not sufficient. … because some [patients] may turn to diverted or illicit opioids. Rather, efforts to identify and treat substance use disorders in these patients are needed,” Dr. Larochelle and his associates said.

Overall, the study findings indicate that nonfatal overdoses provide a meaningful opportunity to improve the safety of opioid prescribing, but that most prescribers at present are missing this opportunity.

The world has become a very complicated place. I suppose it always was, but today’s complexities are new and different and constantly changing with technology. It’s easy to think of ways our professional lives could be simpler and the treatment of our patients more attentive. Reflections, predictions, and all things “Happy New Year” tend to come as lists, and I don’t want to break with tradition. A list of my mental health hopes for 2016 follows:

1. I hope … that as our legislators rethink the Affordable Care Act (Obamacare), they don’t throw out the baby with the bath water, and the gains that were made remain in place. Among the good that’s been done has been the ability to keep adult children on a family policy to age 26, the elimination of “preexisting conditions” as exclusions from health insurance coverage, and the overall expansion of who is able to get some form of health insurance.

2. I hope … psychiatric treatment comes to be about so much more than medications, and that psychiatry resumes the priority of listening to patients on so many different levels. People are about more than checklists of symptoms and side effects, and their problems occur within the context of their lives. This is often more than a psychiatrist can piece together when seeing four or five patients an hour. In addition, there has been the added burden of attending to screens, data collection that is irrelevant to treatment, and paperwork burdens. I’d like to see the end of “meaningful use,” irrelevant maintenance of certification exams, and demands to use electronic medical records that divert psychiatrist time and attention without improving patient care. Technology should facilitate excellent care, not detract from it. And in my continued hope for our Internet-based world, I’ll wish for efficiency and innovation in how we use technology to learn, to communicate with one another, and to offer care to our patients, without compromising patient privacy.

3. I hope … discussions about involuntary treatment come to be about reducing the suffering of our patients, and not about preventing mass murders. It’s an expectation psychiatry simply cannot meet.

4. I hope … our legislators will come to understand that “mental illness” does not cause gun violence, and that a better predictor of violent behavior is a past history of violence, substance abuse, anger, and impulse control problems, and not the presence of a particular diagnosis or the catchall category of mental illness.

5. I hope ... we stop political discussions calling for an end to stigma while simultaneously stigmatizing those with psychiatric disorders.

6. I hope … that insurers and pharmacy benefit managers are required to limit preauthorization requirements to the most expensive and controversial forms of care. They must be required to standardize, simplify, and streamline any preauthorization procedures, and to be held to a level of accountability for the care that is denied.

7. I hope … that Medicare and Medicaid become user friendly entities that are easy to navigate and welcoming to psychiatrists so that our patients with limited incomes have access to treatment.

8. I hope … we come to appreciate the need for “housing-first” options for people who live and sleep on our streets. In a civilized society, this is a disgrace, and it benefits no one. It shouldn’t matter whether people with nowhere else to sleep do so because they are mentally ill, addicted, or simply impoverished: We need to provide better housing options. It is the humane thing to do, and it is more cost effective than paying for the correctional and medical care that result from homelessness. For those who are homeless because of untreated mental illness, it is so much easier to take medications when they have a shelf to put the bottles on.

9. I hope … for an understanding that our world is not black and white: We don’t neatly divide into those who are mentally ill and those who are not any more than we neatly divide into those who are good guys and those who are bad guys. People are complex, and mentally healthy people can behave in very disordered ways given the wrong set of circumstances. And, quite obviously, we all have a bit of both the good guy and the bad guy in us, and to believe otherwise is to be naive.

10. I hope … for both mental health and all of medicine, that all our treatments become available to all of our patients. It doesn’t matter how wonderful new treatments are if they are available only to those patients who are wealthy enough to pay for their own care, or who have Cadillac insurance policies that will reimburse for a given therapy.

Convention (or at least David Letterman) would suggest that I stop at 10 hopes. I never was one to follow arbitrary rules, so please allow me to express more mental health wishes for 2016.

11. I hope … we find some way of addressing the shortage of psychiatrists and services. We need to make it easier for patients to link with psychiatrists they find to be helpful. Our current system is difficult to negotiate for those who are healthy and have resources. Linking to care is nearly impossible for someone with limited resources who is psychotic or severely depressed.

12. And finally, I hope ... for better treatments for our patients, ones that cure mental illnesses without causing side effects, adverse reactions, or trade-offs that sometime make the cures worse than the diseases.

Thank you for bearing with me. I’m sure you have your own mental health hopes for the coming year, and perhaps some of our wishes might even come true. Wishing you a Healthy and Happy New Year!

Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work” (Baltimore: Johns Hopkins University Press, 2011).

The world has become a very complicated place. I suppose it always was, but today’s complexities are new and different and constantly changing with technology. It’s easy to think of ways our professional lives could be simpler and the treatment of our patients more attentive. Reflections, predictions, and all things “Happy New Year” tend to come as lists, and I don’t want to break with tradition. A list of my mental health hopes for 2016 follows:

1. I hope … that as our legislators rethink the Affordable Care Act (Obamacare), they don’t throw out the baby with the bath water, and the gains that were made remain in place. Among the good that’s been done has been the ability to keep adult children on a family policy to age 26, the elimination of “preexisting conditions” as exclusions from health insurance coverage, and the overall expansion of who is able to get some form of health insurance.

2. I hope … psychiatric treatment comes to be about so much more than medications, and that psychiatry resumes the priority of listening to patients on so many different levels. People are about more than checklists of symptoms and side effects, and their problems occur within the context of their lives. This is often more than a psychiatrist can piece together when seeing four or five patients an hour. In addition, there has been the added burden of attending to screens, data collection that is irrelevant to treatment, and paperwork burdens. I’d like to see the end of “meaningful use,” irrelevant maintenance of certification exams, and demands to use electronic medical records that divert psychiatrist time and attention without improving patient care. Technology should facilitate excellent care, not detract from it. And in my continued hope for our Internet-based world, I’ll wish for efficiency and innovation in how we use technology to learn, to communicate with one another, and to offer care to our patients, without compromising patient privacy.

3. I hope … discussions about involuntary treatment come to be about reducing the suffering of our patients, and not about preventing mass murders. It’s an expectation psychiatry simply cannot meet.

4. I hope … our legislators will come to understand that “mental illness” does not cause gun violence, and that a better predictor of violent behavior is a past history of violence, substance abuse, anger, and impulse control problems, and not the presence of a particular diagnosis or the catchall category of mental illness.

5. I hope ... we stop political discussions calling for an end to stigma while simultaneously stigmatizing those with psychiatric disorders.

6. I hope … that insurers and pharmacy benefit managers are required to limit preauthorization requirements to the most expensive and controversial forms of care. They must be required to standardize, simplify, and streamline any preauthorization procedures, and to be held to a level of accountability for the care that is denied.

7. I hope … that Medicare and Medicaid become user friendly entities that are easy to navigate and welcoming to psychiatrists so that our patients with limited incomes have access to treatment.

8. I hope … we come to appreciate the need for “housing-first” options for people who live and sleep on our streets. In a civilized society, this is a disgrace, and it benefits no one. It shouldn’t matter whether people with nowhere else to sleep do so because they are mentally ill, addicted, or simply impoverished: We need to provide better housing options. It is the humane thing to do, and it is more cost effective than paying for the correctional and medical care that result from homelessness. For those who are homeless because of untreated mental illness, it is so much easier to take medications when they have a shelf to put the bottles on.

9. I hope … for an understanding that our world is not black and white: We don’t neatly divide into those who are mentally ill and those who are not any more than we neatly divide into those who are good guys and those who are bad guys. People are complex, and mentally healthy people can behave in very disordered ways given the wrong set of circumstances. And, quite obviously, we all have a bit of both the good guy and the bad guy in us, and to believe otherwise is to be naive.

10. I hope … for both mental health and all of medicine, that all our treatments become available to all of our patients. It doesn’t matter how wonderful new treatments are if they are available only to those patients who are wealthy enough to pay for their own care, or who have Cadillac insurance policies that will reimburse for a given therapy.

Convention (or at least David Letterman) would suggest that I stop at 10 hopes. I never was one to follow arbitrary rules, so please allow me to express more mental health wishes for 2016.

11. I hope … we find some way of addressing the shortage of psychiatrists and services. We need to make it easier for patients to link with psychiatrists they find to be helpful. Our current system is difficult to negotiate for those who are healthy and have resources. Linking to care is nearly impossible for someone with limited resources who is psychotic or severely depressed.

12. And finally, I hope ... for better treatments for our patients, ones that cure mental illnesses without causing side effects, adverse reactions, or trade-offs that sometime make the cures worse than the diseases.

Thank you for bearing with me. I’m sure you have your own mental health hopes for the coming year, and perhaps some of our wishes might even come true. Wishing you a Healthy and Happy New Year!

Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work” (Baltimore: Johns Hopkins University Press, 2011).

The world has become a very complicated place. I suppose it always was, but today’s complexities are new and different and constantly changing with technology. It’s easy to think of ways our professional lives could be simpler and the treatment of our patients more attentive. Reflections, predictions, and all things “Happy New Year” tend to come as lists, and I don’t want to break with tradition. A list of my mental health hopes for 2016 follows:

1. I hope … that as our legislators rethink the Affordable Care Act (Obamacare), they don’t throw out the baby with the bath water, and the gains that were made remain in place. Among the good that’s been done has been the ability to keep adult children on a family policy to age 26, the elimination of “preexisting conditions” as exclusions from health insurance coverage, and the overall expansion of who is able to get some form of health insurance.

2. I hope … psychiatric treatment comes to be about so much more than medications, and that psychiatry resumes the priority of listening to patients on so many different levels. People are about more than checklists of symptoms and side effects, and their problems occur within the context of their lives. This is often more than a psychiatrist can piece together when seeing four or five patients an hour. In addition, there has been the added burden of attending to screens, data collection that is irrelevant to treatment, and paperwork burdens. I’d like to see the end of “meaningful use,” irrelevant maintenance of certification exams, and demands to use electronic medical records that divert psychiatrist time and attention without improving patient care. Technology should facilitate excellent care, not detract from it. And in my continued hope for our Internet-based world, I’ll wish for efficiency and innovation in how we use technology to learn, to communicate with one another, and to offer care to our patients, without compromising patient privacy.

3. I hope … discussions about involuntary treatment come to be about reducing the suffering of our patients, and not about preventing mass murders. It’s an expectation psychiatry simply cannot meet.

4. I hope … our legislators will come to understand that “mental illness” does not cause gun violence, and that a better predictor of violent behavior is a past history of violence, substance abuse, anger, and impulse control problems, and not the presence of a particular diagnosis or the catchall category of mental illness.

5. I hope ... we stop political discussions calling for an end to stigma while simultaneously stigmatizing those with psychiatric disorders.

6. I hope … that insurers and pharmacy benefit managers are required to limit preauthorization requirements to the most expensive and controversial forms of care. They must be required to standardize, simplify, and streamline any preauthorization procedures, and to be held to a level of accountability for the care that is denied.

7. I hope … that Medicare and Medicaid become user friendly entities that are easy to navigate and welcoming to psychiatrists so that our patients with limited incomes have access to treatment.

8. I hope … we come to appreciate the need for “housing-first” options for people who live and sleep on our streets. In a civilized society, this is a disgrace, and it benefits no one. It shouldn’t matter whether people with nowhere else to sleep do so because they are mentally ill, addicted, or simply impoverished: We need to provide better housing options. It is the humane thing to do, and it is more cost effective than paying for the correctional and medical care that result from homelessness. For those who are homeless because of untreated mental illness, it is so much easier to take medications when they have a shelf to put the bottles on.

9. I hope … for an understanding that our world is not black and white: We don’t neatly divide into those who are mentally ill and those who are not any more than we neatly divide into those who are good guys and those who are bad guys. People are complex, and mentally healthy people can behave in very disordered ways given the wrong set of circumstances. And, quite obviously, we all have a bit of both the good guy and the bad guy in us, and to believe otherwise is to be naive.

10. I hope … for both mental health and all of medicine, that all our treatments become available to all of our patients. It doesn’t matter how wonderful new treatments are if they are available only to those patients who are wealthy enough to pay for their own care, or who have Cadillac insurance policies that will reimburse for a given therapy.

Convention (or at least David Letterman) would suggest that I stop at 10 hopes. I never was one to follow arbitrary rules, so please allow me to express more mental health wishes for 2016.

11. I hope … we find some way of addressing the shortage of psychiatrists and services. We need to make it easier for patients to link with psychiatrists they find to be helpful. Our current system is difficult to negotiate for those who are healthy and have resources. Linking to care is nearly impossible for someone with limited resources who is psychotic or severely depressed.

12. And finally, I hope ... for better treatments for our patients, ones that cure mental illnesses without causing side effects, adverse reactions, or trade-offs that sometime make the cures worse than the diseases.

Thank you for bearing with me. I’m sure you have your own mental health hopes for the coming year, and perhaps some of our wishes might even come true. Wishing you a Healthy and Happy New Year!

Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work” (Baltimore: Johns Hopkins University Press, 2011).

For the first time this flu season, the proportion of outpatient visits for influenza-like illness (ILI) was higher than the national baseline level of 2.1%, the Centers for Disease Control and Prevention reported.

According to data from the U.S. Outpatient Influenza-like Illness Surveillance Network, for the week ending Dec. 19 (week 10 of the 2015-2016 season), 2.2% of outpatient visits nationwide involved ILI, the CDC said.

South Carolina remained the only state in the “high” range of activity. New Jersey went up to level 7 – the high end of the “moderate” range – to remain the second most affected state, and Texas jumped from level 2 last week to level 6 this week to move into “moderate” territory. Alabama and Georgia both moved up to “low” status for the first time with ILI activity at level 5, and Virginia stayed at level 4 – the only other state in the “low” range, according to the CDC.

A total of 17 states were at level 2 or higher during week 10, up from 15 states the week before. Arizona, Illinois, Louisiana, Mississippi, and Pennsylvania were at level 3, and Colorado, Hawaii, Minnesota, New Mexico, and Utah were at level 2, data from the Outpatient Influenza-like Illness Surveillance Network revealed.

One influenza-related pediatric death was reported during week 10, bringing the total for the season to four.

[email protected]

For the first time this flu season, the proportion of outpatient visits for influenza-like illness (ILI) was higher than the national baseline level of 2.1%, the Centers for Disease Control and Prevention reported.

According to data from the U.S. Outpatient Influenza-like Illness Surveillance Network, for the week ending Dec. 19 (week 10 of the 2015-2016 season), 2.2% of outpatient visits nationwide involved ILI, the CDC said.

South Carolina remained the only state in the “high” range of activity. New Jersey went up to level 7 – the high end of the “moderate” range – to remain the second most affected state, and Texas jumped from level 2 last week to level 6 this week to move into “moderate” territory. Alabama and Georgia both moved up to “low” status for the first time with ILI activity at level 5, and Virginia stayed at level 4 – the only other state in the “low” range, according to the CDC.

A total of 17 states were at level 2 or higher during week 10, up from 15 states the week before. Arizona, Illinois, Louisiana, Mississippi, and Pennsylvania were at level 3, and Colorado, Hawaii, Minnesota, New Mexico, and Utah were at level 2, data from the Outpatient Influenza-like Illness Surveillance Network revealed.

One influenza-related pediatric death was reported during week 10, bringing the total for the season to four.

[email protected]

For the first time this flu season, the proportion of outpatient visits for influenza-like illness (ILI) was higher than the national baseline level of 2.1%, the Centers for Disease Control and Prevention reported.

According to data from the U.S. Outpatient Influenza-like Illness Surveillance Network, for the week ending Dec. 19 (week 10 of the 2015-2016 season), 2.2% of outpatient visits nationwide involved ILI, the CDC said.

South Carolina remained the only state in the “high” range of activity. New Jersey went up to level 7 – the high end of the “moderate” range – to remain the second most affected state, and Texas jumped from level 2 last week to level 6 this week to move into “moderate” territory. Alabama and Georgia both moved up to “low” status for the first time with ILI activity at level 5, and Virginia stayed at level 4 – the only other state in the “low” range, according to the CDC.

A total of 17 states were at level 2 or higher during week 10, up from 15 states the week before. Arizona, Illinois, Louisiana, Mississippi, and Pennsylvania were at level 3, and Colorado, Hawaii, Minnesota, New Mexico, and Utah were at level 2, data from the Outpatient Influenza-like Illness Surveillance Network revealed.

One influenza-related pediatric death was reported during week 10, bringing the total for the season to four.

[email protected]

From care transitions to antibiotic stewardship

What does that mean? When you experience a success related to being a member, attend an SHM event, or use an SHM resource or program, tweet about it using the hashtag #SHeMpowered and mention SHM, @SHMLive. We’ll retweet and share your fantastic work with our thousands of followers.

What kinds of things can you tweet about? Pretty much anything! Attended Leadership Academy? Finished a course in the Learning Portal? Implemented a checklist from Project BOOST in your hospital? Tweet about it! Just remember to use the hashtag #SHeMpowered to be a part of the larger conversation on social media, and follow the hashtag to see how others are using their SHM membership to enhance patient care.

For more information, visit www.hospitalmedicine.org/getinvolved, and be sure to follow SHM on Twitter @SHMLive. While you’re online, check out our Facebook page, YouTube channel, and LinkedIn group, and get #SHeMpowered!

From care transitions to antibiotic stewardship

What does that mean? When you experience a success related to being a member, attend an SHM event, or use an SHM resource or program, tweet about it using the hashtag #SHeMpowered and mention SHM, @SHMLive. We’ll retweet and share your fantastic work with our thousands of followers.

What kinds of things can you tweet about? Pretty much anything! Attended Leadership Academy? Finished a course in the Learning Portal? Implemented a checklist from Project BOOST in your hospital? Tweet about it! Just remember to use the hashtag #SHeMpowered to be a part of the larger conversation on social media, and follow the hashtag to see how others are using their SHM membership to enhance patient care.

For more information, visit www.hospitalmedicine.org/getinvolved, and be sure to follow SHM on Twitter @SHMLive. While you’re online, check out our Facebook page, YouTube channel, and LinkedIn group, and get #SHeMpowered!

From care transitions to antibiotic stewardship

What does that mean? When you experience a success related to being a member, attend an SHM event, or use an SHM resource or program, tweet about it using the hashtag #SHeMpowered and mention SHM, @SHMLive. We’ll retweet and share your fantastic work with our thousands of followers.

What kinds of things can you tweet about? Pretty much anything! Attended Leadership Academy? Finished a course in the Learning Portal? Implemented a checklist from Project BOOST in your hospital? Tweet about it! Just remember to use the hashtag #SHeMpowered to be a part of the larger conversation on social media, and follow the hashtag to see how others are using their SHM membership to enhance patient care.

For more information, visit www.hospitalmedicine.org/getinvolved, and be sure to follow SHM on Twitter @SHMLive. While you’re online, check out our Facebook page, YouTube channel, and LinkedIn group, and get #SHeMpowered!

I recently attended a CME conference at Johns Hopkins University titled “Infectious Diseases Update for Primary Care and Hospital Medicine.” As one would assume, some things were highly germane to my practice as a hospitalist, while others were, well, not relevant at all.

Don’t get me wrong, the conference was excellent and very thought provoking. It not only taught me clinically useful information, it challenged me to do more than I am used to doing for my patients; thus, I pass this challenge along to you.

One expert presented a case of an otherwise healthy patient who was found to have mildly elevated liver function tests on routine lab work done for life insurance purposes. His ALT and AST were 73 and 36, respectively, numbers that many of us would simply defer to the primary care provider to follow. But what if there is no primary care doctor? What if we are all they have?

Upon further evaluation, this patient was found to have hepatitis C. A more detailed history revealed that he had injected drugs with friends a few times over 20 years ago. The conference presenter shared statistics showing there are 2.7 million to 5 million people living with chronic HCV in America, and an estimated 45% to 60% of them are unaware of their disease – a disease that responds so well to treatment that simply screening baby boomers has the potential to prevent over 120,000 HCV-related deaths! It’s mind boggling to imagine how many people of all ages will die from this disease alone, completely oblivious to its existence.

Many people have obtained health insurance as a direct result of the Affordable Care Act, yet there are still many Americans who remain uninsured. When they are hospitalized for an acute illness, it may be the only encounter they have had with a medical professional in years. So, I ask the question again: What if we are all they have?

We can design all the elaborate hand-offs, discharge summaries, and patient instruction forms we want, but what if patients are unable to actually act on our “easy-to-understand” recommendations? Many of our patients will, out of embarrassment, nod their heads in agreement when we stress the extreme importance of following up with a primary care doctor and getting their prescriptions filled, knowing all the while that they simply don’t have the means to do so. I don’t think I will ever forget how out of touch I felt after giving a patient my spiel about taking his medication as prescribed to decrease his risk of a heart attack. He looked straight into my eyes and frankly, yet ever so respectively said, “Dr. Hester, I can either buy my medicine or I can eat.”

Sometimes it’s just that simple.

We all feel the urgency to provide high-quality care while keeping that care cost effective and time efficient, but hospitalists have a unique opportunity to not only serve our patients’ acute needs when they present via EMS to the ED, but to protect them from unforeseen catastrophes in the future. An extra (needed) test here and there, a little more time spent counseling on lifestyle changes, a few more minutes spent trying to help coordinate affordable (or free) follow-up care can all pay big dividends, and you may never have to see those patients in the hospital again. Isn’t that the goal?

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

I recently attended a CME conference at Johns Hopkins University titled “Infectious Diseases Update for Primary Care and Hospital Medicine.” As one would assume, some things were highly germane to my practice as a hospitalist, while others were, well, not relevant at all.

Don’t get me wrong, the conference was excellent and very thought provoking. It not only taught me clinically useful information, it challenged me to do more than I am used to doing for my patients; thus, I pass this challenge along to you.

One expert presented a case of an otherwise healthy patient who was found to have mildly elevated liver function tests on routine lab work done for life insurance purposes. His ALT and AST were 73 and 36, respectively, numbers that many of us would simply defer to the primary care provider to follow. But what if there is no primary care doctor? What if we are all they have?

Upon further evaluation, this patient was found to have hepatitis C. A more detailed history revealed that he had injected drugs with friends a few times over 20 years ago. The conference presenter shared statistics showing there are 2.7 million to 5 million people living with chronic HCV in America, and an estimated 45% to 60% of them are unaware of their disease – a disease that responds so well to treatment that simply screening baby boomers has the potential to prevent over 120,000 HCV-related deaths! It’s mind boggling to imagine how many people of all ages will die from this disease alone, completely oblivious to its existence.

Many people have obtained health insurance as a direct result of the Affordable Care Act, yet there are still many Americans who remain uninsured. When they are hospitalized for an acute illness, it may be the only encounter they have had with a medical professional in years. So, I ask the question again: What if we are all they have?

We can design all the elaborate hand-offs, discharge summaries, and patient instruction forms we want, but what if patients are unable to actually act on our “easy-to-understand” recommendations? Many of our patients will, out of embarrassment, nod their heads in agreement when we stress the extreme importance of following up with a primary care doctor and getting their prescriptions filled, knowing all the while that they simply don’t have the means to do so. I don’t think I will ever forget how out of touch I felt after giving a patient my spiel about taking his medication as prescribed to decrease his risk of a heart attack. He looked straight into my eyes and frankly, yet ever so respectively said, “Dr. Hester, I can either buy my medicine or I can eat.”

Sometimes it’s just that simple.

We all feel the urgency to provide high-quality care while keeping that care cost effective and time efficient, but hospitalists have a unique opportunity to not only serve our patients’ acute needs when they present via EMS to the ED, but to protect them from unforeseen catastrophes in the future. An extra (needed) test here and there, a little more time spent counseling on lifestyle changes, a few more minutes spent trying to help coordinate affordable (or free) follow-up care can all pay big dividends, and you may never have to see those patients in the hospital again. Isn’t that the goal?

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

I recently attended a CME conference at Johns Hopkins University titled “Infectious Diseases Update for Primary Care and Hospital Medicine.” As one would assume, some things were highly germane to my practice as a hospitalist, while others were, well, not relevant at all.

Don’t get me wrong, the conference was excellent and very thought provoking. It not only taught me clinically useful information, it challenged me to do more than I am used to doing for my patients; thus, I pass this challenge along to you.

One expert presented a case of an otherwise healthy patient who was found to have mildly elevated liver function tests on routine lab work done for life insurance purposes. His ALT and AST were 73 and 36, respectively, numbers that many of us would simply defer to the primary care provider to follow. But what if there is no primary care doctor? What if we are all they have?

Upon further evaluation, this patient was found to have hepatitis C. A more detailed history revealed that he had injected drugs with friends a few times over 20 years ago. The conference presenter shared statistics showing there are 2.7 million to 5 million people living with chronic HCV in America, and an estimated 45% to 60% of them are unaware of their disease – a disease that responds so well to treatment that simply screening baby boomers has the potential to prevent over 120,000 HCV-related deaths! It’s mind boggling to imagine how many people of all ages will die from this disease alone, completely oblivious to its existence.

Many people have obtained health insurance as a direct result of the Affordable Care Act, yet there are still many Americans who remain uninsured. When they are hospitalized for an acute illness, it may be the only encounter they have had with a medical professional in years. So, I ask the question again: What if we are all they have?

We can design all the elaborate hand-offs, discharge summaries, and patient instruction forms we want, but what if patients are unable to actually act on our “easy-to-understand” recommendations? Many of our patients will, out of embarrassment, nod their heads in agreement when we stress the extreme importance of following up with a primary care doctor and getting their prescriptions filled, knowing all the while that they simply don’t have the means to do so. I don’t think I will ever forget how out of touch I felt after giving a patient my spiel about taking his medication as prescribed to decrease his risk of a heart attack. He looked straight into my eyes and frankly, yet ever so respectively said, “Dr. Hester, I can either buy my medicine or I can eat.”

Sometimes it’s just that simple.

We all feel the urgency to provide high-quality care while keeping that care cost effective and time efficient, but hospitalists have a unique opportunity to not only serve our patients’ acute needs when they present via EMS to the ED, but to protect them from unforeseen catastrophes in the future. An extra (needed) test here and there, a little more time spent counseling on lifestyle changes, a few more minutes spent trying to help coordinate affordable (or free) follow-up care can all pay big dividends, and you may never have to see those patients in the hospital again. Isn’t that the goal?

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

Review the PDF of the fact sheet on genetic pathways

After, test your knowledge by answering the 5 practice questions.

Practice Questions

1. A 6-month-old male infant presented to your dermatology clinic with an ash-leaf macule on the right back. What is the most common gene defect seen in this condition?

a. tuberin

b. merlin

c. neurofibromin

d. smoothened

e. hamartin

2. Bilateral acoustic neuromas are associated with what gene mutation?

a. NF1 (neurofibromin 1)

b. NF2 (neurofibromin 2)

c. PTCH1 (patched 1)

d. TSC1 (tuberous sclerosis 1)

e. TSC2 (tuberous sclerosis 2)

3. Which of the following would least likely be seen in neurofibromatosis types 1 or 2?

a. angiofibromas

b. café au lait macules

c. gliomas

d. Lisch nodules

e. neurofibromas

4. What protein is the patched 1 gene a receptor for?

a. fused

b. glioma-associated oncogene

c. smoothened

d. sonic hedgehog

e. suppressor of fused

5. A 20-year-old woman presented to your dermatology clinic with a history of numerous basal cell carcinomas. On physical examination, it is noted that she has numerous palmar pits. What finding could you find from radiograph of the head?

a. calcification of the dura

b. calcifications of the temporal lobe

c. cysts of the mandible

d. thickening of the corpus callosum

e. tumor of the cerebellum

1. A 6-month-old male infant presented to your dermatology clinic with an ash-leaf macule on the right back. What is the most common gene defect seen in this condition?

a. tuberin

b. merlin

c. neurofibromin

d. smoothened

e. hamartin

2. Bilateral acoustic neuromas are associated with what gene mutation?

a. NF1 (neurofibromin 1)

b. NF2 (neurofibromin 2)

c. PTCH1 (patched 1)

d. TSC1 (tuberous sclerosis 1)

e. TSC2 (tuberous sclerosis 2)

3. Which of the following would least likely be seen in neurofibromatosis types 1 or 2?

a. angiofibromas

b. café au lait macules

c. gliomas

d. Lisch nodules

e. neurofibromas

4. What protein is the patched 1 gene a receptor for?

a. fused

b. glioma-associated oncogene

c. smoothened

d. sonic hedgehog

e. suppressor of fused

5. A 20-year-old woman presented to your dermatology clinic with a history of numerous basal cell carcinomas. On physical examination, it is noted that she has numerous palmar pits. What finding could you find from radiograph of the head?

a. calcification of the dura

b. calcifications of the temporal lobe

c. cysts of the mandible

d. thickening of the corpus callosum

e. tumor of the cerebellum

Review the PDF of the fact sheet on genetic pathways

After, test your knowledge by answering the 5 practice questions.

Practice Questions

1. A 6-month-old male infant presented to your dermatology clinic with an ash-leaf macule on the right back. What is the most common gene defect seen in this condition?

a. tuberin

b. merlin

c. neurofibromin

d. smoothened

e. hamartin

2. Bilateral acoustic neuromas are associated with what gene mutation?

a. NF1 (neurofibromin 1)

b. NF2 (neurofibromin 2)

c. PTCH1 (patched 1)

d. TSC1 (tuberous sclerosis 1)

e. TSC2 (tuberous sclerosis 2)

3. Which of the following would least likely be seen in neurofibromatosis types 1 or 2?

a. angiofibromas

b. café au lait macules

c. gliomas

d. Lisch nodules

e. neurofibromas

4. What protein is the patched 1 gene a receptor for?

a. fused

b. glioma-associated oncogene

c. smoothened

d. sonic hedgehog

e. suppressor of fused

5. A 20-year-old woman presented to your dermatology clinic with a history of numerous basal cell carcinomas. On physical examination, it is noted that she has numerous palmar pits. What finding could you find from radiograph of the head?

a. calcification of the dura

b. calcifications of the temporal lobe

c. cysts of the mandible

d. thickening of the corpus callosum

e. tumor of the cerebellum

1. A 6-month-old male infant presented to your dermatology clinic with an ash-leaf macule on the right back. What is the most common gene defect seen in this condition?

a. tuberin

b. merlin

c. neurofibromin

d. smoothened

e. hamartin

2. Bilateral acoustic neuromas are associated with what gene mutation?

a. NF1 (neurofibromin 1)

b. NF2 (neurofibromin 2)

c. PTCH1 (patched 1)

d. TSC1 (tuberous sclerosis 1)

e. TSC2 (tuberous sclerosis 2)

3. Which of the following would least likely be seen in neurofibromatosis types 1 or 2?

a. angiofibromas

b. café au lait macules

c. gliomas

d. Lisch nodules

e. neurofibromas

4. What protein is the patched 1 gene a receptor for?

a. fused

b. glioma-associated oncogene

c. smoothened

d. sonic hedgehog

e. suppressor of fused

5. A 20-year-old woman presented to your dermatology clinic with a history of numerous basal cell carcinomas. On physical examination, it is noted that she has numerous palmar pits. What finding could you find from radiograph of the head?

a. calcification of the dura

b. calcifications of the temporal lobe

c. cysts of the mandible

d. thickening of the corpus callosum

e. tumor of the cerebellum

Review the PDF of the fact sheet on genetic pathways

After, test your knowledge by answering the 5 practice questions.

Practice Questions

1. A 6-month-old male infant presented to your dermatology clinic with an ash-leaf macule on the right back. What is the most common gene defect seen in this condition?

a. tuberin

b. merlin

c. neurofibromin

d. smoothened

e. hamartin

2. Bilateral acoustic neuromas are associated with what gene mutation?

a. NF1 (neurofibromin 1)

b. NF2 (neurofibromin 2)

c. PTCH1 (patched 1)

d. TSC1 (tuberous sclerosis 1)

e. TSC2 (tuberous sclerosis 2)

3. Which of the following would least likely be seen in neurofibromatosis types 1 or 2?

a. angiofibromas

b. café au lait macules

c. gliomas

d. Lisch nodules

e. neurofibromas

4. What protein is the patched 1 gene a receptor for?

a. fused

b. glioma-associated oncogene

c. smoothened

d. sonic hedgehog

e. suppressor of fused

5. A 20-year-old woman presented to your dermatology clinic with a history of numerous basal cell carcinomas. On physical examination, it is noted that she has numerous palmar pits. What finding could you find from radiograph of the head?

a. calcification of the dura

b. calcifications of the temporal lobe

c. cysts of the mandible

d. thickening of the corpus callosum

e. tumor of the cerebellum

1. A 6-month-old male infant presented to your dermatology clinic with an ash-leaf macule on the right back. What is the most common gene defect seen in this condition?

a. tuberin

b. merlin

c. neurofibromin

d. smoothened

e. hamartin

2. Bilateral acoustic neuromas are associated with what gene mutation?

a. NF1 (neurofibromin 1)

b. NF2 (neurofibromin 2)

c. PTCH1 (patched 1)

d. TSC1 (tuberous sclerosis 1)

e. TSC2 (tuberous sclerosis 2)

3. Which of the following would least likely be seen in neurofibromatosis types 1 or 2?

a. angiofibromas

b. café au lait macules

c. gliomas

d. Lisch nodules

e. neurofibromas

4. What protein is the patched 1 gene a receptor for?

a. fused

b. glioma-associated oncogene

c. smoothened

d. sonic hedgehog

e. suppressor of fused

5. A 20-year-old woman presented to your dermatology clinic with a history of numerous basal cell carcinomas. On physical examination, it is noted that she has numerous palmar pits. What finding could you find from radiograph of the head?

a. calcification of the dura

b. calcifications of the temporal lobe

c. cysts of the mandible

d. thickening of the corpus callosum

e. tumor of the cerebellum

To the Editor:

Sebaceous nevus (SN) is a relatively common hamartoma that presents most often as a single congenital hairless plaque on the scalp. After puberty, histologic features characteristically include papillomatous hyperplasia of the epidermis, a large number of mature or nearly mature sebaceous glands, and a lack of terminally differentiated hair follicles; however, histologic findings can be misleading during childhood when sebaceous glands are still underdeveloped. Bright yellow dots, which are thought to indicate the presence of sebaceous glands, may be seen on dermoscopy and can be useful in differentiating SN from aplasia cutis congenita in newborns.

We report a case of an SN in an 18-year-old woman and discuss how the histology findings correlated with features seen on dermoscopy.

An 18-year-old woman presented to our dermatology clinic with an asymptomatic, hairless plaque on the right parietal scalp that had been present since birth. The patient noted that the plaque had recently become larger in size. On physical examination, an 8×3-cm plaque with a smooth, flesh-colored surface was noted with central comedolike structures and an erythematous, verrucous periphery (Figure 1).

Dermoscopy (handheld dermoscope using polarized light) revealed 3 distinct types of round structures within the lesion: (1) comedolike openings (similar to those seen in seborrheic keratosis) that appeared as brownish-yellow, sharply circumscribed structures; (2) milialike cysts (also found in acanthotic seborrheic keratosis), which appeared as bright yellow structures; and (3) multiple whitish structures that were irregular in shape and size and covered the surface of the lesion where there were no other dermoscopic findings (Figure 2). The affected skin was pale to red in color and the verrucous aspect of the surface was better visualized at the edge of the lesion.

Two 4-mm punch biopsies were performed following dermoscopy: one for horizontal sectioning and one for vertical sectioning. Histologic analysis showed an acanthotic epidermis with an anastomosing network of elongated rete ridges in the superficial dermis. Numerous hyperplasic sebaceous glands were found in the mid dermis, with some also located above this level. Immature hair follicles were present and sebaceous gland ducts communicated directly with the epidermis through dilated hyperkeratinized pathways. Eccrine glands were normal, but no apocrine glands were present. A lymphocytic infiltrate was noted around the sebaceous glands and immature hair follicles and also around dilated capillaries in the superficial dermis. Moderate spongiosis and lymphocytic exocytosis were noted in the glandular epithelium and in the basal layer of the hair follicles and the epidermis. Superficial slides of horizontal sections of the biopsy specimen showed a correlation between the histology findings and dermoscopy images: multiple normal-appearing papilla surrounded by a network of anastomosing rete ridges correlated with multiple whitish structures, keratotic cysts with compact keratin corresponded to bright yellow dots, and larger conglomerates of loose lamelar keratin correlated with comedolike openings. Due to the presence of eczematous changes (eg, epithelial spongiosis, inflammatory cells) observed on histology, a diagnosis of an irritated sebaceous nevus was made, which explained the recent enlargement of the congenital lesion.

Sebaceous nevus is a benign, epidermal appendageal tumor with differentiation towards sebaceous glands that is composed of mature or nearly mature skin structures. Histologically, it is classified as a hamartoma.¹ It commonly arises on the scalp as a yellowish or flesh-colored, hairless plaque of variable size. At birth, its surface is smooth and the differential diagnoses include aplasia cutis congenita, congenital triangular alopecia, and alopecia areata.² As the patient ages, hormones stimulate the proliferation of sebaceous glands and the epidermis, and the lesion gradually acquires a verrucous, waxy surface.³ Benign appendageal tumors often develop inside SN. Basal cell epitheliomas are rarely found.⁴ Surgical excision is recommended for aesthetic purposes or to prevent the development of tumors.

Histology also varies with the patient’s age and can be misleading in childhood because the sebaceous glands are underdeveloped.^5,6 After adrenarche, histology becomes more diagnostic, showing a dermis almost completely filled with sebaceous glands with varying degrees of maturity.² The presence of incompletely differentiated follicles without hair shafts can be found in newborns and children and may be helpful for the correct histological diagnosis before puberty.^1,5 The epidermis presents no abnormalities at birth but develops acanthosis and papillomatosis as the patient ages. Ectopic dilated apocrine glands sometimes can be found deeper in the dermis in the late stage of the lesion.⁵

In a report by Neri et al,⁷ multiple bright yellow dots were noted on dermoscopy in 2 children with SN. The investigators concluded that this characteristic feature, which was thought to represent the sebaceous glands, can be useful in differentiating SN from aplasia cutis congenita in early infancy, but no histologic analyses were performed.⁷ In our patient, we identified 3 different dermoscopic features that correlated with histologic findings. Comedolike openings correlated with the accumulated keratin (ie, keratotic plugs) inside dilated sebaceous gland ducts directly connected to the epidermis. The brownish-yellow color of these openings observed on dermoscopy may be due to the oxidation of kerat-inous material, such as those in seborrheic keratosis lesions (Figure 3). We also noted bright yellow dots similar to those reported by Neri et al⁷; however, histologic analysis in our patient showed these dots more closely correlated with keratotic cysts similar to milialike structures seen in acanthotic seborrheic keratosis. The material remained lightly colored because no oxidation process had occurred (Figure 4). The third structure found on dermoscopy in our patient was multiple whitish structures that were irregular in shape and size. According to our comparison of superficial horizontal histology slides with dermoscopy images, we hypothesized this finding was the result of epidermal papillomatosis over a dermis filled with enlarged sebaceous glands (Figure 5). This finding was likely absent in the cases previously reported by Neri et al⁷ because epidermal and glandular changes occur later in the evolution of SN and the patients in these cases were younger than 4 months old.

Our correlation of dermoscopic features with histology findings in an 18-year-old woman with an irritated SN highlights the need for more studies needed in order to establish the prevalence of certain dermoscopic findings in this setting, particularly considering the important morphological changes that occur in these lesions as patients age as well as the histological variation among different hamartomas. Over the last decade, dermoscopy has proven to be a useful tool in the diagnosis of various hair and scalp diseases.⁸ Histologic correlation of dermoscopy findings is essential for more precise understanding of this new imaging technique and should be conducted whenever possible.

To the Editor:

Sebaceous nevus (SN) is a relatively common hamartoma that presents most often as a single congenital hairless plaque on the scalp. After puberty, histologic features characteristically include papillomatous hyperplasia of the epidermis, a large number of mature or nearly mature sebaceous glands, and a lack of terminally differentiated hair follicles; however, histologic findings can be misleading during childhood when sebaceous glands are still underdeveloped. Bright yellow dots, which are thought to indicate the presence of sebaceous glands, may be seen on dermoscopy and can be useful in differentiating SN from aplasia cutis congenita in newborns.

We report a case of an SN in an 18-year-old woman and discuss how the histology findings correlated with features seen on dermoscopy.

An 18-year-old woman presented to our dermatology clinic with an asymptomatic, hairless plaque on the right parietal scalp that had been present since birth. The patient noted that the plaque had recently become larger in size. On physical examination, an 8×3-cm plaque with a smooth, flesh-colored surface was noted with central comedolike structures and an erythematous, verrucous periphery (Figure 1).

Dermoscopy (handheld dermoscope using polarized light) revealed 3 distinct types of round structures within the lesion: (1) comedolike openings (similar to those seen in seborrheic keratosis) that appeared as brownish-yellow, sharply circumscribed structures; (2) milialike cysts (also found in acanthotic seborrheic keratosis), which appeared as bright yellow structures; and (3) multiple whitish structures that were irregular in shape and size and covered the surface of the lesion where there were no other dermoscopic findings (Figure 2). The affected skin was pale to red in color and the verrucous aspect of the surface was better visualized at the edge of the lesion.

Two 4-mm punch biopsies were performed following dermoscopy: one for horizontal sectioning and one for vertical sectioning. Histologic analysis showed an acanthotic epidermis with an anastomosing network of elongated rete ridges in the superficial dermis. Numerous hyperplasic sebaceous glands were found in the mid dermis, with some also located above this level. Immature hair follicles were present and sebaceous gland ducts communicated directly with the epidermis through dilated hyperkeratinized pathways. Eccrine glands were normal, but no apocrine glands were present. A lymphocytic infiltrate was noted around the sebaceous glands and immature hair follicles and also around dilated capillaries in the superficial dermis. Moderate spongiosis and lymphocytic exocytosis were noted in the glandular epithelium and in the basal layer of the hair follicles and the epidermis. Superficial slides of horizontal sections of the biopsy specimen showed a correlation between the histology findings and dermoscopy images: multiple normal-appearing papilla surrounded by a network of anastomosing rete ridges correlated with multiple whitish structures, keratotic cysts with compact keratin corresponded to bright yellow dots, and larger conglomerates of loose lamelar keratin correlated with comedolike openings. Due to the presence of eczematous changes (eg, epithelial spongiosis, inflammatory cells) observed on histology, a diagnosis of an irritated sebaceous nevus was made, which explained the recent enlargement of the congenital lesion.

Sebaceous nevus is a benign, epidermal appendageal tumor with differentiation towards sebaceous glands that is composed of mature or nearly mature skin structures. Histologically, it is classified as a hamartoma.¹ It commonly arises on the scalp as a yellowish or flesh-colored, hairless plaque of variable size. At birth, its surface is smooth and the differential diagnoses include aplasia cutis congenita, congenital triangular alopecia, and alopecia areata.² As the patient ages, hormones stimulate the proliferation of sebaceous glands and the epidermis, and the lesion gradually acquires a verrucous, waxy surface.³ Benign appendageal tumors often develop inside SN. Basal cell epitheliomas are rarely found.⁴ Surgical excision is recommended for aesthetic purposes or to prevent the development of tumors.

Histology also varies with the patient’s age and can be misleading in childhood because the sebaceous glands are underdeveloped.^5,6 After adrenarche, histology becomes more diagnostic, showing a dermis almost completely filled with sebaceous glands with varying degrees of maturity.² The presence of incompletely differentiated follicles without hair shafts can be found in newborns and children and may be helpful for the correct histological diagnosis before puberty.^1,5 The epidermis presents no abnormalities at birth but develops acanthosis and papillomatosis as the patient ages. Ectopic dilated apocrine glands sometimes can be found deeper in the dermis in the late stage of the lesion.⁵

In a report by Neri et al,⁷ multiple bright yellow dots were noted on dermoscopy in 2 children with SN. The investigators concluded that this characteristic feature, which was thought to represent the sebaceous glands, can be useful in differentiating SN from aplasia cutis congenita in early infancy, but no histologic analyses were performed.⁷ In our patient, we identified 3 different dermoscopic features that correlated with histologic findings. Comedolike openings correlated with the accumulated keratin (ie, keratotic plugs) inside dilated sebaceous gland ducts directly connected to the epidermis. The brownish-yellow color of these openings observed on dermoscopy may be due to the oxidation of kerat-inous material, such as those in seborrheic keratosis lesions (Figure 3). We also noted bright yellow dots similar to those reported by Neri et al⁷; however, histologic analysis in our patient showed these dots more closely correlated with keratotic cysts similar to milialike structures seen in acanthotic seborrheic keratosis. The material remained lightly colored because no oxidation process had occurred (Figure 4). The third structure found on dermoscopy in our patient was multiple whitish structures that were irregular in shape and size. According to our comparison of superficial horizontal histology slides with dermoscopy images, we hypothesized this finding was the result of epidermal papillomatosis over a dermis filled with enlarged sebaceous glands (Figure 5). This finding was likely absent in the cases previously reported by Neri et al⁷ because epidermal and glandular changes occur later in the evolution of SN and the patients in these cases were younger than 4 months old.

Our correlation of dermoscopic features with histology findings in an 18-year-old woman with an irritated SN highlights the need for more studies needed in order to establish the prevalence of certain dermoscopic findings in this setting, particularly considering the important morphological changes that occur in these lesions as patients age as well as the histological variation among different hamartomas. Over the last decade, dermoscopy has proven to be a useful tool in the diagnosis of various hair and scalp diseases.⁸ Histologic correlation of dermoscopy findings is essential for more precise understanding of this new imaging technique and should be conducted whenever possible.

To the Editor:

Sebaceous nevus (SN) is a relatively common hamartoma that presents most often as a single congenital hairless plaque on the scalp. After puberty, histologic features characteristically include papillomatous hyperplasia of the epidermis, a large number of mature or nearly mature sebaceous glands, and a lack of terminally differentiated hair follicles; however, histologic findings can be misleading during childhood when sebaceous glands are still underdeveloped. Bright yellow dots, which are thought to indicate the presence of sebaceous glands, may be seen on dermoscopy and can be useful in differentiating SN from aplasia cutis congenita in newborns.

We report a case of an SN in an 18-year-old woman and discuss how the histology findings correlated with features seen on dermoscopy.

An 18-year-old woman presented to our dermatology clinic with an asymptomatic, hairless plaque on the right parietal scalp that had been present since birth. The patient noted that the plaque had recently become larger in size. On physical examination, an 8×3-cm plaque with a smooth, flesh-colored surface was noted with central comedolike structures and an erythematous, verrucous periphery (Figure 1).

Dermoscopy (handheld dermoscope using polarized light) revealed 3 distinct types of round structures within the lesion: (1) comedolike openings (similar to those seen in seborrheic keratosis) that appeared as brownish-yellow, sharply circumscribed structures; (2) milialike cysts (also found in acanthotic seborrheic keratosis), which appeared as bright yellow structures; and (3) multiple whitish structures that were irregular in shape and size and covered the surface of the lesion where there were no other dermoscopic findings (Figure 2). The affected skin was pale to red in color and the verrucous aspect of the surface was better visualized at the edge of the lesion.

Two 4-mm punch biopsies were performed following dermoscopy: one for horizontal sectioning and one for vertical sectioning. Histologic analysis showed an acanthotic epidermis with an anastomosing network of elongated rete ridges in the superficial dermis. Numerous hyperplasic sebaceous glands were found in the mid dermis, with some also located above this level. Immature hair follicles were present and sebaceous gland ducts communicated directly with the epidermis through dilated hyperkeratinized pathways. Eccrine glands were normal, but no apocrine glands were present. A lymphocytic infiltrate was noted around the sebaceous glands and immature hair follicles and also around dilated capillaries in the superficial dermis. Moderate spongiosis and lymphocytic exocytosis were noted in the glandular epithelium and in the basal layer of the hair follicles and the epidermis. Superficial slides of horizontal sections of the biopsy specimen showed a correlation between the histology findings and dermoscopy images: multiple normal-appearing papilla surrounded by a network of anastomosing rete ridges correlated with multiple whitish structures, keratotic cysts with compact keratin corresponded to bright yellow dots, and larger conglomerates of loose lamelar keratin correlated with comedolike openings. Due to the presence of eczematous changes (eg, epithelial spongiosis, inflammatory cells) observed on histology, a diagnosis of an irritated sebaceous nevus was made, which explained the recent enlargement of the congenital lesion.

Sebaceous nevus is a benign, epidermal appendageal tumor with differentiation towards sebaceous glands that is composed of mature or nearly mature skin structures. Histologically, it is classified as a hamartoma.¹ It commonly arises on the scalp as a yellowish or flesh-colored, hairless plaque of variable size. At birth, its surface is smooth and the differential diagnoses include aplasia cutis congenita, congenital triangular alopecia, and alopecia areata.² As the patient ages, hormones stimulate the proliferation of sebaceous glands and the epidermis, and the lesion gradually acquires a verrucous, waxy surface.³ Benign appendageal tumors often develop inside SN. Basal cell epitheliomas are rarely found.⁴ Surgical excision is recommended for aesthetic purposes or to prevent the development of tumors.

Histology also varies with the patient’s age and can be misleading in childhood because the sebaceous glands are underdeveloped.^5,6 After adrenarche, histology becomes more diagnostic, showing a dermis almost completely filled with sebaceous glands with varying degrees of maturity.² The presence of incompletely differentiated follicles without hair shafts can be found in newborns and children and may be helpful for the correct histological diagnosis before puberty.^1,5 The epidermis presents no abnormalities at birth but develops acanthosis and papillomatosis as the patient ages. Ectopic dilated apocrine glands sometimes can be found deeper in the dermis in the late stage of the lesion.⁵

In a report by Neri et al,⁷ multiple bright yellow dots were noted on dermoscopy in 2 children with SN. The investigators concluded that this characteristic feature, which was thought to represent the sebaceous glands, can be useful in differentiating SN from aplasia cutis congenita in early infancy, but no histologic analyses were performed.⁷ In our patient, we identified 3 different dermoscopic features that correlated with histologic findings. Comedolike openings correlated with the accumulated keratin (ie, keratotic plugs) inside dilated sebaceous gland ducts directly connected to the epidermis. The brownish-yellow color of these openings observed on dermoscopy may be due to the oxidation of kerat-inous material, such as those in seborrheic keratosis lesions (Figure 3). We also noted bright yellow dots similar to those reported by Neri et al⁷; however, histologic analysis in our patient showed these dots more closely correlated with keratotic cysts similar to milialike structures seen in acanthotic seborrheic keratosis. The material remained lightly colored because no oxidation process had occurred (Figure 4). The third structure found on dermoscopy in our patient was multiple whitish structures that were irregular in shape and size. According to our comparison of superficial horizontal histology slides with dermoscopy images, we hypothesized this finding was the result of epidermal papillomatosis over a dermis filled with enlarged sebaceous glands (Figure 5). This finding was likely absent in the cases previously reported by Neri et al⁷ because epidermal and glandular changes occur later in the evolution of SN and the patients in these cases were younger than 4 months old.

Our correlation of dermoscopic features with histology findings in an 18-year-old woman with an irritated SN highlights the need for more studies needed in order to establish the prevalence of certain dermoscopic findings in this setting, particularly considering the important morphological changes that occur in these lesions as patients age as well as the histological variation among different hamartomas. Over the last decade, dermoscopy has proven to be a useful tool in the diagnosis of various hair and scalp diseases.⁸ Histologic correlation of dermoscopy findings is essential for more precise understanding of this new imaging technique and should be conducted whenever possible.

Treatment for chronic myeloid leukemia (CML) entails effective but mostly noncurative long-term use of tyrosine kinase inhibitors (TKIs) that require proactive, rational approaches to minimizing cardiovascular toxicities, according to a recent review.

Survival rates of patients with newly diagnosed CML are about 90%, and in those with a complete cytogenetic response, survival is comparable to that of age-matched controls. Although second-generation TKIs have increased efficacy, survival rates are similar to those of imatinib, possibly due in part to mortality from non-CML causes.

TKIs used in CML therapy target BCR-ABL1, but their potencies vary against other kinases, including receptors for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). The relationship between off-target activities and adverse events (AEs) remains unclear, and AE management is largely empirical, said Dr. Javid Moslehi of Vanderbilt University Medical Center, Nashville, Tenn., and Dr. Michael Deininger, professor at the University of Utah Huntsman Cancer Institute, Salt Lake City.

“Reports of cardiovascular AEs with nilotinib, pulmonary arterial hypertension (PAH) on dasatinib, and frequent cardiovascular AEs with ponatinib have caused a reassessment of the situation,” they noted.

“Given the high population frequency of cardiovascular disease and the increased frequency of vascular events with nilotinib and ponatinib, cardiovascular risk assessment and, if necessary, treatment need to be integrated into the management of patients with CML on TKIs,” they wrote (J Clin Onc. 2015 Dec 10. doi: 10.1200/JCO.2015.62.4718).

Retrospective studies have indicated that imatinib may have favorable metabolic and vascular effects, but prospective controlled trials are lacking. Defining the cardiovascular baseline risk of the specific CML population under study will be crucial in future studies.

Dasatinib was approved for front-line CML treatment based on superior cytogenic response rates, compared with imatinib, but in 2011 the Food and Drug Administration warned against cardiopulmonary risks and recommended that patients be evaluated for signs and symptoms of cardiopulmonary disease before and during dasatinib treatment. Results of DASISION (Dasatinib Versus Imatinib Study in Treatment-Naive CML Patients) showed that, at 36 months of follow-up, PAH was reported in 3% of patients on dasatinib and 0% on imatinib.

Nilotinib has shown superior efficacy to imatinib and was FDA approved for first-line therapy, with recommendations for arrhythmia monitoring and avoidance of QT interval–prolonging medications. There have been no subsequent reports of ventricular arrhythmias with nilotinib, but 36% of patients on nilotinib experienced hyperglycemia in the ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients) study, compared with 20% on imatinib. Nilotinib also has been associated with hyperlipidemia and increased body mass. Recent results point to vascular toxicity with nilotinib. At the 6-year follow-up of the ENESTnd study, 10% of patients on nilotinib 300 mg twice per day and 16% on nilotinib 400 mg twice per day had cardiovascular events, compared with 2.5% of patients taking imatinib 400 mg once per day. The dose-dependent increased risk implicates a drug-dependent process.

Ponatinib is the only clinical TKI active against the BCR-ABL1^T315I mutation. It is a potent inhibitor of numerous other kinases as well, including VEGF receptors. In the PACE (Ponatinib Ph-positive Acute Lymphoblastic Leukemia and CML Evaluation) study, 26% of patients on ponatinib developed hypertension, and traditional atherosclerosis risk factors (age, hypertension, and diabetes) predisposed patients to serious vascular AEs. Cardiovascular toxicity was shown to be dose dependent, and older patients with history of diabetes or ischemic events are the least tolerant of high dose intensity. A subset of patients will benefit from ponatinib, particularly those with BCR-ABL1^T315I, but leukemia-related and cardiovascular risks must both be assessed.

Dr. Moslehi reported financial ties with Novartis, ARIAD, Takeda/Millennium, Bristol-Myers Squibb, and Acceleron Pharma. Dr. Deininger reported ties to Novartis, Bristol-Myers Squibb, Incyte, ARIAD, Pfizer, and Cellgene.

Treatment for chronic myeloid leukemia (CML) entails effective but mostly noncurative long-term use of tyrosine kinase inhibitors (TKIs) that require proactive, rational approaches to minimizing cardiovascular toxicities, according to a recent review.

Survival rates of patients with newly diagnosed CML are about 90%, and in those with a complete cytogenetic response, survival is comparable to that of age-matched controls. Although second-generation TKIs have increased efficacy, survival rates are similar to those of imatinib, possibly due in part to mortality from non-CML causes.

TKIs used in CML therapy target BCR-ABL1, but their potencies vary against other kinases, including receptors for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). The relationship between off-target activities and adverse events (AEs) remains unclear, and AE management is largely empirical, said Dr. Javid Moslehi of Vanderbilt University Medical Center, Nashville, Tenn., and Dr. Michael Deininger, professor at the University of Utah Huntsman Cancer Institute, Salt Lake City.

“Reports of cardiovascular AEs with nilotinib, pulmonary arterial hypertension (PAH) on dasatinib, and frequent cardiovascular AEs with ponatinib have caused a reassessment of the situation,” they noted.

“Given the high population frequency of cardiovascular disease and the increased frequency of vascular events with nilotinib and ponatinib, cardiovascular risk assessment and, if necessary, treatment need to be integrated into the management of patients with CML on TKIs,” they wrote (J Clin Onc. 2015 Dec 10. doi: 10.1200/JCO.2015.62.4718).

Retrospective studies have indicated that imatinib may have favorable metabolic and vascular effects, but prospective controlled trials are lacking. Defining the cardiovascular baseline risk of the specific CML population under study will be crucial in future studies.

Dasatinib was approved for front-line CML treatment based on superior cytogenic response rates, compared with imatinib, but in 2011 the Food and Drug Administration warned against cardiopulmonary risks and recommended that patients be evaluated for signs and symptoms of cardiopulmonary disease before and during dasatinib treatment. Results of DASISION (Dasatinib Versus Imatinib Study in Treatment-Naive CML Patients) showed that, at 36 months of follow-up, PAH was reported in 3% of patients on dasatinib and 0% on imatinib.

Nilotinib has shown superior efficacy to imatinib and was FDA approved for first-line therapy, with recommendations for arrhythmia monitoring and avoidance of QT interval–prolonging medications. There have been no subsequent reports of ventricular arrhythmias with nilotinib, but 36% of patients on nilotinib experienced hyperglycemia in the ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients) study, compared with 20% on imatinib. Nilotinib also has been associated with hyperlipidemia and increased body mass. Recent results point to vascular toxicity with nilotinib. At the 6-year follow-up of the ENESTnd study, 10% of patients on nilotinib 300 mg twice per day and 16% on nilotinib 400 mg twice per day had cardiovascular events, compared with 2.5% of patients taking imatinib 400 mg once per day. The dose-dependent increased risk implicates a drug-dependent process.

Ponatinib is the only clinical TKI active against the BCR-ABL1^T315I mutation. It is a potent inhibitor of numerous other kinases as well, including VEGF receptors. In the PACE (Ponatinib Ph-positive Acute Lymphoblastic Leukemia and CML Evaluation) study, 26% of patients on ponatinib developed hypertension, and traditional atherosclerosis risk factors (age, hypertension, and diabetes) predisposed patients to serious vascular AEs. Cardiovascular toxicity was shown to be dose dependent, and older patients with history of diabetes or ischemic events are the least tolerant of high dose intensity. A subset of patients will benefit from ponatinib, particularly those with BCR-ABL1^T315I, but leukemia-related and cardiovascular risks must both be assessed.

Dr. Moslehi reported financial ties with Novartis, ARIAD, Takeda/Millennium, Bristol-Myers Squibb, and Acceleron Pharma. Dr. Deininger reported ties to Novartis, Bristol-Myers Squibb, Incyte, ARIAD, Pfizer, and Cellgene.

Treatment for chronic myeloid leukemia (CML) entails effective but mostly noncurative long-term use of tyrosine kinase inhibitors (TKIs) that require proactive, rational approaches to minimizing cardiovascular toxicities, according to a recent review.

Survival rates of patients with newly diagnosed CML are about 90%, and in those with a complete cytogenetic response, survival is comparable to that of age-matched controls. Although second-generation TKIs have increased efficacy, survival rates are similar to those of imatinib, possibly due in part to mortality from non-CML causes.

TKIs used in CML therapy target BCR-ABL1, but their potencies vary against other kinases, including receptors for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). The relationship between off-target activities and adverse events (AEs) remains unclear, and AE management is largely empirical, said Dr. Javid Moslehi of Vanderbilt University Medical Center, Nashville, Tenn., and Dr. Michael Deininger, professor at the University of Utah Huntsman Cancer Institute, Salt Lake City.

“Reports of cardiovascular AEs with nilotinib, pulmonary arterial hypertension (PAH) on dasatinib, and frequent cardiovascular AEs with ponatinib have caused a reassessment of the situation,” they noted.

“Given the high population frequency of cardiovascular disease and the increased frequency of vascular events with nilotinib and ponatinib, cardiovascular risk assessment and, if necessary, treatment need to be integrated into the management of patients with CML on TKIs,” they wrote (J Clin Onc. 2015 Dec 10. doi: 10.1200/JCO.2015.62.4718).

Retrospective studies have indicated that imatinib may have favorable metabolic and vascular effects, but prospective controlled trials are lacking. Defining the cardiovascular baseline risk of the specific CML population under study will be crucial in future studies.

Dasatinib was approved for front-line CML treatment based on superior cytogenic response rates, compared with imatinib, but in 2011 the Food and Drug Administration warned against cardiopulmonary risks and recommended that patients be evaluated for signs and symptoms of cardiopulmonary disease before and during dasatinib treatment. Results of DASISION (Dasatinib Versus Imatinib Study in Treatment-Naive CML Patients) showed that, at 36 months of follow-up, PAH was reported in 3% of patients on dasatinib and 0% on imatinib.

Nilotinib has shown superior efficacy to imatinib and was FDA approved for first-line therapy, with recommendations for arrhythmia monitoring and avoidance of QT interval–prolonging medications. There have been no subsequent reports of ventricular arrhythmias with nilotinib, but 36% of patients on nilotinib experienced hyperglycemia in the ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Newly Diagnosed Patients) study, compared with 20% on imatinib. Nilotinib also has been associated with hyperlipidemia and increased body mass. Recent results point to vascular toxicity with nilotinib. At the 6-year follow-up of the ENESTnd study, 10% of patients on nilotinib 300 mg twice per day and 16% on nilotinib 400 mg twice per day had cardiovascular events, compared with 2.5% of patients taking imatinib 400 mg once per day. The dose-dependent increased risk implicates a drug-dependent process.

Ponatinib is the only clinical TKI active against the BCR-ABL1^T315I mutation. It is a potent inhibitor of numerous other kinases as well, including VEGF receptors. In the PACE (Ponatinib Ph-positive Acute Lymphoblastic Leukemia and CML Evaluation) study, 26% of patients on ponatinib developed hypertension, and traditional atherosclerosis risk factors (age, hypertension, and diabetes) predisposed patients to serious vascular AEs. Cardiovascular toxicity was shown to be dose dependent, and older patients with history of diabetes or ischemic events are the least tolerant of high dose intensity. A subset of patients will benefit from ponatinib, particularly those with BCR-ABL1^T315I, but leukemia-related and cardiovascular risks must both be assessed.

Dr. Moslehi reported financial ties with Novartis, ARIAD, Takeda/Millennium, Bristol-Myers Squibb, and Acceleron Pharma. Dr. Deininger reported ties to Novartis, Bristol-Myers Squibb, Incyte, ARIAD, Pfizer, and Cellgene.