The National Heart, Lung, and Blood Institute announced the premature termination of TWiTCH, its clinical trial of children with sickle cell disease, because researchers met their goal ahead of schedule.

The NHLBI stated in a press release that the trial was stopped in agreement with the recommendations of the Data and Safety Monitoring Board (DSMB) – an independent group of experts that regularly reviews accumulating data from ongoing clinical trials and makes recommendations to investigators and sponsors on how to move forward.

“The DSMB’s planned first interim analysis of the TWiTCH study data indicated that the study had reached its primary and most important endpoint,” the NHLBI said in the statement. “As such, they recommended that the study end due to early results, particularly given that the strength of the statistical finding was unlikely to change with the collection of additional data.”

TWiTCH (Transcranial Doppler with Transfusions Changing to Hydroxyurea) was a phase III clinical trial created to determine whether daily doses of hydroxyurea lower the transcranial Doppler (TCD) blood velocity in children with sickle cell disease with the same efficacy as that of blood transfusions. Currently, hydroxyurea is the only Food and Drug Administration–approved drug for sickle cell disease, a disorder that affects children and puts them at increased risk for stroke if they have high TCD blood flow velocities.

According to the data accrued by the researchers prior to the study’s termination, hydroxyurea was found to be “not inferior to (that is, no worse than) regular blood transfusions in lowering TCD velocities in children with sickle cell disease who are at high risk for stroke.”

“The results of TWiTCH will allow the families of children with sickle cell disease and who are at increased risk of stroke, to choose between two equally effective preventive therapies,” Dr. Keith Hoots, director of the NHLBI’s division of blood diseases and resources, said in an interview. “The TWiTCH trial is the most recent example of NHLBI’s ongoing commitment to the development of new therapies for the prevention and treatment of stroke in children with sickle cell disease.”

According to information from the American Society of Hematology, the trial included 25 participating centers from around the United States, and was funded by the NHLBI with sponsorship from Cincinnati Children’s Hospital Medical Center.

[email protected]

The National Heart, Lung, and Blood Institute announced the premature termination of TWiTCH, its clinical trial of children with sickle cell disease, because researchers met their goal ahead of schedule.

The NHLBI stated in a press release that the trial was stopped in agreement with the recommendations of the Data and Safety Monitoring Board (DSMB) – an independent group of experts that regularly reviews accumulating data from ongoing clinical trials and makes recommendations to investigators and sponsors on how to move forward.

“The DSMB’s planned first interim analysis of the TWiTCH study data indicated that the study had reached its primary and most important endpoint,” the NHLBI said in the statement. “As such, they recommended that the study end due to early results, particularly given that the strength of the statistical finding was unlikely to change with the collection of additional data.”

TWiTCH (Transcranial Doppler with Transfusions Changing to Hydroxyurea) was a phase III clinical trial created to determine whether daily doses of hydroxyurea lower the transcranial Doppler (TCD) blood velocity in children with sickle cell disease with the same efficacy as that of blood transfusions. Currently, hydroxyurea is the only Food and Drug Administration–approved drug for sickle cell disease, a disorder that affects children and puts them at increased risk for stroke if they have high TCD blood flow velocities.

According to the data accrued by the researchers prior to the study’s termination, hydroxyurea was found to be “not inferior to (that is, no worse than) regular blood transfusions in lowering TCD velocities in children with sickle cell disease who are at high risk for stroke.”

“The results of TWiTCH will allow the families of children with sickle cell disease and who are at increased risk of stroke, to choose between two equally effective preventive therapies,” Dr. Keith Hoots, director of the NHLBI’s division of blood diseases and resources, said in an interview. “The TWiTCH trial is the most recent example of NHLBI’s ongoing commitment to the development of new therapies for the prevention and treatment of stroke in children with sickle cell disease.”

According to information from the American Society of Hematology, the trial included 25 participating centers from around the United States, and was funded by the NHLBI with sponsorship from Cincinnati Children’s Hospital Medical Center.

[email protected]

The National Heart, Lung, and Blood Institute announced the premature termination of TWiTCH, its clinical trial of children with sickle cell disease, because researchers met their goal ahead of schedule.

The NHLBI stated in a press release that the trial was stopped in agreement with the recommendations of the Data and Safety Monitoring Board (DSMB) – an independent group of experts that regularly reviews accumulating data from ongoing clinical trials and makes recommendations to investigators and sponsors on how to move forward.

“The DSMB’s planned first interim analysis of the TWiTCH study data indicated that the study had reached its primary and most important endpoint,” the NHLBI said in the statement. “As such, they recommended that the study end due to early results, particularly given that the strength of the statistical finding was unlikely to change with the collection of additional data.”

TWiTCH (Transcranial Doppler with Transfusions Changing to Hydroxyurea) was a phase III clinical trial created to determine whether daily doses of hydroxyurea lower the transcranial Doppler (TCD) blood velocity in children with sickle cell disease with the same efficacy as that of blood transfusions. Currently, hydroxyurea is the only Food and Drug Administration–approved drug for sickle cell disease, a disorder that affects children and puts them at increased risk for stroke if they have high TCD blood flow velocities.

According to the data accrued by the researchers prior to the study’s termination, hydroxyurea was found to be “not inferior to (that is, no worse than) regular blood transfusions in lowering TCD velocities in children with sickle cell disease who are at high risk for stroke.”

“The results of TWiTCH will allow the families of children with sickle cell disease and who are at increased risk of stroke, to choose between two equally effective preventive therapies,” Dr. Keith Hoots, director of the NHLBI’s division of blood diseases and resources, said in an interview. “The TWiTCH trial is the most recent example of NHLBI’s ongoing commitment to the development of new therapies for the prevention and treatment of stroke in children with sickle cell disease.”

According to information from the American Society of Hematology, the trial included 25 participating centers from around the United States, and was funded by the NHLBI with sponsorship from Cincinnati Children’s Hospital Medical Center.

[email protected]

Two-year folic acid and vitamin B12 supplementation did not improve performance in four cognitive domains in elderly people with elevated homocysteine levels, according to a study published online ahead of print November 12 in Neurology. A total of 2,919 participants with an average age of 74 took either a tablet with 400 μg of folic acid and 500 μg of vitamin B12, or a placebo every day for two years. Tests of memory and thinking skills were performed at the beginning and end of the study. All participants had high blood levels of homocysteine. “While the homocysteine levels decreased by more in the group taking the B vitamins than in the group taking the placebo, unfortunately, there was no difference between the two groups in the scores on the thinking and memory tests,” the researchers stated.

Among more than 43,000 children treated in 25 emergency departments for blunt head trauma, traumatic brain injury (TBI) was identified on CT scans in 7% of the patients, according to a study published November 13 in the New England Journal of Medicine. In children 12 and younger, falls were the most common cause of head injury—among those younger than 2, falls accounted for 77% of head injuries, and in those 2 to 12, falls accounted for 38% of injuries. In children ages 13 to 17, 24% of injuries were due to assault, 19% were sports-related, and 18% resulted from motor vehicle accidents. Among all cases, 98% had mild head trauma. During diagnosis and treatment, cranial CT scans were performed on 37% of the children, “many arguably unnecessarily,” according to the researchers.

Preadmission use of COX-2 inhibitors was associated with increased 30-day mortality after ischemic stroke, but not hemorrhagic stroke, according to a study published online ahead of print November 5 in Neurology. Researchers analyzed records of 100,243 patients hospitalized for a first stroke between 2004 and 2012 and deaths within one month after the stroke. The investigators examined whether participants were current, former, or nonusers of these drugs within two months of the stroke. Overall, people who were current users of COX-2 inhibitors were 19% more likely to die after stroke than were people who did not take the drugs. New users of the older COX-2 drugs were 42% more likely to die from stroke than were those who were not taking the drugs.

Once-daily, low-dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction among patients age 60 or older with atherosclerotic risk factors, according to a study published online ahead of print November 17 in JAMA. This study included 14,464 Japanese patients with hypertension, dyslipidemia, or diabetes mellitus who were randomized to aspirin (100 mg/d) or no aspirin in addition to ongoing medications. The researchers found no statistically significant difference between the two groups in time to the primary end point. The cumulative primary event rate was similar in participants in the aspirin group (2.77%) and those in the no-aspirin group (2.96%) five years after randomization. Aspirin significantly reduced the incidence of nonfatal heart attack and transient ischemic attack, and significantly increased the risk of extracranial hemorrhage requiring transfusion or hospitalization.

Overall symptom burden is the only independent predictor of prolonged symptoms after sport-related concussion, investigators reported online ahead of print November 7 in Neurology. The researchers conducted a prospective cohort study of 531 patients in a sports concussion clinic. Participants completed questionnaires that included the Post-Concussion Symptom Scale (PCSS). Patients ranged in age from 7 to 26 (mean age, 14.6). The mean PCSS score at the initial visit was 26, and mean time to presentation was 12 days. Only total score on symptom inventory was independently associated with symptoms lasting longer than 28 days. No other potential predictor variables were independently associated with symptom duration or were useful in developing the optimal regression decision tree. Most participants with an initial PCSS score of less than 13 had resolution of their symptoms within 28 days of injury.

The ketogenic diet and modified Atkins diet show modest efficacy, although in some patients the effect is “remarkable” in the treatment of refractory epilepsy in adults, according to a study published online ahead of print October 29 in Neurology. Researchers reviewed five studies on the ketogenic diet that included 47 people and five studies on the modified Atkins diet that included 85 people. The investigators found that across all studies, 32% of people treated with the ketogenic diet and 29% of those treated with the modified Atkins diet had a 50% or better reduction in their seizures. Nine percent in the ketogenic treatment group and 5% in the modified Atkins group had a greater than 90% reduction in seizures. “These studies show the diets are moderately to very effective as another option for people with epilepsy,” stated the study authors.

The evaluation of serum micro-RNAs may help to identify the severity of brain injury and the risk of developing adverse effects after traumatic brain injury (TBI), according to a study published November 7 in PLoS One. Researchers identified a unique and specific group of microRNAs, which were detected in blood immediately after injury to the brain in mice. The results suggest that the microRNAs can be measured in the blood as proxies for mild TBI. The microRNA panel identified in this study is unique and does not overlap with blood microRNAs of post-traumatic stress disorder, as previously reported. “This important finding is a step forward in identifying objective biomarkers for mild TBI that may be further validated to accurately and cost effectively identify mild TBI in service members and civilians with brain injuries,” said the investigators.

The FDA has approved Lemtrada (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS). The approval comes nearly one year after the FDA declined to approve the drug, citing a lack of well-controlled data from clinical studies at the time indicating that the benefits had outweighed the risks. After an appeal by Genzyme (Cambridge, Massachusetts) and a new review by the FDA, the agency approved the drug based on two pivotal, randomized phase III, open-label, rater-blinded studies, comparing treatment with Lemtrada to interferon beta-1a, in patients with relapsing-remitting MS who were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II). Lemtrada is recommended for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.

Angiotensin-converting enzyme inhibitors (ACEIs) exhibited a dose-dependent inverse association with amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print November 10 in JAMA Neurology. Researchers included 729 patients diagnosed with ALS between January 2002 and December 2008. The patients were compared with 14,580 controls. Fifteen percent of patients with ALS reported ACEI use between two and five years before their ALS diagnosis, and 18% of the control group without ALS reported ACEI use. When compared with patients who did not use ACEIs, the adjusted odds ratios were 0.83 for the group prescribed ACEIs lower than 449.5 of the cumulative defined daily dose (cDDD) and 0.43 cDDD for the group with a cumulative ACEI use of greater than 449.5 cDDD.

Patients treated at hospitals with higher volumes of subarachnoid hemorrhage (SAH) cases have lower in-hospital mortality, independent of patient and hospital characteristics, according to a study published in the November Neurosurgery. In a large nationwide registry, researchers identified nearly 32,000 patients with SAH treated at 685 United States hospitals between 2003 and 2012. The median annual case volume per hospital was 8.5 patients. Mean in-hospital mortality was 25.7% but was lower with increasing annual SAH volume. Hospital SAH volume was independently associated with in-hospital mortality (adjusted odds ratio, 0.79 for quartile 4 vs quartile 1), independent of patient and other hospital characteristics. “Our results may have significant implications for regional stroke policies and procedures and affirm the recent recommendations that patients with SAH be treated at high-volume centers,” said study authors.

The use of a specialized ambulance—stroke emergency mobile unit (STEMO)—increases the percentage of patients receiving thrombolysis within 60 minutes, according to a study published online ahead of print November 17 in JAMA Neurology. A total of 3,213 emergency calls for suspected stroke occurred during weeks when STEMO was available, and 2,969 calls occurred during control weeks when STEMO was not available. Two hundred of 614 patients with stroke (32.6%) received thrombolysis when the STEMO was deployed, and 330 of 1,497 patients (22%) received thrombolysis in conventional care. Median onset to treatment was 24.5 minutes shorter after STEMO deployment, compared with conventional care. In all ischemic strokes, the rate of “golden hour” thrombolysis increased from 16 of the 1,497 patients (1.1%) during conventional care to 62 of 614 (10.1%) after STEMO deployment. Overall, golden hour thrombolysis entails no risk to the patients’ safety and is associated with better short-term outcomes, according to the researchers.

Granger causality (GC) analysis of intracranial EEG (iEEG) has the potential to increase understanding of preictal network activity and help improve surgical outcomes in cases of otherwise ambiguous iEEG onset, according to a study published online ahead of print November 4 in Epilepsia. In 10 retrospective and two prospective patients with epilepsy, iEEG was recorded at 500 or 1,000 Hz, using as many as 128 surface and depth electrodes. In all patients, the researchers found significant, widespread preictal GC network activity at peak frequencies from 80 to 250 Hz, beginning two to 42 seconds before visible electrographic onset. In the two prospective patients, GC source/sink comparisons supported the exclusion of early ictal regions that were not the dominant causal sources and contributed to planning of more limited surgical resections. Both groups of patients had a class 1 outcome at one year.

Tiny silent acute infarcts may be a cause of leukoaraiosis, a finding that points toward a potentially treatable form of dementia, investigators reported online ahead of print October 4 in Annals of Neurology. The study involved five patients with leukoaraiosis who underwent detailed MRI scanning of their brains every week for 16 consecutive weeks. The MRI scans revealed new tiny spots arising de novo in the cerebral white matter. The lesions were “clinically silent and had the signature features of acute ischemic stroke, according to the researchers. “With time, the characteristics of these lesions approached those of pre-existing leukoaraiosis,” the study authors stated.

—Kimberly D. Williams

Two-year folic acid and vitamin B12 supplementation did not improve performance in four cognitive domains in elderly people with elevated homocysteine levels, according to a study published online ahead of print November 12 in Neurology. A total of 2,919 participants with an average age of 74 took either a tablet with 400 μg of folic acid and 500 μg of vitamin B12, or a placebo every day for two years. Tests of memory and thinking skills were performed at the beginning and end of the study. All participants had high blood levels of homocysteine. “While the homocysteine levels decreased by more in the group taking the B vitamins than in the group taking the placebo, unfortunately, there was no difference between the two groups in the scores on the thinking and memory tests,” the researchers stated.

Among more than 43,000 children treated in 25 emergency departments for blunt head trauma, traumatic brain injury (TBI) was identified on CT scans in 7% of the patients, according to a study published November 13 in the New England Journal of Medicine. In children 12 and younger, falls were the most common cause of head injury—among those younger than 2, falls accounted for 77% of head injuries, and in those 2 to 12, falls accounted for 38% of injuries. In children ages 13 to 17, 24% of injuries were due to assault, 19% were sports-related, and 18% resulted from motor vehicle accidents. Among all cases, 98% had mild head trauma. During diagnosis and treatment, cranial CT scans were performed on 37% of the children, “many arguably unnecessarily,” according to the researchers.

Preadmission use of COX-2 inhibitors was associated with increased 30-day mortality after ischemic stroke, but not hemorrhagic stroke, according to a study published online ahead of print November 5 in Neurology. Researchers analyzed records of 100,243 patients hospitalized for a first stroke between 2004 and 2012 and deaths within one month after the stroke. The investigators examined whether participants were current, former, or nonusers of these drugs within two months of the stroke. Overall, people who were current users of COX-2 inhibitors were 19% more likely to die after stroke than were people who did not take the drugs. New users of the older COX-2 drugs were 42% more likely to die from stroke than were those who were not taking the drugs.

Once-daily, low-dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction among patients age 60 or older with atherosclerotic risk factors, according to a study published online ahead of print November 17 in JAMA. This study included 14,464 Japanese patients with hypertension, dyslipidemia, or diabetes mellitus who were randomized to aspirin (100 mg/d) or no aspirin in addition to ongoing medications. The researchers found no statistically significant difference between the two groups in time to the primary end point. The cumulative primary event rate was similar in participants in the aspirin group (2.77%) and those in the no-aspirin group (2.96%) five years after randomization. Aspirin significantly reduced the incidence of nonfatal heart attack and transient ischemic attack, and significantly increased the risk of extracranial hemorrhage requiring transfusion or hospitalization.

Overall symptom burden is the only independent predictor of prolonged symptoms after sport-related concussion, investigators reported online ahead of print November 7 in Neurology. The researchers conducted a prospective cohort study of 531 patients in a sports concussion clinic. Participants completed questionnaires that included the Post-Concussion Symptom Scale (PCSS). Patients ranged in age from 7 to 26 (mean age, 14.6). The mean PCSS score at the initial visit was 26, and mean time to presentation was 12 days. Only total score on symptom inventory was independently associated with symptoms lasting longer than 28 days. No other potential predictor variables were independently associated with symptom duration or were useful in developing the optimal regression decision tree. Most participants with an initial PCSS score of less than 13 had resolution of their symptoms within 28 days of injury.

The ketogenic diet and modified Atkins diet show modest efficacy, although in some patients the effect is “remarkable” in the treatment of refractory epilepsy in adults, according to a study published online ahead of print October 29 in Neurology. Researchers reviewed five studies on the ketogenic diet that included 47 people and five studies on the modified Atkins diet that included 85 people. The investigators found that across all studies, 32% of people treated with the ketogenic diet and 29% of those treated with the modified Atkins diet had a 50% or better reduction in their seizures. Nine percent in the ketogenic treatment group and 5% in the modified Atkins group had a greater than 90% reduction in seizures. “These studies show the diets are moderately to very effective as another option for people with epilepsy,” stated the study authors.

The evaluation of serum micro-RNAs may help to identify the severity of brain injury and the risk of developing adverse effects after traumatic brain injury (TBI), according to a study published November 7 in PLoS One. Researchers identified a unique and specific group of microRNAs, which were detected in blood immediately after injury to the brain in mice. The results suggest that the microRNAs can be measured in the blood as proxies for mild TBI. The microRNA panel identified in this study is unique and does not overlap with blood microRNAs of post-traumatic stress disorder, as previously reported. “This important finding is a step forward in identifying objective biomarkers for mild TBI that may be further validated to accurately and cost effectively identify mild TBI in service members and civilians with brain injuries,” said the investigators.

The FDA has approved Lemtrada (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS). The approval comes nearly one year after the FDA declined to approve the drug, citing a lack of well-controlled data from clinical studies at the time indicating that the benefits had outweighed the risks. After an appeal by Genzyme (Cambridge, Massachusetts) and a new review by the FDA, the agency approved the drug based on two pivotal, randomized phase III, open-label, rater-blinded studies, comparing treatment with Lemtrada to interferon beta-1a, in patients with relapsing-remitting MS who were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II). Lemtrada is recommended for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.

Angiotensin-converting enzyme inhibitors (ACEIs) exhibited a dose-dependent inverse association with amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print November 10 in JAMA Neurology. Researchers included 729 patients diagnosed with ALS between January 2002 and December 2008. The patients were compared with 14,580 controls. Fifteen percent of patients with ALS reported ACEI use between two and five years before their ALS diagnosis, and 18% of the control group without ALS reported ACEI use. When compared with patients who did not use ACEIs, the adjusted odds ratios were 0.83 for the group prescribed ACEIs lower than 449.5 of the cumulative defined daily dose (cDDD) and 0.43 cDDD for the group with a cumulative ACEI use of greater than 449.5 cDDD.

Patients treated at hospitals with higher volumes of subarachnoid hemorrhage (SAH) cases have lower in-hospital mortality, independent of patient and hospital characteristics, according to a study published in the November Neurosurgery. In a large nationwide registry, researchers identified nearly 32,000 patients with SAH treated at 685 United States hospitals between 2003 and 2012. The median annual case volume per hospital was 8.5 patients. Mean in-hospital mortality was 25.7% but was lower with increasing annual SAH volume. Hospital SAH volume was independently associated with in-hospital mortality (adjusted odds ratio, 0.79 for quartile 4 vs quartile 1), independent of patient and other hospital characteristics. “Our results may have significant implications for regional stroke policies and procedures and affirm the recent recommendations that patients with SAH be treated at high-volume centers,” said study authors.

The use of a specialized ambulance—stroke emergency mobile unit (STEMO)—increases the percentage of patients receiving thrombolysis within 60 minutes, according to a study published online ahead of print November 17 in JAMA Neurology. A total of 3,213 emergency calls for suspected stroke occurred during weeks when STEMO was available, and 2,969 calls occurred during control weeks when STEMO was not available. Two hundred of 614 patients with stroke (32.6%) received thrombolysis when the STEMO was deployed, and 330 of 1,497 patients (22%) received thrombolysis in conventional care. Median onset to treatment was 24.5 minutes shorter after STEMO deployment, compared with conventional care. In all ischemic strokes, the rate of “golden hour” thrombolysis increased from 16 of the 1,497 patients (1.1%) during conventional care to 62 of 614 (10.1%) after STEMO deployment. Overall, golden hour thrombolysis entails no risk to the patients’ safety and is associated with better short-term outcomes, according to the researchers.

Granger causality (GC) analysis of intracranial EEG (iEEG) has the potential to increase understanding of preictal network activity and help improve surgical outcomes in cases of otherwise ambiguous iEEG onset, according to a study published online ahead of print November 4 in Epilepsia. In 10 retrospective and two prospective patients with epilepsy, iEEG was recorded at 500 or 1,000 Hz, using as many as 128 surface and depth electrodes. In all patients, the researchers found significant, widespread preictal GC network activity at peak frequencies from 80 to 250 Hz, beginning two to 42 seconds before visible electrographic onset. In the two prospective patients, GC source/sink comparisons supported the exclusion of early ictal regions that were not the dominant causal sources and contributed to planning of more limited surgical resections. Both groups of patients had a class 1 outcome at one year.

Tiny silent acute infarcts may be a cause of leukoaraiosis, a finding that points toward a potentially treatable form of dementia, investigators reported online ahead of print October 4 in Annals of Neurology. The study involved five patients with leukoaraiosis who underwent detailed MRI scanning of their brains every week for 16 consecutive weeks. The MRI scans revealed new tiny spots arising de novo in the cerebral white matter. The lesions were “clinically silent and had the signature features of acute ischemic stroke, according to the researchers. “With time, the characteristics of these lesions approached those of pre-existing leukoaraiosis,” the study authors stated.

—Kimberly D. Williams

Two-year folic acid and vitamin B12 supplementation did not improve performance in four cognitive domains in elderly people with elevated homocysteine levels, according to a study published online ahead of print November 12 in Neurology. A total of 2,919 participants with an average age of 74 took either a tablet with 400 μg of folic acid and 500 μg of vitamin B12, or a placebo every day for two years. Tests of memory and thinking skills were performed at the beginning and end of the study. All participants had high blood levels of homocysteine. “While the homocysteine levels decreased by more in the group taking the B vitamins than in the group taking the placebo, unfortunately, there was no difference between the two groups in the scores on the thinking and memory tests,” the researchers stated.

Among more than 43,000 children treated in 25 emergency departments for blunt head trauma, traumatic brain injury (TBI) was identified on CT scans in 7% of the patients, according to a study published November 13 in the New England Journal of Medicine. In children 12 and younger, falls were the most common cause of head injury—among those younger than 2, falls accounted for 77% of head injuries, and in those 2 to 12, falls accounted for 38% of injuries. In children ages 13 to 17, 24% of injuries were due to assault, 19% were sports-related, and 18% resulted from motor vehicle accidents. Among all cases, 98% had mild head trauma. During diagnosis and treatment, cranial CT scans were performed on 37% of the children, “many arguably unnecessarily,” according to the researchers.

Preadmission use of COX-2 inhibitors was associated with increased 30-day mortality after ischemic stroke, but not hemorrhagic stroke, according to a study published online ahead of print November 5 in Neurology. Researchers analyzed records of 100,243 patients hospitalized for a first stroke between 2004 and 2012 and deaths within one month after the stroke. The investigators examined whether participants were current, former, or nonusers of these drugs within two months of the stroke. Overall, people who were current users of COX-2 inhibitors were 19% more likely to die after stroke than were people who did not take the drugs. New users of the older COX-2 drugs were 42% more likely to die from stroke than were those who were not taking the drugs.

Once-daily, low-dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction among patients age 60 or older with atherosclerotic risk factors, according to a study published online ahead of print November 17 in JAMA. This study included 14,464 Japanese patients with hypertension, dyslipidemia, or diabetes mellitus who were randomized to aspirin (100 mg/d) or no aspirin in addition to ongoing medications. The researchers found no statistically significant difference between the two groups in time to the primary end point. The cumulative primary event rate was similar in participants in the aspirin group (2.77%) and those in the no-aspirin group (2.96%) five years after randomization. Aspirin significantly reduced the incidence of nonfatal heart attack and transient ischemic attack, and significantly increased the risk of extracranial hemorrhage requiring transfusion or hospitalization.

Overall symptom burden is the only independent predictor of prolonged symptoms after sport-related concussion, investigators reported online ahead of print November 7 in Neurology. The researchers conducted a prospective cohort study of 531 patients in a sports concussion clinic. Participants completed questionnaires that included the Post-Concussion Symptom Scale (PCSS). Patients ranged in age from 7 to 26 (mean age, 14.6). The mean PCSS score at the initial visit was 26, and mean time to presentation was 12 days. Only total score on symptom inventory was independently associated with symptoms lasting longer than 28 days. No other potential predictor variables were independently associated with symptom duration or were useful in developing the optimal regression decision tree. Most participants with an initial PCSS score of less than 13 had resolution of their symptoms within 28 days of injury.

The ketogenic diet and modified Atkins diet show modest efficacy, although in some patients the effect is “remarkable” in the treatment of refractory epilepsy in adults, according to a study published online ahead of print October 29 in Neurology. Researchers reviewed five studies on the ketogenic diet that included 47 people and five studies on the modified Atkins diet that included 85 people. The investigators found that across all studies, 32% of people treated with the ketogenic diet and 29% of those treated with the modified Atkins diet had a 50% or better reduction in their seizures. Nine percent in the ketogenic treatment group and 5% in the modified Atkins group had a greater than 90% reduction in seizures. “These studies show the diets are moderately to very effective as another option for people with epilepsy,” stated the study authors.

The evaluation of serum micro-RNAs may help to identify the severity of brain injury and the risk of developing adverse effects after traumatic brain injury (TBI), according to a study published November 7 in PLoS One. Researchers identified a unique and specific group of microRNAs, which were detected in blood immediately after injury to the brain in mice. The results suggest that the microRNAs can be measured in the blood as proxies for mild TBI. The microRNA panel identified in this study is unique and does not overlap with blood microRNAs of post-traumatic stress disorder, as previously reported. “This important finding is a step forward in identifying objective biomarkers for mild TBI that may be further validated to accurately and cost effectively identify mild TBI in service members and civilians with brain injuries,” said the investigators.

The FDA has approved Lemtrada (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS). The approval comes nearly one year after the FDA declined to approve the drug, citing a lack of well-controlled data from clinical studies at the time indicating that the benefits had outweighed the risks. After an appeal by Genzyme (Cambridge, Massachusetts) and a new review by the FDA, the agency approved the drug based on two pivotal, randomized phase III, open-label, rater-blinded studies, comparing treatment with Lemtrada to interferon beta-1a, in patients with relapsing-remitting MS who were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II). Lemtrada is recommended for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.

Angiotensin-converting enzyme inhibitors (ACEIs) exhibited a dose-dependent inverse association with amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print November 10 in JAMA Neurology. Researchers included 729 patients diagnosed with ALS between January 2002 and December 2008. The patients were compared with 14,580 controls. Fifteen percent of patients with ALS reported ACEI use between two and five years before their ALS diagnosis, and 18% of the control group without ALS reported ACEI use. When compared with patients who did not use ACEIs, the adjusted odds ratios were 0.83 for the group prescribed ACEIs lower than 449.5 of the cumulative defined daily dose (cDDD) and 0.43 cDDD for the group with a cumulative ACEI use of greater than 449.5 cDDD.

Patients treated at hospitals with higher volumes of subarachnoid hemorrhage (SAH) cases have lower in-hospital mortality, independent of patient and hospital characteristics, according to a study published in the November Neurosurgery. In a large nationwide registry, researchers identified nearly 32,000 patients with SAH treated at 685 United States hospitals between 2003 and 2012. The median annual case volume per hospital was 8.5 patients. Mean in-hospital mortality was 25.7% but was lower with increasing annual SAH volume. Hospital SAH volume was independently associated with in-hospital mortality (adjusted odds ratio, 0.79 for quartile 4 vs quartile 1), independent of patient and other hospital characteristics. “Our results may have significant implications for regional stroke policies and procedures and affirm the recent recommendations that patients with SAH be treated at high-volume centers,” said study authors.

The use of a specialized ambulance—stroke emergency mobile unit (STEMO)—increases the percentage of patients receiving thrombolysis within 60 minutes, according to a study published online ahead of print November 17 in JAMA Neurology. A total of 3,213 emergency calls for suspected stroke occurred during weeks when STEMO was available, and 2,969 calls occurred during control weeks when STEMO was not available. Two hundred of 614 patients with stroke (32.6%) received thrombolysis when the STEMO was deployed, and 330 of 1,497 patients (22%) received thrombolysis in conventional care. Median onset to treatment was 24.5 minutes shorter after STEMO deployment, compared with conventional care. In all ischemic strokes, the rate of “golden hour” thrombolysis increased from 16 of the 1,497 patients (1.1%) during conventional care to 62 of 614 (10.1%) after STEMO deployment. Overall, golden hour thrombolysis entails no risk to the patients’ safety and is associated with better short-term outcomes, according to the researchers.

Granger causality (GC) analysis of intracranial EEG (iEEG) has the potential to increase understanding of preictal network activity and help improve surgical outcomes in cases of otherwise ambiguous iEEG onset, according to a study published online ahead of print November 4 in Epilepsia. In 10 retrospective and two prospective patients with epilepsy, iEEG was recorded at 500 or 1,000 Hz, using as many as 128 surface and depth electrodes. In all patients, the researchers found significant, widespread preictal GC network activity at peak frequencies from 80 to 250 Hz, beginning two to 42 seconds before visible electrographic onset. In the two prospective patients, GC source/sink comparisons supported the exclusion of early ictal regions that were not the dominant causal sources and contributed to planning of more limited surgical resections. Both groups of patients had a class 1 outcome at one year.

Tiny silent acute infarcts may be a cause of leukoaraiosis, a finding that points toward a potentially treatable form of dementia, investigators reported online ahead of print October 4 in Annals of Neurology. The study involved five patients with leukoaraiosis who underwent detailed MRI scanning of their brains every week for 16 consecutive weeks. The MRI scans revealed new tiny spots arising de novo in the cerebral white matter. The lesions were “clinically silent and had the signature features of acute ischemic stroke, according to the researchers. “With time, the characteristics of these lesions approached those of pre-existing leukoaraiosis,” the study authors stated.

—Kimberly D. Williams

Amit Nathwani, MBChB, PhD

Credit: University College

London Hospitals

A novel gene therapy can provide lasting clinical improvement for men with severe hemophilia B, according to research published in NEJM.

In a study of 10 men, the therapy increased factor IX levels, reduced bleeding episodes, and decreased the use of prophylactic factor IX concentrate. The therapy also allowed some patients to adopt a more active lifestyle.

Four patients experienced temporary increases in liver enzymes, but none reported late toxic effects at a median follow-up of 3 years.

“The data we are reporting mark a paradigm shift in treatment of hemophilia B and lay the groundwork for curing this major bleeding disorder,” said study author Amit Nathwani, MBChB, PhD, of the University College London Cancer Institute in the UK.

“The results also provide a solid platform for developing this gene transfer approach for treatment of other disorders, ranging from other congenital clotting deficiencies like hemophilia A to inborn errors of metabolism such as phenylketonuria.”

The therapy consists of a serotype 8 pseudotyped, self-complementary adeno-associated virus (AAV8) vector expressing a codon-optimized factor IX transgene (scAAV2/8-LP1-hFIXco).

Dr Nathwani and his colleagues tested scAAV2/8-LP1-hFIXco in 10 men with severe hemophilia B to determine the durability of transgene expression, the vector dose-response relationship, and the level of persistent or late toxicity.

Six of the patients had been enrolled in a phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose of the therapy. The other 4 patients received the high dose (2 × 10¹² vector genomes per kg of body weight). Patients received scAAV2/8-LP1-hFIXco as a single infusion.

Factor IX levels rose in all 10 men following the infusion and have remained stable for a median of 3.2 years (range, 1.5 to 4.3 years).

Overall, episodes of spontaneous bleeding declined 90%. The use of factor IX replacement therapy dropped about 92% in the first 12 months after treatment with scAAV2/8-LP1-hFIXco.

In the 6 participants who received the highest dose of therapy, factor IX levels increased from less than 1% of normal levels to 5% or more.

The increase transformed their disease from severe to mild and enabled participation in sports such as soccer without the need for factor IX replacement therapy or an increase in the risk of bleeding.

Episodes of spontaneous bleeding and the use of factor IX replacement therapy declined for these patients more than 94% in the next 12 months.

Liver enzymes rose in 4 of the 6 patients who received the highest dose of scAAV2/8-LP1-hFIXco, possibly due to an immune response against the vector. The men had no symptoms and remained otherwise healthy. Their liver enzymes returned to the normal range following brief treatment with steroids.

“This study provides the first clear demonstration of the long-term safety and efficacy of gene therapy,” said study author Andrew Davidoff, MD, of St Jude Children’s Research Hospital in Memphis, Tennessee.

“The results so far have made a profound difference in the lives of study participants by dramatically reducing their risk of bleeding.”

Prior to receiving scAAV2/8-LP1-hFIXco, 7 of the men received factor IX replacement therapy at least once a week to prevent bleeding episodes. Others used replacement therapy as needed to halt bleeding or prior to surgeries.

Since joining the trial, 4 of these men ended the routine factor IX injections. And none have suffered spontaneous bleeding despite increased physical activity.

“Some patients have not required clotting factor injections for more than 4 years, which has been life-changing,” Dr Nathwani said.

The researchers estimated that overall spending on factor IX replacement therapy for study participants is down more than $2.5 million.

Twelve men have now joined this ongoing phase 1/2 trial. Half were treated at the University College London and half at St. Jude.

Discussions are underway about expanding the trial to include younger patients with hemophilia B. Meanwhile, work continues to improve and expand use of the vector for the treatment of hemophilia A.

Amit Nathwani, MBChB, PhD

Credit: University College

London Hospitals

A novel gene therapy can provide lasting clinical improvement for men with severe hemophilia B, according to research published in NEJM.

In a study of 10 men, the therapy increased factor IX levels, reduced bleeding episodes, and decreased the use of prophylactic factor IX concentrate. The therapy also allowed some patients to adopt a more active lifestyle.

Four patients experienced temporary increases in liver enzymes, but none reported late toxic effects at a median follow-up of 3 years.

“The data we are reporting mark a paradigm shift in treatment of hemophilia B and lay the groundwork for curing this major bleeding disorder,” said study author Amit Nathwani, MBChB, PhD, of the University College London Cancer Institute in the UK.

“The results also provide a solid platform for developing this gene transfer approach for treatment of other disorders, ranging from other congenital clotting deficiencies like hemophilia A to inborn errors of metabolism such as phenylketonuria.”

The therapy consists of a serotype 8 pseudotyped, self-complementary adeno-associated virus (AAV8) vector expressing a codon-optimized factor IX transgene (scAAV2/8-LP1-hFIXco).

Dr Nathwani and his colleagues tested scAAV2/8-LP1-hFIXco in 10 men with severe hemophilia B to determine the durability of transgene expression, the vector dose-response relationship, and the level of persistent or late toxicity.

Six of the patients had been enrolled in a phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose of the therapy. The other 4 patients received the high dose (2 × 10¹² vector genomes per kg of body weight). Patients received scAAV2/8-LP1-hFIXco as a single infusion.

Factor IX levels rose in all 10 men following the infusion and have remained stable for a median of 3.2 years (range, 1.5 to 4.3 years).

Overall, episodes of spontaneous bleeding declined 90%. The use of factor IX replacement therapy dropped about 92% in the first 12 months after treatment with scAAV2/8-LP1-hFIXco.

In the 6 participants who received the highest dose of therapy, factor IX levels increased from less than 1% of normal levels to 5% or more.

The increase transformed their disease from severe to mild and enabled participation in sports such as soccer without the need for factor IX replacement therapy or an increase in the risk of bleeding.

Episodes of spontaneous bleeding and the use of factor IX replacement therapy declined for these patients more than 94% in the next 12 months.

Liver enzymes rose in 4 of the 6 patients who received the highest dose of scAAV2/8-LP1-hFIXco, possibly due to an immune response against the vector. The men had no symptoms and remained otherwise healthy. Their liver enzymes returned to the normal range following brief treatment with steroids.

“This study provides the first clear demonstration of the long-term safety and efficacy of gene therapy,” said study author Andrew Davidoff, MD, of St Jude Children’s Research Hospital in Memphis, Tennessee.

“The results so far have made a profound difference in the lives of study participants by dramatically reducing their risk of bleeding.”

Prior to receiving scAAV2/8-LP1-hFIXco, 7 of the men received factor IX replacement therapy at least once a week to prevent bleeding episodes. Others used replacement therapy as needed to halt bleeding or prior to surgeries.

Since joining the trial, 4 of these men ended the routine factor IX injections. And none have suffered spontaneous bleeding despite increased physical activity.

“Some patients have not required clotting factor injections for more than 4 years, which has been life-changing,” Dr Nathwani said.

The researchers estimated that overall spending on factor IX replacement therapy for study participants is down more than $2.5 million.

Twelve men have now joined this ongoing phase 1/2 trial. Half were treated at the University College London and half at St. Jude.

Discussions are underway about expanding the trial to include younger patients with hemophilia B. Meanwhile, work continues to improve and expand use of the vector for the treatment of hemophilia A.

Amit Nathwani, MBChB, PhD

Credit: University College

London Hospitals

A novel gene therapy can provide lasting clinical improvement for men with severe hemophilia B, according to research published in NEJM.

In a study of 10 men, the therapy increased factor IX levels, reduced bleeding episodes, and decreased the use of prophylactic factor IX concentrate. The therapy also allowed some patients to adopt a more active lifestyle.

Four patients experienced temporary increases in liver enzymes, but none reported late toxic effects at a median follow-up of 3 years.

“The data we are reporting mark a paradigm shift in treatment of hemophilia B and lay the groundwork for curing this major bleeding disorder,” said study author Amit Nathwani, MBChB, PhD, of the University College London Cancer Institute in the UK.

“The results also provide a solid platform for developing this gene transfer approach for treatment of other disorders, ranging from other congenital clotting deficiencies like hemophilia A to inborn errors of metabolism such as phenylketonuria.”

The therapy consists of a serotype 8 pseudotyped, self-complementary adeno-associated virus (AAV8) vector expressing a codon-optimized factor IX transgene (scAAV2/8-LP1-hFIXco).

Dr Nathwani and his colleagues tested scAAV2/8-LP1-hFIXco in 10 men with severe hemophilia B to determine the durability of transgene expression, the vector dose-response relationship, and the level of persistent or late toxicity.

Six of the patients had been enrolled in a phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose of the therapy. The other 4 patients received the high dose (2 × 10¹² vector genomes per kg of body weight). Patients received scAAV2/8-LP1-hFIXco as a single infusion.

Factor IX levels rose in all 10 men following the infusion and have remained stable for a median of 3.2 years (range, 1.5 to 4.3 years).

Overall, episodes of spontaneous bleeding declined 90%. The use of factor IX replacement therapy dropped about 92% in the first 12 months after treatment with scAAV2/8-LP1-hFIXco.

In the 6 participants who received the highest dose of therapy, factor IX levels increased from less than 1% of normal levels to 5% or more.

The increase transformed their disease from severe to mild and enabled participation in sports such as soccer without the need for factor IX replacement therapy or an increase in the risk of bleeding.

Episodes of spontaneous bleeding and the use of factor IX replacement therapy declined for these patients more than 94% in the next 12 months.

Liver enzymes rose in 4 of the 6 patients who received the highest dose of scAAV2/8-LP1-hFIXco, possibly due to an immune response against the vector. The men had no symptoms and remained otherwise healthy. Their liver enzymes returned to the normal range following brief treatment with steroids.

“This study provides the first clear demonstration of the long-term safety and efficacy of gene therapy,” said study author Andrew Davidoff, MD, of St Jude Children’s Research Hospital in Memphis, Tennessee.

“The results so far have made a profound difference in the lives of study participants by dramatically reducing their risk of bleeding.”

Prior to receiving scAAV2/8-LP1-hFIXco, 7 of the men received factor IX replacement therapy at least once a week to prevent bleeding episodes. Others used replacement therapy as needed to halt bleeding or prior to surgeries.

Since joining the trial, 4 of these men ended the routine factor IX injections. And none have suffered spontaneous bleeding despite increased physical activity.

“Some patients have not required clotting factor injections for more than 4 years, which has been life-changing,” Dr Nathwani said.

The researchers estimated that overall spending on factor IX replacement therapy for study participants is down more than $2.5 million.

Twelve men have now joined this ongoing phase 1/2 trial. Half were treated at the University College London and half at St. Jude.

Discussions are underway about expanding the trial to include younger patients with hemophilia B. Meanwhile, work continues to improve and expand use of the vector for the treatment of hemophilia A.

Doctor examines SCD patient

Credit: St Jude Children’s

Research Hospital

Treatment with hydroxyurea is a comparable alternative to blood transfusions for reducing the risk of stroke in children with sickle cell disease (SCD), according to the National Heart Lung and Blood Institute (NHLBI).

Early results of the phase 3 TWiTCH trial showed that daily doses of hydroxyurea lower the transcranial Doppler (TCD) blood velocity in children with SCD to a similar degree as blood transfusions, thereby decreasing the risk of stroke.

Based on these findings, the NHLBI has terminated the trial early, about a year before it was originally scheduled to end.

“Early results indicate that TWiTCH is a success,” said Russell E. Ware, MD, PhD, principal investigator of the study and director of hematology at Cincinnati Children’s Hospital Medical Center.

“A group of outside experts has been reviewing the TWiTCH data every few months to ensure the safety of children in the clinical trial and to monitor the data. This group met recently and, after careful consideration of the interim data results, recommended that the study be stopped since hydroxyurea worked as well as transfusions to lower TCD velocities.”

The NHLBI said it cannot release results from the TWiTCH trial, but some details are available. Researchers enrolled 121 children between the ages of 4 and 16 who had SCD and abnormally elevated TCD velocities.

Half of patients received transfusions, and the other half received daily hydroxyurea, which has not yet been approved for children with SCD.

The clinical data-collection portion of the study was originally scheduled for the 24-month mark, but collection was stopped after only half of the children completed the treatment phase.

At the first interim analysis, a data and safety monitoring board found that hydroxyurea was not inferior to regular blood transfusions in lowering TCD velocities. And the board said the strength of the statistical finding was unlikely to change with the collection of additional data.

After reviewing the board’s recommendation, the NHLBI decided to end the study early, as the primary endpoint had been met.

Study participants have been notified about the trial’s ending, and they will have the opportunity to receive the care they feel is best suited for them.

“No child should ever suffer a stroke, which is why it was so important for the NHLBI to support the TWiTCH trial,” said Gary Gibbons, MD, director of the NHLBI. “This critical research finding opens the door to more treatment options for clinicians trying to prevent strokes in children living with the sickle cell disease.”

Doctor examines SCD patient

Credit: St Jude Children’s

Research Hospital

Treatment with hydroxyurea is a comparable alternative to blood transfusions for reducing the risk of stroke in children with sickle cell disease (SCD), according to the National Heart Lung and Blood Institute (NHLBI).

Early results of the phase 3 TWiTCH trial showed that daily doses of hydroxyurea lower the transcranial Doppler (TCD) blood velocity in children with SCD to a similar degree as blood transfusions, thereby decreasing the risk of stroke.

Based on these findings, the NHLBI has terminated the trial early, about a year before it was originally scheduled to end.

“Early results indicate that TWiTCH is a success,” said Russell E. Ware, MD, PhD, principal investigator of the study and director of hematology at Cincinnati Children’s Hospital Medical Center.

“A group of outside experts has been reviewing the TWiTCH data every few months to ensure the safety of children in the clinical trial and to monitor the data. This group met recently and, after careful consideration of the interim data results, recommended that the study be stopped since hydroxyurea worked as well as transfusions to lower TCD velocities.”

The NHLBI said it cannot release results from the TWiTCH trial, but some details are available. Researchers enrolled 121 children between the ages of 4 and 16 who had SCD and abnormally elevated TCD velocities.

Half of patients received transfusions, and the other half received daily hydroxyurea, which has not yet been approved for children with SCD.

The clinical data-collection portion of the study was originally scheduled for the 24-month mark, but collection was stopped after only half of the children completed the treatment phase.

At the first interim analysis, a data and safety monitoring board found that hydroxyurea was not inferior to regular blood transfusions in lowering TCD velocities. And the board said the strength of the statistical finding was unlikely to change with the collection of additional data.

After reviewing the board’s recommendation, the NHLBI decided to end the study early, as the primary endpoint had been met.

Study participants have been notified about the trial’s ending, and they will have the opportunity to receive the care they feel is best suited for them.

“No child should ever suffer a stroke, which is why it was so important for the NHLBI to support the TWiTCH trial,” said Gary Gibbons, MD, director of the NHLBI. “This critical research finding opens the door to more treatment options for clinicians trying to prevent strokes in children living with the sickle cell disease.”

Doctor examines SCD patient

Credit: St Jude Children’s

Research Hospital

Treatment with hydroxyurea is a comparable alternative to blood transfusions for reducing the risk of stroke in children with sickle cell disease (SCD), according to the National Heart Lung and Blood Institute (NHLBI).

Early results of the phase 3 TWiTCH trial showed that daily doses of hydroxyurea lower the transcranial Doppler (TCD) blood velocity in children with SCD to a similar degree as blood transfusions, thereby decreasing the risk of stroke.

Based on these findings, the NHLBI has terminated the trial early, about a year before it was originally scheduled to end.

“Early results indicate that TWiTCH is a success,” said Russell E. Ware, MD, PhD, principal investigator of the study and director of hematology at Cincinnati Children’s Hospital Medical Center.

“A group of outside experts has been reviewing the TWiTCH data every few months to ensure the safety of children in the clinical trial and to monitor the data. This group met recently and, after careful consideration of the interim data results, recommended that the study be stopped since hydroxyurea worked as well as transfusions to lower TCD velocities.”

The NHLBI said it cannot release results from the TWiTCH trial, but some details are available. Researchers enrolled 121 children between the ages of 4 and 16 who had SCD and abnormally elevated TCD velocities.

Half of patients received transfusions, and the other half received daily hydroxyurea, which has not yet been approved for children with SCD.

The clinical data-collection portion of the study was originally scheduled for the 24-month mark, but collection was stopped after only half of the children completed the treatment phase.

At the first interim analysis, a data and safety monitoring board found that hydroxyurea was not inferior to regular blood transfusions in lowering TCD velocities. And the board said the strength of the statistical finding was unlikely to change with the collection of additional data.

After reviewing the board’s recommendation, the NHLBI decided to end the study early, as the primary endpoint had been met.

Study participants have been notified about the trial’s ending, and they will have the opportunity to receive the care they feel is best suited for them.

“No child should ever suffer a stroke, which is why it was so important for the NHLBI to support the TWiTCH trial,” said Gary Gibbons, MD, director of the NHLBI. “This critical research finding opens the door to more treatment options for clinicians trying to prevent strokes in children living with the sickle cell disease.”

Diffuse large B-cell lymphoma

BARCELONA—A small molecule inhibitor of EZH2 has shown “encouraging” activity in patients with advanced non-Hodgkin lymphoma (NHL), according to researchers.

In a phase 1 study, 4 of 10 heavily pretreated NHL patients responded to the drug, E7438 (also known as EPZ6438), with 1 patient achieving a complete response.

And E7438’s activity was not dependent upon the presence of an EZH2 mutation, as all 4 patients had wild-type EZH2.

The drug also demonstrated activity in a patient with a malignant rhabdoid tumor in the brain.

“In this study, responses were seen in patients with lymphoma who were refractory to, or relapsed after, prior standard treatments, as well as in a patient with a malignant disease for which there is no available standard medical treatment [rhabdoid tumor in the brain],” said study investigator Vincent Ribrag, MD, of Institut Gustave Roussy in Villejuif, France.

Dr Ribrag and his colleagues also found E7438 to be well-tolerated. There were no grade 3 adverse events and only 1 grade 4 event at the maximum dose level.

The researchers presented these data at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics as abstract LBA6. Investigators from Esai and Epizyme, the companies developing E7438, were involved in this trial.

The study included 24 patients who ranged in age from 24 to 84. Twelve patients had solid tumor malignancies, and 12 had NHL. Six patients had diffuse large B-cell lymphoma (DLBCL), 5 had follicular lymphoma (FL), and 1 had marginal zone lymphoma.

All of the patients were heavily pretreated. Fourteen had received between 2 and 4 prior therapies, and 9 had received more than 4 prior treatments.

E7438 was given in 5 dosing cohorts: 100 mg BID (n=6), 200 mg BID (n=3), 400 mg BID (n=3), 800 mg BID (n=6), and 1600 mg BID (n=6).

‘Encouraging activity’

Twenty patients were evaluable for efficacy as of October 20. Among the 10 patients with solid tumor malignancies, 1 responded. The patient with an INI1-deficient malignant rhabdoid tumor achieved a partial response and remains on study.

Four of the 10 evaluable NHL patients achieved a partial response or better, including 1 complete response. Responses were seen across a range of doses, up to the 800 mg BID dose.

Among the 5 evaluable DLBCL patients, 3 achieved a partial response or better. One patient with a partial response subsequently evolved to a complete response upon continued treatment and remains on study at 41 weeks of treatment. One of the 2 patients who achieved a partial response remains on study.

Among the 4 evaluable patients with FL, 1 achieved a partial response and remains on study. Three FL patients achieved stable disease, and 2 of these patients remain on study.

The patient with marginal zone lymphoma achieved stable disease and remains on study.

Confirmatory sequencing in a central lab showed that all 10 NHL patients who were evaluable for efficacy had wild-type EZH2, and responses were observed in both germinal center and non-germinal center lymphoma.

“These results provide encouraging evidence of antitumor activity with [E7438] . . . , including the potential for responses to improve with continued treatment,” said Peter Ho, MD, PhD, chief development officer at Epizyme.

“Given the clinical activity we saw in both wild-type EZH2 and non-germinal center lymphoma patients, our plan for the first phase 2 NHL study is to evaluate EPZ-6438 in DLBCL and FL patients with and without EZH2 mutations.”

‘Little toxicity’

All 24 patients were evaluable for safety and tolerability. The majority of adverse events were grade 1 or 2. Events occurring in more than 10% of patients included asthenia, decreased appetite, and nausea.

The only grade 3/4 treatment-related adverse event was grade 4 thrombocytopenia in 1 patient who received the drug at 1600 mg, which met the criteria for a dose-limiting toxicity.

There were no adverse events that required treatment withdrawal or dose reduction. However, 3 events resulted in dose interruption.

“The maximum tolerated dose was not reached because there was little toxicity observed,” Dr Ribrag said. “Since we saw that the drug was active at doses lower than the maximum dose of 1600 mg twice a day, the dose used for the phase 2 trials planned for 2015 may be lower.”

E7438 was rapidly absorbed and eliminated, with a terminal half-life of 3 to 6 hours. In addition, H3K27Me3 inhibition in the skin, a marker of biologic activity, correlated to treatment exposure, with near maximal inhibition predicted by pharmacokinetic exposure at 800 mg.

Currently, a phase 2 dose of 800 mg BID is under consideration. A final recommendation for the phase 2 dose will be approved by a data monitoring committee based on efficacy, safety, and pharmacokinetic/pharmacodynamic parameters.

Diffuse large B-cell lymphoma

BARCELONA—A small molecule inhibitor of EZH2 has shown “encouraging” activity in patients with advanced non-Hodgkin lymphoma (NHL), according to researchers.

In a phase 1 study, 4 of 10 heavily pretreated NHL patients responded to the drug, E7438 (also known as EPZ6438), with 1 patient achieving a complete response.

And E7438’s activity was not dependent upon the presence of an EZH2 mutation, as all 4 patients had wild-type EZH2.

The drug also demonstrated activity in a patient with a malignant rhabdoid tumor in the brain.

“In this study, responses were seen in patients with lymphoma who were refractory to, or relapsed after, prior standard treatments, as well as in a patient with a malignant disease for which there is no available standard medical treatment [rhabdoid tumor in the brain],” said study investigator Vincent Ribrag, MD, of Institut Gustave Roussy in Villejuif, France.

Dr Ribrag and his colleagues also found E7438 to be well-tolerated. There were no grade 3 adverse events and only 1 grade 4 event at the maximum dose level.

The researchers presented these data at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics as abstract LBA6. Investigators from Esai and Epizyme, the companies developing E7438, were involved in this trial.

The study included 24 patients who ranged in age from 24 to 84. Twelve patients had solid tumor malignancies, and 12 had NHL. Six patients had diffuse large B-cell lymphoma (DLBCL), 5 had follicular lymphoma (FL), and 1 had marginal zone lymphoma.

All of the patients were heavily pretreated. Fourteen had received between 2 and 4 prior therapies, and 9 had received more than 4 prior treatments.

E7438 was given in 5 dosing cohorts: 100 mg BID (n=6), 200 mg BID (n=3), 400 mg BID (n=3), 800 mg BID (n=6), and 1600 mg BID (n=6).

‘Encouraging activity’

Twenty patients were evaluable for efficacy as of October 20. Among the 10 patients with solid tumor malignancies, 1 responded. The patient with an INI1-deficient malignant rhabdoid tumor achieved a partial response and remains on study.

Four of the 10 evaluable NHL patients achieved a partial response or better, including 1 complete response. Responses were seen across a range of doses, up to the 800 mg BID dose.

Among the 5 evaluable DLBCL patients, 3 achieved a partial response or better. One patient with a partial response subsequently evolved to a complete response upon continued treatment and remains on study at 41 weeks of treatment. One of the 2 patients who achieved a partial response remains on study.

Among the 4 evaluable patients with FL, 1 achieved a partial response and remains on study. Three FL patients achieved stable disease, and 2 of these patients remain on study.

The patient with marginal zone lymphoma achieved stable disease and remains on study.

Confirmatory sequencing in a central lab showed that all 10 NHL patients who were evaluable for efficacy had wild-type EZH2, and responses were observed in both germinal center and non-germinal center lymphoma.

“These results provide encouraging evidence of antitumor activity with [E7438] . . . , including the potential for responses to improve with continued treatment,” said Peter Ho, MD, PhD, chief development officer at Epizyme.

“Given the clinical activity we saw in both wild-type EZH2 and non-germinal center lymphoma patients, our plan for the first phase 2 NHL study is to evaluate EPZ-6438 in DLBCL and FL patients with and without EZH2 mutations.”

‘Little toxicity’

All 24 patients were evaluable for safety and tolerability. The majority of adverse events were grade 1 or 2. Events occurring in more than 10% of patients included asthenia, decreased appetite, and nausea.

The only grade 3/4 treatment-related adverse event was grade 4 thrombocytopenia in 1 patient who received the drug at 1600 mg, which met the criteria for a dose-limiting toxicity.

There were no adverse events that required treatment withdrawal or dose reduction. However, 3 events resulted in dose interruption.

“The maximum tolerated dose was not reached because there was little toxicity observed,” Dr Ribrag said. “Since we saw that the drug was active at doses lower than the maximum dose of 1600 mg twice a day, the dose used for the phase 2 trials planned for 2015 may be lower.”

E7438 was rapidly absorbed and eliminated, with a terminal half-life of 3 to 6 hours. In addition, H3K27Me3 inhibition in the skin, a marker of biologic activity, correlated to treatment exposure, with near maximal inhibition predicted by pharmacokinetic exposure at 800 mg.

Currently, a phase 2 dose of 800 mg BID is under consideration. A final recommendation for the phase 2 dose will be approved by a data monitoring committee based on efficacy, safety, and pharmacokinetic/pharmacodynamic parameters.

Diffuse large B-cell lymphoma

BARCELONA—A small molecule inhibitor of EZH2 has shown “encouraging” activity in patients with advanced non-Hodgkin lymphoma (NHL), according to researchers.

In a phase 1 study, 4 of 10 heavily pretreated NHL patients responded to the drug, E7438 (also known as EPZ6438), with 1 patient achieving a complete response.

And E7438’s activity was not dependent upon the presence of an EZH2 mutation, as all 4 patients had wild-type EZH2.

The drug also demonstrated activity in a patient with a malignant rhabdoid tumor in the brain.

“In this study, responses were seen in patients with lymphoma who were refractory to, or relapsed after, prior standard treatments, as well as in a patient with a malignant disease for which there is no available standard medical treatment [rhabdoid tumor in the brain],” said study investigator Vincent Ribrag, MD, of Institut Gustave Roussy in Villejuif, France.

Dr Ribrag and his colleagues also found E7438 to be well-tolerated. There were no grade 3 adverse events and only 1 grade 4 event at the maximum dose level.

The researchers presented these data at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics as abstract LBA6. Investigators from Esai and Epizyme, the companies developing E7438, were involved in this trial.

The study included 24 patients who ranged in age from 24 to 84. Twelve patients had solid tumor malignancies, and 12 had NHL. Six patients had diffuse large B-cell lymphoma (DLBCL), 5 had follicular lymphoma (FL), and 1 had marginal zone lymphoma.

All of the patients were heavily pretreated. Fourteen had received between 2 and 4 prior therapies, and 9 had received more than 4 prior treatments.

E7438 was given in 5 dosing cohorts: 100 mg BID (n=6), 200 mg BID (n=3), 400 mg BID (n=3), 800 mg BID (n=6), and 1600 mg BID (n=6).

‘Encouraging activity’

Twenty patients were evaluable for efficacy as of October 20. Among the 10 patients with solid tumor malignancies, 1 responded. The patient with an INI1-deficient malignant rhabdoid tumor achieved a partial response and remains on study.

Four of the 10 evaluable NHL patients achieved a partial response or better, including 1 complete response. Responses were seen across a range of doses, up to the 800 mg BID dose.

Among the 5 evaluable DLBCL patients, 3 achieved a partial response or better. One patient with a partial response subsequently evolved to a complete response upon continued treatment and remains on study at 41 weeks of treatment. One of the 2 patients who achieved a partial response remains on study.

Among the 4 evaluable patients with FL, 1 achieved a partial response and remains on study. Three FL patients achieved stable disease, and 2 of these patients remain on study.

The patient with marginal zone lymphoma achieved stable disease and remains on study.

Confirmatory sequencing in a central lab showed that all 10 NHL patients who were evaluable for efficacy had wild-type EZH2, and responses were observed in both germinal center and non-germinal center lymphoma.

“These results provide encouraging evidence of antitumor activity with [E7438] . . . , including the potential for responses to improve with continued treatment,” said Peter Ho, MD, PhD, chief development officer at Epizyme.

“Given the clinical activity we saw in both wild-type EZH2 and non-germinal center lymphoma patients, our plan for the first phase 2 NHL study is to evaluate EPZ-6438 in DLBCL and FL patients with and without EZH2 mutations.”

‘Little toxicity’

All 24 patients were evaluable for safety and tolerability. The majority of adverse events were grade 1 or 2. Events occurring in more than 10% of patients included asthenia, decreased appetite, and nausea.

The only grade 3/4 treatment-related adverse event was grade 4 thrombocytopenia in 1 patient who received the drug at 1600 mg, which met the criteria for a dose-limiting toxicity.

There were no adverse events that required treatment withdrawal or dose reduction. However, 3 events resulted in dose interruption.

“The maximum tolerated dose was not reached because there was little toxicity observed,” Dr Ribrag said. “Since we saw that the drug was active at doses lower than the maximum dose of 1600 mg twice a day, the dose used for the phase 2 trials planned for 2015 may be lower.”

E7438 was rapidly absorbed and eliminated, with a terminal half-life of 3 to 6 hours. In addition, H3K27Me3 inhibition in the skin, a marker of biologic activity, correlated to treatment exposure, with near maximal inhibition predicted by pharmacokinetic exposure at 800 mg.

Currently, a phase 2 dose of 800 mg BID is under consideration. A final recommendation for the phase 2 dose will be approved by a data monitoring committee based on efficacy, safety, and pharmacokinetic/pharmacodynamic parameters.

AML cells

Credit: Lance Liotta

The US Food and Drug Administration (FDA) has granted orphan drug designation for the Axl inhibitor BGB324 to treat acute myeloid leukemia (AML).

BGB324 is a highly selective small molecule inhibitor of the Axl receptor tyrosine kinase. It blocks the epithelial-mesenchymal transition, a key driver in drug resistance and metastasis.

BerGenBio, the company developing BGB324, has estimated that more than 50% of AML patients have elevated levels of Axl.

And a study published in Blood last year showed that Axl inhibition by BGB324 prompts antileukemic activity in FLT3-mutated and FLT3-wild-type AML.

Earlier this month, BerGenBio said the first patient had been dosed in its multicenter phase 1b trial of BGB324 in patients with AML.

The primary goal of this 2-part trial is to investigate the safety and tolerability of BGB324 as a single agent and in combination with cytarabine. Secondary endpoints include clinical response and assessment of novel biomarkers.

The study will be conducted at 6 sites in Norway, Germany, and the US. BerGenBio expects data from this trial to be available in 2015.

The FDA’s orphan designation will provide BerGenBio with access to various development incentives for BGB324.

This includes tax credits for qualified clinical testing, exemption from prescription drug user fees for BGB324 in AML, and 7 years of market exclusivity in the US upon FDA approval.

AML cells

Credit: Lance Liotta

The US Food and Drug Administration (FDA) has granted orphan drug designation for the Axl inhibitor BGB324 to treat acute myeloid leukemia (AML).

BGB324 is a highly selective small molecule inhibitor of the Axl receptor tyrosine kinase. It blocks the epithelial-mesenchymal transition, a key driver in drug resistance and metastasis.

BerGenBio, the company developing BGB324, has estimated that more than 50% of AML patients have elevated levels of Axl.

And a study published in Blood last year showed that Axl inhibition by BGB324 prompts antileukemic activity in FLT3-mutated and FLT3-wild-type AML.

Earlier this month, BerGenBio said the first patient had been dosed in its multicenter phase 1b trial of BGB324 in patients with AML.

The primary goal of this 2-part trial is to investigate the safety and tolerability of BGB324 as a single agent and in combination with cytarabine. Secondary endpoints include clinical response and assessment of novel biomarkers.

The study will be conducted at 6 sites in Norway, Germany, and the US. BerGenBio expects data from this trial to be available in 2015.

The FDA’s orphan designation will provide BerGenBio with access to various development incentives for BGB324.

This includes tax credits for qualified clinical testing, exemption from prescription drug user fees for BGB324 in AML, and 7 years of market exclusivity in the US upon FDA approval.

AML cells

Credit: Lance Liotta

The US Food and Drug Administration (FDA) has granted orphan drug designation for the Axl inhibitor BGB324 to treat acute myeloid leukemia (AML).

BGB324 is a highly selective small molecule inhibitor of the Axl receptor tyrosine kinase. It blocks the epithelial-mesenchymal transition, a key driver in drug resistance and metastasis.

BerGenBio, the company developing BGB324, has estimated that more than 50% of AML patients have elevated levels of Axl.

And a study published in Blood last year showed that Axl inhibition by BGB324 prompts antileukemic activity in FLT3-mutated and FLT3-wild-type AML.

Earlier this month, BerGenBio said the first patient had been dosed in its multicenter phase 1b trial of BGB324 in patients with AML.

The primary goal of this 2-part trial is to investigate the safety and tolerability of BGB324 as a single agent and in combination with cytarabine. Secondary endpoints include clinical response and assessment of novel biomarkers.

The study will be conducted at 6 sites in Norway, Germany, and the US. BerGenBio expects data from this trial to be available in 2015.

The FDA’s orphan designation will provide BerGenBio with access to various development incentives for BGB324.

This includes tax credits for qualified clinical testing, exemption from prescription drug user fees for BGB324 in AML, and 7 years of market exclusivity in the US upon FDA approval.

The variations of family tensions at family gatherings are endless: reenactments of sibling rivalry; favoritism; disappointments; unmet needs; failed expectations; feelings of rejection, abandonment, underappreciation. These tensions often are accompanied by a desire to right old wrongs and protect the vulnerable. Then there are the toxic or personality-disordered family members patients do not want to spend time with, the grieving for family members who have died or have been cut off from the family, managing the impact of divorce or job loss, handling the family member who has an untreated illness such as alcoholism. The list goes on and on.

Successfully navigating these rapids leads to positive self-regard and a sense of accomplishment. For patients with an illness, either medical and/or psychiatric, successful management might be crucial to their health. Those with diabetes need to be able to control their intake of sugars and calories or to say “no” to the pushy aunt when pressed to take more. For patients with epilepsy, increased ER visits were predicted by several factors, including holidays (Eur. J. Neurol. 2013;20:1411-6). There are more deaths from natural causes on Christmas and New Year’s than on any other day of the year (Soc. Sci. and Medicine 2010;71;1463-71). In contrast, suicide rates are actually lower at Thanksgiving and Christmas (J. Emerg. Med. 2014;46:776-81) and (Eur. J. Public Health 2014;pii:cku169). Stressful life events are known to be triggers for mood disorders (J. Affect. Disord. 2012;143:196-202), and tense holiday gatherings qualify as stressful.

As psychiatrists, we shape our discussions with patients with the goal of helping them identify situations that worsen other illnesses and situations that act as triggers. We might offer additional doses of medications to “help them through.” We caution against overeating or using substances to manage stress. We direct patients to one of many websites that provide helpful tips for managing the holidays.

We also help co-parents negotiate an amicable division of time with the children, and assist in getting adults and children come to terms with the “less than perfect family.” We help stepparents come into their new role. We remind blended families that new families need new traditions.

We are trained to resist providing specific advice for patients. However, we can employ strategic and educational interventions. Our patients are dealing with family issues AND mental illness. Discussing strategies helps our patients manage the stress of family gatherings.

Strategy 1: Differentiating levels of knowledge

Help the patient to think about her family’s understanding of mental illness. The public at large, including family members, can be very uninformed about mental illness. For those family members who have some understanding, they may be unsure about the best way to handle a relative with mental illness. They may feel that they should just treat them “the same” or “be tough” or “baby” them, or make special accommodations. Any strategy or intervention depends upon the family member’s level of understanding.

Each family member can be at different stages of acceptance of the illness. These different stages can sharpen division or create divisions in the family. This fracturing of the family will most likely occur along lines that show prior strain. Once this is known, the psychiatrist and the patient can have a more nuanced discussion about the best way to manage specific family members. The strategies can range from ignoring Uncle Bert when he makes ignorant comments, to helping Aunt Sadie who really wants to understand and be helpful.

It helps to remind patients that mental illness is common. According to the National Institute of Mental Health, one in four people will have an episode of mental illness in their lifetime. Also making statements like “My illness is as a common as diabetes” or “my treatment is quite specific” shows a mastery of the situation, rather than shame. If patients can use stock phrases with which they feel comfortable, the family will be more easily settled down.

Handouts on the patient’s specific mental illness that describe facts, such as prevalence and signs and symptoms, are useful. Family members can be very receptive to hospital or clinic educational information. These steps normalize the medical treatment and reduce the fear of the unknown illness. There is no need to make a big production around giving them these. Just have them on hand, in case someone asks. Inviting relatives to meet for an educational session with the psychiatrist can open up the dark and hidden aspects of mental illness, so having your business card on hand is a supportive gesture. Holiday gatherings are neither the time to clear up misunderstandings nor to work on resolving conflicts.

Strategy 2: Managing stigma

Some family members might react negatively because of the stigma of mental illness. A way to help the patient manage a relative who wants to discuss topics that are difficult is through role play. The psychiatrist plays the patient. The patient acts out the responses of the relative. The psychiatrist models good coping styles, using helpful stock phrases that the patient can then practice.

Relatives may say they do not “believe” in mental illness. As if illness could be a matter of belief! Do some relatives think that God and prayer, or hypnosis, or acupuncture and herbal medications are the cure? Help the patient be prepared through role play.

Strategy 3: Managing specific illnesses and symptoms

Patients with depression, bipolar disorder, or anxiety who experience family events as stressful can say to family members: “My doctor told me it is important to reduce my stress/maintain a low stress level. I will therefore take walks/naps or just be able to stay for a short time.” For patients and families that need more specific help to understand, the psychiatrist can provide the patient with a written list of instructions that the patient can present, like a prescription.

Strategy 4: Abusive or angry families

For families in which there is an abusive relative or past history of trauma, special considerations include making a decision about whether or not the patient should actually go. If they do decide to go, a short-time, limited visit works best. The psychiatrist can help the patient identify triggers to pay attention to, so that they can leave when needed.

Strategy 5: Advice about family members who seem to have their own illness

If a patient gives you information that leads you to believe that a family member has an untreated psychiatric illness or a personality disorder, offering some general advice is helpful. Recommend the avoidance of family drama. If other family members get into a scrap, it is not worth getting involved unless someone is in danger.

General comments are helpful: “While I cannot tell you what the issue is with your uncle, from what you are saying, it seems that he has a lifelong pattern of making a scene or provoking others or overreacting to benign comments. If I were in that situation, I would try not to take it personally, disengage, perhaps go to the bathroom, clear the dishes, or go outside for a breath of fresh air. Holidays are not the time to “try to sort things out” or “clear things up.” If there is a need to do this, a separate occasion or a visit to the psychiatrist can be suggested. A polite “ I am feeling tired, exhausted’ is an easy excuse to offer.

Strategy 6: When you don’t know the family dynamic

Often, there are issues that go back several generations, in which family members take sides. A daughter may look or behave like her father who perpetrated violence. This daughter can be unfairly treated. These types of situations can be difficult to ferret out. It is best to say something like: “This seems complicated and too difficult to sort out. Sorry, I cannot do better.”

One technique that can be helpful for the patient is the preparation of a family genogram. The timing of the genogram is important. It is worth considering whether this should be delayed to a time where the patient can be thoughtful and not prior to going to a family gathering that is anticipated to be stressful.

A genogram can help the patient see patterns that extend back through generations. It also can highlight people in the family system who are sympathetic or likely to know about mental illness. If 1 in 4 people have a serious mental illness in their lifetime, the genogram can shed light on these relatives. A genogram also can identify family strengths, thus changing the focus for the patient, from anticipation of conflict to anticipation of renewing and strengthening relationships.

Lastly, providing aphorisms is disarming. Aphorisms bring humor and wisdom to difficult situations. “Our family has its difficulties, but we also have our strengths.” “We have some issues right now, but thinking back through the generations, we have a lot to be thankful for,” or “Mental illness treatment will soon cure all ills.”

In summary, even if patients do not use this advice, the mere fact of thoughtful exploration and practice can help them feel more in control at stressful family gatherings.

Remember, if your patient decides not to attend a family gathering, provide strategies to manage spending the holidays alone. Avoiding these events can lead to feelings of isolation, abandonment, and loss. A plan to work or volunteer, or spend time with friends mitigates the emotional pain of the “not good enough” family.

Dr. Heru is with the department of psychiatry at the University of Colorado at Denver, Aurora. She is editor of the recently published book, “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013).

The variations of family tensions at family gatherings are endless: reenactments of sibling rivalry; favoritism; disappointments; unmet needs; failed expectations; feelings of rejection, abandonment, underappreciation. These tensions often are accompanied by a desire to right old wrongs and protect the vulnerable. Then there are the toxic or personality-disordered family members patients do not want to spend time with, the grieving for family members who have died or have been cut off from the family, managing the impact of divorce or job loss, handling the family member who has an untreated illness such as alcoholism. The list goes on and on.

Successfully navigating these rapids leads to positive self-regard and a sense of accomplishment. For patients with an illness, either medical and/or psychiatric, successful management might be crucial to their health. Those with diabetes need to be able to control their intake of sugars and calories or to say “no” to the pushy aunt when pressed to take more. For patients with epilepsy, increased ER visits were predicted by several factors, including holidays (Eur. J. Neurol. 2013;20:1411-6). There are more deaths from natural causes on Christmas and New Year’s than on any other day of the year (Soc. Sci. and Medicine 2010;71;1463-71). In contrast, suicide rates are actually lower at Thanksgiving and Christmas (J. Emerg. Med. 2014;46:776-81) and (Eur. J. Public Health 2014;pii:cku169). Stressful life events are known to be triggers for mood disorders (J. Affect. Disord. 2012;143:196-202), and tense holiday gatherings qualify as stressful.

As psychiatrists, we shape our discussions with patients with the goal of helping them identify situations that worsen other illnesses and situations that act as triggers. We might offer additional doses of medications to “help them through.” We caution against overeating or using substances to manage stress. We direct patients to one of many websites that provide helpful tips for managing the holidays.

We also help co-parents negotiate an amicable division of time with the children, and assist in getting adults and children come to terms with the “less than perfect family.” We help stepparents come into their new role. We remind blended families that new families need new traditions.

We are trained to resist providing specific advice for patients. However, we can employ strategic and educational interventions. Our patients are dealing with family issues AND mental illness. Discussing strategies helps our patients manage the stress of family gatherings.

Strategy 1: Differentiating levels of knowledge

Help the patient to think about her family’s understanding of mental illness. The public at large, including family members, can be very uninformed about mental illness. For those family members who have some understanding, they may be unsure about the best way to handle a relative with mental illness. They may feel that they should just treat them “the same” or “be tough” or “baby” them, or make special accommodations. Any strategy or intervention depends upon the family member’s level of understanding.

Each family member can be at different stages of acceptance of the illness. These different stages can sharpen division or create divisions in the family. This fracturing of the family will most likely occur along lines that show prior strain. Once this is known, the psychiatrist and the patient can have a more nuanced discussion about the best way to manage specific family members. The strategies can range from ignoring Uncle Bert when he makes ignorant comments, to helping Aunt Sadie who really wants to understand and be helpful.

It helps to remind patients that mental illness is common. According to the National Institute of Mental Health, one in four people will have an episode of mental illness in their lifetime. Also making statements like “My illness is as a common as diabetes” or “my treatment is quite specific” shows a mastery of the situation, rather than shame. If patients can use stock phrases with which they feel comfortable, the family will be more easily settled down.

Handouts on the patient’s specific mental illness that describe facts, such as prevalence and signs and symptoms, are useful. Family members can be very receptive to hospital or clinic educational information. These steps normalize the medical treatment and reduce the fear of the unknown illness. There is no need to make a big production around giving them these. Just have them on hand, in case someone asks. Inviting relatives to meet for an educational session with the psychiatrist can open up the dark and hidden aspects of mental illness, so having your business card on hand is a supportive gesture. Holiday gatherings are neither the time to clear up misunderstandings nor to work on resolving conflicts.

Strategy 2: Managing stigma

Some family members might react negatively because of the stigma of mental illness. A way to help the patient manage a relative who wants to discuss topics that are difficult is through role play. The psychiatrist plays the patient. The patient acts out the responses of the relative. The psychiatrist models good coping styles, using helpful stock phrases that the patient can then practice.

Relatives may say they do not “believe” in mental illness. As if illness could be a matter of belief! Do some relatives think that God and prayer, or hypnosis, or acupuncture and herbal medications are the cure? Help the patient be prepared through role play.

Strategy 3: Managing specific illnesses and symptoms

Patients with depression, bipolar disorder, or anxiety who experience family events as stressful can say to family members: “My doctor told me it is important to reduce my stress/maintain a low stress level. I will therefore take walks/naps or just be able to stay for a short time.” For patients and families that need more specific help to understand, the psychiatrist can provide the patient with a written list of instructions that the patient can present, like a prescription.

Strategy 4: Abusive or angry families

For families in which there is an abusive relative or past history of trauma, special considerations include making a decision about whether or not the patient should actually go. If they do decide to go, a short-time, limited visit works best. The psychiatrist can help the patient identify triggers to pay attention to, so that they can leave when needed.

Strategy 5: Advice about family members who seem to have their own illness

If a patient gives you information that leads you to believe that a family member has an untreated psychiatric illness or a personality disorder, offering some general advice is helpful. Recommend the avoidance of family drama. If other family members get into a scrap, it is not worth getting involved unless someone is in danger.

General comments are helpful: “While I cannot tell you what the issue is with your uncle, from what you are saying, it seems that he has a lifelong pattern of making a scene or provoking others or overreacting to benign comments. If I were in that situation, I would try not to take it personally, disengage, perhaps go to the bathroom, clear the dishes, or go outside for a breath of fresh air. Holidays are not the time to “try to sort things out” or “clear things up.” If there is a need to do this, a separate occasion or a visit to the psychiatrist can be suggested. A polite “ I am feeling tired, exhausted’ is an easy excuse to offer.

Strategy 6: When you don’t know the family dynamic

Often, there are issues that go back several generations, in which family members take sides. A daughter may look or behave like her father who perpetrated violence. This daughter can be unfairly treated. These types of situations can be difficult to ferret out. It is best to say something like: “This seems complicated and too difficult to sort out. Sorry, I cannot do better.”

One technique that can be helpful for the patient is the preparation of a family genogram. The timing of the genogram is important. It is worth considering whether this should be delayed to a time where the patient can be thoughtful and not prior to going to a family gathering that is anticipated to be stressful.

A genogram can help the patient see patterns that extend back through generations. It also can highlight people in the family system who are sympathetic or likely to know about mental illness. If 1 in 4 people have a serious mental illness in their lifetime, the genogram can shed light on these relatives. A genogram also can identify family strengths, thus changing the focus for the patient, from anticipation of conflict to anticipation of renewing and strengthening relationships.

Lastly, providing aphorisms is disarming. Aphorisms bring humor and wisdom to difficult situations. “Our family has its difficulties, but we also have our strengths.” “We have some issues right now, but thinking back through the generations, we have a lot to be thankful for,” or “Mental illness treatment will soon cure all ills.”

In summary, even if patients do not use this advice, the mere fact of thoughtful exploration and practice can help them feel more in control at stressful family gatherings.

Remember, if your patient decides not to attend a family gathering, provide strategies to manage spending the holidays alone. Avoiding these events can lead to feelings of isolation, abandonment, and loss. A plan to work or volunteer, or spend time with friends mitigates the emotional pain of the “not good enough” family.

Dr. Heru is with the department of psychiatry at the University of Colorado at Denver, Aurora. She is editor of the recently published book, “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013).

The variations of family tensions at family gatherings are endless: reenactments of sibling rivalry; favoritism; disappointments; unmet needs; failed expectations; feelings of rejection, abandonment, underappreciation. These tensions often are accompanied by a desire to right old wrongs and protect the vulnerable. Then there are the toxic or personality-disordered family members patients do not want to spend time with, the grieving for family members who have died or have been cut off from the family, managing the impact of divorce or job loss, handling the family member who has an untreated illness such as alcoholism. The list goes on and on.

Successfully navigating these rapids leads to positive self-regard and a sense of accomplishment. For patients with an illness, either medical and/or psychiatric, successful management might be crucial to their health. Those with diabetes need to be able to control their intake of sugars and calories or to say “no” to the pushy aunt when pressed to take more. For patients with epilepsy, increased ER visits were predicted by several factors, including holidays (Eur. J. Neurol. 2013;20:1411-6). There are more deaths from natural causes on Christmas and New Year’s than on any other day of the year (Soc. Sci. and Medicine 2010;71;1463-71). In contrast, suicide rates are actually lower at Thanksgiving and Christmas (J. Emerg. Med. 2014;46:776-81) and (Eur. J. Public Health 2014;pii:cku169). Stressful life events are known to be triggers for mood disorders (J. Affect. Disord. 2012;143:196-202), and tense holiday gatherings qualify as stressful.

As psychiatrists, we shape our discussions with patients with the goal of helping them identify situations that worsen other illnesses and situations that act as triggers. We might offer additional doses of medications to “help them through.” We caution against overeating or using substances to manage stress. We direct patients to one of many websites that provide helpful tips for managing the holidays.

We also help co-parents negotiate an amicable division of time with the children, and assist in getting adults and children come to terms with the “less than perfect family.” We help stepparents come into their new role. We remind blended families that new families need new traditions.

We are trained to resist providing specific advice for patients. However, we can employ strategic and educational interventions. Our patients are dealing with family issues AND mental illness. Discussing strategies helps our patients manage the stress of family gatherings.

Strategy 1: Differentiating levels of knowledge

Help the patient to think about her family’s understanding of mental illness. The public at large, including family members, can be very uninformed about mental illness. For those family members who have some understanding, they may be unsure about the best way to handle a relative with mental illness. They may feel that they should just treat them “the same” or “be tough” or “baby” them, or make special accommodations. Any strategy or intervention depends upon the family member’s level of understanding.

Each family member can be at different stages of acceptance of the illness. These different stages can sharpen division or create divisions in the family. This fracturing of the family will most likely occur along lines that show prior strain. Once this is known, the psychiatrist and the patient can have a more nuanced discussion about the best way to manage specific family members. The strategies can range from ignoring Uncle Bert when he makes ignorant comments, to helping Aunt Sadie who really wants to understand and be helpful.

It helps to remind patients that mental illness is common. According to the National Institute of Mental Health, one in four people will have an episode of mental illness in their lifetime. Also making statements like “My illness is as a common as diabetes” or “my treatment is quite specific” shows a mastery of the situation, rather than shame. If patients can use stock phrases with which they feel comfortable, the family will be more easily settled down.

Handouts on the patient’s specific mental illness that describe facts, such as prevalence and signs and symptoms, are useful. Family members can be very receptive to hospital or clinic educational information. These steps normalize the medical treatment and reduce the fear of the unknown illness. There is no need to make a big production around giving them these. Just have them on hand, in case someone asks. Inviting relatives to meet for an educational session with the psychiatrist can open up the dark and hidden aspects of mental illness, so having your business card on hand is a supportive gesture. Holiday gatherings are neither the time to clear up misunderstandings nor to work on resolving conflicts.

Strategy 2: Managing stigma

Some family members might react negatively because of the stigma of mental illness. A way to help the patient manage a relative who wants to discuss topics that are difficult is through role play. The psychiatrist plays the patient. The patient acts out the responses of the relative. The psychiatrist models good coping styles, using helpful stock phrases that the patient can then practice.

Relatives may say they do not “believe” in mental illness. As if illness could be a matter of belief! Do some relatives think that God and prayer, or hypnosis, or acupuncture and herbal medications are the cure? Help the patient be prepared through role play.

Strategy 3: Managing specific illnesses and symptoms

Patients with depression, bipolar disorder, or anxiety who experience family events as stressful can say to family members: “My doctor told me it is important to reduce my stress/maintain a low stress level. I will therefore take walks/naps or just be able to stay for a short time.” For patients and families that need more specific help to understand, the psychiatrist can provide the patient with a written list of instructions that the patient can present, like a prescription.

Strategy 4: Abusive or angry families

For families in which there is an abusive relative or past history of trauma, special considerations include making a decision about whether or not the patient should actually go. If they do decide to go, a short-time, limited visit works best. The psychiatrist can help the patient identify triggers to pay attention to, so that they can leave when needed.

Strategy 5: Advice about family members who seem to have their own illness

If a patient gives you information that leads you to believe that a family member has an untreated psychiatric illness or a personality disorder, offering some general advice is helpful. Recommend the avoidance of family drama. If other family members get into a scrap, it is not worth getting involved unless someone is in danger.

General comments are helpful: “While I cannot tell you what the issue is with your uncle, from what you are saying, it seems that he has a lifelong pattern of making a scene or provoking others or overreacting to benign comments. If I were in that situation, I would try not to take it personally, disengage, perhaps go to the bathroom, clear the dishes, or go outside for a breath of fresh air. Holidays are not the time to “try to sort things out” or “clear things up.” If there is a need to do this, a separate occasion or a visit to the psychiatrist can be suggested. A polite “ I am feeling tired, exhausted’ is an easy excuse to offer.

Strategy 6: When you don’t know the family dynamic

Often, there are issues that go back several generations, in which family members take sides. A daughter may look or behave like her father who perpetrated violence. This daughter can be unfairly treated. These types of situations can be difficult to ferret out. It is best to say something like: “This seems complicated and too difficult to sort out. Sorry, I cannot do better.”

One technique that can be helpful for the patient is the preparation of a family genogram. The timing of the genogram is important. It is worth considering whether this should be delayed to a time where the patient can be thoughtful and not prior to going to a family gathering that is anticipated to be stressful.

A genogram can help the patient see patterns that extend back through generations. It also can highlight people in the family system who are sympathetic or likely to know about mental illness. If 1 in 4 people have a serious mental illness in their lifetime, the genogram can shed light on these relatives. A genogram also can identify family strengths, thus changing the focus for the patient, from anticipation of conflict to anticipation of renewing and strengthening relationships.

Lastly, providing aphorisms is disarming. Aphorisms bring humor and wisdom to difficult situations. “Our family has its difficulties, but we also have our strengths.” “We have some issues right now, but thinking back through the generations, we have a lot to be thankful for,” or “Mental illness treatment will soon cure all ills.”

In summary, even if patients do not use this advice, the mere fact of thoughtful exploration and practice can help them feel more in control at stressful family gatherings.

Remember, if your patient decides not to attend a family gathering, provide strategies to manage spending the holidays alone. Avoiding these events can lead to feelings of isolation, abandonment, and loss. A plan to work or volunteer, or spend time with friends mitigates the emotional pain of the “not good enough” family.

Dr. Heru is with the department of psychiatry at the University of Colorado at Denver, Aurora. She is editor of the recently published book, “Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals” (New York: Routledge, 2013).

CORONADO, CALIF. – The use of radioactive iodine in patients with papillary thyroid cancer showed a small but statistically significant survival benefit for all tumor size categories, a long-term analysis of national data suggested.

“The incidence of papillary thyroid carcinoma is rapidly rising, but the survival advantage of radioactive iodine ablation has not been confirmed,” Dr. Paritosh Suman said at the annual meeting of the American Thyroid Association.

©Sebastian Kaulitzki/Fotolia.com

To investigate the effect of radioactive iodine (RAI) on papillary thyroid cancer mortality, Dr. Suman and his associates identified 108,565 patients from the National Cancer Data Base who were diagnosed with papillary thyroid cancer and underwent total or near total thyroidectomy between 1998 and 2006.

The investigators classified tumors into one of four groups by diameter size: 10 mm or less, 11-20 mm, 21-40 mm, and greater than 40 mm. The study researchers used Cox regression analysis to quantify the effect of radioactive iodine, adjusting for clinicopathologic, demographic, and socioeconomic variables. A total of 52% of the patients were older than 45 years, 77% were female, and 54% received RAI.

Factors predicting the use of RAI were being male, having positive margins, having cervical lymph node involvement, and having a tumor size greater than 4 cm in diameter, said Dr. Suman, an endocrinology surgery fellow at North Shore University Health System in Evanston, Ill. The 10-year overall survival rate was 90% in those who received RAI, compared with 87.4% among those who did not, for a small but statistically significant survival advantage (P < .0001).

Among patients who received RAI, the 10-year survival advantage by diameter of tumor was 3.4% for those with tumors 10 mm or less; 2.8% with 11-20 mm; 3.3% with 21-40 mm, and 5.7% with greater than 40 mm.

Age also played a factor, with a 10-year survival advantage of 0.5% for those aged 18-35 years; 1.5% for those aged 36-45 years; 0.9% for those aged 46-55 years; 0.6% for those aged 56-65 years; and 2.1% for those older than 65 years. Both men and women who received RAI had a statistically significant survival advantage at 10 years (3.9% and 1.6%, respectively).

When the researchers assessed the 10-year survival advantage by lymph node category of patients who received RAI, the rates were 2.9% for N-0, 4.2% for N-1, 5.2% for N-1A, and 5.8% for N-1B. By margin status, the 10-year survival advantage was 3.1% for negative margins, 3.6% for positive margins, 3.5% for microscopic margins, and 8.8% for gross margins.

In an analysis of all patients with very low-risk, low-risk, and high-risk papillary thyroid carcinoma according to ATA guidelines for the use of RAI, the study authors found a 10-year survival advantage of RAI in each of the three categories.

Among patients with very low-risk papillary thyroid carcinoma, the rate of 10-year survival was 92.2% among those who received RAI, compared with 89% among those who did not (hazard ratio, 0.74). Similar associations were observed in those with low-risk carcinoma (91.8% vs. 89%; HR, 0.80) and in those with high-risk carcinoma (86.2% vs. 79.2%; HR, 0.71).

“RAI is associated with a statistically significant but small overall survival advantage for most patients,” Dr. Suman said. “High-risk patients, defined by large tumor size, lymph node involvement, and gross margins, achieve the greatest benefit with RAI ablation.”

Dr. Suman reported having no relevant financial disclosures.

[email protected]

On Twitter @dougbrunk

CORONADO, CALIF. – The use of radioactive iodine in patients with papillary thyroid cancer showed a small but statistically significant survival benefit for all tumor size categories, a long-term analysis of national data suggested.

“The incidence of papillary thyroid carcinoma is rapidly rising, but the survival advantage of radioactive iodine ablation has not been confirmed,” Dr. Paritosh Suman said at the annual meeting of the American Thyroid Association.

©Sebastian Kaulitzki/Fotolia.com

To investigate the effect of radioactive iodine (RAI) on papillary thyroid cancer mortality, Dr. Suman and his associates identified 108,565 patients from the National Cancer Data Base who were diagnosed with papillary thyroid cancer and underwent total or near total thyroidectomy between 1998 and 2006.

The investigators classified tumors into one of four groups by diameter size: 10 mm or less, 11-20 mm, 21-40 mm, and greater than 40 mm. The study researchers used Cox regression analysis to quantify the effect of radioactive iodine, adjusting for clinicopathologic, demographic, and socioeconomic variables. A total of 52% of the patients were older than 45 years, 77% were female, and 54% received RAI.

Factors predicting the use of RAI were being male, having positive margins, having cervical lymph node involvement, and having a tumor size greater than 4 cm in diameter, said Dr. Suman, an endocrinology surgery fellow at North Shore University Health System in Evanston, Ill. The 10-year overall survival rate was 90% in those who received RAI, compared with 87.4% among those who did not, for a small but statistically significant survival advantage (P < .0001).

Among patients who received RAI, the 10-year survival advantage by diameter of tumor was 3.4% for those with tumors 10 mm or less; 2.8% with 11-20 mm; 3.3% with 21-40 mm, and 5.7% with greater than 40 mm.

Age also played a factor, with a 10-year survival advantage of 0.5% for those aged 18-35 years; 1.5% for those aged 36-45 years; 0.9% for those aged 46-55 years; 0.6% for those aged 56-65 years; and 2.1% for those older than 65 years. Both men and women who received RAI had a statistically significant survival advantage at 10 years (3.9% and 1.6%, respectively).

When the researchers assessed the 10-year survival advantage by lymph node category of patients who received RAI, the rates were 2.9% for N-0, 4.2% for N-1, 5.2% for N-1A, and 5.8% for N-1B. By margin status, the 10-year survival advantage was 3.1% for negative margins, 3.6% for positive margins, 3.5% for microscopic margins, and 8.8% for gross margins.

In an analysis of all patients with very low-risk, low-risk, and high-risk papillary thyroid carcinoma according to ATA guidelines for the use of RAI, the study authors found a 10-year survival advantage of RAI in each of the three categories.

Among patients with very low-risk papillary thyroid carcinoma, the rate of 10-year survival was 92.2% among those who received RAI, compared with 89% among those who did not (hazard ratio, 0.74). Similar associations were observed in those with low-risk carcinoma (91.8% vs. 89%; HR, 0.80) and in those with high-risk carcinoma (86.2% vs. 79.2%; HR, 0.71).

“RAI is associated with a statistically significant but small overall survival advantage for most patients,” Dr. Suman said. “High-risk patients, defined by large tumor size, lymph node involvement, and gross margins, achieve the greatest benefit with RAI ablation.”

Dr. Suman reported having no relevant financial disclosures.

[email protected]

On Twitter @dougbrunk

CORONADO, CALIF. – The use of radioactive iodine in patients with papillary thyroid cancer showed a small but statistically significant survival benefit for all tumor size categories, a long-term analysis of national data suggested.

“The incidence of papillary thyroid carcinoma is rapidly rising, but the survival advantage of radioactive iodine ablation has not been confirmed,” Dr. Paritosh Suman said at the annual meeting of the American Thyroid Association.

©Sebastian Kaulitzki/Fotolia.com

To investigate the effect of radioactive iodine (RAI) on papillary thyroid cancer mortality, Dr. Suman and his associates identified 108,565 patients from the National Cancer Data Base who were diagnosed with papillary thyroid cancer and underwent total or near total thyroidectomy between 1998 and 2006.

The investigators classified tumors into one of four groups by diameter size: 10 mm or less, 11-20 mm, 21-40 mm, and greater than 40 mm. The study researchers used Cox regression analysis to quantify the effect of radioactive iodine, adjusting for clinicopathologic, demographic, and socioeconomic variables. A total of 52% of the patients were older than 45 years, 77% were female, and 54% received RAI.

Factors predicting the use of RAI were being male, having positive margins, having cervical lymph node involvement, and having a tumor size greater than 4 cm in diameter, said Dr. Suman, an endocrinology surgery fellow at North Shore University Health System in Evanston, Ill. The 10-year overall survival rate was 90% in those who received RAI, compared with 87.4% among those who did not, for a small but statistically significant survival advantage (P < .0001).

Among patients who received RAI, the 10-year survival advantage by diameter of tumor was 3.4% for those with tumors 10 mm or less; 2.8% with 11-20 mm; 3.3% with 21-40 mm, and 5.7% with greater than 40 mm.

Age also played a factor, with a 10-year survival advantage of 0.5% for those aged 18-35 years; 1.5% for those aged 36-45 years; 0.9% for those aged 46-55 years; 0.6% for those aged 56-65 years; and 2.1% for those older than 65 years. Both men and women who received RAI had a statistically significant survival advantage at 10 years (3.9% and 1.6%, respectively).

When the researchers assessed the 10-year survival advantage by lymph node category of patients who received RAI, the rates were 2.9% for N-0, 4.2% for N-1, 5.2% for N-1A, and 5.8% for N-1B. By margin status, the 10-year survival advantage was 3.1% for negative margins, 3.6% for positive margins, 3.5% for microscopic margins, and 8.8% for gross margins.

In an analysis of all patients with very low-risk, low-risk, and high-risk papillary thyroid carcinoma according to ATA guidelines for the use of RAI, the study authors found a 10-year survival advantage of RAI in each of the three categories.

Among patients with very low-risk papillary thyroid carcinoma, the rate of 10-year survival was 92.2% among those who received RAI, compared with 89% among those who did not (hazard ratio, 0.74). Similar associations were observed in those with low-risk carcinoma (91.8% vs. 89%; HR, 0.80) and in those with high-risk carcinoma (86.2% vs. 79.2%; HR, 0.71).

“RAI is associated with a statistically significant but small overall survival advantage for most patients,” Dr. Suman said. “High-risk patients, defined by large tumor size, lymph node involvement, and gross margins, achieve the greatest benefit with RAI ablation.”

Dr. Suman reported having no relevant financial disclosures.

[email protected]

On Twitter @dougbrunk

One serious problem with being an advocate of correctional mental health services is that you run the risk of coming across as an apologist, a Pollyanna, or a defender of the status quo. This is true even though every week I meet someone with an addiction problem so severe that he’d be unable to voluntarily seek or stay in treatment in the community. For someone like that, an arrest can be lifesaving. But to point this out will lead people to believe that I must oppose ready access to community care, pretrial diversion, alternative sentencing, mental health courts, or anything related to alternatives to incarceration.

That isn’t the case. Many problems require more than one solution. What I oppose is the idea that the solution has to be a simple dichotomous choice between arrest and incarceration versus community care. I’ve found discussions about criminalization of people with mental illnesses to be polarizing and unproductive. There will always be people with mental illnesses in jail and prison, because – like people with diabetes, heart disease, or AIDS – they sometimes commit very serious crimes. As a care provider, my view is that a patient’s need for treatment is independent of criminal culpability. An ill person deserves appropriate and skilled health care, regardless of the treatment setting. Moving someone from an understaffed, overcrowded correctional facility to an understaffed, overcrowded state hospital hardly solves the problem.

People make the argument that money spent on corrections would be better spent elsewhere, on services for at-risk youth, or on community substance abuse and mental health programs. I agree that all these programs are needed, but what rarely gets mentioned is that when money is diverted from jails and prisons, part of that money also includes funding for inmate health care. Taking away this money is like stealing a coat from a blind beggar in the winter time. If you want to make a serious problem worse, by all means, take away what little we have.

How much money are we talking here, anyway?

By some estimates, the money spent on health care for all American prisons is about $7.7 billion per year. That includes physician and related health care professional costs, laboratory and diagnostic testing, hospitalization costs, as well as medications. Fourteen percent of that, or about $1 billion, goes to mental health care. Those costs are expected to rise as the prison population continues to age. Meanwhile, federal spending on mandatory health care programs in 2013 was about $1 trillion. When the prison health care budget represents less than 1% of health care spending nationally, this doesn’t seem to be enough to be quibbling about and certainly not enough to be cutting or diverting elsewhere.

But of course, the correctional nihilists will respond, “You get what you pay for.” Inevitably, low-cost care becomes equivalent to low-quality care in the eyes of many Americans. But if you compare American medical outcomes globally, it’s been well established that we have fallen behind many countries in life expectancy and infant mortality, despite heavy investment in a broad spectrum of services and interventions.

Let’s compare that to prison. Because of data gathered through the 2000 Federal Death in Custody Reporting Act, as well as other studies, prisons have been able to demonstrate reduced mortality, compared with age-matched men in free society, particularly for minorities. That mortality rate doubles after release. Clearly, prisons appear to be keeping people alive more efficiently and at a fraction of the cost of our community services.

This is not to imply that incarceration should be the answer to every social problem. This is my response to the naysayers and nihilists who believe that jails and prisons are so far gone they are not worth investing in. The lives of many prisoners depend on that investment.

Dr. Hanson is a forensic psychiatrist and coauthor of Shrink Rap: Three Psychiatrists Explain Their Work. The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson’s employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

One serious problem with being an advocate of correctional mental health services is that you run the risk of coming across as an apologist, a Pollyanna, or a defender of the status quo. This is true even though every week I meet someone with an addiction problem so severe that he’d be unable to voluntarily seek or stay in treatment in the community. For someone like that, an arrest can be lifesaving. But to point this out will lead people to believe that I must oppose ready access to community care, pretrial diversion, alternative sentencing, mental health courts, or anything related to alternatives to incarceration.

That isn’t the case. Many problems require more than one solution. What I oppose is the idea that the solution has to be a simple dichotomous choice between arrest and incarceration versus community care. I’ve found discussions about criminalization of people with mental illnesses to be polarizing and unproductive. There will always be people with mental illnesses in jail and prison, because – like people with diabetes, heart disease, or AIDS – they sometimes commit very serious crimes. As a care provider, my view is that a patient’s need for treatment is independent of criminal culpability. An ill person deserves appropriate and skilled health care, regardless of the treatment setting. Moving someone from an understaffed, overcrowded correctional facility to an understaffed, overcrowded state hospital hardly solves the problem.

People make the argument that money spent on corrections would be better spent elsewhere, on services for at-risk youth, or on community substance abuse and mental health programs. I agree that all these programs are needed, but what rarely gets mentioned is that when money is diverted from jails and prisons, part of that money also includes funding for inmate health care. Taking away this money is like stealing a coat from a blind beggar in the winter time. If you want to make a serious problem worse, by all means, take away what little we have.

How much money are we talking here, anyway?

By some estimates, the money spent on health care for all American prisons is about $7.7 billion per year. That includes physician and related health care professional costs, laboratory and diagnostic testing, hospitalization costs, as well as medications. Fourteen percent of that, or about $1 billion, goes to mental health care. Those costs are expected to rise as the prison population continues to age. Meanwhile, federal spending on mandatory health care programs in 2013 was about $1 trillion. When the prison health care budget represents less than 1% of health care spending nationally, this doesn’t seem to be enough to be quibbling about and certainly not enough to be cutting or diverting elsewhere.

But of course, the correctional nihilists will respond, “You get what you pay for.” Inevitably, low-cost care becomes equivalent to low-quality care in the eyes of many Americans. But if you compare American medical outcomes globally, it’s been well established that we have fallen behind many countries in life expectancy and infant mortality, despite heavy investment in a broad spectrum of services and interventions.

Let’s compare that to prison. Because of data gathered through the 2000 Federal Death in Custody Reporting Act, as well as other studies, prisons have been able to demonstrate reduced mortality, compared with age-matched men in free society, particularly for minorities. That mortality rate doubles after release. Clearly, prisons appear to be keeping people alive more efficiently and at a fraction of the cost of our community services.

This is not to imply that incarceration should be the answer to every social problem. This is my response to the naysayers and nihilists who believe that jails and prisons are so far gone they are not worth investing in. The lives of many prisoners depend on that investment.

Dr. Hanson is a forensic psychiatrist and coauthor of Shrink Rap: Three Psychiatrists Explain Their Work. The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson’s employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

One serious problem with being an advocate of correctional mental health services is that you run the risk of coming across as an apologist, a Pollyanna, or a defender of the status quo. This is true even though every week I meet someone with an addiction problem so severe that he’d be unable to voluntarily seek or stay in treatment in the community. For someone like that, an arrest can be lifesaving. But to point this out will lead people to believe that I must oppose ready access to community care, pretrial diversion, alternative sentencing, mental health courts, or anything related to alternatives to incarceration.

That isn’t the case. Many problems require more than one solution. What I oppose is the idea that the solution has to be a simple dichotomous choice between arrest and incarceration versus community care. I’ve found discussions about criminalization of people with mental illnesses to be polarizing and unproductive. There will always be people with mental illnesses in jail and prison, because – like people with diabetes, heart disease, or AIDS – they sometimes commit very serious crimes. As a care provider, my view is that a patient’s need for treatment is independent of criminal culpability. An ill person deserves appropriate and skilled health care, regardless of the treatment setting. Moving someone from an understaffed, overcrowded correctional facility to an understaffed, overcrowded state hospital hardly solves the problem.

People make the argument that money spent on corrections would be better spent elsewhere, on services for at-risk youth, or on community substance abuse and mental health programs. I agree that all these programs are needed, but what rarely gets mentioned is that when money is diverted from jails and prisons, part of that money also includes funding for inmate health care. Taking away this money is like stealing a coat from a blind beggar in the winter time. If you want to make a serious problem worse, by all means, take away what little we have.

How much money are we talking here, anyway?

By some estimates, the money spent on health care for all American prisons is about $7.7 billion per year. That includes physician and related health care professional costs, laboratory and diagnostic testing, hospitalization costs, as well as medications. Fourteen percent of that, or about $1 billion, goes to mental health care. Those costs are expected to rise as the prison population continues to age. Meanwhile, federal spending on mandatory health care programs in 2013 was about $1 trillion. When the prison health care budget represents less than 1% of health care spending nationally, this doesn’t seem to be enough to be quibbling about and certainly not enough to be cutting or diverting elsewhere.

But of course, the correctional nihilists will respond, “You get what you pay for.” Inevitably, low-cost care becomes equivalent to low-quality care in the eyes of many Americans. But if you compare American medical outcomes globally, it’s been well established that we have fallen behind many countries in life expectancy and infant mortality, despite heavy investment in a broad spectrum of services and interventions.

Let’s compare that to prison. Because of data gathered through the 2000 Federal Death in Custody Reporting Act, as well as other studies, prisons have been able to demonstrate reduced mortality, compared with age-matched men in free society, particularly for minorities. That mortality rate doubles after release. Clearly, prisons appear to be keeping people alive more efficiently and at a fraction of the cost of our community services.

This is not to imply that incarceration should be the answer to every social problem. This is my response to the naysayers and nihilists who believe that jails and prisons are so far gone they are not worth investing in. The lives of many prisoners depend on that investment.

Dr. Hanson is a forensic psychiatrist and coauthor of Shrink Rap: Three Psychiatrists Explain Their Work. The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson’s employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

The influence of technology on the patient-physician relationship has been the subject of many discussions and publications. While a physician facing a computer screen throughout much of the office encounter is a vision no one believes is in the best interest of either the patient or the relationship, empathy as an admired professional trait and a successful tool in medicine is gaining support among the medical establishment. The question as to whether physicians can learn empathy has been examined. The benefits (real or potential) of digital technology in revitalizing this human interaction and technology’s potential to convey empathy must be considered. I will attempt to place some of these tools in a bit of a new light.

1. Encourage patients to utilize the patient portal.

Stage 2 of meaningful use requires that 5% of Medicare patients receive information via a patient portal; this has resulted in little less than an exercise in compliance. True interaction via the portal is not taking place. The catch-22 is that the portals provided by electronic health record (EHR) vendors are the least costly, but also the least useful. Providers are not enthusiastic about portals for good reason. Clinicians are fearful that office workflow cannot accommodate the potential volume of digital interactions. They also do not have the digital tools necessary to make the portal experience as beneficial as it can be.

Notwithstanding these barriers, I believe that a physician who encourages the use of the portal with conversations focused on patients’ participation in their own care will be seen as empathetic. Stressing the fact that the patient is being given a tool that delivers information (even if it is only a lab result) portrays the provider as a partner in care. The patient portal is the starting point of introducing patients to digital health technology. If it is the portal which is closest to the patient’s care touch point, other technologies will seem less intimidating and more relevant.

2. Prescribe apps and websites.

The days of a physician’s rolling eyes at a patient’s mention of information garnered on the Internet should be over. More than 90% of physicians use reference apps to treat patients. The power of digital technology to educate patients cannot be minimized. According to the Pew Research Internet Project (2013), one in three American adults have gone online to self-diagnose. Physicians agreed with that diagnosis 41% of the time. Is this reason to tout the Internet as a clinical diagnostician? I would hope not. However, it does demonstrate that the Digital Age of health care has arrived. It cannot be ignored. In the United Kingdom, the National Health Service will begin accrediting apps to be prescribed in 2015. If one thinks of patient education and self-monitoring instructions as important for patient care, then the natural extension of digitally delivering these tools should not send shock waves across the landscape. IMS Health offers technology for the prescribing of health apps and analytics for apps. Clearly, obstacles remain for app prescribing to enter mainstream medicine, the most significant being quality assurance regarding clinical effectiveness and data privacy and security. However, there are some excellent apps from which patients can benefit. In the nutritional arena, GoMeals and Fooducate are useful, as is Alivecor ECG for symptomatic heart rhythm monitoring. There are also several good smoking cessation apps. Further, there are text messaging programs which have proved not only popular but effective, specifically the smoking cessation offering SmokefreeTXT and the prenatal care program text4baby.

3. Participate in social media.

In 2010, the American Medical Association adopted guidelines for professionalism in social media. Among 22 other interesting statistics on health care in social media, are these two: More than 40% of consumers say that information found via social media affects the way they deal with their health, and 60% of social media users are the most likely to trust social media posts and activity by doctors over any other group.

4. Have your hospital start online patient support groups.

There are relative benefits to both in-person support groups and online patient support groups. My mother was a patient at a major cancer center, and I tweeted asking whether they had an online support group, as my mother enjoyed the in-person meetings, which she could no longer attend. The hospital account, having realized the importance of such outreach, responded with the establishment of an online group the following week. This type of patient service creates a sense of health care community, which is invaluable to both patient satisfaction and provider-patient relationships.

5. Utilize mobile technologies to facilitate patient engagement via self-monitoring.

The mere suggestion of recommending an app to have a patient log their blood pressure or follow their glucose is a signal of the importance of shared management and decision making. Apps that allow a person to track their activity or food consumption are simple yet meaningful. Patients are longing for tools they can use themselves or utilize as caregivers.

Empathy can be conveyed directly as emotional support or indirectly with actions described above. It is ironic that technology, cold and inhumane in a solitary context, can be transformed and seen as empathetic if it is offered in a humanistic way.

Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.

The influence of technology on the patient-physician relationship has been the subject of many discussions and publications. While a physician facing a computer screen throughout much of the office encounter is a vision no one believes is in the best interest of either the patient or the relationship, empathy as an admired professional trait and a successful tool in medicine is gaining support among the medical establishment. The question as to whether physicians can learn empathy has been examined. The benefits (real or potential) of digital technology in revitalizing this human interaction and technology’s potential to convey empathy must be considered. I will attempt to place some of these tools in a bit of a new light.

1. Encourage patients to utilize the patient portal.

Stage 2 of meaningful use requires that 5% of Medicare patients receive information via a patient portal; this has resulted in little less than an exercise in compliance. True interaction via the portal is not taking place. The catch-22 is that the portals provided by electronic health record (EHR) vendors are the least costly, but also the least useful. Providers are not enthusiastic about portals for good reason. Clinicians are fearful that office workflow cannot accommodate the potential volume of digital interactions. They also do not have the digital tools necessary to make the portal experience as beneficial as it can be.

Notwithstanding these barriers, I believe that a physician who encourages the use of the portal with conversations focused on patients’ participation in their own care will be seen as empathetic. Stressing the fact that the patient is being given a tool that delivers information (even if it is only a lab result) portrays the provider as a partner in care. The patient portal is the starting point of introducing patients to digital health technology. If it is the portal which is closest to the patient’s care touch point, other technologies will seem less intimidating and more relevant.

2. Prescribe apps and websites.

The days of a physician’s rolling eyes at a patient’s mention of information garnered on the Internet should be over. More than 90% of physicians use reference apps to treat patients. The power of digital technology to educate patients cannot be minimized. According to the Pew Research Internet Project (2013), one in three American adults have gone online to self-diagnose. Physicians agreed with that diagnosis 41% of the time. Is this reason to tout the Internet as a clinical diagnostician? I would hope not. However, it does demonstrate that the Digital Age of health care has arrived. It cannot be ignored. In the United Kingdom, the National Health Service will begin accrediting apps to be prescribed in 2015. If one thinks of patient education and self-monitoring instructions as important for patient care, then the natural extension of digitally delivering these tools should not send shock waves across the landscape. IMS Health offers technology for the prescribing of health apps and analytics for apps. Clearly, obstacles remain for app prescribing to enter mainstream medicine, the most significant being quality assurance regarding clinical effectiveness and data privacy and security. However, there are some excellent apps from which patients can benefit. In the nutritional arena, GoMeals and Fooducate are useful, as is Alivecor ECG for symptomatic heart rhythm monitoring. There are also several good smoking cessation apps. Further, there are text messaging programs which have proved not only popular but effective, specifically the smoking cessation offering SmokefreeTXT and the prenatal care program text4baby.

3. Participate in social media.

In 2010, the American Medical Association adopted guidelines for professionalism in social media. Among 22 other interesting statistics on health care in social media, are these two: More than 40% of consumers say that information found via social media affects the way they deal with their health, and 60% of social media users are the most likely to trust social media posts and activity by doctors over any other group.

4. Have your hospital start online patient support groups.

There are relative benefits to both in-person support groups and online patient support groups. My mother was a patient at a major cancer center, and I tweeted asking whether they had an online support group, as my mother enjoyed the in-person meetings, which she could no longer attend. The hospital account, having realized the importance of such outreach, responded with the establishment of an online group the following week. This type of patient service creates a sense of health care community, which is invaluable to both patient satisfaction and provider-patient relationships.

5. Utilize mobile technologies to facilitate patient engagement via self-monitoring.

The mere suggestion of recommending an app to have a patient log their blood pressure or follow their glucose is a signal of the importance of shared management and decision making. Apps that allow a person to track their activity or food consumption are simple yet meaningful. Patients are longing for tools they can use themselves or utilize as caregivers.

Empathy can be conveyed directly as emotional support or indirectly with actions described above. It is ironic that technology, cold and inhumane in a solitary context, can be transformed and seen as empathetic if it is offered in a humanistic way.

Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.

The influence of technology on the patient-physician relationship has been the subject of many discussions and publications. While a physician facing a computer screen throughout much of the office encounter is a vision no one believes is in the best interest of either the patient or the relationship, empathy as an admired professional trait and a successful tool in medicine is gaining support among the medical establishment. The question as to whether physicians can learn empathy has been examined. The benefits (real or potential) of digital technology in revitalizing this human interaction and technology’s potential to convey empathy must be considered. I will attempt to place some of these tools in a bit of a new light.

1. Encourage patients to utilize the patient portal.

Stage 2 of meaningful use requires that 5% of Medicare patients receive information via a patient portal; this has resulted in little less than an exercise in compliance. True interaction via the portal is not taking place. The catch-22 is that the portals provided by electronic health record (EHR) vendors are the least costly, but also the least useful. Providers are not enthusiastic about portals for good reason. Clinicians are fearful that office workflow cannot accommodate the potential volume of digital interactions. They also do not have the digital tools necessary to make the portal experience as beneficial as it can be.

Notwithstanding these barriers, I believe that a physician who encourages the use of the portal with conversations focused on patients’ participation in their own care will be seen as empathetic. Stressing the fact that the patient is being given a tool that delivers information (even if it is only a lab result) portrays the provider as a partner in care. The patient portal is the starting point of introducing patients to digital health technology. If it is the portal which is closest to the patient’s care touch point, other technologies will seem less intimidating and more relevant.

2. Prescribe apps and websites.

The days of a physician’s rolling eyes at a patient’s mention of information garnered on the Internet should be over. More than 90% of physicians use reference apps to treat patients. The power of digital technology to educate patients cannot be minimized. According to the Pew Research Internet Project (2013), one in three American adults have gone online to self-diagnose. Physicians agreed with that diagnosis 41% of the time. Is this reason to tout the Internet as a clinical diagnostician? I would hope not. However, it does demonstrate that the Digital Age of health care has arrived. It cannot be ignored. In the United Kingdom, the National Health Service will begin accrediting apps to be prescribed in 2015. If one thinks of patient education and self-monitoring instructions as important for patient care, then the natural extension of digitally delivering these tools should not send shock waves across the landscape. IMS Health offers technology for the prescribing of health apps and analytics for apps. Clearly, obstacles remain for app prescribing to enter mainstream medicine, the most significant being quality assurance regarding clinical effectiveness and data privacy and security. However, there are some excellent apps from which patients can benefit. In the nutritional arena, GoMeals and Fooducate are useful, as is Alivecor ECG for symptomatic heart rhythm monitoring. There are also several good smoking cessation apps. Further, there are text messaging programs which have proved not only popular but effective, specifically the smoking cessation offering SmokefreeTXT and the prenatal care program text4baby.

3. Participate in social media.

In 2010, the American Medical Association adopted guidelines for professionalism in social media. Among 22 other interesting statistics on health care in social media, are these two: More than 40% of consumers say that information found via social media affects the way they deal with their health, and 60% of social media users are the most likely to trust social media posts and activity by doctors over any other group.

4. Have your hospital start online patient support groups.

There are relative benefits to both in-person support groups and online patient support groups. My mother was a patient at a major cancer center, and I tweeted asking whether they had an online support group, as my mother enjoyed the in-person meetings, which she could no longer attend. The hospital account, having realized the importance of such outreach, responded with the establishment of an online group the following week. This type of patient service creates a sense of health care community, which is invaluable to both patient satisfaction and provider-patient relationships.

5. Utilize mobile technologies to facilitate patient engagement via self-monitoring.

The mere suggestion of recommending an app to have a patient log their blood pressure or follow their glucose is a signal of the importance of shared management and decision making. Apps that allow a person to track their activity or food consumption are simple yet meaningful. Patients are longing for tools they can use themselves or utilize as caregivers.

Empathy can be conveyed directly as emotional support or indirectly with actions described above. It is ironic that technology, cold and inhumane in a solitary context, can be transformed and seen as empathetic if it is offered in a humanistic way.

Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.