HIV infection is associated with a significantly lower risk of developing multiple sclerosis (MS), according to a study published online ahead of print August 4 in the Journal of Neurology, Neurosurgery, & Psychiatry. Researchers investigated episodes of hospital care between 1999 and 2011 for patients with HIV. Compared with people who did not have HIV, patients with HIV were 62% less likely to develop MS. After more than a year between the two diagnoses, HIV-positive patients were 75% less likely to develop MS. “If subsequent studies demonstrate [that] there is a causal protective effect of HIV or its treatment, and if the magnitude of it proves to be similar … this would be the largest protective effect of any factor yet observed in relation to the development of MS,” the investigators concluded.

Colds and other minor infections may temporarily increase stroke risk in children, according to a study published online ahead of print August 20 in Neurology. Using the Kaiser Permanente database of 2.5 million children, researchers identified 102 children who had had an acute ischemic stroke and compared them with 306 children without stroke. Medical records for the children who had had a stroke were reviewed for minor infections for two years before their strokes. Ten (9.8%) of the 102 children with stroke had visited a physician for an infection within three days of the stroke. In comparison, two controls (0.7%) had an infection during the same time period. “Proposed mechanisms for the link between minor infection and stroke in adults include an inflammatory-mediated prothrombotic state and chronic endothelial injury,” the investigators theorized.

Peripheral pulse monitoring in patients with stroke accurately distinguishes atrial fibrillation from normal heart rhythm, investigators reported in the August 12 issue of Neurology. The prospective study included 256 patients with acute ischemic stroke, as well as the patients’ relatives. Subjects were taught to measure the patient’s pulse to detect atrial fibrillation; measurements from the participants and health care professionals were compared with recordings of electrical activity in the heart. Fifty-seven patients had irregular heartbeats. Measurement of the peripheral pulse by health care professionals had a diagnostic sensitivity of 96.5%, compared with 76.5% for the patients’ relatives, regarding the detection of atrial fibrillation. The specificity was 94.0% for health care professionals and 92.9% for patients’ relatives. Self-measurements were performed by 89.1% of patients with a diagnostic sensitivity of 54.1% and 96.2% specificity.

Reducing smoking among people in a low socioeconomic position and among those with hypertension may reduce social inequality stroke incidence, researchers reported online ahead of print August 14 in Stroke. The findings are based on data from 68,643 adults between ages 30 and 70 who were grouped into low, medium, and high education levels and assessed for smoking status and blood pressure level. About 16% of men and 11% of women had a high risk of stroke because of low education level, high blood pressure, and smoking. Smokers with low education had a greater risk of stroke than smokers with high education, regardless of their blood pressure. About 10% of men and 9% of women at high risk had an ischemic stroke during follow-up. Overall, men had a higher risk of stroke than women, and their risk increased with age.

Motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by slow gait and cognitive complaints, is common in older adults and is a strong and early risk factor for cognitive decline, according to a study published online ahead of print July 16 in Neurology. Among 26,802 participants from 22 cohorts, 2,808 subjects met MCR criteria. MCR prevalence was higher among older individuals, but there were no sex differences. MCR predicted the risk of developing incident cognitive impairment (adjusted hazard ratio, 2.0); in individual cohorts the adjusted hazard ratios ranged from 1.5 to 2.7. MCR also predicted dementia in the pooled sample (adjusted hazard ratio, 1.9). “MCR criteria can be easily applied in clinical settings with simple questions about cognitive complaints and timing gait; 90% of participants had walking timed over fixed distances without requiring major resource commitments,” the investigators stated.

The FDA has approved Plegridy (peginterferon beta-1a) for patients with relapsing forms of multiple sclerosis (MS). Approval of the drug is based on results from the ADVANCE study of more than 1,500 patients with MS. The drug can be administered subcutaneously with an autoinjector or a prefilled syringe. Dosed once every two weeks, the drug significantly reduced annualized relapse rate at one year by 36%, compared with placebo. Plegridy reduced the risk of 12-week confirmed disability progression by 38%, compared with placebo. The drug also significantly reduced the number of new gadolinium-enhancing lesions by 86% and decreased the number of new or newly enlarging T2-hyperintense lesions by 67%, compared with placebo. Common adverse reactions include injection-site reaction and flu-like illness. The drug is manufactured by Biogen Idec, which is headquartered in Cambridge, Massachusetts.

In patients who are hospitalized for surgery, perioperative atrial fibrillation is associated with an increased long-term risk of ischemic stroke, according to a study published in the August 13 issue of JAMA. Researchers studied 1,729,360 patients hospitalized for surgery between 2007 and 2011. Perioperative atrial fibrillation was documented in 24,711 patients (1.43%) during the index hospitalization. After discharge, 13,952 patients (0.81%) had an ischemic stroke. One year after hospitalization for noncardiac surgery, cumulative rates of stroke were 1.47% in patients with perioperative atrial fibrillation and 0.36% in people without atrial fibrillation. One year after cardiac surgery, cumulative rates of stroke were 0.99% in patients with perioperative atrial fibrillation and 0.83% in patients without atrial fibrillation. The association with stroke was stronger for perioperative atrial fibrillation and noncardiac surgery, compared with cardiac surgery.

Approximately one-third of cases of Alzheimer’s disease worldwide might be attributed to potentially modifiable risk factors, investigators reported in the August issue of Lancet Neurology. An international team of researchers used relative risks from existing meta-analyses to estimate the population-attributable risk (PAR) of Alzheimer’s disease worldwide and in the United States, Europe, and the United Kingdom for seven potentially modifiable risk factors. Worldwide, the highest estimated PAR was for low educational attainment. In the US, Europe, and UK the highest estimated PAR was for physical inactivity. Assuming the risk factors’ independence, the combined worldwide PAR for the seven risk factors was 49.4%, which accounts for 16.8 million of the 33.9 million cases. Adjustment for the association between the risk factors decreased the estimate to 28.2%, which equates to 9.6 million cases.

The FDA has approved Belsomra (suvorexant) for adults with insomnia who have difficulty falling and staying asleep. The drug is the first approved orexin receptor antagonist. Orexins are involved in regulating the sleep–wake cycle and play a role in promoting arousal. In clinical trials, Belsomra (Merck; Whitehouse Station, New Jersey) was superior to placebo for reducing sleep latency and improving sleep maintenance, as assessed objectively by polysomnography and subjectively by patient-estimated sleep latency. Belsomra should be taken no more than once per night, within 30 minutes of going to bed, with at least seven hours remaining before the planned time of waking. The total dose should not exceed 20 mg once daily. The most commonly reported adverse reaction among clinical trial participants taking Belsomra was drowsiness.

A clinical diagnosis of Parkinson’s disease identifies patients who will have pathologically confirmed Parkinson’s disease with a sensitivity of 88% and specificity of 68%, researchers reported in the July 29 issue of Neurology. Investigators analyzed data from an aging study to determine the predictive value of clinical diagnosis of Parkinson’s disease using two diagnostic confidence levels: possible and probable Parkinson’s disease. Approximately 26% of patients diagnosed with possible Parkinson’s disease were neuropathologically confirmed as having Parkinson’s disease; 82% of patients diagnosed with probable Parkinson’s disease were confirmed as having Parkinson’s disease. Researchers calculated a 26% accuracy rate for clinical diagnosis of Parkinson’s disease in untreated or not clearly responsive subjects, a 53% accuracy rate in early Parkinson’s disease responsive to medication (less than five year’s duration), and a greater than 85% diagnostic accuracy rate for longer duration, medication-responsive Parkinson’s disease.

Depressive symptoms in old age are associated with cognitive decline that is independent of dementia, according to a study published in the August 19 issue of Neurology. Investigators monitored 1,764 participants with an average age of 77 who had no thinking or memory problems at the start of the study. Participants were screened every year for symptoms of depression and were evaluated for their memory and thinking skills for a mean of 7.8 years. A total of 922 (52%) participants developed mild cognitive impairment, and 315 (18%) developed dementia. Overall, having a higher level of depression symptoms was associated with more rapid decline in thinking and memory skills, which accounted for 4.4% of the difference in decline that could not be attributed to the level of damage in the brain.

Researchers may have found a potential genetic link between epilepsy and neurodegenerative disorders, according to a study published in the July 29 Proceedings of the National Academy of Sciences. The investigators observed that seizure-prone prickle mutant flies have behavioral defects and electrophysiologic defects similar to those of other fly mutants used to study seizures. Altering the balance of two forms of the prickle gene disrupted neural information flow and caused epilepsy. The researchers also observed that reducing either of two motor proteins responsible for directional movement of vesicles along the tracks of structural proteins in axons could suppress seizures. “This is, to our knowledge, the first direct genetic evidence demonstrating that mutations in the fly version of a known human epilepsy gene produce seizures through altered vesicle transport,” stated the authors.

—Kimberly Williams

HIV infection is associated with a significantly lower risk of developing multiple sclerosis (MS), according to a study published online ahead of print August 4 in the Journal of Neurology, Neurosurgery, & Psychiatry. Researchers investigated episodes of hospital care between 1999 and 2011 for patients with HIV. Compared with people who did not have HIV, patients with HIV were 62% less likely to develop MS. After more than a year between the two diagnoses, HIV-positive patients were 75% less likely to develop MS. “If subsequent studies demonstrate [that] there is a causal protective effect of HIV or its treatment, and if the magnitude of it proves to be similar … this would be the largest protective effect of any factor yet observed in relation to the development of MS,” the investigators concluded.

Colds and other minor infections may temporarily increase stroke risk in children, according to a study published online ahead of print August 20 in Neurology. Using the Kaiser Permanente database of 2.5 million children, researchers identified 102 children who had had an acute ischemic stroke and compared them with 306 children without stroke. Medical records for the children who had had a stroke were reviewed for minor infections for two years before their strokes. Ten (9.8%) of the 102 children with stroke had visited a physician for an infection within three days of the stroke. In comparison, two controls (0.7%) had an infection during the same time period. “Proposed mechanisms for the link between minor infection and stroke in adults include an inflammatory-mediated prothrombotic state and chronic endothelial injury,” the investigators theorized.

Peripheral pulse monitoring in patients with stroke accurately distinguishes atrial fibrillation from normal heart rhythm, investigators reported in the August 12 issue of Neurology. The prospective study included 256 patients with acute ischemic stroke, as well as the patients’ relatives. Subjects were taught to measure the patient’s pulse to detect atrial fibrillation; measurements from the participants and health care professionals were compared with recordings of electrical activity in the heart. Fifty-seven patients had irregular heartbeats. Measurement of the peripheral pulse by health care professionals had a diagnostic sensitivity of 96.5%, compared with 76.5% for the patients’ relatives, regarding the detection of atrial fibrillation. The specificity was 94.0% for health care professionals and 92.9% for patients’ relatives. Self-measurements were performed by 89.1% of patients with a diagnostic sensitivity of 54.1% and 96.2% specificity.

Reducing smoking among people in a low socioeconomic position and among those with hypertension may reduce social inequality stroke incidence, researchers reported online ahead of print August 14 in Stroke. The findings are based on data from 68,643 adults between ages 30 and 70 who were grouped into low, medium, and high education levels and assessed for smoking status and blood pressure level. About 16% of men and 11% of women had a high risk of stroke because of low education level, high blood pressure, and smoking. Smokers with low education had a greater risk of stroke than smokers with high education, regardless of their blood pressure. About 10% of men and 9% of women at high risk had an ischemic stroke during follow-up. Overall, men had a higher risk of stroke than women, and their risk increased with age.

Motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by slow gait and cognitive complaints, is common in older adults and is a strong and early risk factor for cognitive decline, according to a study published online ahead of print July 16 in Neurology. Among 26,802 participants from 22 cohorts, 2,808 subjects met MCR criteria. MCR prevalence was higher among older individuals, but there were no sex differences. MCR predicted the risk of developing incident cognitive impairment (adjusted hazard ratio, 2.0); in individual cohorts the adjusted hazard ratios ranged from 1.5 to 2.7. MCR also predicted dementia in the pooled sample (adjusted hazard ratio, 1.9). “MCR criteria can be easily applied in clinical settings with simple questions about cognitive complaints and timing gait; 90% of participants had walking timed over fixed distances without requiring major resource commitments,” the investigators stated.

The FDA has approved Plegridy (peginterferon beta-1a) for patients with relapsing forms of multiple sclerosis (MS). Approval of the drug is based on results from the ADVANCE study of more than 1,500 patients with MS. The drug can be administered subcutaneously with an autoinjector or a prefilled syringe. Dosed once every two weeks, the drug significantly reduced annualized relapse rate at one year by 36%, compared with placebo. Plegridy reduced the risk of 12-week confirmed disability progression by 38%, compared with placebo. The drug also significantly reduced the number of new gadolinium-enhancing lesions by 86% and decreased the number of new or newly enlarging T2-hyperintense lesions by 67%, compared with placebo. Common adverse reactions include injection-site reaction and flu-like illness. The drug is manufactured by Biogen Idec, which is headquartered in Cambridge, Massachusetts.

In patients who are hospitalized for surgery, perioperative atrial fibrillation is associated with an increased long-term risk of ischemic stroke, according to a study published in the August 13 issue of JAMA. Researchers studied 1,729,360 patients hospitalized for surgery between 2007 and 2011. Perioperative atrial fibrillation was documented in 24,711 patients (1.43%) during the index hospitalization. After discharge, 13,952 patients (0.81%) had an ischemic stroke. One year after hospitalization for noncardiac surgery, cumulative rates of stroke were 1.47% in patients with perioperative atrial fibrillation and 0.36% in people without atrial fibrillation. One year after cardiac surgery, cumulative rates of stroke were 0.99% in patients with perioperative atrial fibrillation and 0.83% in patients without atrial fibrillation. The association with stroke was stronger for perioperative atrial fibrillation and noncardiac surgery, compared with cardiac surgery.

Approximately one-third of cases of Alzheimer’s disease worldwide might be attributed to potentially modifiable risk factors, investigators reported in the August issue of Lancet Neurology. An international team of researchers used relative risks from existing meta-analyses to estimate the population-attributable risk (PAR) of Alzheimer’s disease worldwide and in the United States, Europe, and the United Kingdom for seven potentially modifiable risk factors. Worldwide, the highest estimated PAR was for low educational attainment. In the US, Europe, and UK the highest estimated PAR was for physical inactivity. Assuming the risk factors’ independence, the combined worldwide PAR for the seven risk factors was 49.4%, which accounts for 16.8 million of the 33.9 million cases. Adjustment for the association between the risk factors decreased the estimate to 28.2%, which equates to 9.6 million cases.

The FDA has approved Belsomra (suvorexant) for adults with insomnia who have difficulty falling and staying asleep. The drug is the first approved orexin receptor antagonist. Orexins are involved in regulating the sleep–wake cycle and play a role in promoting arousal. In clinical trials, Belsomra (Merck; Whitehouse Station, New Jersey) was superior to placebo for reducing sleep latency and improving sleep maintenance, as assessed objectively by polysomnography and subjectively by patient-estimated sleep latency. Belsomra should be taken no more than once per night, within 30 minutes of going to bed, with at least seven hours remaining before the planned time of waking. The total dose should not exceed 20 mg once daily. The most commonly reported adverse reaction among clinical trial participants taking Belsomra was drowsiness.

A clinical diagnosis of Parkinson’s disease identifies patients who will have pathologically confirmed Parkinson’s disease with a sensitivity of 88% and specificity of 68%, researchers reported in the July 29 issue of Neurology. Investigators analyzed data from an aging study to determine the predictive value of clinical diagnosis of Parkinson’s disease using two diagnostic confidence levels: possible and probable Parkinson’s disease. Approximately 26% of patients diagnosed with possible Parkinson’s disease were neuropathologically confirmed as having Parkinson’s disease; 82% of patients diagnosed with probable Parkinson’s disease were confirmed as having Parkinson’s disease. Researchers calculated a 26% accuracy rate for clinical diagnosis of Parkinson’s disease in untreated or not clearly responsive subjects, a 53% accuracy rate in early Parkinson’s disease responsive to medication (less than five year’s duration), and a greater than 85% diagnostic accuracy rate for longer duration, medication-responsive Parkinson’s disease.

Depressive symptoms in old age are associated with cognitive decline that is independent of dementia, according to a study published in the August 19 issue of Neurology. Investigators monitored 1,764 participants with an average age of 77 who had no thinking or memory problems at the start of the study. Participants were screened every year for symptoms of depression and were evaluated for their memory and thinking skills for a mean of 7.8 years. A total of 922 (52%) participants developed mild cognitive impairment, and 315 (18%) developed dementia. Overall, having a higher level of depression symptoms was associated with more rapid decline in thinking and memory skills, which accounted for 4.4% of the difference in decline that could not be attributed to the level of damage in the brain.

Researchers may have found a potential genetic link between epilepsy and neurodegenerative disorders, according to a study published in the July 29 Proceedings of the National Academy of Sciences. The investigators observed that seizure-prone prickle mutant flies have behavioral defects and electrophysiologic defects similar to those of other fly mutants used to study seizures. Altering the balance of two forms of the prickle gene disrupted neural information flow and caused epilepsy. The researchers also observed that reducing either of two motor proteins responsible for directional movement of vesicles along the tracks of structural proteins in axons could suppress seizures. “This is, to our knowledge, the first direct genetic evidence demonstrating that mutations in the fly version of a known human epilepsy gene produce seizures through altered vesicle transport,” stated the authors.

—Kimberly Williams

HIV infection is associated with a significantly lower risk of developing multiple sclerosis (MS), according to a study published online ahead of print August 4 in the Journal of Neurology, Neurosurgery, & Psychiatry. Researchers investigated episodes of hospital care between 1999 and 2011 for patients with HIV. Compared with people who did not have HIV, patients with HIV were 62% less likely to develop MS. After more than a year between the two diagnoses, HIV-positive patients were 75% less likely to develop MS. “If subsequent studies demonstrate [that] there is a causal protective effect of HIV or its treatment, and if the magnitude of it proves to be similar … this would be the largest protective effect of any factor yet observed in relation to the development of MS,” the investigators concluded.

Colds and other minor infections may temporarily increase stroke risk in children, according to a study published online ahead of print August 20 in Neurology. Using the Kaiser Permanente database of 2.5 million children, researchers identified 102 children who had had an acute ischemic stroke and compared them with 306 children without stroke. Medical records for the children who had had a stroke were reviewed for minor infections for two years before their strokes. Ten (9.8%) of the 102 children with stroke had visited a physician for an infection within three days of the stroke. In comparison, two controls (0.7%) had an infection during the same time period. “Proposed mechanisms for the link between minor infection and stroke in adults include an inflammatory-mediated prothrombotic state and chronic endothelial injury,” the investigators theorized.

Peripheral pulse monitoring in patients with stroke accurately distinguishes atrial fibrillation from normal heart rhythm, investigators reported in the August 12 issue of Neurology. The prospective study included 256 patients with acute ischemic stroke, as well as the patients’ relatives. Subjects were taught to measure the patient’s pulse to detect atrial fibrillation; measurements from the participants and health care professionals were compared with recordings of electrical activity in the heart. Fifty-seven patients had irregular heartbeats. Measurement of the peripheral pulse by health care professionals had a diagnostic sensitivity of 96.5%, compared with 76.5% for the patients’ relatives, regarding the detection of atrial fibrillation. The specificity was 94.0% for health care professionals and 92.9% for patients’ relatives. Self-measurements were performed by 89.1% of patients with a diagnostic sensitivity of 54.1% and 96.2% specificity.

Reducing smoking among people in a low socioeconomic position and among those with hypertension may reduce social inequality stroke incidence, researchers reported online ahead of print August 14 in Stroke. The findings are based on data from 68,643 adults between ages 30 and 70 who were grouped into low, medium, and high education levels and assessed for smoking status and blood pressure level. About 16% of men and 11% of women had a high risk of stroke because of low education level, high blood pressure, and smoking. Smokers with low education had a greater risk of stroke than smokers with high education, regardless of their blood pressure. About 10% of men and 9% of women at high risk had an ischemic stroke during follow-up. Overall, men had a higher risk of stroke than women, and their risk increased with age.

Motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by slow gait and cognitive complaints, is common in older adults and is a strong and early risk factor for cognitive decline, according to a study published online ahead of print July 16 in Neurology. Among 26,802 participants from 22 cohorts, 2,808 subjects met MCR criteria. MCR prevalence was higher among older individuals, but there were no sex differences. MCR predicted the risk of developing incident cognitive impairment (adjusted hazard ratio, 2.0); in individual cohorts the adjusted hazard ratios ranged from 1.5 to 2.7. MCR also predicted dementia in the pooled sample (adjusted hazard ratio, 1.9). “MCR criteria can be easily applied in clinical settings with simple questions about cognitive complaints and timing gait; 90% of participants had walking timed over fixed distances without requiring major resource commitments,” the investigators stated.

The FDA has approved Plegridy (peginterferon beta-1a) for patients with relapsing forms of multiple sclerosis (MS). Approval of the drug is based on results from the ADVANCE study of more than 1,500 patients with MS. The drug can be administered subcutaneously with an autoinjector or a prefilled syringe. Dosed once every two weeks, the drug significantly reduced annualized relapse rate at one year by 36%, compared with placebo. Plegridy reduced the risk of 12-week confirmed disability progression by 38%, compared with placebo. The drug also significantly reduced the number of new gadolinium-enhancing lesions by 86% and decreased the number of new or newly enlarging T2-hyperintense lesions by 67%, compared with placebo. Common adverse reactions include injection-site reaction and flu-like illness. The drug is manufactured by Biogen Idec, which is headquartered in Cambridge, Massachusetts.

In patients who are hospitalized for surgery, perioperative atrial fibrillation is associated with an increased long-term risk of ischemic stroke, according to a study published in the August 13 issue of JAMA. Researchers studied 1,729,360 patients hospitalized for surgery between 2007 and 2011. Perioperative atrial fibrillation was documented in 24,711 patients (1.43%) during the index hospitalization. After discharge, 13,952 patients (0.81%) had an ischemic stroke. One year after hospitalization for noncardiac surgery, cumulative rates of stroke were 1.47% in patients with perioperative atrial fibrillation and 0.36% in people without atrial fibrillation. One year after cardiac surgery, cumulative rates of stroke were 0.99% in patients with perioperative atrial fibrillation and 0.83% in patients without atrial fibrillation. The association with stroke was stronger for perioperative atrial fibrillation and noncardiac surgery, compared with cardiac surgery.

Approximately one-third of cases of Alzheimer’s disease worldwide might be attributed to potentially modifiable risk factors, investigators reported in the August issue of Lancet Neurology. An international team of researchers used relative risks from existing meta-analyses to estimate the population-attributable risk (PAR) of Alzheimer’s disease worldwide and in the United States, Europe, and the United Kingdom for seven potentially modifiable risk factors. Worldwide, the highest estimated PAR was for low educational attainment. In the US, Europe, and UK the highest estimated PAR was for physical inactivity. Assuming the risk factors’ independence, the combined worldwide PAR for the seven risk factors was 49.4%, which accounts for 16.8 million of the 33.9 million cases. Adjustment for the association between the risk factors decreased the estimate to 28.2%, which equates to 9.6 million cases.

The FDA has approved Belsomra (suvorexant) for adults with insomnia who have difficulty falling and staying asleep. The drug is the first approved orexin receptor antagonist. Orexins are involved in regulating the sleep–wake cycle and play a role in promoting arousal. In clinical trials, Belsomra (Merck; Whitehouse Station, New Jersey) was superior to placebo for reducing sleep latency and improving sleep maintenance, as assessed objectively by polysomnography and subjectively by patient-estimated sleep latency. Belsomra should be taken no more than once per night, within 30 minutes of going to bed, with at least seven hours remaining before the planned time of waking. The total dose should not exceed 20 mg once daily. The most commonly reported adverse reaction among clinical trial participants taking Belsomra was drowsiness.

A clinical diagnosis of Parkinson’s disease identifies patients who will have pathologically confirmed Parkinson’s disease with a sensitivity of 88% and specificity of 68%, researchers reported in the July 29 issue of Neurology. Investigators analyzed data from an aging study to determine the predictive value of clinical diagnosis of Parkinson’s disease using two diagnostic confidence levels: possible and probable Parkinson’s disease. Approximately 26% of patients diagnosed with possible Parkinson’s disease were neuropathologically confirmed as having Parkinson’s disease; 82% of patients diagnosed with probable Parkinson’s disease were confirmed as having Parkinson’s disease. Researchers calculated a 26% accuracy rate for clinical diagnosis of Parkinson’s disease in untreated or not clearly responsive subjects, a 53% accuracy rate in early Parkinson’s disease responsive to medication (less than five year’s duration), and a greater than 85% diagnostic accuracy rate for longer duration, medication-responsive Parkinson’s disease.

Depressive symptoms in old age are associated with cognitive decline that is independent of dementia, according to a study published in the August 19 issue of Neurology. Investigators monitored 1,764 participants with an average age of 77 who had no thinking or memory problems at the start of the study. Participants were screened every year for symptoms of depression and were evaluated for their memory and thinking skills for a mean of 7.8 years. A total of 922 (52%) participants developed mild cognitive impairment, and 315 (18%) developed dementia. Overall, having a higher level of depression symptoms was associated with more rapid decline in thinking and memory skills, which accounted for 4.4% of the difference in decline that could not be attributed to the level of damage in the brain.

Researchers may have found a potential genetic link between epilepsy and neurodegenerative disorders, according to a study published in the July 29 Proceedings of the National Academy of Sciences. The investigators observed that seizure-prone prickle mutant flies have behavioral defects and electrophysiologic defects similar to those of other fly mutants used to study seizures. Altering the balance of two forms of the prickle gene disrupted neural information flow and caused epilepsy. The researchers also observed that reducing either of two motor proteins responsible for directional movement of vesicles along the tracks of structural proteins in axons could suppress seizures. “This is, to our knowledge, the first direct genetic evidence demonstrating that mutations in the fly version of a known human epilepsy gene produce seizures through altered vesicle transport,” stated the authors.

—Kimberly Williams

SAN FRANCISCO – Monitoring plasma vascular endothelial growth factor A (VEGF-A) may help identify pediatric heart transplant patients who are at increased risk for poor outcomes, according to a study reported at the 2014 World Transplant Congress.

"Cardiac allograft vasculopathy [CAV] remains the leading cause of chronic allograft failure after heart transplantation. ... Therefore, it’s important for us to be able to anticipate the development of CAV and open up a therapeutic window," said Dr. Kevin P. Daly of Harvard Medical School and Boston Children’s Hospital.

"Our pilot data suggest that plasma VEGF-A levels below 90 pg/mL identify a low-risk patient population in whom a decreased frequency of coronary angiography can be considered. Future studies are needed to determine if using plasma VEGF-A levels to modify CAV screening frequency results in equivalent patient outcomes, with decreased resource utilization and improved quality of life," Dr. Daly commented at the congress, which was sponsored by the American Society of Transplant Surgeons.

As the vascular endothelium is the primary target of the immune response in CAV, the researchers hypothesized that VEGF-A likely contributes to an inflammatory cycle that leads to vascular damage and occlusion in the graft.

Participants in the single-center prospective cohort study were 44 consecutive children aged 2 years or older who were at least 18 months (median, 6 years) out from heart transplantation. They were scheduled for routine annual screening coronary angiography during 2009, and had no or mild CAV.

Moderate or severe CAV developed in 32% of patients who had VEGF-A values above the median value at baseline (90 pg/mL), compared with 5% of patients who had VEGF-A values below the median level (P = .02). Patients who developed this vasculopathy were more likely to die (38% vs. 0%), undergo retransplantation (38% vs. 0%), experience a myocardial infarction (12% vs. 0%), and be listed for retransplantation (12% vs. 0%).

"While this is a biomarker and we have shown it is associated with CAV, we have not shown that it is causal," Dr. Daly cautioned. Any treatment directed against VEGF would have to be conducted in the context of a clinical trial to assess its impact.

A subset of patients becomes nonadherent to therapy; a subset that is highly sensitized before transplant may have donor-specific antibody, Dr. Daly said. So "we don’t think we fully understand the inciting event, ... [but] VEGF-A has been shown before to be elevated in antibody-mediated rejection, so it’s not surprising to see this association."

"We didn’t have these data available clinically because it was all a research study, so we didn’t intervene on any of the patients in this cohort. But we have started to think about whether or not we could use VEGF-A levels at least in our ... patients who might not have arterial access, and it might be difficult to survey them for CAV. I think in order to really understand the appropriate way to use it, we would need a larger study," he remarked.

Dr. Daly disclosed that he had no conflicts of interest relevant to the study.

SAN FRANCISCO – Monitoring plasma vascular endothelial growth factor A (VEGF-A) may help identify pediatric heart transplant patients who are at increased risk for poor outcomes, according to a study reported at the 2014 World Transplant Congress.

"Cardiac allograft vasculopathy [CAV] remains the leading cause of chronic allograft failure after heart transplantation. ... Therefore, it’s important for us to be able to anticipate the development of CAV and open up a therapeutic window," said Dr. Kevin P. Daly of Harvard Medical School and Boston Children’s Hospital.

"Our pilot data suggest that plasma VEGF-A levels below 90 pg/mL identify a low-risk patient population in whom a decreased frequency of coronary angiography can be considered. Future studies are needed to determine if using plasma VEGF-A levels to modify CAV screening frequency results in equivalent patient outcomes, with decreased resource utilization and improved quality of life," Dr. Daly commented at the congress, which was sponsored by the American Society of Transplant Surgeons.

As the vascular endothelium is the primary target of the immune response in CAV, the researchers hypothesized that VEGF-A likely contributes to an inflammatory cycle that leads to vascular damage and occlusion in the graft.

Participants in the single-center prospective cohort study were 44 consecutive children aged 2 years or older who were at least 18 months (median, 6 years) out from heart transplantation. They were scheduled for routine annual screening coronary angiography during 2009, and had no or mild CAV.

Moderate or severe CAV developed in 32% of patients who had VEGF-A values above the median value at baseline (90 pg/mL), compared with 5% of patients who had VEGF-A values below the median level (P = .02). Patients who developed this vasculopathy were more likely to die (38% vs. 0%), undergo retransplantation (38% vs. 0%), experience a myocardial infarction (12% vs. 0%), and be listed for retransplantation (12% vs. 0%).

"While this is a biomarker and we have shown it is associated with CAV, we have not shown that it is causal," Dr. Daly cautioned. Any treatment directed against VEGF would have to be conducted in the context of a clinical trial to assess its impact.

A subset of patients becomes nonadherent to therapy; a subset that is highly sensitized before transplant may have donor-specific antibody, Dr. Daly said. So "we don’t think we fully understand the inciting event, ... [but] VEGF-A has been shown before to be elevated in antibody-mediated rejection, so it’s not surprising to see this association."

"We didn’t have these data available clinically because it was all a research study, so we didn’t intervene on any of the patients in this cohort. But we have started to think about whether or not we could use VEGF-A levels at least in our ... patients who might not have arterial access, and it might be difficult to survey them for CAV. I think in order to really understand the appropriate way to use it, we would need a larger study," he remarked.

Dr. Daly disclosed that he had no conflicts of interest relevant to the study.

SAN FRANCISCO – Monitoring plasma vascular endothelial growth factor A (VEGF-A) may help identify pediatric heart transplant patients who are at increased risk for poor outcomes, according to a study reported at the 2014 World Transplant Congress.

"Cardiac allograft vasculopathy [CAV] remains the leading cause of chronic allograft failure after heart transplantation. ... Therefore, it’s important for us to be able to anticipate the development of CAV and open up a therapeutic window," said Dr. Kevin P. Daly of Harvard Medical School and Boston Children’s Hospital.

"Our pilot data suggest that plasma VEGF-A levels below 90 pg/mL identify a low-risk patient population in whom a decreased frequency of coronary angiography can be considered. Future studies are needed to determine if using plasma VEGF-A levels to modify CAV screening frequency results in equivalent patient outcomes, with decreased resource utilization and improved quality of life," Dr. Daly commented at the congress, which was sponsored by the American Society of Transplant Surgeons.

As the vascular endothelium is the primary target of the immune response in CAV, the researchers hypothesized that VEGF-A likely contributes to an inflammatory cycle that leads to vascular damage and occlusion in the graft.

Participants in the single-center prospective cohort study were 44 consecutive children aged 2 years or older who were at least 18 months (median, 6 years) out from heart transplantation. They were scheduled for routine annual screening coronary angiography during 2009, and had no or mild CAV.

Moderate or severe CAV developed in 32% of patients who had VEGF-A values above the median value at baseline (90 pg/mL), compared with 5% of patients who had VEGF-A values below the median level (P = .02). Patients who developed this vasculopathy were more likely to die (38% vs. 0%), undergo retransplantation (38% vs. 0%), experience a myocardial infarction (12% vs. 0%), and be listed for retransplantation (12% vs. 0%).

"While this is a biomarker and we have shown it is associated with CAV, we have not shown that it is causal," Dr. Daly cautioned. Any treatment directed against VEGF would have to be conducted in the context of a clinical trial to assess its impact.

A subset of patients becomes nonadherent to therapy; a subset that is highly sensitized before transplant may have donor-specific antibody, Dr. Daly said. So "we don’t think we fully understand the inciting event, ... [but] VEGF-A has been shown before to be elevated in antibody-mediated rejection, so it’s not surprising to see this association."

"We didn’t have these data available clinically because it was all a research study, so we didn’t intervene on any of the patients in this cohort. But we have started to think about whether or not we could use VEGF-A levels at least in our ... patients who might not have arterial access, and it might be difficult to survey them for CAV. I think in order to really understand the appropriate way to use it, we would need a larger study," he remarked.

Dr. Daly disclosed that he had no conflicts of interest relevant to the study.

The prevalence of urinary incontinence is 17%-55% among older women and 12%-42% among younger and middle-aged women. Only 45% of women with at least weekly symptoms seek medical care to address their symptoms.

For most of us, offering conservative measures is the most reasonable approach when women present. Pelvic floor muscle training, sometimes referred to as Kegel exercises, is usually one of the first things we discuss. Many women have heard this spiel before and may report having tried but not benefited from the exercises. This real or perceived lack of benefit may be related to either poor adherence or lack of efficacy.

In theory, pelvic floor muscle training builds strength and improves muscle tone, enhances conscious awareness of muscle groups, and increases perineal support by lifting pelvic viscera. But do clinical trial data support the use of pelvic muscle training for reducing urinary incontinence?

Dr. O. Celiker Tosun of Dokuz Eylül University, Izmir, Turkey, and colleagues published the results of a randomized clinical trial evaluating the effectiveness of an individually prescribed 12-week home-based pelvic floor muscle exercise program (Clin. Rehabil. 2014 Aug. 20 [doi:10.1177/0269215514546768]). Women with stress or mixed urinary incontinence were selected from a urogynecology clinic and randomized to pelvic floor muscle training (65 patients) or a control condition (65 patients).

The pelvic floor muscle training group had significant improvement in their symptoms of urinary incontinence and pelvic floor muscle strength, compared with the control group. Symptoms of urinary incontinence were significantly decreased in the training group.

This study is important because it demonstrates the utility of pelvic floor muscle training exercises under ideal circumstances.

However, the intervention provided in this study was intense and sophisticated – and it will be difficult, if not impossible, for most of us to replicate. A physiotherapist provided the training over a 12-week period, with 30-minute sessions three times a week for the first 2 weeks. Women also kept a training diary. Adherence to the protocol was 89% in the training group.

This is very different from the handout on Kegel’s we might be giving to our patients – with adherence to recommendations likely approaching 0%.

But now that we have these data, perhaps we can talk to our female patients more consistently and convincingly about the utility of this approach for reducing incontinence. If we are lucky and have a women’s health clinic with access to this type of expertise, this might be another option – at least before we refer them for higher-risk surgical procedures.

Dr. Ebbert is professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. They should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.

The prevalence of urinary incontinence is 17%-55% among older women and 12%-42% among younger and middle-aged women. Only 45% of women with at least weekly symptoms seek medical care to address their symptoms.

For most of us, offering conservative measures is the most reasonable approach when women present. Pelvic floor muscle training, sometimes referred to as Kegel exercises, is usually one of the first things we discuss. Many women have heard this spiel before and may report having tried but not benefited from the exercises. This real or perceived lack of benefit may be related to either poor adherence or lack of efficacy.

In theory, pelvic floor muscle training builds strength and improves muscle tone, enhances conscious awareness of muscle groups, and increases perineal support by lifting pelvic viscera. But do clinical trial data support the use of pelvic muscle training for reducing urinary incontinence?

Dr. O. Celiker Tosun of Dokuz Eylül University, Izmir, Turkey, and colleagues published the results of a randomized clinical trial evaluating the effectiveness of an individually prescribed 12-week home-based pelvic floor muscle exercise program (Clin. Rehabil. 2014 Aug. 20 [doi:10.1177/0269215514546768]). Women with stress or mixed urinary incontinence were selected from a urogynecology clinic and randomized to pelvic floor muscle training (65 patients) or a control condition (65 patients).

The pelvic floor muscle training group had significant improvement in their symptoms of urinary incontinence and pelvic floor muscle strength, compared with the control group. Symptoms of urinary incontinence were significantly decreased in the training group.

This study is important because it demonstrates the utility of pelvic floor muscle training exercises under ideal circumstances.

However, the intervention provided in this study was intense and sophisticated – and it will be difficult, if not impossible, for most of us to replicate. A physiotherapist provided the training over a 12-week period, with 30-minute sessions three times a week for the first 2 weeks. Women also kept a training diary. Adherence to the protocol was 89% in the training group.

This is very different from the handout on Kegel’s we might be giving to our patients – with adherence to recommendations likely approaching 0%.

But now that we have these data, perhaps we can talk to our female patients more consistently and convincingly about the utility of this approach for reducing incontinence. If we are lucky and have a women’s health clinic with access to this type of expertise, this might be another option – at least before we refer them for higher-risk surgical procedures.

Dr. Ebbert is professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. They should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.

The prevalence of urinary incontinence is 17%-55% among older women and 12%-42% among younger and middle-aged women. Only 45% of women with at least weekly symptoms seek medical care to address their symptoms.

For most of us, offering conservative measures is the most reasonable approach when women present. Pelvic floor muscle training, sometimes referred to as Kegel exercises, is usually one of the first things we discuss. Many women have heard this spiel before and may report having tried but not benefited from the exercises. This real or perceived lack of benefit may be related to either poor adherence or lack of efficacy.

In theory, pelvic floor muscle training builds strength and improves muscle tone, enhances conscious awareness of muscle groups, and increases perineal support by lifting pelvic viscera. But do clinical trial data support the use of pelvic muscle training for reducing urinary incontinence?

Dr. O. Celiker Tosun of Dokuz Eylül University, Izmir, Turkey, and colleagues published the results of a randomized clinical trial evaluating the effectiveness of an individually prescribed 12-week home-based pelvic floor muscle exercise program (Clin. Rehabil. 2014 Aug. 20 [doi:10.1177/0269215514546768]). Women with stress or mixed urinary incontinence were selected from a urogynecology clinic and randomized to pelvic floor muscle training (65 patients) or a control condition (65 patients).

The pelvic floor muscle training group had significant improvement in their symptoms of urinary incontinence and pelvic floor muscle strength, compared with the control group. Symptoms of urinary incontinence were significantly decreased in the training group.

This study is important because it demonstrates the utility of pelvic floor muscle training exercises under ideal circumstances.

However, the intervention provided in this study was intense and sophisticated – and it will be difficult, if not impossible, for most of us to replicate. A physiotherapist provided the training over a 12-week period, with 30-minute sessions three times a week for the first 2 weeks. Women also kept a training diary. Adherence to the protocol was 89% in the training group.

This is very different from the handout on Kegel’s we might be giving to our patients – with adherence to recommendations likely approaching 0%.

But now that we have these data, perhaps we can talk to our female patients more consistently and convincingly about the utility of this approach for reducing incontinence. If we are lucky and have a women’s health clinic with access to this type of expertise, this might be another option – at least before we refer them for higher-risk surgical procedures.

Dr. Ebbert is professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. They should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.

Ten years ago, the Food and Drug Administration required that all antidepressants carry a severe black box warning to alert prescribers to the possibility that these medications could cause worsening suicidal thoughts and behavior. A decade later, this issue had faded from the public eye and the media headlines. Nevertheless, research into their use has continued, and antidepressants continue to be prescribed. Have things changed since all the attention in the past? The results may be surprising.

Although there are undoubtedly different views, here is my summary of the five key points with direct implications for pediatricians:

1. The risk of suicide due to antidepressants was overstated. Subsequent analyses from additional clinical trials comparing suicidal thoughts or behavior between youths taking antidepressants versus placebo have increasingly struggled to find that "signal" related to active drug. Perhaps more importantly, several other studies that have examined actual suicides and/or suicide attempts from large databases have not shown links to the taking of antidepressants and, if anything, have suggested that untreated depression poses a greater risk (BMJ 2014;348:g3596). It is worth repeating that there still has never been an actual suicide in any of the antidepressant trials.

2. The efficacy of antidepressants also was overstated. As people began to examine more closely the issue of suicidal behavior and antidepressants, it became evident that there was much more data on this than was obvious from published studies. Many more trials of depression and antidepressants were performed, usually funded by pharmaceutical companies, and many of these trials did not show that antidepressants were superior to placebo (N. Engl. J. Med. 2008;358:252-60). As opposed to the positive trials, however, the negative ones tended not to be published or featured. Overall, it seems that about 60% of depressed children and adolescents respond to antidepressant medication, compared with 50% who respond to placebo.

3. The prescribing of antidepressants is making a comeback. After the 2004 warnings, the number of antidepressant prescriptions dropped. Since around 2008, however, the rate of antidepressant prescribing has increased again, although not at 2004 levels, according to some studies.

4. Antidepressants don’t work by fixing a serotonin "chemical imbalance." Although it is true that antidepressants result in more serotonin being available in brain synapses acutely, depression is not caused by a simple serotonin deficit. Medications likely work by changing the expression of certain genes that relate to how strongly particular brain pathways are connected. This process may explain why antidepressants take time to be effective.

5. Antidepressants actually work better for youths with anxiety rather than depression. More promising results with antidepressants have been found for children with anxiety disorder and obsessive-compulsive disorder (N. Engl. J. Med. 2008;359:2753-66). Although cognitive-behavior therapy remains the recommended first-line intervention for children with anxiety disorders, antidepressants have been shown to be effective both alone and in combination with cognitive-behavior therapy.

There is still much to learn. Children and adolescents who are extremely irritable, unmotivated, and at times suicidal are a diverse group of people whose difficulties can arise from many factors that deserve investigation. When it comes to antidepressants, it appears that both the amount of risk and the amount of benefit associated with this class of medications may be less than what was believed a decade ago.

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. Follow him on Twitter @pedipsych. Dr. Rettew said he had no financial disclosures relevant to this article.

Ten years ago, the Food and Drug Administration required that all antidepressants carry a severe black box warning to alert prescribers to the possibility that these medications could cause worsening suicidal thoughts and behavior. A decade later, this issue had faded from the public eye and the media headlines. Nevertheless, research into their use has continued, and antidepressants continue to be prescribed. Have things changed since all the attention in the past? The results may be surprising.

Although there are undoubtedly different views, here is my summary of the five key points with direct implications for pediatricians:

1. The risk of suicide due to antidepressants was overstated. Subsequent analyses from additional clinical trials comparing suicidal thoughts or behavior between youths taking antidepressants versus placebo have increasingly struggled to find that "signal" related to active drug. Perhaps more importantly, several other studies that have examined actual suicides and/or suicide attempts from large databases have not shown links to the taking of antidepressants and, if anything, have suggested that untreated depression poses a greater risk (BMJ 2014;348:g3596). It is worth repeating that there still has never been an actual suicide in any of the antidepressant trials.

2. The efficacy of antidepressants also was overstated. As people began to examine more closely the issue of suicidal behavior and antidepressants, it became evident that there was much more data on this than was obvious from published studies. Many more trials of depression and antidepressants were performed, usually funded by pharmaceutical companies, and many of these trials did not show that antidepressants were superior to placebo (N. Engl. J. Med. 2008;358:252-60). As opposed to the positive trials, however, the negative ones tended not to be published or featured. Overall, it seems that about 60% of depressed children and adolescents respond to antidepressant medication, compared with 50% who respond to placebo.

3. The prescribing of antidepressants is making a comeback. After the 2004 warnings, the number of antidepressant prescriptions dropped. Since around 2008, however, the rate of antidepressant prescribing has increased again, although not at 2004 levels, according to some studies.

4. Antidepressants don’t work by fixing a serotonin "chemical imbalance." Although it is true that antidepressants result in more serotonin being available in brain synapses acutely, depression is not caused by a simple serotonin deficit. Medications likely work by changing the expression of certain genes that relate to how strongly particular brain pathways are connected. This process may explain why antidepressants take time to be effective.

5. Antidepressants actually work better for youths with anxiety rather than depression. More promising results with antidepressants have been found for children with anxiety disorder and obsessive-compulsive disorder (N. Engl. J. Med. 2008;359:2753-66). Although cognitive-behavior therapy remains the recommended first-line intervention for children with anxiety disorders, antidepressants have been shown to be effective both alone and in combination with cognitive-behavior therapy.

There is still much to learn. Children and adolescents who are extremely irritable, unmotivated, and at times suicidal are a diverse group of people whose difficulties can arise from many factors that deserve investigation. When it comes to antidepressants, it appears that both the amount of risk and the amount of benefit associated with this class of medications may be less than what was believed a decade ago.

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. Follow him on Twitter @pedipsych. Dr. Rettew said he had no financial disclosures relevant to this article.

Ten years ago, the Food and Drug Administration required that all antidepressants carry a severe black box warning to alert prescribers to the possibility that these medications could cause worsening suicidal thoughts and behavior. A decade later, this issue had faded from the public eye and the media headlines. Nevertheless, research into their use has continued, and antidepressants continue to be prescribed. Have things changed since all the attention in the past? The results may be surprising.

Although there are undoubtedly different views, here is my summary of the five key points with direct implications for pediatricians:

1. The risk of suicide due to antidepressants was overstated. Subsequent analyses from additional clinical trials comparing suicidal thoughts or behavior between youths taking antidepressants versus placebo have increasingly struggled to find that "signal" related to active drug. Perhaps more importantly, several other studies that have examined actual suicides and/or suicide attempts from large databases have not shown links to the taking of antidepressants and, if anything, have suggested that untreated depression poses a greater risk (BMJ 2014;348:g3596). It is worth repeating that there still has never been an actual suicide in any of the antidepressant trials.

2. The efficacy of antidepressants also was overstated. As people began to examine more closely the issue of suicidal behavior and antidepressants, it became evident that there was much more data on this than was obvious from published studies. Many more trials of depression and antidepressants were performed, usually funded by pharmaceutical companies, and many of these trials did not show that antidepressants were superior to placebo (N. Engl. J. Med. 2008;358:252-60). As opposed to the positive trials, however, the negative ones tended not to be published or featured. Overall, it seems that about 60% of depressed children and adolescents respond to antidepressant medication, compared with 50% who respond to placebo.

3. The prescribing of antidepressants is making a comeback. After the 2004 warnings, the number of antidepressant prescriptions dropped. Since around 2008, however, the rate of antidepressant prescribing has increased again, although not at 2004 levels, according to some studies.

4. Antidepressants don’t work by fixing a serotonin "chemical imbalance." Although it is true that antidepressants result in more serotonin being available in brain synapses acutely, depression is not caused by a simple serotonin deficit. Medications likely work by changing the expression of certain genes that relate to how strongly particular brain pathways are connected. This process may explain why antidepressants take time to be effective.

5. Antidepressants actually work better for youths with anxiety rather than depression. More promising results with antidepressants have been found for children with anxiety disorder and obsessive-compulsive disorder (N. Engl. J. Med. 2008;359:2753-66). Although cognitive-behavior therapy remains the recommended first-line intervention for children with anxiety disorders, antidepressants have been shown to be effective both alone and in combination with cognitive-behavior therapy.

There is still much to learn. Children and adolescents who are extremely irritable, unmotivated, and at times suicidal are a diverse group of people whose difficulties can arise from many factors that deserve investigation. When it comes to antidepressants, it appears that both the amount of risk and the amount of benefit associated with this class of medications may be less than what was believed a decade ago.

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. Follow him on Twitter @pedipsych. Dr. Rettew said he had no financial disclosures relevant to this article.

Case summary

Dylan is a bright and lively 10-year-old boy who has always been energetic and passionate. His parents have celebrated his exuberance but now have become concerned that there is "something more," after his teacher has needed to remove him from class for several episodes of impulsive and disruptive behavior. Further history reveals that, compared with his classmates, he can be quite distractible and often needs a lot of prompting and redirection to complete his work. Dylan is an intelligent child who has always managed to do well in school despite some longstanding challenges with attention. His performance has slipped somewhat as the academic load increases, although not to the point that he is in jeopardy of being held back.

At home, Dylan enjoys playing outside but also is drawn to video games, an activity that seems to hold his attention well. His parents get frustrated with needing to repeat requests several times and having to remind him to be quieter in the house.

Discussion

Attention-deficit/hyperactivity disorder, like all other psychiatric disorders, is defined in binary terms as being present or not-present. Nonetheless, it has become abundantly clear from research studies that the symptoms exist dimensionally and are normally distributed in a manner such as height. As such, diagnosing ADHD is analogous to diagnosing someone as being tall. Given this reality, how does a clinician figure out when a child really "has" a disorder, versus the behavior being "just" part of normal behavior?

All of the diagnostic criteria for ADHD include behaviors that at age-appropriate levels are considered completely normal. To qualify as a symptom that is present, the behaviors have to occur "often" and be inappropriate to the child’s developmental level. These subjective judgments about moving targets make drawing the line difficult for clinicians. Most children are well within normal limits and others are clearly beyond them, yet that leaves a sizable group somewhere in that middle "gray zone."

Making matters more complicated is the increasing but still insufficient evidence suggesting that this dimensionality exists when it comes to the underlying neurobiology of ADHD as well. In other words, the genes, environmental factors, brain regions, neurotransmitters, etc., that determine why a child has an average attention span or activity level are the same ones involved in ADHD. Such a revelation, however, in no way should be interpreted as ADHD being not "real," any more than other dimensional nonpsychiatric conditions (hypertension, hyperlipidemia).

This continuum of behaviors, however, does present a real diagnostic challenge. The inconvenient reality is that there really may not be any "true" rate of ADHD at 5%, 7%, or more recently, 11%. Many people make much of assessing whether or not there is associated impairment with the behaviors, but the truth of the matter is that impairment itself is dimensional.

Thus, we need to appreciate the complexities and limitations of this challenging diagnosis without throwing up our hands in frustration and giving up. After all, these problems can get significantly better with treatment. Here are a few tips to consider.

1. In making an ADHD diagnosis, use quantitative rating scales that appreciate this dimensional nature. Ideally, these instruments should be standardized by age and sex so that, for example, scores of 8-year-old boys can be compared to those of other 8-year-old boys. Don’t feel compelled to come up with a diagnosis on the spot if this procedure takes a little time in getting input from multiple people (parents, teachers, self-report).

2. Don’t stop investigating just because you arrive at an ADHD diagnosis. There are many factors that can result in a child struggling with these behaviors. Poor sleep, excessive screen time, inadequate nutrition, suboptimal parenting practices, exposures to lead and other substances, and lack of exercise are some factors that can underlie these problems. Correcting them can often make a big difference and in some cases can obviate the need for medication.

3. Approach a dimensional diagnosis with dimensional treatment. Just as many patients with borderline levels of hypertension or borderline glucose levels might be recommended to try nonpharmacological interventions first, the same principle can be applied to ADHD. Parent behavioral management, skills training, and addressing potential causes or exacerbating causes described in No. 2 can all provide important benefits.

The bottom line here, in my view, is to appreciate and respect the inherent blurriness of these boundaries without it leading to clinical paralysis. Children who struggle with inattention and hyperactivity are well known to be at risk for a variety of negative outcomes. Pediatricians have a large number of options to help these children that have been shown to be effective and can be individually tailored to each specific case.

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. Follow him on Twitter @pedipsych.

Case summary

Dylan is a bright and lively 10-year-old boy who has always been energetic and passionate. His parents have celebrated his exuberance but now have become concerned that there is "something more," after his teacher has needed to remove him from class for several episodes of impulsive and disruptive behavior. Further history reveals that, compared with his classmates, he can be quite distractible and often needs a lot of prompting and redirection to complete his work. Dylan is an intelligent child who has always managed to do well in school despite some longstanding challenges with attention. His performance has slipped somewhat as the academic load increases, although not to the point that he is in jeopardy of being held back.

At home, Dylan enjoys playing outside but also is drawn to video games, an activity that seems to hold his attention well. His parents get frustrated with needing to repeat requests several times and having to remind him to be quieter in the house.

Discussion

Attention-deficit/hyperactivity disorder, like all other psychiatric disorders, is defined in binary terms as being present or not-present. Nonetheless, it has become abundantly clear from research studies that the symptoms exist dimensionally and are normally distributed in a manner such as height. As such, diagnosing ADHD is analogous to diagnosing someone as being tall. Given this reality, how does a clinician figure out when a child really "has" a disorder, versus the behavior being "just" part of normal behavior?

All of the diagnostic criteria for ADHD include behaviors that at age-appropriate levels are considered completely normal. To qualify as a symptom that is present, the behaviors have to occur "often" and be inappropriate to the child’s developmental level. These subjective judgments about moving targets make drawing the line difficult for clinicians. Most children are well within normal limits and others are clearly beyond them, yet that leaves a sizable group somewhere in that middle "gray zone."

Making matters more complicated is the increasing but still insufficient evidence suggesting that this dimensionality exists when it comes to the underlying neurobiology of ADHD as well. In other words, the genes, environmental factors, brain regions, neurotransmitters, etc., that determine why a child has an average attention span or activity level are the same ones involved in ADHD. Such a revelation, however, in no way should be interpreted as ADHD being not "real," any more than other dimensional nonpsychiatric conditions (hypertension, hyperlipidemia).

This continuum of behaviors, however, does present a real diagnostic challenge. The inconvenient reality is that there really may not be any "true" rate of ADHD at 5%, 7%, or more recently, 11%. Many people make much of assessing whether or not there is associated impairment with the behaviors, but the truth of the matter is that impairment itself is dimensional.

Thus, we need to appreciate the complexities and limitations of this challenging diagnosis without throwing up our hands in frustration and giving up. After all, these problems can get significantly better with treatment. Here are a few tips to consider.

1. In making an ADHD diagnosis, use quantitative rating scales that appreciate this dimensional nature. Ideally, these instruments should be standardized by age and sex so that, for example, scores of 8-year-old boys can be compared to those of other 8-year-old boys. Don’t feel compelled to come up with a diagnosis on the spot if this procedure takes a little time in getting input from multiple people (parents, teachers, self-report).

2. Don’t stop investigating just because you arrive at an ADHD diagnosis. There are many factors that can result in a child struggling with these behaviors. Poor sleep, excessive screen time, inadequate nutrition, suboptimal parenting practices, exposures to lead and other substances, and lack of exercise are some factors that can underlie these problems. Correcting them can often make a big difference and in some cases can obviate the need for medication.

3. Approach a dimensional diagnosis with dimensional treatment. Just as many patients with borderline levels of hypertension or borderline glucose levels might be recommended to try nonpharmacological interventions first, the same principle can be applied to ADHD. Parent behavioral management, skills training, and addressing potential causes or exacerbating causes described in No. 2 can all provide important benefits.

The bottom line here, in my view, is to appreciate and respect the inherent blurriness of these boundaries without it leading to clinical paralysis. Children who struggle with inattention and hyperactivity are well known to be at risk for a variety of negative outcomes. Pediatricians have a large number of options to help these children that have been shown to be effective and can be individually tailored to each specific case.

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. Follow him on Twitter @pedipsych.

Case summary

Dylan is a bright and lively 10-year-old boy who has always been energetic and passionate. His parents have celebrated his exuberance but now have become concerned that there is "something more," after his teacher has needed to remove him from class for several episodes of impulsive and disruptive behavior. Further history reveals that, compared with his classmates, he can be quite distractible and often needs a lot of prompting and redirection to complete his work. Dylan is an intelligent child who has always managed to do well in school despite some longstanding challenges with attention. His performance has slipped somewhat as the academic load increases, although not to the point that he is in jeopardy of being held back.

At home, Dylan enjoys playing outside but also is drawn to video games, an activity that seems to hold his attention well. His parents get frustrated with needing to repeat requests several times and having to remind him to be quieter in the house.

Discussion

Attention-deficit/hyperactivity disorder, like all other psychiatric disorders, is defined in binary terms as being present or not-present. Nonetheless, it has become abundantly clear from research studies that the symptoms exist dimensionally and are normally distributed in a manner such as height. As such, diagnosing ADHD is analogous to diagnosing someone as being tall. Given this reality, how does a clinician figure out when a child really "has" a disorder, versus the behavior being "just" part of normal behavior?

All of the diagnostic criteria for ADHD include behaviors that at age-appropriate levels are considered completely normal. To qualify as a symptom that is present, the behaviors have to occur "often" and be inappropriate to the child’s developmental level. These subjective judgments about moving targets make drawing the line difficult for clinicians. Most children are well within normal limits and others are clearly beyond them, yet that leaves a sizable group somewhere in that middle "gray zone."

Making matters more complicated is the increasing but still insufficient evidence suggesting that this dimensionality exists when it comes to the underlying neurobiology of ADHD as well. In other words, the genes, environmental factors, brain regions, neurotransmitters, etc., that determine why a child has an average attention span or activity level are the same ones involved in ADHD. Such a revelation, however, in no way should be interpreted as ADHD being not "real," any more than other dimensional nonpsychiatric conditions (hypertension, hyperlipidemia).

This continuum of behaviors, however, does present a real diagnostic challenge. The inconvenient reality is that there really may not be any "true" rate of ADHD at 5%, 7%, or more recently, 11%. Many people make much of assessing whether or not there is associated impairment with the behaviors, but the truth of the matter is that impairment itself is dimensional.

Thus, we need to appreciate the complexities and limitations of this challenging diagnosis without throwing up our hands in frustration and giving up. After all, these problems can get significantly better with treatment. Here are a few tips to consider.

1. In making an ADHD diagnosis, use quantitative rating scales that appreciate this dimensional nature. Ideally, these instruments should be standardized by age and sex so that, for example, scores of 8-year-old boys can be compared to those of other 8-year-old boys. Don’t feel compelled to come up with a diagnosis on the spot if this procedure takes a little time in getting input from multiple people (parents, teachers, self-report).

2. Don’t stop investigating just because you arrive at an ADHD diagnosis. There are many factors that can result in a child struggling with these behaviors. Poor sleep, excessive screen time, inadequate nutrition, suboptimal parenting practices, exposures to lead and other substances, and lack of exercise are some factors that can underlie these problems. Correcting them can often make a big difference and in some cases can obviate the need for medication.

3. Approach a dimensional diagnosis with dimensional treatment. Just as many patients with borderline levels of hypertension or borderline glucose levels might be recommended to try nonpharmacological interventions first, the same principle can be applied to ADHD. Parent behavioral management, skills training, and addressing potential causes or exacerbating causes described in No. 2 can all provide important benefits.

The bottom line here, in my view, is to appreciate and respect the inherent blurriness of these boundaries without it leading to clinical paralysis. Children who struggle with inattention and hyperactivity are well known to be at risk for a variety of negative outcomes. Pediatricians have a large number of options to help these children that have been shown to be effective and can be individually tailored to each specific case.

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. Follow him on Twitter @pedipsych.

Case summary

Owen, an 8-year-old boy, is brought to his pediatrician by his mother. She has noticed that Owen is spending increasing amounts of time doing some repetitive behaviors such as counting to himself and needing to tap particular objects a specified number of times. Certain numbers seem to have special significance, and Owen has expressed some vague concern that something bad could happen if he does not do these behaviors. The rituals are starting to impact his schoolwork, as he often can get "stuck" during assignments. The mother is aware that many kids have some superstitions and wants to know if this is "something more."

Discussion

Obsessive-compulsive disorder (OCD) is a relatively common condition that can respond quite well to treatment. This case example outlines an approach that pediatricians can take to its diagnosis and management in a primary care setting.

Diagnosis

The diagnosis of OCD, according to DSM-5, requires the presence of distressing or impairing obsessions or compulsions. The definition didn’t change much from DSM-IV. Obsessions in children can revolve around things like contamination, disturbing thoughts of harm coming to others, sexual thoughts, or special numbers or words. Compulsions can include rituals with washing, checking, counting, arranging, and hoarding, among other behaviors.

When beginning to evaluate for possible OCD, it is important to talk to both the child and the parent, as it is common for parents to be unaware of the extent of the problem. An instrument called the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) is considered to be the standard in the quantitative assessment of OCD. The rating scale and checklist are easy to administer and appear to be in the public domain.

While the diagnosis is often fairly straightforward, it does take some time, and pediatricians should feel comfortable with the idea of not trying to do everything in one visit. Instead, consider scheduling another visit or two to obtain more time to do a careful assessment. During this evaluation, a couple questions are good to keep in mind.

1. Was a diagnosis of an autistic spectrum disorder missed? OCD behaviors are extremely common among children with autistic spectrum disorders. It might be worthwhile to make sure that the developmental history (pointing, babbling, social smile, odd mannerisms) doesn’t suggest the possibility of autism.

2. Could this be a case of a PANS? There remains discussion about the possibility of an autoimmune origin to some children with OCD. The previous term of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS) has been changed to Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) to reflect a broader profile of behaviors and possible infectious triggers. While the idea remains debated in some circles, there may be value in making sure that there is not an infection lurking that should be treated.

Pearl

When querying about particular OCD symptoms, go through a list with a patient (such as provided on the CY-BOCS), and don’t rely on self-disclosure, as some symptoms, such as seeing violent or sexual images, can be quite disturbing to the child, who often won’t bring them up on his or her own.

Treatment

The recommended first-line treatment for OCD is a type of cognitive-behavioral therapy called exposure and response prevention (ERP). It is a structured form of therapy that involves patients unlearning the association that rituals are necessary in order for their fears not to be realized. While effective, the challenge is often finding a therapist with this type of training.

In many cases, it is reasonable to wait on medication treatment until after a course of ERP has been tried. For more severe cases, it is also reasonable to use both psychotherapy and medications at the same time. Some patients will say that the medication helps them do the work required in therapy.

When it comes to medications, there are a number of selective serotonin reuptake inhibitors (SSRIs) that have shown to be effective and have Food and Drug Administration approvals for pediatric OCD (for some reason that escapes me, many pharmaceutical companies have sought FDA approval for OCD and not other child psychiatric disorders). Fluoxetine, sertraline, and fluvoxamine all have FDA approval, in addition to the tricyclic clomipramine for use in refractory cases. As in all children, starting at a low dose is usually prudent (5-10 mg of fluoxetine, 12.5-25 mg of sertraline), but with OCD higher doses are often required for maximal response (more than 100 mg of sertraline or 40 mg of fluoxetine, depending on the patient’s age, size, and tolerance). It is also important to remember that the suicide warning present for the SSRIs also applies to children with anxiety disorders.

An overall treatment plan for an OCD patient, according to a previously discussed model for mental health treatment, might look like the following:

• Education. Discuss diagnosis of OCD with children and family. Let them know about support organizations such as the OC Foundation.

• Individual therapy. Referral to a cognitive-behavioral therapist for exposure and response prevention.

• Parents. Screen parents for their own OCD or other psychopathology and refer if positive. Parental guidance regarding how best to approach the child will occur within cognitive-behavioral therapy.

• School. (This is indicated if the child’s symptoms are affecting school.) Consider a request for evaluation at school to assess the need for a 504 or individualized education plan (IEP).

• Environment. Discuss minimizing OCD triggers at home.

• Medications. Begin fluoxetine 5 mg per day. Informed consent is important, including suicide warnings. (You might delay this step if a therapist is available to begin ERP first.)

• Follow-up should take place in 2 weeks, with a possible increase of fluoxetine to 10 mg and reassessment with CY-BOCS.

When to consult? Many patients with relatively uncomplicated OCD can be effectively managed in the primary care setting. Consultation may be useful for instances of poor treatment response, other occurring psychiatric disorders (such as autism, attention-deficit/hyperactivity disorder), family conflict and resistance, or diagnostic uncertainty with other conditions, such as a psychotic disorder.

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. He is the author of "Child Temperament: New Thinking About the Boundary between Traits and Illness." Follow him on Twitter @pedipsych.

Case summary

Owen, an 8-year-old boy, is brought to his pediatrician by his mother. She has noticed that Owen is spending increasing amounts of time doing some repetitive behaviors such as counting to himself and needing to tap particular objects a specified number of times. Certain numbers seem to have special significance, and Owen has expressed some vague concern that something bad could happen if he does not do these behaviors. The rituals are starting to impact his schoolwork, as he often can get "stuck" during assignments. The mother is aware that many kids have some superstitions and wants to know if this is "something more."

Discussion

Obsessive-compulsive disorder (OCD) is a relatively common condition that can respond quite well to treatment. This case example outlines an approach that pediatricians can take to its diagnosis and management in a primary care setting.

Diagnosis

The diagnosis of OCD, according to DSM-5, requires the presence of distressing or impairing obsessions or compulsions. The definition didn’t change much from DSM-IV. Obsessions in children can revolve around things like contamination, disturbing thoughts of harm coming to others, sexual thoughts, or special numbers or words. Compulsions can include rituals with washing, checking, counting, arranging, and hoarding, among other behaviors.

When beginning to evaluate for possible OCD, it is important to talk to both the child and the parent, as it is common for parents to be unaware of the extent of the problem. An instrument called the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) is considered to be the standard in the quantitative assessment of OCD. The rating scale and checklist are easy to administer and appear to be in the public domain.

While the diagnosis is often fairly straightforward, it does take some time, and pediatricians should feel comfortable with the idea of not trying to do everything in one visit. Instead, consider scheduling another visit or two to obtain more time to do a careful assessment. During this evaluation, a couple questions are good to keep in mind.

1. Was a diagnosis of an autistic spectrum disorder missed? OCD behaviors are extremely common among children with autistic spectrum disorders. It might be worthwhile to make sure that the developmental history (pointing, babbling, social smile, odd mannerisms) doesn’t suggest the possibility of autism.

2. Could this be a case of a PANS? There remains discussion about the possibility of an autoimmune origin to some children with OCD. The previous term of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS) has been changed to Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) to reflect a broader profile of behaviors and possible infectious triggers. While the idea remains debated in some circles, there may be value in making sure that there is not an infection lurking that should be treated.

Pearl

When querying about particular OCD symptoms, go through a list with a patient (such as provided on the CY-BOCS), and don’t rely on self-disclosure, as some symptoms, such as seeing violent or sexual images, can be quite disturbing to the child, who often won’t bring them up on his or her own.

Treatment

The recommended first-line treatment for OCD is a type of cognitive-behavioral therapy called exposure and response prevention (ERP). It is a structured form of therapy that involves patients unlearning the association that rituals are necessary in order for their fears not to be realized. While effective, the challenge is often finding a therapist with this type of training.

In many cases, it is reasonable to wait on medication treatment until after a course of ERP has been tried. For more severe cases, it is also reasonable to use both psychotherapy and medications at the same time. Some patients will say that the medication helps them do the work required in therapy.

When it comes to medications, there are a number of selective serotonin reuptake inhibitors (SSRIs) that have shown to be effective and have Food and Drug Administration approvals for pediatric OCD (for some reason that escapes me, many pharmaceutical companies have sought FDA approval for OCD and not other child psychiatric disorders). Fluoxetine, sertraline, and fluvoxamine all have FDA approval, in addition to the tricyclic clomipramine for use in refractory cases. As in all children, starting at a low dose is usually prudent (5-10 mg of fluoxetine, 12.5-25 mg of sertraline), but with OCD higher doses are often required for maximal response (more than 100 mg of sertraline or 40 mg of fluoxetine, depending on the patient’s age, size, and tolerance). It is also important to remember that the suicide warning present for the SSRIs also applies to children with anxiety disorders.

An overall treatment plan for an OCD patient, according to a previously discussed model for mental health treatment, might look like the following:

• Education. Discuss diagnosis of OCD with children and family. Let them know about support organizations such as the OC Foundation.

• Individual therapy. Referral to a cognitive-behavioral therapist for exposure and response prevention.

• Parents. Screen parents for their own OCD or other psychopathology and refer if positive. Parental guidance regarding how best to approach the child will occur within cognitive-behavioral therapy.

• School. (This is indicated if the child’s symptoms are affecting school.) Consider a request for evaluation at school to assess the need for a 504 or individualized education plan (IEP).

• Environment. Discuss minimizing OCD triggers at home.

• Medications. Begin fluoxetine 5 mg per day. Informed consent is important, including suicide warnings. (You might delay this step if a therapist is available to begin ERP first.)

• Follow-up should take place in 2 weeks, with a possible increase of fluoxetine to 10 mg and reassessment with CY-BOCS.

When to consult? Many patients with relatively uncomplicated OCD can be effectively managed in the primary care setting. Consultation may be useful for instances of poor treatment response, other occurring psychiatric disorders (such as autism, attention-deficit/hyperactivity disorder), family conflict and resistance, or diagnostic uncertainty with other conditions, such as a psychotic disorder.

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. He is the author of "Child Temperament: New Thinking About the Boundary between Traits and Illness." Follow him on Twitter @pedipsych.

Case summary

Owen, an 8-year-old boy, is brought to his pediatrician by his mother. She has noticed that Owen is spending increasing amounts of time doing some repetitive behaviors such as counting to himself and needing to tap particular objects a specified number of times. Certain numbers seem to have special significance, and Owen has expressed some vague concern that something bad could happen if he does not do these behaviors. The rituals are starting to impact his schoolwork, as he often can get "stuck" during assignments. The mother is aware that many kids have some superstitions and wants to know if this is "something more."

Discussion

Obsessive-compulsive disorder (OCD) is a relatively common condition that can respond quite well to treatment. This case example outlines an approach that pediatricians can take to its diagnosis and management in a primary care setting.

Diagnosis

The diagnosis of OCD, according to DSM-5, requires the presence of distressing or impairing obsessions or compulsions. The definition didn’t change much from DSM-IV. Obsessions in children can revolve around things like contamination, disturbing thoughts of harm coming to others, sexual thoughts, or special numbers or words. Compulsions can include rituals with washing, checking, counting, arranging, and hoarding, among other behaviors.

When beginning to evaluate for possible OCD, it is important to talk to both the child and the parent, as it is common for parents to be unaware of the extent of the problem. An instrument called the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) is considered to be the standard in the quantitative assessment of OCD. The rating scale and checklist are easy to administer and appear to be in the public domain.

While the diagnosis is often fairly straightforward, it does take some time, and pediatricians should feel comfortable with the idea of not trying to do everything in one visit. Instead, consider scheduling another visit or two to obtain more time to do a careful assessment. During this evaluation, a couple questions are good to keep in mind.

1. Was a diagnosis of an autistic spectrum disorder missed? OCD behaviors are extremely common among children with autistic spectrum disorders. It might be worthwhile to make sure that the developmental history (pointing, babbling, social smile, odd mannerisms) doesn’t suggest the possibility of autism.

2. Could this be a case of a PANS? There remains discussion about the possibility of an autoimmune origin to some children with OCD. The previous term of Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS) has been changed to Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) to reflect a broader profile of behaviors and possible infectious triggers. While the idea remains debated in some circles, there may be value in making sure that there is not an infection lurking that should be treated.

Pearl

When querying about particular OCD symptoms, go through a list with a patient (such as provided on the CY-BOCS), and don’t rely on self-disclosure, as some symptoms, such as seeing violent or sexual images, can be quite disturbing to the child, who often won’t bring them up on his or her own.

Treatment

The recommended first-line treatment for OCD is a type of cognitive-behavioral therapy called exposure and response prevention (ERP). It is a structured form of therapy that involves patients unlearning the association that rituals are necessary in order for their fears not to be realized. While effective, the challenge is often finding a therapist with this type of training.

In many cases, it is reasonable to wait on medication treatment until after a course of ERP has been tried. For more severe cases, it is also reasonable to use both psychotherapy and medications at the same time. Some patients will say that the medication helps them do the work required in therapy.

When it comes to medications, there are a number of selective serotonin reuptake inhibitors (SSRIs) that have shown to be effective and have Food and Drug Administration approvals for pediatric OCD (for some reason that escapes me, many pharmaceutical companies have sought FDA approval for OCD and not other child psychiatric disorders). Fluoxetine, sertraline, and fluvoxamine all have FDA approval, in addition to the tricyclic clomipramine for use in refractory cases. As in all children, starting at a low dose is usually prudent (5-10 mg of fluoxetine, 12.5-25 mg of sertraline), but with OCD higher doses are often required for maximal response (more than 100 mg of sertraline or 40 mg of fluoxetine, depending on the patient’s age, size, and tolerance). It is also important to remember that the suicide warning present for the SSRIs also applies to children with anxiety disorders.

An overall treatment plan for an OCD patient, according to a previously discussed model for mental health treatment, might look like the following:

• Education. Discuss diagnosis of OCD with children and family. Let them know about support organizations such as the OC Foundation.

• Individual therapy. Referral to a cognitive-behavioral therapist for exposure and response prevention.

• Parents. Screen parents for their own OCD or other psychopathology and refer if positive. Parental guidance regarding how best to approach the child will occur within cognitive-behavioral therapy.

• School. (This is indicated if the child’s symptoms are affecting school.) Consider a request for evaluation at school to assess the need for a 504 or individualized education plan (IEP).

• Environment. Discuss minimizing OCD triggers at home.

• Medications. Begin fluoxetine 5 mg per day. Informed consent is important, including suicide warnings. (You might delay this step if a therapist is available to begin ERP first.)

• Follow-up should take place in 2 weeks, with a possible increase of fluoxetine to 10 mg and reassessment with CY-BOCS.

When to consult? Many patients with relatively uncomplicated OCD can be effectively managed in the primary care setting. Consultation may be useful for instances of poor treatment response, other occurring psychiatric disorders (such as autism, attention-deficit/hyperactivity disorder), family conflict and resistance, or diagnostic uncertainty with other conditions, such as a psychotic disorder.

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. He is the author of "Child Temperament: New Thinking About the Boundary between Traits and Illness." Follow him on Twitter @pedipsych.

Doctor examining a child

Credit: Logan Tuttle

Weekend hospitalization can have its pitfalls, according to a study of pediatric patients newly diagnosed with leukemia.

Patients who were admitted to the hospital over the weekend had a longer length of stay, a slightly longer wait to start chemotherapy, and a higher risk for respiratory failure than patients admitted during the week.

Elizabeth K. Goodman, of the Children’s Hospital of Philadelphia, and her colleagues reported these results in JAMA Pediatrics.

The team examined adverse clinical outcomes associated with a weekend admission for the first hospitalization of pediatric patients newly diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).

The researchers used data from the Pediatric Health Information System database, which included patients admitted to 43 children’s hospitals from 1999 through 2011.

There were 10,720 patients with ALL and 1323 with AML. Roughly 17% of these patients (n=2009) were admitted to the hospital on the weekend.

Patients hospitalized on the weekend were similar to those hospitalized during the week with regard to disease type and sex. However, weekend admissions had significantly higher percentages of patients who were younger than 5 years of age, of nonwhite race/ethnicity, and publicly insured.

Patients admitted on the weekend were also more likely to be severely ill. They were significantly more likely to require ICU-level care within the first 2 days of admission (4.8% vs 3.1%, P<0.001).

An unadjusted analysis showed that inpatient mortality was similar for patients admitted to the hospital during the week and on the weekend (0.8% and 1.0%, respectively).

However, patients admitted on the weekend had a significantly longer mean hospital stay (17.8 vs 15.8 days, P<0.001) and a longer mean wait time for chemotherapy (3.9 vs 3.5 days, P<0.001).

Patients admitted on the weekend also had an increased risk of cardiovascular failure (6.4% vs 5.0%, P=0.01), respiratory failure (8.5% vs 5.7%, P<0.001), and andrenal failure (10.2% vs 8.3%, P=0.01).

However, some of these results changed when the researchers adjusted for demographic variables (disease, sex, age, race/ethnicity, and insurance), the presence of severe illness at admission, and hospital-level factors (presence of a fellowship program, Magnet status, percentage of public payers per admissions per hospital per year, and number of oncology admissions per hospital per year).

In the adjusted analysis, weekend admission remained associated with an increase in the length of hospital stay (1.4 days) and an increase in the time to chemotherapy (0.4 days).

Weekend admission also remained associated with an increased risk of respiratory failure (odds ratio, 1.5), but it was no longer associated with an increased risk of cardiovascular or renal failure.

The researchers said these findings highlight a potential area for improvement in patient care and cost reduction. Increasing weekend resources could help reduce patients’ length of stay and ensure they receive comprehensive care.

On the other hand, it might also raise hospital expenditures without decreasing negative outcomes. So additional research is needed to determine the most clinically and cost-effective combination of hospital resources to reduce the length of stay and improve outcomes for pediatric leukemia patients.

An editorial related to this study is available in JAMA Pediatrics.

Doctor examining a child

Credit: Logan Tuttle

Weekend hospitalization can have its pitfalls, according to a study of pediatric patients newly diagnosed with leukemia.

Patients who were admitted to the hospital over the weekend had a longer length of stay, a slightly longer wait to start chemotherapy, and a higher risk for respiratory failure than patients admitted during the week.

Elizabeth K. Goodman, of the Children’s Hospital of Philadelphia, and her colleagues reported these results in JAMA Pediatrics.

The team examined adverse clinical outcomes associated with a weekend admission for the first hospitalization of pediatric patients newly diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).

The researchers used data from the Pediatric Health Information System database, which included patients admitted to 43 children’s hospitals from 1999 through 2011.

There were 10,720 patients with ALL and 1323 with AML. Roughly 17% of these patients (n=2009) were admitted to the hospital on the weekend.

Patients hospitalized on the weekend were similar to those hospitalized during the week with regard to disease type and sex. However, weekend admissions had significantly higher percentages of patients who were younger than 5 years of age, of nonwhite race/ethnicity, and publicly insured.

Patients admitted on the weekend were also more likely to be severely ill. They were significantly more likely to require ICU-level care within the first 2 days of admission (4.8% vs 3.1%, P<0.001).

An unadjusted analysis showed that inpatient mortality was similar for patients admitted to the hospital during the week and on the weekend (0.8% and 1.0%, respectively).

However, patients admitted on the weekend had a significantly longer mean hospital stay (17.8 vs 15.8 days, P<0.001) and a longer mean wait time for chemotherapy (3.9 vs 3.5 days, P<0.001).

Patients admitted on the weekend also had an increased risk of cardiovascular failure (6.4% vs 5.0%, P=0.01), respiratory failure (8.5% vs 5.7%, P<0.001), and andrenal failure (10.2% vs 8.3%, P=0.01).

However, some of these results changed when the researchers adjusted for demographic variables (disease, sex, age, race/ethnicity, and insurance), the presence of severe illness at admission, and hospital-level factors (presence of a fellowship program, Magnet status, percentage of public payers per admissions per hospital per year, and number of oncology admissions per hospital per year).

In the adjusted analysis, weekend admission remained associated with an increase in the length of hospital stay (1.4 days) and an increase in the time to chemotherapy (0.4 days).

Weekend admission also remained associated with an increased risk of respiratory failure (odds ratio, 1.5), but it was no longer associated with an increased risk of cardiovascular or renal failure.

The researchers said these findings highlight a potential area for improvement in patient care and cost reduction. Increasing weekend resources could help reduce patients’ length of stay and ensure they receive comprehensive care.

On the other hand, it might also raise hospital expenditures without decreasing negative outcomes. So additional research is needed to determine the most clinically and cost-effective combination of hospital resources to reduce the length of stay and improve outcomes for pediatric leukemia patients.

An editorial related to this study is available in JAMA Pediatrics.

Doctor examining a child

Credit: Logan Tuttle

Weekend hospitalization can have its pitfalls, according to a study of pediatric patients newly diagnosed with leukemia.

Patients who were admitted to the hospital over the weekend had a longer length of stay, a slightly longer wait to start chemotherapy, and a higher risk for respiratory failure than patients admitted during the week.

Elizabeth K. Goodman, of the Children’s Hospital of Philadelphia, and her colleagues reported these results in JAMA Pediatrics.

The team examined adverse clinical outcomes associated with a weekend admission for the first hospitalization of pediatric patients newly diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).

The researchers used data from the Pediatric Health Information System database, which included patients admitted to 43 children’s hospitals from 1999 through 2011.

There were 10,720 patients with ALL and 1323 with AML. Roughly 17% of these patients (n=2009) were admitted to the hospital on the weekend.

Patients hospitalized on the weekend were similar to those hospitalized during the week with regard to disease type and sex. However, weekend admissions had significantly higher percentages of patients who were younger than 5 years of age, of nonwhite race/ethnicity, and publicly insured.

Patients admitted on the weekend were also more likely to be severely ill. They were significantly more likely to require ICU-level care within the first 2 days of admission (4.8% vs 3.1%, P<0.001).

An unadjusted analysis showed that inpatient mortality was similar for patients admitted to the hospital during the week and on the weekend (0.8% and 1.0%, respectively).

However, patients admitted on the weekend had a significantly longer mean hospital stay (17.8 vs 15.8 days, P<0.001) and a longer mean wait time for chemotherapy (3.9 vs 3.5 days, P<0.001).

Patients admitted on the weekend also had an increased risk of cardiovascular failure (6.4% vs 5.0%, P=0.01), respiratory failure (8.5% vs 5.7%, P<0.001), and andrenal failure (10.2% vs 8.3%, P=0.01).

However, some of these results changed when the researchers adjusted for demographic variables (disease, sex, age, race/ethnicity, and insurance), the presence of severe illness at admission, and hospital-level factors (presence of a fellowship program, Magnet status, percentage of public payers per admissions per hospital per year, and number of oncology admissions per hospital per year).

In the adjusted analysis, weekend admission remained associated with an increase in the length of hospital stay (1.4 days) and an increase in the time to chemotherapy (0.4 days).

Weekend admission also remained associated with an increased risk of respiratory failure (odds ratio, 1.5), but it was no longer associated with an increased risk of cardiovascular or renal failure.

The researchers said these findings highlight a potential area for improvement in patient care and cost reduction. Increasing weekend resources could help reduce patients’ length of stay and ensure they receive comprehensive care.

On the other hand, it might also raise hospital expenditures without decreasing negative outcomes. So additional research is needed to determine the most clinically and cost-effective combination of hospital resources to reduce the length of stay and improve outcomes for pediatric leukemia patients.

An editorial related to this study is available in JAMA Pediatrics.

The US Food and Drug Administration (FDA) has approved eltrombopag (Promacta) for use in patients with severe aplastic anemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST).

Eltrombopag is an oral thrombopoietin receptor agonist that helps to induce the proliferation and differentiation of hematopoietic stem cells to increase blood cell production.

Eltrombopag is already FDA approved to treat patients with chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The drug is also approved to treat thrombocytopenia in patients with chronic hepatitis C to allow for the initiation and maintenance of interferon-based therapy.

The latest FDA approval is based on results from an investigator-sponsored phase 2 study (09-H-0154) conducted by the National Heart, Lung and Blood Institute. Results of this trial were previously published in The New England Journal of Medicine.

Eltrombopag in SAA: Latest trial results

In this study, researchers evaluated eltrombopag in 43 SAA patients who had an insufficient response to at least 1 prior IST and a platelet count of 30 x 10⁹/L or less.

At baseline, the median platelet count was 20 x 10⁹/L, hemoglobin was 8.4 g/dL, the absolute neutrophil count was 0.58 x 10⁹/L, and absolute reticulocyte count was 24.3 x 10⁹/L.

Patients had a median age of 45 years (range, 17 to 77 years), and 56% were male. The majority of patients (84%) received at least 2 prior ISTs.

Patients received eltrombopag at an initial dose of 50 mg once daily for 2 weeks. The dose increased over 2-week periods to a maximum of 150 mg once daily.

The study’s primary endpoint was hematologic response, which was initially assessed after 12 weeks of treatment. Treatment was discontinued after 16 weeks in patients who did not exhibit a hematologic response.

Forty percent of patients (N=17) experienced a hematologic response in at least one lineage—platelets, red blood cells (RBCs), or white blood cells—after week 12.

In the extension phase of the study, 8 patients achieved a multilineage response. Four of these patients subsequently tapered off treatment and maintained the response. The median follow up was 8.1 months (range, 7.2 to 10.6 months).

Ninety-one percent of patients were platelet-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require platelet transfusions for a median of 200 days (range, 8 to 1096 days).

Eighty-six percent of patients were RBC-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require RBC transfusions for a median of 208 days (range, 15 to 1082 days).

The most common adverse events (≥20%) associated with eltrombopag were nausea (33%), fatigue (28%), cough (23%), diarrhea (21%), and headache (21%).

Patients also had bone marrow aspirates evaluated for cytogenetic abnormalities. Eight patients had a new cytogenetic abnormality after treatment, including 5 patients who had complex changes in chromosome 7.

Patients who develop new cytogenetic abnormalities while on eltrombopag may need to be taken off treatment.

Eltrombopag is marketed by GlaxoSmithKline under the brand name Promacta in the US and Revolade in most other countries. For more information on eltrombopag, see the prescribing information.

The US Food and Drug Administration (FDA) has approved eltrombopag (Promacta) for use in patients with severe aplastic anemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST).

Eltrombopag is an oral thrombopoietin receptor agonist that helps to induce the proliferation and differentiation of hematopoietic stem cells to increase blood cell production.

Eltrombopag is already FDA approved to treat patients with chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The drug is also approved to treat thrombocytopenia in patients with chronic hepatitis C to allow for the initiation and maintenance of interferon-based therapy.

The latest FDA approval is based on results from an investigator-sponsored phase 2 study (09-H-0154) conducted by the National Heart, Lung and Blood Institute. Results of this trial were previously published in The New England Journal of Medicine.

Eltrombopag in SAA: Latest trial results

In this study, researchers evaluated eltrombopag in 43 SAA patients who had an insufficient response to at least 1 prior IST and a platelet count of 30 x 10⁹/L or less.

At baseline, the median platelet count was 20 x 10⁹/L, hemoglobin was 8.4 g/dL, the absolute neutrophil count was 0.58 x 10⁹/L, and absolute reticulocyte count was 24.3 x 10⁹/L.

Patients had a median age of 45 years (range, 17 to 77 years), and 56% were male. The majority of patients (84%) received at least 2 prior ISTs.

Patients received eltrombopag at an initial dose of 50 mg once daily for 2 weeks. The dose increased over 2-week periods to a maximum of 150 mg once daily.

The study’s primary endpoint was hematologic response, which was initially assessed after 12 weeks of treatment. Treatment was discontinued after 16 weeks in patients who did not exhibit a hematologic response.

Forty percent of patients (N=17) experienced a hematologic response in at least one lineage—platelets, red blood cells (RBCs), or white blood cells—after week 12.

In the extension phase of the study, 8 patients achieved a multilineage response. Four of these patients subsequently tapered off treatment and maintained the response. The median follow up was 8.1 months (range, 7.2 to 10.6 months).

Ninety-one percent of patients were platelet-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require platelet transfusions for a median of 200 days (range, 8 to 1096 days).

Eighty-six percent of patients were RBC-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require RBC transfusions for a median of 208 days (range, 15 to 1082 days).

The most common adverse events (≥20%) associated with eltrombopag were nausea (33%), fatigue (28%), cough (23%), diarrhea (21%), and headache (21%).

Patients also had bone marrow aspirates evaluated for cytogenetic abnormalities. Eight patients had a new cytogenetic abnormality after treatment, including 5 patients who had complex changes in chromosome 7.

Patients who develop new cytogenetic abnormalities while on eltrombopag may need to be taken off treatment.

Eltrombopag is marketed by GlaxoSmithKline under the brand name Promacta in the US and Revolade in most other countries. For more information on eltrombopag, see the prescribing information.

The US Food and Drug Administration (FDA) has approved eltrombopag (Promacta) for use in patients with severe aplastic anemia (SAA) who have had an insufficient response to immunosuppressive therapy (IST).

Eltrombopag is an oral thrombopoietin receptor agonist that helps to induce the proliferation and differentiation of hematopoietic stem cells to increase blood cell production.

Eltrombopag is already FDA approved to treat patients with chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The drug is also approved to treat thrombocytopenia in patients with chronic hepatitis C to allow for the initiation and maintenance of interferon-based therapy.

The latest FDA approval is based on results from an investigator-sponsored phase 2 study (09-H-0154) conducted by the National Heart, Lung and Blood Institute. Results of this trial were previously published in The New England Journal of Medicine.

Eltrombopag in SAA: Latest trial results

In this study, researchers evaluated eltrombopag in 43 SAA patients who had an insufficient response to at least 1 prior IST and a platelet count of 30 x 10⁹/L or less.

At baseline, the median platelet count was 20 x 10⁹/L, hemoglobin was 8.4 g/dL, the absolute neutrophil count was 0.58 x 10⁹/L, and absolute reticulocyte count was 24.3 x 10⁹/L.

Patients had a median age of 45 years (range, 17 to 77 years), and 56% were male. The majority of patients (84%) received at least 2 prior ISTs.

Patients received eltrombopag at an initial dose of 50 mg once daily for 2 weeks. The dose increased over 2-week periods to a maximum of 150 mg once daily.

The study’s primary endpoint was hematologic response, which was initially assessed after 12 weeks of treatment. Treatment was discontinued after 16 weeks in patients who did not exhibit a hematologic response.

Forty percent of patients (N=17) experienced a hematologic response in at least one lineage—platelets, red blood cells (RBCs), or white blood cells—after week 12.

In the extension phase of the study, 8 patients achieved a multilineage response. Four of these patients subsequently tapered off treatment and maintained the response. The median follow up was 8.1 months (range, 7.2 to 10.6 months).

Ninety-one percent of patients were platelet-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require platelet transfusions for a median of 200 days (range, 8 to 1096 days).

Eighty-six percent of patients were RBC-transfusion-dependent at baseline. Patients who responded to eltrombopag did not require RBC transfusions for a median of 208 days (range, 15 to 1082 days).

The most common adverse events (≥20%) associated with eltrombopag were nausea (33%), fatigue (28%), cough (23%), diarrhea (21%), and headache (21%).

Patients also had bone marrow aspirates evaluated for cytogenetic abnormalities. Eight patients had a new cytogenetic abnormality after treatment, including 5 patients who had complex changes in chromosome 7.

Patients who develop new cytogenetic abnormalities while on eltrombopag may need to be taken off treatment.

Eltrombopag is marketed by GlaxoSmithKline under the brand name Promacta in the US and Revolade in most other countries. For more information on eltrombopag, see the prescribing information.