Literature Review

Using a smartphone or other personal electronic device (PED) to send text messages produces a “reproducible texting rhythm” that can be detected during video-EEG monitoring, according to Mayo Clinic researchers. In a cohort of 129 patients, this texting rhythm was detected in 27 (20.9%) patients. The rhythm existed in 28% of patients with epilepsy and 16% of those with non-epileptic seizures. The unique pattern was not present in patients when they performed independent tasks or when using a cellphone to make audio calls. The investigators concluded that the reproducible text rhythm “represents a novel technology-specific neurophysiological alteration of brain networks” and proposed that “cortical processing in the contemporary brain is uniquely activated by the use of PEDs.”  

Tatum WO, DiCiaccio B, Yelvington KH. Cortical processing during smartphone text messaging. Epilepsy Behav. 2016;59:117-121. 

Using a smartphone or other personal electronic device (PED) to send text messages produces a “reproducible texting rhythm” that can be detected during video-EEG monitoring, according to Mayo Clinic researchers. In a cohort of 129 patients, this texting rhythm was detected in 27 (20.9%) patients. The rhythm existed in 28% of patients with epilepsy and 16% of those with non-epileptic seizures. The unique pattern was not present in patients when they performed independent tasks or when using a cellphone to make audio calls. The investigators concluded that the reproducible text rhythm “represents a novel technology-specific neurophysiological alteration of brain networks” and proposed that “cortical processing in the contemporary brain is uniquely activated by the use of PEDs.”  

Tatum WO, DiCiaccio B, Yelvington KH. Cortical processing during smartphone text messaging. Epilepsy Behav. 2016;59:117-121. 

Using a smartphone or other personal electronic device (PED) to send text messages produces a “reproducible texting rhythm” that can be detected during video-EEG monitoring, according to Mayo Clinic researchers. In a cohort of 129 patients, this texting rhythm was detected in 27 (20.9%) patients. The rhythm existed in 28% of patients with epilepsy and 16% of those with non-epileptic seizures. The unique pattern was not present in patients when they performed independent tasks or when using a cellphone to make audio calls. The investigators concluded that the reproducible text rhythm “represents a novel technology-specific neurophysiological alteration of brain networks” and proposed that “cortical processing in the contemporary brain is uniquely activated by the use of PEDs.”  

Tatum WO, DiCiaccio B, Yelvington KH. Cortical processing during smartphone text messaging. Epilepsy Behav. 2016;59:117-121. 

A cross-sectional data analysis derived from the Epilepsy Birth Control Registry recently found that among nearly 800 patients who were at risk for unintended pregnancy, 69.7% were using effective contraceptive methods, which included hormonal contraceptives, intrauterine devices, tubal ligation, and vasectomy. Despite the high number of patients with epilepsy using what are generally considered highly effective forms of birth control, the efficacy of these methods in this population "remains to be proven" according to researchers from Columbia University and Beth Israel Deaconess Medical Center. The analysis suggests that there is a need for evidence-based guidelines that demonstrate the efficacy and safety of various contraceptive methods in this special population.

Herzog AG, Mandle HB, Cahill KE, Fowler KM, Hauser WA, Davis AR. Contraceptive practices of women with epilepsy: Findings of the epilepsy birth control registry. Epilepsia. 2016;57(4):630-637. 

A cross-sectional data analysis derived from the Epilepsy Birth Control Registry recently found that among nearly 800 patients who were at risk for unintended pregnancy, 69.7% were using effective contraceptive methods, which included hormonal contraceptives, intrauterine devices, tubal ligation, and vasectomy. Despite the high number of patients with epilepsy using what are generally considered highly effective forms of birth control, the efficacy of these methods in this population "remains to be proven" according to researchers from Columbia University and Beth Israel Deaconess Medical Center. The analysis suggests that there is a need for evidence-based guidelines that demonstrate the efficacy and safety of various contraceptive methods in this special population.

Herzog AG, Mandle HB, Cahill KE, Fowler KM, Hauser WA, Davis AR. Contraceptive practices of women with epilepsy: Findings of the epilepsy birth control registry. Epilepsia. 2016;57(4):630-637. 

A cross-sectional data analysis derived from the Epilepsy Birth Control Registry recently found that among nearly 800 patients who were at risk for unintended pregnancy, 69.7% were using effective contraceptive methods, which included hormonal contraceptives, intrauterine devices, tubal ligation, and vasectomy. Despite the high number of patients with epilepsy using what are generally considered highly effective forms of birth control, the efficacy of these methods in this population "remains to be proven" according to researchers from Columbia University and Beth Israel Deaconess Medical Center. The analysis suggests that there is a need for evidence-based guidelines that demonstrate the efficacy and safety of various contraceptive methods in this special population.

Herzog AG, Mandle HB, Cahill KE, Fowler KM, Hauser WA, Davis AR. Contraceptive practices of women with epilepsy: Findings of the epilepsy birth control registry. Epilepsia. 2016;57(4):630-637. 

Clinical question: What is the relationship between crowding in the ED and the number of interventions adopted by the ED to address this?

Background: ED crowding results in long waits, prolonged lengths of stay, and delays in providing treatments, which can result in adverse events. Numerous interventions, including bedside registration, ED observation units, fast track, bed czar, surgical schedule smoothing, and pooled nursing, have been implemented to reduce crowding.

Study design: Retrospective, cross-sectional analysis.

Setting: U.S. hospitals in the National Hospital Ambulatory Medical Care Survey (NHAMCS).

Synopsis: From 2007 to 2010, an average of 341 hospitals per year were analyzed from the NHAMCS, representing 139,502 patient encounters. This study evaluated the adoption of nine crowding interventions at the emergency department level (bedside registration, electronic dashboard, RFID tracking, etc.) and eight crowding interventions at the hospital level (bed czar, pooled nursing, full-capacity protocol, board patients in inpatient hallways, etc.).

Bedside registration, electronic dashboard, RFID tracking, bed census, pooled nursing, full-capacity protocol, and boarding patients in the hallway had the highest statistically significant increases in adoption over the study period.

The average number of interventions adopted increased to 6.6 from 5.2, and more-crowded EDs adopted a greater number of interventions than less-crowded EDs. However, in the most-crowded quartile of EDs, 19% did not use bedside registration, and 94% did not use surgical schedule smoothing.

Given that this study is a retrospective, cross-sectional study, it is difficult to determine causality.

Bottom line: More interventions are being adopted by EDs and hospitals to decrease ED crowding, but several of the busiest EDs and hospitals have room for improvement.

Citation: Warner LS, Pines JM, Chambers JG, Schuur JD. The most crowded US hospital emergency departments did not adopt effective interventions to improve flow, 2007–10. Health Aff. 2015;34(12):2151-2159.

Clinical question: What is the relationship between crowding in the ED and the number of interventions adopted by the ED to address this?

Background: ED crowding results in long waits, prolonged lengths of stay, and delays in providing treatments, which can result in adverse events. Numerous interventions, including bedside registration, ED observation units, fast track, bed czar, surgical schedule smoothing, and pooled nursing, have been implemented to reduce crowding.

Study design: Retrospective, cross-sectional analysis.

Setting: U.S. hospitals in the National Hospital Ambulatory Medical Care Survey (NHAMCS).

Synopsis: From 2007 to 2010, an average of 341 hospitals per year were analyzed from the NHAMCS, representing 139,502 patient encounters. This study evaluated the adoption of nine crowding interventions at the emergency department level (bedside registration, electronic dashboard, RFID tracking, etc.) and eight crowding interventions at the hospital level (bed czar, pooled nursing, full-capacity protocol, board patients in inpatient hallways, etc.).

Bedside registration, electronic dashboard, RFID tracking, bed census, pooled nursing, full-capacity protocol, and boarding patients in the hallway had the highest statistically significant increases in adoption over the study period.

The average number of interventions adopted increased to 6.6 from 5.2, and more-crowded EDs adopted a greater number of interventions than less-crowded EDs. However, in the most-crowded quartile of EDs, 19% did not use bedside registration, and 94% did not use surgical schedule smoothing.

Given that this study is a retrospective, cross-sectional study, it is difficult to determine causality.

Bottom line: More interventions are being adopted by EDs and hospitals to decrease ED crowding, but several of the busiest EDs and hospitals have room for improvement.

Citation: Warner LS, Pines JM, Chambers JG, Schuur JD. The most crowded US hospital emergency departments did not adopt effective interventions to improve flow, 2007–10. Health Aff. 2015;34(12):2151-2159.

Clinical question: What is the relationship between crowding in the ED and the number of interventions adopted by the ED to address this?

Background: ED crowding results in long waits, prolonged lengths of stay, and delays in providing treatments, which can result in adverse events. Numerous interventions, including bedside registration, ED observation units, fast track, bed czar, surgical schedule smoothing, and pooled nursing, have been implemented to reduce crowding.

Study design: Retrospective, cross-sectional analysis.

Setting: U.S. hospitals in the National Hospital Ambulatory Medical Care Survey (NHAMCS).

Synopsis: From 2007 to 2010, an average of 341 hospitals per year were analyzed from the NHAMCS, representing 139,502 patient encounters. This study evaluated the adoption of nine crowding interventions at the emergency department level (bedside registration, electronic dashboard, RFID tracking, etc.) and eight crowding interventions at the hospital level (bed czar, pooled nursing, full-capacity protocol, board patients in inpatient hallways, etc.).

Bedside registration, electronic dashboard, RFID tracking, bed census, pooled nursing, full-capacity protocol, and boarding patients in the hallway had the highest statistically significant increases in adoption over the study period.

The average number of interventions adopted increased to 6.6 from 5.2, and more-crowded EDs adopted a greater number of interventions than less-crowded EDs. However, in the most-crowded quartile of EDs, 19% did not use bedside registration, and 94% did not use surgical schedule smoothing.

Given that this study is a retrospective, cross-sectional study, it is difficult to determine causality.

Bottom line: More interventions are being adopted by EDs and hospitals to decrease ED crowding, but several of the busiest EDs and hospitals have room for improvement.

Citation: Warner LS, Pines JM, Chambers JG, Schuur JD. The most crowded US hospital emergency departments did not adopt effective interventions to improve flow, 2007–10. Health Aff. 2015;34(12):2151-2159.

Clinical question: What is the appropriate frequency of INR monitoring in the hospital and its relationship to the risk of over-anticoagulation and warfarin-related adverse events?

Background: Warfarin use is a common cause of adverse drug events in hospitalized patients due to narrow therapeutic windows, drug interactions, and variability of metabolism. Current guidelines, including those by the American College of Chest Physicians, do not provide recommendations on how often to monitor INR or adjust warfarin dosing in the hospital.

Study design: Retrospective cohort.

Setting: Hospitalized patients included in the Medicare Patient Safety Monitoring System.

Synopsis: The study included 14,217 adult patients ≥18 years of age from the Medicare Patient Safety Monitoring System admitted from 2009 to 2013 with pneumonia, acute cardiac disease (myocardial infarction or congestive heart failure), or surgery and taking warfarin. Of those, 1,055 (7.4%) developed a warfarin-associated adverse event (bleeding, drop in hematocrit ≥3, hematoma, death, intracranial bleeding, or cardiac arrest). Patients admitted for acute cardiac disease (acute myocardial infarction or heart failure) or surgery on warfarin for ≥3 days but not monitored for ≥2 days had more warfarin-associated adverse events (OR 1.48; 95% CI, 1.02–2.17), but this association was not true in pneumonia patients. Cardiac and pneumonia patients with ≥1 day without INR being measured had higher rates of INR ≥6.0 (OR 1.61; 95% CI, 1.07–2.41, and OR 1.92, 95% CI, 1.36–2.71, respectively). A single-day rise in INR ≥0.9 had a likelihood ratio of 4.2 in predicting subsequent INR ≥6.0.

Bottom line: Frequent monitoring of INR may decrease warfarin-associated adverse events in hospitalized patients.

Citation: Metersky ML, Eldridge N, Wang Y, et al. Predictors of warfarin-associated adverse events in hospitalized patients: opportunities to prevent harm. J Hosp Med. 2016;11(4):276-282.

Short Take

CDC Guidelines on Prescribing Opioids

New CDC guidelines for chronic pain management stress the importance of non-pharmacologic (physical therapy, etc.) and non-opioid therapy (NSAIDs, etc.), using opioid therapy only if the expected benefits outweigh the risks.

Citation: CDC. CDC guideline for prescribing opioids for chronic pain. Available at: http://www.cdc.gov/drugoverdose/prescribing/guideline.html. Published March 16, 2016. Accessed April 8, 2016.

Clinical question: What is the appropriate frequency of INR monitoring in the hospital and its relationship to the risk of over-anticoagulation and warfarin-related adverse events?

Background: Warfarin use is a common cause of adverse drug events in hospitalized patients due to narrow therapeutic windows, drug interactions, and variability of metabolism. Current guidelines, including those by the American College of Chest Physicians, do not provide recommendations on how often to monitor INR or adjust warfarin dosing in the hospital.

Study design: Retrospective cohort.

Setting: Hospitalized patients included in the Medicare Patient Safety Monitoring System.

Synopsis: The study included 14,217 adult patients ≥18 years of age from the Medicare Patient Safety Monitoring System admitted from 2009 to 2013 with pneumonia, acute cardiac disease (myocardial infarction or congestive heart failure), or surgery and taking warfarin. Of those, 1,055 (7.4%) developed a warfarin-associated adverse event (bleeding, drop in hematocrit ≥3, hematoma, death, intracranial bleeding, or cardiac arrest). Patients admitted for acute cardiac disease (acute myocardial infarction or heart failure) or surgery on warfarin for ≥3 days but not monitored for ≥2 days had more warfarin-associated adverse events (OR 1.48; 95% CI, 1.02–2.17), but this association was not true in pneumonia patients. Cardiac and pneumonia patients with ≥1 day without INR being measured had higher rates of INR ≥6.0 (OR 1.61; 95% CI, 1.07–2.41, and OR 1.92, 95% CI, 1.36–2.71, respectively). A single-day rise in INR ≥0.9 had a likelihood ratio of 4.2 in predicting subsequent INR ≥6.0.

Bottom line: Frequent monitoring of INR may decrease warfarin-associated adverse events in hospitalized patients.

Citation: Metersky ML, Eldridge N, Wang Y, et al. Predictors of warfarin-associated adverse events in hospitalized patients: opportunities to prevent harm. J Hosp Med. 2016;11(4):276-282.

Short Take

CDC Guidelines on Prescribing Opioids

New CDC guidelines for chronic pain management stress the importance of non-pharmacologic (physical therapy, etc.) and non-opioid therapy (NSAIDs, etc.), using opioid therapy only if the expected benefits outweigh the risks.

Citation: CDC. CDC guideline for prescribing opioids for chronic pain. Available at: http://www.cdc.gov/drugoverdose/prescribing/guideline.html. Published March 16, 2016. Accessed April 8, 2016.

Clinical question: What is the appropriate frequency of INR monitoring in the hospital and its relationship to the risk of over-anticoagulation and warfarin-related adverse events?

Background: Warfarin use is a common cause of adverse drug events in hospitalized patients due to narrow therapeutic windows, drug interactions, and variability of metabolism. Current guidelines, including those by the American College of Chest Physicians, do not provide recommendations on how often to monitor INR or adjust warfarin dosing in the hospital.

Study design: Retrospective cohort.

Setting: Hospitalized patients included in the Medicare Patient Safety Monitoring System.

Synopsis: The study included 14,217 adult patients ≥18 years of age from the Medicare Patient Safety Monitoring System admitted from 2009 to 2013 with pneumonia, acute cardiac disease (myocardial infarction or congestive heart failure), or surgery and taking warfarin. Of those, 1,055 (7.4%) developed a warfarin-associated adverse event (bleeding, drop in hematocrit ≥3, hematoma, death, intracranial bleeding, or cardiac arrest). Patients admitted for acute cardiac disease (acute myocardial infarction or heart failure) or surgery on warfarin for ≥3 days but not monitored for ≥2 days had more warfarin-associated adverse events (OR 1.48; 95% CI, 1.02–2.17), but this association was not true in pneumonia patients. Cardiac and pneumonia patients with ≥1 day without INR being measured had higher rates of INR ≥6.0 (OR 1.61; 95% CI, 1.07–2.41, and OR 1.92, 95% CI, 1.36–2.71, respectively). A single-day rise in INR ≥0.9 had a likelihood ratio of 4.2 in predicting subsequent INR ≥6.0.

Bottom line: Frequent monitoring of INR may decrease warfarin-associated adverse events in hospitalized patients.

Citation: Metersky ML, Eldridge N, Wang Y, et al. Predictors of warfarin-associated adverse events in hospitalized patients: opportunities to prevent harm. J Hosp Med. 2016;11(4):276-282.

Short Take

CDC Guidelines on Prescribing Opioids

New CDC guidelines for chronic pain management stress the importance of non-pharmacologic (physical therapy, etc.) and non-opioid therapy (NSAIDs, etc.), using opioid therapy only if the expected benefits outweigh the risks.

Citation: CDC. CDC guideline for prescribing opioids for chronic pain. Available at: http://www.cdc.gov/drugoverdose/prescribing/guideline.html. Published March 16, 2016. Accessed April 8, 2016.

In an attempt to protect patients with epilepsy from harm, clinicians and relatives sometimes take an overcautious view and advise them to avoid sports and exercise. A recent consensus paper from the International League Against Epilepsy (ILAE) Task Force on Sports and Epilepsy provides a more objective evaluation of the benefits and risks of exercise in this patient population, offering suggestions on issuing medical fitness certificates in various sports. The consensus paper divides sports into three categories. In group 1, the paper discusses activities that are not associated with any significant risk; category 2 includes sports that incur significant risk to persons with epilepsy but that do not pose a risk to bystanders, while the third group includes major risk factors for both patients and observers. Among the factors that ILAE takes into account when making its recommendations: the type of sport, the likelihood of a seizure occurring during participation, the type and severity of the seizures, and the "usual timing of seizure occurrence."

Capovilla G, Kaufman KR, Perucca E, Moshé SL, Arida RM. Epilepsy, seizures, physical exercise, and sports: A report from the ILAE Task Force on Sports and Epilepsy. Epilepsia. 2016;57(1):6-12.

In an attempt to protect patients with epilepsy from harm, clinicians and relatives sometimes take an overcautious view and advise them to avoid sports and exercise. A recent consensus paper from the International League Against Epilepsy (ILAE) Task Force on Sports and Epilepsy provides a more objective evaluation of the benefits and risks of exercise in this patient population, offering suggestions on issuing medical fitness certificates in various sports. The consensus paper divides sports into three categories. In group 1, the paper discusses activities that are not associated with any significant risk; category 2 includes sports that incur significant risk to persons with epilepsy but that do not pose a risk to bystanders, while the third group includes major risk factors for both patients and observers. Among the factors that ILAE takes into account when making its recommendations: the type of sport, the likelihood of a seizure occurring during participation, the type and severity of the seizures, and the "usual timing of seizure occurrence."

Capovilla G, Kaufman KR, Perucca E, Moshé SL, Arida RM. Epilepsy, seizures, physical exercise, and sports: A report from the ILAE Task Force on Sports and Epilepsy. Epilepsia. 2016;57(1):6-12.

In an attempt to protect patients with epilepsy from harm, clinicians and relatives sometimes take an overcautious view and advise them to avoid sports and exercise. A recent consensus paper from the International League Against Epilepsy (ILAE) Task Force on Sports and Epilepsy provides a more objective evaluation of the benefits and risks of exercise in this patient population, offering suggestions on issuing medical fitness certificates in various sports. The consensus paper divides sports into three categories. In group 1, the paper discusses activities that are not associated with any significant risk; category 2 includes sports that incur significant risk to persons with epilepsy but that do not pose a risk to bystanders, while the third group includes major risk factors for both patients and observers. Among the factors that ILAE takes into account when making its recommendations: the type of sport, the likelihood of a seizure occurring during participation, the type and severity of the seizures, and the "usual timing of seizure occurrence."

Capovilla G, Kaufman KR, Perucca E, Moshé SL, Arida RM. Epilepsy, seizures, physical exercise, and sports: A report from the ILAE Task Force on Sports and Epilepsy. Epilepsia. 2016;57(1):6-12.

Patients with epilepsy are more likely to have difficulty accessing health care services, according to the National Health Interview Survey during 2010 and 2013. The survey, which included data from more than 27,000 and 34,000 adults in these respective years, revealed that patients with epilepsy had more problems affording medication (relative risk [RR]: 2.40), gaining access to mental health services (RR = 3.23), getting eyeglasses (RR= 2.36), and obtaining dental services (RR = 1.98). Similarly, this patient population was more than five times as likely to report transportation problems as a barrier to obtaining health care services. The survey data suggested that the relative lack of private health insurance may have contributed to these disparities (RR = 0.58).

Thurman DJ, Kobau R, Luo Y-H, Helmers SL, Zack MM. Health-care access among adults with epilepsy: The U.S. National Health Interview Survey, 2010 and 2013. Epilepsy Behav. 2016;55:184-188.

Patients with epilepsy are more likely to have difficulty accessing health care services, according to the National Health Interview Survey during 2010 and 2013. The survey, which included data from more than 27,000 and 34,000 adults in these respective years, revealed that patients with epilepsy had more problems affording medication (relative risk [RR]: 2.40), gaining access to mental health services (RR = 3.23), getting eyeglasses (RR= 2.36), and obtaining dental services (RR = 1.98). Similarly, this patient population was more than five times as likely to report transportation problems as a barrier to obtaining health care services. The survey data suggested that the relative lack of private health insurance may have contributed to these disparities (RR = 0.58).

Thurman DJ, Kobau R, Luo Y-H, Helmers SL, Zack MM. Health-care access among adults with epilepsy: The U.S. National Health Interview Survey, 2010 and 2013. Epilepsy Behav. 2016;55:184-188.

Patients with epilepsy are more likely to have difficulty accessing health care services, according to the National Health Interview Survey during 2010 and 2013. The survey, which included data from more than 27,000 and 34,000 adults in these respective years, revealed that patients with epilepsy had more problems affording medication (relative risk [RR]: 2.40), gaining access to mental health services (RR = 3.23), getting eyeglasses (RR= 2.36), and obtaining dental services (RR = 1.98). Similarly, this patient population was more than five times as likely to report transportation problems as a barrier to obtaining health care services. The survey data suggested that the relative lack of private health insurance may have contributed to these disparities (RR = 0.58).

Thurman DJ, Kobau R, Luo Y-H, Helmers SL, Zack MM. Health-care access among adults with epilepsy: The U.S. National Health Interview Survey, 2010 and 2013. Epilepsy Behav. 2016;55:184-188.

Among 207 patients with epilepsy, 43% reported clinically significant insomnia, while 51% had at least mild insomnia according to investigators from the University of Virginia. Their results, derived from an Insomnia Severity Index survey, also found that younger patients, those with a shorter duration of epilepsy, and patients taking sedatives or hypnotics, reported more severe insomnia. Similarly, patients with delayed sleep timing and depression were more likely to experience more severe insomnia. However, even after researchers factored out these covariates, they found that more severe insomnia was significantly associated with seizures and poorer quality of life.

Quigg M, Gharai S, Ruland J, et al. Insomnia in epilepsy is associated with continuing seizures and worse quality of life. Epilepsy Res. 2016;122:91-96.

Among 207 patients with epilepsy, 43% reported clinically significant insomnia, while 51% had at least mild insomnia according to investigators from the University of Virginia. Their results, derived from an Insomnia Severity Index survey, also found that younger patients, those with a shorter duration of epilepsy, and patients taking sedatives or hypnotics, reported more severe insomnia. Similarly, patients with delayed sleep timing and depression were more likely to experience more severe insomnia. However, even after researchers factored out these covariates, they found that more severe insomnia was significantly associated with seizures and poorer quality of life.

Quigg M, Gharai S, Ruland J, et al. Insomnia in epilepsy is associated with continuing seizures and worse quality of life. Epilepsy Res. 2016;122:91-96.

Among 207 patients with epilepsy, 43% reported clinically significant insomnia, while 51% had at least mild insomnia according to investigators from the University of Virginia. Their results, derived from an Insomnia Severity Index survey, also found that younger patients, those with a shorter duration of epilepsy, and patients taking sedatives or hypnotics, reported more severe insomnia. Similarly, patients with delayed sleep timing and depression were more likely to experience more severe insomnia. However, even after researchers factored out these covariates, they found that more severe insomnia was significantly associated with seizures and poorer quality of life.

Quigg M, Gharai S, Ruland J, et al. Insomnia in epilepsy is associated with continuing seizures and worse quality of life. Epilepsy Res. 2016;122:91-96.

A report on seven cases of severe myasthenia gravis suggests that autologous hematopoietic stem cell transplantation (HSCT) may result in long-term remission. The report was published online April 4 in JAMA Neurology.

In this retrospective study, each patient who underwent autologous HSCT from January 1, 2001, through December 31, 2014, in the Ottawa Hospital Bone Marrow Transplant Programme Database was observed. Lead author Adam Bryant, MD, of the Division of Hematology at the University of Ottawa, Canada, and colleagues reported that every patient who received HSCT experienced relief of symptoms and a prolonged period of treatment-free remission. Prior to treatment, the condition of each patient in the study was labeled as moderate (grade III) to life threatening (grade V) by the Myasthenia Gravis Foundation of America's classification system.

Treatment consisted of high-dose chemotherapy and antilymphocyte antibodies to eliminate the autoreactive immune system, followed by an infusion of stem cells previously harvested from the patient. No unexpected acute toxic effects were observed, no patient was admitted to the ICU for treatment-related effects, and there were no treatment-related deaths. Viral reactivation occurred in three patients (43%) as a result of the initial immune dysregulation.

This study suggests that autologous HSCT is rigorous enough to eliminate autoreactivity and that it re-establishes a long-lasting immune system that is functional and self-tolerant, thus eliminating the need for maintenance immunosuppression or additional treatment, the researchers said. HSCT has effectively treated other severe autoimmune neurologic conditions and maybe an option for patients with myasthenia gravis who do not respond to conventional treatment.

In an accompanying editorial, Daniel Drachman, MD, of the Johns Hopkins School of Medicine in Baltimore, explained that HSCT "is a major undertaking, involving skilled and experienced management, hospitalization, and important risks."

Current therapies used for myasthenia gravis, including cyclophosphamide and monoclonal antibodies like rituximab, have led to clinical improvement, but complete remission, as was seen with HSCT, is rare.

—Adaeze Stephanie Onyechi

A report on seven cases of severe myasthenia gravis suggests that autologous hematopoietic stem cell transplantation (HSCT) may result in long-term remission. The report was published online April 4 in JAMA Neurology.

In this retrospective study, each patient who underwent autologous HSCT from January 1, 2001, through December 31, 2014, in the Ottawa Hospital Bone Marrow Transplant Programme Database was observed. Lead author Adam Bryant, MD, of the Division of Hematology at the University of Ottawa, Canada, and colleagues reported that every patient who received HSCT experienced relief of symptoms and a prolonged period of treatment-free remission. Prior to treatment, the condition of each patient in the study was labeled as moderate (grade III) to life threatening (grade V) by the Myasthenia Gravis Foundation of America's classification system.

Treatment consisted of high-dose chemotherapy and antilymphocyte antibodies to eliminate the autoreactive immune system, followed by an infusion of stem cells previously harvested from the patient. No unexpected acute toxic effects were observed, no patient was admitted to the ICU for treatment-related effects, and there were no treatment-related deaths. Viral reactivation occurred in three patients (43%) as a result of the initial immune dysregulation.

This study suggests that autologous HSCT is rigorous enough to eliminate autoreactivity and that it re-establishes a long-lasting immune system that is functional and self-tolerant, thus eliminating the need for maintenance immunosuppression or additional treatment, the researchers said. HSCT has effectively treated other severe autoimmune neurologic conditions and maybe an option for patients with myasthenia gravis who do not respond to conventional treatment.

In an accompanying editorial, Daniel Drachman, MD, of the Johns Hopkins School of Medicine in Baltimore, explained that HSCT "is a major undertaking, involving skilled and experienced management, hospitalization, and important risks."

Current therapies used for myasthenia gravis, including cyclophosphamide and monoclonal antibodies like rituximab, have led to clinical improvement, but complete remission, as was seen with HSCT, is rare.

—Adaeze Stephanie Onyechi

A report on seven cases of severe myasthenia gravis suggests that autologous hematopoietic stem cell transplantation (HSCT) may result in long-term remission. The report was published online April 4 in JAMA Neurology.

In this retrospective study, each patient who underwent autologous HSCT from January 1, 2001, through December 31, 2014, in the Ottawa Hospital Bone Marrow Transplant Programme Database was observed. Lead author Adam Bryant, MD, of the Division of Hematology at the University of Ottawa, Canada, and colleagues reported that every patient who received HSCT experienced relief of symptoms and a prolonged period of treatment-free remission. Prior to treatment, the condition of each patient in the study was labeled as moderate (grade III) to life threatening (grade V) by the Myasthenia Gravis Foundation of America's classification system.

Treatment consisted of high-dose chemotherapy and antilymphocyte antibodies to eliminate the autoreactive immune system, followed by an infusion of stem cells previously harvested from the patient. No unexpected acute toxic effects were observed, no patient was admitted to the ICU for treatment-related effects, and there were no treatment-related deaths. Viral reactivation occurred in three patients (43%) as a result of the initial immune dysregulation.

This study suggests that autologous HSCT is rigorous enough to eliminate autoreactivity and that it re-establishes a long-lasting immune system that is functional and self-tolerant, thus eliminating the need for maintenance immunosuppression or additional treatment, the researchers said. HSCT has effectively treated other severe autoimmune neurologic conditions and maybe an option for patients with myasthenia gravis who do not respond to conventional treatment.

In an accompanying editorial, Daniel Drachman, MD, of the Johns Hopkins School of Medicine in Baltimore, explained that HSCT "is a major undertaking, involving skilled and experienced management, hospitalization, and important risks."

Current therapies used for myasthenia gravis, including cyclophosphamide and monoclonal antibodies like rituximab, have led to clinical improvement, but complete remission, as was seen with HSCT, is rare.

—Adaeze Stephanie Onyechi

As Colorado was among the first states to allow the medical use of marijuana, neurologists there have experience treating children with seizures who use cannabinoids. Their findings and recommendations regarding parent perceptions, administrative policies, and clinical practice may be useful to pediatric neurologists in other states.

At Marijuana and Cannabinoids: A Neuroscience Research Summit, convened by the NIH, Amy Brooks-Kayal, MD, Chief of Pediatric Neurology at the University of Colorado School of Medicine and Children’s Hospital Colorado in Aurora, described her facility’s experiences caring for this patient group.

Amy Brooks-Kayal, MD

Colorado has allowed the medical use of marijuana since November 2000, while other states more recently have legalized its use. Of the 107,798 patients in Colorado who hold a card that permits medical marijuana use, 349, or about 0.3%, are minors.

Seizures are a relatively rare reason for medical marijuana use. Dr. Brooks-Kayal said that she is not aware of any neurologists or pediatricians who prescribe cannabinoids for pediatric seizures. Any physician in Colorado who has a relationship with a patient can issue a card permitting marijuana use, and two physicians are needed to issue cards to minors.

To examine the use of medical mari­juana in Colorado in children with seizure disorders, Craig Press, MD, PhD, and his coauthors conducted an observational study of 75 patients with pediatric seizures who used medical marijuana, when Dr. Press was a pediatric neurology resident at Children’s Hospital Colorado. The study was published in the April 2015 issue of Epilepsy & Behavior. “We had no ability to determine what was in the substances given, other than parental report,” Dr. Brooks-Kayal said.

Parents’ Perception of Response

Overall, 33% of parents reported a greater than 50% reduction in seizures; this group was judged to be responders, with no significant difference in response rate by seizure type. A variety of cannabis products were used, including cannabidiol alone and cannabidiol with other oral cannabis extracts (OCEs). All produced similar response rates.

However, only 30 patients had pre- and post-cannabis EEGs. Of this group, none of the cannabis responders had an improvement in their EEGs after cannabis use, whereas three of the nonresponders showed EEG improvement. “The most interesting finding that we saw was that the response rate dramatically varied depending on whether the families had moved out of state,” Dr. Brooks-Kayal said. Families who had moved to Colorado from another state for treatment were three times more likely to report response to OCEs, compared with those families who were from Colorado (47% vs 22%; odds ratio, 3.16).

This result, she said, raised the possibility that “the degree of investment that the family had made in getting this therapy might be impacting the parents’ perception of response.”

Navigating State and Federal Policies

Since state and federal policies vary, it’s hard to know what to do when a family comes to you asking about cannabis for pediatric seizure control, Dr. Brooks-Kayal said.

She therefore outlined Children’s Hospital Colorado’s approach. There, “providers do not recommend use of cannabinoids for treatment of epilepsy outside of a clinical trial,” she said.

However, families are provided with the most current information about cannabinoids. This includes being frank about the current lack of evidence regarding efficacy and safety, as well as unknowns around dosing and drug interactions. She said providers also share concerns about what’s in artisanal marijuana products, since purity and consistency of content aren’t regulated.

It’s critical for families to feel comfortable disclosing whether their children with seizures are using cannabinoids, so providers can help track safety and efficacy. Disclosure may be more likely if you reinforce that you won’t stop caring for these children if they are on cannabinoids, Dr. Brooks-Kayal said. “We strongly encourage disclosure,” and it’s a standard part of intake at every appointment to ask about cannabinoids, she said.

When cannabinoids are being used, Dr. Brooks-Kayal recommends obtaining the following tests at baseline and monthly thereafter: complete blood count, liver function tests, basic metabolic panel, and trough antiseizure medication levels. Clobazam, N-desmethylclobazam, and valproic acid levels have all been seen to change with concomitant cannabinoid use, she said.

“We ask families not to change other medications,” Dr. Brooks-Kayal said. Her practice frequently sees statusepilepticus when other medications are stopped and cannabinoids started, she said. “That is a huge risk.”

Tracking Efficacy

To help families and providers track efficacy when cannabinoids are used, Dr. Brooks-Kayal asks families to keep a seizure diary. She obtains a baseline EEG and another EEG about three months later. Since the EEG should capture seizure frequency, the length of the EEG is tailored to the patient’s seizure frequency. Dr. Brooks-Kayal often obtains 24-hour EEGs for her patients.

If it’s appropriate, families can enroll their children in an observational research study. Families can also consider participating in pharmaceutical double-blind, placebo-controlled trials. Other practical tips include standardizing the way neurologists care for children who use cannabinoids in their practice, and working in advance with hospital administrators and the inpatient pharmacy to address the use of these products for inpatients.

A 2014 Cochrane review concluded that “no reliable conclusions can be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy,” Dr. Brooks-Kayal said. A systematic review by the American Academy of Neurology reached the same conclusion. The American Epilepsy Society, the American Academy of Pediatrics, and the American Medical Association do not recommend routine clinical use of cannabinoids for seizures, but call for additional research. “We need better data,” Dr. Brooks-Kayal said.

—Kari Oakes

As Colorado was among the first states to allow the medical use of marijuana, neurologists there have experience treating children with seizures who use cannabinoids. Their findings and recommendations regarding parent perceptions, administrative policies, and clinical practice may be useful to pediatric neurologists in other states.

At Marijuana and Cannabinoids: A Neuroscience Research Summit, convened by the NIH, Amy Brooks-Kayal, MD, Chief of Pediatric Neurology at the University of Colorado School of Medicine and Children’s Hospital Colorado in Aurora, described her facility’s experiences caring for this patient group.

Amy Brooks-Kayal, MD

Colorado has allowed the medical use of marijuana since November 2000, while other states more recently have legalized its use. Of the 107,798 patients in Colorado who hold a card that permits medical marijuana use, 349, or about 0.3%, are minors.

Seizures are a relatively rare reason for medical marijuana use. Dr. Brooks-Kayal said that she is not aware of any neurologists or pediatricians who prescribe cannabinoids for pediatric seizures. Any physician in Colorado who has a relationship with a patient can issue a card permitting marijuana use, and two physicians are needed to issue cards to minors.

To examine the use of medical mari­juana in Colorado in children with seizure disorders, Craig Press, MD, PhD, and his coauthors conducted an observational study of 75 patients with pediatric seizures who used medical marijuana, when Dr. Press was a pediatric neurology resident at Children’s Hospital Colorado. The study was published in the April 2015 issue of Epilepsy & Behavior. “We had no ability to determine what was in the substances given, other than parental report,” Dr. Brooks-Kayal said.

Parents’ Perception of Response

Overall, 33% of parents reported a greater than 50% reduction in seizures; this group was judged to be responders, with no significant difference in response rate by seizure type. A variety of cannabis products were used, including cannabidiol alone and cannabidiol with other oral cannabis extracts (OCEs). All produced similar response rates.

However, only 30 patients had pre- and post-cannabis EEGs. Of this group, none of the cannabis responders had an improvement in their EEGs after cannabis use, whereas three of the nonresponders showed EEG improvement. “The most interesting finding that we saw was that the response rate dramatically varied depending on whether the families had moved out of state,” Dr. Brooks-Kayal said. Families who had moved to Colorado from another state for treatment were three times more likely to report response to OCEs, compared with those families who were from Colorado (47% vs 22%; odds ratio, 3.16).

This result, she said, raised the possibility that “the degree of investment that the family had made in getting this therapy might be impacting the parents’ perception of response.”

Navigating State and Federal Policies

Since state and federal policies vary, it’s hard to know what to do when a family comes to you asking about cannabis for pediatric seizure control, Dr. Brooks-Kayal said.

She therefore outlined Children’s Hospital Colorado’s approach. There, “providers do not recommend use of cannabinoids for treatment of epilepsy outside of a clinical trial,” she said.

However, families are provided with the most current information about cannabinoids. This includes being frank about the current lack of evidence regarding efficacy and safety, as well as unknowns around dosing and drug interactions. She said providers also share concerns about what’s in artisanal marijuana products, since purity and consistency of content aren’t regulated.

It’s critical for families to feel comfortable disclosing whether their children with seizures are using cannabinoids, so providers can help track safety and efficacy. Disclosure may be more likely if you reinforce that you won’t stop caring for these children if they are on cannabinoids, Dr. Brooks-Kayal said. “We strongly encourage disclosure,” and it’s a standard part of intake at every appointment to ask about cannabinoids, she said.

When cannabinoids are being used, Dr. Brooks-Kayal recommends obtaining the following tests at baseline and monthly thereafter: complete blood count, liver function tests, basic metabolic panel, and trough antiseizure medication levels. Clobazam, N-desmethylclobazam, and valproic acid levels have all been seen to change with concomitant cannabinoid use, she said.

“We ask families not to change other medications,” Dr. Brooks-Kayal said. Her practice frequently sees statusepilepticus when other medications are stopped and cannabinoids started, she said. “That is a huge risk.”

Tracking Efficacy

To help families and providers track efficacy when cannabinoids are used, Dr. Brooks-Kayal asks families to keep a seizure diary. She obtains a baseline EEG and another EEG about three months later. Since the EEG should capture seizure frequency, the length of the EEG is tailored to the patient’s seizure frequency. Dr. Brooks-Kayal often obtains 24-hour EEGs for her patients.

If it’s appropriate, families can enroll their children in an observational research study. Families can also consider participating in pharmaceutical double-blind, placebo-controlled trials. Other practical tips include standardizing the way neurologists care for children who use cannabinoids in their practice, and working in advance with hospital administrators and the inpatient pharmacy to address the use of these products for inpatients.

A 2014 Cochrane review concluded that “no reliable conclusions can be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy,” Dr. Brooks-Kayal said. A systematic review by the American Academy of Neurology reached the same conclusion. The American Epilepsy Society, the American Academy of Pediatrics, and the American Medical Association do not recommend routine clinical use of cannabinoids for seizures, but call for additional research. “We need better data,” Dr. Brooks-Kayal said.

—Kari Oakes

As Colorado was among the first states to allow the medical use of marijuana, neurologists there have experience treating children with seizures who use cannabinoids. Their findings and recommendations regarding parent perceptions, administrative policies, and clinical practice may be useful to pediatric neurologists in other states.

At Marijuana and Cannabinoids: A Neuroscience Research Summit, convened by the NIH, Amy Brooks-Kayal, MD, Chief of Pediatric Neurology at the University of Colorado School of Medicine and Children’s Hospital Colorado in Aurora, described her facility’s experiences caring for this patient group.

Amy Brooks-Kayal, MD

Colorado has allowed the medical use of marijuana since November 2000, while other states more recently have legalized its use. Of the 107,798 patients in Colorado who hold a card that permits medical marijuana use, 349, or about 0.3%, are minors.

Seizures are a relatively rare reason for medical marijuana use. Dr. Brooks-Kayal said that she is not aware of any neurologists or pediatricians who prescribe cannabinoids for pediatric seizures. Any physician in Colorado who has a relationship with a patient can issue a card permitting marijuana use, and two physicians are needed to issue cards to minors.

To examine the use of medical mari­juana in Colorado in children with seizure disorders, Craig Press, MD, PhD, and his coauthors conducted an observational study of 75 patients with pediatric seizures who used medical marijuana, when Dr. Press was a pediatric neurology resident at Children’s Hospital Colorado. The study was published in the April 2015 issue of Epilepsy & Behavior. “We had no ability to determine what was in the substances given, other than parental report,” Dr. Brooks-Kayal said.

Parents’ Perception of Response

Overall, 33% of parents reported a greater than 50% reduction in seizures; this group was judged to be responders, with no significant difference in response rate by seizure type. A variety of cannabis products were used, including cannabidiol alone and cannabidiol with other oral cannabis extracts (OCEs). All produced similar response rates.

However, only 30 patients had pre- and post-cannabis EEGs. Of this group, none of the cannabis responders had an improvement in their EEGs after cannabis use, whereas three of the nonresponders showed EEG improvement. “The most interesting finding that we saw was that the response rate dramatically varied depending on whether the families had moved out of state,” Dr. Brooks-Kayal said. Families who had moved to Colorado from another state for treatment were three times more likely to report response to OCEs, compared with those families who were from Colorado (47% vs 22%; odds ratio, 3.16).

This result, she said, raised the possibility that “the degree of investment that the family had made in getting this therapy might be impacting the parents’ perception of response.”

Navigating State and Federal Policies

Since state and federal policies vary, it’s hard to know what to do when a family comes to you asking about cannabis for pediatric seizure control, Dr. Brooks-Kayal said.

She therefore outlined Children’s Hospital Colorado’s approach. There, “providers do not recommend use of cannabinoids for treatment of epilepsy outside of a clinical trial,” she said.

However, families are provided with the most current information about cannabinoids. This includes being frank about the current lack of evidence regarding efficacy and safety, as well as unknowns around dosing and drug interactions. She said providers also share concerns about what’s in artisanal marijuana products, since purity and consistency of content aren’t regulated.

It’s critical for families to feel comfortable disclosing whether their children with seizures are using cannabinoids, so providers can help track safety and efficacy. Disclosure may be more likely if you reinforce that you won’t stop caring for these children if they are on cannabinoids, Dr. Brooks-Kayal said. “We strongly encourage disclosure,” and it’s a standard part of intake at every appointment to ask about cannabinoids, she said.

When cannabinoids are being used, Dr. Brooks-Kayal recommends obtaining the following tests at baseline and monthly thereafter: complete blood count, liver function tests, basic metabolic panel, and trough antiseizure medication levels. Clobazam, N-desmethylclobazam, and valproic acid levels have all been seen to change with concomitant cannabinoid use, she said.

“We ask families not to change other medications,” Dr. Brooks-Kayal said. Her practice frequently sees statusepilepticus when other medications are stopped and cannabinoids started, she said. “That is a huge risk.”

Tracking Efficacy

To help families and providers track efficacy when cannabinoids are used, Dr. Brooks-Kayal asks families to keep a seizure diary. She obtains a baseline EEG and another EEG about three months later. Since the EEG should capture seizure frequency, the length of the EEG is tailored to the patient’s seizure frequency. Dr. Brooks-Kayal often obtains 24-hour EEGs for her patients.

If it’s appropriate, families can enroll their children in an observational research study. Families can also consider participating in pharmaceutical double-blind, placebo-controlled trials. Other practical tips include standardizing the way neurologists care for children who use cannabinoids in their practice, and working in advance with hospital administrators and the inpatient pharmacy to address the use of these products for inpatients.

A 2014 Cochrane review concluded that “no reliable conclusions can be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy,” Dr. Brooks-Kayal said. A systematic review by the American Academy of Neurology reached the same conclusion. The American Epilepsy Society, the American Academy of Pediatrics, and the American Medical Association do not recommend routine clinical use of cannabinoids for seizures, but call for additional research. “We need better data,” Dr. Brooks-Kayal said.

—Kari Oakes