Positive anxiety or depression screen despite ongoing antidepressant prescription in people with epilepsy: A large cross-sectional analysis.

Purpose: While antidepressants are recommended to manage anxiety or depression in epilepsy, limited effectiveness data exist in real-world epilepsy samples, and prior work indicated frequent positive screens despite antidepressant prescription. In response, this study evaluates factors associated with positive anxiety or depression screen during ongoing antidepressant prescription. Methods: Clinical and sociodemographic characteristics were collected among consecutive adult epilepsy clinic patients completing validated anxiety and depression instruments. The sample was divided by presence vs absence of existing antidepressant prescription at time of screening. Among those on an antidepressant, multivariable logistic regression was performed on pre-selected characteristics to evaluate for association with positive anxiety and/or depression screen. Pre-selected characteristics included: antidepressant dose, antidepressant prescriber specialty, antiseizure medications (number, potential psychotropic effects), seizure frequency, employment, visit no-shows, and medical insurance. Results: Of 563 people with epilepsy, 152 had evidence of antidepressant prescription at time of screening and 73/152(48%) had positive anxiety and/or depression screen. Multivariable modeling demonstrated low antidepressant dose and no-show visit(s) were associated with positive screens (adjusted OR 2.29, CI 1.00-5.48 and 3.11, 1.26-8.22 respectively). Conclusion: Low antidepressant dose and factors potentially associated with adherence (visit no-shows) may contribute to persistent anxiety and/or depression among epilepsy patients on an antidepressant.

DOISNORE50: a perioperative sleep questionnaire predictive of obstructive sleep apnea and postoperative medical emergency team activation. A learning health system approach to sleep questionnaire development and screening.

STUDY OBJECTIVES: Patients with obstructive sleep apnea (OSA) have a disproportionate increase in postoperative complications and medical emergency team activation (META). We previously introduced DOISNORE50 (Diseases, Observed apnea, Insomnia, Snoring, Neck circumference > 18 inches, Obesity with BMI > 32, R = are you male, Excessive daytime sleepiness, 50 = age ≥ 50) from sleep questionnaire ISNORED using features associated with increased odds of META in perioperative patients. Performance of DOISNORE50 (DOISNORE) had yet to be tested. METHODS: The performance of DOISNORE was tested along with questionnaire ISNORED and STOP-BANG questionnaires among 300 out of 392 participants without known OSA referred to the sleep lab. In study 2, the performance of DOISNORE was tested among 64,949 lives screened in perioperative assessment clinic from 2016 to 2020. RESULTS: Receiver operating characteristic curve demonstrated that best performance was achieved with responses, with area under curve of 0.801. DOISNORE's predictability of OSA risk remained stable from 2018 to 2020 with area under curve of 0.78 and a Cronbach alpha of 0.65. Patients at high risk for OSA (DOISNORE ≥ 6) were associated with an increase of META (odds ratio 1.30, 95% confidence interval 1.12-1.45). Higher relative risk was noted among patients with congestive heart failure and hypercapnia. CONCLUSIONS: DOISNORE is predictive of OSA and postoperative META. Perioperative strategies against META should consider DOISNORE questionnaire and focused screening among patients with heart failure and hypercapnia. CITATION: Namen AM, Forest D, Saha AK, et al. DOISNORE50: a perioperative sleep questionnaire predictive of obstructive sleep apnea and postoperative medical emergency team activation. A learning health system approach to sleep questionnaire development and screening. J Clin Sleep Med. 2022;18(8):1909-1919.

Reduction in medical emergency team activation among postoperative surgical patients at risk for undiagnosed obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is an under-recognized condition that results in morbidity and mortality. Postoperative complications, including medical emergency team activation (META), are disproportionally increased among surgical patients at risk for OSA. A systematic approach is needed to improve provider recognition and treatment, but protocols that demonstrate improvement in META are lacking. As part of a multidisciplinary quality improvement project, DOISNORE50 (DIS), a sleep apnea questionnaire and proactive safety measure, was algorithmically applied to all perioperative patients. METHODS: Consecutive sleep screening was conducted among perioperative patients. Of the 49,567 surgical navigation center patients, 11,932 had previous diagnosis of OSA. Of the 37,572 (96%) patients screened with DIS, 25,171 (66.9%) were Low Risk (DIS < 4), 9,211 (24.5%) were At Risk (DIS ≥ 4), and 3,190 (8.5%) were High Risk (DIS ≥ 6) for OSA, respectively. High Risk patients received same-day sleep consultation. On the day of surgery, patients with Known OSA, At Risk, and High Risk for OSA received an "OSA Precaution Band." An electronic chart reminder alerted admission providers to order postoperative continuous positive airway pressure (CPAP) machine and sleep consult for patients High Risk for OSA. RESULTS: Implementation of a comprehensive program was associated with increased sleep consultation, sleep testing, and inpatient CPAP use (P < .001). For every 1,000 surgical patients screened, 30 fewer META, including rapid responses, reintubation, code blues, and code strokes, were observed. However, inpatient sleep consultation and inpatient CPAP use were not independently associated with reduced META. In the subgroup of patients hospitalized longer than 3 days, inpatient CPAP use was independently associated with reduced META. CONCLUSIONS: In this single-center, institution-wide, multidisciplinary-approach, quality improvement project, a comprehensive OSA screening process and treatment algorithm with appropriate postoperative inpatient CPAP therapy and inpatient sleep consultations was associated with increased CPAP use and reduced META. Further prospective studies are needed to assess cost, feasibility, and generalizability of these findings. CITATION: Namen AM, Forest D, Saha AK, et al. Reduction in medical emergency team activation among postoperative surgical patients at risk for undiagnosed obstructive sleep apnea. J Clin Sleep Med. 2022;18(8):1953-1965.

Adherence to levetiracetam for management of epilepsy: Assessment with electronic monitors.

INTRODUCTION: Anti-seizure medications are used to manage epilepsy and require long-term adherence to maintain therapeutic drug levels. We assessed adherence to levetiracetam and the use of a digital intervention to improve adherence in patients with epilepsy. METHODS: 30 participants with epilepsy were randomized 1:1 either to a digital email adherence intervention or control group. All patients were provided levetiracetam equipped with electronic monitoring caps to assess patient adherence to medication. Patients were followed for 6 months, with return visits at 1 month, 3 months, and 6 months. RESULTS: Subjects randomized to the control arm (n = 15) took 66% of the prescribed doses compared to the intervention group, who took 65% of prescribed doses (n = 15). Nine participants did not complete the study. Of the twenty-one participants that completed the study, the overall rate of adherence was 72% of prescribed doses taken. Two subjects in the control group and three subjects in the intervention group were adherent every month of the study-taking at least 80% of prescribed doses. Those randomized to the control group took the correct number of doses 44% of days in the study, and those in the intervention group took the correct number of doses 37% of days. DISCUSSION: Poor adherence to levetiracetam is common. An internet-based email survey intervention did not improve adherence to levetiracetam in epilepsy patients. Further advances in adherence are needed to help patients receive the maximum benefit of their medical treatments.

Chronic levetiracetam (Keppra®) treatment increases the reinforcing strength of cocaine in rhesus monkeys.

BACKGROUND: Drugs that increase inhibitory neuronal activity in the brain have been proposed as potential medications for stimulant use disorders. OBJECTIVE: The present study assessed the ability of chronically administered levetiracetam (Keppra®), a clinically available anticonvulsant drug that increases GABA by binding to synaptic vesicle glycoprotein 2A, to modulate the reinforcing strength of cocaine in monkeys. METHODS: Three adult male rhesus monkeys (Macaca mulatta) self-administered cocaine intravenously each day under a progressive-ratio (PR) schedule of reinforcement. Two monkeys also responded to receive food pellets under a 50-response fixed-ratio schedule (FR 50) each morning. After determining a cocaine dose-response curve (0.001-0.3 mg/kg per injection, i.v.) in the evening, levetiracetam (5-75 mg/kg, p.o., b.i.d.) was administered for 12-16 days per dose. To model a treatment setting, cocaine self-administration sessions were conducted using the PR schedule every 4 days during levetiracetam treatment. After tapering the dose of levetiracetam over two weeks in the absence of cocaine sessions, cocaine dose-effect curves were re-determined. RESULTS: Lower doses of levetiracetam produced non-systematic fluctuations in numbers of cocaine injections received in each subject, whereas the highest tested dose significantly increased the reinforcing strength of cocaine; no effects on food-maintained responding were observed. After termination of levetiracetam treatment, dose-effect curves for cocaine self-administration were shifted to the left in two monkeys. CONCLUSION: These data suggest that levetiracetam is not likely to be an efficacious pharmacotherapy for cocaine dependence. Rather, sensitivity to cocaine may be increased during and after levetiracetam treatment.

Neurologist prescribing versus psychiatry referral: Examining patient preferences for anxiety and depression management in a symptomatic epilepsy clinic sample.

OBJECTIVE: Anxiety and depression symptoms in epilepsy are common, impactful and under-recognized and undertreated. While prior survey data suggests equipoise among epileptologists for managing anxiety and/or depression via prescribing in the epilepsy clinic versus psychiatry referral, patient preferences are unknown and should potentially influence practice habits among epileptologists. Thus, the primary objective of this study was to determine patient preference for anxiety and/or depression prescribing by neurologists versus psychiatry referral among an adult epilepsy clinic sample of symptomatic patients. METHODS: Management preferences for anxiety and/or depression were surveyed in an adult tertiary care epilepsy clinic. Individuals who screened positive for anxiety and/or depression symptoms on validated instruments during a routine care-embedded learning health system study were recruited. Demographics, social variables, psychiatric treatment history, and treatment priorities and preferences were surveyed. Preference was defined as a slightly greater than 2:1 ratio in favor neurology prescribing or psychiatry referral. The study was powered to assess this primary objective using a two-sample binomial test. Multinomial logistic regression examined an a priori multivariable model of treatment preference (secondary objective). RESULTS: The study sample included N = 63 symptomatic adults, with 64% women and mean age 42.2 years. Most reported past or current treatment for anxiety and/or depression, and treatment for these symptoms was a high or moderate priority among 65.1% of the sample. Neurologist prescribing was preferred in 83.0% (nearly 5:1) over psychiatry referral among those who chose neurology or psychiatry (as opposed to neither of the two; p < 0.001, 95% CI 0.702-0.919). Overall, 69.8% of the total study sample preferred neurology prescribing. Multivariable modeling indicated preference for neither management option (compared with neurologist prescribing) was associated with low overall treatment prioritization and having never received neurologist medication management. None of the factors examined in the a priori multivariable model were associated with selecting psychiatry referral (compared to neurologist prescribing). CONCLUSION: In this sample, most patients indicated a preference for neurologists to prescribe for anxiety or depression symptoms in the epilepsy clinic. Care models involving neurologist prescribing for anxiety and depression symptoms merit further investigation and potential adoption in clinical practice.

Who is willing to participate in research? A screening model for an anxiety and depression trial in the epilepsy clinic.

OBJECTIVE: Anxiety and depression in epilepsy are prevalent, associated with poor outcomes, underrecognized, undertreated, and thus a key area of need for treatment research. The objective of this study was to assess factors associated with research participation among epilepsy clinic patients who screened positive for anxiety or depression. This was accomplished by characterizing clinical and psychiatric factors among patients seen in an epilepsy clinic and evaluating which factors were associated with consent for potential research participation, via a combined clinical and research screening model. METHODS: In a pragmatic trial of anxiety and depression treatment in epilepsy, individuals with a positive screen for anxiety and/or depression at a routine epilepsy clinic visit were invited to opt-in (via brief electronic consent) to further eligibility assessment for a randomized treatment study. Information on psychiatric symptoms and treatment characteristics were collected for dual clinical care and research screening purposes. Cross-sectional association of demographic, clinical, and psychiatric factors with opting-in to research was analyzed by multiple logistic regression. RESULTS: Among N = 199 unique adults with a first positive screen for anxiety and/or depression among 786 total screening events, 154 (77.4%) opted-in to further potential research assessment. Higher depression scores and current treatment with an antidepressant were independently associated with opting-in to research (depression odds ratio (OR) = 1.13 per 1-point increase in Neurological Disorders Depression Inventory-Epilepsy (NDDI-E) score, p = 0.028, 95% confidence interval (CI): 1.01-1.26; antidepressant OR = 2.37, p = 0.041, CI: 1.04-5.41). Nearly half of the 199 individuals (43.7%) with anxiety and/or depression symptoms were already being treated with an antidepressant, and 46.7% were receiving neither antidepressant therapy nor mental health specialty care. One-quarter (24.1%) reported a past psychiatric hospitalization, yet only half of these individuals were receiving mental health specialty care. SIGNIFICANCE: Our results demonstrate a high willingness to participate in research using a brief electronic consent approach at a routine clinic visit. Adults with persistent anxiety or depression symptoms despite antidepressant therapy and those with higher depression scores were more willing to consider a randomized treatment study. This has implications for future study design, as individuals already on treatment or those with more severe symptoms are often excluded from traditional research designs. We also found a high burden of psychiatric disease and high prevalence of persistent symptoms despite ongoing antidepressant treatment.

Organizational strategies to reduce physician burnout and improve professional fulfillment.

Burnout is highly prevalent among physicians and has been associated with negative outcomes for physicians, patients, staff, and health-care organizations. Reducing physician burnout and increasing physician well-being is a priority. Systematic reviews suggest that organization-based interventions are more effective in reducing physician burnout than interventions targeted at individual physicians. This consensus review by leaders in the field across multiple institutions presents emerging trends and exemplary evidence-based strategies to improve professional fulfillment and reduce physician burnout using Stanford's tripartite model of physician professional fulfillment as an organizing framework: practice efficiency, culture, and personal resilience to support physician well-being. These strategies include leadership traits, latitude of control and autonomy, collegiality, diversity, teamwork, top-of-license workflows, electronic health record (EHR) usability, peer support, confidential mental health services, work-life integration and reducing barriers to practicing a healthy lifestyle. The review concludes with evidence-based recommendations on establishing an effective physician wellness program.

Burnout, career satisfaction, and well-being among US neurology residents and fellows in 2016.

OBJECTIVE: To study prevalence of and factors contributing to burnout, career satisfaction, and well-being in US neurology residents and fellows. METHODS: A total of 938 US American Academy of Neurology member neurology residents and fellows were surveyed using standardized measures of burnout, career satisfaction, and well-being from January 19 to March 21, 2016. RESULTS: Response rate was 37.7% (354/938); about 2/3 of responders were residents and 1/3 were fellows. Median age of participants was 32 years and 51.1% were female. Seventy-three percent of residents and 55% of fellows had at least one symptom of burnout, the difference largely related to higher scores for depersonalization among residents. For residents, greater satisfaction with work-life balance, meaning in work, and older age were associated with lower risk of burnout; for fellows, greater satisfaction with work-life balance and effective support staff were associated with lower risk of burnout. Trainees experiencing burnout were less likely to report career satisfaction. Career satisfaction was more likely among those reporting meaning in work and more likely for those working in the Midwest compared with the Northeast region. CONCLUSIONS: Burnout is common in neurology residents and fellows. Lack of work-life balance and lack of meaning in work were associated with reduced career satisfaction and increased risk of burnout. These results should inform approaches to reduce burnout and promote career satisfaction and well-being in US neurology trainees.

Long-term treatment with responsive brain stimulation in adults with refractory partial seizures.

OBJECTIVE: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. METHODS: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. RESULTS: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). CONCLUSIONS: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years.

Localization of interictal epileptiform activity using magnetoencephalography with synthetic aperture magnetometry in patients with a vagus nerve stimulator.

Magnetoencephalography (MEG) provides useful and non-redundant information in the evaluation of patients with epilepsy, and in particular, during the pre-surgical evaluation of pharmaco-resistant epilepsy. Vagus nerve stimulation (VNS) is a common treatment for pharmaco-resistant epilepsy. However, interpretation of MEG recordings from patients with a VNS is challenging due to the severe magnetic artifacts produced by the VNS. We used synthetic aperture magnetometry (g2) [SAM(g2)], an adaptive beamformer that maps the excessive kurtosis, to map interictal spikes to the coregistered MRI image, despite the presence of contaminating VNS artifact. We present a series of eight patients with a VNS who underwent MEG recording. Localization of interictal epileptiform activity by SAM(g2) is compared to invasive electrophysiologic monitoring and other localizing approaches. While the raw MEG recordings were uninterpretable, analysis of the recordings with SAM(g2) identified foci of peak kurtosis and source signal activity that was unaffected by the VNS artifact. SAM(g2) analysis of MEG recordings in patients with a VNS produces interpretable results and expands the use of MEG for the pre-surgical evaluation of epilepsy.

Proposal: different types of alteration and loss of consciousness in epilepsy.

There are at least five types of alterations of consciousness that occur during epileptic seizures: auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma. Each of these types of alterations of consciousness has a specific semiology and a distinct pathophysiologic mechanism. In this proposal we emphasize the need to clearly define each of these alterations/loss of consciousness and to apply this terminology in semiologic descriptions and classifications of epileptic seizures. The proposal is a consensus opinion of experienced epileptologists, and it is hoped that it will lead to systematic studies that will allow a scientific characterization of the different types of alterations/loss of consciousness described in this article.

Two-year seizure reduction in adults with medically intractable partial onset epilepsy treated with responsive neurostimulation: final results of the RNS System Pivotal trial.

OBJECTIVE: To demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci. METHODS: Randomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow-up. RESULTS: All 191 subjects were randomized. The percent change in seizures at the end of the blinded period was -37.9% in the active and -17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p < 0.0001). The serious adverse event rate was not different between subjects receiving active and sham stimulation. Adverse events were consistent with the known risks of an implanted medical device, seizures, and of other epilepsy treatments. There were no adverse effects on neuropsychological function or mood. SIGNIFICANCE: Responsive stimulation to the seizure focus reduced the frequency of partial-onset seizures acutely, showed improving seizure reduction over time, was well tolerated, and was acceptably safe. The RNS System provides an additional treatment option for patients with medically intractable partial-onset seizures.

Successful ECT treatment for medically refractory nonconvulsive status epilepticus in pediatric patient.

Status epilepticus is a life threatening condition with a high mortality rate in spite of aggressive treatment. There is little consensus on third and fourth line approaches in refractory cases. While electroconvulsive therapy (ECT) has been employed successfully as a treatment for refractory epilepsy and status epilepticus (SE) after exhausting conventional therapy, its use for pediatric patients is limited. We describe a 7-year-old pediatric case in which ECT was used successfully to treat medically refractory nonconvulsive status epilepticus (NCSE) without complete withdrawal of antiepileptic drugs (AED).