Primary care electronic medical records can be used to predict risk and identify potentially modifiable factors for early and late death in adult onset epilepsy.

OBJECTIVE: To use clinically informed machine learning to derive prediction models for early and late premature death in epilepsy. METHODS: This was a population-based primary care observational cohort study. All patients meeting a case definition for incident epilepsy in the Health Improvement Network database for inclusive years 2000-2012 were included. A modified Delphi process identified 30 potential risk factors. Outcome was early (within 4 years of epilepsy diagnosis) and late (4 years or more from diagnosis) mortality. We used regularized logistic regression, support vector machines, Gaussian naive Bayes, and random forest classifiers to predict outcomes. We assessed model calibration, discrimination, and generalizability using the Brier score, mean area under the receiver operating characteristic curve (AUC) derived from stratified fivefold cross-validation, plotted calibration curves, and extracted measures of association where possible. RESULTS: We identified 10 499 presumed incident cases from 11 194 182 patients. All models performed comparably well following stratified fivefold cross-validation, with AUCs ranging from 0.73 to 0.81 and from 0.71 to 0.79 for early and late death, respectively. In addition to comorbid disease, social habits (alcoholism odds ratio [OR] for early death = 1.54, 95% confidence interval [CI] = 1.12-2.11 and OR for late death = 2.62, 95% CI = 1.66-4.16) and treatment patterns (OR for early death when no antiseizure medication [ASM] was prescribed at baseline = 1.33, 95% CI = 1.07-1.64 and OR for late death after receipt of enzyme-inducing ASM at baseline = 1.32, 95% CI = 1.04-1.66) were significantly associated with increased risk of premature death. Baseline ASM polytherapy (OR = 0.55, 95% CI = 0.36-0.85) was associated with reduced risk of early death. SIGNIFICANCE: Clinically informed models using routine electronic medical records can be used to predict early and late mortality in epilepsy, with moderate to high accuracy and evidence of generalizability. Medical, social, and treatment-related risk factors, such as delayed ASM prescription and baseline prescription of enzyme-inducing ASMs, were important predictors.

High diagnostic yield and novel variants in very late-onset spasticity.

Hereditary spastic paraplegias (HSPs) are a diverse group of genetic conditions with variable severity and onset age. From a neurogenetic clinic, we identified 14 patients with very late-onset HSP, with symptoms starting after the age of 35. In this cohort, sequencing of known genetic causes was performed using clinically available HSP sequencing panels. We identified 4 patients with mutations in SPG7 and 3 patients with SPAST mutations, representing 50% of the cohort and indicating a very high diagnostic yield. In the SPG7 group, we identified novel variants in two patients. We have also identified two novel mutations in the SPAST group. We present sequencing data from cDNA and RT-qPCR to support the pathogenicity of these variants, and provide observations regarding the poor genotype-phenotype correlation in these conditions that should be the subject of future study.

Coercive Parent-Adolescent Interactions Predict Substance use and Antisocial Behaviors Through Early Adulthood: A Dynamic Systems Perspective.

This study revisits the association between coercive parent-adolescent interactions and adolescent externalizing behaviors. Specifically, we investigate the moment-to-moment coercive exchanges between parents and adolescents and how these dynamic processes map to the long-term development of substance use and antisocial behavior from middle adolescence to early adulthood. We collected videotaped observations with 794 adolescents (ages 16-17 years) and their parents during interactions and coded their real-time behavioral exchanges. State Space Grid analyses were used to measure the proportion of time in which each parent-adolescent dyad engaged in the Dyadic Coercion region as an indicator of rigidity in dyadic coercion. We also measured adolescents' substance use and antisocial behavior at ages 16-17, ages 18-19, and ages 21-22. The enduring impact of parent-adolescent coercive interaction on substance use and antisocial behavior was tested using categorical latent growth curve models and path models. Adolescents with more coercive interactions with parents showed higher rates of increase in alcohol use and higher levels of antisocial behavior through early adulthood. The findings highlight the unique contribution of using intensive data to understand coercive interactions on a micro-timescale and how these dynamics influence long-term development in externalizing behaviors. Implications for intervention studies are discussed.

Patient perceptions and barriers to epilepsy surgery: evaluation in a large health region.

PURPOSE: Despite evidence that carefully selected patients with refractory focal epilepsy benefit from epilepsy surgery, significant delays remain. We examined patient knowledge and perceptions regarding epilepsy surgery. METHODS: A 5-minute questionnaire was administered to consecutive adults with focal epilepsy seen in the epilepsy clinic in a large Canadian health region. Survey items assessed the following: (1) knowledge of surgical options, (2) perceptions about the risks of surgery vs. ongoing seizures, (3) disease disability, (4) treatment goals, and (5) demographic and socioeconomic variables. Patient responses were compiled to calculate a "Barriers to Epilepsy Surgery Composite" (BESC) score. RESULTS: Of 129 eligible patients, 107 completed the questionnaire (response rate: 83%). The average BESC score was 60/100. Apprehension about epilepsy surgery was less likely among patients who had previously undergone epilepsy surgery and those born in Canada. DISCUSSION: People with epilepsy often have hindering perceptions that can contribute to delays in surgical care.

Patient knowledge about issues related to pregnancy in epilepsy: a cross-sectional study.

In 2009, new guidelines were established by the American Academy of Neurology regarding pregnancy in women with epilepsy. A questionnaire was developed to assess patient knowledge of current guidelines related to epilepsy and pregnancy. Patients were recruited from a single outpatient clinic in a large Canadian tertiary care center. Patients were eligible to participate if they were female, of reproductive age, had active epilepsy for at least 6 months and were not cognitively impaired. One hundred women completed the survey (response rate 87%) with a median score of 40%. A significant association was found between total score and years of education (p<0.001). Significant associations were not found between total score and epilepsy duration (p=0.37), previously being pregnant (p=0.22), and polytherapy (p=0.31). Patient knowledge of the impact of epilepsy on pregnancy is low. More knowledge translation efforts are required to increase knowledge of issues related to pregnancy for women with epilepsy.

Effect of Integrating Access to a Prescription Drug Monitoring Program Within the Electronic Health Record on the Frequency of Queries by Primary Care Clinicians: A Cluster Randomized Clinical Trial.

Importance: Tools that are directly integrated with the electronic health record (EHR) workflow can reduce the hassle cost of certain guideline-concordant practices, such as querying a prescription drug monitoring program (PDMP) before prescribing opioids. Objective: To investigate the effect of integrating access to a PDMP within the EHR on the frequency of program queries by primary care clinicians. Design Settings and Participants: The PRINCE (Prescribing Interventions for Chronic Pain Using the Electronic Health Record) randomized trial used a factorial cluster design at the clinic level in 43 primary care clinics in Minnesota. In all, 309 clinicians participated; 161 clinicians were given EHR-integrated access to PDMP at the intervention clinics, and 148 clinicians had the usual access at the control clinics. The intervention went live on August 27, 2020, and data were collected through March 3, 2021. Intervention: Single sign-on access to the Minnesota PDMP was integrated into the EHR, allowing clinicians to query a patient's controlled substance prescription and dispensing history as recorded in the Minnesota PDMP directly from the patient's EHR record without logging into a separate web portal. Additionally, the integration tool alerted clinicians and reminded them to review the PDMP if a patient had 3 or more opioid prescriptions in the past year and 1 or more in the past 6 months. Clinics in the control group did not receive access to the EHR-integrated PDMP tool; instead, these participants logged into the PDMP web portal separately. Main Outcomes and Measures: Monthly PDMP query counts for primary care clinicians, overall and by modality (EHR-based, web-based, via a clinical delegate), adjusted for clinician characteristics, including type (physician, nurse practitioner, physician assistant), sex, and years in practice. Data were analyzed from August 2021 to May 2022. Results: Of the 43 participating clinics with 309 clinicians, 21 clinics with 161 clinicians (102 [63.4%] women; 114 [70.8%] physicians; tenure, 10.6 [4.4] years) received the PDMP integration intervention. Baseline unadjusted monthly PDMP query rates for the average clinician were 6.6 (95% CI, 4.4-9.9) vs 8.8 (95% CI, 6.0-13.1) queries in the control vs the PDMP integration group, respectively. During the intervention, PDMP query rates for the average clinician were 6.9 (95% CI, 4.7-10.3) vs 14.8 (95% CI, 10.0-22.0) queries among the control vs the PDMP integration group, respectively. Compared with the control group, the EHR-integrated PDMP tool produced a 60% greater increase in the relative change in monthly PDMP queries (95% CI, 51%-70%). An increase in PDMP queries via the EHR-integrated PDMP tool drove this increase, while web-based and delegate queries declined by 39% more among the intervention compared with the control group (95% CI, 34%-43%). Conclusions and Relevance: This cluster randomized clinical trial found that integrating access to the PDMP in the EHR increased PDMP-querying rates, suggesting that direct access reduced hassle costs and can dramatically improve adherence to guideline-concordant care practices among primary care clinicians. Trial Registration: ClinicalTrials.gov Identifier: NCT04601506.

PRescribing Interventions for Chronic pain using the Electronic health record (PRINCE): Study protocol.

BACKGROUND: Primary care is a frequent source of pain treatment and opioid prescribing. The objective of the Prescribing Interventions for Chronic Pain using the Electronic health record (PRINCE) study is to assess the effects of two behavioral economics-informed interventions embedded within the electronic health record (EHR) on guideline-concordant pain treatment and opioid prescribing decisions in primary care settings. METHODS: Setting: The setting for this study is 43 primary care clinics in Minnesota. DESIGN: The PRINCE study uses a cluster-randomized 2 × 2 factorial design to test the effects of two interventions. An adaptive design allows for the possibility of secondary randomization to test if interventions can be titrated while maintaining efficacy. INTERVENTIONS: One intervention alters the "choice architecture" within the EHR to nudge clinicians toward non-opioid treatments for opioid-naïve patients and toward tapering for patients currently receiving a "high risk" opioid. The other intervention integrates the prescription drug monitoring program (PDMP) directly within the EHR. OUTCOME: The primary outcome for opioid-naïve patients is whether an opioid is prescribed in a primary care visit without a non-opioid alternative pain treatment. The primary outcome for current opioid-using patients is whether opioid prescriptions were tapered with a documented rationale. DISCUSSION: The PRINCE study will provide real-world evidence on two approaches to improving pain treatment in primary care using the EHR. The adaptive study design strikes a balance between establishing intervention efficacy and testing whether efficacy varies with intervention intensity.

Neurologists' and neurology residents' knowledge of issues related to pregnancy for women with epilepsy.

We aimed to assess physician knowledge for 2009 guidelines established by the American Academy of Neurology and American Epilepsy Society regarding issues related to pregnancy for women with epilepsy. A questionnaire was developed and distributed to all neurologists and neurology residents practicing in a large Canadian health region serving a population of 1.4 million. Descriptive statistics were obtained and percentage of correct responses was calculated. Forty-five physicians completed the survey (response rate = 83.3%), with a median correct score of 50%. Residents were more likely (93.3%) to state that this information was important to their practice than staff physicians (40.0%). Overall knowledge of outcomes associated with specific AEDs was poor; less than half of the physicians correctly indicated which AEDs were associated with adverse outcomes for the majority of drug-related questions. We recommend multifaceted, interactive implementation strategies for increasing knowledge of guideline contents.

An investigation of the relation between sibilant production and somatosensory and auditory acuity.

The relation between auditory acuity, somatosensory acuity and the magnitude of produced sibilant contrast was investigated with data from 18 participants. To measure auditory acuity, stimuli from a synthetic sibilant continuum ([s]-[ʃ]) were used in a four-interval, two-alternative forced choice adaptive-staircase discrimination task. To measure somatosensory acuity, small plastic domes with grooves of different spacing were pressed against each participant's tongue tip and the participant was asked to identify one of four possible orientations of the grooves. Sibilant contrast magnitudes were estimated from productions of the words 'said,' 'shed,' 'sid,' and 'shid'. Multiple linear regression revealed a significant relation indicating that a combination of somatosensory and auditory acuity measures predicts produced acoustic contrast. When the participants were divided into high- and low-acuity groups based on their median somatosensory and auditory acuity measures, separate ANOVA analyses with sibilant contrast as the dependent variable yielded a significant main effect for each acuity group. These results provide evidence that sibilant productions have auditory as well as somatosensory goals and are consistent with prior results and the theoretical framework underlying the DIVA model of speech production.

The syndrome of stroke-like migraine attacks after radiation therapy associated with prolonged unresponsiveness in an adult patient.

INTRODUCTION: The syndrome of stroke-like migraine attacks after radiation therapy (SMART) is an extremely rare complication of cerebral irradiation. It is characterized by reversible episodic neurological dysfunction, commonly associated with headaches and occasionally with seizures, occurring years after cranial radiotherapy. Approximately a dozen cases have been reported in adult patients to date. CASE REPORT: In 1997, a 48-year-old man underwent resection of a right cerebellar metastasis from renal cell carcinoma, followed by whole-brain irradiation. Two years later he began experiencing recurrent episodes of headache associated with reversible left hemiparesis, dysphasia, visual field defects, and confusion. Over subsequent years these episodes increased in frequency, and in 2009 and 2010 the patient experienced 2 episodes associated with seizures and characterized by severe depression in level of consciousness (GCS 5); the latter of these was particularly prolonged, with neurological recovery requiring almost 6 months. Cortical and leptomeningeal gadolinium enhancement was demonstrated on magnetic resonance imaging during the second episode. Repeated electroencephalography studies did not demonstrate any epileptiform activity, and extensive workup including brain biopsy failed to identify any neoplastic, vascular, or infective pathology. The diagnosis of SMART syndrome was therefore made. CONCLUSIONS: Reduced level of consciousness of such severity and duration as observed here has not previously been described in SMART syndrome. This report, however, suggests that an excellent prognosis can be expected even in cases of prolonged unresponsiveness. The pathogenic mechanisms of SMART syndrome remain unclear, but may involve pathways common to both migraine and epilepsy.

Feasibility of using an online tool to assess appropriateness for an epilepsy surgery evaluation.

OBJECTIVES: To examine the applicability of applying an online tool to determine the appropriateness of referral for an epilepsy surgical evaluation and to determine whether appropriateness scores are concordant with the clinical judgment of epilepsy specialists. METHODS: We prospectively applied the tool in 107 consecutive patients with focal epilepsy seen in an epilepsy outpatient clinic. Variables collected included seizure type, epilepsy duration, seizure frequency, seizure severity, number of antiepileptic drugs (AEDs) tried, AED-related side effects, and the results of investigations. Appropriateness ratings were then compared with retrospectively collected information concerning whether a surgical evaluation had been considered. RESULTS: Thirty-nine patients (36.4%) were rated as appropriate for an epilepsy surgical evaluation, all of whom had adequately tried 2 or more appropriate AEDs. The majority of patients (84.6%) rated as appropriate had previously been considered or referred for an epilepsy surgical evaluation. Tool feasibility of use was high, with the exception of assessing whether previous AED trials had been adequate and discrepancies between physician and patient reports of AED side effects. CONCLUSIONS: Our evidence-based, online clinical decision tool is easily applied and able to determine whether patients with focal epilepsy are appropriate for a surgical evaluation. Future validation of this tool will require application in clinical practice and assessment of potential improvements in patient outcomes.