Examining brief and ultra-brief anxiety and depression screening methods in a real-world epilepsy clinic sample.

OBJECTIVE: Recent epilepsy quality measure recommendations for depression and anxiety screening endorse ultra-brief screeners, the Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2). Thus, it is important to assess how symptom detection may be affected using ultra-brief screeners compared with slightly longer, well-validated instruments: Neurological Disorders Depression Inventory-Epilepsy (NDDI-E) and Generalized Anxiety Disorder-7 (GAD-7). The objective was to compare symptom detection by brief versus ultra-brief depression and anxiety screeners in a large real-world epilepsy clinic sample. METHODS: This was a prospective, cross-sectional assessment of consecutive patients in an adult tertiary epilepsy practice who completed the GAD-7 and NDDI-E with embedded ultra-brief scales (GAD-2; GAD-Single Item: GAD-SI; NDDI-E 2 item: NDDIE-2) on a tablet and had clinic staff administered ultra-brief PHQ-2 (yes/no version) documented in the medical record at the same visit. Prevalences of positive anxiety and depression screens were calculated for each instrument overall, and by epilepsy status. Concordance correlation coefficients (CCC) were calculated comparing the ultra-brief with brief anxiety and depression instruments, and receiver operating curves (ROC) were calculated using the longer instruments as alternative standards. RESULTS: Among N = 422 individuals the prevalence of positive anxiety screen by GAD-7 was 24% and positive depression screen by NDDI-E was 20%. Positive anxiety and depression screens were significantly less prevalent among seizure-free individuals than those with continued seizures. The verbally administered yes/no PHQ-2 had only 1 positive screen (0.2%). Other than poor concordance between the PHQ-2 and NDDI-E, the screener pairs had acceptable concordance (CCC 0.79 to 0.92). Areas under the ROC curves were acceptable for the NDDIE-2, GAD-2 and GAD-SI (0.96, 0.98, and 0.89, respectively). SIGNIFICANCE: In this sample, clinic staff interview-administered yes/no PHQ-2 had exceedingly low sensitivity compared with the NDDI-E self-reported on a tablet. Further investigation is warranted to assess if poor detection is due to characteristics of this PHQ-2 in epilepsy samples, or method of administration in this clinic. The other ultra-brief anxiety and depression instruments demonstrated good concordance with the longer, well-validated instruments and may be useful in clinical practice.

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.

Practical applications of physical activity for successful cognitive aging.

As patients lose cognitive function, they lose autonomy and increasingly use fiscal, social, and medical resources. Healthcare costs for Americans older than age 65 years are three to five times higher than for the remaining population, and dementia is the third most costly disease in the United States. Interventions that promote successful aging can help patients and reduce the financial, workforce, and treatment resource burdens on the population. Because a relationship between physical activity, particularly aerobic exercise, and cognitive decline has been established, physical activity interventions may prove practical, affordable, and effective. Attention to empiric research and knowledge of evidence-based strategies for prescribing physical activity are critical for PAs to embrace.

Cutaneous erosions: a herald for impending pancytopenia in methotrexate toxicity.

Psoriatic plaque erosion is a rare toxic side effect of low-dose methotrexate (LDMTX) that has been reported during the treatment of psoriasis and described as a herald for impending pancytopenia. Fatalities from this have rarely been reported. Even rarer is methotrexate (MTX)-induced erosions of clinically normal skin in patients without a history of psoriasis. We report 3 rare presentations of MTX-induced cutaneous erosions, 2 fatalities occurring with MTX-induced psoriatic plaque erosions, and the sixth reported case of MTX-induced erosions with no prior history of psoriasis. Each were elderly patients on proton pump inhibitors with a history of chronic non-steroidal anti-inflammatory drug (NSAID) use. They all presented with acute onset of erosions after a recent change in their MTX dose. Pancytopenia followed in each case. Physicians' awareness of the sequelae in MTX-induced cutaneous erosions is imperative so MTX can be discontinued and treatment instituted to prevent fatal bone marrow suppression.

What is the role of screening instruments in the management of psychiatric comorbidities in epilepsy? Tools and practical tips for the most common comorbidities: Depression and anxiety.

Depression and anxiety are the most common psychiatric comorbidities in epilepsy and are known to increase healthcare utilization, the risk of refractory epilepsy, and anti-seizure medication intolerability. Despite this, depression and anxiety continue to be underrecognized and undertreated in people with epilepsy (PWE). Several barriers to the identification of depression and anxiety in PWE exist, including reliance on unstructured interviews rather than standardized, validated instruments. Moreover, there is a dearth of behavioral health providers to manage these comorbidities once identified. The use of validated screening instruments in epilepsy clinics can assist with both the identification of psychiatric symptoms and monitoring of treatment response by the epilepsy clinician for PWE with comorbid depression and/or anxiety. While screening instruments can identify psychiatric symptoms occurring within a specified time, they are not definitively diagnostic. Screeners can be time efficient tools to identify patients requiring further evaluation for diagnostic confirmation. This article reviews recent literature on the utility of depression and anxiety screening instruments in epilepsy care, including commonly used screening instruments, and provides solutions for potential barriers to clinical implementation. Validated depression and anxiety screening instruments can increase identification of depression and anxiety and guide epilepsy clinician management of these comorbidities which has the potential to positively impact patient care.

Post stroke pain: Is there under-diagnosis in Black versus White patients?

Stroke incidence is higher and stroke outcomes are poorer in Black patients compared to White patients. Poststroke pain, however, is not a well understood stroke outcome. Using the National Institutes of Health All of Us Research Program database, we hypothesized that the dataset would demonstrate proportionately higher relative risk of poststroke pain in the Black poststroke patient population compared to the White poststroke patient population. However, our analysis showed that Black stroke patients were diagnosed with poststroke pain at a similar rate as White stroke patients. As our results are not consistent with other poststroke outcomes in the literature, this study identifies a potentially underdiagnosed patient population, highlighting the need for further research.

Quality of life during usual epilepsy care for anxiety or depression symptoms: Secondary patient-reported outcomes in a randomized trial of remote assessment methods.

BACKGROUND AND OBJECTIVES: Anxiety and depression are highly prevalent and impactful in epilepsy. American Academy of Neurology quality measures emphasize anxiety and depression screening and quality of life (QOL) measurement, yet usual epilepsy care QOL and anxiety/depression outcomes are poorly characterized. The main objective was to assess 6-month QOL, anxiety and depression during routine care among adults with epilepsy and baseline anxiety or depression symptoms; these were prespecified secondary outcomes within a pragmatic randomized trial of remote assessment methods. METHODS: Adults with anxiety or depression symptoms and no suicidal ideation were recruited from a tertiary epilepsy clinic via an electronic health record (EHR)-embedded process. Participants were randomized 1:1 to 6 month outcome collection via patient portal EHR questionnaires vs. telephone interview. This report focuses on an a priori secondary outcomes of the overall trial, focused on patient-reported health outcomes in the full sample. Quality of life, (primary health outcome), anxiety, and depression measures were collected at 3 and 6 months (Quality of Life in Epilepsy-10, QOLIE-10, Generalized Anxiety Disorder-7, Neurological Disorders Depression Inventory-Epilepsy). Change values and 95 % confidence intervals were calculated. In post-hoc exploratory analyses, patient-reported anxiety/depression management plans at baseline clinic visit and healthcare utilization were compared with EHR-documentation, and agreement was calculated using the kappa statistic. RESULTS: Overall, 30 participants (15 per group) were recruited and analyzed, of mean age 42.5 years, with 60 % women. Mean 6-month change in QOLIE-10 overall was 2.0(95 % CI -6.8, 10.9), and there were no significant differences in outcomes between the EHR and telephone groups. Mean anxiety and depression scores were stable across follow-up (all 95 % CI included zero). Outcomes were similar regardless of whether an anxiety or depression action plan was documented. During the baseline interview, most participants with clinic visit EHR documentation indicating action to address anxiety and/or depression reported not being offered a treatment(7 of 12 with action plan, 58 %), and there was poor agreement between patient report and EHR documentation (kappa=0.22). Healthcare utilization was high: 40 % had at least one hospitalization or emergency/urgent care visit reported and/or identified via EHR, but a third (4/12) failed to self-report an EHR-identified hospitalization/urgent visit. DISCUSSION: Over 6 months of usual care among adults with epilepsy and anxiety or depression symptoms, there was no significant average improvement in quality of life or anxiety/depression, suggesting a need for interventions to enhance routine neurology care and achieve quality of life improvement for this group.

Coma blisters with hypoxemic respiratory failure.

A 24-year-old woman with quadriplegia was admitted with respiratory failure because of pneumonia. She was on multiple medications including diazepam, oxycodone, and amitriptyline, known to be associated with coma blisters, though she did not overdose on any of them. On hospital day 2, she developed multiple blisters on both sides of her right forearm and hand. Skin biopsy showed eccrine gland degeneration consistent with coma blisters. It was felt that hypoxemia from her pneumonia contributed to the development of these blisters, which occurred on both pressure and non-pressure bearing areas of the arm. Coma blisters are self-limited skin lesions that occur at sites of maximal pressure, mostly in the setting of drug overdose. However, coma blisters may occur with metabolic and neurological conditions resulting in coma.

Brown recluse spider bite to the upper lip.

Brown recluse spiders are predominantly found in south central United States. Their bites usually cause mild self-limiting reactions, although localized tissue necrosis and rare systemic, potentially fatal, envenomations are known to occur. Herein, we report an atypical presentation of a brown recluse bite in a 20 year old female who was admitted to the intensive care unit due to angioedema and cellulitis. We photographically document the bite site for twenty-four hours following envenomation. She received glucocorticoids, antihistamines, antibiotics and dapsone while hospitalized and was subsequently discharged with complete resolution of symptoms without the development of tissue necrosis or scarring.

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.

Highlights From AES2020, a Virtual American Epilepsy Society Experience.

Due to COVID-19 a live, in-person meeting was not possible for the American Epilepsy Society in 2020. An alternative, virtual event, the AES2020, was held instead. AES2020 was a great success with 4679 attendees from 70 countries. The educational content was outstanding and spanned the causes, treatments, and outcomes from epileptic encephalopathy to the iatrogenicity of epilepsy interventions to neurocognitive disabilities to the approach to neocortical epilepsies. New gene therapy approaches such as antisense oligonucleotide treatment for Dravet syndrome were introduced and neuromodulation devices were discussed. There were many other topics discussed in special interest groups and investigators' workshops. A highlight was having a Nobel prize winner speak about memory processing. Human intracranial electrophysiology contributes insights into memory processing and complements animal work. In a special COVID symposium, the impact of COVID on patients with epilepsy was reviewed. Telehealth has been expanded rapidly and may be well suited for some parts of epilepsy care. In summary, the epilepsy community was alive and engaged despite being limited to a virtual platform.

Vaccines under study: non-HIV vaccines.

The development of effective vaccines has been an amazing public health achievement and has resulted in countless lives being saved. Dermatologic therapy has recently been greatly advanced by the licensure of an effective human papillomavirus vaccine and herpes zoster vaccine. Despite these successes, many infectious diseases do not currently have a preventive vaccine. We review potential vaccines against selected infectious agents, including viruses, bacteria, fungi, and protozoa that have cutaneous and mucocutaneous manifestations. The road to licensure of a new vaccine begins with exhaustive preclinical and clinical studies, and many of these will fail before a successful vaccine candidate is approved. This article focuses on vaccines that have yet to be approved for licensure.

Cutaneous metastasis of breast carcinoma presenting as alopecia neoplastica.

Alopecia neoplastica is defined as hair loss secondary to a visceral malignancy that has metastasized to the scalp. We describe a woman with adenocarcinoma of the breast who developed alopecia neoplastica while receiving antineoplastic therapy. Alopecia neoplastica has been observed in 25 women. Breast cancer was the primary malignancy in 84% of patients with alopecia neoplastica. Other primary tumors whose metastases presented as neoplasm-related hair loss each occurred in one individual with gastric carcinoma, colon carcinoma, cervical carcinoma, and trophoblastic tumor.

AT1 receptor antagonism does not influence early radiation-induced changes in microglial activation or neurogenesis in the normal rat brain.

Blockers of the renin-angiotensin-aldosterone system (RAAS) ameliorate cognitive deficits and some aspects of brain injury after whole-brain irradiation. We investigated whether treatment with the angiotensin II type 1 receptor antagonist L-158,809 at a dose that protects cognitive function after fractionated whole-brain irradiation reduced radiation-induced neuroinflammation and changes in hippocampal neurogenesis, well-characterized effects that are associated with radiation-induced brain injury. Male F344 rats received L-158,809 before, during and after a single 10-Gy dose of radiation. Expression of cytokines, angiotensin II receptors and angiotensin-converting enzyme 2 was evaluated by real-time PCR 24 h, 1 week and 12 weeks after irradiation. At the latter times, microglial density and proliferating and activated microglia were analyzed in the dentate gyrus of the hippocampus. Cell proliferation and neurogenesis were also quantified in the dentate subgranular zone. L-158,809 treatment modestly increased mRNA expression for Ang II receptors and TNF-α but had no effect on radiation-induced effects on hippocampal microglia or neurogenesis. Thus, although L-158,809 ameliorates cognitive deficits after whole-brain irradiation, the drug did not mitigate the neuroinflammatory microglial response or rescue neurogenesis. Additional studies are required to elucidate other mechanisms of normal tissue injury that may be modulated by RAAS blockers.

Effects of the AT1 receptor antagonist L-158,809 on microglia and neurogenesis after fractionated whole-brain irradiation.

Cognitive dysfunction develops in approximately 50% of patients who receive fractionated whole-brain irradiation and survive 6 months or more. The mechanisms underlying these deficits are unknown. A recent study demonstrated that treatment with the angiotensin II type 1 receptor antagonist (AT(1)RA) L-158,809 before, during and after fractionated whole-brain irradiation prevents or ameliorates radiation-induced cognitive deficits in adult rats. Given that (1) AT(1)RAs may function as anti-inflammatory drugs, (2) inflammation is thought to contribute to radiation injury, and (3) radiation-induced inflammation alters progenitor cell populations, we tested whether the cognitive benefits of L-158,809 treatment were associated with amelioration of the sustained neuroinflammation and changes in neurogenesis that are induced by fractionated whole-brain irradiation. In rats examined 28 and 54 weeks after irradiation, L-158,809 treatment did not alter the effects of radiation on the number and activation of microglia in the perirhinal cortex and hippocampus, nor did it prevent the radiation-induced decrease in proliferating cells and immature neurons in the hippocampus. These findings suggest that L-158,809 does not prevent or ameliorate radiation-induced cognitive deficits by modulation of chronic inflammatory mechanisms, but rather may reduce radiation-induced changes that occur earlier in the postirradiation period and that lead to cognitive dysfunction.