A placebo controlled, randomized clinical trial of galcanezumab for vestibular migraine: The INVESTMENT study.

OBJECTIVE: To study if galcanezumab is effective for vestibular migraine (VM). BACKGROUND: There are currently no placebo-controlled trials showing that treatment is effective for VM. Therefore, we performed the first placebo controlled, randomized clinical trial of a calcitonin gene-related peptide-targeted monoclonal antibody for VM. METHODS: This was a single site, prospective, double-blind placebo controlled randomized clinical trial. Key inclusion criteria were as follows: participants aged 18-75 years with a diagnosis of VM or probable VM per Barany Society criteria. The primary outcome was change in VM-PATHI (Vestibular Migraine Patient Assessment Tool and Handicap Inventory) score, and secondary outcomes included change in DHI (Dizziness Handicap Inventory) score, and count of definite dizzy days (DDDs). Participants were randomized 1:1 to 3 months of treatment with galcanezumab or placebo via subcutaneous injection with a pre-filled syringe, 240 mg the first month, and 120 mg for the second and third months. RESULTS: Forty participants were randomized, and 38 participants were in the modified intent to treat analysis. VM-PATHI score was reduced 5.1 points (95% confidence interval [CI] -13.0 to 2.7) for placebo (N = 21), and 14.8 points (95% CI -23.0 to -6.5) for galcanezumab (N = 17), a difference of -9.6 (95% CI -20.7 to 1.5, p = 0.044). DHI dropped 8.3 points in the placebo arm (95% CI -15.0 to 1.6), and 22.0 points in the galcanezumab arm (95% CI -31.9 to -12.1), a difference of -13.7 (95% CI -20.4 to -8.5, p = 0.018). The count of DDDs per month dropped from 18 days (standard deviation [SD] 7.6) in the baseline month to 12.5 days (SD 11.2) in month 4 for those in the placebo arm, and from 17.9 days (SD 7.9) in the baseline month to 6.6 days (SD 7.3) in month 4 for those in the galcanezumab arm, a difference of -5.7 days (95% CI -10.7 to -0.7, p = 0.026). No serious adverse events were observed. CONCLUSIONS: In this pilot study, galcanezumab was effective in treating VM.

Visually enhanced vestibulo-ocular reflex gain in patients with vestibular disease.

Objective: Vestibular migraine (VM) is a diagnostic challenge. Visually enhanced vestibulo-ocular reflex (VVOR) gain, a measure of the visual-vestibular interaction, has been proposed as a tool for diagnosing VM. This study seeks to evaluate VVOR gain's diagnostic capability to predict VM and to compare the phenotypes of vestibular patients with elevated versus normal/low VVOR gain. Methods: A retrospective review of consecutive adult patients at a dizziness clinic from October 2016 and December 2020 was conducted. VVOR gain's diagnostic performance was assessed with the area under the receiver operating characteristic (AUROC) analysis. Demographic factors and clinical presentations were compared between vestibular patients with elevated versus normal/low VVOR gain. Results: One hundred forty patients (70 with VM) were analyzed. VVOR gain was elevated in 68.6% of patients with VM, compared to 52.9% of patients without VM (p = .057). The AUROC of VVOR gain was 0.5902 (95% confidence interval: 0.4958-0.6846). Vestibular patients with elevated VVOR gain were younger than those with normal/low VVOR gain (mean age 50 vs. 62, p < .0001). A higher proportion of subjects with elevated VVOR gain had symptoms triggered by certain foods (17.6% vs. 5.5%, p = .040) and experienced sound sensitivity (34.1% vs. 18.2%, p = .040) and motion sensitivity (23.5% vs. 9.1%, p = .041). A greater proportion of VM patients with elevated VVOR gain were triggered by certain foods (27.1% vs. 0%, p = .006). Conclusion: VVOR gain alone has limited ability to discriminate VM from other vestibular conditions and must be interpreted carefully. VVOR gain elevation may be associated with food triggers and motion and sound sensitivity. Level of Evidence: IV.

The impact of a structured onboarding program for newly hired nurse practitioners and physician assistants.

BACKGROUND: The return on investment for onboarding programs and their effect on attrition and engagement within health systems across the United States are unclear. LOCAL PROBLEM: The existing onboarding program for nurse practitioners (NPs) and physician assistants (PAs) at a hospital on the west coast was varied and lacked a clinician focus. A structured onboarding program was created to standardize their entry to our workforce. METHODS: A needs assessment was completed with a stakeholder focus group, for which an onboarding curriculum was then created. Participants completed presurveys/postsurveys during the data collection period as the primary outcome. A Plan-Do-Study-Act approach was used to revise session content and improve participant experience. Onboarding costs and attrition were tracked as secondary outcomes. INTERVENTIONS: From July 2017 through June 2019, newly hired NPs and PAs were invited to participate in the program. Six quarterly cohorts attended five in-person 2-hour onboarding sessions over 12 months. RESULTS: One hundred twenty-nine eligible NPs and PAs completed an anonymous pre/post Qualtrics survey. The aggregate responses were significantly improved using Fisher exact test. Measured onboarding value was not significantly changed. Mean pre-onboarding attrition was 10.3% compared with 4.5% for onboarding participants. The annual cost for onboarding participants was $63,470 versus $256,826 as the estimated mean cost of one separation within their first year. CONCLUSIONS: Workforce engagement, standardized knowledge, and participant attrition revealed an improving trend with this structured onboarding program. The investment to formalize onboarding newly hired NPs and PAs was modest, and the findings suggest that an onboarding program has financial and engagement merit.

Broadening vestibular migraine diagnostic criteria: A prospective cohort study on vestibular migraine subtypes.

BACKGROUND: Current Bárány Society criteria for vestibular migraine (VM) include only episodic symptoms. Anecdotal observations suggest that some patients have episodic forms and others have chronic forms of VM, with interplay and evolution of both subtypes over time. OBJECTIVE: To better understand VM subtypes and evaluate a more inclusive diagnostic schema. METHODS: Four VM groups were studied: definite episodic (dVM), probable episodic (pVM), definite chronic (dCVM), and probable chronic (pCVM). Chronic VM was defined as having more than 15 dizzy days per month. Sociodemographic and clinical characteristics were analyzed, along with Dizziness Handicap Inventory (DHI) and Vestibular Migraine Patient Assessment Tool and Handicap Inventory (VM-PATHI) scores. RESULTS: 54 adults with a mean age of 47.0 years (SD 13.7) were enrolled. 10 met criteria for dVM, 11 pVM, 22 dCVM, and 11 pCVM. Overall, there were strong similarities in clinical characteristics between dVM, pVM, dCVM, and pCVM. Compared to subjects with episodic VM, those with chronic VM had a higher average number of VM triggers (8.7 vs. 6.4, P = 0.019), including motion (93.9% vs. 66.7%, P = 0.009), scrolling on a screen (78.8% vs. 47.6%, P = 0.018), skipped meal (57.6% vs. 23.8%, P = 0.015), and air travel (57.6% vs. 23.8%, P = 0.015). They also had higher symptom severity (DHI = 53.3, P = 0.194) and burden of disease (VM-PATHI = 48.2, P = 0.030) scores. CONCLUSIONS: Many patients do not meet current Bárány Society criteria for VM based on their duration of vestibular symptoms. Yet, these patients with chronic VM endorse several indistinguishable symptoms from those who do meet criteria. A more inclusive diagnostic schema should be adopted where patients with vestibular symptoms shorter than 5 minutes or longer than 72 hours are also recognized as having VM.

Understanding Dizzy Patients a Cross-Sectional Analysis of Attitudes toward Diagnosis, Providers, and Treatment.

OBJECTIVE: To evaluate patients' attitudes regarding their dizziness, provider capabilities, and receptiveness toward treatment. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary care vestibular clinic. PATIENTS: Ages 18 years or older, fluent in English, and who presented with a chief complaint of dizziness or vertigo. INTERVENTION(S): N/A. MAIN OUTCOMES MEASURE(S): Non-validated questionnaire surveying patients' beliefs regarding the cause of their dizziness, likelihood of successful treatment, and openness to various treatment modalities. RESULTS: Patients were asked to complete an online non-validated survey regarding their dizziness prior to being evaluated in neurotology clinic. About 67 surveys were completed between January 2017 and September 2018. A majority of patients attributed their dizziness to their ears (n = 47, 70%), followed by the brain (n = 29, 43%). Most subjects chose "neither agree nor disagree" about whether their provider could identify the cause of their dizziness (27%). Most subjects also chose "neither agree nor disagree" that their dizziness would resolve with treatment (31%). These attitudes were not influenced by demographics, dizziness severity, anxiety, depression, or quality of life on multivariate ordinal regression modeling. CONCLUSIONS: Patients who experience dizziness have neutral attitudes with regards to believing that their provider will be able to identify the cause of their dizziness and whether their dizziness will resolve with treatment. These neutral attitudes are experienced by a plurality of patients and do not differ by demographic information, dizziness handicap, quality of life, depression, or anxiety.

Patient Use of Low-cost Digital Videoscopes and Smartphones for Remote Ear and Oropharyngeal Examinations.

Importance: During the novel coronavirus disease 2019 pandemic, telehealth has become a vital component of health care delivery. For otolaryngology evaluations, examination of the ear and oropharynx is important but difficult to achieve remotely. Objective: To assess the feasibility of patient use of low-cost digital videoscopes and smartphones for examination of the ear and oropharynx. Design, Setting, and Participants: A prospective quality improvement study was conducted in an academic adult otolaryngology clinic including 23 patients who presented for an in-person appointment and owned a smartphone device. The study was conducted from July 1 to 15, 2020. Interventions: Participants were asked to capture pictures and videos of their ear canals and oropharynx with digital videoscopes and their smartphones under real-time guidance over a telehealth platform. They were then surveyed about their experience. Main Outcomes and Measures: The primary outcomes were ratings by health care clinicians and a blinded otolaryngologist reviewer of image acceptability. Secondary outcomes included participant time to image acquisition and willingness to purchase digital videoscopes for telehealth use. Results: Of the 23 participants included, 14 were women (61%); mean age was 50 years (range, 21 to 80 years). Of the images obtained using the digital otoscope ear examination, 95% were considered acceptable by the health care clinicians and 91% were considered acceptable by the blinded reviewer; 16 participants (70%) reported that the otoscope was easy to use. The mean time to acquire images for both ears was 114 seconds (95% CI, 84-145 seconds). Twenty-one participants (91%) were willing to pay for a digital otoscope for telehealth use. For the oropharyngeal examination, a greater proportion of smartphone video examinations were considered acceptable by clinicians (63% acceptability) and the blinded reviewer (55%) compared with the digital endoscope (clinicians, 40%; blinded reviewer, 14%). The mean time required for the oropharyngeal examination smartphone video capture was shorter at 35 seconds compared with both the digital endoscope (difference, -27 seconds; 95% CI, -7 to -47 seconds) and smartphone photo capture (difference, -53 seconds; 95% CI, -20 to -87 seconds). Conclusions and Relevance: Digital otoscopes and smartphones apparently can facilitate remote head and neck physical examination in telehealth. Digital otoscopes were useful for ear examinations, and smartphone videos appeared to be the most useful for oropharyngeal examinations. Further studies are required to determine specific diagnostic capabilities in various telehealth practice settings.

Development and Validation of VM-PATHI: Vestibular Migraine Patient Assessment Tool and Handicap Inventory.

OBJECTIVE: The aim of this article is to develop and validate a disease-specific, patient-reported outcome measure for vestibular migraine. SETTING: Tertiary care vestibular center. PATIENTS: Adult patients with definite or probable vestibular migraine per Barany Society Criteria. STUDY DESIGN: This was a prospective cohort study. VM-PATHI (Vestibular Migraine Patient Assessment Tool and Handicap Inventory) was developed with expert input, literature review, and patient feedback. VM-PATHI scores were compared between those with vestibular migraine and controls, across several time points, and to other dizziness and quality of life (QoL) measures. RESULTS: A 25-item questionnaire was developed. Cronbach's α was high at 0.92. Test-retest reliability was excellent (r = 0.90, p < 0.001). Scores were much higher in patients with vestibular migraine (mean 42.5, SD = 16.1) than control patients (mean = 9.6, SD = 8.5). VM-PATHI scores were responsive to treatment (p = 0.01). Scores were well correlated with general QoL, depression, and anxiety scores. Scores were also correlated with the Dizziness Handicap Inventory (r = 0.69). An exploratory factor analysis was performed, which revealed 6 distinct factors that corresponded well to different aspects of disease-related symptomatology. CONCLUSION: VM-PATHI is a valid, reliable, and responsive measure of disease severity in vestibular migraine.

Understanding the Dizziness Handicap Inventory (DHI): A Cross Sectional Analysis of Symptom Factors That Contribute to DHI Variance.

OBJECTIVE: The Dizziness Handicap Inventory (DHI) is the most commonly used quality of life measure for vestibular disorders. However, there is wide variability in scores, and little is known about which variables contribute to dizziness-related quality of life. Our goal was to investigate the key demographic and symptom-related factors to that account for DHI variance. STUDY DESIGN: Cross-sectional survey. SETTING: Tertiary referral center. PATIENTS: Adult patients presenting to a dizziness clinic. MAIN OUTCOME MEASURE: DHI variance explained by multiple linear regression. RESULTS: Seventy subjects were included in our study. We performed univariate analyses on numerous demographic and dizziness-related factors, and constructed a multivariate model based on explaining the highest variance in the data with the least number of independent variables. Several validated quality of life and mental health survey scores (SF-36-quality of life; PHQ-9-depression; and GAD-7-anxiety) were significantly correlated with higher DHI scores. Additional factors, including the number of dizzy days per month, the number of dizziness descriptors (spinning, lightheadedness, disequilibrium, etc.), and the number of dizziness triggers (loud sounds, stress, riding in a car, etc.), were all significantly associated with higher DHI scores; a multiple linear regression model showed that these three aforementioned factors combined accounted for 56% of the variability in the DHI scores (p < 0.0001). Adding an index of depression, as measured by the PHQ-9, increased the adjusted R to 64% (p < 0.0001). CONCLUSIONS: DHI score variability is explained by mental health and quality-of-life measures in addition to the daily burden of dizziness.

Pharmacogenetics and the pharmacological management of depression.

Depression is a chronic disease seen in many healthcare settings. Current pharmacological treatment options are successful in two-thirds of patients. One CYP450 enzyme, CYP2D6, is responsible for the metabolism of 30% of all drugs including many antidepressants. Phenotypes of metabolizer status affect antidepressant treatment outcomes and adverse drug reactions.