Real-world effectiveness and satisfaction with intravenous eptinezumab treatment in patients with chronic migraine: REVIEW, an observational, multi-site, US-based study.

BACKGROUND: Despite recent advancements in migraine treatment, some patients continue to endure significant disease burden. Due to the controlled nature of randomized trials in migraine prevention, many real-world patients with comorbidities or prior exposure to certain therapies are excluded. Capturing evidence of the effectiveness of treatment in real-world clinical settings can further shape treatment paradigms. The objective of this study was to develop a comprehensive understanding of both patients' and physicians' real-world experiences with eptinezumab for chronic migraine (CM). METHODS: REVIEW (Real-world EVidence and Insights into Experiences With eptinezumab) is an observational, multi-site (n = 4), US-based study designed to evaluate real-world experiences of patients treated with eptinezumab and their treating physicians. Patients were ≥ 18 years of age, with a diagnosis of CM, who had completed ≥ 2 consecutive eptinezumab infusion cycles (≥ 6 months of exposure). The study included a retrospective chart review, a patient survey, and a semi-structured physician interview that assessed patient and/or physician satisfaction with elements of daily living / well-being, migraine symptomology, and perspectives of the eptinezumab infusion experience. RESULTS: Of the 94 patients enrolled, 83% (78/94) were female, the mean age was 49.2 years, and the mean time since migraine diagnosis was 15.4 years. Before eptinezumab treatment, patients experienced a mean of 8 self-reported "good" days/month, which increased to 18 after treatment. Most patients took, on average, ≥ 10 days/month of prescription and/or over-the-counter medication (81% [75/93] and 66% [61/93], respectively) to treat migraine attacks before eptinezumab treatment, which dropped to 26% (24/93) and 23% (21/93) following eptinezumab treatment. Prior to receiving eptinezumab, 62% (58/93) of patients indicated being at least slightly concerned about infusions; after eptinezumab infusion, this dropped to 14% (13/93). These patient survey findings were consistent with physician responses. CONCLUSION: This real-world evidence study demonstrated high overall satisfaction with the effectiveness of eptinezumab treatment for CM among most patients and their physicians.

A Pilot Study of Symptoms of Major Depressive Disorder in Medical Students at an Osteopathic Medical School Before and After High-Stakes Examinations.

Background: Given the high prevalence of symptoms of major depressive disorder (MDD) in medical students, identifying factors that impact the development of such symptoms is important. Previous data suggest that medical students can experience symptoms of MDD after medical school exams. It is not known if medical students experience more symptoms of MDD directly before or after exams. The aim of the current study is to determine the prevalence of symptoms of MDD in first- and second-year medical students directly before and after high-stakes medical school examinations. Methods: Two anonymous surveys were sent via REDCap to first- and second-year medical students at the University of New England College of Osteopathic Medicine. A pre-exam survey on the day of the exam asking about the past three days' MDD symptoms, and a post-exam survey sent three days after the exam asking about MDD symptoms experienced after the exam was sent out to a total of 391 students with a response rate of 23%. Results: First- and second-year medical students regardless of gender experienced symptoms of MDD at higher rates before exams than afterwards. Female students experienced symptoms of MDD (as defined by the DSM-5) including sadness, sleep disturbances, and feelings of guilt or worthlessness at a greater rate compared to males before exams. After exams, females were more likely to experience sleep disturbances and decreased energy. Second-year male students were the least likely to experience symptoms of MDD. Conclusion: First- and second-year medical students can experience symptoms of MDD surrounding exams. This study highlights the emotional burden that students may carry near exams. It underscores the importance of further research on this topic to evaluate the effect exams have on the mental health of medical students during their training.

Detection of Suicide Clusters using Small-Area Geographic Data from the Virginia Violent Death Reporting System, 2010 - 2015.

Introduction: From 1999 to 2020, the suicide rate in Virginia increased from 13.1 to 15.9 per 100,000 persons aged 10 years and older. Few studies have examined spatial patterns of suicide geographies smaller than the county level. Methods: We analyzed data from suicide decedents aged ≥10 years from 2010 through 2015 in the Virginia Violent Death Reporting System. We identified spatial clusters of high suicide rates using spatially adaptive filtering with standardized mortality ratio (SMR) significantly higher than the state SMR (p < 0.001). We compared demographic characteristics, method of injury, and suicide circumstances of decedents within each cluster to decedents outside any cluster. Results: We identified 13 high-risk suicide clusters (SMR between 1.7 and 2.0). Suicide decedents in the clusters were more likely to be older (40+ years), non-Hispanic white, widowed/divorced/separated, and less likely to have certain precipitating suicide circumstances than decedents outside the clusters. Suicide by firearm was more common in four clusters, and suicide by poisoning was more common in two clusters compared to the rest of the state. Conclusions: There are important differences between geographic clusters of suicide in Virginia. These results suggest that place-specific risk factors for suicide may be relevant for targeted suicide prevention.

Investigating SH-SY5Y Neuroblastoma Cell Surfaceome as a Model for Neuronal-Targeted Novel Therapeutic Modalities.

The SH-SY5Y neuroblastoma cells are a widely used in vitro model approximating neurons for testing the target engagement of therapeutics designed for neurodegenerative diseases and pain disorders. However, their potential as a model for receptor-mediated delivery and uptake of novel modalities, such as antibody-drug conjugates, remains understudied. Investigation of the SH-SY5Y cell surfaceome will aid in greater in vitro to in vivo correlation of delivery and uptake, thereby accelerating drug discovery. So far, the majority of studies have focused on total cell proteomics from undifferentiated and differentiated SH-SY5Y cells. While some studies have investigated the expression of specific proteins in neuroblastoma tissue, a global approach for comparison of neuroblastoma cell surfaceome to the brain and dorsal root ganglion (DRG) neurons remains uninvestigated. Furthermore, an isoform-specific evaluation of cell surface proteins expressed on neuroblastoma cells remains unexplored. In this study, we define a bioinformatic workflow for the identification of high-confidence surface proteins expressed on brain and DRG neurons using tissue proteomic and transcriptomic data. We then delineate the SH-SY5Y cell surfaceome by surface proteomics and show that it significantly overlaps with the human brain and DRG neuronal surface proteome. We find that, for 32% of common surface proteins, SH-SY5Y-specific major isoforms are alternatively spliced, maintaining their protein-coding ability, and are predicted to localize to the cell surface. Validation of these isoforms using surface proteomics confirms a SH-SY5Y-specific alternative NRCAM (neuron-glia related cell adhesion molecule) isoform, which is absent in typical brain neurons, but present in neuroblastomas, making it a receptor of interest for neuroblastoma-specific therapeutics.

A Genotype-Phenotype Analysis of Glutathione Peroxidase 4 in Human Atrial Myocardium and Its Association with Postoperative Atrial Fibrillation.

Heterogeneity in the incidence of postoperative atrial fibrillation (POAF) following heart surgery implies that underlying genetic and/or physiological factors impart a higher risk of this complication to certain patients. Glutathione peroxidase-4 (GPx4) is a vital selenoenzyme responsible for neutralizing lipid peroxides, mediators of oxidative stress known to contribute to postoperative arrhythmogenesis. Here, we sought to determine whether GPX4 single nucleotide variants are associated with POAF, and whether any of these variants are linked with altered GPX4 enzyme content or activity in myocardial tissue. Sequencing analysis was performed across the GPX4 coding region within chromosome 19 from a cohort of patients (N = 189) undergoing elective coronary artery bypass graft (−/+ valve) surgery. GPx4 enzyme content and activity were also analyzed in matching samples of atrial myocardium from these patients. Incidence of POAF was 25% in this cohort. Five GPX4 variants were associated with POAF risk (permutated p ≤ 0.05), and eight variants associated with altered myocardial GPx4 content and activity (p < 0.05). One of these variants (rs713041) is a well-known modifier of cardiovascular disease risk. Collectively, these findings suggest GPX4 variants are potential risk modifiers and/or predictors of POAF. Moreover, they illustrate a genotype−phenotype link with this selenoenzyme, which will inform future mechanistic studies.

Radiographic Assessment of the Nasal Septum and Trends in Donor Cartilage Availability.

Objective: To compare the harvestable donor septal cartilage among patients. Background: Trends in donor septal cartilage anatomy are not well quantified in the literature. Methods: Harvestable septal cartilage area and length (preserving a 1-cm L-strut) were measured on fine-cut maxillofacial computed tomography (CT) for 200 patients in four self-described racial/ethnic groups: African American, Asian American, European American, and Latin American. Height, sex, and age were recorded. Demographic variables were modeled by multivariate logistic regression to determine characteristics predictive of harvestable septal cartilage. Results: Older age, shorter height, African American or Asian American self-described race, and female sex were independently associated with smaller harvestable area and shorter length (all p < 0.05). On multivariate regression, Asian American [odds ratio (OR) 5.23, p = 0.005] and African American (OR 3.75, p = 0.015) patients were more likely than Latin American or European Americans patients have a smaller harvestable area. Age (OR 1.02, p = 0.043) and height (OR 0.94, p = 0.029) were also correlated with smaller cartilage area and length, respectively. Conclusions: CT scan and demographic characteristics predicted donor septal cartilage availability.

Quality-Based Evaluation of Patient-Facing Online Education Materials Regarding Facial Filler Procedures.

Injectable facial fillers have become tremendously more popular in recent years, and the Internet offers a proportional amount of consumer-facing educational material. This study sought to explore the quality of these online materials. The top 20 Web sites offering educational materials about facial filler were identified via Google search and sorted by source: Medical Professional Boards, Hospitals and Providers, Medical News and Reference, and Fashion. The materials were assessed for overall quality with the validated DISCERN instrument. The authors also assessed understandability and actionability (Patient Education Material Assessment Tool - PEMAT), accuracy, comprehensiveness, and readability (Flesch-Kincaid Grade Level and Flesch Reading Ease). The mean DISCERN score was 46.9 ± 7.6, which is considered "fair" quality educational material; above "poor," but below "good" and "excellent." Understandability and actionability scores were low, particularly with respect to visual aids. The materials were generally accurate (76-99%), but scored poorly in comprehensiveness, as 15% failed to mention any risks/adverse effects and only 35% mentioned cost. On average, readability was at an 11th grade level, far more complex than ideal (< 6th grade level). Information disseminated from seemingly reputable sources such as professional boards and hospitals/providers were not of higher quality or superior in any of the above studied domains. In conclusion, online educational materials related to injectable facial fillers are of subpar quality, including those from academic and professional organizations. Visual aids were particularly weak. The facial rejuvenation community should make a concerted effort to set a higher standard for disseminating such information.

Genetic and epigenetic analysis of the serotonin 2A receptor in the context of cocaine abuse.

Despite more than 2 million American cocaine users monthly, there is no approved drug for treating cocaine use disorder. Cocaine use disorder has a multifactorial aetiology, including both genetic and environmental factors. Both cocaine use and genetic variations demonstrably alter DNA methylation and gene expression in the brain in a complex manner. How these factors interact in the context of cocaine abuse in humans is unknown. We propose that we can identify potential drug targets for treating cocaine use disorders by examining genetic, epigenetic, and expression changes in the brains of individuals that abused cocaine. In this study, we identified the interaction between the epigenetics changes (DNA CpG methylation) and genetic variants (SNPs) in the HTR2A gene in the context of cocaine addiction by using brain tissue collected from individuals that overdosed on cocaine (N = 14) and healthy matched controls (N = 16). We generated DNA CpG methylation profiles in eight regions of HTR2A harbouring frequent SNPs, measuring both allelic and total methylation, and compared these methylation profiles with HTR2A mRNA expression. Furthermore, we examined the influence of common variants rs6311 and rs6313 on cocaine abuse, methylation, and gene expression. We found evidence that rs6311 regulates HTR2A methylation, consistent with earlier studies. Furthermore, the minor alleles for rs6311 and rs6313 are associated with significantly increased expression of a splice isoform in which exon 2 is truncated in both cocaine and control samples. These results reveal specific roles for HTR2A in the context of cocaine abuse, highlighting opportunities to modulate this target for treating cocaine use disorder.

Comparison of Suicides Among Younger and Older Adolescents in Virginia, 2008-2017.

Objective: Suicide is the second leading cause of death in youth and is of public health importance. Characteristics and precipitating circumstances may differ by adolescent age groups. Understanding these differences may inform prevention efforts that are population-specific. Therefore, we sought to compare suicides between younger and older adolescents in Virginia from 2008 to 2017.Methods: We used data from the Virginia Violent Death Reporting System (VVDRS), part of the National Violent Death Reporting System (NVDRS). We included suicides of all adolescents aged 10-17 who were residents of Virginia from 2008 to 2017. Descriptive statistics and unadjusted logistic regression were used to compare characteristics and circumstances between younger (10-14) and older (15-17) adolescents.Results: Three hundred and 24 (324) adolescents died by suicide between 2008 and 2017 in Virginia, of which 20% were younger adolescents, and 80% were older adolescents. Suicides of younger adolescents increased significantly over the 10-year period. Younger adolescent suicides seemed to occur after a crisis, while suicides among older adolescents occurred due to intimate partner problems and substance use. Mental health issues were common in both.Conclusions: Suicides may be more impulsive among younger adolescents and warrants further attention, while strategies to cope with intimate partner problems and substance use may be important for older adolescents and should be considered when implementing services and interventions. HIGHLIGHTSImpulsivity may be an issue among younger adolescents.Strategies for relationship and substance use issues may benefit older adolescents.Targeted interventions may be necessary for younger and older adolescents.

Hypoglossal and Masseteric Nerve Transfer for Facial Reanimation: A Systematic Review and Meta-Analysis.

Background: Hypoglossal and masseteric nerve transfer are currently the most popular cranial nerve transfer techniques for patients with facial paralysis. The authors performed a systematic review and meta-analysis to compare functional outcomes and adverse effects of these procedures. Methods: A review of online databases was performed to include studies with four or more patients undergoing hypoglossal or masseter nerve transfer without muscle transfer or other cranial nerve transposition. Facial nerve outcomes, time to reinnervation, and adverse events were pooled and studied. Results: A total of 71 studies were included: 15 studies included 220 masseteric-facial transfers, and 60 studies included 1312 hypoglossal-facial transfers. Oral commissure symmetry at rest was better for hypoglossal transfer (2.22 ± 1.6 mm vs. 3.62 ± 2.7 mm, p = 0.047). The composite Sunnybrook Facial Nerve Grading Scale was better for masseteric transfer (47.7 ± 7.4 vs. 33.0 ± 6.4, p < 0.001). Time to first movement (in months) was significantly faster in masseteric transfer (4.6 ± 2.6 vs. 6.3 ± 1.3, p < 0.001). Adverse effects were rare (<5%) for both procedures. Conclusions: Both nerve transfer techniques are effective for facial reanimation, and the surgeon should consider the nuanced differences in selecting the correct procedure for each patient.

Beauty is in the eye of the follower: Facial aesthetics in the age of social media.

BACKGROUND: The advent of social media has influenced the relationship between aesthetic surgeons and their patients, as well as the motivations of such patients to seek cosmetic surgery. AIMS & OBJECTIVES: To determine how the cephalometric proportions of modern social media models fit with historical canons of beauty. MATERIALS & METHODS: Frontal and lateral photographs of 20 high-influence female Instagram models were obtained and evaluated for cephalometric measures. The means of these measures were compared with previous reports in the literature. RESULTS: Cephalometric measurements of social media models were in agreement with historical ideals of beauty for Nostril axis (120.7°), Goode's ratio (0.6), Nasofacial angle (35.7°), Nasofrontal angle (130.9°), and the horizontal thirds. Results were discrepant from historical ideals for the Nasolabial angle (82.6°) and the vertical facial fifths. CONCLUSION: Cephalometric measurements of social media models in the digital age closely resemble the ideal values proposed by previous authors. Due to a preference for larger or altered lip profiles, nostril axis is a more reliable measure of nasal tip rotation than nasolabial angle.

Sexual Dimorphism of the Nasal Skin and Soft Tissue Envelope.

Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Level of Evidence in Facial Plastic Surgery Research: A Procedure-Level Analysis.

BACKGROUND: As evidence-based medicine has taken hold across medical specialties, the level of evidence within the facial plastic surgery literature has risen, but remains weak in comparison. There has not yet been a systematic, critical appraisal of the relative strength of evidence among subsets of the practice of facial plastic surgery. METHODS: The current study is a systematic review, designed to evaluate the level of evidence observed in the facial plastic surgery literature. Five journals were queried using facial plastic surgery terms for four selected years over a 10-year period. Following screening, articles were assigned to a category regarding subject matter, assessed for the presence of various methodological traits, and evaluated for overall level of evidence. Comparisons were made in regard to level of evidence across the breadth of facial plastic surgery subject matter. RESULTS: A total of 826 articles were included for final review. Studies on operative facial rejuvenation and rhinoplasty had significantly fewer authors on average than studies on cancer reconstruction or craniofacial topics. Craniofacial studies demonstrated higher levels of evidence relative to all other categories, with the exception of facial paralysis and facial trauma studies, from which there was no significant difference. In general, reconstructive studies had significantly more authors and higher levels of evidence than did articles with an aesthetic focus. CONCLUSION: Level of evidence in facial plastic surgery remains relatively weak overall. Reconstructive and particularly craniofacial studies demonstrate higher mean level of evidence, relative to other subsets of facial plastic surgery. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Nasal Skin and Soft Tissue Thickness Variation Among Differing Races and Ethnicities: An Objective Radiographic Analysis.

Importance: Nasal skin and soft tissue envelope (SSTE) thickness has considerable effects on procedural planning and postoperative outcomes in rhinoplasty surgery. Objective understanding of relative SSTE thickness in patients is essential to optimal outcomes in rhinoplasty, and knowledge of its variation by demographic group is of aid to surgeons. Objective: To measure and compare nasal SSTE thickness across different races and nasal subsites and to determine whether objective variability exists for these parameters. Design, Setting, Participants: Retrospective cross-sectional radiographic analysis was carried out on 200 adult patients, without nasal deformity, presenting to an academic otolaryngology clinic at a tertiary care academic referral center. Blinded evaluators measured nasal SSTE thickness at six sites on maxillofacial computed tomography (CT) scans and comparisons were made based on patient-reported race/ethnicity categories available in the electronic medical record. Intervention: N/A Main Outcomes and Measures: Nasal SSTE thickness was measured at six predefined anatomic sites using high-resolution CT imaging. Statistical comparisons between races/ethnicities were made based on these measurements. Results: Mean age of patients was 48.8 years, and 47% were male. Nasal SSTE showed thicker soft tissue at the sellion in Latin American (LA; mean (SD) 6.1 (1.8) mm) and white (5.8 (1.8) mm) patients vs. African American (AfA) and Asian American (AsA) patients. The supratip was thicker in AfA patients (5.2 (1.3) mm) vs. all other races. The tip SSTE was thinner in white patients (2.4 (0.7) mm) vs. all other races. Composite nasal SSTE thickness was thinner in AsA patients (3.22 (0.8) mm) relative to AfA and LA patients. Conclusions and Relevance: SSTE thickness influences surgical planning and postoperative outcomes in rhinoplasty patients. This study supports varied thickness of the nasal SSTE among patients of different races. These data are foundational in providing a framework for developing treatment strategies specific to the SSTE properties of a multicultural patient population.

Setbacks in Forehead Feminization Cranioplasty: A Systematic Review of Complications and Patient-Reported Outcomes.

IMPORTANCE: Forehead feminization cranioplasty (FFC) is an important component of gender-affirming surgery and has become increasingly popular in recent years. Little objective evidence exists for the procedure's safety and clinical impact via patient-reported outcome measures (PROMs). OBJECTIVE: To determine what complications are observed following FFC, the relative frequency of complications by surgical technique, and what impact the procedure has on patient's quality of life. DATA SOURCES: Database searches were performed in PubMed/MEDLINE, Scopus, CINAHL, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, and PsycINFO. The search terms included variations of forehead setback/FFC. Both controlled vocabularies (i.e., MeSH and CINAHL's Suggested Subject Terms) and keywords in the title or abstract fields were searched. STUDY SELECTION: Two independent reviewers screened the titles and abstracts of all articles. Two independent surgeon reviewers evaluated the full text of all included articles, and relevant data points were extracted. MAIN OUTCOMES AND MEASURES: Complications and complication rate observed following FFC. Additional outcome measures were the approach utilized, concurrent procedures performed, and the use and findings of a PROM. RESULTS: Ten articles describing FFC were included, encompassing 673 patients. The overall pooled complication rate was 1.3%. PROMs were used in half of studies, with no standardization among studies. CONCLUSIONS AND RELEVANCE: Complications following FFC are rare and infrequently require reoperation. Further studies into standardized and validated PROMs in facial feminization patients are warranted. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

An Update on Level of Evidence Trends in Facial Plastic Surgery Research.

Background: Knowledge of the quality of evidence in facial plastic surgery research is essential for the implementation of evidence-based practices. The purpose of this study is to provide an update over the past decade as to whether the level of evidence in leading journals featuring topics in facial plastic surgery has changed in comparison with prior reports. Materials and Methods: This study is a systematic review, designed to evaluate the level of evidence observed in the facial plastic surgery literature over time. Five journals were queried using facial plastic surgery keywords for four selected years for a 10-year period. After screening, articles were assessed for the presence of various methodological traits and were evaluated for overall level of evidence. These variables were compared across the years studied to evaluate trends in level of evidence. Results: A total of 826 articles were included for final review. For all selected years, level IV or level V evidence was the most prevalent level of evidence. Over time, significantly less level IV (p = 0.009) and significantly more level II (p = 0.007) evidence was published. The proportion of studies reporting confidence intervals (p < 0.001) and p-values (p = 0.02) were significantly greater in later years. Conclusions: The level of evidence of facial plastic surgery literature has increased over time, as demonstrated by an increased proportion of level II evidence, decreased proportion of level IV evidence, and increased use of p-values and confidence intervals. The absolute number of randomized controlled trials continues to remain low.

The Selfie View: Perioperative Photography in the Digital Age.

BACKGROUND: The aesthetics of social media have become increasingly important to cosmetic surgery patients in recent years; however, aesthetic treatments have not kept pace with the desires of modern patients. The current study investigates the most common angles employed by various user cohorts when posting a selfie on social media platforms and proposes that aesthetic surgeons consider utilizing a selfie angle alongside standard pre- and postoperative photographic views. METHODS: Full face photographs published on the social media platform Instagram™ with the tag #selfie were divided into three cohorts: female models/influencers, amateur females, and amateur males. Each cohort contained 100 photographs. The photographs were analyzed using cloud-based facial analysis software for facial pan, roll, and tilt relative to the camera. RESULTS: One hundred photographs from each cohort were analyzed and demonstrated that amateur females (AF) take photographs from higher angles than amateur males (AM) or model females (MF). Roll-off-midline was significantly greater for AF and MF as compared to AM. The MF group had significantly a greater pan-off-midline as compared to AF and AM, while AF had significantly a greater pan-off-midline than AM. CONCLUSIONS: Common photography practices employed within selfie photographs utilize angles not captured in standard perioperative photographs. This study supports the implementation of a selfie photograph into the standard set of pre- and postoperative photographs taken by aesthetic surgeons to evaluate the effects of interventions in the context of selfie photography. The angle employed can vary depending upon the demographic profile of the patient. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.