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Background: Intersection of gender and race and/or ethnicity in academic medicine is understudied; we aim to understand these factors in relation to scholarly achievements for neurology faculty. Methods: Faculty from 19 US neurology departments completed a survey (2021-2022) to report rank, leadership positions, publications, funded projects, awards, and speaker invitations. Regression analyses examined effects of gender, race, and their intersectionality on these achievements. Women, Black/Indigenous/People of Color (BIPOC), and BIPOC women were comparator groups. Results: Four hundred sixty-two faculty responded: 55% women, 43% men; 31% BIPOC, 63% White; 21% BIPOC women, 12% BIPOC men, 36% White women, 31% White men. Men and White faculty are more likely to be full professors than women and BIPOC faculty. The number of leadership positions, funded projects, awards, and speaker invitations are significantly greater in White compared to BIPOC faculty. Relative to BIPOC women, the number of leadership positions is significantly higher among BIPOC men, White women, and White men. Publication numbers for BIPOC men are lower, number of funded projects and speaker invitations for White women are higher, and number of awards among White men and White women is higher compared to BIPOC women. Discussion: Our study highlights that inequities in academic rank, award number, funded projects, speakership invitations, and leadership roles disproportionately impacted BIPOC women. More studies are needed to evaluate gender and race and/or ethnicity intersectionality effects on faculty achievements, reasons for inequities, recognition, and potential solutions.

Objective: To investigate the perceptions of lactation experiences of neurology faculty and the impact of lactation time on academic achievement. Materials and Methods: This was a cross-sectional study utilizing a survey administered across 19 academic neurology centers in the United States. Respondents self-identified as having children and answered questions about lactation at work. Demographic information; academic achievement including publications, guest speakerships, awards, leadership roles, and funding; and perception of lactation experience were analyzed. Results: Among 162 respondents, 83% took lactation time at work. Thirty-seven percent reported lack of employer support for lactation, 46% were dissatisfied with their lactation experience, 59% did not receive compensation for lactation time, 62% did not have blocked clinical time, 73% reported relative value units were not adjusted to accommodate lactation, and 43% reported lack of access to private lactation space. Women spent on average 9.5 months lactating per child and desired 2.4 further months of lactation. There was no difference in all measures of self-reported academic achievement between women who did and did not take lactation time when measured across all career stages. Conclusions: Although a majority of respondents took lactation time at work, perceptions of employer support for lactation were low, and expectations for work productivity were not adjusted to accommodate lactation time. Taking lactation time at work did not decrease self-reported academic achievement. System-level best practices designed to support lactating faculty should be developed to guide academic institutions.

Rapid eye movement sleep-related bradyarrhythmia syndrome is a rare condition marked by abnormal sinus arrest or atrioventricular conduction disturbance blocks during REM sleep unassociated with sleep disordered breathing. We present a case of a young man without a cardiovascular history exhibiting pauses of up to 9.7 seconds during polysomnography (PSG). Initially referred for suspected obstructive sleep apnea due to nocturnal awakenings with shortness of breath, confusion, and dizziness. PSG results were unremarkable apart from electrocardiogram findings revealing prolonged sinus pauses related to REM sleep. Evaluation via extended 14-day patch monitor revealed an overall normal sinus rhythm with the lowest heart rate recorded at 14 beats per minute and 412 pauses exceeding 2 seconds, with the longest pause lasting 12.5 seconds during nocturnal hours. A permanent pacemaker was considered, but after shared decision making with the patient, the decision was to continue monitoring without any intervention., (© 2024 American Academy of Sleep Medicine.)

Carcinomas are associated with metastasis to specific organs while sparing others. Breast cancer presents with lung metastasis but rarely kidney metastasis. Using this difference as an example, we queried the mechanism(s) behind the proclivity for organ-specific metastasis. We used spontaneous and implant models of metastatic mammary carcinoma coupled with inflammatory tissue fibrosis, single-cell sequencing analyses and functional studies to unravel the causal determinants of organ-specific metastasis. Here we show that lung metastasis is facilitated by angiopoietin 2 (Ang2)-mediated suppression of lung-specific endothelial tight junction protein Claudin 5, which is augmented by the inflammatory fibrotic microenvironment and prevented by anti-Ang2 blocking antibodies, while kidney metastasis is prevented by non-Ang2-responsive Claudins 2 and 10. Suppression of Claudins 2 and 10 was sufficient to induce the emergence of kidney metastasis. This study illustrates the influence of organ-specific vascular heterogeneity in determining organotropic metastasis, independent of cancer cell-intrinsic mechanisms., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Cortical hyperarousal and ruminative thinking are common aspects of insomnia that have been linked with greater connectivity in the default mode network (DMN). Therefore, disrupting network activity within the DMN may reduce cortical and cognitive hyperarousal and facilitate better sleep., Objective: This trial aims to establish a novel, noninvasive method for treating insomnia through disruption of the DMN with repetitive transcranial magnetic stimulation, specifically with continuous theta burst stimulation (cTBS). This double-blind, pilot randomized controlled trial will assess the efficacy of repetitive transcranial magnetic stimulation as a novel, nonpharmacological approach to improve sleep through disruption of the DMN prior to sleep onset for individuals with insomnia. Primary outcome measures will include assessing changes in DMN functional connectivity before and after stimulation., Methods: A total of 20 participants between the ages of 18 to 50 years with reported sleep disturbances will be recruited as a part of the study. Participants will then conduct an in-person screening and follow-on enrollment visit. Eligible participants then conduct at-home actigraphic collection until their first in-residence overnight study visit. In a double-blind, counterbalanced, crossover study design, participants will receive a 40-second stimulation to the left inferior parietal lobule of the DMN during 2 separate overnight in-residence visits. Participants are randomized to the order in which they receive the active stimulation and sham stimulation. Study participants will undergo a prestimulation functional magnetic resonance imaging scan and a poststimulation functional magnetic resonance imaging scan prior to sleep for each overnight study visit. Sleep outcomes will be measured using clinical polysomnography. After their first in-residence study visit, participants conduct another at-home actigraphic collection before returning for their second in-residence overnight study visit., Results: Our study was funded in September 2020 by the Department of Defense (W81XWH2010173). We completed the enrollment of our target study population in the October 2022 and are currently working on neuroimaging processing and analysis. We aim to publish the results of our study by 2024. Primary neuroimaging outcome measures will be tested using independent components analysis, seed-to-voxel analyses, and region of interest to region of interest analyses. A repeated measures analysis of covariance (ANCOVA) will be used to assess the effects of active and sham stimulation on sleep variables. Additionally, we will correlate changes in functional connectivity to polysomnography-graded sleep., Conclusions: The presently proposed cTBS protocol is aimed at establishing the initial research outcomes of the effects of a single burst of cTBS on disrupting the network connectivity of the DMN to improve sleep. If effective, future work could determine the most effective stimulation sites and administration schedules to optimize this potential intervention for sleep problems., Trial Registration: ClinicalTrials.gov NCT04953559; https://clinicaltrials.gov/ct2/show/NCT04953559., International Registered Report Identifier (irrid): DERR1-10.2196/51212., (©Lindsey Hildebrand, Alisa Huskey, Natalie Dailey, Samantha Jankowski, Kymberly Henderson-Arredondo, Christopher Trapani, Salma Imran Patel, Allison Yu-Chin Chen, Ying-Hui Chou, William D S Killgore. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 26.01.2024.)

Purpose: The aim of this study was to utilize an intersectional framework to examine academic faculty's lived experiences during COVID-19. Specifically, we set out to: (1) describe the multiple intersectional identities ( e.g. , gender, race/ethnicity, rank, caregiver status, disability status) represented by the faculty, (2) examine potential disparities in well-being, workload, and productivity linked to these intersectional factors, and (3) identify qualitative themes endorsed by faculty as they relate to lived experiences during COVID-19. Methods: This was a cross-sectional mixed-methods research study. The Center for Women in Medicine and Science (CWIMS) at the University of Minnesota developed and implemented a survey between February-June of 2021 in response to national reports of disparities in the impacts of COVID-19 on faculty with lived experiences from multiple intersections. Results: There were 291 full-time faculty who participated in the study. Quantitative findings indicated that faculty with multiple intersectional identities ( e.g. , woman+assistant professor+caregiver+underrepresented in medicine) reported greater depression symptoms, work/family conflict, and stress in contrast to faculty with fewer intersectional identities. Furthermore, faculty with more intersectional identities reported higher clinical workloads and service responsibilities and lower productivity with regard to research article submissions, publications, and grant submissions in contrast to faculty with fewer intersectional identities. Qualitative findings supported quantitative findings and broadened understanding of potential underlying reasons. Conclusions: Findings confirm anecdotal evidence that faculty with lived experiences from multiple intersections may be disproportionately experiencing negative outcomes from the pandemic. These findings can inform decisions about how to address these disparities moving into the next several years with regard to promotion and tenure, burnout and well-being, and faculty retention in academic medical settings. Given these findings, it is also important to intentionally plan responses for future public health crises to prevent continued disparities for faculty with multiple intersectional identities.

Prior research suggests COVID-19 has amplified stress on Academic Clinician Frontline-Workers (ACFW). The aim of this paper is: (1) to better understand the experiences of ACFW during the COVID-19 pandemic including their mental-emotional wellbeing, academic productivity, clinical experiences, and (2) to examine any gender differences. A cross-sectional survey was administered to University of Minnesota/M Health Fairview systems' faculty February-June 2021. Of the 291 respondents, 156 were clinicians, with 91 (58 %) identifying as Frontline-Workers (ACFW). Faculty wellbeing was assessed using validated measures in addition to measures of productivity and sociodemographics. For example, ACFW reported a higher Work-Family Conflict (WFC) scores compared to non-ACFW (26.5 vs. 24.1, p = 0.057) but did not report higher Family-Work Conflict (FWC) scores (17.7 vs. 16.3, p = 0.302). Gender sub-analyses, revealed that women ACFW compared to men ACFW reported higher WFC scores (27.7 vs. 24.1, p = 0.021) and FWC (19.3 vs. 14.3, p = 0.004). Academically, ACFW reported submitting fewer grants and anticipated delays in promotion and tenure due to the COVID-19 (p = 0.035). Results suggest COVID-19 has exacerbated ACFW stress and gender inequities. Reports of anticipated delay in promotion for ACFW may pose a challenge for the long-term academic success of ACFW, especially women ACFW. In addition, women may experience higher FWC and WFC as compared to men. Schools of academic medicine should consider re-evaluating promotion/tenure processes and creating resources to support women ACFW as well as ACFW caregivers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Insomnia is often accompanied by excessive pre-sleep rumination. Such ruminative thinking is also associated with increased connectivity of the default mode network (DMN). It is likely that DMN connectivity and associated rumination contribute to the pathogenesis of insomnia. We hypothesized that resting state functional connectivity (rsFC) between the DMN and other brain regions prior to bedtime would predict objectively measured sleep among individuals with insomnia. Twenty participants (12 female; M age = 26.9, SD = 6.6 years) with symptoms of insomnia underwent an rsFC scan in the early evening followed by a night of polysomographically (PSG) measured sleep. Connectivity of the DMN with other brain regions was regressed against several PSG sleep metrics, including time in wake, N1, N2, N3, REM, total sleep time (TST), and sleep efficiency (SE) at a cluster corrected false discovery rate (FDR) correction P < 0.05. The connectivity between DMN and cortical regions was negatively correlated with PSG indices of poorer sleep including time in wake (right angular gyrus) and N1 (precuneus) but positively correlated with time in REM (orbitofrontal cortex), TST (insula, orbitofrontal cortex, superior frontal gyrus, paracingulate gyrus), SE (orbitofrontal cortex). Connectivity between DMN and the pons was negatively correlated with SE. Among individuals with symptoms of insomnia, better sleep was predicted by rsFC between the DMN and cortical regions involved in executive functioning, consciousness, and complex cognition. Findings raise the possibility that future interventions aimed at suppressing pre-sleep DMN activation may weaken synergy between pre-sleep ruminative worry and complex cognitions, potentially ameliorating problems falling asleep., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Super-refractory status epilepticus (SRSE) has high rates of morbidity and mortality. Few published studies have investigated neurostimulation treatment options in the setting of SRSE. This systematic literature review and series of 10 cases investigated the safety and efficacy of implanting and activating the responsive neurostimulation (RNS) system acutely during SRSE and discusses the rationale for lead placement and selection of stimulation parameters., Methods: Through a literature search (of databases and American Epilepsy Society abstracts that were last searched on March 1, 2023) and direct contact with the manufacturer of the RNS system, 10 total cases were identified that utilized RNS acutely during SE (9 SRSE cases and 1 case of refractory SE [RSE]). Nine centers obtained IRB approval for retrospective chart review and completed data collection forms. A tenth case had published data from a case report that were referenced in this study. Data from the collection forms and the published case report were compiled in Excel., Results: All 10 cases presented with focal SE: 9 with SRSE and 1 with RSE. Etiology varied from known lesion (focal cortical dysplasia in 7 cases and recurrent meningioma in 1) to unknown (2 cases, with 1 presenting with new-onset refractory focal SE [NORSE]). Seven of 10 cases exited SRSE after RNS placement and activation, with a time frame ranging from 1 to 27 days. Two patients died of complications due to ongoing SRSE. Another patient's SE never resolved but was subclinical. One of 10 cases had a device-related significant adverse event (trace hemorrhage), which did not require intervention. There was 1 reported recurrence of SE after discharge among the cases in which SRSE resolved up to the defined endpoint., Conclusions: This case series offers preliminary evidence that RNS is a safe and potentially effective treatment option for SRSE in patients with 1-2 well-defined seizure-onset zone(s) who meet the eligibility criteria for RNS. The unique features of RNS offer multiple benefits in the SRSE setting, including real-time electrocorticography to supplement scalp EEG for monitoring SRSE progress and response to treatment, as well as numerous stimulation options. Further research is indicated to investigate the optimal stimulation settings in this unique clinical scenario.

Introduction: Patients with obstructive sleep apnea (OSA) are at risk for QTc prolongation, a known risk factor for increased mortality. The pro-QTc score can help identify individuals at increased risk for mortality associated with increased QTc however, it has not been evaluated in patients with OSA. The goal of this study was to evaluate the pro-QTc score in patients with OSA., Methods: Medical records of patients undergoing a sleep study at our sleep center from February 2012 to August 2020 were analyzed. Presence or absence of OSA was determined by polysomnography. The pro-QTc score was calculated with 1 point assigned for each of the following: female sex, QT-prolonging diagnoses and conditions, QT-prolonging electrolyte abnormalities, and medications with known risk for QT-prolongation. Mortality was determined from the electronic medical record of an integrated healthcare system., Results: There were 2246 patients (age 58 ± 15 years, 54% male, 82 dead) with OSA and 421 patients (age 54 ± 18 years, 43% male, 18 dead) without OSA. Of those with OSA, 1628 (72.5%) had at least one risk factor for QTc prolongation. A higher pro-QTc score was associated with greater mortality in patients with OSA (HR 1.48 per pro-QTc score, p < 0.001, 95% CI 1.3-1.7) but not in patients without OSA (HR 1.25 per pro-QTc score, p = 0.30, 95% CI 0.82-1.9), after adjusting for age, body mass index (BMI), and smoking status., Conclusion: In patients with OSA, a higher pro-QTc score was associated with greater mortality., Competing Interests: Declaration of competing interest There are no conflicts of interest to report., (Copyright © 2023 Elsevier B.V. All rights reserved.)

BACKGROUND Chlorhexidine (CHX) is not prescribed as a mouthwash for long-term use; therefore, probiotic/herbal mouthwashes are being investigated. This study compared the effect of 3 commercial mouthwashes on plaque index (PI), gingival index (GI), and bleeding index (BI) in patients with chronic gingivitis. MATERIAL AND METHODS Forty-five patients (all with moderate plaque) were randomly allocated into 3 groups (Gp): Gp 1 (CHX), Gp 2 (Manuka), and Gp 3 (Pro-Dental). Three periodontal clinical parameters - PI, GI, and BI - were recorded at baseline and on days 7, 14, and 28. An oral hygiene maintenance program was followed by a double-blinded intervention (coded bottle containing mouthwash). Both inter-group and intra-group comparisons were made using analysis of variance (ANOVA) with multiple t tests. All probable values were considered to have various levels of significance at P<0.05 or below. RESULTS All indices for all groups showed higher values (mean) at baseline, which were lower on days 7, 14, and 28. No differences in any clinical parameter at any point of time existed between Gp 1 and Gp 2. There were, however, significant differences (P<0.05) between Gp 1/Gp 3 and Gp 2/Gp 3 for all clinical parameters at all observed time periods (days 7, 14, 28). Intra-group comparison for all groups demonstrated highly significant differences between baseline values and other time points. CONCLUSIONS For managing chronic gingivitis, Manuka mouthwash is as effective as a CHX mouthwash, as there were no differences observed in any clinical parameters at any point points.

Purpose: To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL., Patients and Methods: Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients., Results: AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS ( P = .412) and OS ( P = .600)., Conclusion: Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse., Competing Interests: David T. TeacheyConsulting or Advisory Role: SobiResearch Funding: Novartis (Inst), Beam Therapeutics (Inst), NeoImmuneTech (Inst) Meenakshi DevidasHonoraria: Novartis Brent L. WoodHonoraria: Amgen, Seattle Genetics, AbbVie, Janssen, Amgen, Astellas Pharma, Roche Diagnostics, Beckman CoulterConsulting or Advisory Role: SysmexResearch Funding: Amgen (Inst), Seattle Genetics (Inst), Pfizer (Inst), Juno Therapeutics (Inst), BiolineRx (Inst), Biosight (Inst), Stemline Therapeutics (Inst), Janssen Oncology (Inst), Novartis, Kite, a Gilead company (Inst), Macrogenics (Inst)Travel, Accommodations, Expenses: Amgen, Amgen Robert J. HayashiConsulting or Advisory Role: Magenta Therapeutics Michelle HermistonStock and Other Ownership Interests: Gladiator Biosciences, Coagulant TherapeuticsConsulting or Advisory Role: Novartis, Sobi, Kalivir ImmunotherapeuticsPatents, Royalties, Other Intellectual Property: Spouse has patents pending for platform technology with application to oncology, diagnostics, anti-infections, and for antibleeding technology Michelle L. HermistonStock and Other Ownership Interests: Gladiator Biosciences, Coagulant TherapeuticsConsulting or Advisory Role: Novartis, Sobi, Kalivir ImmunotherapeuticsPatents, Royalties, Other Intellectual Property: Spouse has patents pending for platform technology with application to oncology, diagnostics, anti-infections, and for antibleeding technology J. Hunter ArcherStock and Other Ownership Interests: Johnson & Johnson/Janssen, AbbVie, Merck, Abbott Laboratories, Lilly, Zomedica, GlaxoSmithKline, Artelo Biosciences, Becton Dickinson, Bristol Myers Squibb Company, Tonix Pharmaceuticals, Cerebain Biotech Company, Gentech Keith J. AugustConsulting or Advisory Role: Jazz Pharmaceuticals, Beam TherapeuticsSpeakers' Bureau: Novartis Steve Y. ChoConsulting or Advisory Role: Progenics, Blue Earth Diagnostics, Bristol Myers Squibb, Radmetrix, Haymarket Medical EducationResearch Funding: Progenics (Inst), Advanced Accelerator Applications (Inst)Other Relationship: RadmetrixUncompensated Relationships: Focus-X Therapeutics Kimberly P. DunsmoreEmployment: DexcomStock and Other Ownership Interests: DexcomTravel, Accommodations, Expenses: Dexcom Brian T. FisherConsulting or Advisory Role: Astellas PharmaResearch Funding: Pfizer (Inst), Merck (Inst) Jason L. FreedmanStock and Other Ownership Interests: Massive BioConsulting or Advisory Role: Massive Bio Paul J. GalardyStock and Other Ownership Interests: AbbVie, Abbott Laboratories, Johnson & Johnson/Janssen Paul Harker-MurrayConsulting or Advisory Role: Consultancy for Regeneron Pharmaceuticals (2019) Terzah M. HortonResearch Funding: Takeda Alok I. JajuStock and Other Ownership Interests: Gilead Sciences Eric S. SchaferConsulting or Advisory Role: Beam Therapeutics Stuart S. WinterHonoraria: Jazz PharmaceuticalsConsulting or Advisory Role: Jazz PharmaceuticalsPatents, Royalties, Other Intellectual Property: Therapeutic use of the PreBCR to target B-cell acute leukemiasTravel, Accommodations, Expenses: Jazz Pharmaceuticals Patrick Zweidler-McKayEmployment: ImmunogenStock and Other Ownership Interests: ImmunogenPatents, Royalties, Other Intellectual Property: Patent applications submitted, no royalties Catherine M. BollardLeadership: Cabaletta BioConsulting or Advisory Role: Mana Therapeutics, Catamaran Bio Mignon L. LohConsulting or Advisory Role: MediSix Therapeutics Stephen P. HungerStock and Other Ownership Interests: Amgen, MerckHonoraria: Jazz Pharmaceuticals, Servier/Pfizer Elizabeth A. RaetzResearch Funding: Pfizer (Inst)Other Relationship: CelgeneNo other potential conflicts of interest were reported.

Introduction: Variability and prolongation of ventricular repolarization - measured by changes in QT interval and QT variability are independently associated with ventricular arrhythmias, sudden death, and mortality but such studies did not examine the role of sleep-disordered breathing. We aimed to determine whether sleep-disordered breathing moderated the association between measures of ventricular repolarization and overall mortality., Methods: Eight hundred participants were randomly selected from each of the following four groups in the Sleep Heart Health Study: mild, moderate, severe or no sleep disordered breathing (n = 200 each). Overnight electrocardiograms were analyzed for QTc duration and QT variability (standard deviation of QT intervals, normalized QT interval variance and the short-term interval beat-to-beat QT variability). Cox proportional hazards penalized regression modeling was used to identify predictors of mortality., Results: Eight hundred of 5600 participants were randomly selected. The participants (68 ± 10 years; 56.8% male) were followed for an average of 8.2 years during which time 222 (28.4%) died. QTc, SDQT, and QTVN were associated with the presence of SDB (p = 0.002, p = 0.014, and p = 0.024, respectively). After adjusting for covariates, the presence of sleep-disordered breathing did not moderate the association between QTc length, QT variability and mortality (p > 0.05)., Conclusion: Sleep-disordered breathing was associated with some measures of ventricular repolarization. However, sleep-disordered breathing was not an effect modifier for the relationship between QTc and QT variability and mortality., Competing Interests: Declaration of competing interest There are no conflicts of interest to report., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The novel corona virus that is now known as (SARS-CoV-2) has killed more than six million people worldwide. The disease presentation varies from mild respiratory symptoms to acute respiratory distress syndrome and ultimately death. Several risk factors have been shown to worsen the severity of COVID-19 outcomes (such as age, hypertension, diabetes mellitus, and obesity). Since many of these risk factors are known to be influenced by obstructive sleep apnea, this raises the possibility that OSA might be an independent risk factor for COVID-19 severity. A shift in the gut microbiota has been proposed to contribute to outcomes in both COVID-19 and OSA. To further evaluate the potential triangular interrelationships between these three elements, we conducted a thorough literature review attempting to elucidate these interactions. From this review, it is concluded that OSA may be a risk factor for worse COVID-19 clinical outcomes, and the shifts in gut microbiota associated with both COVID-19 and OSA may mediate processes leading to bacterial translocation via a defective gut barrier which can then foster systemic inflammation. Thus, targeting biomarkers of intestinal tight junction dysfunction in conjunction with restoring gut dysbiosis may provide novel avenues for both risk detection and adjuvant therapy.

Purpose: For curative treatment of Hodgkin lymphoma, radiation therapy benefit must be weighed against toxicity. Although more costly, proton radiation therapy reduces dose to healthy tissue, potentially improving the therapeutic ratio compared with photons. We sought to determine the cost-effectiveness of proton versus photon therapy for mediastinal Hodgkin lymphoma (MHL) based on reduced heart disease., Methods and Materials: Our model approach was 2-fold: (1) Use patient-level dosimetric information for a cost-effectiveness analysis using a Markov cohort model. (2) Use population-based data to develop guidelines for policymakers to determine thresholds of proton therapy favorability for a given photon dose. The HD14 trial informed relapse risk; coronary heart disease risk was informed by the Framingham risk calculator modified by the mean heart dose (MHD) from radiation. Sensitivity analyses assessed model robustness and identified the most influential model assumptions. A 30-year-old adult with MHL was the base case using 30.6-Gy proton therapy versus photon intensity modulated radiation therapy., Results: Proton therapy was not cost-effective in the base case for male ($129,000/ quality-adjusted life years [QALYs]) or female patients ($196,000/QALY). A 5-Gy MHD decrease was associated with proton therapy incremental cost-effectiveness ratio <$100,000/QALY in 40% of scenarios. The hazard ratio associating MHD and heart disease was the most influential clinical parameter., Conclusions: Proton therapy may be cost-effective a select minority of patients with MHL based on age, sex, and MHD reduction. We present guidance for clinicians using MHD to aid decision-making for radiation therapy modality., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Study Objectives: Z-drugs (eszopiclone, zolpidem, and zaleplon) are commonly used for insomnia but are also associated with suicide risk. However, it is unclear if this association is unique to Z-drugs. Therefore, the present study estimated the associations between multiple prescription insomnia medications and suicidal thoughts and behaviors., Methods: Data were acquired from the National Survey on Drug Use and Health for 2015-2018 and the National Health and Nutrition Examination Survey for 2005-2018. Samples were balanced on sociodemographic and mental health covariates using inverse probability of treatment weighting. Associations of Z-drugs, trazodone, and sedative benzodiazepines (temazepam, triazolam, flurazepam) with suicidal ideation, planning, and attempts were estimated using binomial logistic regression., Results: In the National Survey on Drug Use and Health, Z-drugs were associated with suicidal ideation (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.14-1.54]), suicide planning (OR, 1.44; 95% CI, 1.19-1.75), and suicide attempts (OR, 1.45; 95% CI, 1.13-1.86) after adjusting for age, sex, race/ethnicity, income, depression, illicit substance use, and the 6-item Kessler Psychological Distress Scale and World Health Organization Disability Assessment Schedule II scores. When analyses accounted for the same factors, sedative benzodiazepines were associated with suicide attempts (OR, 1.76; 95% CI, 1.06-2.87) but not suicidal ideation (OR, 1.37; 95% CI, 0.99-1.88) or suicide planning (OR, 1.39; 95% CI, 0.97-2.00). In the National Health and Nutrition Examination Survey, Z-drugs were associated with suicidal ideation (OR, 2.44; 95% CI, 1.41-4.22), as was trazodone (OR, 2.33; 95% CI, 1.45-3.75), after analyses adjusted for age, sex, race/ethnicity, and exposure to various psychotropic medications., Conclusions: Multiple classes of prescription insomnia medications are associated with suicidal thinking and behaviors, even after analyses adjusted for measures of mental health., (© 2021 American Academy of Sleep Medicine.)

Study Objectives: Prior studies have shown a morning chronotype for African Americans compared with non-Hispanic Whites, yet self-reported sleep timing is delayed in African Americans compared with Whites., Methods: We analyzed data from the Multi-Ethnicity Study of Atherosclerosis, a multisite community-based cohort. Self-reported and actigraphic sleep timing, chronotype measured by the modified Horne-Östberg Morningness-Eveningness Questionnaire, and risk of depression measured by the Center for Epidemiologic Studies Depression scale were examined using nonparametric approaches and linear or logistic regression while comparing between African Americans and Whites and evaluating the effects of delayed sleep phase., Results: In 1,401 participants, there was no difference in chronotype between African Americans and Whites. African Americans were 80% more likely to report a delayed sleep phase (defined as bedtime after midnight) on weekdays and 50% more likely on weekends than were Whites. Actigraphic data showed similar results. Actigraphic midsleep time was delayed 38 minutes on weekdays and 24 minutes on weekends in African Americans compared with Whites. Stratified analysis by chronotype showed that African Americans with a morning or intermediate chronotype had a significantly delayed sleep phase compared with Whites, but there was no difference between African Americans and Whites with an evening chronotype. Delayed sleep phase was associated with depression, but this relationship was only significant in White participants., Conclusions: African Americans had a delayed sleep phase compared with Whites that was more pronounced in individuals with a morning or intermediate chronotype. Consequences of delayed sleep phase may vary by race and ethnicity., (© 2021 American Academy of Sleep Medicine.)

Obstructive sleep apnea (OSA) is a common sleep disorder that affects all age groups and is associated with many co-morbid diseases (especially cardiovascular diseases). Continuous positive airway pressure (CPAP) is the gold standard for treating OSA. However, adherence to PAP therapy has been a major challenge with an estimated adherence between 20% and 80%. Mandibular advancement devices (MAD) are a good alternative option if used in the appropriate patient. MAD are most effective in mild and moderate OSA but not severe OSA. Surgical options are invasive, not appropriate for severe OSA, and associated with pain and long healing time. Hypoglossal nerve stimulation (HGNS), or upper airway stimulation (UAS), is a novel therapy in treating moderate and severe degrees of OSA in patients who cannot tolerate CPAP therapy. We reviewed the MEDLINE (PubMed) database. The search process yielded 303 articles; 31 met the inclusion and exclusion criteria and were included. We concluded that hypoglossal nerve stimulation is a very effective and novel alternative therapy for moderate and severe OSA in patients who cannot tolerate CPAP therapy. Adherence to HGNS is superior to CPAP. However, more developments are needed to ensure the highest safety profile.

Study Objectives: The purpose of this study was to determine whether a wearable sleep-tracker improves perceived sleep quality in healthy participants and to test whether wearables reliably measure sleep quantity and quality compared with polysomnography., Methods: This study included a single-center randomized crossover trial of community-based participants without medical conditions or sleep disorders. A wearable device (WHOOP, Inc.) was used that provided feedback regarding sleep information to the participant for 1 week and maintained sleep logs versus 1 week of maintained sleep logs alone. Self-reported daily sleep behaviors were documented in sleep logs. Polysomnography was performed on 1 night when wearing the wearable. The Patient-Reported Outcomes Measurement Information System sleep disturbance sleep scale was measured at baseline, day 7 and day 14 of study participation., Results: In 32 participants (21 women; 23.8 ± 5 years), wearables improved nighttime sleep quality (Patient-Reported Outcomes Measurement Information System sleep disturbance: B = -1.69; 95% confidence interval, -3.11 to -0.27; P = .021) after adjusting for age, sex, baseline, and order effect. There was a small increase in self-reported daytime naps when wearing the device (B = 3.2; SE, 1.4; P = .023), but total daily sleep remained unchanged (P = .43). The wearable had low bias (13.8 minutes) and precision (17.8 minutes) errors for measuring sleep duration and measured dream sleep and slow wave sleep accurately (intraclass coefficient, 0.74 ± 0.28 and 0.85 ± 0.15, respectively). Bias and precision error for heart rate (bias, -0.17%; precision, 1.5%) and respiratory rate (bias, 1.8%; precision, 6.7%) were very low compared with that measured by electrocardiogram and inductance plethysmography during polysomnography., Conclusions: In healthy people, wearables can improve sleep quality and accurately measure sleep and cardiorespiratory variables., Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: Assessment of Sleep by WHOOP in Ambulatory Subjects; Identifier: NCT03692195., (© 2020 American Academy of Sleep Medicine.)

(a) Background: In patients with sleep apnea, poor adherence to positive airway pressure (PAP) therapy has been associated with mortality. Regional studies have suggested that lower socioeconomic status is associated with worse PAP adherence but population-level data is lacking. (b) Methods: De-identified data from a nationally representative database of PAP devices was geo-linked to sociodemographic information. (c) Results: In 170,641 patients, those in the lowest quartile of median household income had lower PAP adherence (4.1 + 2.6 hrs/night; 39.6% adherent by Medicare criteria) than those in neighborhoods with highest quartile median household income (4.5 + 2.5 hrs/night; 47% adherent by Medicare criteria; p < 0.0001). In multivariate regression, individuals in neighborhoods with the highest income quartile were more adherent to PAP therapy than those in the lowest income quartile after adjusting for various confounders (adjusted Odds Ratio (adjOR) 1.18; 95% confidence interval (CI) 1.14, 1.21; p < 0.0001). Over the past decade, PAP adherence improved over time (adjOR 1.96; 95%CI 1.94, 2.01), but health inequities in PAP adherence remained even after the Affordable Care Act was passed. (d) Conclusion: In a nationally representative population, disparities in PAP adherence persist despite Medicaid expansion. Interventions aimed at promoting health equity in sleep apnea need to be undertaken.

Introduction: Risk assessment for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains complex. The goal of this study was to assess electrocardiogram (ECG)-derived risk factors on SCD in a large HCM population Methods: Retrospective review of adults with HCM evaluated at Mayo Clinic, Rochester, MN from 1 December 2002 to 31 December 2012 was performed. Data inclusive of ECG and 24-hour ambulatory Holter monitor were assessed. SCD events were documented by ventricular fibrillation (VF) noted on implantable cardioverter defibrillator (ICD), or appropriate VT or VF-terminating ICD shock., Results: Overall, 1615 patients (mean age 53.7 ± 15.2 years; 943 males, 58.4%) were assessed, with mean follow-up 2.46 years and 110 SCD events. Via logistic regression (n = 820), the odds of SCD increased with increasing number of conventional risk factors. With one risk factor the OR was 4.88 (p < .0001; CI 2.22-10.74), two risk factors the OR was 6.922 (p < .0001; CI 2.94-16.28) and three or more risk factors, the OR was 13.997 (p < .0001; CI 5.649-34.68). Adding QTc > 450 to this logistic regression model had OR 1.722 (p = .04, CI 1.01-2.937) to predict SCD. QTc ≥ 450 was a significant predictor for death (HR 1.88, p = .021, CI 1.10-3.20). There was no correlation between sinus bradycardia, sinus tachycardia, first degree AV block, atrial fibrillation, left bundle branch block, right bundle branch block, premature atrial complexes, premature ventricular complexes, supraventricular tachycardia, PR interval, QRS interval and SCD., Conclusions: Prolonged QTc was a risk factor for SCD and death even when controlling for typical risk factors.

Study Objectives: At the sleep laboratory, noninvasive positive pressure ventilation titration protocols in patients with neuromuscular disease (NMD) are based on standard pressure cycle devices in a spontaneous/timed mode (BPAP-ST). Experience integrating protocols on average volume-assured pressure support (AVAPS) mode is limited, prompting us to develop a practical single-night titration protocol that provides information to assist clinicians and patients as they decide between BPAP-ST and AVAPS modes., Methods: We implemented a sequential titration protocol of BPAP-ST followed by AVAPS during a single-night polysomnography study in patients with NMD and reported polysomnographic and clinical metrics., Results: There were 27 patients who completed the protocol: 14 (52%) were male with median and interquartile range (IQR) 64 (59 to 70) years of age and body mass index of 29.6 (25.6-32) kg/m 2 . They had median (IQR) maximal percent predicted inspiratory and expiratory pressures, and percent vital capacity of 33 (24 to 54), 34 (22 to 47) and 60 (47 to 74), respectively. At final titration of each device, average tidal volume and nadir non-rapid eye movement sleep oxyhemoglobin saturation (SpO 2 ) were higher and respiratory rate/tidal volume, transcutaneous CO 2 , and arousal index were lower on AVAPS ( P < .05) in comparison with BPAP-ST. Full face mask was used in 23 patients (85%). None of the other ventilatory or sleep parameters differed significantly between BPAP-ST and AVAPS ( P > .05) sessions., Conclusions: A practical single-night split-titration protocol with BPAP-ST and AVAPS can successfully be implemented in patients with NMD, assisting clinicians and patients with the decision on initial treatment modalities and settings., (© 2018 American Academy of Sleep Medicine.)

We summarize the evidence for the safety and efficacy of catheter-directed thrombolysis (CDT) with and without ultrasound-assisted therapy for treating submassive and massive pulmonary embolism (PE) in a systematic review. The primary efficacy outcome was mortality. Outcomes were pooled across studies with the random-effects model. Twenty-four studies enrolled 700 patients in total; 653 received mechanical thromboembolectomy treatments for PE (mortality rate, 9% [95% confidence interval (CI), 6%-13%], P = .12; rate of minor complications, 6% [95% CI, 2%-13%]). In the ultrasound-accelerated thrombolysis (USAT) studies, the mortality rate was 4% (95% CI, 1%-11%) and in the non-USAT studies, it was 9% (95% CI, 6%-13%). Secondary safety outcomes were all bleeding events, which occurred in 12% (95% CI, 7%-20%) of the USAT studies and in 10% (95% CI, 5%-20%) of the non-USAT studies. Current clinical evidence does not prove USAT is superior over CDT methods.

Objective: To objectively assess whether a dog in the bedroom or bed disturbs sleep., Participants and Methods: From August 1, 2015, through December 31, 2015, we evaluated the sleep of humans and dogs occupying the same bedroom to determine whether this arrangement was conducive to sleep. The study included 40 healthy adults without sleep disorders and their dogs (no dogs <6 months old). Each participant wore an accelerometer and their dog a validated dog accelerometer for 7 nights., Results: The mean ± SD age of the participants (88% women) was 44±14 years and body mass index was 25±6. The mean ± SD age of the dogs was 5±3 years and weight was 15±13 kg. Mean ± SD actigraphy data showed 475±101 minutes in bed, 404±99 minutes total sleep time, 81%±7% sleep efficiency, and 71±35 minutes wake time after sleep onset. The dogs' accelerometer activity during the corresponding human sleep period was characterized as mean ± SD minutes at rest, active, and at play of 413±102, 62±43, and 2±4. The dogs had mean ± SD 85%±15% sleep efficiency. Human sleep efficiency was lower if the dog was on the bed as opposed to simply in the room (P=.003)., Conclusion: Humans with a single dog in their bedroom maintained good sleep efficiency; however, the dog's position on/off the bed made a difference. A dog's presence in the bedroom may not be disruptive to human sleep, as was previously suspected., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Patients with end-stage renal disease undergoing kidney transplant often have diffuse atherosclerosis and high cardiovascular morbidity and mortality rates. We analyzed the correlation of peripheral arterial disease (PAD), here quantified by an abnormal ankle-brachial index (ABI) measured within the 5 years prior to kidney transplant, with graft failure and mortality rates (primary end points) after adjusting for known cardiovascular risk factors (age, sex, smoking history, hypertension, diabetes, stroke, known coronary artery disease or heart failure, years of dialysis). Of 1055 patients in our transplant population, 819 had arterial studies within the 5 years prior to transplant. Secondary end points included myocardial infarction; cerebrovascular accident; and limb ischemia, gangrene, or amputation. Low ABI was an independent and significant predictor of organ failure (OR, 2.77 (95% CI, 1.68-4.58), p<0.001), secondary end points (HR, 1.39 (95% CI, 0.97-1.99), p<0.076), and death (HR, 1.84 (95% CI, 1.26-2.68), p=0.002). PAD was common in this population: of 819 kidney transplant recipients, 46% had PAD. Low ABI was associated with a threefold greater risk of graft failure, a twofold greater risk of death after transplant, and a threefold greater risk of secondary end points. Screening for PAD is important in this patient population because of the potential impact on long-term outcomes.

Objective: To determine if the CHA 2 DS 2 -VASc score (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65-74 years, sex category) predicts thromboembolism and death in patients without atrial fibrillation in a population with implantable cardiac monitoring devices., Patients and Methods: A retrospective review utilizing the Rochester Epidemiology Project research infrastructure was conducted to evaluate the CHA 2 DS 2 -VASc tool as a predictor of mortality and ischemic stroke, transient ischemic attack, or systemic embolism in patients without atrial fibrillation. An implantable device was required in the inclusion criteria to discern the absence of atrial fibrillation. The study period was January 1, 2004, through March 7, 2016., Results: The study population (N=1606) had a mean (SD) age of 69.8 (12.6) years and median follow-up of 4.8 years (range, 0-12 years; quartile 1, 2.6 years and quartile 3, 8.1 years). The number of thromboembolic and mortality events stratified by CHA 2 DS 2 -VASc score groupings of 0 to 2 (399 patients), 3 to 5 (756 patients), and 6 to 9 (451 patients) were 12 (3.0%), 109 (14.4%), and 123 (27.3%) and 22 (5.5%), 205 (27.1%), and 214 (47.4%), respectively. The CHA 2 DS 2 -VASc score predicted thromboembolism and death. The hazard ratios (HRs) for thromboembolic events for CHA 2 DS 2 -VASc scores 3 to 5 and 6 to 9 were 4.84 (95% CI, 2.66-8.80) and 10.53 (95% CI, 5.77-19.21) (reference group, scores 0-2). The HRs for death for the corresponding score categories were 4.45 (95% CI, 2.86-6.91) and 8.18 (95% CI, 5.23-12.78). The CHA 2 DS 2 -VASc score also predicted development of atrial fibrillation, for which the HRs for scores 3 to 5 and 6 to 9 were 1.51 (95% CI, 1.13-2.00) and 2.17 (95% CI, 1.60-2.95)., Conclusion: The CHA 2 DS 2 -VASc tool predicts thromboembolic events and overall mortality in patients without atrial fibrillation who have implantable devices., (Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Context: Direct oral anticoagulants (DOACs) may be as effective as, and at times safer than, warfarin. Because DOACs do not require regular serum level monitoring, patients' interaction with the health care system may be reduced. To the authors' knowledge, although studies have evaluated warfarin adherence, few studies have evaluated the real-world adherence to DOACs., Objective: To evaluate whether a difference exists between medication adherence of patients taking DOACs vs patients taking warfarin., Methods: The electronic medical records of the Anticoagulation Clinic database at Mayo Clinic in Scottsdale, Arizona, were reviewed. Inclusion criteria were adults taking DOACs and a matching cohort taking warfarin between January 1, 2011, and December 30, 2013. The Morisky Medication Adherence Scale-8 item, a validated medication adherence tool, was used to evaluate adherence in both cohorts, and the qualitative covariates were analyzed using ordinal logistic regression., Results: Of 324 surveys that were sent, 110 patients (34.0%) responded. Most patients took DOACs for atrial fibrillation, and few took DOACs for venous thromboembolism. Overall, 60 of 66 patients (90.9%) in the DOAC group and 42 of 44 patients (95.5%) in the warfarin group reported medium or high adherence. Difference in adherence scores between the 2 groups was not statistically significant (P=.8)., Conclusion: Similar adherence was noted between DOACs and warfarin regardless of the frequency of serum level monitoring.

Background: This study evaluated referral patterns for preoperative evaluations of patients with poorly controlled diabetes mellitus (DM) and determined whether intervals between evaluations and surgery day were associated with preoperative glucose levels., Results/methodology: In this retrospective analysis of DM patients with a hemoglobin A 1c level greater than 8.0%, of the 163 patients who underwent preoperative medical evaluation, only 45% were evaluated by endocrinology. Patients who had surgery earlier than 10 days after the preoperative medical evaluation had preoperative glucose levels 18% higher than those of patients who waited more than 10 days. Preoperative outpatient contact with endocrinology was not associated with preoperative glucose level (p = 0.90)., Conclusion: For poorly controlled DM, more than 10 days are needed to achieve preoperative glycemic control., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

The clinical management of women with epilepsy on antiepileptic drugs (AEDs) during pregnancy presents unique challenges. The goal of treatment is optimal seizure control with minimal in utero fetal exposure to AEDs in an effort to reduce the risk of structural and neurodevelopmental teratogenic effects. This paper reviews the following key issues pertaining to women with epilepsy during pregnancy: AED pharmacokinetics; clinical management of AEDs; seizure frequency; major congenital malformation; neurodevelopmental outcomes; perinatal complications; and breast feeding.

Intravenous and intramuscular antiseizure drugs (ASDs) are essential in the treatment of clinical seizure emergencies as well as in replacement therapy when oral administration is not possible. The parenteral formulations provide rapid delivery and complete (intravenous) or nearly complete (intramuscular) bioavailability. Controlled administration of the ASD is feasible with intravenous but not intramuscular formulations. This article reviews the literature and discusses the chemistry, pharmacology, pharmacokinetics, and clinical use of currently available intravenous and intramuscular ASD formulations as well as the development of new formulations and agents. Intravenous or intramuscular formulations of lorazepam, diazepam, midazolam, and clonazepam are typically used as the initial treatment agents in seizure emergencies. Recent studies also support the use of intramuscular midazolam as easier than the intravenous delivery of lorazepam in the pre-hospital setting. However, benzodiazepines may be associated with hypotension and respiratory depression. Although loading with intravenous phenytoin was an early approach to treatment, it is associated with cardiac arrhythmias, hypotension, and tissue injury at the injection site. This has made it less favored than fosphenytoin, a water-soluble, phosphorylated phenytoin molecule. Other drugs being used for acute seizure emergencies are intravenous formulations of valproic acid, levetiracetam, and lacosamide. However, the comparative effectiveness of these for status epilepticus (SE) has not been evaluated adequately. Consequently, guidelines for the medical management of SE continue to recommend lorazepam followed by fosphenytoin, or phenytoin if fosphenytoin is not available. Intravenous solutions for carbamazepine, lamotrigine, and topiramate have been developed but remain investigational. The current ASDs were not developed for use in emergency situations, but were adapted from ASDs approved for chronic oral use. New approaches for bringing drugs from experimental models to treatment of human SE are needed.

Background: Cerebral venous thrombosis (CVT) is rare and involves thrombosis of the veins and sinuses of the brain, most commonly the superior sagittal sinus. Approximately 5 CVT cases occur per 1 million persons in western countries. CVT causes 0.5% of strokes. Early diagnosis is crucial to prevent such outcomes as hydrocephalus, intracranial hypertension, and further seizures. Standard medical treatment of CVT consists of low-molecular-weight heparin and endovascular thrombolysis. Small case reports have found that the newer oral anticoagulants can be used for CVT treatment; however, they are associated with increased risk of bleeding and other adverse effects., Review Summary: CVT can be triggered by an imbalance of the body's homeostasis or reduced action of the intrinsic antithrombotic mechanism. Factors influencing this change include infection, brain tumor, inflammatory conditions, genetic thrombophilias, head trauma that causes intracranial bleeding, and certain medications. CVT may cause brain infarction and increased intracranial pressure. Sometimes, idiopathic intracranial hypertension presents as the only clinical manifestation. Confirmation of the diagnosis typically is through neuroimaging. Current CVT treatment depends on disease extent and severity., Conclusions: CVT is a rare neurological disease with potentially serious implications and high neurological morbidity and mortality rates. Understanding the role of risk factors-such as genetic or acquired thrombophilia, pregnancy, use of oral contraceptives, and hyperhomocysteinemia-in CVT development is important. Although heparin and warfarin have been used for more than 50 years, newer oral anticoagulants (eg, dabigatran, rivaroxaban, apixaban) might offer an alternative to traditional therapy.

Aim: Tropical theileriosis is fatal hemoprotozoal disease of dairy animals caused by Theileria annulata. The aim of the present study was to detect the T. annulata and comparison of results of molecular and microscopic techniques., Materials and Methods: A total of 52 blood samples were collected from the cattle suspected for theileriosis across the Banaskantha district. All the samples were screened for theileriosis using Giemsa's staining technique and polymerase chain reaction (PCR)., Results: Total of 17 (32.69%) and 24 (46.15%) samples were found positive for theileriosis by microscopic examination and PCR test, respectively. It revealed that the study area is endemic for theileriosis, and the microscopic technique has 70.83% sensitivity and 100% specificity with respect to PCR technique., Conclusion: It may be concluded from the present study that the PCR is comparatively sensitive technique than microscopic examination and may be recommended to use in the field for screening of theileriosis in the study area, where a high prevalence of diseases have been reported due to intensive dairy farming.

Background: Although the population of diverse applicants applying to medical school has increased over recent years (AAMC Diversity in Medical Education: Facts and Figures 2012); efforts persist to ensure the continuance of this increasing trend. Mentoring students at an early age may be an effective method by which to accomplish diversity within the applicant pool. Having a diverse physician population is more likely able to adequately address the healthcare needs of our diverse population., Purpose: The purpose of this study is to initiate a pipeline program, called the Medical Student Mentorship Program (MSMP), designed to specifically target high school students from lower economic status, ethnic, or racial underrepresented populations. High school students were paired with medical students, who served as primary mentors to facilitate exposure to processes involved in preparing and training for careers in medicine and other healthcare-related fields as well as research., Methods: Mentors were solicited from first and second year medical students at the University of Arizona College of Medicine-Phoenix (UACOM-P). Two separate cohorts of mentees were selected based on an application process from a local high school for the school years 2010-2011 and 2011-2012. Anonymous mentee and mentor surveys were used to evaluate the success of the MSMP., Results: A total of 16 pairs of mentees and mentors in the 2010-2011 (Group 1) and 2011-2012 (Group 2) studies participated in MSMP. High school students reported that they were more likely to apply to medical school after participating in the program. Mentees also reported that they received a significant amount of support, helpful information, and guidance from their medical student mentors. Overall, feedback from mentees and mentors was positive and they reported that their participation was rewarding. Mentees were contacted 2 to 3 years post MSMP participation as sophomores or juniors in college, and all reported that they were on a pre-healthcare career track., Conclusion: The MSMP may serve as an effective pipeline program to promote future diversity in college and graduate training programs for future careers in science and medicine.

The intramuscular (IM) and rectal routes are alternative routes of delivery for antiepileptic drugs (AEDs) when the intravenous route is not practical or possible. For treatment of acute seizures, the AED used should have a short time to maximum concentration (Tmax). Some AEDs have preparations that may be given intramuscularly. These include the benzodiazepines (diazepam, lorazepam, and midazolam) and others (fosphenytoin, levetiracetam). Although phenytoin and valproate have parenteral preparations, these should not be given intramuscularly. A recent study of prehospital treatment of status epilepticus evaluated a midazolam (MDZ) autoinjector delivering IM drug compared to IV lorazepam (LZP). Seizures were absent on arrival to the emergency department in 73.4% of the IM MDZ compared to a 63.4% response in LZP-treated subjects (p < 0.001 for superiority). Almost all AEDs have been evaluated for rectal administration as solutions, gels, and suppositories. In a placebo-controlled study, diazepam (DZP) was administered at home by caregivers in doses that ranged from 0.2 to 0.5 mg/kg. Diazepam was superior to placebo in reduced seizure frequency in children (p < 0.001) and in adults (p = 0.02) and time to recurrent seizures after an initial treatment (p < 0.001). Thus, at this time, only MZD given intramuscularly and DZP given rectally appear to have the properties required for rapid enough absorption to be useful when intravenous routes are not possible. Some drugs cannot be administered rectally owing to factors such as poor absorption or poor solubility in aqueous solutions. The relative rectal bioavailability of gabapentin, oxcarbazepine, and phenytoin is so low that the current formulations are not considered to be suitable for administration by this route. When administered as a solution, diazepam is rapidly absorbed rectally, reaching the Tmax within 5-20 min in children. By contrast, rectal administration of lorazepam is relatively slow, with a Tmax of 1-2h. The dependence of gabapentin on an active transport system, and the much-reduced surface area of the rectum compared with the small intestine, may be responsible for its lack of absorption from the rectum. This article is part of a Special Issue entitled "Status Epilepticus"., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To determine the relationship between sacroiliac joint (SIJ) contrast dispersal patterns during SIJ corticosteroid injection and pain relief at 2 and 8 weeks after the procedure. The association between the number of positive provocative SIJ physical examination maneuvers (minimum of one in all patients undergoing SIJ injection) and the patient's response to the intervention was also assessed., Design: Retrospective chart review., Setting: Academic outpatient musculoskeletal practice., Patients: Fifty-four subjects who underwent therapeutic SIJ corticosteroid injection were screened for inclusion; 49 subjects were included in the final analysis., Methods: A retrospective review of electronic medical records identified patients who underwent SIJ corticosteroid injection. Fluoroscopic contrast flow patterns were categorized as type I (intra-articular injection with cephalad extension within the SIJ) or type II (intra-articular injection with poor cephalad extension). Self-reported numeric pain rating scale (NPRS) values at the time of injection and 2 and 8 weeks after the procedure were recorded. The number of positive provocative SIJ physical examination maneuvers at the time of the initial evaluation was also recorded., Main Outcome Measures: The primary outcome measure was the effect of contrast patterns (type I or type II) on change in NPRS values at 2 weeks and 8 weeks after the injection. The secondary outcome measure was the association between the number of positive provocative SIJ physical examination maneuvers and decrease in the level of pain after the procedure., Results: At 2 weeks after the procedure, type I subjects demonstrated a significantly lower mean NPRS value compared with type II subjects (2.8 ± 1.4 versus 3.8 ± 1.6, respectively, P = .02). No statistically significant difference was observed at 8 weeks after the procedure. NPRS values were significantly reduced both at 2 weeks and 8 weeks, compared with baseline, in both subjects identified as having type I flow and those with type II flow (P < .0001 for all within-group comparisons)., Conclusions: Fluoroscopically guided corticosteroid injections into the SIJ joint are effective in decreasing NPRS values in patients with SIJ-mediated pain. Delivery of corticosteroid to the superior portion of the SIJ leads to a greater reduction in pain at 2 weeks, but not at 8 weeks. Patients with at least one positive provocative maneuver should benefit from an intra-articular corticosteroid injection., (Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to assess the accuracy and operating characteristics of the Patient Health Questionnaire-9 (PHQ-9) for depression screening in adults with epilepsy., Methods: Tertiary epilepsy center patients served as the study population, with 237 agreeing to structured interview using the Mini-International Neuropsychiatric Interview (MINI), a "gold standard" instrument developed for rapid diagnosis of neuropsychiatric disorders, including major depressive disorder (MDD); 172 also completed the PHQ-9, and 127 completed both the PHQ-9 and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) within two days of the MINI. Sensitivity, specificity, positive and negative predictive values, and areas under the ROC curves for each instrument were determined. Cut-points of 10 for the PHQ-9 and 15 for the NDDI-E were used, and ratings at or above the cut-points were considered screen-positive. The PHQ-9 was divided into cognitive/affective (PHQ-9/CA) and somatic (PHQ-9/S) subscales to determine comparative depression screening accuracy., Results: The calculated areas under the ROC curves for the PHQ-9 (n=172) and the PHQ-9/CA and PHQ-9/S subscales were 0.914, 0.924, and 0.846, respectively, with the PHQ-9 more accurate than the PHQ-9/S (p=0.002) but not different from the PHQ-9/CA (p=0.378). At cut-points of 10 and 15, respectively, the PHQ-9 had higher sensitivity (0.92 vs 0.87) but lower specificity (0.74 vs 0.89) compared with the NDDI-E. The areas under the ROC curves of the PHQ-9 and the NDDI-E showed similar accuracy (n=127; 0.930 vs 0.934; p=0.864)., Significance: The PHQ-9 is an efficient and nonproprietary depression screening instrument with excellent accuracy validated for use in adult patients with epilepsy as well as multiple other medical populations., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Mentoring plays an important role in career success of academic medical faculty. New mentoring models such as peer mentoring have emerged., Aim: To evaluate the long-term impact of a facilitated peer mentoring program on academic achievements., Method: Women faculty at the instructor or assistant professor rank were recruited to voluntarily participate in a facilitated peer mentoring program. Recruitment occurred over 3.8 years between 2005 and 2009. A 26-item questionnaire to assess academic skill, career satisfaction, and self-efficacy was administered before program participation and again with seven additional questions in 2011. Curriculum vitae were reviewed retrospectively to tally peer-reviewed publications, other academic activities, and promotions., Results: Participants had long-term improvement in their perceived mastery of academic skills. Peer-reviewed publications, book chapters, abstracts, posters, and other academic activities increased when activities before the program were compared to those in the five years after program enrollment. At follow-up, participants reported positive perceptions of the program and 44% continued to work with their original peer mentor groups., Conclusions: Involvement in the facilitated peer mentoring program was associated with increased skills and academic activities for most participants. Future studies are needed to assess its applicability and success among various demographic groups in academic medicine.

Electrocardiographic (ECG) artifacts occur with the use of internal or external monitoring and therapeutic devices. Other common cause of ECG artifact is patient's motion. Electrocardiographic artifact during electroconvulsive therapy is not reported in the literature. We report ECG artifacts due to 2 different mechanisms in the same patient.

A new technique for performing nerve blocks of the ganglion impar (ganglion Walther) is presented. These injections have been reported to relieve coccydynia (tailbone pain), as well as other malignant and nonmalignant pelvic pain syndromes. A variety of techniques have been previously described for blocking this sympathetic nerve ganglion, which is located in the retrorectal space just anterior to the upper coccygeal segments. Prior techniques have included approaches through the anococcygeal ligament, through the sacrococcygeal joint, and through intracoccygeal joint spaces. This article presents a new, paracoccygeal approach whereby the needle is inserted alongside the coccyx and the needle is guided through three discrete steps with a rotating or corkscrew trajectory. Compared with some of the previously published techniques, this paracoccygeal corkscrew approach has multiple potential benefits, including ease of fluoroscopic guidance using the lateral view, ability to easily use a stylet for the spinal needle, and use of a shorter, thinner needle. While no single technique works best for all patients and each technique has potential advantages and disadvantages, this new technique adds to the available options.