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Introduction: Smoking-related diseases affect 16 million Americans, causing approximately 480,000 deaths annually. The prevalence of cigarette smoking varies regionally across the United States, and previous research indicates that regional rates of smoking-related diseases demonstrate a negative association with altitude. The purpose of this study was to determine the relationship between altitude and the prevalence of cigarette smoking by county (N = 3106) in the United States. We hypothesized that smoking prevalence among adults would be negatively associated with mean county altitude. Methods: A multivariate linear regression was performed to examine the relationship between county-level mean altitude and county smoking rate. Covariates were individually correlated with 2020 smoking data, and significant associations were included in the final model. Results: The multivariate linear regression indicated that the county-level smoking rates are significantly reduced at high altitudes (p < 0.001). The model accounted for 89.5% of the variance in smoking prevalence, and for each 1000-foot increase in altitude above sea level, smoking rates decreased by 0.143%. Based on multivariate linear regression, the following variables remained independently and significantly associated: race, sex, educational attainment, socioeconomic status, unemployment, physical inactivity, drinking behavior, mental distress, and tobacco taxation. Conclusions: Our results indicate that smoking rates are negatively associated with altitude, which may suggest that altitude affects the pharmacokinetics, pharmacodynamics, and mechanistic pathways involved in cigarette use. Further research is needed to explore the relationship between altitude and smoking and how altitude may serve as a protective factor in the acquisition and maintenance of tobacco use disorders.

AbstractBackgroundKetamine is increasingly used for treatment‐resistant depression (TRD) while its mechanism of action is still being investigated. In this systematic review, we appraise the current evidence of metabolomic biomarkers for racemic ketamine and esketamine in patients with TRD and healthy controls (HCs).MethodsA comprehensive search of several databases (Ovid MEDLINE®, Embase, and Epub Ahead of Print) was performed from each database's inception to June 29, 2022, in any language, was conducted. We included studies wherein the metabolomic biomarkers for racemic ketamine or esketamine were investigated in TRD or HCs. Our main outcomes were to examine changes in metabolites among patients treated with ketamine/esketamine and explore the association with response to ketamine/esketamine.ResultsA total of 1859 abstracts were screened of which 11 were included for full‐text review. Of these, a total of five articles were included (N = 147), including three RCTs (n = 129) and two open‐label trials (n = 18). All studies used racemic ketamine; one study additionally used esketamine. The included studies evaluated patients with treatment‐resistant bipolar depression (n = 22), unipolar depression (n = 91), and HCs (n = 34). The included studies reported alteration in several metabolites including acylcarnitines, lipids, kynurenine (KYN), and arginine with ketamine in TRD. Studies suggest the involvement of energy metabolism, KYN, and arginine pathways. In HCs, acetylcarnitine decreased post‐infusion, whereas inconsistent findings were observed after the ketamine infusion in TRD patients.ConclusionsThis systematic review provides preliminary evidence that ketamine may cause changes in several important pathways involved in energy metabolism and inflammation. Larger and more rigorous studies are needed.

Background: Granulomatosis with polyangiitis (GPA) is a vasculitis with multi-organ involvement. Some cases of gynecologic involvement have been described, but there are no systematic reviews in the literature. Objectives: to provide a systematic review of the literature of GPA patients with gynecological involvement. Search Strategy: PubMed and Embase, were searched from inception to July 2012 for GPA patients with gynecological involvement Medical Subject Headings (MeSH) and free-text terms. Selection Criteria: Patients with GPA and primary gynecologic involvement, and/or genital recurrence. Exclusion criteria were other language, review articles, pregnancy, fertility or male patients. Data Collection and Analysis: Data were extracted on clinical evolution, symptoms, examinations findings, diagnosis delay, treatment, outcome, patient status, and follow-up. The main limitation of the studies was the high heterogeneity, which resulted in a narrative review and could lead to publication bias. Main Results: Seventeen studies included data from patients with GPA and primary or relapsed gynecological involvement. In GPA patients, the genitourinary system is affected in <1%. 61% of the authors of this review thought the patient had cancer. The main gynecological symptom is bleeding, but exclusive gynecologic symptomatology is rare (ENT: 63%, lungs: 44%, kidneys-urinary tract: 53%). GPA could affect all areas of the genital tract, but the most frequent location is the uterine cervix. Medical treatment for GPA is effective. Conclusions: GPA of the female genital tract must be considered when biopsies of an ulcerated malignant-appearing cervical or vaginal mass are negative for malignancy even when they are unspecific. Rheumatology consultation is indicated.

Achieving health equity in populations with congenital heart disease (CHD) requires recognizing existing disparities throughout the lifespan that negatively and disproportionately impact specific groups of individuals. These disparities occur at individual, institutional, or system levels and often result in increased morbidity and mortality for marginalized or racially minoritized populations (population subgroups (e.g., ethnic, racial, social, religious) with differential power compared to those deemed to hold the majority power in the population). Creating actionable strategies and solutions to address these health disparities in patients with CHD requires critically examining multilevel factors and health policies that continue to drive health inequities, including varying social determinants of health (SDOH), systemic inequities, and structural racism. In this comprehensive review article, we focus on health equity solutions and health policy considerations for minoritized and marginalized populations with CHD throughout their lifespan in the United States. We review unique challenges that these populations may face and strategies for mitigating disparities in lifelong CHD care. We assess ways to deliver culturally competent CHD care and to help lower-health-literacy populations navigate CHD care. Finally, we review system-level health policies that impact reimbursement and research funding, as well as institutional policies that impact leadership diversity and representation in the workforce.

AbstractBackgroundThe cardiac and respiratory cycles have been suggested as major drivers of cerebrospinal fluid(CSF) flow. The glymphatic system, one of the mechanisms for the clearance of amyloid‐beta and tau proteins, relies heavily on the movement(flow) of the CSF, and thus, investigating the forces that modulate the CSF flow is essential for understanding the glymphatic flux. Because breathing is trainable through exercise and self‐directed methods, various breathing methods may enhance the CSF flow.MethodReal‐time phase‐contrast MRI(pc‐MRI) was used to measure the CSF flow at the foramen magnum on a 3T. Fast resting‐state fMRI(rsfMRI;TR400ms) was conducted on a compact 3T. Under an IRB‐approved protocol, participants were instructed to breathe slowly and deeply, and subsequently switch to their spontaneous breathing. For rsfMRI data preprocessing, we performed motion correction, skull stripping, spatial smoothing(4mm), temporal filtering(0.01 to 0.1Hz), and linear and quadratic temporal trends removal. fMRI time courses were then normalized to Z‐score at each voxel before being averaged. On the pcMRI, the phase was summed in a CSF region‐of‐interest and plotted vs time. Additionally, we confirmed for possible confounding effects such as head motion or motion‐induced susceptibility changes.ResultrsfMRI findings showed that deep breathing promoted large oscillations in the CSF flow in the ventricles, while spontaneous breathing did not(Figure 1). Additionally, deep breathing resulted in large oscillations in lobar cortical regions. Similar results were observed in the pcMRI, with larger CSF velocity through the foramen magnum during the deep breathing compared to the spontaneous breathing(Figure 2A‐B). The cumulative summation result showed that the volume of CSF flow was increased during deep breathing(Figure 2C).ConclusionThis study provides new evidence that slow and deep breathing promotes CSF flow and global brain BOLD signal, which may be useful in promoting circulation in the brain. The study’s findings also open new avenues for research in the field of neurovascular coupling and mechanisms associated with glymphatic clearance. As hampered CSF flow and/or worsen glymphatic clearance have been shown to associate with pathological aging and dementia, including Alzheimer’s disease and Parkinson’s disease, future research is needed explore the potential of breathing training methods as a non‐pharmacological intervention to support brain health.

Ketamine has shown rapid antidepressant and anti-suicidal effects in treatment-resistant depression (TRD) with single and serial intravenous (IV) infusions, but the effectiveness for depressive episodes of bipolar disorder is less clear. We conducted an updated systematic review and meta-analysis to appraise the current evidence on the efficacy and tolerability of ketamine/esketamine in bipolar depression. A search was conducted to identify randomized controlled trials (RCTs) and non-randomized studies examining single or multiple infusions of ketamine or esketamine treatments. A total of 2657 articles were screened; 11 studies were included in the systematic review of which 7 studies were included in the meta-analysis (five non-randomized, N = 159; two RCTs, N = 33) with a mean age of 42.58 ± 13.1 years and 54.5% females. Pooled analysis from two RCTs showed a significant improvement in depression symptoms measured with MADRS after receiving a single infusion of ketamine (1-day WMD = −11.07; and 2 days WMD = −12.03). Non-randomized studies showed significant response (53%, p < 0.001) and remission rates (38%, p < 0.001) at the study endpoint. The response (54% vs. 55%) and remission (30% vs. 40%) rates for single versus serial ketamine infusion studies were similar. The affective switch rate in the included studies approximated 2.4%. Esketamine data for bipolar depression are limited, based on non-randomized, small sample-sized studies. Further studies with larger sample sizes are required to strengthen the evidence.

Abstract Background HIV knowledge and prevention strategies, like PrEP/PEP is a core element in current medical practice but represents a challenge for medical students’ curricula. In countries like Dominican Republic (DR), the stigma towards HIV infection restricts the delivery of HIV related information to the general population. Our study aims to understand the level of knowledge between different academical years pose regarding HIV/AIDS, PrEP and PEP and how their curricula content is covered across the years. Methods We survey medical students in the DR to measure knowledge on HIV, PrEP/PEP. Students who agreed to participate filled in a survey with 3 sections. Each section had 10 true or false questions. Responses were compared mean knowledge for each topic based on a score out of 10. We analyzed mean scores using ANOVA with Post Hoc analysis, assuming significance when p&lt; 0.05. Results A total of 503 participants participated in the survey. ANOVA results showed that there was a statistically significant difference in mean HIV knowledge (F (3, 499) = [25,58], p&lt; 0.001) and PEP knowledge (F (3, 499) = [13,77], p&lt; 0.001) between the academical years. Post-hoc analysis revealed that MS4 had a higher mean score for HIV knowledge (M= 9.3) than MS2 (8.7, p&lt; 0.01) and MS1 (m= 8.2, p&lt; 0.01). Similarly, MS3 had a higher mean HIV knowledge than MS2 (p&lt; 0.01) and MS1 (p&lt; 0.01). Likewise, MS2 had an increased mean HIV knowledge when compared to MS1 (p&lt; 0.01). When we compare mean PEP knowledge, we found that MS3 (m= 7.45) had increased knowledge than MS1 (6.4, p&lt; 0.01) and MS2 (m= 6.9, p&lt; 0.05). Similarly, we found that MS4 had increased mean PEP Knowledge (m= 7.5) when compared to MS1 and MS2 (p&lt; 0.001). When we studied mean PrEP knowledge, ANOVA analysis found no significant difference (F (3, 499) = [1,24], p= 0.29). Conclusion Our study suggests that the mean knowledge of HIV and PEP increases throughout the academic progression of medical school. Although there is no difference in PEP knowledge, this may suggest that medical schools are teaching PEP during MS3-MS4 cycle rather than the M1-M2 cycle. Also, the homogenous mean PrEP knowledge could suggest that the students are learning from non-academic sources. This emphasizes the curricular designers of medical schools to review the contents on prevention of communicable diseases. Disclosures All Authors: No reported disclosures

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Background: Antidepressants are among the most prescribed medications in the United States. The aim of this study was to explore the prevalence of antidepressant prescriptions and investigate sex differences and age-sex interactions in adults enrolled in the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment (RIGHT) study. Materials and Methods: We conducted a retrospective analysis of the RIGHT study. Using electronic prescriptions, we assessed 12-month prevalence of antidepressant treatment. Sex differences and age-sex interactions were evaluated using multivariable logistic regression and flexible recursive smoothing splines. Results: The sample consisted of 11,087 participants (60% women). Antidepressant prescription prevalence was 22.24% (27.96% women, 13.58% men). After adjusting for age and enrollment year, women had significantly greater odds of antidepressant prescription (odds ratio = 2.29; 95% confidence interval = 2.07, 2.54). Furthermore, selective serotonin reuptake inhibitors (SSRIs) had a significant age-sex interaction. While SSRI prescriptions in men showed a sustained decrease with age, there was no such decline for women until after reaching ∼50 years of age. There are important limitations to consider in this study. Electronic prescription data were cross-sectional; information on treatment duration or adherence was not collected; this cohort is not nationally representative; and enrollment occurred over a broad period, introducing confounding by changes in temporal prescribing practices. Conclusions: Underscored by the significant interaction between age and sex on odds of SSRI prescription, our results warrant age to be incorporated as a mediator when investigating sex differences in mental illness, especially mood disorders and their treatment.