COVID-19 Incidence After Emergency Department Visit.

Background: The emergency department (ED) at the Veterans Affairs Greater Los Angeles Healthcare System (VAGLAHS) saw a decrease in the number of visits during the early stages of the COVID-19 pandemic. Little is known whether risk mitigation procedures may help reduce the spread of COVID-19 infections for veterans visiting the ED. Therefore, we reviewed patient visits to the ED for diagnoses other than COVID-19 to assess whether these patients had an increased COVID-19 positivity rate within 21 days of the initial visit. Observations: Risk mitigation procedures instituted by the VAGLAHS ED included a COVID-19 outdoor testing tent, immediate isolation of persons under investigation for COVID-19, disinfection protocols between high-risk patient encounters, dedicated training in donning and doffing personal protective equipment, implementation of 2-physician airway teams for COVID-19 intubations, use of electronic tablets to communicate with COVID-19 patients, and implementation of social distancing initiatives in the waiting room to minimize COVID-19 exposures. The average positivity rate at the VAGLAHS ED during this time frame was 0% to 6.7%, compared with 6.9% to 33.3% within the wider VAGLAHS. Conclusions: Implementing risk mitigation procedures in the VAGLAHS ED helped minimize exposure and subsequent diagnosis of COVID-19 for veterans who visited the VAGLAHS ED for symptoms not associated with COVID-19 infection. Seeking acute medical care in the ED did not put patients at higher risk of contracting COVID-19.

Veteran knowledge, perceptions, and receipt of care following visits to VA emergency departments for ambulatory care sensitive conditions.

OBJECTIVE: Receipt of follow-up care after emergency department (ED) visits for chronic ambulatory care sensitive conditions (ACSCs)-asthma, chronic obstructive pulmonary disease, heart failure, diabetes, and/or hypertension-is crucial. We assessed Veterans' follow-up care knowledge, perceptions, and receipt of care after visits to Veterans Health Administration (VA) EDs for chronic ACSCs. METHODS: Using explanatory sequential mixed methods, we interviewed Veterans with follow-up care needs after ACSC-related ED visits, and manually reviewed ED notes, abstracting interviewees' documented follow-up needs and care received. RESULTS: We interviewed and reviewed ED notes of 35 Veterans, 12-27 (mean 19) days after ED visits. Follow-up care was completely received/scheduled in 20, partially received/scheduled in eight, and not received in seven Veterans. Among those who received care, it was received within specified time frames half the time. However, interviewees often did not recall these time frames or reported them to be longer than specified in the ED notes. Veterans who had not yet received or scheduled follow-up care commonly did not recall follow-up care instructions, believed that they did not need this care since they were not currently having symptoms, or thought that such care would be difficult to obtain due to appointment unavailability and/or difficulties communicating with follow-up care providers. Among the 28 Veterans in whom all or some follow-up care had been received/scheduled, for 25 cases VA staff reached out to the Veteran or the appointment was scheduled prior to or during the ED visit. CONCLUSIONS: VA should prioritize implementing processes for EDs to efficiently communicate Veterans' needs to follow-up care providers and systems for reaching out to Veterans and/or arranging for care prior to Veterans leaving the ED. VA should also enhance practices using multimodal approaches for educating Veterans about recommended ED follow-up care and improve mechanisms for Veterans to communicate with follow-up care providers.

Resident Clinical Experience in the Emergency Department: Patient Encounters by Postgraduate Year.

BACKGROUND: During emergency medicine (EM) training, residents are exposed to a wide spectrum of patient complaints. We sought to determine how resident clinical experience changes based on training level in relation to the patient acuity levels, chief complaints, and dispositions. METHODS: We performed a retrospective chart review of patients seen at a safety-net, academic hospital in Los Angeles from July 1, 2015, to June 30, 2016. Resident postgraduate year (PGY) level and specialty, patient acuity (based on the Emergency Severity Index), chief complaint (based on one of 30 categories), and disposition were abstracted. Our primary objective was to examine the progression of EM resident experience throughout the course of training. As a secondary objective, we compared the cases seen by EM and off-service PGY-1s. RESULTS: A total of 49,535 visits were examined, and of these, 32,870 (66.4%) were in the adult ED (AED) and 16,665 (33.6%) were in the pediatric ED (PED). The median acuity level was 3, and 27.4% of AED patients and 7.3% of PED patients were admitted. Data from 126 residents were analyzed. This included 94 PGY-1 residents (16 EM and 78 off-service), 16 PGY-2 EM, and 16 PGY-3 EM residents. Residents of different training levels evaluated different types of patients. Senior EM residents were more likely to care for higher-acuity patients than junior EM residents. EM PGY-3s saw higher percentages of acuity level 1 and 2 patients (2.3 and 37.8%, respectively, of their total patients) than EM PGY-1s (0.3 and 18.7%, respectively). Conversely, EM PGY-1s saw higher percentages of acuity level 4 and 5 patients (27.9 and 1.6%, respectively) compared to EM PGY-3s (10.7 and 0.7%, respectively). There was a significant linear trend for increasing acuity with training year among EM residents (p < 0.001). EM PGY-1s saw more patients than off-service PGY-1s with slightly higher acuities and admission rates. CONCLUSION: The clinical experience of EM residents varies based on their level of training. EM residents show a progression throughout residency and are more likely to encounter higher volumes of patients with higher acuity as they progress in their training. When designing EM residency curriculums, this is a model of an EM residency program.

Androgens Mediate Sex-Dependent Gonadotropin Expression During Late Prenatal Development in the Mouse.

Central organization of the hypothalamic-pituitary-gonadal axis is initiated during fetal life. At this critical time, gonadal hormones mediate sex-specific development of the hypothalamic-pituitary axis, which then dictates reproductive physiology and behavior in adulthood. Although studies have investigated the effects of prenatal androgens on central factors influencing gonadotropin-releasing hormone (GnRH) release, the impact of fetal androgens on gonadotrope function has been overlooked. In the current study, we demonstrated that gonadotropin gene expression and protein production were robustly elevated in female mice compared with males during late fetal development and that this sex difference was dependent on fetal androgens. Treatment of dams from embryonic day (E)15.5 to E17.5 with testosterone, dihydrotestosterone (DHT), or the androgen antagonist flutamide eliminated the sex difference at E18.5. Specifically, flutamide relieved the suppression in male gene expression, elevating the level to that of females, whereas testosterone or DHT attenuated female gene expression to male levels. The gonadotrope population is equivalent in males and females, and gonadotropic cells in both sexes express androgen receptors, suggesting that androgen-dependent transcriptional regulation can occur in these cells in either sex. Studies using mouse models lacking GnRH signaling show that GnRH is necessary for enhanced gonadotropin expression in females and is therefore required to observe the sex difference. Collectively, these data suggest that circuits controlling GnRH input to the fetal pituitary are unrestrained in females yet robustly inhibited in males via circulating androgens and demonstrate plasticity in gonadotropin synthesis and secretion in both sexes depending on the androgen milieu during late prenatal development.

Equivalent weight loss with marked metabolic benefit observed in a matched cohort with and without type 2 diabetes 12 months following gastric bypass surgery.

BACKGROUND: Bariatric surgery results in dramatic weight loss and improves metabolic syndrome and type 2 diabetes (T2DM). However, previous studies have noted that morbidly obese patients with T2DM experience less weight loss benefits than non-diabetic patients following bariatric surgery. We sought to determine longitudinal effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) on percent excess body mass index (BMI) loss (%EBMIL) and clinical metabolic syndrome parameters in patients with T2DM compared with appropriately matched cohort without T2DM. METHODS: Retrospective cohort analysis of T2DM patients (n = 126) to non-T2DM patients (n = 126) matched on age (M = 48.1 ± 9.5), sex (81 % female), race (81 % Caucasian), and pre-surgical BMI (M = 49.3 ± 9.5). Lipids, glucose, hemoglobin A1c, blood pressure, co-morbidities of obesity, medications for co-morbidities, and T2DM medications were collected at baseline, 6 months and 12 months post-surgery. %EBMIL was collected at 1, 3, 6, 9, and 12 months post-surgery. One-way analyses of variance with effect sizes estimates were conducted to compare the two groups. RESULTS: As expected, T2DM subjects had significantly greater pre-surgical HbA1c, blood glucose, blood pressure, and lipid parameters at baseline vs. non-T2DM (all p values of<0.05). At 1, 3, 6, 9, and 12 months after LRYRB, both groups had similar reduction in %EBMIL (p > 0.10). At 6 months, there was a significant reduction in HbA1c, blood glucose, and lipid in the T2DM cohort compared with pre-surgical levels (p < 0.0001). At 12 months, these values were not different to that of the non-T2DM subjects (p > 0.10). CONCLUSIONS: When matched on appropriate factors associated with weight loss outcomes, severely obese patients with T2DM have similar post-LRYGB weight loss outcomes in the first 12 months following surgery compared with non-T2DM patients. Furthermore, T2DM surgical patients achieved significant improvement in metabolic syndrome components.

Mutational analysis of the necdin gene in patients with congenital isolated hypogonadotropic hypogonadism.

CONTEXT: Necdin activates GNRH gene expression and is fundamental for the development, migration, and axonal extension of murine GNRH neurons. In humans, necdin plays a potential role in the hypogonadotropic hypogonadism phenotype in patients with Prader-Willi syndrome. AIM: To investigate necdin gene (NDN) variants in patients with isolated hypogonadotropic hypogonadism (IHH). PATIENTS AND METHODS: We studied 160 Brazilian patients with IHH, which includes 92 with Kallmann syndrome and 68 with normosmic IHH. Genomic DNA was extracted and the single NDN exon was amplified and sequenced. To measure GNRH transcriptional activity, luciferase reporter plasmids containing GNRH regulatory regions were transiently transfected into GT1-7 cells in the presence and absence of overexpressed wild-type or mutant necdin. RESULTS: A heterozygous variant of necdin, p.V318A, was identified in a 23-year-old male with Kallmann syndrome. The p.V318A was also present in affected aunt and his father and was absent in 100 Brazilian control subjects. Previous FGFR1 gene analysis revealed a missense mutation (p.P366L) in this family. Functional studies revealed a minor difference in the activation of GNRH transcription by mutant protein compared with wild type in that a significant impairment of the necdin protein activity threshold was observed. CONCLUSION: A rare variant of necdin (p.V318A) was described in a family with Kallmann syndrome associated with a FGFR1 mutation. Familial segregation and in vitro analysis suggested that this non-synonymous variant did not have a direct causative role in the hypogonadism phenotype. NDN mutations are not a frequent cause of congenital IHH.

Enhancers of GnRH transcription embedded in an upstream gene use homeodomain proteins to specify hypothalamic expression.

GnRH, the central regulator of reproductive function, is produced by only approximately 800 highly specialized hypothalamic neurons. Previous studies identified a minimal promoter [GnRH minimal promoter (GnRH-P)] (-173/+1) and a neuron-specific enhancer [GnRH-enhancer (E)1] (-1863/-1571) as regulatory regions in the rat gene that confer this stringent specificity of GnRH expression to differentiated GnRH neurons. In transgenic mice, these two elements target only GnRH neurons but fail to drive expression in the entire population, suggesting the existence of additional regulatory regions. Here, we define two novel, highly conserved, upstream enhancers in the GnRH gene termed GnRH-E2 (-3135/-2631) and GnRH-E3 (-4199/-3895) that increase neuron-specific GnRH expression through interactions with GnRH-E1 and GnRH-P. GnRH-E2 and GnRH-E3 regulate GnRH expression through similar mechanisms via Oct-1, Msx1, and Dlx2, which bind both GnRH-E2 and the GnRH-E3 critical region at -3952/-3895. Overexpression of Dlx2 increases transcription through GnRH-E2 and GnRH-E3. Remarkably, these novel elements are contained within the 3' untranslated region of the neighboring upstream gene, yet are marked endogenously by histone modification signatures consistent with those of enhancers. Thus, GnRH-E2 and GnRH-E3 are novel regulatory elements that, together with GnRH-E1 and GnRH-P, confer the specificity of GnRH expression to differentiated and mature GnRH neurons.