Canonical BMP–Smad Signalling Promotes Neurite Growth in Rat Midbrain Dopaminergic Neurons

Ventral midbrain (VM) dopaminergic (DA) neurons project to the dorsal striatum via the nigrostriatal pathway to regulate voluntary movements, and their loss leads to the motor dysfunction seen in Parkinson’s disease (PD). Despite recent progress in the understanding of VM DA neurogenesis, the factors regulating nigrostriatal pathway development remain largely unknown. The bone morphogenetic protein (BMP) family regulates neurite growth in the developing nervous system and may contribute to nigrostriatal pathway development. Two related members of this family, BMP2 and growth differentiation factor (GDF)5, have neurotrophic effects, including promotion of neurite growth, on cultured VM DA neurons. However, the molecular mechanisms regulating their effects on DA neurons are unknown. By characterising the temporal expression profiles of endogenous BMP receptors (BMPRs) in the developing and adult rat VM and striatum, this study identified BMP2 and GDF5 as potential regulators of nigrostriatal pathway development. Furthermore, through the use of noggin, dorsomorphin and BMPR/Smad plasmids, this study demonstrated that GDF5- and BMP2-induced neurite outgrowth from cultured VM DA neurons is dependent on BMP type I receptor activation of the Smad 1/5/8 signalling pathway

Reliable Rapid Assay for Gonorrhea and Chlamydia in the Emergency Department.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are common sexually transmitted infections seen in the emergency department (ED). Due to an inability to reliably make accurate diagnosis by physical examination, concern for unreliable follow-up, and current delays in diagnostic nucleic acid amplification testing (NAAT), presumptive treatment active against CT and NG, as described by Centers for Disease Control clinical practice guidelines, is often performed. OBJECTIVES: The purpose of this study was to determine whether a rapid, urine NAAT performed in the ED is noninferior in its diagnostic sensitivity compared with a traditional, swab NAAT assay. METHODS: We performed a prospective, noninferiority study comparing two U.S. Food and Drug Administration-approved NAAT assays for CT and NG: a 90-min rapid assay, the Xpert CT/NG Assay (Cepheid, Sunnyvale, CA) using a urine sample vs. a traditional assay, the Aptima Combo 2 Assay (Gen-Probe Incorporated, San Diego, CA) using a swab sample. This study was registered on Clinicaltrials.gov (NCT02386514). RESULTS: A total of 1162 patient samples were included in the primary analysis. We observed excellent kappa agreement between assays: NG for men, 1.00 (95% confidence interval [CI] 1.00-1.00); NG for women, 0.87 (95% CI 0.79-0.94); CT for men, 0.81 (95% CI 0.59-1.00); and CT for women: 0.85 (95% CI 0.80-0.90), as well as excellent negative and positive predictive values for the rapid assay. CONCLUSION: Although the rapid Xpert CT/NG assay\u27s diagnostic sensitivity did not meet our prespecified threshold for noninferiority, the diagnostic characteristics are robust enough to fit into a management pathway that may reduce unnecessary antibiotic use. There may be an opportunity to utilize the rapid Xpert CT/NG assay to improve accuracy of treatment in the ED

Gonorrhea and chlamydia in the emergency department: Continued need for more focused treatment for men, women and pregnant women.

INTRODUCTION: Delay in current nucleic acid amplification testing for Neisseria gonorrhoeae and Chlamydia trachomatis has led to recommendations for presumptive treatment in patients with concern for infection and unreliable follow-up. In the urban setting, it is assumed that many patients have unreliable follow-up, therefore presumptive therapy is thought to be used frequently. We sought to measure the frequency of disease and accuracy of presumptive treatment for these infections. METHODS: This was an observational cohort study performed at an urban academic Level 1 trauma center ED with an annual census of 95,000 visits per year. Testing was performed using the APTIMA Unisex swab assay (Gen-Probe Incorporated, San Diego, CA). Presumptive therapy was defined as receiving treatment for both infections during the initial encounter without confirmation of diagnosis. RESULTS: A total of 1162 patients enrolled. Infection was present in 26% of men, 14% of all women and 11% of pregnant women. Despite high frequency of presumptive treatment, \u3e4% of infected patients in each category went untreated. CONCLUSION: Inaccuracy of presumptive treatment was common for these sexually transmitted infections. There is an opportunity to improve diagnostic accuracy for treatment

Cerebral Blood Flow Response to Fluid Challenge in Acute Ischemic Stroke

Background: Debate exists on the efficacy of intravenous fluids to improve cerebral blood flow in acute ischemic stroke (AIS). Objective: We tested the hypothesis that bolus crystalloid therapy would improve cerebral blood flow velocity as measured using transcranial Doppler (TCD) in patients with AIS. Secondarily, we determined the modifying effect of key, non-invasive hemodynamic parameters on this relationship. Methods: Prospective, quasi-experimental study of patients confirmed AIS and a NIHSS \u3e 3. Exclusion criteria were: age \u3c 18 years, time of onset \u3e 12 hours, brain hemorrhage, inadequate temporal windows for TCD measurement, and contraindication to bolus fluids per treating team. We performed baseline noninvasive, continuous non-invasive hemodynamic monitoring using the Nexfin device, and we measured cerebral blood flow velocity with TCD insonation of the middle cerebral arteries (MCA) fixed to a headframe. Next, each patient received a 500 mL bolus of crystalloid, followed by repeat hemodynamic and TCD measurements. We performed univariate comparisons of the change in mean flow velocity (MFV) of the MCA on the affected side following confirmation of stroke location and multiple linear regression to test the modifying effect of hemodynamic variables such as systolic blood pressure (sBP), stroke volume index (SVI) and cardiac index (CI). Results: We enrolled 30 patients with confirmed AIS. The mean age was 53 (± 13) years and 50% were female. The median NIHSS was 6 (IQR 4,7) and baseline sBP 155 mmHg. Following the fluid bolus, there was significant increase in sBP (+7, 95%CI 0.6-13 mmHg) and SVI (+2.2, 95%CI 0.3-4.1 mL/m2). The average change in MFV was not significant (0.3, 95%CI -3.7 to 4.3 cm/sec). In a model adjusting for NIHSS, BUN/Cr ratio, age, and baseline CI and sBP, increasing age and lower baseline CI were associated with an increase in MFV after a fluid bolus. Conclusion: In this sample of AIS patients, a fluid bolus did not increase MFV overall. However, on adjusted subanalysis, older individuals with reduced baseline CI appeared to respond better suggesting the potential for targeted therapeutic intervention in such patients

Derivation of Patient Decision Tool for Sore Throat

Background: Most diagnostic support tools are designed for clinicians. Although web or mobile based symptom-based tools are widely available, few if any have been validated. Particularly in under-served communities, such tools could reduce healthcare cost if they are able to guide patients to avoid ED or urgent care when unneccessary. Objective: To derive a patient decision tool for sore throat and assess patients\u27 capacity for using such a tool. Methods: A prospective observation study inclusive of patients presenting to an urban ED and urgent care center. We included ages 2 to 50 years with complaints of sore throat and upper respiratory complaints. We excluded patients outside this age range or if they or their guardian were unable to provide informed consent. We collected extensive symptom and clinical information that would be available to any patient at home. The primary outcome was streptococcal pharyngitis confirmed by throat culture or a related complication such as peritonsillar abscess. We also queried patients on their capacity and willingness to use such information at home through a web-based score tool to guide their care. Analysis consisted of multivariable logistic regression modeling to derive a score tool and to determine its diagnostic test characteristics for predicting the diagnosis. Results: We enrolled 176 patients, 64% female, 88% African American, and 31% \u3c 18 years. There were 46 (26%) patients that had strep pharyngitis. The most common alternative diagnosis was a viral upper respiratory infection (67%). A derived score tool had an area under the curve of 0.76 (95%CI 0.68-0.84). Patients scoring \u3c 5 (n=76, 43%) on a 0 - 20 scale had a NPV of 89% (95% CI 80-95%) for streptococcal pharyngitis. 52% of patients stated they had no access to a clinic to seek medical advice for their current medical problem. Nearly all participants (98%) stated that they have phone internet access, 76% routinely use mobile apps, and 95% affirmed that they would use a mobile tool designed to help them choose the appropriate level of medical care. Conclusions: This study indicates that a patient administered score tool for sore throat may perform similar to existing physician administered score tools. Patient willingness to use such a tool to guide their choices for medical care is high

Cerebrovascular risks with rapid blood pressure lowering in the absence of hypertensive emergency.

STUDY OBJECTIVE: In the Emergency Department (ED) setting, clinicians commonly treat severely elevated blood pressure (BP) despite the absence of evidence supporting this practice. We sought to determine if this rapid reduction of severely elevated BP in the ED has negative cerebrovascular effects. METHODS: This was a prospective quasi-experimental study occurring in an academic emergency department. The study was inclusive of patients with a systolic BP (SBP) \u3e 180 mm Hg for whom the treating clinicians ordered intensive BP lowering with intravenous or short-acting oral agents. We excluded patients with clinical evidence of hypertensive emergency. We assessed cerebrovascular effects with measurements of middle cerebral artery flow velocities and any clinical neurological deterioration. RESULTS: There were 39 patients, predominantly African American (90%) and male (67%) and with a mean age of 50 years. The mean pre-treatment SBP was 210 ± 26 mm Hg. The mean change in SBP was -38 mm Hg (95% CI -49 to -27) mm Hg. The average change in cerebral mean flow velocity was -5 (95% CI -7 to -2) cm/s, representing a -9% (95% CI -14% to -4%) change. Two patients (5.1%, 95% CI 0.52-16.9%) had an adverse neurological event. CONCLUSION: While this small cohort did not find an overall substantial change in cerebral blood flow, it demonstrated adverse cerebrovascular effects from rapid BP reduction in the emergency setting

Potential of Mobile Health Technology to Reduce Health Disparities in Underserved Communities.

INTRODUCTION: Mobile health (mHealth) has the potential to change how patients make healthcare decisions. We sought to determine the readiness to use mHealth technology in underserved communities. METHODS: We conducted a cross-sectional survey of patients presenting with low-acuity complaints to an urban emergency department (ED) with an underserved population. Patients over the age of two who presented with low-acuity complaints were included. We conducted structured interview with each patient or parent (for minors) about willingness to use mHealth tools for guidance. Analysis included descriptive statistics and univariate analysis based on age and gender. RESULTS: Of 560 patients included in the survey, 80% were adults, 64% female, and 90% Black. The mean age was 28 ± 9 years for adults and 9 ± 5 years for children. One-third of patients reported no primary care physician, and 55% reported no access to a nurse or clinician for medical advice. Adults were less likely to have access to phone consultation than parents of children (odds ratio [OR] 0.49, 95% confidence interval [CI], 0.32 - 0.74), as were males compared to females (OR 0.52, 95% CI, 0.37-0.74). Most patients (96%) reported cellular internet access. Two-thirds of patients reported using online references. When asked how they would behave if an mHealth tool advised them that their current health problem was low risk, 69% of patients responded that they would seek care in an outpatient clinic instead of the ED (30%), stay home and not seek urgent medical care (28%), or use telehealth (11%). CONCLUSION: In this urban community we found a large capacity and willingness to use mHealth technology in medical triage

Potential of Mobile Health Technology to Reduce Health Disparities in Underserved Communities

Introduction: Mobile health (mHealth) has the potential to change how patients make healthcare decisions. We sought to determine the readiness to use mHealth technology in underserved communities.Methods: We conducted a cross-sectional survey of patients presenting with low-acuity complaints to an urban emergency department (ED) with an underserved population. Patients over the age of two who presented with low-acuity complaints were included. We conducted  structured interview with each patient or parent (for minors) about willingness to use mHealth tools for guidance. Analysis included descriptive statistics and univariate analysis based on age and gender.Results: Of 560 patients included in the survey, 80% were adults, 64% female, and 90% Black. The mean age was 28 ± 9 years for adults and 9 ± 5 years for children. One-third of patients reported no primary care physician, and 55% reported no access to a nurse or clinician for medical advice. Adults were less likely to have access to phone consultation than parents of children (odds ratio [OR] 0.49, 95% confidence interval [CI], 0.32 – 0.74), as were males compared to females (OR 0.52, 95% CI, 0.37– 0.74). Most patients (96%) reported cellular internet access. Two-thirds of patients reported using online references. When asked how they would behave if an mHealth tool advised them that their current health problem was low risk, 69% of patients responded that they would seek care in an outpatient clinic instead of the ED (30%), stay home and not seek urgent medical care (28%), or use telehealth (11%).Conclusion: In this urban community we found a large capacity and willingness to use mHealth technology in medical triage

Potential of Mobile Health Technology to Reduce Health Disparities in Underserved Communities

INTRODUCTION: Mobile health (mHealth) has the potential to change how patients make healthcare decisions. We sought to determine the readiness to use mHealth technology in underserved communities. METHODS: We conducted a cross-sectional survey of patients presenting with low-acuity complaints to an urban emergency department (ED) with an underserved population. Patients over the age of two who presented with low-acuity complaints were included. We conducted structured interview with each patient or parent (for minors) about willingness to use mHealth tools for guidance. Analysis included descriptive statistics and univariate analysis based on age and gender. RESULTS: Of 560 patients included in the survey, 80% were adults, 64% female, and 90% Black. The mean age was 28 ± 9 years for adults and 9 ± 5 years for children. One-third of patients reported no primary care physician, and 55% reported no access to a nurse or clinician for medical advice. Adults were less likely to have access to phone consultation than parents of children (odds ratio [OR] 0.49, 95% confidence interval [CI], 0.32 - 0.74), as were males compared to females (OR 0.52, 95% CI, 0.37-0.74). Most patients (96%) reported cellular internet access. Two-thirds of patients reported using online references. When asked how they would behave if an mHealth tool advised them that their current health problem was low risk, 69% of patients responded that they would seek care in an outpatient clinic instead of the ED (30%), stay home and not seek urgent medical care (28%), or use telehealth (11%). CONCLUSION: In this urban community we found a large capacity and willingness to use mHealth technology in medical triage

Cardiac Stroke Volume Index Is Associated With Early Neurological Improvement in Acute Ischemic Stroke Patients

Early neurological improvement as assessed with the NIH stroke scale (NIHSS) at 24 h has been associated with improved long-term functional outcomes following acute ischemic stroke (AIS). Cardiac dysfunction is often present in AIS, but its association with outcomes is incompletely defined. We performed a pilot study to evaluate the association between non-invasively measured cardiac parameters and 24-h neurological improvement in prospectively enrolled patients with suspected AIS who presented within 12 h of symptom-onset and had an initial systolic blood pressure\u3e140 mm Hg. Patients receiving thrombolytic therapy or mechanical thrombectomy were excluded. Non-invasive pulse contour analysis was used to measure mean arterial blood pressure (MAP), cardiac stroke volume index (cSVI), cardiac output (CO) and cardiac index (CI). Transcranial Doppler recorded mean middle cerebral artery flow velocity (MFV). We defined a decrease of 4 NIHSS points or NIHSS ≤ 1 at 24-h as neurological improvement. Of 75 suspected, 38 had confirmed AIS and did not receive reperfusion therapy. Of these, 7/38 (18.4%) had neurological improvement over 24 h. MAP was greater in those without improvement (108, IQR 96-123 mm Hg) vs. those with (89, IQR 73-104 mm Hg). cSVI, CO, and MFV were similar between those without and with improvement: 37.4 (IQR 30.9-47.7) vs. 44.7 (IQR 42.3-55.3) ml/m(2); 5.2 (IQR 4.2-6.6) vs. 5.3 (IQR 4.7-6.7) mL/min; and 39.9 (IQR 32.1-45.7) vs. 34.4 (IQR 27.1-49.2) cm/s, respectively. Multivariate analysis found MAP and cSVI as predictors for improvement (OR 0.93, 95%CI 0.85-0.98 and 1.14, 95%CI 1.03-1.31). In this pilot study, cSVI and MAP were associated with 24-h neurological improvement in AIS