The first two blastomeres contribute unequally to the human embryo.

Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to the 2-cell stage embryo. However, whether and how such clonal asymmetries arise in the embryo is unclear. Here, we performed prospective lineage tracing of human embryos using live imaging, non-invasive cell labeling, and computational predictions to determine the contribution of each 2-cell stage blastomere to the epiblast (body), hypoblast (yolk sac), and trophectoderm (placenta). We show that the majority of epiblast cells originate from only one blastomere of the 2-cell stage embryo. We observe that only one to three cells become internalized at the 8-to-16-cell stage transition. Moreover, these internalized cells are more frequently derived from the first cell to divide at the 2-cell stage. We propose that cell division dynamics and a cell internalization bottleneck in the early embryo establish asymmetry in the clonal composition of the future human body.

Patent Ductus Arteriosus Response to Treatment by Course and Associations with Perinatal and Clinical Factors.

OBJECTIVE: The objective of this study is to examine patent ductus arteriosus (PDA) response by treatment course and investigate associations with postmenstrual age (PMA), chronological age (CA), gestational age (GA), antenatal steroid exposure (ANS), birthweight (BW), weight at treatment initiation (WT), and PDA/left pulmonary artery (LPA) ratio. STUDY DESIGN: This is a single-center retrospective cohort study of preterm infants less than 37 weeks' GA born January 1, 2016 to December 31, 2018 who received acetaminophen and/or indomethacin for PDA treatment. Cox proportional hazards regression models were used to determine whether factors of interest were associated with PDA response to medical treatment. RESULTS: In total, 289 treatment courses were administered to 132 infants. Thirty-one (23%) infants experienced treatment-associated PDA closure. Ninety-four (71%) infants had evidence of PDA constriction following any treatment course. Ultimately, 84 (64%) infants experienced definitive PDA closure. For each 7-day increase in CA at the time of treatment initiation, the PDA was 59% less likely to close (p = 0.04) and 42% less likely to respond (i.e., constrict or close) to treatment (p < 0.01). PDA/LPA ratio was associated with treatment-associated PDA closure (p = 0.01). For every 0.1 increase in the PDA/LPA ratio, the PDA was 19% less likely to close in response to treatment. CONCLUSION: In this cohort, PDA closure is independent of PMA, GA, ANS, BW, and WT; however, CA at treatment initiation predicted both treatment-associated PDA closure and PDA response (i.e., constriction or closure), and PDA/LPA ratio was associated with treatment-associated closure. Most infants experienced PDA constriction rather than closure, despite receiving up to four treatment courses. KEY POINTS: · Detailed PDA responses for up to four treatment courses provide a novel perspective.. · Chronological age at the start of treatment predicted treatment-associated PDA closure and response.. · For each 7-day increase in chronological age, the PDA was 59% less likely to close..

Surgical Techniques and Adjuvants for the Management of Pterygium.

OBJECTIVE: To provide an updated review of surgical techniques and adjuvants for the management of pterygium. METHODS: A literature search was conducted in PubMed for studies published since January 2011. "Pterygium surgery" and the MeSH term "Pterygium/surgery" was used. The results were filtered for randomized controlled trials in English, yielding 60 citations. RESULTS: One study compared topical anesthetic agents. One study compared methods of corneal polishing of the corneoscleral bed after pterygium excision. Numerous studies evaluated the use of conjunctival autograft versus amniotic membrane, superior versus inferior conjunctival autograft, and conjunctival versus limbal-conjunctival autograft. Many studies evaluated graft fixation methods. Several studies evaluated the adjuvant use of mitomycin C, 5-fluorouracil, and bevacizumab. A few studies evaluated the adjuvant use of steroids. Eleven studies evaluated various methods of postoperative management. CONCLUSIONS: Current evidence supports pterygium excision with conjunctival autograft fixation using fibrin glue, followed by patching until the first postoperative visit. Surgical adjuvants and postoperative use of artificial tears and topical cyclosporine 0.05% may further reduce recurrence. Postoperative use of topical steroids is highly variable because there is no consensus regarding the optimal dose, frequency, and duration of treatment.

Antimicrobial Resistance in Africa-How to Relieve the Burden on Family Farmers.

Although currently available data indicate that Africa has the lowest usage of antimicrobials in animals in the world (adjusted by animal biomass), data show a high prevalence of antimicrobial resistance in foodborne pathogens isolated from animals and animal products. Apart from the lack of solid data on antimicrobial use in many countries in Africa, different hypotheses could explain this situation. Qualitative interviews of farmers show a lack of knowledge and uninformed use of antimicrobials. Considering the development of animal farming to meet an increasing demand for proteins, this deficiency represents a serious public health issue. We advocate for policies that consider the specific challenges faced by family farmers in Africa, to simultaneously improve access to veterinary drugs while strengthening the regulation of their use. We propose a global approach targeting the agri-food system, offering innovative social and technical interventions on antimicrobial usage, adapted to family farmers.

Infection and treatment method (ITM) vaccine against East Coast fever: reducing the number of doses per straw for use in smallholder dairy herds by thawing, diluting and refreezing already packaged vaccine.

BACKGROUND: The Infection and Treatment Method (ITM) of vaccination is the only immunization procedure currently available to protect cattle against East Coast fever (ECF), a tick-transmitted disease responsible for losses of several hundreds of millions of dollars per year in sub-Saharan Africa. The vaccine comprises a homogenized preparation of infected ticks packaged in straws and stored in liquid nitrogen. The current manufacturing protocol results in straws containing 30-40 doses (ILRI 0804), which is impractical for immunizing small herds as found in dairy and smallholder farming systems. The ILRI 0804 SD stabilate was prepared as a 1:5 dilution of the parent stabilate, with the aim of producing vaccine stabilate straws containing between four to eight doses and thus suitable for smallholder farming systems. Infectivity of the diluted stabilate was assessed and the protective efficacy of the diluted stabilate was determined by performing experimental and field immunizations. RESULTS: Two groups of six cattle were inoculated with 1 ml of the diluted stabilate at 1:20 (equivalent to the recommended field dose for ILRI 0804, assuming no loss of sporozoite viability during thawing and refreezing) and 1:14 (assuming 30-35% loss of sporozoite viability). Schizonts were detected in all 12 animals, showing viability of sporozoites. Ten animals from the infectivity study and two control animals not previously exposed to T. parva were challenged with the parental ILRI 0804 stabilate. The results show that the two control animals displayed severe ECF reactions and were treated 14 days after challenge. Of the previously infected animals, only one underwent a severe reaction following challenge, a result in accord with the challenge experiments performed previously with the parent stabilate [Ticks Tick-Borne Dis 7:306-314, 2016]. The animal that displayed a severe reaction had no detectable schizonts and did not seroconvert following the initial inoculation with ILRI 0804 SD. In addition, 62 animals immunized under field conditions showed a mean seroconversion rate of 82%. CONCLUSION: The results presented in this article demonstrate that it is possible to prepare straws suitable for use in smallholder herds by thawing, diluting and refreezing already packaged vaccine.

Radicular Pain Syndromes: Cervical, Lumbar, and Spinal Stenosis.

Back pain is a top primary and urgent care complaint; radicular pain can be caused by herniation of the nucleus pulposus (intervertebral disc), spinal stenosis, or degenerative changes to the vertebrae. The focus of this clinical review will be the clinical approach and treatment of lumbar radicular pain, cervical radicular pain, and spinal stenosis. Usually localized through neurological history, exam, and imaging, specific signs and symptoms for lumbar radicular, spinal stenosis, and cervical radicular pain can help determine etiology. Once radicular back pain has been diagnosed, a multitude of treatment options are available from rest and physical therapy to medications, epidurals, and surgery. The most common and accepted are reviewed. With accurate diagnosis, safe and effective pain management can be employed to shorten radicular episodes and manage recurrent or chronic radicular syndromes. Using a step-wise approach from diagnosis to conservative therapy to potential surgery, radicular pain syndromes can improve or resolve, and patients may achieve a better functional status and quality of life.

Proteomics goes forensic: Detection and mapping of blood signatures in fingermarks.

A bottom up in situ proteomic method has been developed enabling the mapping of multiple blood signatures on the intact ridges of blood fingermarks by Matrix Assisted Laser Desorption Mass Spectrometry Imaging (MALDI-MSI). This method, at a proof of concept stage, builds upon recently published work demonstrating the opportunity to profile and identify multiple blood signatures in bloodstains via a bottom up proteomic approach. The present protocol addresses the limitation of the previously developed profiling method with respect to destructivity; destructivity should be avoided for evidence such as blood fingermarks, where the ridge detail must be preserved in order to provide the associative link between the biometric information and the events of bloodshed. Using a blood mark reference model, trypsin concentration and spraying conditions have been optimised within the technical constraints of the depositor eventually employed; the application of MALDI-MSI and Ion Mobility MS have enabled the detection, confirmation and visualisation of blood signatures directly onto the ridge pattern. These results are to be considered a first insight into a method eventually informing investigations (and judicial debates) of violent crimes in which the reliable and non-destructive detection and mapping of blood in fingermarks is paramount to reconstruct the events of bloodshed.

STAT3 signaling contributes to the high effector activities of interleukin-15-derived dendritic cells.

Dendritic cells (DCs) are important innate and adaptive immune effectors, and have a key role in antigen presentation and T-cell activation. Different lineages of DCs can be developed from hematopoietic progenitors following cytokine signaling, and the various lineages of DCs display distinct morphology, phenotype and functions. There has been limited information on differential cytokine-mediated molecular signaling in DCs. Analyses of surface molecules by flow cytometry and quantitative RNA profiling revealed differences between DCs derived from interleukin-4 (IL-4) versus IL-15 signaling, yet both lineages of DCs exhibited similar levels of surface molecules key to immune activation. Functional assays confirmed that IL-15-derived DCs elicited greater antigen-specific, primary and secondary CD8 and CD4 T-cell responses than did IL-4-derived DCs. Importantly, IL-15 DCs secreted substantial amounts of proinflammatory cytokines, including IL-6, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNFα), which helped polarize a strong T-cell response. Assessment of signaling pathways revealed that IL-15 DCs exhibited a lower levels of activated signal transducer and activator of transcription 5 (STAT5), STAT6 and extracellular signal-regulated kinase 1/2 than IL-4 DCs, but after lipopolysaccharide (LPS)/TNFα treatment, the STAT3 and p38 mitogen-activated protein kinase (MAPK) activities were significantly enhanced in the IL-15 DCs. Surprisingly, contrary to the canonical IL-15-mediated STAT5 signaling pathway in lymphoid cells, IL-15 did not mediate a strong STAT5 or STAT3 activation in DCs. Further analysis using specific inhibitors to STAT3 and p38 MAPK pathways revealed that the STAT3 signaling, but not p38 MAPK signaling, contributed to IFN-γ production in DCs. Therefore, while IL-15 does not promote the STAT signaling in DCs, the increased STAT3 activity after LPS/TNFα treatment of the IL-15 DCs has a key role in their high IFN-γ effector activities.

Interleukin-6 inhibits apoptosis of exocrine gland tissues under inflammatory conditions.

Interleukin (IL)-6 is a multi-functional cytokine that can either promote or suppress tissue inflammation depending on the specific disease context. IL-6 is elevated in the exocrine glands and serum of patients with Sjögren's syndrome (SS), but the specific role of IL-6 in the pathogenesis of this disease has not been defined. In this study, we showed that IL-6 expression levels were increased with age in C56BL/6.NOD-Aec1Aec2 mice, a primary SS model, and higher than the control C57BL/6 mice. To assess the role of IL-6 during the immunological phase of SS development, a neutralizing anti-IL-6 antibody was administered into 16 week-old female C56BL/6.NOD-Aec1Aec2 mice, 3 times weekly for a consecutive 8 weeks. Neutralization of endogenous IL-6 throughout the immunological phase of SS development led to increased apoptosis, caspase-3 activation, leukocytic infiltration, and IFN-γ- and TNF-α production in the salivary gland. To further determine the effect of IL-6 on the apoptosis of exocrine gland cells, recombinant human IL-6 or the neutralizing anti-IL-6 antibody was injected into female C57BL/6 mice that received concurrent injection of anti-CD3 antibody to induce the apoptosis of exocrine gland tissues. Neutralization of IL-6 enhanced, whereas administration of IL-6 inhibited apoptosis and caspase-3 activation in salivary and lacrimal glands in this model. The apoptosis-suppressing effect of IL-6 was associated with up-regulation of Bcl-xL and Mcl-1 in both glands. Moreover, IL-6 treatment induced activation of STAT3 and up-regulated Bcl-xL and Mcl-1 gene expression in a human salivary gland epithelial cell line. In conclusion, IL-6 inhibits the apoptosis of exocrine gland tissues and exerts a tissue-protective effect under inflammatory conditions including SS. These findings suggest the possibility of using this property of IL-6 to preserve exocrine gland tissue integrity and function under autoimmune and inflammatory conditions.

A retrospective review of the prehospital use of activated charcoal.

OBJECTIVE: We studied the complications and timing implications of prehospital activated charcoal (PAC). Appropriateness of PAC administration was also evaluated. METHODS: We retrospectively reviewed prehospital records over 32 months for overdose cases, where PAC was administered. Cases were assessed for amount and type of ingestant, clinical findings, timing of PAC, timing of transport and arrival into the emergency department (ED), and complications. Encounter duration in cases of PAC was compared with that, for all cases during the study period, where an overdose patient who did not receive activated charcoal was transported. RESULTS: Two thousand eight hundred forty-five total cases were identified. In 441 cases, PAC was given; and complications could be assessed. Two hundred eighty-one of these had complete information regarding timing of ingestion, activated charcoal administration, and transport. The average time between overdose and PAC was 49.8 minutes (range, 7-199 minutes; median, 41.0 minutes; SD, 30.4 minutes). Complications included emesis (7%), declining mental status (4%), declining blood pressure (0.4%), and declining oxygen saturation (0.4%). Four hundred seventeen cases of PAC had documentation of timing of emergency medical service (EMS) arrival on scene and arrival at the ED. Average EMS encounter time was 29 minutes (range, 10-53 minutes; median, 27.9 minutes). Two thousand forty-four poisoning patients were transported who did not receive PAC. The average EMS encounter time for this group was 28.1 minutes (range, 4-82 minutes; median, 27.3 minutes), not significantly different (P =.114). CONCLUSIONS: Prehospital activated charcoal did not appear to markedly delay transport or arrival of overdose patients into the ED and was generally safe.

Blastomere size in the human 2-cell embryo predicts the division order that leads to imbalanced lineage contribution to the future body.

Retrospective tracing of somatic mutations predicted that most cells in the human body could be traced back to a single cell of the 2-cell stage embryo. Accordingly, a recent prospective study of the developmental trajectory of blastomeres in human embryos confirmed that progeny of the first 2-cell stage blastomere to divide generates more epiblast cells (future body). How the 2-cell blastomeres differ is unknown. Here, we show that 2-cell stage blastomeres in human embryos are asymmetric; they differ in size and the bigger blastomere divides first to 4-cell stage. We propose that this asymmetry might originate differences in cell fate.

Outcome differences between males and females undergoing deep brain stimulation for treatment-resistant depression: systematic review and individual patient data meta-analysis.

BACKGROUND: Treatment-resistant depression (TRD) occurs more commonly in women. Deep brain stimulation (DBS) is an emerging treatment for TRD, and its efficacy continues to be explored. However, differences in treatment outcomes between males and females have yet to be explored in formal analysis. METHODS: A PRISMA-compliant systematic review of DBS for TRD studies was conducted. Patient-level data were independently extracted by two authors. Treatment response was defined as a 50 % or greater reduction in depression score. Percent change in depression scores by gender were evaluated using random-effects analyses. RESULTS: Of 737 records, 19 studies (129 patients) met inclusion criteria. The mean reduction in depression score for females was 57.7 % (95 % CI, 64.33 %-51.13 %), whereas for males it was 35.2 % (95 % CI, 45.12 %-25.23 %) (p < 0.0001). Females were more likely to respond to DBS for TRD when compared to males (OR = 2.44, 95 % CI 1.06, 1.95). These differences varied in significance when stratified by DBS anatomical target, age, and timeframe for responder classification. LIMITATIONS: Studies included were open-label trials with small sample sizes. CONCLUSIONS: Our findings suggest that females with TRD respond at higher rates to DBS treatment than males. Further research is needed to elucidate the implications of these results, which may include connectomic sexual dimorphism, depression phenotype variations, or unrecognized symptom reporting differences. Methodological standardization of outcome scales, granular demographic data, and individual subject outcomes would allow for more robust comparisons between trials.

XTX301, a Tumor-Activated Interleukin-12 Has the Potential to Widen the Therapeutic Index of IL12 Treatment for Solid Tumors as Evidenced by Preclinical Studies.

IL12 is a proinflammatory cytokine, that has shown promising antitumor activity in humans by promoting the recruitment and activation of immune cells in tumors. However, the systemic administration of IL12 has been accompanied by considerable toxicity, prompting interest in researching alternatives to drive preferential IL12 bioactivity in the tumor. Here, we have generated XTX301, a tumor-activated IL12 linked to the human Fc protein via a protease cleavable linker that is pharmacologically inactivated by an IL12 receptor subunit beta 2 masking domain. In vitro characterization demonstrates multiple matrix metalloproteases, as well as human primary tumors cultured as cell suspensions, can effectively activate XTX301. Intravenous administration of a mouse surrogate mXTX301 demonstrated significant tumor growth inhibition (TGI) in inflamed and non-inflamed mouse models without causing systemic toxicities. The superiority of mXTX301 in mediating TGI compared with non-activatable control molecules and the greater percentage of active mXTX301 in tumors versus other organs further confirms activation by the tumor microenvironment-associated proteases in vivo. Pharmacodynamic characterization shows tumor selective increases in inflammation and upregulation of immune-related genes involved in IFNγ cell signaling, antigen processing, presentation, and adaptive immune response. XTX301 was tolerated following four repeat doses up to 2.0 mg/kg in a nonhuman primate study; XTX301 exposures were substantially higher than those at the minimally efficacious dose in mice. Thus, XTX301 has the potential to achieve potent antitumor activity while widening the therapeutic index of IL12 treatment and is currently being evaluated in a phase I clinical trial.

Synergistic effects of interleukin-7 and pre-T cell receptor signaling in human T cell development.

The role of IL-7 in pre-T cell receptor (TCR) signaling during human T cell development is poorly understood. To study this, we engineered Molt3, a T cell progenitor T-acute lymphoblastic leukemia cell line, using lentiviral IL-7 receptor α (IL-7Rα) to serve as a model system. IL-7 promoted pre-TCR activation in IL-7Rα(hi) Molt3 as illustrated by CD25 up-regulation after anti-CD3 stimulation. Anti-CD3 treatment activated Akt and Erk1/2 signaling pathways as proven using specific inhibitors, and IL-7 further enhanced both signaling pathways. The close association of IL-7Rα with CD3ζ in the pre-TCR complex was illustrated through live imaging confocal fluorescence microscopy. These results demonstrate a direct and cooperative role of IL-7 in pre-TCR signaling.

Assessment of the addition of prehospital continuous positive airway pressure (CPAP) to an urban emergency medical services (EMS) system in persons with severe respiratory distress.

BACKGROUND: The use of continuous positive airway pressure (CPAP) assisted ventilation in the emergency department(ED) has been well described. OBJECTIVES: The purpose of this study was to measure the efficacy of adding pre-hospital CPAP to an urban emergency medical service (EMS) respiratory distress protocol on persons with respiratory distress. METHODS: A historical cohort analysis of consecutive patients between 2005 and 2010. Groups were matched for severity of respiratory distress. Physiologic variables were the primary outcome obtained from first responders and upon triage in the ED. Additional outcomes included endotracheal intubation rate, hospital mortality, overall hospital length of stay(LOS), intensive care unit (ICU) admission, and ICU length of stay (ICU LOS). RESULTS: There were 410 consecutive patients with predetermined criteria for severe respiratory distress, 235 historical controls matched with 175 post-implementation patients. Average age was 67 years, 54% being male. There were significant median differences in heart and respiratory rates favoring the historical cohort (p < 0.05). There were no significant differences in intubation rate, overall hospital LOS, ICU admission rate, ICU LOS, and hospital mortality (p > 0.05).Patients that were continued on noninvasive ventilatory assistance had a significantly improved rate of intubation and ICU LOS (p < 0.05). CONCLUSIONS: The addition of CPAP to our pre-hospital respiratory distress protocol did not improve physiologic variables.There were no differences in overall and ICU LOS between groups. Persons with apparent continued ventilatory assistance appeared to have improved rates of intubation and ICU LOS [corrected].

Molecular docking and dynamic simulation studies of isoflavones inhibiting Lox-2 activity for reducing beany flavor in soybean seeds.

Low-lipoxygenase soybean cultivars are highly desirable because lower lipoxygenase content in soybean seeds leads to better quality soybean-based products and oils that are free from off-flavor or beany flavor. The expression of the Lox-2 gene is mainly responsible for this flavor. Over the years, natural antioxidants have been tested biochemically to inhibit Lox-2 activity, but in-silico studies are still lacking. To investigate the structural basis of inhibition, site-specific docking, as well as molecular dynamics (MD) simulations, were performed. Molecular docking analysis revealed that daidzein and genistein could be effective Lox2 receptor inhibitors. Furthermore, docked complexes were subjected to 100 ns MD simulation studies to analyze the structural conformations and stability of the complex. The analysis demonstrated that daidzein formed a more stable complex with the Lox-2 receptor and showed a higher H-bond propensity with the Asp775 residue. We discovered that the initial conformation of Lox2-daidzein complex changed to a more stable conformation at the beginning of the MD simulation and remained stable until the end with minor fluctuations. Furthermore, our analysis suggested that daidzein acts as a potential Lox-2 inhibitor and is a better candidate compared to genistein, which could be used to solve the beany flavor problem in soybean.Communicated by Ramaswamy H. Sarma.

Adolescent Experiences With Social Media and Suicidality.

OBJECTIVE: Examine social media experiences of the suicidal adolescent presenting to the emergency department with an acute mental health crisis. METHODS: We used qualitative interviews to obtain in-depth understanding of both negative and positive impacts of social media use on acute adolescent suicidal behavior. A bilingual transcriptionist transcribed audio recordings. Three investigators independently reviewed transcripts to identify themes and develop initial coding scheme through "open coding." Using grounded theory, data collection proceeded along with cultivation of themes until thematic saturation was achieved. Thematic saturation was determined when no new themes were generated from the data. Data were coded in Dedoose software to facilitate reporting of themes and quotes. Techniques to ensure trustworthiness included iterative data collection, use of a coding framework, and multiple coders. RESULTS: Seventeen interviews were conducted from May to October 2020. Median participant age was 15 years. Twenty-four percent were of Hispanic ethnicity and 82% identified as cisgender. Major themes include distraction from negative emotions; facilitated communication resulting in improved social connectedness; metric of connectedness; comparison of self to others; and desensitization and normalization to suicidal acts. Minor theme of increased time on social media is also discussed. These themes echoed components of current suicide theory. CONCLUSIONS: Acutely suicidal adolescents report social media experiences that reflect themes of social alienation and learned capacity for suicidal acts. Themes echo components of current suicide theory. Our participants also reported positive uses of social media. These protective experiences should be leveraged to inform strategies to interrupt behaviors leading to acute suicidality.

Regulation of in vitro human T cell development through interleukin-7 deprivation and anti-CD3 stimulation.

BACKGROUND: The role of IL-7 and pre-TCR signaling during T cell development has been well characterized in murine but not in human system. We and others have reported that human BM hematopoietic progenitor cells (HPCs) display poor proliferation, inefficient double negative (DN) to double positive (DP) transition and no functional maturation in the in vitro OP9-Delta-like 1 (DL1) culture system. RESULTS: In this study, we investigated the importance of optimal IL-7 and pre-TCR signaling during adult human T cell development. Using a modified OP9-DL1 culture ectopically expressing IL-7 and Fms-like tyrosine kinase 3 ligand (Flt3L), we demonstrated enhanced T cell precursor expansion. IL-7 removal at various time points during T cell development promoted a slight increase of DP cells; however, these cells did not differentiate further and underwent cell death. As pre-TCR signaling rescues DN cells from programmed cell death, we treated the culture with anti-CD3 antibody. Upon pre-TCR stimulation, the IL-7 deprived T precursors differentiated into CD3+TCRαß+DP cells and further matured into functional CD4 T cells, albeit displayed a skewed TCR Vß repertoire. CONCLUSIONS: Our study establishes for the first time a critical control for differentiation and maturation of adult human T cells from HPCs by concomitant regulation of IL-7 and pre-TCR signaling.

Effects of an emergency medical services-based resource access program on frequent users of health services.

BACKGROUND: A small group of adults disproportionately and ineffectively use acute services including emergency medical services (EMS) and emergency departments (EDs). The resulting episodic, uncoordinated care is of lower quality and higher cost and simultaneously consumes valuable public safety and acute care resources. OBJECTIVE: To address this issue, we measured the impact of a pilot, EMS-based case management and referral intervention termed the San Diego Resource Access Program (RAP) to reduce EMS, ED, and inpatient (IP) visits. METHODS: This was a historical cohort study of RAP records and billing data of EMS and one urban hospital for 51 individuals sequentially enrolled in the program. The study sample consisted of adults with ≥ 10 EMS transports within 12 months and others reported by prehospital personnel with significant recent increases in transports. Data were collected over a 31-month time period from December 2006 to June 2009. Data were collected for equal pre- and postenrollment time periods based on date of initial RAP contact, and comparisons were made using the Wilcoxon signed-rank test. Overall use for subjects is reported. RESULTS: The majority of subjects were male (64.7%), homeless (58.8%), and 40 to 59 years of age (72.5%). Between the pre and post periods, EMS encounters declined 37.6% from 736 to 459 (p = 0.001), resulting in a 32.1% decrease in EMS charges from $689,743 to $468,394 (p = 0.004). The EMS task time and mileage decreased by 39.8% and 47.5%, respectively, accounting for 262 (p = 0.008) hours and 1,940 (p = 0.006) miles. The number of ED encounters at the one participating hospital declined 28.1% from 199 to 143, which correlated with a 12.7% decrease in charges from $413,410 to $360,779. The number of IP admissions declined by 9.1% from 33 to 30, corresponding to a 5.9% decrease in IP charges from $687,306 to $646,881. Hospital length of stay declined 27.9%, from 122 to 88 days. Across all services, total charges declined by $314,406. CONCLUSIONS: This pilot study demonstrated that an EMS-based case management and referral program was an effective means of decreasing EMS transports by frequent users, but had only a limited impact on use of hospital services.

Gender differences in scene time, transport time, and total scene to hospital arrival time determined by the use of a prehospital electrocardiogram in patients with complaint of chest pain.

BACKGROUND: Recent studies have described a gender bias against women in the setting of acute coronary syndrome (ACS). OBJECTIVES: We sought to measure the impact that a prehospital electrocardiogram (PH ECG) has on prehospital total scene time to hospital arrival time, comparing men and women with the complaint of chest pain (cCP). METHODS: This study retrospectively analyzed San Diego Emergency Medical Services (EMS) runsheets of patients with cCP before and after implementation of the PH ECG protocol. The average scene time (ST), transport time (TT), and total scene-to-arrival-at-hospital time (STH) were compared. After stratification by gender, times were compared in patients with ST-elevation myocardial infarction (STEMI) to those without STEMI. RESULTS: Of 21,742 EMS activations for patients with cCP, there were no significant differences overall. When stratified by gender, there was a significant reduction of ST (00:19:16 min vs. 00:20:48 min, p<0.001, 95% CI 00:01:17-00:01:48) and STH (00:33:22 min vs. 00:35:44 min, p<0.001, 95% CI 00:01:21-00:02:24) favoring men in cases without STEMI. In cases of STEMI, men had a significant reduction in ST (00:17:27 min vs. 00:20:29 min, p<0.001, 95% CI 00:01:24-00:04:40) and STH (00:30:30 min vs. 00:34:25 min, p<0.01, 95% CI 00:01:23-00:06:26) times compared to women. CONCLUSION: Prehospital ECG implementation led to no significant differences in pre- and post-implementation times. In cases of STEMI, men had significantly reduced scene time and scene-to-hospital time when compared to women. The precise reason for these disparities remains unknown.