Propensity weighted analysis of chemical venous thromboembolism prophylaxis agents in isolated severe traumatic brain injury: An EAST sponsored multicenter study.

BACKGROUND: In patients with severe traumatic brain injury (TBI), clinicians must balance preventing venous thromboembolism (VTE) with the risk of intracranial hemorrhagic expansion (ICHE). We hypothesized that low molecular weight heparin (LMWH) would not increase risk of ICHE or VTE as compared to unfractionated heparin (UH) in patients with severe TBI. METHODS: Patients ≥ 18 years of age with isolated severe TBI (AIS ≥ 3), admitted to 24 level I and II trauma centers between January 1, 2014 to December 31, 2020 and who received subcutaneous UH and LMWH injections for chemical venous thromboembolism prophylaxis (VTEP) were included. Primary outcomes were VTE and ICHE after VTEP initiation. Secondary outcomes were mortality and neurosurgical interventions. Entropy balancing (EBAL) weighted competing risk or logistic regression models were estimated for all outcomes with chemical VTEP agent as the predictor of interest. RESULTS: 984 patients received chemical VTEP, 482 UH and 502 LMWH. Patients on LMWH more often had pre-existing conditions such as liver disease (UH vs LMWH 1.7 % vs. 4.4 %, p = 0.01), and coagulopathy (UH vs LMWH 0.4 % vs. 4.2 %, p < 0.001). There were no differences in VTE or ICHE after VTEP initiation. There were no differences in neurosurgical interventions performed. There were a total of 29 VTE events (3 %) in the cohort who received VTEP. A Cox proportional hazards model with a random effect for facility demonstrated no statistically significant differences in time to VTE across the two agents (p = 0.44). The LMWH group had a 43 % lower risk of overall ICHE compared to the UH group (HR = 0.57: 95 % CI = 0.32-1.03, p = 0.062), however was not statistically significant. CONCLUSION: In this multi-center analysis, patients who received LMWH had a decreased risk of ICHE, with no differences in VTE, ICHE after VTEP initiation and neurosurgical interventions compared to those who received UH. There were no safety concerns when using LMWH compared to UH. LEVEL OF EVIDENCE: Level III, Therapeutic Care Management.

Pneumoperitoneum Secondary to Necrotic Intra-abdominal Lymph Node.

Pneumoperitoneum is often treated as a surgical emergency as the most common etiology is perforated hollow viscus. Here, we present the case of a man in his 70s who presented to the emergency department with fever and abdominal pain. On physical exam, he was diffusely tender in the bilateral lower quadrants with guarding. Imaging demonstrated moderate volume pneumoperitoneum. On review of his imaging, the pneumoperitoneum was centered around a 7 cm necrotic lymph node. Repeat CT scan with positive oral (PO) and rectal contrast demonstrated no extraluminal contrast extravasation, but air bubbles were seen extending from the necrotic lymph node into the lower abdominal cavity. He underwent CT-guided drain placement and was started on antibiotics, and improved without surgical intervention. In stable patients presenting with pneumoperitoneum and known intra-abdominal lymphadenopathy, perforated viscus should be ruled out prior to surgical intervention, and necrotic intra-abdominal lymph node should be considered as a differential diagnosis.

Clinical outcomes for patients on antiplatelet and anticoagulants in thoracoabdominal trauma.

Introduction: Trauma outcomes can be greatly affected by antiplatelet and anticoagulant (AP/AC) use. The goal of this study was to compare outcomes in trauma patients on AP/AC undergoing emergent surgery for thoracoabdominal trauma at 35 level 1 and 2 trauma centers from 2014 to 2021. Methods: This was a retrospective cohort study of 2460 adult patients with a chest, abdomen, or pelvis abbreviated injury score (AIS) of 2 or more who underwent surgery within 24 h of admission. These patients were segregated into four main cohorts based on antiplatelet/anticoagulation use: those not on AP/AC, those taking direct-acting oral anticoagulants (DOACs), those taking clopidogrel, and those taking warfarin. Patients were excluded if they had surgery >24 h after presentation, were dead on arrival, or had any other body system AIS score of 3 or higher. Results: The mean injury severity score (ISS) in all four groups ranged from 16.3 to 18.6 (p = 0.834) with a mean time to operating room from 208 to 478 min (p < 0.001). Laparotomy was performed in 60 to 71 % (p > 0.01) of patients, regardless of AP/AC status, and thoracic procedures were performed in 3.1 to 9.3 % (p = 0.42) of patients. In-hospital mortality and hospice rates were highest in the clopidogrel group at 21.9 %, followed by warfarin at 13 %, DOACs at 15 %, and no AP/AC at 7.63 % (p = 0.008). Serious complications occurred in 61 % of patients on warfarin, 50 % of those on DOACs, and 44 % of those on clopidogrel. All of these groups demonstrated significantly higher complication rates than patients in the no AP/AC control group at 25 % (p < 0.001). Total transfusion of packed red blood cells and fresh frozen plasma did not differ significantly between the groups; however, 24-h platelet transfusion did. Patients on clopidogrel received 14 packs of platelets, while those on warfarin and DOACs received 8 and 13 packs respectively (p = 0.011). Patients on warfarin had the longest hospital length of stay (LOS) at 13 days and ICU LOS at 9 days, compared to those on DOACs (8 and 4), those on clopidogrel (7 and 3), and those not taking AC/AP (7 and 4) (hospital LOS p = 0.03, ICU LOS p = 0.019). Those on AC/AP were also noted to be significantly older than those on neither, with those taking these medications averaging out to be approximately 69 years old and those not on these medications averaging 37 years old (p < 0.001). Conclusion: There was significantly higher mortality in patients on clopidogrel and increased length of stay and risk of serious complications in patients taking DOACs and warfarin. In patients on AP/AC there was also a significantly longer time to surgery than in those not taking either. Given these associations trauma surgeons should consider intervening sooner on patients taking AP/AC on admission, as the delay to intervention may contribute to the risks for trauma patients and result in worse outcomes as well as higher rates of mortality.

Early VTE prophylaxis in severe traumatic brain injury: A propensity score weighted EAST multicenter study.

BACKGROUND: Patients with traumatic brain injury (TBI) are at high risk of venous thromboembolism events (VTE). We hypothesized that early chemical VTE prophylaxis initiation (≤24 hours of a stable head CT) in severe TBI would reduce VTE without increasing risk of intracranial hemorrhage expansion (ICHE). METHODS: A retrospective review of adult patients 18 years or older with isolated severe TBI (Abbreviated Injury Scale score, ≥ 3) who were admitted to 24 Level I and Level II trauma centers from January 1, 2014 to December 31 2020 was conducted. Patients were divided into those who did not receive any VTE prophylaxis (NO VTEP), who received VTE prophylaxis ≤24 hours after stable head CT (VTEP ≤24) and who received VTE prophylaxis >24 hours after stable head CT (VTEP>24). Primary outcomes were VTE and ICHE. Covariate balancing propensity score weighting was utilized to balance demographic and clinical characteristics across three groups. Weighted univariate logistic regression models were estimated for VTE and ICHE with patient group as predictor of interest. RESULTS: Of 3,936 patients, 1,784 met inclusion criteria. Incidences of VTE was significantly higher in the VTEP>24 group, with higher incidences of DVT in the group. Higher incidences of ICHE were observed in the VTEP≤24 and VTEP>24 groups. After propensity score weighting, there was a higher risk of VTE in patients in VTEP >24 compared with those in VTEP≤24 (odds ratio, 1.51; 95% confidence interval, 0.69-3.30; p = 0.307), however was not significant. Although, the No VTEP group had decreased odds of having ICHE compared with VTEP≤24 (odds ratio, 0.75; 95% confidence interval, 0.55-1.02, p = 0.070), the result was not statistically significant. CONCLUSION: In this large multi-center analysis, there were no significant differences in VTE based on timing of initiation of VTE prophylaxis. Patients who never received VTE prophylaxis had decreased odds of ICHE. Further evaluation of VTE prophylaxis in larger randomized studies will be necessary for definitive conclusions. LEVEL OF EVIDENCE: Therapeutic Care Management; Level III.

Effect of Antiplatelet and Anticoagulant Agents on Outcomes Following Emergent Surgery for Traumatic Brain Injuries.

PURPOSE: Traumatic brain injury (TBI) is the largest cause of death from injury in the United States. This study utilized the Michigan Trauma Quality Improvement Program (MTQIP) database to determine the effect that antiplatelets and anticoagulants (AP/AC) have on outcomes following emergent surgery for TBI patients. BASIC PROCEDURES: Patients were included with age ≥18 years, maximum head/neck abbreviated injury score (AIS) ≥2, and underwent a neurosurgical procedure within 24 hours. Patients were excluded if they had an AIS ≥3 in other body region or no signs of life at initial evaluation. MAIN FINDINGS: Within the 1,932 patients analyzed, 139 (8.74%) were in the warfarin with or without (+/-) aspirin cohort, 101 (6.35%) in the direct oral anticoagulants (DOAC) +/- aspirin cohort, 169 (10.62%) in the clopidogrel +/- aspirin cohort, and 1,182 (74.29%) in the no AP/AC cohort (control group). After controlling for demographic and clinical characteristics, no significant difference in mortality rates was observed in the treatment groups (P > 0.05). However, our subgroup analysis did reveal a significantly higher mortality rate within the warfarin and aspirin subgroup when compared to the control group (odds ratio [OR], 2.368; confidence interval [CI], 1.306-4.294, P = 0.005). With regards to hospital complications, there was a significant increase in this outcome within the DOAC +/- aspirin (OR, 1.825; CI, 1.143-2.915, P = 0.012) and clopidogrel +/- aspirin (OR, 1.82; CI, 1.244-2.663, P=0.002) groups. CONCLUSION: Patients on AP/AC who experience a TBI requiring an emergent operation do not have an increased risk of mortality compared to patients not on AP/AC.

Academic Medical Centers Experienced Higher Rates of Post-Operative Health-Care-Associated Infections during the COVID-19 Pandemic: A Post Hoc Analysis of an Eastern Association for the Surgery of Trauma Multicenter Trial.

Background: We sought to examine health-care-associated infections (HAIs) among patients undergoing an appendectomy at academic medical centers (AMCs) and non-AMCs during the coronavirus disease 2019 (COVID-19) peri-pandemic. We hypothesized that AMCs would have higher rates of post-operative HAIs during the first wave of the pandemic. Patients and Methods: We performed a post hoc analysis of a prospective, observational, multi-center study of patients aged >18 years who underwent an appendectomy for acute appendicitis before (pre-CoV), during (CoV), and after pandemic restrictions were lifted (post-CoV). Patients were grouped according to hospital type (AMC vs. non-AMC). Our primary outcome was the incidence of post-operative HAIs. Results: There were 1,003 patients; 69.5% (n = 697) were treated at AMCs and 30.5% (n = 306) at non-AMCs. Patients at AMCs had greater rates of concomitant COVID-19 infections (5.5% vs. 0.7%; p < 0.0001) and worse operative appendicitis severity (p = 0.01). Greater rates of HAIs were seen at AMCs compared with non-AMCs (4.9% vs. 2%; p = 0.03). Surgical site infections were the most common HAI and occurred more often at AMCs (4.3% vs. 1.6%; p = 0.04). Only during CoV were there more HAIs at AMCs (5.1% vs. 0.3%; p = 0.02). Undergoing surgery at an AMC during CoV was a risk factor for HAIs (adjusted odds ratio [aOR], 8.55; 95% confidence interval [CI], 1.03-71.03; p = 0.04). Conclusions: During the COVID-19 pandemic, appendectomies performed at AMCs were an independent risk factor for post-operative HAIs. Our findings stress the importance of adherence to standard infection prevention efforts during future healthcare crises.

Case report: A rare presentation of high risk epithelioid hemangioendothelioma on leg treated with surgical excision.

INTRODUCTION: A rare vascular tumor, epithelioid hemangioendothelioma (EHE), can be difficult to diagnose for physicians. Although uncommon, EHE has the potential to become malignant and cause patient death. The five year mortality rate with the diagnosis of the high risk type has been reported to be as high as 41. Thus this finding requires aggressive treatment to prevent amputation or death (Deyrup et al., 2008). PRESENTATION OF CASE: In this case, a 60-year-old male patient was evaluated for a suspicious subepidermal nodule on the upper lateral aspect of the lower right leg just distal to the knee. It was excised to the level of muscle with appropriate margins of 1 cm circumferentially. The specimen underwent appropriate pathological testing and did reveal a high-risk-type epithelioid hemangioendothelioma with remaining tumor present at the deep margin. The patient had additional surgery by an orthopedic surgeon in order to obtain clear margins of the lesion and retain maximum function of leg. Despite surgical excision with ultimately clean margins, the lesion did metastasize to the right groin area seven months after surgery and the secondary metastatic site also required surgical excision. DISCUSSION: There is very little information available to the identification and treatment of a finding of EHE. The only definitive treatments to prevent malignancy is excision or amputation, possibly in conjunction with radiation therapy. The role of oncology intervention should be considered because the finding may be either a cause or an effect of malignancy. CONCLUSION: The goal of this paper is to raise awareness of the importance of pathology for soft issue lesions even if there is initially a low clinical index of suspicion. Unique characteristics in the pathology is the cornerstone to the identification and treatment. Although surgical excision can appear to be a curative treatment, EHE may inevitably metastasize, so aggressive and definitive treatment is best.

Biliary hyperkinesia, a new diagnosis or misunderstood pathophysiology of dyskinesia: A case report.

INTRODUCTION: Biliary colic, characterized by intermittent right upper quadrant abdominal pain is a common complaint in the United States population. Patients whose pain is undiagnosed by ultrasound generally undergo hepatobiliary iminodiacetic acid scan with cholecystokinin stimulation (HIDA-CCK) to assess function of the gallbladder and biliary tree. Traditionally, two outcomes are possible based on a measured ejection fraction of the gallbladder: either dyskinesia or normal function is diagnosed. Biliary dyskinesia, or hypokinesia of the gallbladder, is accepted as an ejection fraction less than 35%, while an accepted normal functioning gallbladder ejection fraction is greater than 35%. CASE: We report a case of a fifteen-year-old female who had functional gallbladder disease per Rome IV criteria due to intermittent biliary colic, with exception to the ejection fraction measurement which was elevated at 96.5%. She underwent laparoscopic cholecystectomy with complete symptom resolution. DISCUSSION: As demonstrated in the literature reviewed here, these subsets of patients, who present with normal to high ejection fractions, have undergone laparoscopic cholecystectomy with resolution of pain in several case studies. CONCLUSION: Many unknown variables still exist due to lack of prospective studies, most notably the pathophysiology and definitive indications for surgical treatment. As such, we propose that surgical options should not be limited to those who display the traditional findings of biliary dyskinesia, but also patients who demonstrate typical symptoms with normal to elevated ejection fraction, following work up to rule out the extensive differential diagnoses for right upper quadrant abdominal pain.

Dynamic changes in gene expression and signalling during trophoblast development in the horse

Equine chorionic girdle trophoblast cells play important endocrine and immune functions critical in supporting pregnancy. Very little is known about the genes and pathways that regulate chorionic girdle trophoblast development. Our aim was to identify genes and signalling pathways active in vivo in equine chorionic girdle trophoblast within a critical 7-days window. We exploited the late implantation of the equine conceptus to obtain trophoblast tissue. An Agilent equine 44K microarray was performed using RNA extracted from chorionic girdle and chorion (control) from equine pregnancy days 27, 30, 31 and 34 (n = 5), corresponding to the initiation of chorionic girdle trophoblast proliferation, differentiation and migration. Data were analysed using R packages limma and maSigPro, Ingenuity Pathway Analysis and DAVID and verified using qRT-PCR, promoter analysis, western blotting and migration assays. Microarray analysis showed gene expression (absolute log FC >2, FDR-adjusted P < 0.05) was rapidly and specifically induced in the chorionic girdle between days 27 and 34 (compared to day 27, day 30 = 116, day 31 = 317, day 34 = 781 genes). Pathway analysis identified 35 pathways modulated during chorionic girdle development (e.g. FGF, integrin, Rho GTPases, MAPK) including pathways that have limited description in mammalian trophoblast (e.g. IL-9, CD40 and CD28 signalling). Rho A and ERK/MAPK activity was confirmed as was a role for transcription factor ELF5 in regulation of the CGB promoter. The purity and accessibility of chorionic girdle trophoblast proved to be a powerful resource to identify candidate genes and pathways involved in early equine placental development.

After the embo: predicting non-hemorrhagic indications for splenectomy after angioembolization in patients with blunt trauma.

BACKGROUND: Successful non-operative management (NOM) of blunt splenic trauma is enhanced with splenic angioembolization (SAE). Patients may still require splenectomy post-SAE for splenic infarction/necrosis. Prior studies have used white blood cell count (WBC), platelet count (PLT), and PLT:WBC ratio after splenectomy to predict complications, but none have evaluated these findings prior to splenectomy in patients who have undergone SAE. Changes in these values may indicate clinically significant splenic infarction, facilitating management of these patients. METHODS: Patients admitted to an American College of Surgeons verified level 1 trauma center from January 2007 to August 2017 who underwent SAE were identified. Patients with successful NOM after SAE (SAE/NOM) were compared with those requiring splenectomy (SAE/SPLEN). Data included demographics, splenic injury grade, Injury Severity Score (ISS), time to SAE and splenectomy, intensive care unit and hospital length of stay (LOS), and complete blood count. Lab values were analyzed immediately post-SAE (time 1) and day 5 post-SAE (or day of discharge) for SAE/NOM patients and day of SPLEN for SAE/SPLEN patients (time 2). Data were analyzed using Mann-Whitney U, χ2 tests, and receiver operating characteristic (ROC) curves with significance attributed to P<0.05. RESULTS: Of 124 patients undergoing SAE, 16 (13%) later required SPLEN for infarction/necrosis at a median of 5 days post-SAE (IQR: 3-10 days). SAE/SPLEN and SAE/NOM patients did not differ by age, gender, ISS, or grade of splenic injury. SAE/SPLEN patients had longer hospital LOS (23 vs. 10 days, P<0.001). WBC, PLT, and PLT:WBC ratio did not differ between the groups at time 1. At time 2, WBC was higher and PLT:WBC ratio was lower in SAE/SPLEN patients. Using ROC curves at time 2, the area under the curve was 0.90 (P<0.001) for WBC and 0.71 (P<0.007) for PLT:WBC ratio. DISCUSSION: Patients requiring splenectomy for clinically significant infarction/necrosis after SAE develop leukocytosis and decreased PLT:WBC ratio when compared with SAE/NOM patients. Monitoring these parameters allows more prompt diagnosis and operative intervention. LEVEL OF EVIDENCE: Therapeutic/care management, level III.

Glial Cells Missing 1 Regulates Equine Chorionic Gonadotrophin Beta Subunit via Binding to the Proximal Promoter.

Equine chorionic gonadotrophin (eCG) is a placental glycoprotein critical for early equine pregnancy and used therapeutically in a number of species to support reproductive activity. The factors in trophoblast that transcriptionally regulate eCGß-subunit (LHB), the gene which confers the hormones specificity for the receptor, are not known. The aim of this study was to determine if glial cells missing 1 regulates LHB promoter activity. Here, studies of the LHB proximal promoter identified four binding sites for glial cells missing 1 (GCM1) and western blot analysis confirmed GCM1 was expressed in equine chorionic girdle (ChG) and surrounding tissues. Luciferase assays demonstrated endogenous activity of the LHB promoter in BeWo choriocarcinoma cells with greatest activity by a proximal 335 bp promoter fragment. Transactivation studies in COS7 cells using an equine GCM1 expression vector showed GCM1 could transactivate the proximal 335 bp LHB promoter. Chromatin immunoprecipitation using primary ChG trophoblast cells showed GCM1 to preferentially bind to the most proximal GCM1-binding site over site 2. Mutation of site 1 but not site 2 resulted in a loss of endogenous promoter activity in BeWo cells and failure of GCM1 to transactivate the promoter in COS-7 cells. Together, these data show that GCM1 binds to site 1 in the LHB promoter but also requires the upstream segment of the LHB promoter between -119 bp and -335 bp of the translation start codon for activity. GCM1 binding partners, ETV1, ETV7, HOXA13, and PITX1, were found to be differentially expressed in the ChG between days 27 and 34 and are excellent candidates for this role. In conclusion, GCM1 was demonstrated to drive the LHB promoter, through direct binding to a predicted GCM1-binding site, with requirement for another factor(s) to bind the proximal promoter to exert this function. Based on these findings, we hypothesize that ETV7 and HOXA13 act in concert with GCM1 to initiate LHB transcription between days 30 and 31, with ETV1 partnering with GCM1 to maintain transcription.

How does decision complexity affect shared decision making? An analysis of patient-provider antiretroviral initiation dialogue.

OBJECTIVES: This study analyzed patient-provider dialogue regarding anti-retroviral therapy (ART) initiation, assessing the degree to which shared decision making (SDM) occurred. METHODS: We analyzed 24 audio-recorded dialogues between 14 HIV providers and their patients regarding ART initiation. We coded transcribed dialogues for seven SDM elements. We stratified dialogues into three levels of decision complexity (basic, intermediate, complex) based on patient CD4 counts and evaluated SDM criteria fulfillment at each level of decision complexity. RESULTS: There were five basic, twelve intermediate, and seven complex decisions in our sample. While only two met the defined criteria for SDM, the mean number of SDM elements present increased with each level of decision complexity. Discussion of the clinical issue requiring the decision occurred most frequently (88%), while discussion of pros/cons (13%), patient's understanding (21%), and decision alternatives (29%) occurred least frequently. CONCLUSION/PRACTICE IMPLICATIONS: While few dialogues met the defined SDM criteria, providers are having conversations that respond to decision complexity. Clinicians should be aware that discussion of pros/cons, alternatives, and uncertainties are frequently skipped, even when these elements are clearly relevant, as in complex decisions. In addition, rhetorical questions to assess patient preferences and understanding are insufficient to fully engage patients in SDM.

Linguistic and Cultural Adaptation of a Computer-Based Counseling Program (CARE+ Spanish) to Support HIV Treatment Adherence and Risk Reduction for People Living With HIV/AIDS: A Randomized Controlled Trial.

BACKGROUND: Human immunodeficiency virus (HIV) disease in the United States disproportionately affects minorities, including Latinos. Barriers including language are associated with lower antiretroviral therapy (ART) adherence seen among Latinos, yet ART and interventions for clinic visit adherence are rarely developed or delivered in Spanish. OBJECTIVE: The aim was to adapt a computer-based counseling tool, demonstrated to reduce HIV-1 viral load and sexual risk transmission in a population of English-speaking adults, for use during routine clinical visits for an HIV-positive Spanish-speaking population (CARE+ Spanish); the Technology Acceptance Model (TAM) was the theoretical framework guiding program development. METHODS: A longitudinal randomized controlled trial was conducted from June 4, 2010 to March 29, 2012. Participants were recruited from a comprehensive HIV treatment center comprising three clinics in New York City. Eligibility criteria were (1) adults (age ≥18 years), (2) Latino birth or ancestry, (3) speaks Spanish (mono- or multilingual), and (4) on antiretrovirals. Linear and generalized mixed linear effects models were used to analyze primary outcomes, which included ART adherence, sexual transmission risk behaviors, and HIV-1 viral loads. Exit interviews were offered to purposively selected intervention participants to explore cultural acceptability of the tool among participants, and focus groups explored the acceptability and system efficiency issues among clinic providers, using the TAM framework. RESULTS: A total of 494 Spanish-speaking HIV clinic attendees were enrolled and randomly assigned to the intervention (arm A: n=253) or risk assessment-only control (arm B, n=241) group and followed up at 3-month intervals for one year. Gender distribution was 296 (68.4%) male, 110 (25.4%) female, and 10 (2.3%) transgender. By study end, 433 of 494 (87.7%) participants were retained. Although intervention participants had reduced viral loads, increased ART adherence and decreased sexual transmission risk behaviors over time, these findings were not statistically significant. We also conducted 61 qualitative exit interviews with participants and two focus groups with a total of 16 providers. CONCLUSIONS: A computer-based counseling tool grounded in the TAM theoretical model and delivered in Spanish was acceptable and feasible to implement in a high-volume HIV clinic setting. It was able to provide evidence-based, linguistically appropriate ART adherence support without requiring additional staff time, bilingual status, or translation services. We found that language preferences and cultural acceptability of a computer-based counseling tool exist on a continuum in our urban Spanish-speaking population. Theoretical frameworks of technology's usefulness for behavioral modification need further exploration in other languages and cultures. TRIAL REGISTRATION: ClinicalTrials.gov NCT01013935; https://clinicaltrials.gov/ct2/show/NCT01013935 (Archived by WebCite at http://www.webcitation.org/6ikaD3MT7).

Convergent evolution of pregnancy-specific glycoproteins in human and horse.

Pregnancy-specific glycoproteins (PSGs) are members of the carcinoembryonic antigen cell adhesion molecule (CEACAM) family that are secreted by trophoblast cells. PSGs may modulate immune, angiogenic and platelet responses during pregnancy. Until now, PSGs are only found in species that have a highly invasive (hemochorial) placentation including humans, mice and rats. Surprisingly, analyzing the CEACAM gene family of the horse, which has a non-invasive epitheliochorial placenta, with the exception of the transient endometrial cups, we identified equine CEACAM family members that seem to be related to PSGs of rodents and primates. We identified seven genes that encode secreted PSG-like CEACAMs Phylogenetic analyses indicate that they evolved independently from an equine CEACAM1-like ancestor rather than from a common PSG-like ancestor with rodents and primates. Significantly, expression of PSG-like genes (CEACAM44, CEACAM48, CEACAM49 and CEACAM55) was found in non-invasive as well as invasive trophoblast cells such as purified chorionic girdle cells and endometrial cup cells. Chorionic girdle cells are highly invasive trophoblast cells that invade the endometrium of the mare where they form endometrial cups and are in close contact with maternal immune cells. Therefore, the microenvironment of invasive equine trophoblast cells has striking similarities to the microenvironment of trophoblast cells in hemochorial placentas, suggesting that equine PSG-like CEACAMs and rodent and primate PSGs have undergone convergent evolution. This is supported by our finding that equine PSG-like CEACAM49 exhibits similar activity to certain rodent and human PSGs in a functional assay of platelet-fibrinogen binding. Our results have implications for understanding the evolution of PSGs and their functions in maternal-fetal interactions.

Assessing Problematic Substance Use in HIV Care: Which Questions Elicit Accurate Patient Disclosures?

BACKGROUND: Substance use is associated with higher rates of antiretroviral non-adherence and poor HIV outcomes. This study examined how HIV care providers assess substance use, and which questions elicit accurate patient disclosures. METHODS: We conducted a conversation analysis of audio-recorded encounters between 56 providers and 162 patients living with HIV (PLWH) reporting active substance use in post-encounter interviews (cocaine or heroin use in the past 30 days, > 4 days intoxicated in past 30 days, or AUDIT score ≥ 8). We assessed the frequency of substance use discussion, characterized the types of questions used by providers, and determined the frequency of accurate patient disclosure by question type. RESULTS: In 55 reports of active substance use, providers already knew about the use (n = 16) or patients disclosed unpromptednn = 39). Among the remaining 155 instances of substance use in which providers had the opportunity to elicit disclosure, 78 reports (50 %) of substance use were not discussed. Of the remaining 77 reports in which the provider asked about substance use, 55 (71 %) patients disclosed and 22 (29 %) did not disclose. Questions were classified as: open-ended (n = 18, "How's the drinking going?"); normalizing (n = 14, "When was the last time you used?"); closed-ended (n = 36, "Have you used any cocaine?"); leading towards non-use (n = 9, "Have you been clean?"). Accurate disclosure followed 100 % of open-ended and normalizing questions, 58 % of closed-ended questions, and 22 % of leading questions. After adjusting for drug type, closed-ended questions were 41 % less likely (p < 0.001), and 'leading' questions 78 % less likely (p = 0.016) than broad and normalizing questions to elicit disclosures. CONCLUSION: Providers in this sample missed almost half of the opportunities to identify and discuss substance use with PLWH. Providers can increase the probability of patient disclosure by using open-ended or normalizing questions that ask about the "last time" that the patient used drugs or alcohol.

Clinician empathy is associated with differences in patient-clinician communication behaviors and higher medication self-efficacy in HIV care.

OBJECTIVE: We examined associations of clinicians' empathy with patient-clinician communication behaviors, patients' rating of care, and medication self-efficacy. METHODS: We analyzed 435 adult patients and 45 clinicians at four outpatient HIV care sites in the United States. Negative binomial regressions investigated associations between clinician empathy and patient-clinician communication, assessed using the Roter Interaction Analysis System (RIAS). Logistic regressions investigated associations between clinician empathy and patient ratings of clinician communication, overall satisfaction, and medication self-efficacy. RESULTS: Clinicians in the highest vs. lowest empathy tertile engaged in less explicitly emotional talk (IRR 0.79, p<0.05), while clinicians in the middle vs. lowest engaged in more positive talk (IRR 1.31, p<0.05), more questions (IRR 1.42, p<0.05), and more patient activating talk (IRR 1.43, p<0.05). Patients of higher empathy clinicians disclosed more psychosocial and biomedical information. Patients of clinicians in both the middle and highest (vs. lowest) empathy tertiles had greater odds of reporting highest medication self-efficacy (OR 1.80, 95% CI 1.16-2.80; OR 2.13, 95% CI 1.37-3.32). CONCLUSIONS: Clinician empathy may be expressed through addressing patient engagement in care, by fostering cognitive, rather than primarily emotional, processing. PRACTICE IMPLICATIONS: Clinicians should consider enhancing their own empathic capacity, which may encourage patients' self-efficacy in medication adherence.

Respecting patients is associated with more patient-centered communication behaviors in clinical encounters.

OBJECTIVE: Attitudes towards patients may influence how clinicians interact. We investigated whether respect for patients was associated with communication behaviors during HIV care encounters. METHODS: We analyzed audio-recordings of visits between 413 adult HIV-infected patients and 45 primary HIV care providers. The independent variable was clinician-reported respect for the patient and outcomes were clinician and patient communication behaviors assessed by the Roter Interaction Analysis System (RIAS). We performed negative binomial regressions for counts outcomes and linear regressions for global outcomes. RESULTS: When clinicians had higher respect for a patient, they engaged in more rapport-building, social chitchat, and positive talk. Patients of clinicians with higher respect for them engaged in more rapport-building, social chitchat, positive talk, and gave more psychosocial information. Encounters between patients and clinicians with higher respect for them had more positive clinician emotional tone [regression coefficient 2.97 (1.92-4.59)], more positive patient emotional tone [2.71 (1.75-4.21)], less clinician verbal dominance [0.81 (0.68-0.96)] and more patient-centeredness [1.28 (1.09-1.51)]. CONCLUSIONS: Respect is associated with positive and patient-centered communication behaviors during encounters. PRACTICE IMPLICATIONS: Clinicians should be mindful of their respectful attitudes and work to foster positive regard for patients. Educators should consider methods to enhance trainees' respect in communication skills training.

Impact of a brief patient and provider intervention to improve the quality of communication about medication adherence among HIV patients.

INTRODUCTION: Medication adherence is essential in HIV care, yet provider communication about adherence is often suboptimal. We designed this study to improve patient-provider communication about HIV medication adherence. METHODS: We randomized 26 providers at three HIV care sites to receive or not receive a one-hour communication skills training based on motivational interviewing principles applied to medication adherence. Prior to routine office visits, non-adherent patients of providers who received the training were coached to discuss adherence with their providers. Patients of providers who did not receive the training providers were not coached. We audio-recorded and coded patient-provider interactions using the roter interaction analysis system (RIAS). RESULTS: There was more dialogue about therapeutic regimen in visits with intervention patients and providers (167 vs 128, respectively, p=.004), with the majority of statements coming from providers. These visits also included more brainstorming solutions to nonadherence (41% vs. 22%, p=0.026). Intervention compared with control visit providers engaged in more positive talk (44 vs. 38 statements, p=0.039), emotional talk (26 vs. 18 statements, p<0.001), and probing of patient opinion (3 vs. 2 statements, p=0.009). CONCLUSION: A brief provider training combined with patient coaching sessions, improved provider communication behaviors and increased dialogue regarding medication adherence.

A mixed methods study of patient-provider communication about opioid analgesics.

OBJECTIVE: To describe patient-provider communication about opioid pain medicine and explore how these discussions affect provider attitudes toward patients. METHODS: We audio-recorded 45 HIV providers and 423 patients in routine outpatient encounters at four sites across the country. Providers completed post-visit questionnaires assessing their attitudes toward patients. We identified discussions about opioid pain management and analyzed them qualitatively. We used logistic regression to assess the association between opioid discussion and providers' attitudes toward patients. RESULTS: 48 encounters (11% of the total sample) contained substantive discussion of opioid-related pain management. Most conversations were initiated by patients (n=28, 58%) and ended by the providers (n=36, 75%). Twelve encounters (25%) contained dialog suggesting a difference of opinion or conflict. Providers more often agreed than disagreed to give the prescription (50% vs. 23%), sometimes reluctantly; in 27% (n=13) of encounters, no decision was made. Fewer than half of providers (n=20, 42%) acknowledged the patient's experience of pain. Providers had a lower odds of positive regard for the patient (adjusted OR=0.51, 95% CI: 0.27-0.95) when opioids were discussed. CONCLUSIONS: Pain management discussions are common in routine outpatient HIV encounters and providers may regard patients less favorably if opioids are discussed during visits. The sometimes-adversarial nature of these discussions may negatively affect provider attitudes toward patients. PRACTICE IMPLICATIONS: Empathy and pain acknowledgment are tools that clinicians can use to facilitate productive discussions of pain management.