Research protocol for bridging research, accurate information and dialogue (BRAID)-clinical trials: a mixed-methods study of a community-based intervention to improve trust and diversify participation in clinical trials.

Cultural beliefs, personal experiences, and historic abuses within the healthcare system-rooted in structural racism-all contribute to community distrust in science and medicine. This lack of trust, particularly within underserved communities, contributes to decreased participation in clinical trials and a lack of representation in the data. Open dialogue about community concerns and experiences related to research participation and medical care processes can help build trust and change attitudes and behaviors that affect community health. This protocol outlines an approach to increase trust in science and clinical trials among communities in the Bronx, New York that are typically underrepresented in research data. Bridging Research, Accurate Information and Dialogue (BRAID) is a two-phased, evidence-based community engagement model that creates safe spaces for bilateral dialogues between trusted community messengers, and clinicians and scientists. The team will conduct a series of BRAID Conversation Circles on the topic of clinical trials with local trusted community messengers. Participants will be members of the community who are perceived as "trusted messengers" and can represent the community's voice because they have insight into "what matters" locally. Conversation Circles will be audiotaped, transcribed, and analyzed to identify emergent challenges and opportunities surrounding clinical trial participation. These key themes will subsequently inform the codesign and co-creation of tailored messages and outreach efforts that community participants can disseminate downstream to their social networks. Surveys will be administered to all participants before and after each Conversation Circle to understand participants experience and evaluate changes in knowledge and attitudes about clinical trials, including protections for research participants the advantages of having diverse representation. Changes in motivation and readiness to share accurate clinical trial information downstream will also be assessed. Lastly, we will measure participants dissemination of codesigned science messages through their social networks by tracking participant specific resource URLs of materials and videos posted on a BRAID website. This protocol will assess the effectiveness and adoptability of an innovative CBPR model that can be applied to a wide range of public health issues and has the potential to navigate the ever-changing needs of the communities that surround health systems.

Utilization and Staff Perspectives on an On-Demand Telemedicine Model for People with Intellectual and Developmental Disabilities Who Reside in Certified Group Residences.

Background: Non-emergent medical problems that arise when a usual provider is unavailable can often result in emergency department or urgent care visits, which can be particularly distressing to people with intellectual and developmental disabilities (PIDD). On-demand, synchronous telemedicine may be a promising supplement when immediate care from usual sources is unavailable. Prior research demonstrated that high-quality telemedicine can be effectively delivered to PIDD. The aim of this article is to describe the utilization and staff perspectives on the implementation of the Telemedicine Triage Project (TTP), an innovative model that provides telemedicine consultations for PIDD who reside in state-certified group residences and present with an urgent but non-emergent medical concern when their usual provider is unavailable. Methods: Call frequency data for calendar years 2020 and 2021 were reviewed. The study team conducted semi-structured interviews, with 19 key informants representing organizational- and agency-level leadership and staff. The interview data were analyzed using a protocol-driven, rapid qualitative methodology. Results: Telemedicine consultations increased from 7953 in 2020 to 15,011 calls in 2021, and call volume peaked between 10 am and 1 pm. Key informants reported high satisfaction with TTP; universal benefits and a few barriers to implementation; and strong interest in maintaining the program beyond the grant period. Discussion: Over the first 2 years of its implementation, the TTP program was widely utilized and proved extremely feasible and acceptable to staff. This model is a promising and highly feasible way to provide equitable access to telemedicine for PIDD by addressing barriers to and disparities in access to health care that affect PIDD.

Enhanced care coordination improves HIV viral load suppression rates.

OBJECTIVES: Optimizing HIV treatment benefits the health of the individual and the community at large. Health department HIV surveillance data matched with Medicaid managed care rosters can be used to target people with HIV infection who have an unsuppressed viral load or are unengaged in care. MetroPlus Health Plan, a Medicaid managed care organization, implemented a 2-pronged approach: street outreach and peer care connection interventions. STUDY DESIGN: A cohort study that included demographics, program contact type and frequency, antiretroviral therapy refill pattern, and CD4 count and HIV viral load values/ranges and dates. METHODS: Members without a viral load test result during the prior 9 months (not engaged) received outreach, and those with unsuppressed viral loads received intensified care coordination and peer support. A retrospective statistical analysis was conducted on cohort members with sufficient viral load data. A subanalysis excluded members who had suppressed viral loads at baseline. RESULTS: A total of 1429 (82%) members in the state cross-referenced list were still enrolled in the plan at study initiation. Successful contact with targeted members by outreach was 60% compared with 40% by care coordination and peer support combined. Members who were successfully contacted by the program had a 44% suppression rate (<200 copies/mL) and a greater likelihood of achieving viral load suppression (odds ratio, 1.55; 95% CI, 1.23-1.95; P <.01) than those who were not. CONCLUSIONS: Surveillance data were successfully used to target HIV-positive Medicaid members who had an unsuppressed viral load or were unengaged in care. Individuals with an unsuppressed viral load can achieve suppression through intensified outreach, care coordination, and peer support by a Medicaid managed care plan.

Testicular Rupture: A Tough Nut to Crack.

Blunt scrotal injury represents a diagnostic dilemma for emergency physicians (EP). Consequently, point-of-care ultrasound (POCUS) has emerged as a tool for early investigation of the acute scrotum in the emergency department. We describe a case where an EP used scrotal POCUS to immediately visualize the loss of testicular contour and underlying heterogeneous parenchyma to rapidly make the diagnosis of testicular rupture in a young male presenting with scrotal trauma. The use of POCUS in this case expedited therapy, likely improving the patient's outcome. To our knowledge, this is the first detailed description of testicular rupture diagnosed with POCUS by an EP.

Check the Head: Emergency Ultrasound Diagnosis of Fetal Anencephaly.

BACKGROUND: Early pregnancy complaints in emergency medicine are common. Emergency physicians (EP) increasingly employ ultrasound (US) in the evaluation of these complaints. As a result, it is likely that rare and important diagnoses will be encountered. We report a case of fetal anencephaly diagnosed by bedside emergency US in a patient presenting with first-trimester vaginal bleeding. CASE REPORT: A 33-year-old patient at 10 weeks gestation presented with vaginal bleeding. After initial history and physical examination, a bedside US was performed. The EP noted the abnormal appearance of the fetal cranium and anencephaly was suspected. This finding was confirmed by a consultative high-resolution fetal US. Making the diagnosis at the point of care allowed earlier detection and more comprehensive maternal counseling about pregnancy options. This particular patient underwent elective abortion which was able to be performed at an earlier gestation, thus decreasing maternal risk. If this diagnosis would not have been recognized by the EP at the point of care, it may not have been diagnosed until the second trimester, and lower-risk maternal options would not have been available.

Retained Products of Conception: An Atypical Presentation Diagnosed Immediately with Bedside Emergency Ultrasound.

Background. Retained products of conception is an important diagnosis to consider in patients presenting with postpartum complaints. Bedside ultrasound is a rapid, accurate, noninvasive modality to evaluate these patients. Objective. To report an atypical case of retained products of conception diagnosed with bedside ultrasound in the emergency department. Case Report. A 27-year-old female who was 1-month postpartum presented with vaginal bleeding, pelvic pain, and no fever. At the time of initial H&P, bedside ultrasound revealed echogenic material within the endometrial cavity with blood flow seen by color Doppler consistent with retained products of conception. The bedside ultrasound rapidly narrowed the differential and allowed a definitive diagnosis immediately. Ob/Gyn was consulted and dilation and curettage was performed in the operating room. Conclusions. Retained products of conception is an important diagnosis for the emergency physician to consider in at-risk patients. The sonographic findings are easily obtained and interpreted by emergency physicians. Earlier diagnosis of this disease process should lead to more focused patient evaluations and management.

A role for CD54 (intercellular adhesion molecule-1) in leukocyte recruitment to the lung during the development of experimental idiopathic pneumonia syndrome.

BACKGROUND: Idiopathic pneumonia syndrome (IPS) is a frequently fatal complication of allogeneic bone marrow transplantation (BMT). IPS is associated with elevated bronchoalveolar lavage (BAL) fluid levels of tumor necrosis factor-alpha and lipopolysaccharide, both of which are potent activators of endothelial cells (ECs). EC expression of the adhesion molecule CD54 (intercellular adhesion molecule [ICAM]-1) has been shown to be a major regulator of pulmonary inflammation in various experimental models. METHODS: Using a well-established murine BMT system in which lung injury and graft-versus-host disease (GvHD) are induced by minor histocompatibility antigenic differences between donor and host, the RNase Protection Assay, mice deficient in ICAM-1 expression, and a monoclonal blocking antibody to ICAM, we evaluated the role of the pulmonary vascular expression of CD54 in the development of IPS. RESULTS: Enhanced pulmonary vascular expression of ICAM-1 coincided with the development of IPS. When ICAM-1 -/- mice were used as allogeneic BMT recipients, IPS severity (measured by lung histopathology, BAL cellularity, and cytokine expression) was significantly reduced compared with wild-type controls. Similar results were also observed when wild-type recipients were treated with a monoclonal blocking antibody to ICAM-1. Surprisingly, ICAM-1 had differential effects on leukocyte infiltration into GvHD target organs; ICAM-1 deficiency had no impact on intestinal histopathology, whereas ICAM-1-/- BMT recipients had significantly enhanced hepatic injury. CONCLUSIONS: These data demonstrate that although the expression of ICAM-1 is critical for the development of IPS, different mechanisms of leukocyte recruitment are operative in other GvHD target organs.

Comprehension of idioms by children with learning disabilities: metaphoric transparency and syntactic frozenness.

Third and fifth grade children with and without learning disabilities participated in this study. Syntactically frozen and flexible idioms and transparent and opaque idioms were used as stimuli to examine the ability to identify the correct idiom and to explain idiom meanings. Grade and diagnostic category affected performance on the explanation task but not on the forced choice task. Idiom type was also a factor affecting comprehension and explanation. Literal responses occurred rarely and were more likely to occur on the forced choice task.

A critical role for CCR2/MCP-1 interactions in the development of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation.

Idiopathic pneumonia syndrome (IPS) is a major complication after allogeneic bone marrow transplantation (allo-BMT) and involves the infiltration of donor leukocytes and the secretion of inflammatory cytokines. We hypothesized that leukocyte recruitment during IPS is dependent in part upon interactions between chemokine receptor 2 (CCR2) and its primary ligand monocyte chemoattractant protein-1 (MCP-1). To test this hypothesis, IPS was induced in a lethally irradiated parent --> F1 mouse BMT model. Compared with syngeneic controls, pulmonary expression of MCP-1 and CCR2 mRNA was significantly increased after allo-BMT. Transplantation of CCR2-deficient (CCR2-/-) donor cells resulted in a significant reduction in IPS severity compared with transplantation of wild-type (CCR2+/+) cells and in reduced bronchoalveolar lavage (BAL) fluid cellularity and BAL fluid levels of tumor necrosis factor-alpha (TNF-alpha) and soluble p55 TNF receptor (sTNFRI). In addition, neutralization of MCP-1 resulted in significantly decreased lung injury compared with control-treated allogeneic recipients. Experimental data correlated with preliminary clinical findings; patients with IPS have elevated levels of MCP-1 in the BAL fluid at the time of diagnosis. Collectively, these data demonstrate that CCR2/MCP-1 interactions significantly contribute to the development of experimental IPS and suggest that interventions blocking these receptor-ligand interactions may represent novel strategies to prevent or treat this lethal complication after allo-BMT.

Role of CXCR3-induced donor T-cell migration in acute GVHD.

OBJECTIVE: The chemokine receptor CXCR3 has an important role in the migration of effector T cells. To investigate the role of CXCR3 on donor cells in acute graft vs host disease (GVHD) we used a well-defined experimental bone marrow transplantation (BMT) model where acute GVHD is mediated by donor CD8(+) T cells against minor histocompatibility antigens. METHODS; Lethally irradiated C3H.SW recipients were transplanted from either wild-type B6 or CXCR3(-/-) B6 donors. Donor T-cell expansion was analyzed in the spleen and small intestine of recipients by FACS. Donor T-cell function was analyzed by cytokine secretion. The severity of acute GVHD was assessed by histopathological analysis of intestine and liver, GVHD clinical scores, and survival after BMT. RESULTS: Significantly higher numbers of donor CD8(+) CXCR3(-/-) T cells were found in the spleen on days +7 and +14 compared to donor wild-type T cells. By contrast, the number of CD8(+) T cells in the small bowel of BMT recipients from CXCR3(-/-) donors was sevenfold lower than from wild-type donors. Systemic concentrations of INF-gamma and TNF-alpha were equivalent between groups. Animals that received CXCR3(-/-) donor T cells demonstrated diminished GI tract and liver damage and showed improved survival after BMT compared to recipients of wild-type donor cells (43% vs 0%, p<0.001). CONCLUSION: The migration of donor CD8(+) T cells to GVHD target organs such as the intestine depends on the expression of CXCR3 and contributes significantly to GVHD damage and overall mortality.

Impaired thymic negative selection causes autoimmune graft-versus-host disease.

Animal models with impaired thymic negative selection do not always cause autoimmune diseases despite the development of an autoreactive T-cell repertoire. We investigated the requirements for the development of systemic autoimmune disease by using bone marrow chimeras that lacked expression of major histocompatibility complex (MHC) class II on thymic antigen-presenting cells (APCs), leading to impaired negative selection. We found that impaired negative selection mediated by absence of MHC class II, but not MHC class I, permitted the development of systemic autoimmune disease that is indistinguishable from acute graft-versus-host disease (GVHD). Thymectomy prevented disease, confirming the causal association of the thymus with its development. Adoptive transfer of CD4+ T cells caused GVHD in secondary hosts only when they were irradiated, and cotransfer of peripheral CD4+ and CD8+ T cells from naive mice prevented the disease. These results demonstrate that impaired thymic negative selection can cause lethal autoimmune disease indistinguishable from acute GVHD in the context of a proinflammatory milieu when peripheral regulatory mechanisms are absent.

Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays.

The liver, skin, and gastrointestinal tract are major target organs of acute graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT). In order to gain a better understanding of acute GVHD in the liver, we compared the gene expression profiles of livers after experimental allogeneic and syngeneic BMT using oligonucleotide microarray. At 35 days after allogeneic BMT when hepatic GVHD was histologically evident, genes related to cellular effectors and acute-phase proteins were up-regulated, whereas genes largely related to metabolism and endocrine function were down-regulated. At day 7 after BMT before the development of histologic changes in the liver, interferon gamma (IFN-gamma)-inducible genes, major histocompatibility (MHC) class II molecules, and genes related to leukocyte trafficking had been up-regulated. Immunohistochemistry demonstrated that expression of IFN-gamma protein itself was increased in the spleen but not in hepatic tissue. These results suggest that the increased expression of genes associated with the attraction and activation of donor T cells induced by IFN-gamma early after BMT is important in the initiation of hepatic GVHD in this model and provide new potential molecular targets for early detection and intervention of acute GVHD.

Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects.

Interleukin-18 (IL-18) is a unique cytokine that modulates both T(H)1/T(H)2 responses, but its ability to modulate diseases through induction of T(H)2 cytokines is unclear. It has been shown to play an important role in allogeneic bone marrow transplantation (BMT). Because immune responses of allogeneic BM donors may affect acute graft-versus-host disease (GVHD), we investigated the effect of pretreating BM transplant donors with IL-18 on the severity of acute GVHD using a well-characterized experimental BMT model (BALB/c-->B6). Pretreatment of allogeneic BM transplant donors with IL-18 significantly improved survival (80% vs 0%; P <.001), and reduced clinical, biochemical, and pathologic indices of acute GVHD in BM transplant recipients. IL-18 pretreatment was associated with reduced interferon gamma (IFN-gamma) and greater IL-4 secretion by donor T cells after BMT. Acute GVHD mortality was reduced when IL-18 was administered to donors deficient in IFN-gamma and signal transducer and activator of transcription 4 (STAT4) but not STAT6 signaling molecules, suggesting a critical role for STAT6 signaling in IL-18's protective effect. IL-18 treatment did not alter donor CD8(+) cytotoxic T-lymphocyte (CTL) activity and preserved graft-versus-leukemia (GVL) effects after allogeneic BMT (70% vs 10%; P <.01). Together these data illustrate that pretreatment of donors with IL-18 prior to allogeneic BMT attenuates acute GVHD in a STAT6-dependent mechanism while preserving GVL effects.

Acute kidney failure: a pediatric experience over 20 years.

BACKGROUND: Acute kidney failure in children is a catastrophic, life-threatening event. OBJECTIVE: To compare and contrast 2 decades of data, analyzing the underlying causes, associated multiple organ system failures, outcome of dialysis procedures, and other variables of interest. DESIGN: Retrospective examination of clinical data collected between January 1, 1979, and December 31, 1998. SETTING: Regional health care center in the mid-Atlantic area. PARTICIPANTS: Two hundred twenty-eight patients, aged from 1 day to 18 years, had acute kidney failure and were referred to a pediatric nephrology service. MAIN OUTCOME MEASURES: Characteristics, percentage of mortality, intensive care unit admission, procedures, and other variables and causes of acute renal failure. RESULTS: The total number of cases analyzed represented 7% of all patients presented to the pediatric nephrology service. Sex distribution, ethnicity, and survival statistics were unchanged between both decades. The overall survival rate was 73%. One hundred fifty-four patients (68%) were admitted to the pediatric intensive care unit. The following 106 acute extracorporeal procedures were performed on 93 patients (41%): 12 patients received extracorporeal membrane oxygenation, 52 patients underwent peritoneal dialysis, 32 underwent hemodialysis, 3 patients received continuous venovenous hemofiltration, and 7 patients received continuous arteriovenous hemofiltration. Sepsis and burns, other leading causes of acute renal failure in the first decade, are replaced in the second decade by hematologic-oncologic complications and pulmonary failure. CONCLUSIONS: Acute kidney failure following repair of cardiac lesions remains unchanged as a leading risk factor of mortality in both decades. Three organ system failures were associated with more than a 50% mortality rate. Predialysis low serum albumin concentrations emerged as a significant copredictor of mortality.

Role of toll-like receptors in changes in gene expression and NF-kappa B activation in mouse hepatocytes stimulated with lipopolysaccharide.

The liver is an important site of host-microbe interaction. Although hepatocytes have been reported to be responsive to lipopolysaccharide (LPS), the global gene expression changes by LPS and mechanism(s) by which LPS stimulates cultured hepatocytes remain uncertain. Cultures of primary mouse hepatocytes were incubated with LPS to assess its effects on the global gene expression, hepatic transcription factors, and mitogen-activated protein (MAP) kinase activation. DNA microarray analysis indicated that LPS modulates the selective expression of more than 80 genes and expressed sequence tags. We have shown previously that hepatocytes express CD14, which is required both for uptake and responsiveness to LPS. In other cells, responsiveness to microbial products requires expression of Toll-like receptors (TLR) and their associated accessory molecules. Hepatocytes expressed TLR1 through TLR9 as well as MyD88 and MD-2 transcripts, as shown by reverse transcriptase PCR analysis, indicating that hepatocytes express all known microbe recognition molecules. The MAP kinase extracellular signal-regulated kinase 1/2 was phosphorylated in response to LPS in mouse hepatocytes, and the levels of phosphorylation were lower in hepatocytes from TLR4-null mice. NF-kappa B activation was reduced in TLR4-mutant or -null hepatocytes compared to control hepatocytes, and this defect was partially restored by adenoviral transduction of mouse TLR4. Thus, hepatocytes respond to nanogram concentrations of LPS through a TLR4 response pathway.