A mixed-method approach to generate and deliver rapid-cycle evaluation feedback: lessons learned from a multicenter implementation trial in pediatric surgery.

BACKGROUND: Rapid-cycle feedback loops provide timely information and actionable feedback to healthcare organizations to accelerate implementation of interventions. We aimed to (1) describe a mixed-method approach for generating and delivering rapid-cycle feedback and (2) explore key lessons learned while implementing an enhanced recovery protocol (ERP) across 18 pediatric surgery centers. METHODS: All centers are members of the Pediatric Surgery Research Collaborative (PedSRC, www.pedsrc.org ), participating in the ENhanced Recovery In CHildren Undergoing Surgery (ENRICH-US) trial. To assess implementation efforts, we conducted a mixed-method sequential explanatory study, administering surveys and follow-up interviews with each center's implementation team 6 and 12 months following implementation. Along with detailed notetaking and iterative discussion within our team, we used these data to generate and deliver a center-specific implementation report card to each center. Report cards used a traffic light approach to quickly visualize implementation status (green = excellent; yellow = needs improvement; red = needs significant improvement) and summarized strengths and opportunities at each timepoint. RESULTS: We identified several benefits, challenges, and practical considerations for assessing implementation and using rapid-cycle feedback among pediatric surgery centers. Regarding potential benefits, this approach enabled us to quickly understand variation in implementation and corresponding needs across centers. It allowed us to efficiently provide actionable feedback to centers about implementation. Engaging consistently with center-specific implementation teams also helped facilitate partnerships between centers and the research team. Regarding potential challenges, research teams must still allocate substantial resources to provide feedback rapidly. Additionally, discussions and consensus are needed across team members about the content of center-specific feedback. Practical considerations include carefully balancing timeliness and comprehensiveness when delivering rapid-cycle feedback. In pediatric surgery, moreover, it is essential to actively engage all key stakeholders (including physicians, nurses, patients, caregivers, etc.) and adopt an iterative, reflexive approach in providing feedback. CONCLUSION: From a methodological perspective, we identified three key lessons: (1) using a rapid, mixed method evaluation approach is feasible in pediatric surgery and (2) can be beneficial, particularly in quickly understanding variation in implementation across centers; however, (3) there is a need to address several methodological challenges and considerations, particularly in balancing the timeliness and comprehensiveness of feedback. TRIAL REGISTRATION: NIH National Library of Medicine Clinical Trials. CLINICALTRIALS: gov Identifier: NCT04060303. Registered August 7, 2019, https://clinicaltrials.gov/ct2/show/NCT04060303.

Implementation of Enhanced Recovery Protocols for Gastrointestinal Surgery in Children: Practical Tools From Key Stakeholders.

INTRODUCTION: We explored patient, caregiver, and provider recommendations for development of a tool kit to implement enhanced recovery protocols (ERPs) for pediatric patients undergoing gastrointestinal surgery. ERPs are widely used for adults to decrease hospital length of stay, hospital costs, and complications while hastening patient recovery after surgery. With limited data available for ERPs among pediatric populations informed modification of adult ERPs is needed to facilitate successful implementation for pediatric surgery. METHODS: Using a qualitative research design, semistructured interviews were conducted with hospital-based teams including surgeons, anesthesiologists, gastroenterologists, nursing, and physician assistants. Four in-person focus groups were held at two pediatric hospitals with patients and caregivers. Codes were developed and applied to interview and focus groups transcripts for structural content analysis. Thematic analysis guided by the Active Implementation Framework, included recommendations that informed ERP implementation tool kit development. RESULTS: Key components of the ERP tool kit included the need for a structured and systematic approach, leadership support from key champions, and buy-in from surgical partners and hospital management. Providers identified the need for multimodal educational materials on ERP elements for staff and patients; use of uniform checklists, care sets and an electronic repository to collect outcome data for quality assurance assessment. Patients and caregivers endorsed expansion of the team to include child-life specialists, nutritionists, and patient-parent supporters to help navigate the surgical experience. CONCLUSIONS: This study is the first to leverage key input from patients, caregivers, and providers to identify practical components for an ERP implementation tool kit for children undergoing gastrointestinal surgery.

A qualitative examination of barriers and facilitators of pediatric enhanced recovery protocol implementation among 18 pediatric surgery services.

BACKGROUND: Enhanced recovery protocols (ERPs) are an evidence-based intervention to optimize post-surgical recovery. Several studies have demonstrated that the use of an ERP for gastrointestinal surgery results in decreased length of stay, shortened time to a regular diet, and fewer administered opioids, while also trending toward lower complication and 30-day readmission rates. Yet, implementation of ERPs in pediatric surgery is lagging compared to adult surgery. The study's purpose was to conduct a theory-guided evaluation of barriers and facilitators to ERP implementation at US hospitals with a pediatric surgery service. METHODS: We conducted semi-structured interviews at 18 hospitals with 48 participants, including pediatric surgeons, anesthesiologists, gastroenterologists, nurses, and physician assistants. Interviews were conducted online, audio-recorded, and transcribed verbatim. To identify barriers and facilitators to ERP implementation, we conducted an analysis using deductive logics based on the five Active Implementation Frameworks (AIFs). RESULTS: Effective practices (usable innovations) were challenged by a lack of compliance to ERP elements, and facilitators were having standardized protocols in place and organization support for implementation. Effective implementation (stages of implementation and implementation drivers) had widespread barriers to implementation across the stages from exploration to full implementation. Barriers included needing dedicated teams for ERP implementation and buy-in from hospital leadership. These items, when present, were strong facilitators of effective implementation, in addition to on-site, checklists, protected time to oversee ERP implementation, and order sets for ERP elements built into the electronic medical record. The enabling context (teams) focused on teams' engagement in ERP implementation and how they collaborated to implement ERPs. Barriers included having surgical team members resistant to change or who were not bought into ERPs in pediatric practice. Facilitators included engaging a multi-disciplinary team and engaging patients and families early in the implementation process. CONCLUSIONS: Barriers to ERP implementation in pediatric surgery highlighted can be addressed through providing guidelines to ERP implementation, team-based support for change management, and protocols for developing an ERP implementation team. Future steps are to apply and evaluate these strategies in a stepped-wedge, cluster randomized trial to increase the implementation of ERPs at these 18 hospitals.

Age- and Sex-Specific Needs for Children Undergoing Inflammatory Bowel Disease Surgery: A Qualitative Study.

INTRODUCTION: The use of enhanced recovery protocols (ERP) is extending to pediatric surgical populations, such as patients with inflammatory bowel diseases (IBDs). Given the variation in age- and sex-specific characteristics of pediatric IBD patients, it is important to understand the unique needs of subgroups, such as male versus female or preadolescent versus older patients, when implementing ERPs. We gathered clinician, patient, and caregiver perspectives on age- and sex-specific needs for children undergoing IBD surgery. METHODS: We used semistructured interviews and focus groups to assess ERP needs and perceived differences in needs between preadolescent (10-13 y), older (14-19 y), male, and female IBD patients. Participants included clinicians, patients who had recent IBD surgery, and patients' caregivers. RESULTS: Forty-eight clinicians, six patients, and eight caregivers participated. Three broad categories of themes emerged: concerns, needs, and experiences related to the (1) surgical care process; (2) continuum of IBD care; and (3) suggestions to make surgical care more patient centered. With regard to surgical care processes, stakeholders reported different communication needs for preadolescent and older children. Key themes about the continuum of IBD care were the need (1) for support from child life specialists and (b) to address young women's health issues. Suggestions to make surgical care more patient centered included providing older children with patient experiences that reflect their perspective as young adults. CONCLUSIONS: The findings highlight the need to adopt a patient-centered approach for ERP use that actively addresses age- and sex-specific factors while engaging patients and caregivers as partners with clinicians to improve surgical care for children with IBD.

Influences on Women's Care Seeking at Planned Parenthood Health Centers in Two Southern States.

INTRODUCTION: In the context of a shifting health care landscape, better understanding of the factors that motivate women to seek services from specialized family planning clinics like Planned Parenthood (PP) can provide insights about potential changes in the role of specialized family planning clinics. METHODS: We surveyed 725 women seeking services at two PP health centers in Louisiana and Kentucky from March 2016 to May 2017. We examined differences in care-seeking between women who had varying levels of access including those who did and did not have insurance instability or a regular source of care (RSOC) besides the clinic. RESULTS: More than 60% of women attending the health centers did not have a regular source of care and nearly 40% experienced instability in insurance. Women who experienced insurance instability and a lack of a regular source of care more frequently sought primary preventive services such as pap tests and well-woman care at PP than women with better access. For women with better access, PP health centers also served important roles for those seeking contraceptive and sexually transmitted infection-related services. The most frequent reasons for choosing PP were that it was faster to get an appointment, wanting to go to the PP clinic more than other clinics, and the confidentiality of services. CONCLUSIONS: Our analysis suggests that PP health centers in Southern states still provide vital services for women with and without other sources of care and are critical for women needing access to timely services for preventive and sexually transmitted infection-related care.

A baseline assessment of enhanced recovery protocol implementation at pediatric surgery practices performing inflammatory bowel disease operations.

BACKGROUND: Enhanced recovery protocols (ERPs) have been used to improve patient outcomes and resource utilization after surgery. These evidence-based interventions include patient education, standardized anesthesia protocols, and limited fasting, but their use among pediatric populations is lagging. We aimed to determine baseline recovery practices within pediatric surgery departments participating in an ERP implementation trial for elective inflammatory bowel disease (IBD) operations. METHODS: To measure baseline ERP adherence, we administered a survey to a staff surgeon in each of the 18 participating sites. The survey assessed demographics of each department and utilization of 21 recovery elements during patient encounter phases. Mixed-methods analysis was used to evaluate predictors and barriers to ERP element implementation. RESULTS: The assessment revealed an average of 6.3 ERP elements being practiced at each site. The most commonly practiced elements were using minimally invasive techniques (100%), avoiding intraabdominal drains (89%), and ileus prophylaxis (72%). The preoperative phase had the most elements with no adherence including patient education, optimizing medical comorbidities, and avoiding prolonged fasting. There was no association with number of elements utilized and total number of surgeons in the department, annual IBD surgery volume, and hospital size. Lack of buy-in from colleagues, electronic medical record adaptation, and resources for data collection and analysis were identified barriers. CONCLUSIONS: Higher intervention utilization for IBD surgery was associated with elements surgeons directly control such as use of laparoscopy and avoiding drains. Elements requiring system-level changes had lower use. The study characterizes the scope of ERP utilization and the need for effective tools to improve adoption. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Mixed-methods survey.

Radial versus femoral vascular access in ST-elevation myocardial infarction: Are the results of femoral operators unfairly represented in observational research?

BACKGROUND: Recent randomized controlled trials comparing femoral and radial access in primary percutaneous coronary intervention (PPCI) have shown conflicting results regarding the incidence of major adverse cardiovascular events (MACE) and major bleeding. METHODS: Using data from the HEAT-PPCI trial, we compared the primary efficacy (all-cause mortality, stroke, new myocardial infarction or unplanned repeat revascularization) and safety (major bleeding BARC 3-5) outcomes at 28 days, by final access site used (radial or femoral) and by default operator type. We then assessed outcomes in femoral cases performed by both operator types. RESULTS: Radial access (RA) was associated with fewer MACE (91/1472 = 6.2% vs. 36/332 = 10.8% P = .003) and major bleeding events (38/1472 = 2.6% vs 22/332 = 6.6% P = .001) when compared to femoral access (FA). When analyzing outcomes by default operator type, there was a similar incidence of MACE (111/1575 = 7% vs 16/229 = 7% P = .97) and major bleeding events (49/1575 = 3.1% vs 11/229 = 4.8% P = .18). In cases where FA was performed by default radial operators, there was a higher rate of MACE (22/122 = 18% vs 14/210 = 6.7% P = .003) and major bleeding events (11/122 = 9% vs 11/210 = 5.2% P < .001), potentially explained by a higher risk profile in these cases. CONCLUSION: Default femoral operators achieved comparable outcomes when compared to default radial operators. The less favorable outcomes observed in FA cases may result from its selective use by radial operators in high risk cases.

Cognitive impairment in older patients undergoing colorectal surgery.

Background With increasing numbers of older people being referred for elective colorectal surgery, cognitive impairment is likely to be present and affect many aspects of the surgical pathway. This study is aimed to determine the prevalence of cognitive impairment and assess it against surgical outcomes. Methods The Montreal Cognitive Assessment (MoCA) was carried out in patients aged more than 65 years. We recorded demographic information. Data were collected on length of hospital stay, complications and 30-day mortality. Results There were 101 patients assessed, median age was 74 years (interquartile range = 68-80), 54 (53.5%) were women. In total, 58 people (57.4%) 'failed' the Montreal Cognitive Assessment test (score ≤ 25). There were two deaths (3.4%) within 30 days of surgery in the abnormal Montreal Cognitive Assessment group and none in the normal group. Twenty-nine (28.7%) people experienced a complication. The percentage of patients with complications was higher in the group with normal Montreal Cognitive Assessment (41.9%) than abnormal Montreal Cognitive Assessment (19.9%) ( p = 0.01) and the severity of those complications were greater (chi-squared for trend p = 0.01). The length of stay was longer in people with an abnormal Montreal Cognitive Assessment (mean 8.1 days vs. 5.8 days, p = 0.03). Conclusion Cognitive impairment was common, which has implications for informed consent. Cognitive impairment was associated with less postoperative complications but a longer length of hospital stay.

Enhancing screening and early detection among women transitioning to Medicare from the NBCCEDP in Georgia.

PURPOSE: The National Breast and Cervical Cancer Early Detection Program through each state's administration serves millions of low-income and uninsured women aged 40-64. Our purpose was to assess whether cases screened through Georgia's Breast and Cervical Cancer Program (BCCP) were diagnosed at an earlier stage of disease and whether those who used the state's program regularly continued to obtain age-appropriate screens as they aged out of BCCP into Medicare between 2000 and 2005. METHODS: We used BCCP screening data to identify women with more than one screen and an interval of 18 months or less between screens as "regular" users of BCCP. Using the linked BCCP and Medicare enrollment/claims data, we tested whether women with any BCCP use (n = 3,134) or "regular" users (n = 1,590) were more likely than women not using BCCP (n = 10,086) to exhibit regular screening under Medicare. We used linked BCCP and Georgia Cancer Registry data to examine breast cancer incidence and stage at diagnosis of BCCP women compared to the Georgia population. RESULTS: Under Medicare, almost 63 % of women with any BCCP use were re-screened versus 51 % of non-BCCP users. The probability of being screened within 18 months of Medicare enrollment was 3.5 % points higher for any BCCP user and 17.7 points higher for "regular" BCCP users, compared to nonusers. Among Black non-Hispanics, the difference for any BCCP user was 13.7 % points and for regular users, 22.4 % points. A larger percentage of BCCP users were diagnosed at in situ or localized disease stage than overall. CONCLUSIONS: The majority of women aging out of the GA BCCP 2000-2005 had used the program to obtain regular mammography. Regular users of GA BCCP continued to be screened within appropriate intervals once enrolled in Medicare due perhaps to educational and support components of BCCP.

Facilitators and barriers to cervical cancer screening, diagnosis, and enrollment in Medicaid: experiences of Georgia's Women's Health Medicaid Program enrollees.

Although cervical cancer incidence and mortality rates have declined in the USA, African American women have a higher incidence rate of cervical cancer and a higher percentage of late-stage diagnosis than white women. Previous analyses by the authors showed that, even after adjusting for age, provider location, and availability, African American women were almost half as likely as white women to be diagnosed or enter Medicaid while at an early stage of their cervical cancer. To understand why these differences exist, we undertook a qualitative examination of the cervical cancer experiences of women enrolled in Georgia's Women's Health Medicaid Program (WHMP). Life history interviews were conducted with 24 WHMP enrollees to understand what factors shaped their cervical cancer experiences, from screening through enrollment in Medicaid. We also examined whether these factors differed by race in order to identify opportunities for increasing awareness of cervical cancer screening among underserved women. Results suggest that many women, especially African Americans, lacked understanding and recognition of early symptoms of cervical cancer, which prevented them from receiving a timely diagnosis. Additionally, participants responded positively to provider support and good communication but wished that their doctors explained their diagnosis more clearly. Finally, women were able to enroll in Medicaid without difficulty due largely to the assistance of clinical staff. These findings support the need to strengthen provider education and public health efforts to reach low-income and minority communities for screening and early detection of cervical cancer.

Takes two to tango.

A 17-year-old girl was admitted with acute abdominal pain, vomiting and a leucocytosis, and was initially thought to have appendicitis. She underwent laparoscopic appendicectomy, where the tip of the appendix was noted to be mildly inflamed and she was discharged home the day after surgery. Two days later, she re-presented with small bowel obstruction which was subsequently demonstrated to be due to ingestion of five magnetic beads. She required a laparotomy and small bowel resection to resolve the obstruction, but has since fully recovered. This case highlights the potential intestinal complications caused by the intake of magnetic objects, and based on a literature review a number of recommendations are made to guide clinicians when managing similar cases.

Breast cancer treatment experiences by race and location in Georgia's Women's Health Medicaid Program.

BACKGROUND: This study seeks to understand the breast cancer treatment patterns and experiences of women enrolled in Georgia's Breast and Cervical Cancer Prevention and Treatment Act program, the Women's Health Medicaid Program (WHMP), and whether these experiences vary by race or location. METHODS: We conducted a mixed-methods analysis of WHMP breast cancer enrollees by race and urban/rural location. Quantitative analysis used a hazard rate model approach to identify differences in the timing of diagnosis, enrollment into Medicaid, and various modalities of treatment for 810 enrollees. Qualitative analysis used a systematic retrieval and review of coded data from 34 in-depth disease life history interview transcripts to a complete, focused analysis of enrollees' cancer treatment experiences. FINDINGS: African-American women began treatment, on average, 6 days later after diagnosis than White women, driven by delays of one month among African-American women with late-stage cancers. This time delay for African-American women was not significant on multivariate analysis of time from enrollment to treatment. Once enrolled in WHMP, women reported gaining access to equitable breast cancer treatment regardless of race or location, with the exception of breast reconstruction, for which some women in our sample reported barriers to care. CONCLUSIONS: The equitable access to cancer treatment and other health services provided by WHMP to low-income, uninsured women in Georgia with breast cancer makes it a critical health care safety net program in Georgia, the need for which will continue through the implementation of the Affordable Care Act.

Efforts by commercial health plans to increase Chlamydia trachomatis screening among their members.

BACKGROUND: The screening rate for Chlamydia trachomatis (Ct) is below 38% nationally, despite the high prevalence of Ct nationally and the low cost of both the screening test and the treatment. The purposes of this study are (a) to ascertain what activities commercial health plans have attempted (if any) to increase their Ct screening rates and (b) to identify barriers to improving Ct screening rates in commercial health plans. METHODS: Qualitative research methods were used, including structured interviews. In-depth telephone interviews with commercial health plans were conducted to identify health plan activities that led to high Ct screening rates by providers. Plans were selected, which were either in the top or in the bottom quarter of all plans or had either an increase or decrease in Ct screening rates of at least 3 percentage points over the previous 2 to 3 years. Interviews were restricted to plans reporting Ct screening rates to the National Committee for Quality Assurance for at least 3 years, plans with enrollment of at least 500 commercially insured women aged 15 to 26 years, and plans that were not staff model-managed care plans. A total of 35 structured interviews were completed with a response rate of 64%. RESULTS: Overall Ct screening rates in commercial health plans are quite low, with a median rate of 35%. All interviewed plans-both successful and not successful-reimbursed for Ct screening and used clinical guidelines. All but 3 plans had some type of intervention in place designed to improve Ct screening rats. The interventions varied-some aimed at providers, others at patients, and others at data collection-but the health plans were actively trying to improve screening rates. Health plans identified several barriers to improving screening rates in the commercially insured population. These include difficulties in identifying sexually active members for screening, limited health plan resources to target the problem, concerns about contacting minors, and cultural barriers to discussing sexually transmitted diseases. CONCLUSIONS: Both high- and low-performing plans are actively trying to increase the Ct screening rates. However, efforts to date have not been successful, suggesting the need for alternative approaches to address existing barriers.

Recruitment for the National Breast and Cervical Cancer Early Detection Program.

BACKGROUND: To reduce disparities in breast and cervical cancer in the U.S., it is essential that programs such as CDC's National Breast and Cervical Cancer Early Detection Program (NBCCEDP) use evidence-based strategies. Recommendations for interventions to increase breast and cervical cancer screening have been disseminated by national public health organizations. To increase screening, cancer control planners would benefit from use of evidence-based strategies for recruitment of participants in their communities. PURPOSE: The purpose of the study was to inventory recruitment activities for cancer screening within NBCCEDP programs and assess if activities used to increase cancer screening are evidence-based. METHODS: Interviews were conducted with 61 recruitment coordinators in 2008 to elicit their recruitment activities, use of evidence-based resources, and barriers to using evidence-based interventions (EBIs). Study data were analyzed in 2009. RESULTS: Of the 340 activities reported, many were categorized as educational materials, one-on-one education, mass media, group education, and special events. Two thirds of inventoried activities matched an EBI. Coordinators reported that colleagues and the CDC are their primary sources of information about EBIs and few coordinators had used evidence-based resources. Lack of money or funding, questionable applicability to priority populations, limited staffing or staff time, and insufficient evidence-based research were the most important barriers to EBI use. CONCLUSIONS: Although the majority of NBCCEDP recruitment activities were evidence-based, one third were not. Additional training and technical assistance are recommended to help public health agencies adopt the use of these strategies.

TRAF1 is a critical regulator of JNK signaling by the TRAF-binding domain of the Epstein-Barr virus-encoded latent infection membrane protein 1 but not CD40.

The oncogenic Epstein-Barr virus (EBV)-encoded latent infection membrane protein 1 (LMP1) mimics a constitutive active tumor necrosis factor (TNF) family receptor in its ability to recruit TNF receptor-associated factors (TRAFs) and TNF receptor-associated death domain protein (TRADD) in a ligand-independent manner. As a result, LMP1 constitutively engages signaling pathways, such as the JNK and p38 mitogen-activated protein kinases (MAPK), the transcription factor NF-kappaB, and the JAK/STAT cascade, and these activities may explain many of its pleiotropic effects on cell phenotype, growth, and transformation. In this study we demonstrate the ability of the TRAF-binding domain of LMP1 to signal on the JNK/AP-1 axis in a cell type- dependent manner that critically involves TRAF1 and TRAF2. Thus, expression of this LMP1 domain in TRAF1-positive lymphoma cells promotes significant JNK activation, which is blocked by dominant-negative TRAF2 but not TRAF5. However, TRAF1 is absent in many established epithelial cell lines and primary nasopharyngeal carcinoma (NPC) biopsy specimens. In these cells, JNK activation by the TRAF-binding domain of LMP1 depends on the reconstitution of TRAF1 expression. The critical role of TRAF1 in the regulation of TRAF2-dependent JNK signaling is particular to the TRAF-binding domain of LMP1, since a homologous region in the cytoplasmic tail of CD40 or the TRADD-interacting domain of LMP1 signal on the JNK axis independently of TRAF1 status. These data further dissect the signaling components used by LMP1 and identify a novel role for TRAF1 as a modulator of oncogenic signals.

The oncogenic protein kinase Tpl-2/Cot contributes to Epstein-Barr virus-encoded latent infection membrane protein 1-induced NF-kappaB signaling downstream of TRAF2.

The Epstein-Barr virus-encoded latent infection membrane protein 1 (LMP1) is a pleiotropic protein, the activities of which include effects on cell transformation and phenotype, growth, and survival. The ability of LMP1 to mediate at least some of these phenomena could be attributed to the activation of the transcription factor NF-kappaB. LMP1 promotes NF-kappaB activation through the recruitment of the adapter protein TRAF2 and the formation of a dynamic multiprotein complex that includes the NF-kappaB kinase, the IkappaB kinases, and their downstream targets, IkappaBs and p105. In this study, we have identified the oncogenic kinase Tpl-2/Cot as a novel component of LMP1-induced NF-kappaB signaling. We show that Tpl-2 is expressed in primary biopsies from patients with nasopharyngeal carcinoma and Hodgkin's disease, where LMP1 is also found. Inducible expression of LMP1 promotes the activation of Tpl-2, and a catalytically inactive Tpl-2 mutant suppresses LMP1-induced NF-kappaB signaling. In colocalization and coimmunoprecipitation experiments, Tpl-2 and TRAF2 were found to interact with Tpl-2 functioning downstream of TRAF2. Consistent with this observation, catalytically inactive Tpl-2 also blocked CD40-mediated NF-kappaB activation, which largely depends on TRAF2. The ability of Tpl-2 to influence LMP1-induced NF-kappaB occurs through modulation of both IkappaBalpha and p105 functions. Furthermore, Tpl-2 was found to influence the expression of angiogenic mediators, such as COX-2 in LMP1-transfected cells. These data identify Tpl-2 as a component of LMP1 signaling downstream of TRAF2 and as a modulator of LMP1-mediated effects.