Lindsay Anne Sceats MD

All Publications

• Questioning the Higher Abscess Rate and Overall Cost of Care Associated With Nonoperative Management of Uncomplicated Acute Appendicitis-Reply. JAMA surgery Sceats, L. A., Kin, C., Staudenmayer, K. L. 2019

  View details for PubMedID 31090887

• Sex Differences in Treatment Strategies Among Patients With Ulcerative Colitis: A Retrospective Cohort Analysis of Privately Insured Patients DISEASES OF THE COLON & RECTUM Sceats, L. A., Morris, A. M., Bundorf, M., Park, K. T., Kin, C. 2019; 62 (5): 586?94

  View details for DOI 10.1097/DCR.0000000000001342

  View details for Web of Science ID 000469491700017

• Local and Visiting Physician Perspectives on Short Term Surgical Missions in Guatemala: A Qualitative Study. Annals of surgery Coughran, A. J., Merrell, S. B., Pineda, C., Sceats, L. A., Yang, G. P., Morris, A. M. 2019

  Abstract

  OBJECTIVE: To explore the impact of short-term surgical missions (STMs) on medical practice in Guatemala as perceived by Guatemalan and foreign physicians.SUMMARY BACKGROUND DATA: STMs send physicians from high-income countries to low and middle-income countries to address unmet surgical needs. Although participation among foreign surgeons has grown, little is known of the impact on the practice of foreign or local physicians.METHODS: Using snowball sampling, we interviewed 22 local Guatemalan and 13 visiting foreign physicians regarding their perceptions of the impact of Guatemalan STMs. Interviews were transcribed verbatim, iteratively coded, and analyzed to identify emergent themes. Findings were validated through triangulation and searching for disconfirming evidence.RESULTS: We identified 2 overarching domains. First, the delivery of surgical care by both Guatemalan and foreign physicians was affected by practice in the STM setting. Differences from usual practice manifested as occasionally inappropriate utilization of skills, management of postoperative complications, the practice of perioperative care versus "pure surgery," and the effect on patient-physician communication and trust. Second, both groups noted professional and financial implications of participation in the STM.CONCLUSIONS: While Guatemalan physicians reported a net benefit of STMs on their careers, they perceived STMs as an imperfect solution to unmet surgical needs. They described missed opportunities for developing local capacity, for example through education and optimal resource planning. Foreign physicians described costs that were manageable and high personal satisfaction with STM work. STMs could enhance their impact by strengthening working relationships with local physicians and prioritizing sustainable educational efforts.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

  View details for PubMedID 31009390

• Association of opioid use and peripheral artery disease. Journal of vascular surgery Itoga, N. K., Sceats, L. A., Stern, J. R., Mell, M. W. 2019

  Abstract

  BACKGROUND: Prescription opioids account for 40% of all U.S. opioid overdose deaths, and national efforts have intensified to reduce opioid prescriptions. Little is known about the relationship between peripheral artery disease (PAD) and high-risk opioid use. The objectives of this study were to evaluate this relationship and to assess the impact of PAD treatment on opiate use.METHODS: In this retrospective cohort study, the Truven Health MarketScan database (Truven Health Analytics, Ann Arbor, Mich), a deidentified national private insurance claims database, was queried to identify patients with PAD (two or more International Classification of Diseases, Ninth Revision diagnosis codes of PAD ?2months apart, with at least 2years of continuous enrollment) from 2007 to 2015. Critical limb ischemia (CLI) was defined as the presence of rest pain, ulcers, or gangrene. The primary outcome was high opioid use, defined as two or more opioid prescriptions within a 1-year period. Multivariable analysis was used to determine risk factors for high opioid use.RESULTS: A total of 178,880 patients met the inclusion criteria, 35% of whom had CLI. Mean± standard deviation follow-up time was 5.3± 2.1years. An average of 24.7% of patients met the high opioid use criteria in any given calendar year, with a small but significant decline in high opioid use after 2010 (P< .01). During years of high opioid use, 5.9± 5.5 yearly prescriptions were filled. A new diagnosis of PAD increased high opioid use (21.7% before diagnosis vs 27.3% after diagnosis; P<.001). A diagnosis of CLI was also associated with increased high opioid use (25.4% before diagnosis vs 34.5% after diagnosis; P< .001). Multivariable analysis identified back pain (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.84-1.93; P< .001) and illicit drug use (OR, 1.87; 95% CI, 1.72-2.03; P< .001) as the highest predictors of high opioid use. A diagnosis of CLI was also associated with higher risk (OR, 1.61; 95% CI, 1.57-1.64; P< .001). A total of 43,443 PAD patients (24.3%) underwent 80,816 PAD-related procedures. After exclusion of periprocedural opioid prescriptions (4.9% of all opioid prescriptions), the yearly percentage of high opioid users increased from 25.8% before treatment to 29.6% after treatment (P< .001).CONCLUSIONS: Patients with PAD are at increased risk for high opioid use, with nearly one-quarter meeting described criteria. CLI and treatment for PAD additionally increase high opioid use. In addition to heightened awareness and active opioid management, our findings warrant further investigation into underlying causes and deterrents of high-risk opioid use.

  View details for PubMedID 30922747

• Shared Decision Making in Appendicitis Treatment: Optimized, Standardized, or Usual Communication. JAMA network open Sceats, L., Kin, C., Morris, A. M. 2019; 2 (6): e194999

  View details for DOI 10.1001/jamanetworkopen.2019.4999

  View details for PubMedID 31173112

• Comparative Incidence of Inflammatory Bowel Disease in Different Age Groups in the United States. Inflammatory bowel diseases Keyashian, K., Dehghan, M., Sceats, L., Kin, C., Limketkai, B. N., Park, K. T. 2019

  Abstract

  Data on the incidence of inflammatory bowel disease (IBD) by age group are available in countries outside of the United States or localized populations within the United States. We aimed to estimate the incidence rates (IRs) of IBD by age group using a US multiregional data set.We used the Optum Research Database to identify incident IBD patients with a disease-free interval of 1.5 years between 2005 and 2015. Overall and age-specific IRs were calculated for 4 different age groups: pediatric (0-17 years), young adult (18-25 years), adult (26-59 years), elderly (>60 years). Time trends of incidence were evaluated in each age group. Perianal phenotype (in Crohn's disease [CD]) was also compared.The mean IR for the cohort (n = 60,247) from 2005 to 2015 was 37.5/100,000. The IR was highest in adult and elderly cohorts (36.4 and 36.7/100,000 respectively). In the adult and elderly groups, the IR for UC was higher than that for CD, whereas the opposite was true in the pediatric and young adult groups. The IR increased over the 10-year study period for all age groups (time trends P < 0.001). The elderly group had less perianal disease than the adult group (20.8 vs 22.3%, respectively; P < 0.05).In one of the most comprehensive evaluations of the incidence of IBD in the United States, we found an incidence rate similar to those of other national populations. We also confirmed differences of specific IBD phenotypes based on age groups, with lower rates of perianal disease in the elderly.

  View details for PubMedID 31095681

• Patient Decision-Making in Severe Inflammatory Bowel Disease: The Need for Improved Communication of Treatment Options and Preferences. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland Lai, C., Sceats, L., Qiu, W., Park, K. T., Morris, A. M., Kin, C. 2019

  Abstract

  Patients with inflammatory bowel disease and their physicians must navigate ever-increasing options for treatment. The aim of this study was to elucidate the key drivers of treatment decision-making in inflammatory bowel disease.We conducted qualitative semi-structured in-person interviews of 20 adult patients undergoing treatment for inflammatory bowel disease at an academic medical centre who either recently initiated biologic therapy or underwent an operation or surgical evaluation. Interviews were audio-recorded, transcribed verbatim, iteratively coded, and discussed to consensus by five researchers. We used thematic analysis to explore factors influencing decision-making.Four major themes emerged as key drivers of treatment decision-making: perceived clinical state and disease severity, the patient-physician relationship, knowledge, attitudes, and beliefs about treatment options, and social isolation and stigma. Patients described experiencing a clinical turning point as the impetus for proceeding with a previously undesired treatment such as infusion medication or surgery. Patients reported delays in care or diagnosis, inadequate communication with their physicians, and lack of control over their disease management. Patients often stated that they considered surgery to be the treatment of last resort, which further compounded the complexity of making treatment decisions.Patients described multiple barriers to making informed and collaborative decisions about treatment, especially when considering surgical options. Our study reveals a need for more comprehensive communication between the patient and their physician about the range of medical and surgical treatment options. We recommend a patient-centred approach toward the decision-making process that accounts for patient decision-making preferences, causes of social stress, and clinical status. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/codi.14759

  View details for PubMedID 31295766

• Sex Differences in Treatment Strategies Among Patients With Ulcerative Colitis: A Retrospective Cohort Analysis of Privately Insured Patients. Diseases of the colon and rectum Sceats, L. A., Morris, A. M., Bundorf, M. K., Park, K. T., Kin, C. 2019

  Abstract

  Sex-based treatment disparities occur in many diseases. Women undergo fewer procedural interventions, and their care is less consistent with guideline-based therapy. There is limited research exploring sex-based differences in ulcerative colitis treatment. We hypothesized that women are less likely to be treated with strategies consistent with long-term disease remission, including surgery and maintenance medications.The aim of this study was to determine if patient sex is associated with choice of treatment strategy for ulcerative colitis.This is a retrospective cohort analysis.Data were gathered from a large commercial insurance claims database (Truven MarketScan) from 2007 to 2015.We identified a cohort of 38,851 patients newly diagnosed with ulcerative colitis, aged 12 to 64 years with at least 1 year of follow-up.The primary outcomes measured were the differences between male and female patients in 1) rates and types of index ulcerative colitis operations, 2) rates and types of ulcerative colitis medication prescriptions, and 3) rates of opioid prescriptions.Men were more likely to undergo surgical treatment for ulcerative colitis (2.94% vs 1.97%, p < 0.001, OR 1.51, p < 0.001). The type of index operation performed did not vary by sex. Men were more likely to undergo treatment with maintenance medications, including biologic (12.4% vs 10.2%, p < 0.001, OR 1.22, p < 0.001), immunomodulatory (16.3% vs 14.9%, p < 0.001, OR 1.08, p = 0.006), and 5-aminosalicylate medications (67.0% vs 63.2%, p < 0.001, OR 1.18, p < 0.001). Women were more likely to undergo treatment with rescue therapies and symptomatic control with corticosteroids (55.5% vs 54.0%, p = 0.002, OR 1.07, p = 0.002) and opioids (50.2% vs 45.9%, p < 0.001, OR 1.17, p < 0.001).Claims data lack clinical characteristics acting as confounders.Men with ulcerative colitis were more likely to undergo treatment consistent with long-term remission or cure, including maintenance medications and definitive surgery. Women were more likely to undergo treatment consistent with short-term symptom management. Further studies to explore underlying mechanisms of sex-related differences in ulcerative colitis treatment strategies and disease trajectories are warranted. See Video Abstract at http://links.lww.com/DCR/Axxx.

  View details for PubMedID 30762599

• Fragility of Life: Recurrent Intestinal Perforation Due to Vascular Ehlers-Danlos Syndrome. Digestive diseases and sciences Sceats, L. A., Sukerkar, P. A., Raghavan, S. S., Esmaeili Shandiz, A., Shelton, A., Kin, C. 2019

  View details for PubMedID 30656563

• Nonoperative Management of Uncomplicated Appendicitis Among Privately Insured Patients. JAMA surgery Sceats, L. A., Trickey, A. W., Morris, A. M., Kin, C., Staudenmayer, K. L. 2018

  Abstract

  Importance: Health care professionals have shown significant interest in nonoperative management for uncomplicated appendicitis, but long-term population-level data are lacking.Objective: To compare the outcomes of nonoperatively managed appendicitis against appendectomy.Design, Setting, and Participants: This national retrospective cohort study used claims data from a private insurance database to compare patients admitted with uncomplicated appendicitis from January 1, 2008, through December 31, 2014, undergoing appendectomy vs nonoperative management. Coarsened exact matching was applied before multivariate analysis to reduce imbalance between groups. Data were analyzed from February 12 through May 1, 2018.Exposures: Appendectomy (control arm) or nonoperative management (treatment arm).Main Outcomes and Measures: Short-term primary clinical outcomes included emergency department visits, hospital readmission, abdominal abscess, and Clostridium difficile infections. Long-term primary clinical outcomes were small-bowel obstructions, incisional hernias, and appendiceal cancers. Nonoperative management failure was defined by hospital readmission with appendicitis diagnosis and an appendicitis-associated operation or procedure. Secondary outcomes included number of follow-up visits, length and cost of index hospitalization, and total cost of appendicitis-associated care. Covariates included age, sex, region, insurance plan type, admission year, and Charlson comorbidity index.Results: Of 58?329 patients with uncomplicated appendicitis (52.7% men; mean [SD] age, 31.9 [16.5] years), 55?709 (95.5%) underwent appendectomy and 2620 (4.5%) underwent nonoperative management. Patients in the nonoperative management group were more likely to have appendicitis-associated readmissions (adjusted odds ratio, 2.13; 95% CI, 1.63-2.77; P<.001) and to develop an abscess (adjusted odds ratio, 1.42; 95% CI, 1.05-1.92; P=.02). Patients in the nonoperative management group required more follow-up visits in the year after index admission (unadjusted mean [SD], 1.6 [6.3] vs 0.3 [1.4] visits; adjusted +1.11 visits; P<.001) and had lower index hospitalization cost (unadjusted mean [SD], $11?502 [$9287] vs $13?551 [$10 160]; adjusted -$2117, P<.001), but total cost of appendicitis care was higher when follow-up care was considered (unadjusted, $14?934 [$31 122] vs $14?186 [$10 889]; adjusted +$785; P=.003). During a mean (SD) of 3.2 (1.7) years of follow-up, failure of nonoperative management occurred in 101 patients (3.9%); median time to recurrence was 42 days (interquartile range, 8-125 days). Among the patients who experienced treatment failure, 44 did so within 30 days.Conclusions and Relevance: According to results of this study, nonoperative management failure rates were lower than previously reported. Nonoperative management was associated with higher rates of abscess, readmission, and higher overall cost of care. These data suggest that nonoperative management may not be the preferred first-line therapy for all patients with uncomplicated appendicitis.

  View details for PubMedID 30427983

• Nonoperative Management of Appendicitis in Privately Insured Patients Sceats, L. A., Trickey, A. W., Morris, A. M., Kin, C. J., Staudenmayer, K. D. ELSEVIER SCIENCE INC. 2018: S156?S157

  View details for DOI 10.1016/j.jamcollsurg.2018.07.332

  View details for Web of Science ID 000447760600303

• Operative vs Nonoperative Management of Appendicitis: A Long-Term Cost-Effectiveness Analysis Sceats, L. A., Coughran, A., Barnes, B., Grimm, E. L., Muffly, M., Spain, D. A., Kin, C. J., Owens, D. K., Fiebert, J. ELSEVIER SCIENCE INC. 2018: S157?S158

  View details for DOI 10.1016/j.jamcollsurg.2018.07.334

  View details for Web of Science ID 000447760600305

• Should Surgery Feel Like the Last Resort? Drivers of Decision Making in Inflammatory Bowel Disease Lai, C., Sceats, L. A., Qiu, W., Park, K. T., Morris, A. M., Kin, C. J. ELSEVIER SCIENCE INC. 2018: S163?S164

  View details for DOI 10.1016/j.jamcollsurg.2018.07.347

  View details for Web of Science ID 000447760600318

• Depression and Healthcare Utilization in Patients with Inflammatory Bowel Disease. Journal of Crohn's & colitis Wong, J. J., Sceats, L., Dehghan, M., Wren, A. A., Sellers, Z. M., Limketkai, B. N., Bensen, R., Kin, C., Park, K. T. 2018

  Abstract

  Background: Depression frequently co-occurs in patients with inflammatory bowel disease (IBD) and is a driver in health care costs and utilization.Aim: This study examined the associations between depression and total health care costs, emergency department (ED) visits, computed tomography (CT) scans during ED/inpatient visits, and IBD-related surgery among IBD patients.Methods: Our sample included 331,772 IBD patients from a national administrative claims database (Truven Health MarketScan Database). Gamma and Poisson regression analyses assessed differences related to depression controlling for key variables.Results: Approximately 16% of the IBD cohort was classified as having depression. Depression was associated with a $17,706 (95% CI [$16,892, 18,521]) increase in mean annual IBD-related health care costs and an increased incidence of ED visits (aIRR of 1.5; 95% CI [1.5, 1.6]). Among patients who had ?1 ED/inpatient visits, depression was associated with an increased probability of receiving repeated CT scans (1-4 CT scans aOR of 1.6; 95% CI [1.5, 1.7]; ?5 CT scans aOR 4.6; 95% CI [2.9, 7.3]) and increased odds of undergoing an IBD-related surgery (aOR of 1.2; 95% CI [1.1, 1.2]). Secondary analysis with a pediatric subsample revealed approximately 12% of this cohort was classified as having depression, and depression was associated with increased costs and incidence rates of ED visits and CT scans, but not IBD-related surgery.Conclusion: Quantifiable differences in healthcare costs and patterns of utilization exist among patients with IBD and depression. Integration of mental health services within IBD care may improve overall health outcomes and costs of care.

  View details for PubMedID 30256923

• Lost in translation: Informed consent in the medical mission setting. Surgery Sceats, L. A., Morris, A. M., Narayan, R. R., Mezynski, A., Woo, R. K., Yang, G. P. 2018

  Abstract

  BACKGROUND: Informed consent is a fundamental tenet of ethical care, but even under favorable conditions, patient comprehension of consent conversations may be limited. Little is known about providing informed consent in more uncertain situations such as medical missions. We sought to examine the informed consent process in the medical mission setting.METHODS: We studied informed consent for adult patients undergoing inguinal herniorrhaphy during a medical mission to Guatemala using a convergent mixed-methods design. We audiotaped informed consents during preoperative visits and immediately conducted separate surveys to elicit comprehension of risks. Informed consent conversations and survey responses were translated and transcribed. We used descriptive statistics to examine informed consent content, including information provided by surgeon, the translation of information, and patient comprehension, and used thematic analysis to examine the consent process.RESULTS: Thirteen adult patients (median age 53 years, 69% male) participated. Surgeons conveyed 4 standard risks in 10 out of 13 encounters (77%); all 4 risks were translated to patients in 10 out of 13 encounters (77%). No patient could recall all 4 risks. Qualitative themes regarding the informed consent process included limited physician language skills, verbal domination by physicians and interpreters, and mistranslation of risks. Patients relied on faith and prior or vicarious experiences to qualify surgical risks instead of consent conversations. Many patients restated surgical instructions when asked about risks.CONCLUSION: Despite physicians' attempts to provide informed consent, medical mission patients did not comprehend surgical risks. Our data reveal a critical need to develop more effective methods for communicating surgical risks during medical missions.

  View details for PubMedID 30061041

• Association of Opioid Abuse and Peripheral Arterial Disease Itoga, N. K., Sceats, L. A., Stern, J. R., Mell, M. W. MOSBY-ELSEVIER. 2018: E87

  View details for Web of Science ID 000433036700076

• Risk of post-operative surgical site infections after vedolizumab vs anti-tumour necrosis factor therapy: a propensity score matching analysis in inflammatory bowel disease. Alimentary pharmacology & therapeutics Park, K. T., Sceats, L., Dehghan, M., Trickey, A. W., Wren, A., Wong, J. J., Bensen, R., Limketkai, B. N., Keyashian, K., Kin, C. 2018

  Abstract

  Perioperative vedolizumab (VDZ) and anti-tumour necrosis factor (TNFi) therapies are implicated in causing post-operative complications in inflammatory bowel disease (IBD).To compare the risk of surgical site infections (SSIs) between VDZ- and TNFi-treated IBD patients in propensity-matched cohorts.The Optum Research Database was used to identify IBD patients who received VDZ or TNFi within 30 days prior to abdominal surgery between January 2015 and December 2016. The date of IBD-related abdominal surgery was defined as the index date. SSIs were determined by ICD-9/10 and CPT codes related to superficial wound infections or deep organ space infections after surgery. Propensity score 1:1 matching established comparable cohorts based on VDZ or TNFi exposure before surgery based on evidence-based risk modifiers.The propensity-matched sample included 186 patients who received pre-operative biologic therapy (VDZ, n = 94; TNFi, n = 92). VDZ and TNFi cohorts were similar based on age, gender, IBD type, concomitant immunomodulator exposure, chronic opioid or corticosteroid therapy, Charlson Comorbidity Index and malnutrition. VDZ patients were more likely to undergo an open bowel resection with ostomy. After propensity score matching, there was no significant difference in post-operative SSIs (TNFi 12.0% vs VDZ 14.9%, P = 0.56). Multivariable analysis indicated that malnutrition was the sole risk factor for developing SSI (OR 3.1, 95% CI 1.11-8.71) regardless of the type of biologic exposure.In the largest, risk-adjusted cohort analysis to date, perioperative exposure to VDZ therapy was not associated with a significantly higher risk of developing an SSI compared to TNFi therapy.

  View details for PubMedID 29876995

• Frequency and timing of short-term complications following abdominoperineal resection. The Journal of surgical research Tooley, J. E., Sceats, L. A., Bohl, D. D., Read, B., Kin, C. 2018; 231: 69?76

  Abstract

  Abdominoperineal resection (APR) is primarily used for rectal cancer and is associated with a high rate of complications. Though the majority of APRs are performed as open procedures, laparoscopic APRs have become more popular. The differences in short-term complications between open and laparoscopic APR are poorly characterized.We conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database to determine the frequency and timing of onset of 30-d postoperative complications after APR and identify differences between open and laparoscopic APR.A total of 7681 patients undergoing laparoscopic or open APR between 2011 and 2015 were identified. The total complication rate for APR was high (45.4%). APRs were commonly complicated by blood transfusion (20.1%), surgical site infection (19.3%), and readmission (12.3%). Laparoscopic APR was associated with a 14% lower total complication rate compared to open APR (36.0% versus 50.1%, P < 0.001). This was primarily driven by a decreased rate of transfusion (10.7% versus 24.9%, P < 0.001) and surgical site infection (15.5% versus 21.2%, P < 0.001). Laparoscopic APR had shorter length of stay and decreased reoperation rate but similar rates of readmission and death. Cardiopulmonary complications occurred earlier in the postoperative period after APR, whereas infectious complications occurred later.Short-term complications following APR are common and occur more frequently in patients who undergo open APR. This, along with factors such as risk of positive pathologic margins, surgeon skill set, and patient characteristics, should contribute to the decision-making process when planning rectal cancer surgery.

  View details for PubMedID 30278971

• Frequency and Timing of Short-Term Complications Following Abdominoperineal Resection Journal of Surgical Research Tooley, J. E., Sceats, L. A., Bohl, D. D., Read, B., Kin, C. 2018; 231: 69-76

  View details for DOI 10.1016/j.jss.2018.05.009

• Starting Young: Trends in Opioid Therapy Among US Adolescents and Young Adults With Inflammatory Bowel Disease in the Truven MarketScan Database Between 2007 and 2015. Inflammatory bowel diseases Wren, A. A., Bensen, R., Sceats, L., Dehghan, M., Yu, H., Wong, J. J., MacIsaac, D., Sellers, Z. M., Kin, C., Park, K. T. 2018

  Abstract

  Opioids are commonly prescribed for relief in inflammatory bowel disease (IBD). Emerging evidence suggests that adolescents and young adults are a vulnerable population at particular risk of becoming chronic opioid users and experiencing adverse effects.This study evaluates trends in the prevalence and persistence of chronic opioid therapy in adolescents and young adults with IBD in the United States.A longitudinal retrospective cohort analysis was conducted with the Truven MarketScan Database from 2007 to 2015. Study subjects were 15-29 years old with ?2 IBD diagnoses (Crohn's: 555/K50; ulcerative colitis: 556/K51). Opioid therapy was identified with prescription claims within the Truven therapeutic class 60: opioid agonists. Persistence of opioid use was evaluated by survival analysis for patients who remained in the database for at least 3 years following index chronic opioid therapy use.In a cohort containing 93,668 patients, 18.2% received chronic opioid therapy. The annual prevalence of chronic opioid therapy increased from 9.3% in 2007 to 10.8% in 2015 (P < 0.01), peaking at 12.2% in 2011. Opioid prescriptions per patient per year were stable (approximately 5). Post hoc Poisson regression analyses demonstrated that the number of opioid pills dispensed per year increased with age and was higher among males. Among the 2503 patients receiving chronic opioid therapy and followed longitudinally, 30.5% were maintained on chronic opioid therapy for 2 years, and 5.3% for all 4 years.Sustained chronic opioid use in adolescents and young adults with IBD is increasingly common, underscoring the need for screening and intervention for this vulnerable population.

  View details for PubMedID 29986015

• Association between Latent Proviral Characteristics and Immune Activation in Antiretrovirus-Treated Human Immunodeficiency Virus Type 1-Infected Adults. Journal of virology Liang, E. C., Sceats, L., Bayless, N. L., Strauss-Albee, D. M., Kubo, J., Grant, P. M., Furman, D., Desai, M., Katzenstein, D. A., Davis, M. M., Zolopa, A. R., Blish, C. A. 2014; 88 (15): 8629-8639

  Abstract

  Generalized immune activation during HIV infection is associated with an increased risk of cardiovascular disease, neurocognitive disease, osteoporosis, metabolic disorders, and physical frailty. The mechanisms driving this immune activation are poorly understood, particularly for individuals effectively treated with antiretroviral medications. We hypothesized that viral characteristics such as sequence diversity may play a role in driving HIV-associated immune activation. We therefore sequenced proviral DNA isolated from peripheral blood mononuclear cells from HIV-infected individuals on fully suppressive antiretroviral therapy. We performed phylogenetic analyses, calculated viral diversity and divergence in the env and pol genes, and determined coreceptor tropism and the frequency of drug resistance mutations. Comprehensive immune profiling included quantification of immune cell subsets, plasma cytokine levels, and intracellular signaling responses in T cells, B cells, and monocytes. These antiretroviral therapy-treated HIV-infected individuals exhibited a wide range of diversity and divergence in both env and pol genes. However, proviral diversity and divergence in env and pol, coreceptor tropism, and the level of drug resistance did not significantly correlate with markers of immune activation. A clinical history of virologic failure was also not significantly associated with levels of immune activation, indicating that a history of virologic failure does not inexorably lead to increased immune activation as long as suppressive antiretroviral medications are provided. Overall, this study demonstrates that latent viral diversity is unlikely to be a major driver of persistent HIV-associated immune activation.Chronic immune activation, which is associated with cardiovascular disease, neurologic disease, and early aging, is likely to be a major driver of morbidity and mortality in HIV-infected individuals. Although treatment of HIV with antiretroviral medications decreases the level of immune activation, levels do not return to normal. The factors driving this persistent immune activation, particularly during effective treatment, are poorly understood. In this study, we investigated whether characteristics of the latent, integrated HIV provirus that persists during treatment are associated with immune activation. We found no relationship between latent viral characteristics and immune activation in treated individuals, indicating that qualities of the provirus are unlikely to be a major driver of persistent inflammation. We also found that individuals who had previously failed treatment but were currently effectively treated did not have significantly increased levels of immune activation, providing hope that past treatment failures do not have a lifelong "legacy" impact.

  View details for DOI 10.1128/JVI.01257-14

  View details for PubMedID 24850730

  View details for PubMedCentralID PMC4135944

• Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2 IMMUNITY Acton, S. E., Astarita, J. L., Malhotra, D., Lukacs-Kornek, V., Franz, B., Hess, P. R., Jakus, Z., Kuligowski, M., Fletcher, A. L., Elpek, K. G., Bellemare-Pelletier, A., Sceats, L., Reynoso, E. D., Gonzalez, S. F., Graham, D. B., Chang, J., Peters, A., Woodruff, M., Kim, Y., Swat, W., Morita, T., Kuchroo, V., Carroll, M. C., Kahn, M. L., Wucherpfennig, K. W., Turley, S. J. 2012; 37 (2): 276-289

  Abstract

  To initiate adaptive immunity, dendritic cells (DCs) move from parenchymal tissues to lymphoid organs by migrating along stromal scaffolds that display the glycoprotein podoplanin (PDPN). PDPN is expressed by lymphatic endothelial and fibroblastic reticular cells and promotes blood-lymph separation during development by activating the C-type lectin receptor, CLEC-2, on platelets. Here, we describe a role for CLEC-2 in the morphodynamic behavior and motility of DCs. CLEC-2 deficiency in DCs impaired their entry into lymphatics and trafficking to and within lymph nodes, thereby reducing T cell priming. CLEC-2 engagement of PDPN was necessary for DCs to spread and migrate along stromal surfaces and sufficient to induce membrane protrusions. CLEC-2 activation triggered cell spreading via downregulation of RhoA activity and myosin light-chain phosphorylation and triggered F-actin-rich protrusions via Vav signaling and Rac1 activation. Thus, activation of CLEC-2 by PDPN rearranges the actin cytoskeleton in DCs to promote efficient motility along stromal surfaces.

  View details for DOI 10.1016/j.immuni.2012.05.022

  View details for Web of Science ID 000308261800012

  View details for PubMedID 22884313

  View details for PubMedCentralID PMC3556784