Browsing by Author "Lynch, Sheryl"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Development and Validation of a Prediction Model for Admission After Endoscopic Retrograde Cholangiopancreatography
    (Elsevier, 2015-12) Coté, Gregory A.; Lynch, Sheryl; Easler, Jeffrey J.; Keen, Alyson; Vassell, Patricia A.; Sherman, Stuart; Hui, Siu; Xu, Huiping; Department of Medicine, IU School of Medicine
    BACKGROUND & AIMS: In outpatients undergoing endoscopic retrograde cholangiopancreatography (ERCP) with anesthesia, rates of and risk factors for admission are unclear. We aimed to develop a model that would allow physicians to predict hospitalization of patients during postanesthesia recovery. METHODS: We conducted a retrospective study of data from ERCPs performed on outpatients from May 2012 through October 2013 at the Indiana University School of Medicine. Medical records were abstracted for preanesthesia, intra-anesthesia, and early (within the first hour) postanesthesia characteristics potentially associated with admission. Significant factors associated with admission were incorporated into a logistic regression model to identify subgroups with low, moderate, or high probabilities for admission. The population was divided into training (first 12 months) and validation (last 6 months) sets to develop and test the model. RESULTS: We identified 3424 ERCPs during the study period; 10.7% of patients were admitted to the hospital, and 3.7% developed post-ERCP pancreatitis. Postanesthesia recovery times were significantly longer for patients requiring admission (362.6 ± 213.0 minutes vs 218.4 ± 71.8 minutes for patients not admitted; P < .0001). A higher proportion of admitted patients had high-risk indications. Admitted patients also had more severe comorbidities, higher baseline levels of pain, longer procedure times, performance of sphincter of Oddi manometry, higher pain during the first hour after anesthesia, and greater use of opiates or anxiolytics. A multivariate regression model identified patients who were admitted with a high level of accuracy in the training set (area under the curve, 0.83) and fair accuracy in the validation set (area under the curve, 0.78). On the basis of this model, nearly 50% of patients could be classified as low risk for admission. CONCLUSION: By using factors that can be assessed through the first hour after ERCP, we developed a model that accurately predicts which patients are likely to be admitted to the hospital. Rates of admission after outpatient ERCP are low, so a policy of prolonged observation might be unnecessary.
  • Thumbnail Image
    Item
    Development of a Multifaceted Program for Pharmacogenetics Adoption at an Academic Medical Center: Practical Considerations and Lessons Learned
    (Wiley, 2024) Shugg, Tyler; Tillman, Emma M.; Breman, Amy M.; Hodge, Jennelle C.; McDonald, Christine A.; Ly, Reynold C.; Rowe, Elizabeth J.; Osei, Wilberforce; Smith, Tayler B.; Schwartz, Peter H.; Callaghan, John T.; Pratt, Victoria M.; Lynch, Sheryl; Eadon, Michael T.; Skaar, Todd C.; Medicine, School of Medicine
    In 2019, Indiana University launched the Precision Health Initiative to enhance the institutional adoption of precision medicine, including pharmacogenetics (PGx) implementation, at university-affiliated practice sites across Indiana. The overarching goal of this PGx implementation program was to facilitate the sustainable adoption of genotype-guided prescribing into routine clinical care. To accomplish this goal, we pursued the following specific objectives: (i) to integrate PGx testing into existing healthcare system processes; (ii) to implement drug-gene pairs with high-level evidence and educate providers and pharmacists on established clinical management recommendations; (iii) to engage key stakeholders, including patients to optimize the return of results for PGx testing; (iv) to reduce health disparities through the targeted inclusion of underrepresented populations; (v) and to track third-party reimbursement. This tutorial details our multifaceted PGx implementation program, including descriptions of our interventions, the critical challenges faced, and the major program successes. By describing our experience, we aim to assist other clinical teams in achieving sustainable PGx implementation in their health systems.
  • Thumbnail Image
    Item
    Effect of Covered Metallic Stents Compared With Plastic Stents on Benign Biliary Stricture Resolution A Randomized Clinical Trial
    (JAMA, 2016-03) Coté, Gregory A.; Slivka, Adam; Tarnasky, Paul; Mullady, Daniel K.; Elmunzer, B. Joseph; Elta, Grace; Fogel, Evan; Lehman, Glen; McHenry, Lee; Romagnuolo, Joseph; Menon, Shyam; Siddiqui, Uzma D.; Watkins, James; Lynch, Sheryl; Denski, Cheryl; Xu, Huiping; Sherman, Stuart; Department of Biostatistics, Richard M. Fairbanks School of Public Health
    Importance Endoscopic placement of multiple plastic stents in parallel is the first-line treatment for most benign biliary strictures; it is possible that fully covered, self-expandable metallic stents (cSEMS) may require fewer endoscopic retrograde cholangiopancreatography procedures (ERCPs) to achieve resolution. Objective To assess whether use of cSEMS is noninferior to plastic stents with respect to stricture resolution. Design, Setting, and Participants Multicenter (8 endoscopic referral centers), open-label, parallel, randomized clinical trial involving patients with treatment-naive, benign biliary strictures (N = 112) due to orthotopic liver transplant (n = 73), chronic pancreatitis (n = 35), or postoperative injury (n = 4), who were enrolled between April 2011 and September 2014 (with follow-up ending October 2015). Patients with a bile duct diameter less than 6 mm and those with an intact gallbladder in whom the cystic duct would be overlapped by a cSEMS were excluded. Interventions Patients (N = 112) were randomized to receive multiple plastic stents or a single cSEMS, stratified by stricture etiology and with endoscopic reassessment for resolution every 3 months (plastic stents) or every 6 months (cSEMS). Patients were followed up for 12 months after stricture resolution to assess for recurrence. Main Outcomes and Measures Primary outcome was stricture resolution after no more than 12 months of endoscopic therapy. The sample size was estimated based on the noninferiority of cSEMS to plastic stents, with a noninferiority margin of −15%. Results There were 55 patients in the plastic stent group (mean [SD] age, 57 [11] years; 17 women [31%]) and 57 patients in the cSEMS group (mean [SD] age, 55 [10] years; 19 women [33%]). Compared with plastic stents (41/48, 85.4%), the cSEMS resolution rate was 50 of 54 patients (92.6%), with a rate difference of 7.2% (1-sided 95% CI, −3.0% to ∞; P < .001). Given the prespecified noninferiority margin of −15%, the null hypothesis that cSEMS is less effective than plastic stents was rejected. The mean number of ERCPs to achieve resolution was lower for cSEMS (2.14) vs plastic (3.24; mean difference, 1.10; 95% CI, 0.74 to 1.46; P < .001). Conclusions and Relevance Among patients with benign biliary strictures and a bile duct diameter 6 mm or more in whom the covered metallic stent would not overlap the cystic duct, cSEMS were not inferior to multiple plastic stents after 12 months in achieving stricture resolution. Metallic stents should be considered an appropriate option in patients such as these.
  • Thumbnail Image
    Item
    Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.
    (Wiley, 2022-07-28) Cavallari, Larisa H.; Cicali, Emily; Wiisanen, Kristin; Fillingim, Roger B.; Chakraborty, Hrishikesh; Myers, Rachel A.; Blake, Kathryn V.; Asiyanbola, Bolanle; Baye, Jordan F.; Bronson, Wesley H.; Cook, Kelsey J.; Elwood, Erica N.; Gray, Chancellor F.; Gong, Yan; Hines, Lindsay; Kannry, Joseph; Kucher, Natalie; Lynch, Sheryl; Nguyen, Khoa A.; Obeng, Aniwaa Owusu; Pratt, Victoria M.; Prieto, Hernan A.; Ramos, Michelle; Sadeghpour, Azita; Singh, Rajbir; Rosenman, Marc; Starostik, Petr; Thomas, Cameron D.; Tillman, Emma; Dexter, Paul R.; Horowitz, Carol R.; Orlando, Lori A.; Peterson, Josh F.; Skaar, Todd C.; Van Driest, Sara L.; Volpi, Simona; Voora, Deepak; Parvataneni, Hari K.; Johnson, Julie A.
    Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks.
  • Thumbnail Image
    Item
    Implementing a pragmatic clinical trial to tailor opioids for chronic pain on behalf of the IGNITE ADOPT PGx investigators
    (Wiley, 2024) Skaar, Todd C.; Myers, Rachel A.; Fillingim, Roger B.; Callaghan, John T.; Cicali, Emily; Eadon, Michael T.; Elwood, Erica N.; Ginsburg, Geoffrey S.; Lynch, Sheryl; Nguyen, Khoa A.; Obeng, Aniwaa Owusu; Park, Haesuk; Pratt, Victoria M.; Rosenman, Marc; Sadeghpour, Azita; Shuman, Saskia; Singh, Rajbir; Tillman, Emma M.; Volpi, Simona; Wiisanen, Kristin; Winterstein, Almut G.; Horowitz, Carol R.; Voora, Deepak; Orlando, Lori; Chakraborty, Hrishikesh; Van Driest, Sara; Peterson, Josh F.; Cavallari, Larisa A.; Johnson, Julie A.; Dexter, Paul R.; IGNITE Pragmatic Trials Network; Medicine, School of Medicine
    Chronic pain is a prevalent condition with enormous economic burden. Opioids such as tramadol, codeine, and hydrocodone are commonly used to treat chronic pain; these drugs are activated to more potent opioid receptor agonists by the hepatic CYP2D6 enzyme. Results from clinical studies and mechanistic understandings suggest that CYP2D6-guided therapy will improve pain control and reduce adverse drug events. However, CYP2D6 is rarely used in clinical practice due in part to the demand for additional clinical trial evidence. Thus, we designed the ADOPT-PGx (A Depression and Opioid Pragmatic Trial in Pharmacogenetics) chronic pain study, a multicenter, pragmatic, randomized controlled clinical trial, to assess the effect of CYP2D6 testing on pain management. The study enrolled 1048 participants who are taking or being considered for treatment with CYP2D6-impacted opioids for their chronic pain. Participants were randomized to receive immediate or delayed (by 6 months) genotyping of CYP2D6 with clinical decision support (CDS). CDS encouraged the providers to follow the CYP2D6-guided trial recommendations. The primary study outcome is the 3-month absolute change in the composite pain intensity score assessed using Patient-Reported Outcomes Measurement Information System (PROMIS) measures. Follow-up will be completed in July 2024. Herein, we describe the design of this trial along with challenges encountered during enrollment.