Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

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.

Design and rationale of GUARDD-US: A pragmatic, randomized trial of genetic testing for APOL1 and pharmacogenomic predictors of antihypertensive efficacy in patients with hypertension.

RATIONALE AND OBJECTIVE: APOL1 risk alleles are associated with increased cardiovascular and chronic kidney disease (CKD) risk. It is unknown whether knowledge of APOL1 risk status motivates patients and providers to attain recommended blood pressure (BP) targets to reduce cardiovascular disease. STUDY DESIGN: Multicenter, pragmatic, randomized controlled clinical trial. SETTING AND PARTICIPANTS: 6650 individuals with African ancestry and hypertension from 13 health systems. INTERVENTION: APOL1 genotyping with clinical decision support (CDS) results are returned to participants and providers immediately (intervention) or at 6 months (control). A subset of participants are re-randomized to pharmacogenomic testing for relevant antihypertensive medications (pharmacogenomic sub-study). CDS alerts encourage appropriate CKD screening and antihypertensive agent use. OUTCOMES: Blood pressure and surveys are assessed at baseline, 3 and 6 months. The primary outcome is change in systolic BP from enrollment to 3 months in individuals with two APOL1 risk alleles. Secondary outcomes include new diagnoses of CKD, systolic blood pressure at 6 months, diastolic BP, and survey results. The pharmacogenomic sub-study will evaluate the relationship of pharmacogenomic genotype and change in systolic BP between baseline and 3 months. RESULTS: To date, the trial has enrolled 3423 participants. CONCLUSIONS: The effect of patient and provider knowledge of APOL1 genotype on systolic blood pressure has not been well-studied. GUARDD-US addresses whether blood pressure improves when patients and providers have this information. GUARDD-US provides a CDS framework for primary care and specialty clinics to incorporate APOL1 genetic risk and pharmacogenomic prescribing in the electronic health record. TRIAL REGISTRATION: ClinicalTrials.govNCT04191824.

Effect of Covered Metallic Stents Compared With Plastic Stents on Benign Biliary Stricture Resolution: A Randomized Clinical Trial.

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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01221311.

Low ERCP Volume Is Associated with More Industry Representative Interactions but Similar Training of Nurses.

BACKGROUND: Data on ERCP nurses and associate (ERCP-NA) training and comfort are lacking. Healthcare industry representative (HCIR) influence may be greater in low-volume units (LVUs) due to decreased procedure and device familiarity. AIM: The aim of this study was to compare ERCP-NA training, safety, and HCIR relationships between LVU and high-volume unit (HVU) ERCP facilities. METHODS: We conducted an electronic survey of all Society of Gastroenterology Nurses and Associates (SGNA) members assessing: (1) demographics and procedure volume, (2) ERCP training and radiation safety, and (3) HCIR interactions. Responses were stratified by ERCP volume. RESULTS: Among 832 SGNA member respondents (median age 55), 615 (74%) worked as an ERCP-NA; 41% derived from LVUs. The majority of ERCP-NAs, irrespective of unit volume, had observed <50 ERCPs before starting. Except for lead glasses, the majority (>80%) adhered to basic radiation safety, irrespective of unit volume. LVUs were more likely than HVU ERCP-NAs to agree that HCIRs were requested for intra-procedure assistance (24 vs. 19%, p = 0.008), asked for input on the next choice of device (22 vs. 15%, p = 0.01), and assist in device usage (27 vs. 22%, p = 0.04). Irrespective of volume, 30% agreed that they were more likely to utilize a company's devices if that HCIR was present. CONCLUSIONS: ERCP-NA training before independent participation in ERCP is suboptimal. HCIRs are frequently requested for assistance during ERCPs, especially in LVUs. HCIR impact on ERCP outcomes and device utilization and whether enhanced ERCP-NA training will impact the role of HCIR, require further study.

Development and Validation of a Prediction Model for Admission After Endoscopic Retrograde Cholangiopancreatography.

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.

Prevalence and risk factors for musculoskeletal injuries related to endoscopy.

BACKGROUND: There are limited data regarding work-related injury among endoscopists. OBJECTIVE: To define the prevalence of endoscopy-related musculoskeletal injuries and their impact on clinical practice and to identify physician and practice characteristics associated with their development. DESIGN: Survey. SETTING: Electronic survey of active members of the American Society for Gastrointestinal Endoscopy with registered e-mail addresses. PARTICIPANTS: Physicians who currently or ever performed endoscopy and responded to the survey between February 2013 and November 2013. INTERVENTION: A 25-question, self-administered, electronic survey. MAIN OUTCOME MEASUREMENTS: Prevalence, location, and ramifications of work-related injuries and endoscopist characteristics and workload parameters associated with endoscopy-related injury. RESULTS: The survey was completed by 684 endoscopists. Of those, 362 (53%) experienced a musculoskeletal injury perceived definitely (n = 204) or possibly (n = 158) related to endoscopy. Factors associated with a higher rate of endoscopy-related injury included higher procedure volume (>20 cases/week; P < .001), greater number of hours per week spent performing endoscopy (>16 hours/week; P < .001), and total number of years performing endoscopy (P = .004). The most common sites of injury were neck and/or upper back (29%) and thumb (28%). Only 55% of injured endoscopists used practice modifications in response to injuries. Specific treatments included medications (57%), steroid injection (27%), physiotherapy (45%), rest (34%), splinting (23%), and surgery (13%). LIMITATIONS: Self-reported data of endoscopy-related injury. CONCLUSION: Among endoscopists there is a high prevalence of injuries definitely or potentially related to endoscopy. Higher procedure volume, more time doing endoscopy per week, and cumulative years performing endoscopy are associated with more work-related injuries.