Varices

The Clinformatics™ Data Mart captures administrative health claims across the United States for members of a large national managed care company affiliated with OptumInsight (Eden Prairie, MN). We examined claims from January 1, 2012 to June 30, 2015 among adults ages 18 to 64 to capture surgical procedures performed between 2013 and 2014 to account for the 12-month preoperative and 6-month postoperative study period. We included only individuals with continuous medical and prescription drug coverage to evaluate the complete health care experience. We excluded patients ages 18 and younger, as well as patients older than 64 years due to incomplete capture of Medicare Part D prescriptions claims data. The study was deemed exempt from review by the University of Michigan Institutional Review Board.
We selected 13 common elective surgical procedures, and categorized these into minor and major groups based on prior literature. Minor surgical procedures included varicose vein removal, laparoscopic cholecystectomy, laparoscopic appendectomy, hemorrhoidectomy, thyroidectomy, transurethral prostate surgeries, and parathyroidectomy. Major surgical procedures included ventral incisional hernia repair, colectomy, reflux surgery, bariatric surgery, and hysterectomy. We identified patients undergoing surgery using Current Procedural Terminology (CPT) or International Statistical Classification of Diseases and Related Health Problems (ICD9_ procedure codes (Supplemental Table 1).
We sought to determine new persistent opioid use after surgery, and included only patients who filled an opioid prescription fill either in the month prior to surgery or within two weeks after discharge. Comparable to previous studies of opioid naïve surgical populations,^{7 (link),8} patients who had filled one or more prescriptions for opioids 12 months to 31 days prior to their surgical procedure were excluded from the analysis (Figure 1). To account for prescriptions provided preoperatively for postoperative pain control, patients filling opioids in the 30 days prior to surgery were included, and prescriptions filled in this time was included as a covariate in the analyses. Lastly, we excluded patients who underwent additional surgical procedures during the study period using subsequent procedural codes for anesthesia in the 6-month postoperative period.
As a comparison cohort of patients who did not undergo surgery, we identified a random 10% sample patients ages 18 to 64 years of age who did not undergo surgery in the study period We included only patients in the nonoperative group who did not fill an opioid prescription during a 12 month period and did not have any codes for surgical procedures or anesthesia during this period. These patients were then given a random date of surgery. No patients had an opioid fill in the year prior to their fictitious surgery date nor did they have any anesthesia codes in the 6 months following their fictitious surgery date.

Chronic DILI is defined at 6 months after DILI onset as one of the following: (i) for subjects with normal or unknown baseline liver biochemistries, a serum AST, ALT, alkaline phosphatase, INR or total bilirubin that is persistently elevated on two separate occasions; (ii) for liver DILI subjects, a serum AST, ALT, alkaline phosphatase, INR or total bilirubin level that exceeds 1.25 times the baseline value on two separate occasions; (iii) any evidence of portal hypertension such as ascites on imaging, varices on upper endoscopy or clinical evidence of hepatic encephalopathy; (iv) any histological evidence of persistent liver injury at least 6 months after DILI onset; or (v) any radiological evidence of chronic liver disease such as ascites, hepatomegaly, nodular liver or intra-abdominal varices. Subjects with pre-existing chronic HBV or HCV infection, liver transplant recipients since the baseline visit and patients with cirrhosis or clinical evidence of portal hypertension before starting the suspect medication are excluded from the chronic DILI protocol.
Subjects with chronic DILI are seen at 12 and 24 months after the baseline visit wherein incremental medical history, medication use, laboratory and imaging studies and questionnaires are completed. A final written narrative is also generated by the site investigator summarizing the course of the DILI episode. For subjects who die during follow-up, a death narrative recording whether the death was attributable to a liver or non-liver related cause is generated by the site investigator for review by the causality committee.