Objective To report the design and implementation of the Right Drug, Right Dose, Right Time: Using Genomic Data to Individualize Treatment Protocol that was developed to test the concept that prescribers can deliver genome guided therapy at the point-of-care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated in the electronic medical record (EMR). Patients and Methods We used a multivariable prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among Mayo Clinic Biobank participants with a recruitment goal of 1000 patients. Cox proportional hazards model was utilized using the variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR. Results The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for ICD-9 codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 50% provided blood samples, 13% refused, 28% did not respond, and 9% consented but did not provide a blood sample within the recruitment window (October 4, 2012 – March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS is integrated in the EMR and flags potential patient-specific drug-gene interactions and provides therapeutic guidance. Conclusion These interventions will improve understanding and implementation of genomic data in clinical practice.

AMAs are detectable by indirect immunofluorescence (IF)We examined the clinical usefulness of measurements on tissue substrates in 93% to 99% of patients with PBC, but of antimitochondrial autoantibodies (AMA) in prethis method also detects AMAs of differing specificities in dicting disease progression in patients with primary bilother diseases. The mitochondrial antigens recognized by iary cirrhosis (PBC). We determined the relationships AMAs in patients' sera have been classified numerically as between AMA levels measured by indirect immunofluo-M1 through M9, with the M2 antigen complex recognized by rescence (IF) and those measured by quantitative enAMAs in sera from 95% to 99% of PBC patients. M2 antigen is zyme immunoassays (EIAs) using recombinant 2-oxocomposed of enzyme proteins of the 2-oxo-acid dehydrogenase acid dehydrogenase complex (2-OADC) proteins and the complex (2-OADC) family that are located on inner mitochonMayo Risk Score, an established indicator of disease prodrial membranes. Included in this group of autoantigens are gression in primary biliary cirrhosis (PBC). Results of tests for AMA by either method correlated weakly (r Å pyruvate dehydrogenase complex (PDC), branched-chain 2-.24 to .30) with disease progression as indicated by Mayo oxo-acid dehydrogenase complex (BCOADC), and 2-oxo-gluRisk Scores. The levels of AMA to 2-OADC proteins var-tarate dehydrogenase complex (OGDC). The 2-OADC enied by more than 200-fold between patients but re-zymes are complex multimers composed of E1, E2, and E3 mained relatively constant over time in individual pa-subunits; the E2 subunits contribute immunodominant epitients. Despite being positively correlated with Mayo topes recognized by anti-M2 autoantibodies. 3 ImmunoreacRisk Score results, the levels of AMA to 2-OADC proteins tive epitopes of the E2 subunits of 2-OADC enzymes have were not useful for predicting disease progression in been cloned, and enzyme immunoassays (EIAs) that use reindividual patients with PBC. In addition, we found no combinant PDC-E2 and BCOADC-E2 proteins as capture ansignificant differences in the levels of autoantibodies to tigens detect autoantibodies in sera from more than 95% of 2-OADC proteins among patients with different histolog-patients with PBC. 4 Approximately 10% of sera from PBC ical stages of disease. Our results show that measure-patients contain autoantibodies to BCOADC-E2 but not PDCments of AMA by IF or by quantitative EIA methods with E2. Recently, Leung et al. 5 constructed a recombinant hybrid recombinant 2-OADC proteins are not useful parameters molecule that contains the immunodominant epitopes of both for predicting disease progression in patients with PBC. PDC-E2 and BCOADC-E2, and this hybrid molecule is recog-(HEPATOLOGY 1997;25:6-11.)nized by AMAs specific for either antigen. No study to date has reported on the levels of AMA to 2-OADC enzyme proteins in sera from a large number of PBC Primary biliary cirrhosis (PBC) is a progressive liver dispatients who have been followed up longitudinally throu...

Summary Background Pregabalin is a calcium channel α2δ ligand that modifies visceral hypersensitivity in IBS patients. Clinical data for pregabalin in IBS are lacking. Aim To test the efficacy of pregabalin on gastrointestinal symptoms in IBS patients. Methods A double‐blind, placebo‐controlled trial was performed. Adults meeting IBS Rome III criteria with ≥3 pain attacks per month were randomised to pregabalin 225 mg vs placebo twice daily for 12 weeks. Questionnaires were completed weekly. The primary endpoint was average pain Bowel Symptom Scale (BSS) scores weeks 9‐12. An intention‐to‐treat analysis of covariance evaluated treatment effects on quantitative endpoints, adjusting for age and gender. Adequate relief and change in pain score were assessed using a chi‐squared test. Results Eighty‐five patients were recruited and randomised. Sample characteristics include: mean age 39.4 (SD = 14.6); 73 (86%) female; 37 (44%) IBS‐D, 29 (35%) IBS‐M, 18 (21%) IBS‐C. The pregabalin arm had lower average pain‐BSS scores weeks 9‐12 (25 vs 42, P = 0.008). Compared with placebo, the overall IBS BSS severity score was lower in the pregabalin arm (26 vs 42, P = 0.009). Differences were observed for the diarrhoea‐BSS and bloating‐BSS scores (P = 0.049 and 0.016, respectively). No differences between groups were seen for constipation‐BSS scores. Adequate relief was not different between the two arms (46% vs 36%, P = 0.35). 63% pregabalin vs 45% placebo had a change in pain score ≥30 at week 12 from baseline (P = 0.10). Post‐treatment IBS‐QoL scores did not differ between groups. Conclusion This trial suggests that pregabalin may be beneficial for IBS abdominal pain, bloating and diarrhoea.

Patient comfort is often assessed during gastrointestinal procedures to guide sedation. There are, however, no validated scales appropriate for routine comfort assessment. This study validated a single-item La Crosse (WI) intra-endoscopy sedation comfort score (L-WISC) by determining interobserver agreement and correlation with patient outcomes. The study was conducted in prospective outpatient cohorts of patients undergoing outpatient esophagogastroduodenoscopy and/or colonoscopy at a regional healthcare medical center endoscopy unit. In Phase 1, independent assessments of 100 patients' intraprocedural comfort by the endoscopist and nurse determined interobserver agreement. In Phase 2, nurses assessed 200 patients, who were provided surveys to self-report their comfort 2 weeks postprocedure. In Phase 1, there was fair interobserver agreement (weighted κ = 0.36, with 95% confidence intervals [CI] [0.19, 0.53]). After L-WISC revisions, Phase 1 was repeated with moderate agreement (weighted κ = 0.45; 95% CI [0.31, 0.60]). In Phase 2, using the revised score, there was poor agreement (weighted κ = 0.098; 95% CI [-0.0020, 0.20]) between nurses' and patients' scores. The L-WISC is the first intraprocedural gastrointestinal comfort score appropriate for routine use to be validated with interobserver agreement and correlation with patient outcomes. It has reproducibility between endoscopists and nurses. It does not predict patient recollection of sedation comfort, but it remains unclear whether such prediction is possible with the use of amnestic sedatives. The L-WISC provides standardized levels of patient comfort to guide sedation titration routinely during outpatient endoscopy.