Randomised clinical trial: pregabalin vs placebo for irritable bowel syndrome.

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.

Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time-using genomic data to individualize treatment protocol.

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 into the electronic medical record (EMR). PATIENTS AND METHODS: We used a multivariate 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 the Mayo Clinic Biobank participants, with a recruitment goal of 1000 patients. We used a Cox proportional hazards model with 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 International Classification of Diseases, Ninth Revision 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, 1013 (51%) provided blood samples, 256 (13%) declined participation, 555 (28%) did not respond, and 176 (9%) consented but did not provide a blood sample within the recruitment window (October 4, 2012, through March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS was integrated into the EMR and flagged potential patient-specific drug-gene interactions and provided therapeutic guidance. CONCLUSION: This translational project provides an opportunity to begin to evaluate the impact of preemptive sequencing and EMR-driven genome-guided therapy. These interventions will improve understanding and implementation of genomic data in clinical practice.

Intraprocedural evaluation of comfort for sedated outpatient upper endoscopy and colonoscopy: the La Crosse (WI) intra-endoscopy sedation comfort score.

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.