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Irritable bowel syndrome is a common, oftentimes disabling, gastrointestinal disorder whose full range of symptoms has no satisfactory medical or dietary treatment. One of the few empirically validated treatments includes a specific psychological therapy called cognitive behavior therapy which, if available, is typically administered over several months by trained practitioners in tertiary care settings. There is an urgent need to develop more efficient versions of CBT that require minimal professional assistance but retain the efficacy profile of clinic based CBT. The Irritable Bowel Syndrome Outcome Study (IBSOS) is a multicenter, placebo-controlled randomized trial to evaluate whether a self-administered version of CBT is, at least as efficacious as standard CBT and more efficacious than an attention control in reducing core GI symptoms of IBS and its burden (e.g. distress, quality of life impairment, etc.) in moderately to severely affected IBS patients. Additional goals are to assess, at quarterly intervals, the durability of treatment response over a 12 month period; to identify clinically useful patient characteristics associated with outcome as a way of gaining an understanding of subgroups of participants for whom CBT is most beneficial; to identify theory-based change mechanisms (active ingredients) that explain how and why CBT works; and evaluate the economic costs and benefits of CBT. Between August 2010 when IBSOS began recruiting subjects and February 2012, the IBSOS randomized 171 of 480 patients. Findings have the potential to improve the health of IBS patients, reduce its social and economic costs, conserve scarce health care resources, and inform evidence-based practice guidelines.

BACKGROUND Reduced atazanavir exposure has been demonstrated during pregnancy with standard atazanavir/ritonavir dosing. We studied an increased dose during the third trimester of pregnancy. METHODS International Maternal Pediatric Adolescent AIDS Clinical Trials Group 1026s is a prospective, nonblinded, pharmacokinetic study of HIV-infected pregnant women taking antiretrovirals for clinical indications, including 2 cohorts (with or without tenofovir) receiving atazanavir/ritonavir 300/100 mg once daily during the second trimester, 400/100 mg during the third trimester, and 300/100 mg postpartum (PP). Intensive steady-state 24-hour pharmacokinetic profiles were performed. Atazanavir concentrations were measured by high-performance liquid chromatography. Pharmacokinetic targets were the 10th percentile atazanavir area under the concentration versus time curve (AUC) (29.4 μg·hr·mL·) in nonpregnant adults on standard dose and 0.15 μg/mL, minimum trough concentration. RESULTS Atazanavir pharmacokinetic data were available for 37 women without tenofovir, 35 with tenofovir; median (range) pharmacokinetic parameters are presented for second trimester, third trimester, and PP and number who met target/total. ATAZANAVIR WITHOUT TENOFOVIR: AUC 30.5 (9.19-93.8), 45.7 (11-88.3), and 48.8 (9.9-112.2) μg·hr·mL, and 8/14, 29/37, and 27/34 met target. C24 h was 0.49 (0.09-4.09), 0.71 (0.14-2.09), and 0.90 (0.05-2.73) μg/mL; 13/14, 36/37, and 29/34 met target. ATAZANAVIR WITH TENOFOVIR: AUC 26.2 (6.8-60.9) (P < 0.05 compared with PP), 37.7 (0.72-88.2) (P < 0.05 compared with PP), and 58.6 (6-149) μg·hr·mL, and 7/17, 23/32, and 27/29 met target. C24 h was 0.44 (0.12-1.06) (P < 0.05 compared with PP), 0.57 (0.02-2.06) (P < 0.05 compared with PP), and 1.26 (0.09-5.43) μg/mL; 7/17, 23/32, and 27/29 met target. Atazanavir/ritonavir was well tolerated with no unanticipated adverse events. CONCLUSIONS Atazanavir/ritonavir increased to 400/100 mg provides adequate atazanavir exposure during the third trimester and should be considered during the second trimester.