Background & Aims Weight loss following pharmacotherapy varies greatly. We aimed to examine associations of quantitative gastrointestinal and psychological traits with obesity, and to validate the ability of these traits to predict responses of obese individuals to pharmacotherapy. Methods In a prospective study, we measured gastric emptying (GE) of solids and liquids, fasting and postprandial gastric volume, satiation by nutrient drink test (volume to fullness and maximal tolerated volume), satiety following an ad-libitum buffet meal, gastrointestinal hormones, and psychological traits in 328 normal weight, overweight, or obese adults. We also analyzed data from 181 previously studied adults to assess associations between a subset of traits with body mass index and waist circumference. Latent dimensions associated with overweight or obesity were appraised by principal component analyses. We performed a proof-of-concept, placebo-controlled trial of extended-release phentermine and topiramate in 24 patients, to validate associations between quantitative traits and response to weight-loss therapy. Results In the prospective study, obesity was associated with fasting gastric volume (P=.03), accelerated GE (P<.001 for solids and P=.011 for liquids), lower postprandial levels of peptide tyrosine tyrosine (P=.003), and higher postprandial levels of glucagon-like peptide 1 (P<.001). In a combined analysis of data from all studies, obesity was associated with higher volume to fullness (n=509; P=.038) and satiety with abnormal waist circumference (n=271; P=.016). Principal component analysis identified latent dimensions that accounted for ∼81% of the variation among overweight and obese subjects, including satiety or satiation (21%), gastric motility (14%), psychological factors (13%), and gastric sensorimotor factors (11%). The combination of phentermine and topiramate caused significant weight loss, slowed GE, and decreased calorie intake; weight loss in response to phentermine and topiramate was significantly associated with calorie intake at the prior satiety test. Conclusion Quantitative traits are associated with high body mass index; they can distinguish obesity phenotypes and, in a proof-of-concept clinical trial, predicted response to pharmacotherapy for obesity.

Background Gastric emptying (GE) is measured in pharmacodynamic and diagnostic studies. Aims To assess inter- and intra-subject coefficients of variation (COV) of scintigraphic GE measurements in healthy subjects, and associations of GE with gender and BMI. Methods Data from participants with scintigraphic measurements of gastric emptying of solids were analyzed. Primary endpoints were gastric emptying T1/2 (GE T1/2) and GE at 1, 2, 3 and 4 hours. Results The patient cohort consisted of 105 males and 214 females; at least 2 studies were performed in 47 subjects [16 males (M), 32 females (F)]. Inter-subject COV (COVinter) for GE T1/2 were similar in M and F: overall 24.5% (M 26.0%, F 22.5%); COV are predictably lowest for GE at 4h (COVinter 9.6%). COVintra for T1/2 and GE4h were overall 23.8% and 12.6%, and were similar to COVinter values. Gender (but not age or body mass index [BMI]) was significantly associated with GE T1/2 [p<0.001, F 127.6 ± 28.7 (SD) min; M 109.9 ± 28.6 min] and with GE at 1h and 2h. Repeat GE T1/2 values in 47 participants were significantly correlated (r= 0.459, p<0.001) with median difference of −6 min (mean −1.6, range −56 to 72 min). Bland-Altman plots showed Δ GE T1/2 similarly distributed across mean GE T1/2 100–155 minutes, and across studies conducted 90 to 600 days apart. Conclusion Inter-subject variations in scintigraphic GE results are only slightly higher than the intra-subject measurements, which are also reproducible over time in healthy volunteers. Gender, but not BMI, is significantly associated with GE results.

Objective-To differentiate dys-synergic defaecation (DD) from normal function and slow transit constipation (STC).Methods-The medical records of 1411 patients evaluated by a single gastroenterologist over a 16-year period at a tertiary medical centre were reviewed. DD was characterised by anorectal manometry and balloon expulsion test. There were 390 patients with DD, and 61 with STC without DD. Transit data from 211 healthy individuals served as controls. The primary endpoints were overall colonic transit (geometric centre) at 24 h and 48 h (GC24 and GC48). Regional transit was measured as ascending colon half-emptying time (AC t 1/2 ) and residual content in descending rectosigmoid colon and stool (DRS).Results-Age and body mass index were similar in the STC and DD groups. DD was associated with smaller perineal descent and a greater difference in rectoanal pressure than STC. Both STC and DD were associated with lower GC24 and GC48 and slower AC t 1/2 than controls. GC48 differentiated DD from healthy controls (p<0.001) and DD from STC (p=0.007). AC t 1/2 values differentiated healthy controls from DD (p=0.006) and STC (p<0.001) and were associated with constipation (DD vs STC, p=0.007). The regional content of DRS at 48 h discriminated DD from STC (AUC=0.82) and stool content at 48 h, increasing the odds for DD over STC (OR per 5% in stool 2.4, 95% CI 1.1 to 5.5, p=0.03). Competing interests None. Ethics approval Ethics approval was provided by Mayo Clinic Institutional Review Board.Contributors SN analysed the patient records and wrote the manuscript. TN analysed the patient records and critically reviewed the paper. MC was the sole clinician who managed the patients, developed the study protocol, identified aims and hypotheses, helped in interpreting the statistical analysis and wrote and finalised the manuscript. DB assisted in analysing patient records, calculated the transit times, critically reviewed the paper and participated with MC in the clinical appraisal and management of the patients. JI constructed the different databases, aided in selecting suitable patients and critically reviewed the paper. MV-R constructed the different databases, aided in correctly selecting patients and critically reviewed the paper. ARZ performed the statistical analysis and critically reviewed the paper.

It is commonly believed that blinding to treatment assignment is necessary for placebos to have an effect. However, placebos administered without concealment (ie, open-label placebos [OLPs]) have recently been shown to be effective in some conditions. This study had 2 objectives: first, to determine whether OLP treatment is superior to no-pill control (NPC) in irritable bowel syndrome (IBS) and, second, to compare the efficacy of OLP against double-blind placebo (DBP). In a 6-week, 3-arm, randomized clinical trial, participants were randomized in equal proportions to 3 arms: OLP, DBP, or NPC. Two hundred sixty-two adults (72.9% women), with a mean age of 42.0 (SD = 18.1) years, participated in the primary study. The mean improvement on the IBS Severity Scoring System from baseline to the 6-week end point was significantly greater in OLP compared with that in NPC (90.6 vs 52.3, P = 0.038). Open-label placebo and DBP did not differ significantly on IBS Severity Scoring System improvement (100.3 vs 90.6, P = 0.485). Standardized effect sizes were moderate for OLP vs NPC (d = 0.43) and small for OLP vs DBP (d = 0.10). Participants treated with OLP reported clinically meaningful improvements in IBS symptoms that were significantly greater than those on NPC. Open-label placebo and DBP had similar effects that did not differ significantly, suggesting that blinding may not be necessary for placebos to be effective and that OLP could play a role in the management of patients with refractory IBS.