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To compare the effects of the κ-opioid agonist asimadoline and placebo on visceral sensation and gastrointestinal (GI) motor functions in humans, 91 healthy participants were randomized in a double-blind fashion to 0.15, 0.5, or 1.5 mg of asimadoline or placebo orally twice a day for 9 days. We assessed satiation (nutrient drink test), colonic compliance, tone, perception of colonic distension (barostat), and whole gut transit (scintigraphy). Treatment effect was assessed by analysis of covariance. Asimadoline increased nutrient drink intake ( P = 0.03). Asimadoline decreased colonic tone during fasting ( P = 0.03) without affecting postprandial colonic contraction, compliance, or transit. Gas scores in response to colonic distension were decreased with 0.5 mg of asimadoline at low levels (8 mmHg above operating pressure) of distension ( P = 0.04) but not at higher levels of distension. Asimadoline at 1.5 mg increased gas scores at 16 mmHg of distension ( P = 0.03) and pain scores at distensions of 8 and 16 mmHg ( P = 0.003 and 0.03, respectively) but not at higher levels of distension. Further studies of this compound in diseases with altered satiation or visceral sensation are warranted.

This study evaluated the effects of serotonergic psychoactive agents on gastrointestinal functions in healthy human subjects. Participants received one of four regimens in a randomized, double-blind manner: buspirone, a 5-HT 1A receptor agonist (10 mg twice daily); paroxetine, a selective serotonin reuptake inhibitor (20 mg daily); venlafaxine-XR, a selective serotonin and norepinephrine reuptake inhibitor (75 mg daily); or placebo for 11 days. Physiological testing performed on days 8–11included scintigraphic assessment of gastrointestinal and colonic transit, the nutrient drink test, and assessment of the postprandial change in gastric volume. Fifty-one healthy adults (40 females, 11 males) participated in this study. No effects on gastric emptying or colonic transit were identified with any agent. Small bowel transit of a solid meal was accelerated by paroxetine. Buspirone decreased postprandial aggregate symptom and nausea scores. Venlafaxine-XR increased the postprandial change in gastric volume. Buspirone, paroxetine, and venlafaxine-XR affect upper gastrointestinal functions in healthy humans. These data support the need for clinical and physiological studies of these agents in functional gastrointestinal disorders.

To determine if enteral delivery of glucose influences splanchnic glucose metabolism, 10 subjects were studied when glucose was either infused into the duodenum at a rate of 22 μmol · kg −1 · min −1 and supplemental glucose given intravenously or when all glucose was infused intravenously while saline was infused intraduodenally. Hormone secretion was inhibited with somatostatin, and glucose (∼8.5 mmol/l) and insulin (∼450 pmol/l) were maintained at constant but elevated levels. Intravenously infused [6,6- 2 H 2 ]glucose was used to trace the systemic appearance of intraduodenally infused [3- 3 H]glucose, whereas UDP-glucose flux (an index of hepatic glycogen synthesis) was measured using the acetaminophen glucuronide method. Despite differences in the route of glucose delivery, glucose production (3.5 ± 1.0 vs. 3.3 ± 1.0 μmol · kg −1 · min −1 ) and glucose disappearance (78.9 ± 5.7 vs. 85.0 ± 7.2 μmol · kg −1 · min −1 ) were comparable on intraduodenal and intravenous study days. Initial splanchnic glucose extraction (17.5 ± 4.4 vs. 14.5 ± 2.9%) and hepatic UDP-glucose flux (9.0 ± 2.0 vs. 10.3 ± 1.5 μmol · kg −1 · min −1 ) also did not differ on the intraduodenal and intravenous study days. These data argue against the existence of an “enteric” factor that directly (i.e., independently of circulating hormone concentrations) enhances splanchnic glucose uptake or hepatic glycogen synthesis in nondiabetic humans.

AbstractBackgroundOpioids are effective for acute and chronic pain conditions, but their use is associated with often difficult‐to‐manage constipation and other gastrointestinal (GI) effects due to effects on peripheral μ‐opioid receptors in the gut. The mechanism of opioid‐induced constipation (OIC) differs from that of functional constipation (FC), and OIC may not respond as well to most first‐line treatments for FC. The impact of OIC on quality of life (QoL) induces some patients to decrease or stop their opioid therapy to relieve or avoid constipation.PurposeAt a roundtable meeting on OIC, a working group developed a consensus definition for OIC diagnosis across disciplines and reviewed current OIC treatments and the potential of treatments in development. By consensus, OIC is defined as follows: ‘A change when initiating opioid therapy from baseline bowel habits that is characterized by any of the following: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency’. The working group noted the prior validation of a patient response outcome and end point for clinical trials and recommended future efforts to create treatment guidelines and QoL measures specific for OIC. Details from the working group's discussion and consensus recommendations for patient care and research are presented in this article.

Summary Background About one‐third of patients with IBS ‐diarrhoea (irritable bowel syndrome‐D) have evidence of increased bile acid synthesis or excretion. Aims To assess effects of the bile acid sequestrant, colesevelam, on faecal excretion of BA s, hepatic BA synthesis and diarrhoea in IBS ‐D; to appraise whether individual or random stool samples accurately reflect 48‐h total faecal bile acid excretion and proportions of the main bile acids excreted and to study the faecal fat excretion in response to colesevelam. Methods A single‐centre, unblinded, single‐dose trial of effects of colesevelam, 1875 mg [3 tablets (625 mg tablets)] orally, twice daily, for 10 days on total 48‐h faecal bile acid excretion and fasting serum C4 (7α‐hydroxy‐4‐cholesten‐3‐one; surrogate of hepatic bile acid synthesis). Stool diaries documented bowel functions for 8 days prior and 8 days during colesevelam treatment. Stool 48‐h samples and fasting serum were collected for faecal fat, faecal bile acid and serum C4. Results Colesevelam was associated with significantly increased faecal total bile acid excretion and deoxycholic acid excretion, increased serum C4 and more solid stool consistency. There was a significant inverse correlation between number of bowel movements per week and the total bile acid sequestered into stool during the last 48 h of treatment. Random stool samples did not accurately reflect 48‐h total or individual faecal bile acid excretion. Sequestration of bile acids by colesevelam did not increase faecal fat. Conclusions Colesevelam increases delivery of bile acids to stool while improving stool consistency, and increases hepatic bile acid synthesis, avoiding steatorrhoea in patients with IBS ‐D. Overall effects are consistent with luminal bile acid sequestration by colesevelam.

AbstractBackgroundPrucalopride is a high‐affinity 5‐HT4 receptor agonist for the treatment of chronic constipation. The aims of this study were to investigate the relationship between health‐related quality of life (HRQoL) and symptoms of constipation, and to assess the response of HRQoL to treatment using integrated data from three phase III trials of prucalopride.MethodsThis was an integrated analysis of data from three pivotal multicenter, double‐blind, randomized, placebo‐controlled, parallel‐group trials (ClinicalTrials.gov Identifiers: NCT00488137, NCT00483886 and NCT00485940). Relationships were investigated between Patient Assessment of Constipation Quality of Life (PAC‐QOL) scores, Patient Assessment of Constipation Symptoms (PAC‐SYM) scores, bowel movement frequency (assessed using daily diaries), and treatment.Key ResultsPatients treated with prucalopride 2 mg (n = 659) and placebo (n = 661) were included in the analysis. An improvement in PAC‐SYM scores correlated well with an improvement in PAC‐QOL overall score (r = 0.711) and satisfaction subscale score (r = 0.589). After 12 weeks, PAC‐QOL overall score and satisfaction subscale score significantly (p < 0.001) improved by ≥1 point (clinically relevant) in 36.5% and 44.1% of patients treated with prucalopride, compared with 18.5% and 22.4% with placebo respectively. Moreover, 39.0% of patients with an improvement in satisfaction of ≥1 point achieved ≥3 spontaneous complete bowel movements/week, compared with 7.4% of those with no improvement in satisfaction (<1 point).Conclusions & InferencesImprovements in PAC‐QOL overall score and satisfaction score were associated with improvements in symptoms of chronic constipation. Compared with placebo, treatment with prucalopride significantly improved HRQoL.

AbstractBackgroundSynthetic ghrelin agonists, predominantly small molecules, are being developed as prokinetic agents that may prove useful in the treatment of gastrointestinal motility disorders. Relamorelin (RM‐131) is a pentapeptide synthetic ghrelin analog that activates the growth hormone secretagogue (GHS)‐1a (also called the ghrelin) receptor with approximately sixfold greater potency than natural ghrelin. The ability of relamorelin to stimulate growth hormone (GH) release is comparable to that of native ghrelin. Relamorelin has enhanced efficacy and plasma stability compared to native ghrelin.PurposeIn this review, we discuss the pharmacokinetics, pharmacodynamics and potential indications for relamorelin. Relamorelin is administered subcutaneously, dosed daily or twice daily. Relamorelin is being studied for the treatment of patients with gastrointestinal motility disorders. Phase IIA pharmacodynamic studies have demonstrated acceleration of gastric emptying in patients with type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) and upper gastrointestinal symptoms. In a phase IIA study in patients with diabetic gastroparesis, relamorelin accelerated gastric emptying and significantly improved vomiting frequency compared to placebo and improved other symptoms of gastroparesis in a prespecified subgroup of patients with vomiting at baseline. In patients with chronic idiopathic constipation with defined transit profile at baseline, relamorelin relieved constipation and accelerated colonic transit compared to placebo. These characteristics suggest that this new ghrelin analog shows great promise to relieve patients with upper or lower gastrointestinal motility disorders.

AbstractBackgroundIntensive treatment options are lacking for patients with severe skin disease recalcitrant to outpatient therapy. The availability of inpatient dermatology care has almost disappeared in many parts of the United States. One possible solution for this is a day treatment center for patients with severe dermatologic disease recalcitrant to outpatient therapy.MethodsDescriptive study based on retrospective medical record review of all patients attending the day hospital for treatment in 2010. We collected data on patient demographics, distribution of admission diagnosis, treatments used, and length of stay.ResultsA total of 211 patients had 235 admissions. Mean age was 57.7 years (range 3.8–92.1 years). The most common indications for admission were dermatitis (139 admissions [59.2%]), psoriasis (58 [24.7%]), and mycosis fungoides (eight [3.4%]). The main treatment interventions were wet dressings (195 admissions [83.0%]) and Goeckerman treatment (38 [16.2%]). The median number of days of treatment was three (interquartile range, 2–5 days) for wet dressings and 22 days (interquartile range, 21–24 days) for Goeckerman therapy.ConclusionsThe dermatology day treatment center provided intensive skin‐directed therapy and filled a critical practice gap in the management of our patients with severe widespread skin diseases recalcitrant to outpatient therapy. We propose that the dermatology day treatment center is a valuable model that could be considered by both private practitioners and academic centers in the United States as an important adjunct to fill the gap in availability of intensive topical treatments for patients with severe skin disease.

AbstractBackgroundDermatology consultations are frequently requested by inpatient hospital services. As inpatient dermatology services in the USA decline, dermatology hospital consultations are becoming increasingly important.ObjectivesWe aim to describe the spectrum of skin diseases encountered and the health care subspecialties requesting dermatology hospital consultations.MethodsWe performed a retrospective chart review of adult patient (age: ≥18 years) dermatology hospital consultations from January 1 to December 31, 2010. We examined patient demographic characteristics, consultation requesting services, and consultation diagnoses.ResultsAmong dermatology services, 614 patients had 674 separate inpatient dermatology consultations during 2010. Of these patients, 55.9% were male (mean age: 59 years). In total, 205 consultations (30.4%) were requested by the internal medicine subspecialty, 137 (20.3%) by the hematology and oncology subspecialty, and 93 (13.8%) by the surgical subspecialty. The most common conditions seen by the hospital dermatology consulting service were skin infections (n = 125, 18.5%), dermatitis (n = 120, 17.8%), drug eruptions (n = 87, 12.9%), chronic wounds and ulcers (n = 55, 8.1%), cutaneous neoplasms (n = 39, 5.8%), graft‐versus‐host disease (n = 37, 5.5%), ecchymosis, purpura simplex or petechia (n = 26, 3.8%), intertrigo (n = 21, 3.1%), and urticaria (n = 20, 3.0%).ConclusionsThe majority of consultations conducted by the dermatology hospital consulting service were for the management of common skin diseases, such as cutaneous infections, dermatitis, and drug eruptions. Most consultations were requested by the departments of internal medicine, hematology and oncology, and surgical services.