BouSaba, Joelle

ABSTRACT Background Bile acid diarrhoea, a common cause of diarrhoea‐predominant irritable bowel syndrome, has a similar prevalence to coeliac disease and inflammatory bowel diseases. The mainstay of treatment is bile acid sequestrants (BAS). The effectiveness of using bile acid‐targeted therapies remains unclear. Aim To compare BAS with placebo for bile acid diarrhoea. Methods We conducted a systematic review and meta‐analysis of randomised controlled trials comparing BAS to placebo using a comprehensive search of databases from inception to 8/1/2023. Inclusion required unequivocal diagnosis using serum or faecal biochemical parameters, or 75 SeHCAT. Co‐primary endpoints were ≥ 30% improvement in bowel movement consistency and frequency averaged over 7 days. Adverse effects were also summarised. Results Database search resulted in 1152 citations; 1 additional study was added. Ultimately, 6 trials (5 parallel arm, 1 crossover) involving 182 participants evaluated the effectiveness of BAS over 1–8 weeks. Participants were between the third and seventh decades of life and mostly female. The risk of bias was low except in one parallel and one crossover trial. Meta‐analysis of parallel‐design trials of sequestrants only showed a clinically significant reduction in stool consistency and frequency with pooled relative risks of 1.50 (95% CI: 1.14–1.96) and 2.80 (95% CI: 1.68–4.67), respectively. There was no observable heterogeneity ( I 2 = 0%), and the certainty of evidence was moderate. There was no statistically significant difference in adverse effects. Conclusions This study quantifies the significant and rapid improvement in both stool consistency and frequency with BAS in patients with objective diagnosis of bile acid diarrhoea. Sequestrants also appear well tolerated.

Abstract Aim To identify patient factors, including gastrointestinal functions, that are predictive or associated with weight loss in response to once‐daily 3 mg liraglutide administered subcutaneously (SQ) or placebo in obesity. Methods One hundred and thirty‐six obese adults (87% female) were randomized in a placebo‐controlled, 16‐week trial of liraglutide, escalated to 3 mg administered SQ daily. Gastrointestinal functions were measured at baseline and 16 weeks: gastric emptying of solids (GET 1/2 ); fasting and postprandial gastric volumes; kcal ingested during ad libitum buffet meal and the nutrient drink test. GET 1/2 was also measured at 5 weeks. A multiple variable regression model examined variables associated with weight loss of more than 4 kg at 16 weeks. A parsimonious model using backward selection identified the final model. Results Weight loss of more than 4 kg at 16 weeks occurred in 71% of liraglutide‐ and 16% of placebo‐treated patients. In all participants combined, parameters univariately associated with a weight loss of more than 4 kg were GET 1/2 at 5 and 16 weeks, weight loss at 5 weeks and kcal intake during the buffet meal at 16 weeks. The final parsimonious model (area under the receiver operator characteristics [AUROC] curve = 0.832) identified that factors associated with more than 4‐kg weight loss were GET 1/2 at 5 weeks (OR = 2.505; 95% CI: 1.57‐3.997) per 50 minutes and kcal intake during ad libitum meal at 16 weeks (OR = 0.721; 95% CI: 0.602‐0.864) per 100 kcal. Among only the 60 liraglutide‐treated subjects, kcal intake at 16 weeks was associated with 4‐kg weight loss (AUROC = 0.757). Conclusions Slower GET 1/2 and weight loss at 5 weeks predicted a weight loss of more than 4 kg at 16 weeks in all participants. Among liraglutide‐treated adults, weight loss of more than 4 kg was associated with ad libitum meal kcal intake at 16 weeks.

Current selection of different treatments for patients with gastroparesis is empiric or based on trial and error, though pyloric distensibility and diameter may predict response to pyloric interventions. High-resolution antropyloroduodenal manometry (HR-ADM) can characterize a variety of postprandial antral contractile and pyloric motility dysfunctions in patients with suspected gastroparesis. HR-ADM shows promise to provide guidance for selection and individualization of treatments such as prokinetic agents or pyloric interventions for patients with gastroparesis based on documented pathophysiology.

Chronic noncancer pain (CNCP) affects up to 20% of adults and can interfere with activities of daily living. Up to 4% of adults in the United States receive chronic opioid therapy and up to 57% of patients on long-term opioids for CNCP report opioid-induced constipation (OIC). OIC is essentially constipation occurring after starting opioid treatment. While laxatives are traditionally the first-line therapy for OIC, 81% of patients taking daily laxatives and opioids still reported OIC and considered that it negatively affected their quality of life. Naldemedine is a peripherally acting µ-opioid receptor antagonists (PAMORA) approved for the treatment of OIC in patients with CNCP. This article reviews the mechanism of action, efficacy, and safety of naldemedine in CNCP patients. Naldemedine improves OIC in patients with CNCP by acting as an opioid receptor antagonist in the gastrointestinal tract. It does not interfere with the analgesic properties of opioids or cause withdrawal symptoms since these effects are centrally mediated, and naldemedine does not cross the blood brain barrier. Naldemedine showed significant and sustained improvement in frequency of bowel movements, quality of life, and constipation-related symptoms. It is generally well tolerated with a higher incidence of gastrointestinal adverse events of mild or moderate severity such as diarrhea, abdominal pain, or vomiting compared to placebo. While there are no randomized, controlled trials that compare head-to-head pharmacological therapies used for treatment of OIC, network meta-analysis shows that naldemedine has an overall good benefit-risk profile compared to the other approved medications.

AbstractPain relief remains a significant challenge in the management of irritable bowel syndrome (IBS): “Does anything really help relieve the pain in patients with IBS?”. Interventions aimed at pain relief in patients with IBS include diet, probiotics or antibiotics, antidepressants, antispasmodics, and drugs targeting specific gastrointestinal receptors such as opioid or histamine receptors. In the systematic review and meta‐analysis published in this journal, Lambarth et al. examined the literature on the role of oral and parenteral anti‐neuropathic agents in the management of pain in patients with IBS. This review article appraises their assessment of the efficacy of the anti‐neuropathic agents amitriptyline, pregabalin, gabapentin, and duloxetine in the relief of abdominal pain or discomfort, and impact on overall IBS severity and quality of life. This commentary provides an update of current evidence on the efficacy of the dietary and pharmacological treatments that are available or in development, as well psychological and cognitive behavioral therapy for pain in IBS. Advances in recent years augur well for efficacious treatments that may expand the therapeutic arsenal for pain in IBS.