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Background: Prokinetics are a class of pharmacological drugs designed to improve gastrointestinal (GI) motility, either regionally or across the whole gut. Each drug has its merits and drawbacks, and based on current evidence as high‐quality studies are limited, we have no clear recommendation on one class or other. However, there remains a large unmet need for both regionally selective and/or globally acting prokinetic drugs that work primarily intraluminally and are safe and without systemic side effects. Purpose: Here, we describe the strengths and weaknesses of six classes of prokinetic drugs, including their pharmacokinetic properties, efficacy, safety and tolerability and potential indications. [ABSTRACT FROM AUTHOR]

Background and Aims: The role of preoperative pharmacological prophylaxis in preventing aspiration pneumonitis under general anesthesia (GA) in patients at low risk of aspiration pneumonitis is still under debate. We addressed the need for routine pharmacological aspiration prophylaxis in at-risk population by assessing the change in gastric volume using ultrasound with and without pharmacological acid aspiration prophylaxis. Material and Methods: A single-center, randomized double-blinded trial, with 200 adult patients scheduled for elective surgical procedures under GA, were randomized into a prophylaxis group, in which the patients received oral famotidine and metoclopramide, and a no prophylaxis group, in which the patients did not receive any prophylaxis. Gastric volume derived from preinduction measurement of gastric antral volume by ultrasound, postinduction gastric pH, and incidences of aspiration pneumonitis were compared. Bland-Altman plot was used to determine the level of agreement between measured gastric volume and ultrasonography based on calculated gastric volume. Results: The gastric antral cross-sectional area (CSA) and volume in the no prophylaxis group (3.12 cm2 and 20.11 ml, respectively) were comparable to the prophylaxis group (2.56 cm2 and 19.67 ml, respectively) (P-values 0.97 and 0.63, respectively). Although there was a statistically significant decrease in gastric pH in the no prophylaxis group (P-value 0.01), it was not clinically significant to increase the risk of aspiration pneumonitis based on Roberts and Shirley criteria (P-value 0.39). Conclusion: In an adequately fasted low-risk population, the amount of residual gastric volume was similar and below the aspiration threshold, regardless of the aspiration prophylaxis status. [ABSTRACT FROM AUTHOR]

L'atteinte digestive au cours de la sclérodermie systémique peut être sévère et occasionner une véritable pseudo-obstruction intestinale chronique, secondaire à des troubles profonds de la motilité de l'intestin grêle. Elle est associée à certaines caractéristiques cliniques et biologiques, notamment la positivité des anticorps anti fibrillarine/U3RNP. La pseudo-obstruction intestinale chronique se complique d'une pullulation microbienne qui nécessite une antibiothérapie cyclique. Elle entraîne nécessairement une réduction du bol alimentaire compte-tenu des symptômes douloureux, nausées et vomissements engendrés par les repas et, in fine , une dénutrition sévère. La stratégie de fractionnement des repas n'est souvent que transitoirement efficace et les patients nécessitent un authentique support nutritionnel, principalement par voie parentérale. La sclérodermie systémique ne constitue pas un frein à l'initiation et la poursuite de ce traitement dans le temps. Les dispositifs veineux implantables ne s'accompagnent pas d'un surrisque de complications locales ou infectieuses. La poursuite d'une nutrition parentérale au long cours nécessite toutefois un suivi conjoint dans un centre expert en nutrition, afin d'adapter les volumes et apports nutritifs et d'en limiter les complications cardiaques et hépatobiliaires potentiellement mortelles. À la nutrition s'associent des traitements prokinétiques dont les effets secondaires – notamment antagonistes sur la motilité digestive – doivent être connus, ainsi que des procédures invasives dont la balance bénéfice-risque doit être évaluée avec précaution. Gastrointestinal involvement in systemic sclerosis can be severe, reaching the critical point of chronic intestinal pseudo-obstruction, secondary to major disorders of small bowel motility. It is associated with some clinical and biological characteristics, in particular the positivity of anti-fibrillarin/U3RNP antibodies. Chronic intestinal pseudo-obstruction (CIPO) is complicated by a small intestinal bacterial overgrowth that requires cyclic antibiotic therapy. CIPO leads to a reduction of the food intake, due to painful symptoms, nausea and vomiting caused by meals, and ultimately to severe malnutrition. Meal splitting is often transiently effective and patients require exogenous nutritional support, mostly parenteral. Systemic sclerosis is not an obstacle to initiation and long-term continuation of parenteral nutrition and central venous catheter implantation is not associated with an increased risk of cutaneous or infectious complications. However, continuation of long-term parenteral nutrition requires monitoring in an expert nutrition center in order to adapt nutritional volumes and intakes and to limit potentially fatal cardiac and hepatobiliary complications. In addition to nutrition, prokinetic treatments, whose side effects must be known, can be associated. Invasive procedures, whose risk-benefit ratio must be carefully assessed, can also be used to treat symptoms exclusively. [ABSTRACT FROM AUTHOR]

Background/Aims Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment. Methods Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life. Results One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline. Conclusion Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia. [ABSTRACT FROM AUTHOR]

Abstract Background Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD. Methods An updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software. Results A total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70–7.47), domperidone (OR: 2.29, 95%CI: 1.16–4.63), itopride(OR: 2.77, 95%CI: 1.41–5.59), acotiamide(OR: 2.63, OR: 1.33–5.36), and placebo(OR: 5.68, 95%CI: 2.98–11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75–3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16–4.14) and placebo (OR: 3.52, 95%CI: 2.01–6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics. Conclusions Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.

Background: Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD. Methods: An updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software. Results: A total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70–7.47), domperidone (OR: 2.29, 95%CI: 1.16–4.63), itopride(OR: 2.77, 95%CI: 1.41–5.59), acotiamide(OR: 2.63, OR: 1.33–5.36), and placebo(OR: 5.68, 95%CI: 2.98–11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75–3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16–4.14) and placebo (OR: 3.52, 95%CI: 2.01–6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics. Conclusions: Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed. [ABSTRACT FROM AUTHOR]

Background. Proton pump inhibitors (PPIs) are currently the reference drugs for gastroesophageal reflux disease (GERD), but symptoms often recur after their withdrawal. Moreover, whether prokinetics or barrier drugs used alongside PPIs are more effective remains under debate. Objectives. The aim of the study was to assess the efficacy of different therapeutic approaches to GERD treatment. Materials and methods. We enrolled 211 grade A reflux esophagitis patients who consented to participate in this non-randomized, open-label trial. The study consisted of 6 sequentially administered medical treatments for GERD, lasting 2 months, with a 3-week washout period between each drug schedule: Group A: PPI (esomeprazole 40 mg/day before breakfast); Group B: mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, 3 times daily after a meal); Group C: prokinetics (levosulpiride 25 mg or domperidone 10 mg, 3 times daily before a meal); Group D: barrier drug (alginate 3 times daily after a meal); Group E: PPI (esomeprazole 40 mg/day before breakfast) and mucosal protective drugs (a combination of hyaluronic acid, chondroitin sulfate and poloxamer 407, or a combination of hyaluronic acid, chondroitin sulfate and aluminum, before sleep); Group F: PPI (esomeprazole 40 mg/day before breakfast) and prokinetics (levosulpiride 25 mg or domperidone 10 mg before lunch and dinner). Symptoms were evaluated using the visual analogue scale (VAS) and global symptomatic score (GSS), as follows: heartburn: 0-3; retrosternal chest pain: 0-3; regurgitation: 0-3. Results. All but 2 treatments (groups C and D) significantly improved VAS and GSS, with group E showing the most significant GSS improvement. Group C had the highest number of dropouts due to treatment failure and reported more side effects. Conclusions. Using PPIs and mucosal protective drugs resulted in significant symptom alleviation. However, the administration of prokinetics caused higher dropouts due to treatment failure. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate cardiac indices using M-mode echocardiography after the administration of metoclopramide and ondansetron in donkeys. For this purpose, 10 apparently healthy Egyptian Baladi donkeys (Equus asinus) were used in a crossover prospective study. Two trials were conducted with the administration of metoclopramide hydrochloride anhydrous at a dose of 0.25 mg Kg−1 and ondansetron hydrochloride sodium at a dose of 0.15 mg Kg−1. The control group (placebo) received a total volume of 50 mL of isotonic saline at 0.9%. An echocardiographic examination was performed using a Digital Color Doppler Ultrasound System equipped with a 2–3.9 MHz phased array sector scanner transducer. In general, the fractional shortening (FS%) was significantly affected by the time for metoclopramide (p = 0.031) and ondansetron (p = 0.047) compared with those of placebo, with treatment with metoclopramide provoking significantly higher percentages of FS% at T60 (p = 0.009) and T90 (p = 0.028) compared with those for ondansetron and placebo. The interaction of time x treatment also showed a statistically significant alteration of FS% (p

Gastroparesis is characterized by symptoms suggesting gastric retention of food and objective evidence of delayed gastric emptying in the absence of a mechanical obstruction. Nausea, vomiting, early satiety, and postprandial fullness are the classic symptoms of gastroparesis. Gastroparesis is increasingly encountered by physicians. There are several recognized etiologies of gastroparesis, including diabetic, post-surgical, medication-induced, post-viral, and idiopathic. A comprehensive literature review was conducted to identify studies discussing gastroparesis management. Dietary modifications, medication adjustments, glucose control, antiemetic agents, and prokinetic agents are all part of gastroparesis management. In this manuscript, we detail treatments evolving for gastroparesis, including nutritional, pharmaceutical, device, and recent advanced endoscopic and surgical therapies. This manuscript concludes with a speculative viewpoint on how the field will evolve in 5 years' time. Identification of the dominant symptoms (fullness, nausea, abdominal pain, and heartburn) helps to direct management efforts of the patients. Treatments for refractory (treatment resistant) symptoms may include gastric electric stimulation and intra-pyloric interventions like botulinum toxin and endoscopic pyloromyotomy. Understanding the pathophysiology of gastroparesis, relating pathophysiologic abnormalities to specific symptoms, new efficacious pharmacotherapies, and better understanding of the clinical predictors of response of therapies, are priorities for future research in the field of gastroparesis. [ABSTRACT FROM AUTHOR]

Clinical symptoms attributed to gastro-esophageal reflux disease (GERD) in healthy term infants are non-specific and overlap with age-appropriate behaviours. This practice point reviews the evidence for medically recommended management of this common condition. Current recommendations to manage GERD include feeding modifications such as thickening feeds or avoiding cow's milk protein. There is limited evidence for pharmacological management, including acid suppressive therapy or prokinetic agents, with the risks of such treatments often outweighing possible benefits due to significant safety and side effect concerns. Acid-suppressive therapy should not be routinely used for infants with GERD and is most likely to be useful in the context of symptoms that suggest erosive esophagitis. Evidence for managing symptoms attributed to GERD in otherwise healthy term infants less than 1 year of age is presented, and the over-prescription of medications in this population is discouraged. Anticipatory guidance regarding the natural resolution of reflux symptoms is recommended. [ABSTRACT FROM AUTHOR]

Introduction: It is strongly recommended that laxatives be routinely prescribed for the prevention of opioid-induced constipation (OIC). The evidence supporting the effectiveness of prokinetics for this indication is sparse. This study aims to verify if itopride, added to preventive OIC therapy, increases the effectiveness of the prevention of opioid-induced constipation in adult palliative care patients.Material and methods: In a questionnaire-based observational study, all patients received regular laxatives plus one of the following: oxycodone/naloxone (OXN); itopride (ITP); or oxycodone/naloxone + itopride (OXN + ITP). The primary measure was the decrease in the necessity of laxative use in a 0-4 scale assessed after 7 days of treatment.Results: Ninety-two patients met the inclusion criteria in the four groups: OXN (n = 12), ITP (11), OXN + ITP (9), and the control group (laxatives only if needed) (60). The necessity of laxatives decreased in groups where itopride was used, with a statistically significant difference versus control, oxycodone/naloxone (p = 0.009), or in combination. The OXN did not decrease laxative use (p = 0.22).Conclusions: All interventions appeared similarly effective in the prevention of OIC. However, adding itopride, but not oxycodone/naloxone, resulted in a decrease in the necessity of laxative use in OIC patients, and it seems to be valuable in this often refractory condition. Randomised, controlled trials would be valuable to obtain good quality evidence without systematic bias. [ABSTRACT FROM AUTHOR]

Background and Aims: Feed intolerance (FI) is common in cirrhosis patients in intensive care units (ICU). Prokinetics are the first line treatment for FI but their efficacy and safety in critically ill patient with cirrhosis is unknown. We evaluated the role of prokinetics in reversal of FI and clinical outcomes. Methods: Consecutive patients admitted in ICU developing new-onset FI, were randomized to receive either intravenous metoclopramide (Gr.A, n = 28), erythromycin (Gr.B, n = 27) or placebo (Gr.C, n = 28). FI was defined with the presence of 3 of 5 variables- absence of bowel sounds, gastric residual volume ≥ 500 ml, vomiting, diarrhoea and bowel distension. Primary end-point was complete resolution of FI (≥ 3 variables resolved) within 24-h and secondary end-points included resolution within 72-h and survival at 7-days. Results: Of the 1030 ICU patients, 201 (19.5%) developed FI and 83 patients were randomized. Baseline parameters between the groups were comparable. Complete resolution at 24-h was higher in Gr.A (7.14%) and B (22.2%) than C (0%, p = 0.017). Overall, 58 (69.9%) patients achieved resolution within 72 h, more with metoclopramide (n = 24, 85.7%) and erythromycin (n = 25, 92.6%) than with placebo (n = 9, 32.1%, p < 0.001). The 7-day survival was better in patients who achieved resolution within 72-h (65.5 vs. 36%, p = 0.011) than non-responders. High lactate (OR-3.32, CI-1.45–7.70, p = 0.005), shock at baseline (OR-6.34, CI-1.67–24.1, p = 0.007) and resolution of FI within 72 h (OR-0.11, CI, 0.03–0.51, p = 0.04) predicted 7-day mortality. Conclusions: FI is common in critically-ill cirrhosis patients and non-resolution carries high mortality. Early recognition and treatment with prokinetics is recommended to improve short-term survival. [ABSTRACT FROM AUTHOR]

Introduction: Gastroesophageal reflux disease (GERD) is a chronic disease of the esophagus characterized by the regurgitation of stomach contents into the esophagus, causing troublesome symptoms and/or complications. Among patients with GERD, around 30% of patients have visible mucosal damage, while 70% have normal esophageal mucosa. Accordingly, the optimal pharmacological treatment of GERD should address different disease manifestations, including symptoms, the mucosal damage when present, and possible chronic complications, including strictures, Barrett's esophagus, and esophageal adenocarcinoma., Areas Covered: Available medical treatments for GERD include proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), histamine receptor antagonists (H2-RAs), prokinetics, and mucosal protectants, such as alginates, hyaluronic acid/chondroitin-sulfate, and poliprotect. Each compound has its own advantages and disadvantages, and knowledge of expected benefits and tips for their use is paramount for the success of treatment. In addition, the appropriateness of indications for initiating treatment is also crucial to achieve positive results when managing GERD patients., Expert Opinion: PPIs, PCABs, H2-RAs, prokinetics, and mucosal protectants can all be used in patients with GERD, but careful assessment of patients' characteristics as well as advantages and disadvantages of each therapeutic compound is essential to ensure successful treatment of GERD.

Introduction: Proton pump inhibitor (PPI) has revolutionized the treatment of erosive esophagitis (EE) in the past few decades. However, roughly 30-40% of the patients, especially those with severe EE (Los Angeles Grade C/D), remain poorly responsive to this medication. Novel drugs have been formulated and/or repurposed to address this problem., Areas Covered: This review highlights novel drugs that have been investigated for use in EE, such as mucosal protectants, prokinetics, transient lower esophageal sphincter relaxation (TLESR) reducers, novel PPIs, and the new potassium-competitive acid blocker (PCAB). Studies have demonstrated that PCAB has promising results (efficacy and safety) compared to PPI for the healing of EE, especially in severe diseases., Expert Opinion: PCAB has gained interest in recent years, with pharmacokinetics and pharmacodynamics properties surpassing PPI. Although recent data on PCABs, which comprised mainly of Vonoprazan, have shown promising results, more randomized controlled trials for other PCAB drugs are needed to elucidate and confirm the superiority of this drug class to PPI, the current first-line treatment of EE.

Gabrio Bassotti,1 Paolo Usai Satta,2 Massimo Bellini3 1Gastroenterology & Hepatology Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; 2Gastrointestinal Unit, “G. Brotzu” Hospital, Cagliari, Italy; 3Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, ItalyCorrespondence: Gabrio BassottiClinica di Gastroenterologia ed Epatologia, Ospedale Santa Maria della Misericordia, Piazzale Menghini, 1, San Sisto (Perugia), 06156, ItalyEmail gabassot@tin.itAbstract: Chronic idiopathic constipation (CIC) is a common functional bowel disorder characterized by difficult, infrequent, and/or incomplete defecation. It has a great impact on the quality of life and on health care system and represents a heavy economic burden. The diagnosis is based on symptoms, classified by the Rome IV criteria. The aim of this review was to evaluate the current therapeutic guidelines for adult CIC and highlight new emerging treatments. In detail, European, French, Spanish and Korean guidelines have been identified and compared. Osmotic laxatives, and in particular polyethylene glycol, represent the first-line therapeutic approach. Stimulant laxatives are recommended as a second-line therapy. Pelvic floor rehabilitation is recommended in patients with ano-rectal dyssynergia. In patients who fail to improve with pharmacological therapies sacral nerve stimulation is considered as last chance before surgery. Surgical approach has however limited indications in selected cases. Inertia coli refractory to any approach and obstructed defecation are two subtypes which can benefit from surgery. Among emerging agents, prucalopride, a prokinetic agent, is recommended as a second-line treatment in refractory CIC patients. In addition, the secretagogues linaclotide and plecanatide and the bile acid transported inhibitor elobixibat can be effective in patients not responsive to a second-line therapeutic regimen, although they are not worldwide commercially available.Keywords: chronic idiopathic constipation, guidelines, osmotic laxatives, pelvic floor rehabilitation, prokinetics, secretagogues

Abstract Background Bacterial translocation is considered the pathophysiological hallmark in the development of spontaneous bacterial peritonitis (SBP). Prokinetics can increase gastrointestinal (GIT) motility, reduce small bowel transit time, decrease bacterial translocation, and the possibility of SBP. The aim of this work was to compare the effectiveness and safety of itopride and norfloxacin versus norfloxacin only in secondary prophylaxis for cirrhotic ascitic patients with spontaneous bacterial peritonitis. Results Regarding the baseline clinical manifestations and laboratory investigations, there was no significant difference between both groups. The incidence of a recurrent SBP in group I, who had received itopride plus norfloxacin, reduced with a significant difference than other group II (P=0.018). The median time for recurrence of SBP was highly longer in group I than group II with a significant difference (P=0.042). Conclusions The combined usage of itopride with norfloxacin in patients with cirrhosis and ascites can decrease the occurrence of a recurrent SBP and significantly improve the survival of patients. Trial registration ClinicalTrials.gov Identifier: NCT04161768 .

Abstract Background Motility disorders of upper gastrointestinal tract are common in critical illness and associated with significant clinical consequences. However, detailed quantitative and qualitative analyses of esophageal motor functions are lacking. Therefore, we aimed to characterize the key features of esophageal motility functions using high-resolution impedance manometry (HRIM) and to evaluate an objective link between esophageal motor patterns, gastric emptying, and gastroesophageal reflux. We also studied the prokinetic effects of metoclopramide. Methods We prospectively performed HRIM for 16 critically ill hemodynamically stable patients. Patients were included if they had low gastric volume (LGV; 500 mL/24 h, n = 8). The HRIM data were collected for 5 h with intravenous metoclopramide administration (10 mg) after the first 2 h. Results The findings were grossly abnormal for all critically ill patients. The esophageal contraction vigor was markedly increased, indicating prevailing hypercontractile esophagus. Ineffective propulsive force was observed for 73% of esophageal activities. Panesophageal pressurization was the most common pressurization pattern (64%). Gastroesophageal reflux predominantly occurred with transient lower esophageal sphincter relaxation. The common features of the LGV group were a hyperreactive pattern, esophagogastric outflow obstruction, and frequent reflux. Ineffective motility with reduced lower esophageal sphincter tone, and paradoxically fewer reflux episodes, was common in the HGV group. Metoclopramide administration reduced the number of esophageal activities but did not affect the number of reflux episodes in either group. Conclusion All critically ill patients had major esophageal motility abnormalities, and motility patterns varied according to gastric emptying status. Well-preserved gastric emptying and maintained esophagogastric barrier functions did not eliminate reflux. Metoclopramide failed to reduce the number of reflux episodes regardless of gastric emptying status. Trial registration ISRCTN, ISRCTN14399966. Registered 3.9.2020, retrospectively registered. https://www.isrctn.com/ISRCTN14399966 .

The use of domperidone (DOM) for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) Registries (GpR). The GpCRC cohort consisted of patients with GP (75%) and with GP-like symptoms but with normal gastric emptying (25%). The DOM group initiated therapy during the 96 weeks of enrollment in GpR1 and GpR2. Patients who had previously taken or who were on DOM therapy at enrollment were excluded from this analysis. The control group did not use domperidone (non-DOM group) before or after enrollment. The following outcome measures were identified: change from baseline in Gastroparesis Cardinal Symptom Index total score, with 3 subscales, plus Gastroesophageal Reflux Disease and Patient Assessment of Upper Gastrointestinal Disorders–Quality of Life scores. Overall, of 748 patients, 181 (24%) were in the DOM group, whereas 567 were in the non-DOM group. Sixty-three percent of participants had idiopathic GP. At baseline, DOM patients compared with non-DOM patients were significantly younger, had lower body mass index, non-Hispanic ethnicity, a higher annual household income, lower narcotic utilization, lower supplemental and complimentary medication use, and were more likely to have delayed gastric emptying time, as well as worse nausea and fullness scores. Compared with non-DOM patients, DOM patients experienced moderate but significantly more improvement in GP outcome measures: Gastroparesis Cardinal Symptom Index total score (P =.003), nausea (P =.003), and fullness subscales (P =.005), upper abdominal pain score (P =.04), Gastroesophageal Reflux Disease score (P =.05), and Patient Assessment of Upper Gastrointestinal Disorders–Quality of Life score (P =.05). Utilizing the method of pragmatic modeling to evaluate long-term treatment of GP in a large GpCRC database, DOM treatment resulted in moderately but significantly improved GP. This project was based on data generated by 2 GpCRC Registry studies recognized under the Clinicaltrial.gov numbers: NCT00398801 and NCT01696747 symptoms compared with a group receiving standard-of-care but not DOM. [ABSTRACT FROM AUTHOR]

Background: Functional dyspepsia (FD) is a disorder that presents with chronic dyspepsia, which is not only very common but also highly affects quality of life of the patients. In Japan, FD became a disease name for national insurance in 2013, and has been gradually recognized, though still not satisfactory. Following the revision policy of Japanese Society of Gastroenterology (JSGE), the first version of FD guideline was revised this time. Method: Like previously, the guideline was created by the GRADE (grading of recommendations assessment, development and evaluation) system, but this time, the questions were classified to background questions (BQs, 24 already clarified issues), future research questions (FRQs, 9 issues cannot be addressed with insufficient evidence), and 7 clinical questions that are mainly associated with treatment. Results and Conclusion: These revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. While endoscopy was required to all cases for diagnosis of FD, the revised guidelines specify the necessity of endoscopy only in cases where organic disease is suspected. The second feature is that the drug treatment options have been changed to reflect the latest evidence. The first-line treatment includes gastric acid-secretion inhibitors, acetylcholinesterase (AChE) inhibitors (acotiamide, a prokinetic agent), and Japanese herbal medicine (rikkunshito). The second-line treatment includes anxiolytics /antidepressant, prokinetics other than acotiamide (dopamine receptor antagonists, 5-HT4 receptor agonists), and Japanese herbal medicines other than rikkunshito. The patients not responding to these treatment regimens are regarded as refractory FD. [ABSTRACT FROM AUTHOR]

Background: Constipation is a common problem in gastroenterological practice. The prevalence of constipation is about 16%. Constipation can be primary or secondary. Summary: The diagnostic and therapeutic approach to patients with constipation begins with a detailed history and physical examination. In selected cases, the use of additional diagnostic procedures is very important. This includes the use of laboratory, endoscopic, and radiological examinations, as well as advanced physiological testing (anorectal manometry, balloon expulsion test, colonic transit studies, and defecography). Constipation therapy can be both nonoperative and operative. Nonoperative therapy includes the application of a lifestyle measures, pharmacotherapy and biofeedback therapy. Key Messages: Two key things when taking a medical history and physical examination are to rule out the existence of alarm symptoms/signs and to rule out secondary constipation (primarily drug-induced). Therapy begins with lifestyle modification, and in case of failure, bulk or osmotic laxatives are used. In case of failure, the use of lubiprostone is indicated, as well as linaclotide. Surgical treatment of constipation is reserved for cases of refractory constipation, with delayed intestinal transit. [ABSTRACT FROM AUTHOR]

The human gut microbiome is composed of communities of bacteria, viruses and fungi. Bacteria live in each part of digestive tract, increasing their density and changing composition in distal parts. The composition of gut microbiome mainly depends on method of childbirth, age, gender, diet, stress, infections, alcohol intake, diurnal variation, smoking, drugs (antibiotics), physical activity. Dysbiosis is defined as an imbalance or maladaptation in the gut microbial community. This imbalance favors many pathological states and it could be due to some diseases. Non-alcoholic fatty liver disease (NAFLD) has become increasingly common in parallel with the increasing prevalence of obesity and other components of the metabolic syndrome. In year 2020, a more comprehensive new definition of NAFLD was proposed - fatty liver disease associated with metabolic dysfunction (MAFLD). NAFLD/MALFD will become the major form of chronic liver disease in adults and children and could become the leading indication for liver transplantation within a decade. An increased level of Bacteroidetes and decreased level of Firmicutes is observed in fatty liver disease. This imbalance favors the collection of energy and insulin resistance. The prevention and treatment of dysbiosis in NAFLD/MAFLD is essential. The purpose of this review is an understanding related to the dysbiosis and non-alcoholic fatty liver disease in order to help physicians of different specialties in their clinical practice because of growing in population patients with metabolic syndrome and liver steatosis. [ABSTRACT FROM AUTHOR]

Gastroparesis is a gastrointestinal motility disorder characterized by nausea, vomiting, early satiation, postprandial fullness, bloating, and upper abdominal pain. The diagnosis requires documented delay in gastric emptying with an optimal test such as scintigraphy or stable isotope gastric emptying breath test in the absence of mechanical obstruction. The pathophysiologic mechanisms of gastroparesis are multifactorial, including antroduodenal hypomotility, pylorospasm, impaired gastric accommodation, and visceral hypersensitivity. The etiologies of gastroparesis are broad, but the most common subtypes are idiopathic, diabetic, and postsurgical. Less frequent etiologies are neurodegenerative disorder (Parkinson disease), myopathies (scleroderma, amyloidosis), and neoplastic syndrome. Symptoms of gastroparesis can be refractory and challenging to manage, leading to reduced quality of life and significant health care expenditure. This article introduces the epidemiology, clinical presentation, diagnosis, and differential diagnoses of gastroparesis, followed by a focused discussion on its management, including nutritional support, prokinetic and antiemetic agents, and emerging interventions directed at the pylorus. Robust sham-controlled trials are needed to evaluate the long-term efficacy of gastric peroral endoscopic myotomy. A multidisciplinary approach with individualized strategies based on characterization of the pathophysiology is deemed necessary to enhance clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction It is strongly recommended that laxatives be routinely prescribed for the prevention of opioid-induced constipation (OIC). The evidence supporting the effectiveness of prokinetics for this indication is sparse. This study aims to verify if itopride, added to preventive OIC therapy, increases the effectiveness of the prevention of opioid-induced constipation in adult palliative care patients. Material and methods In a questionnaire-based observational study, all patients received regular laxatives plus one of the following: oxycodone/naloxone (OXN); itopride (ITP); or oxycodone/naloxone + itopride (OXN + ITP). The primary measure was the decrease in the necessity of laxative use in a 0–4 scale assessed after 7 days of treatment. Results Ninety-two patients met the inclusion criteria in the four groups: OXN (n = 12), ITP (11), OXN + ITP (9), and the control group (laxatives only if needed) (60). The necessity of laxatives decreased in groups where itopride was used, with a statistically significant difference versus control, oxycodone/naloxone (p = 0.009), or in combination. The OXN did not decrease laxative use (p = 0.22). Conclusions All interventions appeared similarly effective in the prevention of OIC. However, adding itopride, but not oxycodone/naloxone, resulted in a decrease in the necessity of laxative use in OIC patients, and it seems to be valuable in this often refractory condition. Randomised, controlled trials would be valuable to obtain good quality evidence without systematic bias.

Background: Motility disorders of upper gastrointestinal tract are common in critical illness and associated with significant clinical consequences. However, detailed quantitative and qualitative analyses of esophageal motor functions are lacking. Therefore, we aimed to characterize the key features of esophageal motility functions using high-resolution impedance manometry (HRIM) and to evaluate an objective link between esophageal motor patterns, gastric emptying, and gastroesophageal reflux. We also studied the prokinetic effects of metoclopramide.Methods: We prospectively performed HRIM for 16 critically ill hemodynamically stable patients. Patients were included if they had low gastric volume (LGV; < 100 mL/24 h, n = 8) or high gastric volume (HGV; > 500 mL/24 h, n = 8). The HRIM data were collected for 5 h with intravenous metoclopramide administration (10 mg) after the first 2 h.Results: The findings were grossly abnormal for all critically ill patients. The esophageal contraction vigor was markedly increased, indicating prevailing hypercontractile esophagus. Ineffective propulsive force was observed for 73% of esophageal activities. Panesophageal pressurization was the most common pressurization pattern (64%). Gastroesophageal reflux predominantly occurred with transient lower esophageal sphincter relaxation. The common features of the LGV group were a hyperreactive pattern, esophagogastric outflow obstruction, and frequent reflux. Ineffective motility with reduced lower esophageal sphincter tone, and paradoxically fewer reflux episodes, was common in the HGV group. Metoclopramide administration reduced the number of esophageal activities but did not affect the number of reflux episodes in either group.Conclusion: All critically ill patients had major esophageal motility abnormalities, and motility patterns varied according to gastric emptying status. Well-preserved gastric emptying and maintained esophagogastric barrier functions did not eliminate reflux. Metoclopramide failed to reduce the number of reflux episodes regardless of gastric emptying status. Trial registration ISRCTN, ISRCTN14399966. Registered 3.9.2020, retrospectively registered. https://www.isrctn.com/ISRCTN14399966 . [ABSTRACT FROM AUTHOR]

There are an estimated 1.5 million pet rabbits in the UK, when compared to cats (11 million) and dogs (9.4 million) this figure may seem small; however, rabbits have been domesticated for a relatively shorter period of time and their population is rapidly increasing in comparison. Rabbits rise in popularity as pets has caused an increase in presentation in veterinary practice. Rabbit owners expect the same high standards of care that dogs and cats receive in veterinary practice, therefore it is essential that veterinary professionals achieve a better understanding about the species to provide efficient care. Rabbits being a prey species often conceal their illness until they are in critical condition, posing a significant challenge to both owners and veterinary professionals in early recognition of clinical signs. Therefore it is essential that registered veterinary nurses (RVN's) and veterinary surgeons (VS) are confident in identifying changes in rabbit behaviour which includes eating habits and faecal output. Recognising symptoms early will aid in implementing treatment and reducing mortality rates. [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder. Proton pump inhibitors (PPIs) are first-line drugs for GERD. For those who fail to respond to PPIs, adding prokinetics to PPIs is recommended and several trials have been conducted to evaluate the efficacy of prokinetic–PPI combination therapy. Methods: A systematic literature search was performed using PubMed and the Cochrane Library databases before February 2019 for randomized controlled trials (RCTs), which compared the efficacy of prokinetics plus PPI treatment with that of PPI monotherapy. Relevant studies were examined and data were extracted independently by two investigators. The risk ratios (RRs) with 95% CIs were used to evaluate the responder rate, and standard mean differences (SMDs) or mean differences (MDs) with 95% CIs were used for symptom score changes. Statistical heterogeneity was evaluated by the I2 statistic. Either a fixed-effect or a random-effect model was established for calculating the pooled data. Results: A total of 14 studies, comprising 1,437 patients were ultimately included in the meta-analysis. The pooled analysis showed that compared to PPI monotherapy, addition of prokinetics to PPI did not elevate the rate of endoscopic responders (RR = 0.996, 95% CI 0.929 − 1.068, p = 0.917), but improved symptom response (RR = 1.185, 95% CI 1.042 − 1.348, p = 0.010). Additionally, the combined therapy achieved a greater symptom relief than monotherapy both in FSSG and GERD-Q subgroups (MD = − 2.978, 95% CI − 3.319 to − 2.638, p < 0.001; MD = − 0.723, 95% CI − 0.968 to − 0.478, p < 0.001). Conclusions: Adding prokinetics to PPIs achieves symptomatic improvement compared to PPI monotherapy, thus can enhance life quality of GERD patients. However, the combined treatment seems to have no significant effect on mucosal healing. [ABSTRACT FROM AUTHOR]

The radionuclide gastric emptying study is the gold standard for the diagnosis of gastroparesis. Methods: We performed a retrospective analysis of 510 patients to evaluate how often a diagnosis of slow gastric emptying determined by gastric emptying scintigraphy (GES) changes clinical management at our institution. Results: We found evidence of gastroparesis in 100 patients. A change in management was recommended for 62% within 1 mo of the GES. Conclusion: Our results illustrate the importance of performing GES on patients with clinically suspected gastroparesis., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Danny J Avalos,1 Irene Sarosiek,1 Priyadarshini Loganathan,2 Richard W McCallum1 1Division of Gastroenterology, Center for Neurogastroenterology and GI Motility, Texas Tech University Health Sciences Center, El Paso, TX, USA; 2Department of Internal Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX, USA Abstract: Diabetic gastroparesis (DMGP) is a condition of delayed gastric emptying after gastric outlet obstruction has been excluded. Symptoms of nausea, vomiting, early satiety, bloating, and abdominal pain are associated with DMGP. Uncontrolled symptoms can lead to overall poor quality of life and financial burdens on the healthcare system. A combination of antiemetics and prokinetics is used in symptom control; metoclopramide is the main prokinetic available for clinical use and is the only U.S. Food and Drug Administration-approved agent in the United States. However, a black box warning in 2009 reporting its association with tardive dyskinesia and recommending caution in chronically using this agent beyond 3 months has decreased its role in clinical practice. There is an unmet need for new prokinetics with good efficacy and safety profiles. Currently, there are several new drugs with different mechanisms of action in the pipeline that are under investigation and show promising preliminary results. Surgically combining gastric electrical stimulation with pyloroplasty is considered “gold” standard. Advances in therapeutic endoscopic intervention with gastric per-oral endoscopic pyloromyotomy have also been shown to improve gastric emptying and gastroparesis (GP) symptoms. In this review, we will comment on the challenges encountered when managing patients with DMGP and provide an update on advances in drug development and endoscopic and surgical interventions. Keywords: bloating, fullness, nausea, vomiting, Enterra, diabetes

Gastric disorders have clinical implications in both anaesthesia and critical care medicine. Aspiration of acidic gastric contents in the perioperative setting is linked to pneumonitis and later development of pneumonia. Pharmacological strategies to minimize this risk include histamine-2 receptor antagonists, sucralfate, proton pump inhibitors and sodium citrate. Use of gastric acid suppressing therapy is widespread in intensive care units to reduce the incidence of stress-related mucosal bleeding. Intestinal failure is common in critical illness. Medications that decrease gastric motility and contribute to ileus include opioid analgesics, catecholamines and α 2 -adrenoceptor antagonists. Current pharmacological strategies for increasing gastric motility include the use of metoclopramide and erythromycin, either alone or in combination, though their effectiveness in clinical practice is limited. A range of further medications, with different drug targets, are being investigated as alternatives. These include specific motilin receptor agonists, peripherally acting opioid receptor antagonists, cholecystokinin antagonists, 5HT 4 antagonists and cholinesterase inhibitors. [ABSTRACT FROM AUTHOR]

Despite the extensive recent development of different techniques for endoscopic evaluation for both diagnostic and therapeutic reasons, the small bowel remains quite difficult to visualize. Capsule endoscopy and device assisted enteroscopy are presently considered the best diagnostic tools for examination of small bowel disorders, assessing diverse pathologies such as obscure gastrointestinal bleeding, iron deficiency anemia, Crohn disease, small bowel tumors and polyposis syndromes. Like any other imagistic method, it has specific indications, and contraindications, and possibly it is more important to consider limitations. In order to obtain a better result, it is necessary to respect the procedural quality indicators. Among them the use of prokinetics - diverse pharmacological substances increasing the success rate of capsule endoscopy have raised debates. Capsule endoscopy small bowel evaluation is a reliable, non-invasive and safe with many advantages and minimum risks, with a proper selection of patients, and can be used as first line investigation. [ABSTRACT FROM AUTHOR]

Background: Muscarinic receptor 1 positive allosteric modulators (M1PAMs) enhance colonic propulsive contractions and defecation through the facilitation of M1 receptor (M1R)‐mediated signaling. We examined M1R expression in the colons of 5 species and compared colonic propulsion and defecation caused by the M1PAM, T440, the 5‐HT4 agonist, prucalopride, and the cholinesterase inhibitor, neostigmine, in rats and dogs. Methods: M1R expression was profiled by immunostaining and in situ hybridization. In vivo studies utilized male SD rats and beagle dogs. Colonic propulsive contractions were recorded by manometry in anesthetized rats. Gut contractions in dogs were assessed using implanted force transducers in the ileum, proximal, mid, and distal colons. Key Results: M1R was localized to neurons of myenteric and submucosal plexuses and the epithelium of the human colon. A similar receptor localization was observed in rat, dog, mouse, and pig. T440 enhanced normal defecation in rats in a dose‐dependent manner. Prucalopride also enhanced defecation in rats, but the maximum effect was half that of T440. Neostigmine and T440 were similarly effective in enhancing defecation, but the effective dose of neostigmine was close to its lethal dose. In rats, all 3 compounds induced colonic contractions, but the associated propulsion was strongest with T440. In dogs, intestinal contractions elicited by T440 propagated from ileum to distal colon. Prucalopride and neostigmine also induced intestinal contractions, but these were less well coordinated. No loss of effectiveness of T440 on defecation occurred after 5 days of repeated dosing. Conclusion and Inferences: These results suggest that M1PAMs produce highly coordinated propagating contraction by actions on the enteric nervous system of the colon. The localization of M1R to enteric neurons in both animals and humans suggests that the M1PAM effects would be translatable to human. M1PAMs provide a potential novel therapeutic option for constipation disorders. [ABSTRACT FROM AUTHOR]

Functional dyspepsia (FD) is a disease with different prevailing pathogenetic mechanisms. The prevalence of FD varies widely from 10 to 30 % of the population, depending on the country and the surveyed cohort. There are two forms of FD: postprandial distress syndrome manifested by a fullness/early satiety after eating, and epigastric pain syndrome — pain/burning in the epigastrium, which may worsen after eating. In a significant part of patients with FD, there are manifestations of both syndromes, the so-called overlap, or a mixed type. In the Ukrainian population, all patients with dyspepsia should be diagnosed and, if found, — undergo mandatory eradication of H.pylori. In patients with persistent symptoms or in those initially not infected with H.pylori, in our opinion, it is advisable to use the combination of proton pomp inhibitor and prokinetic as starting treatment. In our country, a fixed combination of omeprazole and domperidone is available in two dosages. This is Omez D containing 10 mg of both components and a more highly dosed Omez DSR containing 20 mg of omeprazole and 30 mg of domperidone in the form of sustained-release pellets.

Abstract Background Controversies persist regarding the effect of prokinetics for the treatment of functional dyspepsia (FD). This study aimed to assess the comparative efficacy of prokinetic agents for the treatment of FD. Methods Randomized controlled trials (RCTs) of prokinetics for the treatment of FD were identified from core databases. Symptom response rates were extracted and analyzed using odds ratios (ORs). A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method in WinBUGS and NetMetaXL. Results In total, 25 RCTs, which included 4473 patients with FD who were treated with 6 different prokinetics or placebo, were identified and analyzed. Metoclopramide showed the best surface under the cumulative ranking curve (SUCRA) probability (92.5%), followed by trimebutine (74.5%) and mosapride (63.3%). However, the therapeutic efficacy of metoclopramide was not significantly different from that of trimebutine (OR:1.32, 95% credible interval: 0.27–6.06), mosapride (OR: 1.99, 95% credible interval: 0.87–4.72), or domperidone (OR: 2.04, 95% credible interval: 0.92–4.60). Metoclopramide showed better efficacy than itopride (OR: 2.79, 95% credible interval: 1.29–6.21) and acotiamide (OR: 3.07, 95% credible interval: 1.43–6.75). Domperidone (SUCRA probability 62.9%) showed better efficacy than itopride (OR: 1.37, 95% credible interval: 1.07–1.77) and acotiamide (OR: 1.51, 95% credible interval: 1.04–2.18). Conclusions Metoclopramide, trimebutine, mosapride, and domperidone showed better efficacy for the treatment of FD than itopride or acotiamide. Considering the adverse events related to metoclopramide or domperidone, the short-term use of these agents or the alternative use of trimebutine or mosapride could be recommended for the symptomatic relief of FD.

Small intestinal bacterial overgrowth (SIBO) is common in patients with systemic sclerosis (SSc) yet often goes underrecognized in clinical practice. In patients with SSc, untreated SIBO may result in marked morbidity and possible mortality. The pathogenesis of SIBO is multifactorial and relates to immune dysregulation, vasculopathy, and dysmotility. This article reviews various diagnostic approaches and therapeutic options for SIBO. Treatment modalities mainly include prokinetics, probiotics, and antibiotics.

Background/aims: Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment., Methods: Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life., Results: One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline., Conclusion: Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.

Introduction: Gastroesophageal Reflux Disease (GERD) is a common public health problem causing increased economic burden and decreased quality of life. Proton Pump Inhibitor (PPI) and prokinetics are the frequently used medications. The efficacy and safety of combined prokinetic and PPI therapy for GERD remains controversial. Aim: The study was conducted to perform pharmacoeconomic evaluation of Pantoprazole and Pantoprazole plus Domperidone in the management of GERD which helps to provide quality care within limited financial resources. Materials and Methods: This RCT was conducted on 80 patients suffering from GERD. These patients were randomly divided into two groups; Pantoprazole (40 mg once daily) and, Pantoprazole plus Domperidone (40 mg+30 mg once daily), respectively. The clinical outcomes were observed and analysed after two weeks of treatment. Cost-effectiveness ratio for pantoprazole and pantoprazole plus Domperidone was calculated by dividing the cost of treatment by its clinical outcome that is, Frequency Scale for the Symptoms of GERD (FSSG) score. Cost minimization analysis was done in accordance with the cost of both drugs available in market (over the counter) and Hospital pharmacy. All the data was recorded in the entry form and presented as mean±SEM/SD for numerical data, and proportion (%) for the categorical data. In all tests mean values of test groups (A and B) compared with Student's paired t-test. Results: After two weeks of treatment, the total improvement rate was found to be higher in Pantoprazole plus Domperidone group than in Pantoprazole group (improvement score 12.93 vs 11.32 but statistically not significant, p-0.21). But Pantoprazole was found to be more cost effective than Pantoprazole plus Domperidone group (ACER 9.7 vs 11.2). Cost minimisation analysis showed that Pantoprazole is the most economical medicine in hospital pharmacy as well as available in market. Conclusion: Pantoprazole monotherapy is more cost effective than combination of Pantoprazole with Domperidone in GERD patients. Substitution by Pantoprazole alone would be expected to produce cost savings. A combination should be preferred for PPI resistant GERD, patients with nausea and vomiting, in the subgroup of severely symptomatic patients.

Background: Although feeding intolerance is a common complication in trauma patients, the incidence, development, and effects are poorly understood.Methods: We performed a retrospective study in which trauma patients were classified as having feeding intolerance based on time to reach feeding goal. Subsequently, we sorted patients by gastric residual volumes (GRVs) or symptoms of slowed gastrointestinal motility.Results: One-third of trauma patients experienced delayed time to reach feeding goal after diet initiation. Delayed feeding was associated with prolonged intensive care unit (ICU) stays, increased readmission rates, and increased incidence of sepsis. Patients with elevated GRV (>500 mL) had significantly prolonged ICU and hospital stays and increase incidence of sepsis. Patients with >2 symptoms of slowed gastrointestinal motility had prolonged ICU and hospital stays, delayed time to reach feeding goals, significantly increased readmission rates, increased incidence of infectious and thromboembolic complications and sepsis, decreased serum prealbumin levels, and increased CRP levels.Conclusion: Decreased gastrointestinal motility in trauma patients is associated with worse outcomes and increased systemic inflammation. [ABSTRACT FROM AUTHOR]

1. The pharmacokinetics (PKs) analysis of compounds absorbed after the oral administration of Si-Ni-San (SNS) decoction to functional dyspepsia (FD) patients was designed to detect whether the effects were similar to prokinetics administered to healthy rats, without ethical limitation. 2. First, the absorbed compounds, liquiritigenin (L), naringenin (N) and hesperitin (H) in the plasma were identified by UPLC-MS/MS following the oral administration of SNS decoction to subjects with FD. Next, the natural ratio of LNH in the SNS decoction was determined by UPLC. Third, gastric emptying and intestinal transit after the oral administration of LNH, in combination or alone, was compared with those observed after SNS administration in healthy rats. Additionally, the clinical PKs of LNH was studied. 3. The prokinetic efficacy of LNH administered at their natural ratios (7.5:5:1) increased dose-dependently and was better than the observed efficacy when administered alone in rats. Analysis of the clinical PK parameters, calculated using a one-compartment model, showed that the Cmax parameters of LNH in 3, 4 and 4 h were 639.17, 410.00 and 181.67 μg/L, respectively. 4. The clinical herbal PK analysis of the absorbed LNH preclinical prokinetic compounds, in their natural ratio from SNS, highlights the impact of an herbal translational pharmacology study. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) often thought to be psychological in origin is now understood to have multifactorial origins because of the realisation that gut dysbiosis, including SIBO, causes IBS. SIBO is a condition characterised by microbial overload in the small intestine leading to fermentation of starches and carbohydrates producing gases, inflammation and microvilli damage in the small intestine. A significant proportion of IBS sufferers also have SIBO. Many providers may not be aware of SIBO. This case history highlights a clinical case of IBS and SIBO including history, clinical presentation, diagnostic workup and treatment. Management involved an integrative medicine, patient centred, SIBO treatment protocol targeting gut microbes with diet, antibiotics, probiotics, prokinetics, supplements and biofilm disruptors. Prevalence and pathophysiology will also be discussed. [ABSTRACT FROM AUTHOR]

Introduction: Gastroesophageal Reflux Disease (GERD) is a common public health problem causing increased economic burden and decreased quality of life. Proton Pump Inhibitor (PPI) and prokinetics are the frequently used medications. The efficacy and safety of combined prokinetic and PPI therapy for GERD remains controversial. Aim: The study was conducted to perform pharmacoeconomic evaluation of Pantoprazole and Pantoprazole plus Domperidone in the management of GERD which helps to provide quality care within limited financial resources. Materials and Methods: This RCT was conducted on 80 patients suffering from GERD. These patients were randomly divided into two groups; Pantoprazole (40 mg once daily) and, Pantoprazole plus Domperidone (40 mg+30 mg once daily), respectively. The clinical outcomes were observed and analysed after two weeks of treatment. Cost-effectiveness ratio for pantoprazole and pantoprazole plus Domperidone was calculated by dividing the cost of treatment by its clinical outcome that is, Frequency Scale for the Symptoms of GERD (FSSG) score. Cost minimization analysis was done in accordance with the cost of both drugs available in market (over the counter) and Hospital pharmacy. All the data was recorded in the entry form and presented as mean±SEM/SD for numerical data, and proportion (%) for the categorical data. In all tests mean values of test groups (A and B) compared with Student's paired t-test. Results: After two weeks of treatment, the total improvement rate was found to be higher in Pantoprazole plus Domperidone group than in Pantoprazole group (improvement score 12.93 vs 11.32 but statistically not significant, p-0.21). But Pantoprazole was found to be more cost effective than Pantoprazole plus Domperidone group (ACER 9.7 vs 11.2). Cost minimisation analysis showed that Pantoprazole is the most economical medicine in hospital pharmacy as well as available in market. Conclusion: Pantoprazole monotherapy is more cost effective than combination of Pantoprazole with Domperidone in GERD patients. Substitution by Pantoprazole alone would be expected to produce cost savings. A combination should be preferred for PPI resistant GERD, patients with nausea and vomiting, in the subgroup of severely symptomatic patients. [ABSTRACT FROM AUTHOR]

Introduction. Diabetes mellitus (DM) is considered to be one of the most serious problems in internal medicine due to multiple organ lesions and irreversible changes in the functioning of the organism. At present, despite the continuous advancement in medical science pathogenetic mechanisms of the development and progression of gastrointestinal form of autonomic neuropathy, particularly one of its manifestations – diabetic gastroparesis (DG) remains insufficiently studied. Purpose of the study. In the scientific literature there are insufficient data on the clinical efficacy of itopride hydrochloride in patients with impaired motor-evacuation function (MEF) of the stomach. There are no answers to the questions about pathogenetic mechanisms of possible effects of prokinetics on the parameters of glycemic control, the incidence of hypoglycemic events, the progression of gastrointestinal manifestations, etc. Therefore, the objective of the research was to determine therapeutic efficacy of itopride in treatment of gastroparesis considering the state of carbohydrate metabolism in patients with type 2 diabetes mellitus. Materials and research methods. To clarify the relationship between the results of itopride hydrochloride therapy and the dynamics of changes in carbohydrate metabolism were examined 48 patients with type 2 DM. They were divided into two groups. In addition to the standard 6-week course of pathogenetically grounded therapy patients of Group I (n = 24) received itopride hydrochloride at a daily dose of 150 mg (50 mg three times a day 30 min before their main meal). Patients of Group II (the control group) (n = 24) underwent the standard therapy without using medicines affecting MEF of the stomach. The clinical severity of DG was determined using the questionnaire ″Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index″ (PAGI-SYM), which allows the patient to assess the severity of symptoms by himself. According to the survey (D-ABS) the prevalence and intensity of the hypoglycemic episodes were determined. To assess MEF of the stomach all the patients underwent 13C-octanoic acid breath test. Results of the investigation and their discussion. According to the results of additional methods of examination there was a direct correlation between the mean PAGI-SYM scores and the results of 13C-octanoic acid breath test (r = 0.63 ± 0.03, p < 0.001). There was also a strong direct correlation between the state of compensation of carbohydrate metabolism (НbA1C, %) and the degree of slowing of gastrointestinal motility according to the results of 13C-octanoic acid breath test (r = 0.64 ± 0.03, p < 0.001). Thus, the course of DG depends on the effectiveness of glycemic control. Total PAGI-SYM scores indicated the positive effect of treatment which was significantly different in patients of Group I before (14.21 ± 3.28 points – moderate DG) and after the treatment (7.28 ± 0.9 points – mild DG) compared to the control group. The results of 13C-octanoic acid breath test confirmed the effectiveness of a 6-week course of treatment with itopride hydrochloride at a daily dose of 150 mg (50 mg three times a day 30 min before a meal) with recovery of gastrointestinal motility (according to treatment Т ½ – 98.24 ± 3.14 min, in dynamics Т ½ – 68.32 ± 3.55 min; р < 0.05) in patients of Group I. In patients of Group II (the control group) the normalization of MEF of the stomach after the course of treatment was not observed (before treatment Т ½ – 97.23 ± 2.61 min, after treatment Т ½ – 92.12 ± 0.16 min; р >0.05). Conclusions. The effectiveness of using itopride hydrochloride at a daily dose of 150 mg has been proven. It has been established that it contributes to normalizing MEF of the stomach in patients with type 2 DM and signs of DG as well as achieving better compensation of carbohydrate metabolism of both prandial and postprandial glucose levels. The possibility of using prokinetic agents to prevent the labile course of DM should be taken into consideration.

The aim of the present study was to evaluate cardiac indices using M-mode echocardiography after the administration of metoclopramide and ondansetron in donkeys. For this purpose, 10 apparently healthy Egyptian Baladi donkeys ( Equus asinus ) were used in a crossover prospective study. Two trials were conducted with the administration of metoclopramide hydrochloride anhydrous at a dose of 0.25 mg Kg -1 and ondansetron hydrochloride sodium at a dose of 0.15 mg Kg -1 . The control group (placebo) received a total volume of 50 mL of isotonic saline at 0.9%. An echocardiographic examination was performed using a Digital Color Doppler Ultrasound System equipped with a 2-3.9 MHz phased array sector scanner transducer. In general, the fractional shortening (FS%) was significantly affected by the time for metoclopramide ( p = 0.031) and ondansetron ( p = 0.047) compared with those of placebo, with treatment with metoclopramide provoking significantly higher percentages of FS% at T60 ( p = 0.009) and T90 ( p = 0.028) compared with those for ondansetron and placebo. The interaction of time x treatment also showed a statistically significant alteration of FS% ( p < 0.05), while the values returned to the basal line at T240. Metoclopramide induced a significant decrease in E-point to septal separation (EPSS) at T90 ( p = 0.005), and T240 ( p = 0.007) compared with ondansetron and placebo. The time x treatment interaction also showed a significant ( p < 0.05) variation in EPSS, with values returning to the basal line at T300. Mitral valve opening velocity (DE SLP) values were significantly affected by time ( p = 0.004) in the metoclopramide group compared with those of ondansetron and placebo. Administration of metoclopramide and ondansetron provoked significant alterations of DE SLP at T60 ( p = 0.039), T120 ( p = 0.036), and T300 ( p = 0.005) compared with placebo. In conclusion, caution should be exercised when administering both treatments, especially to animals with suspected cardiac problems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest., (Copyright © 2023 Marzok, Kandeel, Alkhodair, Abdel-Raheem, Ismail, Farag, Ibrahim, El-Ashkar, Shousha and El-Khodery.)

Objectives Almost all patients with SSc have gastrointestinal manifestations. Small intestinal bacterial overgrowth (SIBO) occurs in 30–60% of patients and leads to malnutrition and impaired quality of life. Recent systematic reviews have reported efficacy of treatments for SIBO, but these are not specific to patients with SSc. We conducted a systematic review of the evidence for all possible SIBO treatments in the SSc population. Methods The following databases were searched: MEDLINE, EMBASE and the Cochrane Library, from database inception to 1 January 2017. All evidence for all possible SIBO treatments including antibiotics, prokinetics, probiotics and alternative treatments was included. Treatment outcomes included symptomatic relief or demonstrated SIBO eradication. Results Of 5295 articles, five non-randomized studies were reviewed with a total of 78 SSc patients with SIBO. One trial assessed octreotide while the remaining four trials investigated the effectiveness of ciprofloxacin, rifaximin, norfloxacin and metronidazole, and the combination of amoxicillin, ciprofloxacin and metronidazole. Studies were generally of low quality and most were un-controlled. Conclusion Data indicate that, for some SSc patients, antibiotics can eradicate SIBO. There is a paucity of data reporting the effectiveness of either prokinetics or probiotics in SSc. [ABSTRACT FROM AUTHOR]

Background: Recent increase in the non-specific use of prokinetics in clinical practice may alter the etiological profile of hyperprolactinemia and galactorrhea. Hence, we have studied the etiological profile of patients presenting with galactorrhea and characteristics of drug-induced galactorrhea. Materials and Methods: This retrospective study was conducted at a tertiary health care center from South India. Patients who presented with or referred for galactorrhea and/or hyperprolactinemia to the Department of Endocrinology between January 2017 and December 2017 were included in the study. Results: Forty women presented with or referred for galactorrhea to the Department of Endocrinology during the study period. Thirty-two patients had received drugs that are associated with hyperprolactinemia (levosulpiride in 15, domperidone in 13, ranitidine in 2, oral contraceptive pill in 1, and amisulpiride in 1) of whom etiology was proved in 27 patients, whereas in four patients the cause was inconclusive due to lack of follow-up. The patient on amisulpiride was found to have concomitant pituitary microadenoma. Idiopathic galactorrhea (n = 2), idiopathic hyperprolactinemia (n = 2), and prolactinoma (n = 4) accounted for the remaining cases. Six patients with prokinetic-induced galactorrhea had received cabergoline inspite of which hyperprolactinemia and/or galactorrhea persisted and six patients had also undergone pituitary magnetic resonance imaging (MRI) for evaluation of galactorrhea. Conclusions: Prokinetic use is the most common cause of galactorrhea in our study and often was investigated with costly tests and treated with D2 agonists unnecessarily. Hence, there is a need to ensure measures to reduce the non-specific use of prokinetics and increase awareness regarding the occurrence of galactorrhea with prokinetics use, to reduce unnecessary investigations and treatment. [ABSTRACT FROM AUTHOR]

Background and study aims Several studies have demonstrated the superiority of proton-pump inhibitors (PPIs) in resolving erosive gastro-oesophageal reflux disease (GORD). However, this first line of treatment can fail to control symptoms in around 30% of cases, especially in the presence of non-erosive GORD. In situations where the first line of treatment fails, there is a lack of concordance regarding the best strategy to apply. This study presents a systematic review of the trials which have tested second-line treatments after PPI failure. Methods The study was conducted according to the PRISMA statement. The systematic review included medical trials written in English which were published between 2000 and 2016 and were retrieved from PubMed and Scopus using the keywords ‘PPI-resistant gastro-oesophageal reflux’, ‘alginate AND gastro-oesophageal reflux’, ‘hyaluronic acid AND gastro-oesophageal reflux’, ‘prokinetics AND gastro-oesophageal reflux’, ‘sucralfate AND gastro-oesophageal reflux’ and ‘baclofen AND gastro-oesophageal reflux’. Results Ten randomised and non-randomised studies were included, which included 1515 patients of both sexes (mean age = 49.19 years, age range = 18–85, males = 700; 46.2%). Conclusions A personalised choice of the best treatment for PPI-resistant GORD should be based on the results of an upper endoscopy and pH/MII monitoring. For patients in situations where the first line of treatment fails, we encourage the execution of trials for testing double doses of PPIs against alternative medicaments. [ABSTRACT FROM AUTHOR]

Introduction: Chronic abdominal pain is a common problem in pediatric practice. The majority of cases fulfill the Rome IV criteria for functional abdominal pain disorders (FAPDs). At times, these disorders may lead to rather serious repercussions. Area covered: We have attempted to cover current knowledge on epidemiology, pathophysiology, risk factors related to pathophysiology, clinical evaluation and management of children with FAPDs. Expert commentary: FAPDs are a worldwide problem with a pooled prevalence of 13.5%. There are a number of predisposing factors and pathophysiological mechanisms including stressful events, child maltreatment, visceral hypersensitivity, altered gastrointestinal motility and change in intestinal microbiota. It is possible that the environmental risk factors intricately interact with genes through epigenetic mechanisms to contribute to the pathophysiology. The diagnosis mainly depends on clinical evaluation. Commonly used pharmacological interventions do not play a major role in relieving symptoms. Centrally directed, nonpharmacological interventions such as hypnotherapy and cognitive behavioral therapy have shown both short and long term efficacy in relieving pain in children with FAPDs. However, these interventions are time consuming and need specially trained staff and therefore, not currently available at grass root level. Clinicians and researchers should join hands in searching for more pragmatic and effective therapeutic modalities to improve overall care of children with FAPDs. [ABSTRACT FROM AUTHOR]

Gastric disorders have clinical implications in both anaesthesia and critical care medicine. Aspiration of acidic gastric contents in the perioperative setting is linked to pneumonitis and later development of pneumonia. Pharmacological strategies to minimize this risk include histamine-2 receptor antagonists, sucralfate, proton pump inhibitors and sodium citrate. Use of gastric acid suppressing therapy is widespread in intensive care units to reduce the incidence of stress-related mucosal bleeding. Intestinal failure is common in critical illness. Medications that decrease gastric motility and contribute to ileus include opioid analgesics, catecholamines and α 2 -adrenoceptor antagonists. Current pharmacological strategies for increasing gastric motility include the use of metoclopramide and erythromycin, either alone or in combination, though their effectiveness in clinical practice is limited. A range of further medications, with different drug targets, are being investigated as alternatives. These include specific motilin receptor agonists, peripherally acting opioid receptor antagonists, cholecystokinin antagonists, 5HT 4 antagonists and cholinesterase inhibitors. [ABSTRACT FROM AUTHOR]