Efficacy and Safety of Mecobalamin Combined with Prokinetic Agents in the Treatment of Diabetic Gastroparesis: A Meta-Analysis

Background: The aim of the present study was to systematically review the efficacy and safety of mecobalamin combined with prokinetic agents in diabetic gastroparesis (DGP). Methods: A variety of databases were searched from inception to Nov 2, 2018. RCTs of mecobalamin combined with prokinetic agents group (experimental group) versus prokinetic agents only group (control group) in DGP were included. RevMan 5.3 and Stata 12.0 were used to perform the meta-analysis. Finally, 24 RCTs with 1,878 patients were included. Results: The total efficacy rate was significantly higher in the experimental group (mecobalamin combined with prokinetic drugs) compared with the control group (prokinetic drugs alone) (P<0.001), and the improvement was observed regardless of the administration route. Furthermore, the treatment group exhibited a significantly improved gastric emption rate (P<0.001), motilin (P<0.001) and recurrence rate (P<0.001), and there was no statistical difference in the incidence of adverse reactions between two groups (P=0.49). Conclusion: Mecobalamin combined with prokinetic agents can significantly improve total efficacy rate and gastric emptying rate, decrease serum motilin and the recurrence rate without increasing adverse reactions in DGP. Thus, mecobalamin may can be used as a new therapeutic option for DGP.

Management of Ineffective Esophageal Hypomotility

Esophageal hypomotility in general and especially ineffective esophageal motility according to the Chicago criteria of primary motility disorders of the esophagus, is one of the most frequently diagnosed motility disorders on high resolution manometry and results in a large number of patients visiting gastroenterologists. Most patients with esophageal hypomotility present with gastroesophageal reflux symptoms or dysphagia. The clinical relevance of the motility pattern, however, is not well established but seems to be correlated with disease severity in reflux patients. The correlation with dysphagia is less clear. Prokinetic agents are commonly prescribed as first line pharmacologic intervention to target esophageal smooth muscle contractility and improve esophageal motor functions. However, the beneficial effects of these medications are limited and only confined to some specific drugs. Serotonergic agents, including buspirone, mosapride and prucalopride have been shown to improve parameters of esophageal motility although the effect on symptoms is less clear. Understanding on the complex correlation between esophageal hypomotility and esophageal symptoms as well as the limited evidence of prokinetic agents is necessary for physicians to appropriately manage patients with Ineffective Esophageal Motility (IEM).

Could prokinetic agents protect long-term nasogastric tube-dependent patients from being hospitalized for pneumonia? A nationwide population-based case-crossover study

Background Some studies have indicated that the use of prokinetic agents may reduce pneumonia risk in some populations. Nasogastric tube insertion is known to increase the risk of pneumonia because it disrupts lower esophageal sphincter function. The aim of this study was to evaluate whether prokinetic agents could protect long-term nasogastric tube-dependent patients in Taiwan from being hospitalized for pneumonia. Methods A case-crossover study design was applied in this study. Long-term nasogastric tube-dependent patients who had a first-time admission to a hospital due to pneumonia from 1996 to 2013 that was recorded in the Taiwan National Health Insurance Research Database were included. The case period was set to be 30 days before admission, and two control periods were selected for analysis. Prokinetic agent use during those three periods was then assessed for the included patients. Conditional logistic regression was used to calculate the odds ratio (OR) for pneumonia admission with the use of prokinetic agents. Results A total of 639 first-time hospitalizations for pneumonia among patients with long-term nasogastric tube dependence were included. After adjusting the confounding factors for pneumonia, no negative association between prokinetic agent use and pneumonia hospitalization was found, and the adjusted OR was 1.342 (95% CI 0.967–1.86). In subgroup analysis, the adjusted ORs were 1.401 (0.982–1.997), 1.256 (0.87–1.814), 0.937 (0.607–1.447) and 2.222 (1.196–4.129) for elderly, stroke, diabetic and parkinsonism patients, respectively. Conclusion Prokinetic agent use had no negative association with pneumonia admission among long-term nasogastric tube-dependent patients in Taiwan.

The independent risk factors of early diarrhoea in enteral nutrition for ICU patients

Objective To investigate the prevalence of and factors associated with diarrhoea in the early stage of enteral nutrition in critically ill patients in intensive care units (ICUs). Methods This prospective, multicentre, observational study enrolled consecutive patients who were newly admitted to ICUs and received enteral nutrition treatment. Events were observed continuously for 7 days or until patients were transferred out of the ICU after enteral nutrition. Demographic and clinical data, enteral nutrition data, diarrhoea-related data and outcomes were recorded. A multivariate logistic regression analysis was used to analyse the risk factors for diarrhoea. Results The study included 533 patients, of whom 164 (30.8%) developed diarrhoea. Diarrhoea was most commonly observed on the first to third days after starting enteral nutrition treatment. The median (interquartile range) duration of diarrhoea was 2 (1–3) days. The administration of gastrointestinal prokinetic agents, the increase in acute physiological and chronic health scores and the pyloric posterior feeding method were independent risk factors for diarrhoea. Conclusion The increased severity of illness, the administration of gastrointestinal prokinetic agents and the pyloric posterior feeding method were independent risk factors for diarrhoea in critically ill ICU patients undergoing enteral nutrition treatment.

A Meta-Analysis of the Efficacy of Prokinetic Agents against Glycemic Control

Background. Prokinetic agents are used in diabetic gastroparesis patients to improve gastric emptying and upper gastrointestinal (GI) symptoms. However, the efficacy of prokinetic agents against glycemic control is questionable. Therefore, we conducted a systemic review and meta-analysis to determine the efficacy of prokinetic agents against glycemic control. Methods. Randomized controlled trials (RCTs) evaluating the effect of prokinetics were identified by searching PubMed, Embase, and the Cochrane Library databases until April 2018. The primary outcome was changes in the mean value of glycosylated hemoglobin (HbA1c), fasting blood sugar (FBS), and fasting serum insulin (FINS). The pooled standardized mean differences (SMD) with 95% confidence intervals (CIs) were calculated by evaluating the strength of the association. We used the random effect models to analyze these markers. The effects of each component of the prokinetic agents on glycemic control were separately analyzed. Results. Five RCTs with 190 patients met the criteria and were included in the meta-analysis. There were statistically significant SMD between prokinetics and placebo-controlled groups with respect to the reduction of HbA1c (-1.141, 95% CI -1.843, -0.438; P<0.01). No statistically significant differences were noted between the two groups for FBS (-1.270, 95% CI -2.613, -0.074; P=0.06) and FINS (0.359, 95% CI -1.205~1.923; P=0.65). Conclusions. Prokinetics have a positive effect on glycemic control. Further large-scale prospective studies are needed.

Prucalopride: novel drug for chronic idiopathic constipation

Chronic Idiopathic Constipation (CIC), defined as constipation in which the underlying cause is unknown, is a common medical illness with a profound negative impact on health-related quality of life and increased propensity for life threatening complications. Current treatment for CIC includes lifestyle modifications, over-the-counter medications, and prescription medications. Presently, the only approved, prescription products for CIC in the US are prosecretory agents. However, the current knowledge that serotonin plays an important role in colonic motility has opened new horizons in the treatment of CIC promoting use of prokinetic agents with a different mechanism of action. Prucalopride is a highly selective 5-hydroxytryptamine type 4 (5-HT4) receptor agonist that enhances propulsive motor patterns in the large intestine due to a high affinity for 5-HT4 receptors in gastrointestinal (GI) tissues. The onset of action of Prucalopride is fast, shows rapid absorption, oral bioavailability of 93% and linear pharmacokinetics. Most common adverse reactions seen are headache, nausea, diarrhea, and abdominal pain. Clinical trials for Prucalopride have been positive, and results suggest that the drug may be a new safe and effective option for CIC treatment, especially for patient’s refractory to prosecretory agents. As a prescription drug for the management of constipation and given the virtual demise of other prokinetic agents for this indication, prucalopride competes primarily with another class of agents: those that stimulate secretion. With Shire Pharmaceuticals having already received US FDA approval in Dec 2018, Prucalopride may soon be a new addition to the mounting armoury of drugs against CIC.