Correction to: What to Do and What Not to Do in the Management of Opioid-Induced Constipation: A Choosing Wisely Report.

The original article can be found online.

What to Do and What Not to Do in the Management of Opioid-Induced Constipation: A Choosing Wisely Report.

INTRODUCTION: Despite the essential utility of opioids for the clinical management of pain, opioid-induced constipation (OIC) remains an important obstacle in clinical practice. In patients, OIC hinders treatment compliance and has negative effects on quality of life. From a clinician perspective, the diagnosis and management of OIC are hampered by the absence of a clear, universal diagnostic definition across disciplines and a lack of standardization in OIC treatment and assessment. METHODS: A multidisciplinary panel of physician experts who treat OIC was assembled to identify a list of ten corrective actions-five "things to do" and five "things not to do"-for the diagnosis and management of OIC, utilizing the Choosing Wisely methodology. RESULTS: The final list of corrective actions to improve the diagnosis and clinical management of OIC emphasized a need for: (i) better physician and patient education regarding OIC; (ii) systematic use of diagnostically validated approaches to OIC diagnosis and assessment (i.e., Rome IV criteria and Bristol Stool Scale, respectively) across various medical contexts; and (iii) awareness about appropriate, evidence-based treatments for OIC including available peripheral mu-opioid receptor antagonists (PAMORAs). CONCLUSIONS: Physicians who prescribe long-term opioids should be forthcoming with patients about the possibility of OIC and be adequately versed in the most recent guideline recommendations for its management.

Two-week Triple Therapy with either Standard or High-dose Esomeprazole for First-line H. pylori Eradication.

BACKGROUND AND AIMS: The updated Italian guidelines advise a standard 14-day triple therapy for first-line H. pylori eradication. This prospective study evaluated the cure rate following a 14-day triple therapy with either a standard or double-dose proton pump inhibitor (PPI). METHODS: A total of 145 consecutive patients with H. pylori infection were randomized to receive a 14-day, first-line triple therapy with clarithromycin 500 mg, amoxicillin 1 g and esomeprazole at either 20 mg (standard therapy) or 40 mg (double-dose therapy), each given twice daily. RESULTS: At intention-to-treat analysis, H. pylori infection was cured in 73.9% (95% CI: 63.9-84) and 81.9% (95% CI: 73-90.8) following standard and double-dose therapy, respectively, and in 78.2% (95% CI: 68.5-87.9) and 85.5% (95% CI: 77.2-93.8) at per-protocol analysis. No statistically significant difference occurred. Overall, 16.4% and 19.4% patients in the standard and double-dose therapy regimen complained of side effects. CONCLUSION: The success rate of both standard and double-dose 14-day triple therapies for first-line H. pylori treatment was unsatisfactory. A prolonged 14-day levofloxacin-based triple therapy for second-line H. pylori eradication seems to be promising.

Alpha-1 adrenergic receptor agonists modulate ductal secretion of BDL rats via Ca(2+)- and PKC-dependent stimulation of cAMP.

Acetylcholine potentiates secretin-stimulated ductal secretion by Ca(2+)-calcineurin-mediated modulation of adenylyl cyclase. D2 dopaminergic receptor agonists inhibit secretin-stimulated ductal secretion via activation of protein kinase C (PKC)-gamma. No information exists regarding the effect of adrenergic receptor agonists on ductal secretion in a model of cholestasis induced by bile duct ligation (BDL). We evaluated the expression of alpha-1A/1C, -1beta and beta-1 adrenergic receptors in liver sections and cholangiocytes from normal and BDL rats. We evaluated the effects of the alpha-1 and beta-1 adrenergic receptor agonists (phenylephrine and dobutamine, respectively) on bile and bicarbonate secretion and cholangiocyte IP(3) and Ca(2+) levels in normal and BDL rats. We measured the effect of phenylephrine on lumen expansion in intrahepatic bile duct units (IBDUs) and cyclic adenosine monophosphate (cAMP) levels in cholangiocytes from BDL rats in the absence or presence of BAPTA/AM and Gö6976 (a PKC-alpha inhibitor). We evaluated if the effects of phenylephrine on ductal secretion were associated with translocation of PKC isoforms leading to increased protein kinase A activity. Alpha-1 and beta-1 adrenergic receptors were present mostly in the basolateral domain of cholangiocytes and, following BDL, their expression increased. Phenylephrine, but not dobutamine, increased secretin-stimulated choleresis in BDL rats. Phenylephrine did not alter basal but increased secretin-stimulated IBDU lumen expansion and cAMP levels, which were blocked by BAPTA/AM and Go6976. Phenylephrine increased IP(3) and Ca(2+) levels and activated PKC-alpha and PKC-beta-II. In conclusion, coordinated regulation of ductal secretion by secretin (through cAMP) and adrenergic receptor agonist activation (through Ca(2+)/PKC) induces maximal ductal bicarbonate secretion in liver diseases. (Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).