Educational Intervention Improves Proton Pump Inhibitor Stewardship in Outpatient Gastroenterology Clinics.

BACKGROUND: Improper chronic proton pump inhibitor (PPI) use has risen significantly in the last few decades. In our gastroenterology trainees' clinics, we aimed to optimize PPI usage. METHODS: We collected baseline data on patients' PPI use for 8 weeks. Based on gastroenterology society guidelines, we determined conditions for appropriate PPI use. If the indication could not be determined, it was categorized as "unknown". Generated from the three most frequent causes for inappropriate PPI use, interventions were developed to correct each issue. Following a brief educational session, trainees implemented these interventions over a subsequent 8-week interval. RESULTS: During our pre-intervention period, trainees evaluated 263 patients who were prescribed a PPI. In 49% of the cases, the use of PPI was deemed inappropriate. The most common reasons were: gastroesophageal reflux disease (GERD) which was never titrated to the lowest effective dose, twice daily dosing for Barrett's esophagus (BE) chemoprevention and unknown indication. During our intervention period, trainees evaluated 145 patients prescribed a PPI for GERD with well-controlled symptoms in 101 cases. PPI had not been titrated to lowest effective dose in 37 cases prompting intervention which was successful in 23 cases. PPI indication was unknown in 17 cases prompting a message to the prescribing provider to review appropriateness. Two cases of BE chemoprevention with twice daily dosing were appropriately reduced to daily dosing. Ultimately, after intervention, PPI use was deemed appropriate after intervention in 172 (77%) cases. CONCLUSIONS: Improper chronic PPI use was significant. Focusing intervention efforts on PPI use for GERD, BE and unknown indications substantially increased appropriateness of PPI use.

Diagnostic Approach for Classic Compared With Localized Whipple Disease.

BACKGROUND: Whipple disease (WD), a rare systemic infection caused by Tropheryma whipplei, can be a diagnostic challenge due to its variable presentation. The role of T. whipplei polymerase chain reaction (PCR) is unclear as small bowel biopsy with Periodic acid-Schiff (PAS) staining remains the diagnostic gold standard. Individualized diagnostic approaches based on variable clinical manifestations are underutilized. We investigated the methodologies employed at our institution to diagnose WD. METHODS: We retrospectively collected all cases of WD diagnosed from 1994 to 2016. Microbiology laboratory and anatomic pathology databases were queried. Case characteristics and disease clinical phenotypes (classical, localized WD arthritis, and localized central nervous system [CNS] disease) were described. The diagnostic approach and testing yield were analyzed and reported. RESULTS: Thirty-three cases of WD were diagnosed (18 classic WD [CWD], 9 localized WD arthritis [LWD], 6 CNS WD). Misdiagnosis and delay in diagnosis were frequent. Diagnostic approach and test yield differed by classical vs localized WD involvement. Small bowel tissue biopsy PAS stain/PCR was overwhelmingly positive (86%/92%) in CWD, yet seldom positive (12%/42%) in LWD (P < .001). Affected joint synovial fluid PCR was frequently positive in both CWD (100%, 3/3) and LWD (85%, 6/7). CONCLUSIONS: These results support the role of small bowel biopsy PAS stain/PCR in the diagnosis of CW, though this approach may be of limited utility in LWD or CNS WD without gastrointestinal symptoms. Affected joint synovial fluid or cerebrospinal fluid PCR was frequently positive in both CWD and LWD, supporting its diagnostic usefulness.

Prevalence and Predictors of Gastroesophageal Reflux Complications in Community Subjects.

BACKGROUND: Predictors of erosive esophagitis (EE) and Barrett's esophagus (BE) and the influence of number of risk factors in the community are not well defined. METHODS: Rates of BE and EE among community residents identified in a randomized screening trial were defined. The risk of EE and BE associated with single and multiple risk factors (gender, age, GERD, Caucasian ethnicity, ever tobacco use, excess alcohol use, family history of BE or EAC, and central obesity) was analyzed. RESULTS: Sixty-eight (33 %) of 205 subjects had EE and/or BE. BE prevalence was 7.8 % with dysplasia present in 1.5 %. Rates were comparable between subjects with and without GERD. Male sex and central obesity were independent risk factors. The odds of EE or BE were 3.7 times higher in subjects with three or four risk factors and 5.7 times higher in subjects with five or more risk factors compared with those with two or less factors. CONCLUSIONS: EE and BE are prevalent in the community regardless of the presence of GERD. Risk appeared to be additive, increasing substantially with three or more risk factors.

Predictors of double balloon endoscopy outcomes in the evaluation of gastrointestinal bleeding.

AIM: To identify patients' characteristics associated with double balloon endoscopy (DBE) outcomes in investigation of obscure gastrointestinal bleeding (OGIB). METHODS: Retrospective study performed at an academic tertiary referral center. Evaluated endpoints were clinical factors associated with no diagnostic yield or non-therapeutic intervention of DBE performed for OGIB evaluation. RESULTS: We included fifty-five DBE between August 2010 and April 2012. The mean age of the sample was 67 with 32 males (58.2%). Twenty-four DBE had no diagnostic yield and 30 DBE did not require therapy. Non-diagnostic yield was associated with performing two or more DBE studies in one day [odds ratio (OR): 13.72, P = 0.008], absence of blood transfusions within a year of the DBE (OR: 7.16, P = 0.03) and absence of ulcers or arteriovenous malformations (AVMs) on prior esophagogastroduodenoscopy (EGD) or colonoscopy (OR: 19.30, P = 0.033). Non-therapeutic DBE was associated with performing two or more DBE per day (OR: 18.579, P = 0.007), gastrointestinal bleeding episode within a week of the DBE (OR: 11.48, P = 0.003), fewer blood transfusion requirements prior to DBE (OR: 4.55, P = 0.036) and absence of ulcers or AVMs on prior EGD or colonoscopy (OR: 8.47, P = 0.027). CONCLUSION: Predictors of DBE yield and therapeutic intervention on DBE include blood transfusion requirements, previous endoscopic findings and possibly endoscopist fatigue.

Morphine modulation of thrombospondin levels in astrocytes and its implications for neurite outgrowth and synapse formation.

Opioid receptor signaling via EGF receptor (EGFR) transactivation and ERK/MAPK phosphorylation initiates diverse cellular responses that are cell type-dependent. In astrocytes, multiple µ opioid receptor-mediated mechanisms of ERK activation exist that are temporally distinctive and feature different outcomes. Upon discovering that chronic opiate treatment of rats down-regulates thrombospondin 1 (TSP1) expression in the nucleus accumbens and cortex, we investigated the mechanism of action of this modulation in astrocytes. TSP1 is synthesized in astrocytes and is released into the extracellular matrix where it is known to play a role in synapse formation and neurite outgrowth. Acute morphine (hours) reduced TSP1 levels in astrocytes. Chronic (days) opioids repressed TSP1 gene expression and reduced its protein levels by µ opioid receptor and ERK-dependent mechanisms in astrocytes. Morphine also depleted TSP1 levels stimulated by TGFß1 and abolished ERK activation induced by this factor. Chronic morphine treatment of astrocyte-neuron co-cultures reduced neurite outgrowth and synapse formation. Therefore, inhibitory actions of morphine were detected after both acute and chronic treatments. An acute mechanism of morphine signaling to ERK that entails depletion of TSP1 levels was suggested by inhibition of morphine activation of ERK by a function-blocking TSP1 antibody. This raises the novel possibility that acute morphine uses TSP1 as a source of EGF-like ligands to activate EGFR. Chronic morphine inhibition of TSP1 is reminiscent of the negative effect of µ opioids on EGFR-induced astrocyte proliferation via a phospho-ERK feedback inhibition mechanism. Both of these variations of classical EGFR transactivation may enable opiates to diminish neurite outgrowth and synapse formation.