An Objective Structured Clinical Examination to Assess Competency Acquired During an Introductory Pharmacy Practice Experience.

Objective. To evaluate the use of an objective structured clinical examinations (OSCE) to assess clinical competency acquired during an off-campus introductory pharmacy practice experience (IPPE). Methods. Third-year pharmacy students completed an IPPE in transitions of care and completed 24 experiential contact hours at one of 17 practice sites. Students were assessed using two OSCEs, the first occurring prior to beginning an off-site IPPE (pre-experience OSCE) and the second occurring after completion of the off-site IPPE (post-experience OSCE). Each OSCE consisted of 10 stations and covered five graded competency domains. The primary outcome was the degree of change in student performance from the pre-experience OSCE to the post-experience OSCE. Secondary outcomes included changes in each graded domain, OSCE pass rate, and failure conversion rate. Results. Of 111 students, 109 completed both the pre- and post-experience OSCE. Significant improvements were observed in overall score and cohort pass rate. Overall scores improved from 80 for the pre-experience OSCE to 87 for the post-experience OSCE. The OSCE pass rate also improved from 47% to 84%. Conclusion. Although preceptor evaluations have traditionally served as the primary summative assessment for IPPE and APPE, this study indicates that OSCEs may be a reliable alternative to assess clinical competency acquired from off-site practice experiences.

Safety and efficacy of endoscopic spray cryotherapy for esophageal cancer.

Although surgery is traditionally the standard of care for esophageal cancer, esophagectomy carries significant morbidity. Alternative endoscopic therapies are needed for patients who are not candidates for conventional treatment. The objective of this study is to assess the safety, efficacy, and tolerability of spray cryotherapy of esophageal adenocarcinoma. This study includes patients with esophageal adenocarcinoma who had failed or were not candidates for conventional therapy enrolled retrospectively and prospectively in an open-label registry and patients in a retrospective cohort from 11 academic and community practices. Endoscopic spray cryotherapy was performed until biopsy proven local tumor eradication or until treatment was halted due to progression of disease, patient withdrawal or comorbidities. Eighty-eight patients with esophageal adenocarcinoma (median age 76, 80.7% male, mean length 5.1 cm) underwent 359 treatments (mean 4.4 per patient). Tumor stages included 39 with T1a, 25 with T1b, 9 with unspecified T1, and 15 with T2. Eighty-six patients completed treatment with complete response of intraluminal disease in 55.8%, including complete response in 76.3% for T1a, 45.8% for T1b, 66.2% for all T1, and 6.7% for T2. Mean follow-up was 18.4 months. There were no deaths or perforations related to spray cryotherapy. Strictures developed in 12 of 88 patients (13.6%) but were present before spray cryotherapy in 3 of 12. This study suggests that endoscopic spray cryotherapy is a safe, well-tolerated, and effective treatment option for early esophageal adenocarcinoma.

Safety and efficacy of endoscopic spray cryotherapy for Barrett's dysplasia: results of the National Cryospray Registry.

Retrospective series have shown the efficacy of endoscopic spray cryotherapy in eradicating high-grade dysplasia (HGD) in Barrett's esophagus (BE); however, prospective data are lacking, and efficacy for low-grade dysplasia (LGD) is unclear. The aim of this study was to assess the efficacy and safety of spray cryotherapy in patients with LGD or HGD. A multicenter, prospective open-label registry enrolled patients with dysplastic BE. Spray cryotherapy was performed every 2-3 months until there was no endoscopic evidence of BE and no histological evidence of dysplasia, followed by surveillance endoscopies up to 2 years. Primary outcome measures were complete eradication of dysplasia (CE-D) and complete eradication of all intestinal metaplasia (CE-IM). Ninety-six subjects with Barrett's dysplasia (67% HGD; 65% long-segment BE; mean length 4.5 cm) underwent 321 treatments (mean 3.3 per subject). Mean age was 67 years, 83% were male. Eighty patients (83%) completed treatment with follow-up endoscopy (mean duration 21 months). In patients with LGD, rate of CE-D was 91% (21/23) and rate of CE-IM was 61% (14/23). In HGD, CE-D rate was 81% (46/57) and CE-IM was 65% (37/57). In patients with short-segment BE (SSBE) with any dysplasia, CE-D was achieved in 97% (30/31) and CE-IM in 77% (24/31). There were no esophageal perforations or related deaths. One subject developed a stricture, which did not require dilation. One patient was hospitalized for bleeding in the setting of non-steroidal anti-inflammatory drug use. In the largest prospective cohort to date, data suggest endoscopic spray cryotherapy is a safe and effective modality for eradication of BE with LGD or HGD, particularly with SSBE.

Nicotinic acid receptor abnormalities in human skin cancer: implications for a role in epidermal differentiation.

BACKGROUND: Chronic UV skin exposure leads to epidermal differentiation defects in humans that can be largely restored by pharmacological doses of nicotinic acid. Nicotinic acid has been identified as a ligand for the human G-protein-coupled receptors GPR109A and GPR109B that signal through G(i)-mediated inhibition of adenylyl cyclase. We have examined the expression, cellular distribution, and functionality of GPR109A/B in human skin and skin derived epidermal cells. RESULTS: Nicotinic acid increases epidermal differentiation in photodamaged human skin as judged by the terminal differentiation markers caspase 14 and filaggrin. Both GPR109A and GPR109B genes are transcribed in human skin and in epidermal keratinocytes, but expression in dermal fibroblasts is below limits of detection. Receptor transcripts are greatly over-expressed in squamous cell cancers. Receptor protein in normal skin is prominent from the basal through granular layers of the epidermis, with cellular localization more dispersive in the basal layer but predominantly localized at the plasma membrane in more differentiated epidermal layers. In normal human primary and immortalized keratinocytes, nicotinic acid receptors show plasma membrane localization and functional G(i)-mediated signaling. In contrast, in a squamous cell carcinoma derived cell line, receptor protein shows a more diffuse cellular localization and the receptors are nearly non-functional. CONCLUSIONS: The results of these studies justify future genetic and pharmacological intervention studies to define possible specific role(s) of nicotinic acid receptors in human skin homeostasis.

The Effect of Metformin and Standard Therapy versus Standard Therapy alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial.

Nonalcoholic steatohepatitis (NASH) is increasing in prevalence and is related to underlying insulin resistance. The aim of this study was to assess the efficacy of metformin on the characteristic histopathologic lesions of NASH. This was a 12-month prospective, randomized, placebo-controlled trial comparing diet and exercise alone to diet, exercise and metformin in nondiabetic patients with insulin resistance and NASH. Patients were randomized to either group A or B. Group A received placebo, dietary counseling, recommendations for weight loss and exercise four times per week. Group B received long-acting metformin 500 mg daily (titrated to 1000 mg daily) plus dietary counseling, recommendations for weight loss and exercise four times per week. Histopathology was assessed at 12 months and biopsies were scored by two pathologists who were blinded to all data. Twenty-three subjects were screened and 19 were randomized to either group A (n »10) or group B (n» 9). Seven of the 10 subjects in group A completed the study including repeat liver biopsy while all patients in group B completed the study. Body mass index improved in both groups decreasing by 1.7 kg/m(2) in group A and 0.9 kg/m(2) in group B (not significant, control versus treatment). Homeostasis model assessment of insulin resistance scores improved in both groups decreasing by 1.14 in group A and 1.58 in group B (not significant, control versus treatment). No significant difference in histopathology was seen between groups on follow-up liver biopsy. Metformin appeared to have little effect in improvement in liver function tests or liver histology in nondiabetic patients with insulin resistance and NASH. Decrease in BMI through diet and exercise significantly improved HOMA-IR scores, serum aminotransferases and liver histology.

Effect of myristyl nicotinate on retinoic acid therapy for facial photodamage.

Based on the hypothesis that skin barrier impairment is a contributor to side-effects associated with retinoic acid therapy, a double-blind, placebo-controlled pilot study examined the combined use of retinoic acid with myristyl nicotinate (MN), a lipophilic derivative of niacin that enhances skin barrier function, in female subjects with mild to moderate facial photodamage. The study involved a 1-month run-in period with placebo or MN prior to initiation of retinoic acid therapy for 3 months. Analysis of skin biopsies revealed that retinoic acid therapy resulted in stratum corneum thinning of approximately 25% (P = 0.006 versus baseline) that was ameliorated by MN use (P < 0.005). Therapy resulted in an increased rate of transepidermal water loss (TEWL) of approximately 45% (P = 0.001 versus baseline) and use of MN protected against the increase in TEWL with the strongest protection provided by prior use of MN (P = 0.056 versus placebo). MN use reduced the incidence of side-effects of the therapy and again prior use provided the greatest reduction of side-effects. Subjects showed statistically significant clinical improvement (P < 0.05 versus baseline) during the study. MN use did not interfere with any clinical improvement parameters and improved effects on temple laxity (P = 0.01 versus placebo). Analysis of changes in epidermal thickness, Ki67-positive cells and intensity of loricrin staining demonstrated that MN either improved or did not interfere with retinoic acid efficacy. These results show that prior and concurrent use of MN can mitigate barrier impairment and improve the tolerability of retinoic acid therapy for facial photodamage without interfering with efficacy.

A topical lipophilic niacin derivative increases NAD, epidermal differentiation and barrier function in photodamaged skin.

The effects of myristyl nicotinate (MN), a nicotinic acid derivative designed to deliver nicotinic acid to skin without vasodilatation, on subjects with photodamaged skin have been studied. MN increased skin cell nicotinamide adenine dinucleotide (NAD) by 25% (P = 0.001) demonstrating effective delivery of nicotinic acid to skin. Relative to placebo, MN treatment of photodamaged facial skin increased stratum corneum thickness by approximately 70% (P = 0.0001) and increased epidermal thickness by approximately 20% (P = 0.001). In two separate studies, MN treatment increased rates of epidermal renewal by 6% (P = 0.003) to 11% (P = 0.001) and increased the minimal erythemal dose by 8.9 (P = 0.07) and 10% (P = 0.05) relative to placebo. MN treatment resulted in reductions in the rates of transepidermal water loss (TEWL) of approximately 20% relative to placebo on cheeks (P = 0.012) and arms (P = 0.017) of study subjects. Results of a tape stripping challenge before and after MN treatment demonstrated a significant correlation (P = 0.03) between increased skin NAD content and resistance to changes in TEWL for MN treated but not placebo subjects. Rates of TEWL changed more rapidly and to a greater extent in atopic subjects compared with normal subjects. The results indicate that MN enhances epidermal differentiation and barrier function in skin, suggesting that this method of nicotinic acid delivery may prove useful in limiting progression of actinic skin damage and possibly in treating other conditions involving skin barrier impairment.

Thermal and photochemistry of a pyrene dihydrodioxin (PDHD) and its radical cation: a photoactivated masking group for ortho-quinones.

Pyrene dihydrodioxins (1 and 2) have been synthesized and shown to be effective photochemical blocking groups for pyrene-4,5-dione (3). The mechanism of quinone release proceeds through the formation of a remarkably stable radical cation. Direct evidence is provided that this radical cation is not only thermally labile but also photochemically labile, and that both pathways lead to quinone extrusion. Once initiated with UV light, the pyrene quinone product serves as an electron-transfer photosensitizer for the further release of quinone with visible light.

Evaluation of unexplained acute and acute recurrent pancreatitis using endoscopic retrograde cholangiopancreatography, sphincter of Oddi manometry and endoscopic ultrasound.

BACKGROUND AND STUDY AIMS: Unexplained pancreatitis represents a diagnostic challenge. The aim of this study was to determine the diagnostic utility of endoscopic retrograde cholangiopancreatography (ERCP) with sphincter of Oddi manometry (SOM), bile analysis, and endoscopic ultrasound (EUS) in evaluating such patients. PATIENTS AND METHODS: Of 162 patients referred for evaluation of pancreatitis, 72 with a known cause were excluded. The remainder ( n=90) was classified as having prior acute ( n=24) or recurrent acute pancreatitis ( n=66). Bile sampling and SOM were performed at the time of ERCP. EUS was used to assess for tumors and for chronic pancreatitis. Clinical outcomes were evaluated by questionnaire. RESULTS: ERCP was successful in 88/89 patients (99 %). Manometry was successful in 63/67 patients (94 %), and 56 patients underwent EUS. Findings were categorized into five distinct etiologies: sphincter of Oddi dysfunction (SOD) ( n=28; 31 %), pancreas divisum ( n=18; 20 %), biliary ( n=18; 20 %), idiopathic ( n=18; 20 %) and tumor-related ( n=8; 9 %). Features of moderate or severe chronic pancreatitis by EUS and ERCP criteria were found in 18 patients (21 %); an additional nine patients had chronic pancreatitis by EUS criteria alone. EUS identified all the tumors. The condition was improved in 96 % of all patients undergoing endoscopic therapy. CONCLUSION: An etiology was identified in the majority of patients with unexplained pancreatitis. SOD represented the most common finding. Moderate to severe chronic pancreatitis was found in over one-fifth of these patients. Bile analysis, SOM, and EUS are useful tools in the evaluation of unexplained acute pancreatitis.

EUS and fine-needle aspiration in the evaluation of mediastinal masses superior to the aortic arch.

BACKGROUND: Mediastinal lesions require a tissue diagnosis. This cannot be obtained with CT-guided biopsy or bronchoscopy in many patients. Co-morbid diseases increase the risk of mediastinoscopy in some of these patients. EUS with fine-needle aspiration (FNA) is frequently used to obtain tissue from the mediastinum, but there have been no case series published of FNA of lesions superior to the aortic arch. METHODS: This is the report of a case series of 4 patients with mediastinal masses superior to the aortic arch. EUS with a linear array echoendoscope and FNA were performed to evaluate each lesion. OBSERVATIONS: All 4 patients underwent the procedure without complication, and cytologic material obtained in 3 was diagnostic. One patient had a nondiagnostic aspirate and underwent mediastinoscopy. CONCLUSIONS: EUS with FNA is a safe and effective method for tissue diagnosis of mediastinal lesions. Heretofore, mediastinoscopy or transtracheal biopsy was required for diagnosis in patients with lesions superior to the aortic arch. However, for such lesions EUS with FNA appears to be an excellent alternative for establishing a diagnosis.

Eradication of Helicobacter pylori normalizes elevated mucosal levels of epidermal growth factor and its receptor.

OBJECTIVE: Helicobacter pylori (H. pylori) infection has been linked to gastric cancer. The factors that promote carcinogenesis remain unknown. Epidermal growth factor (EGF) has been shown to be a potent epithelial mitogen and oncoprotein when sustained over expression occurs. Our aim was to compare gastric mucosal levels of EGF and its receptor (EGFR) among controls, H. pylori infected subjects, and subjects following H. pylori eradication using quantitative flow cytometric analysis. METHODS: Patients referred for evaluation of dyspepsia underwent EGD and six antral biopsies were performed (two each for rapid urease testing (RUT), histopathology, and flow cytometry). Controls were those found to be H. pylori negative while subjects had confirmed infection. The study patients were treated, then had repeat EGD with biopsies. RESULTS: There were 17 controls and 28 cases. Mean EGF and EGFR values were 2.69 and 2.46 for controls and 4.67 and 4.64 for subjects. Subjects' mean EGF was 73% higher (p = .035) and EGFR was 88% higher (p = 0.029) than controls. After treatment, the subjects' mean values declined 55% (p = 0.0001) for EGF and 40% (p = 0.002) for EGFR. Three subjects had persistent infection and showed no change in their EGF/EGFR levels. No difference was found among factor levels with respect to endoscopic findings. CONCLUSIONS: Both EGF and EGFR from gastric antral biopsies are increased nearly 2-fold in infection with H. pylori. Infection eradication reduces levels of both factors to those of controls. One major pathogenic mechanism for gastric mucosal hyperproliferation and possibly carcinogenesis related to H. pylori may be the over expression of EGF and increased receptor density of EGFR on gastric mucosal cells.

Sphincter of Oddi dysfunction is associated with chronic pancreatitis.

OBJECTIVES: Chronic pancreatitis can be caused by ductal obstruction resulting from cicatricial papillary stenosis, but sphincter of Oddi motility studies have been inconclusive in patients with established chronic pancreatitis. We sought to determine whether there is an association between papillary sphincter dysfunction and changes of early chronic pancreatitis. METHODS: Consecutive patients who underwent sphincter of Oddi manometry to investigate unexplained upper abdominal pain (n = 104) were assessed for evidence of chronic pancreatitis by pancreatic ductography, endoscopic ultrasound, and pancreatic fluid bicarbonate concentration. RESULTS: Sphincter of Oddi dysfunction patients were four times more likely (odds ratio = 4.6) to have evidence of chronic pancreatitis than were those without sphincter dysfunction (p = 0.01). Of 68 patients with sphincter of Oddi dysfunction, 20 (29%) had structural evidence of chronic pancreatitis. Twenty of 23 (87%) patients with chronic pancreatitis had sphincter of Oddi dysfunction. CONCLUSIONS: Sphincter of Oddi dysfunction is associated with changes of chronic pancreatitis in patients with unexplained pancreaticobiliary pain. Longitudinal follow-up is required to confirm these preliminary findings.

Upper gastrointestinal tract bleeding.

Upper GI bleeding is a serious and common emergency. Most upper GI bleeding will stop spontaneously but determining which patients will continue to bleed or rebleed is very difficult in the ED. Resuscitation and stabilization are the primary goals of the emergency physician. Hemorrhage control with pharmacotherapy or balloon tamponade may be necessary until urgent or emergent consultation with a gastroenterologist or surgeon is obtained. Early detection and treatment of H. pylori and the development of safer NSAIDs should alter the future of upper GI bleeding dramatically.

Efficacy of ciprofloxacin in the eradication of Helicobacter pylori.

In small preliminary trials, ciprofloxacin has failed to eradicate Helicobacter pylori. Since fluoroquinolones have a marked reduction in bactericidal activity at acidic pH, we altered the gastric pH using omeprazole and investigated the efficacy of ciprofloxacin in eradicating H pylori. Forty-four consecutive patients infected with H pylori were prospectively studied in a randomized, double-blind, controlled trial comparing ciprofloxacin with a placebo for 2 weeks. Both treatment groups received bismuth and omeprazole. In 36 patients, follow-up endoscopy was done 4 weeks after the cessation of all study drugs. The H pylori infection cleared in 13 of 17 patients (76%) in the ciprofloxacin group versus 5 of 19 (26%) in the placebo group. Concurrent administration of omeprazole with ciprofloxacin resulted in increased bactericidal activity against H pylori. Ciprofloxacin when combined with omeprazole and bismuth is efficacious for eradication of H pylori.