Angiotensin-converting enzyme inhibitor therapy and colorectal cancer risk.

BACKGROUND: Laboratory data suggest a role of angiotensin II in the pathogenesis of colorectal cancer (CRC). Whether angiotensin converting enzyme inhibitor (ACE-I) and/or angiotensin receptor blocker (ARB) use reduces the risk of colorectal neoplasia remains unclear. Given their widespread use, we sought to determine whether exposure to these agents would have a secondary benefit on CRC incidence. METHODS: A nested case-control study was conducted using EPIC's General Practice Research Database (1987-2002). The study cohort consisted of hypertensive patients. Case patients were those diagnosed with CRC after the diagnosis of hypertension. Each case patient was matched to up to 10 control subjects on age, sex, and both calendar year and duration of follow-up using incidence density sampling. The association between CRC and ACE-I/ARB exposure was assessed with conditional logistic regression. All statistical tests were two-sided. RESULTS: Two thousand eight-hundred forty-seven case patients were matched with 28239 control subjects. The adjusted odds ratios (ORs) of CRC were 0.84 (95% confidence interval [CI] = 0.72 to 0.98; P = .03) for or more years of ACE-I/ARB therapy and 0.75 (95% CI = 0.58 to 0.97; P = .03) for 5 or more years of exposure. The strength of this association increased with high-dose exposure (OR = 0.53; 95% CI = 0.35 to 0.79; P = .003 for ≥3 years of high-dose exposure). Among patients receiving antihypertensive medications, the association with long-term therapy was no longer statistically significant for ≥5 years), but the benefit of high-dose therapy remained (OR = 0.59; 95% CI = 0.39 to 0.89; P = .01 for ≥3 years of high-dose exposure). CONCLUSIONS: Long-term/high dose exposure to ACE-Is/ARBs may be associated with a decreased incidence of CRC.

Poor discriminatory function for endoscopic skills on a computer-based simulator.

BACKGROUND: Computer-based endoscopy simulators may enable trainees to learn and develop technical skills before performing on patients. Simulators require validation as adequate models of live endoscopy before being used for training or assessment purposes. OBJECTIVE: To evaluate content and criterion validity of the CAE EndoscopyVR Simulator colonoscopy and EGD modules as predictors of clinical endoscopic skills. DESIGN: Prospective, observational, non-randomized, parallel cohort study. SETTING: Single academic center with accredited gastroenterology training program. PARTICIPANTS: Five novice first-year gastroenterology fellows and 6 expert gastroenterology attending physicians. INTERVENTION: Participants performed 18 simulated colonoscopies and 6 simulated EGDs. The simulator recorded objective performance parameters. Participants then completed feedback surveys. MAIN OUTCOME MEASUREMENTS: The 57 objective performance parameters measured by the endoscopy simulator were compared between the two study groups. Novice and expert survey responses were analyzed. RESULTS: Significant differences between novice and expert performance were detected in only 19 of 57 (33%) performance metrics. Eight of these 19 (42%) were time-related metrics, such as total procedure time, time to anatomic landmarks, and time spent in contact with GI mucosa. Of 49 non-time related measures, the few additional statistically significant differences between novices and experts involved air insufflation, sedation management, endoscope force, and patient comfort. These findings are of uncertain clinical significance. Survey data found multiple aspects of the simulation to be unrealistic compared with human endoscopy. LIMITATIONS: Small sample size. CONCLUSION: The CAE EndoscopyVR Simulator displays poor content and criterion validity and is thereby incapable of predicting skill during in vivo endoscopy.

Liver transplantation in patients with cystic fibrosis: analysis of United Network for Organ Sharing data.

The improved life expectancy of patients with cystic fibrosis (CF) has led to a change in the impact of liver disease on the prognosis of this population. Liver transplantation has emerged as the procedure of choice for patients with CF and features of hepatic decompensation and for intractable variceal bleeding as a major manifestation. We retrospectively reviewed the United Network for Organ Sharing database to analyze the outcomes of 55 adults and 148 children with CF who underwent liver transplantation, and we compared them to patients who underwent transplantation for other etiologies. We additionally compared the benefits of liver transplantation among patients who underwent transplantation for cystic fibrosis-related liver disease (CFLD) and those who remained on the waiting list. The 5-year survival rates for children and adults undergoing liver transplantation were 85.8% and 72.7%, respectively (P = 0.016). A multivariate Cox regression analysis comparing pediatric and adult CF patients to patients who underwent transplantation for other etiologies noted lower 5-year survival rates (P < 0.0001). However, compared to those remaining on the waiting list, pediatric transplant recipients with CF (hazard ratio = 0.33, 95% confidence interval = 0.16-0.70, P = 0.004) and adult transplant recipients with CF (hazard ratio = 0.25, 95% confidence interval = 0.11-0.57, P = 0.001) gained a significant survival benefit. In conclusion, long-term outcomes in patients with CFLD are acceptable but are inferior in comparison with the outcomes of those undergoing transplantation for other etiologies. Despite such observations, a survival benefit was noted in transplant patients versus those who remained on the waiting list.

Lack of a discriminatory function for endoscopy skills on a computer-based simulator.

BACKGROUND: Computer-based endoscopy simulators have been developed to enable trainees to learn and gain technical endoscopic skills before operating on patients. However, these simulators have not been validated as models of patient-based endoscopy. This study aimed to determine whether a computer-based simulator can accurately represent an actual esophagogastroduodenoscopy (EGD) and colonoscopy and to evaluate its ability to discriminate between varying levels of expertise in performing endoscopic procedures based on objective parameters. METHODS: In a prospective, observational trial, five first-year gastroenterology fellows and six gastroenterology attendings from a single academic center completed six endoscopy cases on the Simbionix GI Mentor II endoscopy simulator. The cases were selected to represent common clinical scenarios. The performance parameters were collected by the simulator. The 13 performance parameters measured by the endoscopy simulator were compared between the two study groups. After the simulator cases, the participants completed a survey evaluating the realism of the simulator. RESULTS: Novices and experts were able to complete the tasks in the simulated cases with no significant overall differences between the two groups. The computer-based simulator was able to discriminate levels of expertise only for parameters related to the time spent on the procedure (total time, time to reach the second duodenum, time to reach the cecum, and efficiency of screening). No statistically significant differences were found for the other nine performance parameters measured by the simulator. Based on the survey data, expert opinion concluded that the simulator does not offer a realistic simulation of human endoscopy. CONCLUSIONS: The computer-based endoscopy simulator displays a lack of ability to discriminate between novices and experts in terms of endoscopic skills based on measured objective performance parameters. The findings of this study suggest that the computer-based simulator lacks fidelity and that upgrades are necessary to increase the simulator's ability to reproduce human endoscopy more accurately.

Presumed corneal copper deposition and oral contraceptive use.

PURPOSE: To report a case of presumed bilateral corneal copper deposition secondary to oral contraceptive use. METHODS: A 23-year-old woman was referred for evaluation of bilateral corneal opacities. The location of the deposits deep in Descemet's membrane and appearance made copper deposition a likely consideration. RESULTS: Subsequent laboratory results revealed an elevated serum copper level (189 µg/dL). Other causes of cupremia were subsequently ruled out, and the patient's corneal copper deposition was attributed to her oral contraceptive use. With cessation of the oral contraceptive, her serum copper levels normalized, but the corneal deposits remained after 5 months of follow up. CONCLUSION: To our knowledge, we report the first case in the ophthalmic literature of presumed corneal copper deposition in the setting of oral contraceptive use. It is important to recognize the corneal findings associated with copper deposition, because it may lead to the diagnosis and treatment of other serious systemic conditions causing elevated serum copper levels.

Incidence and prevalence of abnormal liver associated enzymes in patients with atrial fibrillation in a routine clinical care population.

UNLABELLED: The prevalence of elevated liver enzymes has not been described in patients with atrial fibrillation (AF) who may be more likely to develop these abnormalities due to comorbidities and medications. As signals of liver injury lead to termination of drug development programs, an attempt to better define the background prevalence would aid in interpreting these elevations in the setting of exposure to a new drug. The aim of this study was to estimate the prevalence and incidence of alanine aminotransferase (ALT) elevations in a cohort with AF. METHODS: Retrospective cohort of patients with AF using the outpatient medical record of the University of Pennsylvania Health System (UPHS). Primary outcomes were prevalence and incidence of ALT elevations (>40 U/L). We also examined the prevalence of risk factors for ALT elevations. RESULTS: Liver enzymes were measured at least once in 1630 of 2151 patients (76%). The prevalence of ALT >40 U/L was 27.6% (95%CI 25.7-29.5%). The incidence of new ALT elevations was 14.5/100 person-years (95%CI 13.0-16.1) for ALT > 40 U/L and 2.1/100 person-years (95%CI 1.6-2.8) for ALT elevations above twice the upper limit of normal (ULN). New persistent ALT elevations above twice the ULN were identified in 0.2% of patients. CONCLUSION: Elevated ALT is common among patients with AF, although new and persistent elevation greater than twice the ULN is uncommon. In the setting of a new drug, these factors make it difficult to delineate drug-induced liver injury from incident elevations due to comorbidities.

Therapy insight: approaching endoscopy in anticoagulated patients.

Over the past decade, the application of anticoagulant and antiplatelet agents for various cardiovascular and hematologic conditions has become more widespread. Optimal management of these agents during the periendoscopic period requires consideration, but limited prospective data mean that guidelines have largely relied on expert opinion. Elective procedures should be delayed in patients on temporary anticoagulation therapy (e.g. those with deep vein thrombosis). For procedures considered to have a low risk of bleeding (e.g. diagnostic endoscopy and colonoscopy without polypectomy) there is no need to discontinue or adjust anticoagulation. For procedures with a higher risk of bleeding (e.g. polypectomy and biliary sphincterotomy) an individual approach is required. This approach might include stopping oral anticoagulant therapy with or without the administration of unfractionated heparin or low-molecular-weight heparin for the preprocedure and postprocedure periods, during which the patient's international normalized ratio is in the subtherapeutic range.