An analysis of the placebo effect in Crohn's disease over time.

BACKGROUND: Randomized, placebo controlled trials are used to assess the efficacy of therapies for Crohn's disease. The placebo response and remission rates vary among studies. AIM: To analyse how the placebo response and remission rates in Crohn's trials have changed over time in the era of parenteral biologic therapies. METHODS: A search for randomized, placebo-controlled trials of parenteral biologic therapies for active Crohn's disease was conducted using online databases. The placebo response and remission rates and study week of evaluation were recorded for each trial. The placebo response and remission rates were analysed as functions of publication date and study week of evaluation. RESULTS: The odds of a placebo-induced remission and response significantly increased as the week of evaluation increased. The placebo remission rate increased significantly with year of publication. Adjusted for week of evaluation, this increase in placebo remission rate over time was no longer significant. The increase in the placebo response over this time period was not statistically significant. CONCLUSION: The observed increase in placebo remission rates over time in trials of parenteral biologic therapies in Crohn's disease is explained by longer times to the primary endpoint in more recent trials.

The rate of lesions found within reach of esophagogastroduodenoscopy during push enteroscopy depends on the type of obscure gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: Many lesions found during push enteroscopy to evaluate obscure gastrointestinal bleeding are within the reach of standard endoscopes. The aim of this study was to determine whether the rate of proximal lesions varies in relation to the type of obscure bleeding that is present. PATIENTS AND METHODS: A retrospective review of consecutive push enteroscopies carried out for obscure gastrointestinal bleeding between July 1996 and July 2000 was conducted. The patients were categorized into three groups: those with recurrent obscure/overt gastrointestinal bleeding; those with persistent obscure/overt gastrointestinal bleeding; and those with obscure/occult gastrointestinal bleeding. RESULTS: A total of 63 patients (24 men, 39 women; mean age 69.8) were included. Push enteroscopy examinations were conducted for recurrent obscure/overt bleeding in 32 patients; for persistent obscure/overt bleeding in 12 patients; and for obscure/occult bleeding in 19 patients. The overall diagnostic yield of push enteroscopy was 47 % (15 of 32) in the group with recurrent obscure/overt bleeding; 66 % (eight of 12) in the group with persistent obscure/overt bleeding; and 63 % (12 of 19) in the group with obscure/occult bleeding. However, when lesions within the reach of standard esophagogastroduodenoscopy (EGD) were excluded, the yield of push enteroscopy was slightly higher in the group with recurrent obscure/overt bleeding (41 %) than in the groups with persistent obscure/overt bleeding (33 %) and obscure/occult bleeding (26 %). There were fewer lesions within the reach of EGD in the group with recurrent obscure/overt bleeding than in the groups with persistent obscure/overt bleeding (6 % vs. 33 %; P < 0.05) or obscure/occult bleeding (6 % vs. 37 %; P < 0.05). CONCLUSIONS: Patients undergoing push enteroscopy for recurrent obscure/overt bleeding were significantly less likely to have lesions within the reach of EGD than patients with persistent obscure/overt bleeding or obscure/occult bleeding. Patients in the latter two groups would be able to undergo a repeat EGD examination before more intense evaluation with push enteroscopy or capsule endoscopy.

Mercaptopurine metabolite results in clinical gastroenterology practice.

BACKGROUND: Azathioprine (AZA) and its active metabolite mercaptopurine (MP) are frequently used in the management of inflammatory bowel disease. Measurement of the AZA/MP metabolites, thioguanine (TG) and methylmercaptopurine (MMP), has been suggested as a means to optimize therapy with AZA/MP in inflammatory bowel disease. AIM: To evaluate the results of initial AZA/MP metabolite panels sent by gastroenterologists during the first year of its widespread availability. METHODS: Initial AZA/MP metabolite panels sent by gastroenterologists to a single laboratory were reviewed and the metabolite panels were interpreted. RESULTS: Initial metabolite levels were reviewed for 9187 patients. Noncompliance was detected in 263 patients (3%) and under-dosing in 4260 patients (46%). 534 patients (6%) had levels that were consistent with preferential metabolism via the TPMT pathway. The therapeutic goal was achieved in 2444 patients (27%) and an additional 552 patients (6%) had appropriate TG levels but potential hepatotoxicity. 936 patients (10%) had potential TPMT deficiency, and 58 patients (1%) had potential TPMT absence and were at risk for leukopenia. 140 patients (2%) had too high a dose. CONCLUSIONS: Measurement of AZA/MP metabolites can be used by practising gastroenterologists to identify potential reasons for nonresponse to AZA or MP, and to identify patients at risk for certain drug-related toxicities.

Endoscopic therapy of acute diverticular hemorrhage.

OBJECTIVE: Diverticular hemorrhage is a common cause of lower GI bleeding and can be diagnosed acutely during colonoscopy. However, whether early diagnosis leads to effective intervention remains controversial. The aim of this study was to evaluate whether urgent colonoscopic therapy is effective as acute and long term treatment for diverticular bleeding with stigmata of hemorrhage. METHODS: We reviewed the medical records of all patients who underwent endoscopic therapy for diverticular bleeding from January, 1994 to June, 2000 at Duke University Medical Center. Patients or their families were contacted to obtain complete follow-up including data on subsequent bleeding. RESULTS: We identified 13 patients who underwent colonoscopic hemostatic management for the treatment of acute diverticular bleeding. Therapy consisted of epinephrine injection and/or multipolar electrocoagulation. Five patients (38%) experienced early rebleeding, within 30 days of the index bleed, four of whom required surgery, and three patients (23%) had late rebleeding. There were no complications of endoscopic therapy. CONCLUSIONS: Endoscopic therapy can provide early hemostasis in some cases of acute diverticular hemorrhage. However, its value in preventing subsequent diverticular bleeding is unclear.

Provocative angiography in patients with gastrointestinal hemorrhage of obscure origin.

OBJECTIVE: A standard diagnostic evaluation including upper and/or lower endoscopy, tagged red blood cell scintigraphy, and visceral angiography identifies the source of GI bleeding in the majority of patients who present with acute GI hemorrhage. However, in a small group of patients the source of bleeding remains obscure; this form of GI hemorrhage is uncommon but represents a considerable diagnostic challenge. Some investigators have advocated provocation of bleeding with vasodilators, anticoagulants, and/or thrombolytics in association with tagged red blood cell scans or angiography. Unfortunately, the available literature on this topic is limited. Therefore, the purpose of this study is to report our experience with provocative GI bleeding studies. METHODS: The radiology databases at Duke University Medical Center and the Durham Veterans Administration Medical Center were reviewed from 1994 to 1999. Any patient who received a vasodilator, anticoagulant, or thrombolytic to induce bleeding during a tagged red blood cell scan or visceral angiogram was included. RESULTS: Seven provocative bleeding studies were performed on seven patients. All patients underwent a visceral angiogram with intra-arterial administration of tolazoline (a vasodilator), heparin (an anticoagulant), and/or urokinase (a thrombolytic). Of the seven provocative studies, only two induced angiographically identifiable bleeding. Both of these patients underwent surgical therapy. There were no complications attributed to the provocative bleeding studies. CONCLUSIONS: These results suggest that provocative GI bleeding studies can be performed safely. However, because an active bleeding source was identified in only a small proportion of patients, we believe that further study is required to optimize patient selection and to clarify the cost-effectiveness of this approach in patients with GI hemorrhage of obscure origin.

Diagnosis and management of lower gastrointestinal bleeding.

There are few randomized, prospective trials evaluating the optimal diagnostic and therapeutic strategies in the management of lower gastrointestinal bleeding. However, recent data suggest that urgent colonoscopy represents a safe and effective initial diagnostic approach. The role of tagged erythrocyte scintigraphy is yet to be defined, but it may be of utility as a screening test for visceral angiography. Colonoscopy and angiography both offer substantial therapeutic options but remain of unproved benefit from a treatment standpoint; surgery continues to play an important role in the management of lower gastrointestinal bleeding. Obscure gastrointestinal bleeding, which often presents as lower gastrointestinal bleeding, continues to be one of the most challenging diagnostic and therapeutic problems in gastroenterology. Occult gastrointestinal bleeding, often arising from the lower gastrointestinal tract, usually mandates gastrointestinal evaluation.

Alterations of chemosensory function in end-stage liver disease.

Taste and smell dysfunction has been documented in patients with both acute and chronic liver disease. The purpose of this study was to determine if chemosensory function is improved after restoration of hepatic function with liver transplantation. Nine subjects (seven women and two men) with end-stage liver disease participated in the study. Taste and smell detection and recognition thresholds were determined before and after transplantation. A significant improvement in detection of the taste of sodium chloride and the odor of phenethyl alcohol was found after transplantation. These findings may have clinical significance in food choices and nutritional status of these patients.

A report of a gastrinoma localized preoperatively by endoscopic ultrasound only and a review of the approach to imaging in Zollinger-Ellison syndrome.

The addition of somatostatin receptor scintigraphy and endoscopic ultrasound to the preoperative assessment of patients with Zollinger-Ellison syndrome has improved the ability to localize gastrinomas. We report a patient with Zollinger-Ellison syndrome with a gastrinoma localized preoperatively by endoscopic ultrasound only. We review the literature regarding the sensitivity of somatostatin receptor scintigraphy and endoscopic ultrasound and discuss the approach to imaging in Zollinger-Ellison syndrome.

A computer-based biomechanical analysis of the three-dimensional motion of cementless hip prostheses.

A computer-based mathematical technique was developed to measure and completely describe the migration and micromotion of a femoral hip prosthesis relative to the femur. This technique utilized the mechanics of rigid-body motion analysis and apparatus of seven linear displacement transducers to measure and describe the complete three-dimensional motion of the prosthesis during cyclic loading. Computer acquisition of the data and custom analysis software allowed one to calculate the magnitude and direction of the motion of any point of interest on the prostheses from information about the motion of two points on the device. The data were also used to replay the tests using a computer animation technique, which allowed a magnified view of the three-dimensional motion of the prosthesis. This paper describes the mathematical development of the rigid-body motion analysis, the experimental method and apparatus for data collection, the technique used to animate the motion, the sources of error and the effect of the assumptions (rigid bodies) on the results. Selected results of individual test runs of uncemented and cemented prostheses are presented to demonstrate the efficacy of the method. The combined effect of the vibration and electrical noise resulted in a resolution of the system of about 3-5 microns motion for each transducer. Deformation effects appear to contribute about 3-15 microns to the measurement error. This measurement and analysis technique is a very sensitive and powerful means of assessing the effects of different design parameters on the migration and micromotion of total joint prostheses and can be applied to any other case (knee, dental implant) where three-dimensional relative motion between two bodies is important.

Electromyographic analysis of postural adjustments in two methods of balance testing.

The primary purpose of this study was to compare postural responses during two methods of balance testing: 1) a platform perturbation test (PP), with destabilizing forces of uniform magnitude given at the base of support, and 2) a postural stress test (PST), with destabilizing forces of increasing magnitude given at the waist. A secondary purpose was to examine the relationship between balance strategy scores and the patterns of muscle responses as determined by electromyographic analysis on the PST. Postural responses to backward sway of 17 healthy subjects, aged 60 to 79 years (means = 69.0, s = 5.3), were characterized bilaterally by EMG recording of the tibialis anterior, quadriceps femoris, gastrocnemius, and hamstring muscles. We examined three measures of bilateral postural responses: 1) latency to first muscle response (FR) among the four lower extremity muscle groups, 2) tibialis anterior muscle latency (TA), and 3) patterns of muscle responses. Our results demonstrated significantly shorter (p less than .001) TAs and FRs (in milliseconds) on the PST than on the PP (PST TA: = means = 80.3, s = 12.4; PP TA: = means = 142.6, s = 13.4; PST FR: means = 75.9, s = 10.4; PP FR: = means = 140.4, s = 13.6). The ankle strategy was the most frequently used pattern of muscle response during both the PP and the PST, but it occurred less frequently on the PST than on the PP (PP = 72.5%, PST = 50.9%) (p less than .05). No consistent relationship was observed between the balance strategy scores as determined by videotape analysis of the PST and the patterns of muscle responses as determined by EMG analysis.