Ineffective esophageal motility: clinical, manometric, and outcome characteristics in patients with and without abnormal esophageal acid exposure.

The etiology and clinical impact of ineffective esophageal motility (IEM) remain poorly understood. Unless gastroesophageal acid reflux (GERD) is identified, symptomatic patients with IEM are challenging to treat. We sought to determine whether any clinical or functional characteristics could distinguish those patients with IEM and either normal or abnormal esophageal acid exposure.In this retrospective cohort study, we identified 46 consecutive patients presenting with heartburn, and other GER symptoms who underwent clinical, endoscopic, and functional evaluation that included high-resolution manometry (HRM) and ambulatory pH monitoring. IEM was defined using the Chicago Classification criteria (v.3) as ≥50% ineffective swallows (DCI ≤ 450 mmHg.s.cm). Esophageal acid exposure by ambulatory pH monitoring was considered abnormal when total time with esophageal pH < 4 exceeded 4.2%.Of the 46 IEM patients identified, 19 (mean age: 42 years, 37% female), had normal esophageal acid exposure and 27 patients, mean age 54 years, 33% female, evidence of pathologic acid reflux. There was a 12 years age difference between the groups, with those with normal acid exposure being significantly younger (P < 0.01); the mean body mass index (BMI) was 22.6 ± 0.6 in the normal group and 25.4 ± 0.7 in the abnormal group (P < 0.001); otherwise the groups were endoscopically and histologically similar. Symptoms were not discriminatory and heartburn and regurgitation were the most prevalent in both groups. HRM did not discriminate symptomatic patients with IEM and either normal or abnormal esophageal acid exposure. Proton pump inhibition (PPI) therapy was significantly more effective (74% vs. 10%) in patients with pathologic acid reflux (P < 0.001). As pH exposure becomes abnormal in the context of IEM, there is dominance for supine reflux.IEM appears to be an early, primary event, eventually associated with pathologic acid exposure, particularly supine. Higher BMI is also associated with abnormal esophageal acid exposure in such patients. GER symptoms are not discriminatory in patients with IEM with and without underlying pathologic acid reflux. Clinical response to PPI in such patients depends on the presence of esophageal pathologic acid exposure. Those with IEM and normal acid exposure remain symptomatic and mostly resistant to therapy.

Does body mass index differ between patients with Barrett's oesophagus and patients with chronic gastro-oesophageal reflux disease?

BACKGROUND: Obesity has been demonstrated to be a risk factor for the development of gastro-oesophageal reflux disease (GERD). AIM: To perform a prospective cohort study to determine whether there was a difference in body mass index (BMI) between patients with GERD and patients with Barrett's oesophagus (BE). METHODS: We prospectively enrolled patients undergoing endoscopic evaluation for GERD and collected information regarding BMI, tobacco and/or alcohol use, and family history of GERD. Patients with non-erosive reflux disease underwent confirmatory 24-h pH testing. RESULTS: Seven hundred and fifty one patients with GERD (mean +/- s.d. age of 55.4 +/- 14.2 years, 74% male) entered the study, and BE was present in 165 (22%, 90% male, 79% Caucasian) patients. The mean GERD symptom duration was 10.3 +/- 0.4 years (range 1-62 years) with a mean body mass index of 27.8 +/- 0.2 kg/m(2) (range 15-55) Compared with patients having GERD alone, patients with BE were more likely to be older (P = 0.001), male (P < 0.001), current or prior tobacco users (P = 0.002), and with greater duration of GERD symptoms (P < 0.001). There was no significant difference in the BMI for patients with and without BE. CONCLUSIONS: While obesity is a risk factor for both GERD and BMI, patients with BE did not demonstrate increased BMI compared with patients having chronic GERD.

Control of intra-oesophageal and intra-gastric pH with proton pump inhibitors in patients with Barrett's oesophagus.

BACKGROUND: A significant percentage of patients with Barrett's oesophagus (BE) will continue to manifest abnormal intra-oesophageal pH profiles regardless of proton pump inhibitor (PPI) therapy. AIMS: We conducted a prospective study in order to determine whether a change in PPI therapy would alter intra-oesophageal and intra-gastric acid suppression in BE patients. PATIENTS: Seventeen Helicobacter pylori-negative BE patients (16 males, 1 female; mean+/-S.D. age, 63.5+/-13.2). METHODS: Twenty-four-hour pH monitoring was performed on omeprazole or lansoprazole, followed by repeat pH monitoring on rabeprazole at a dose titrated for symptom relief. Patients completed validated symptom and health-related quality-of-life (HRQL) surveys while on and off therapy. RESULTS: Ten (59%) of the 17 patients had abnormal baseline intra-oesophageal pH profiles. Oesophageal pH monitoring values on rabeprazole were abnormal in five out of five (100%) of the omeprazole cohort and three out of five (60%) of the lansoprazole cohort that had abnormal pH profiles on initial testing. Intra-gastric pH control was inadequate in BE patients on all PPIs; the mean percentage time with intra-gastric pH below 4.0 was 46% on omeprazole, 71% on lansoprazole and 51% on rabeprazole (p=0.25). All of the patients demonstrated the phenomenon of nocturnal acid breakthrough while undergoing PPI therapy. CONCLUSIONS: Change in PPI therapy did not alter intra-oesophageal or intra-gastric control in patients with BE.

Heart rate recovery: validation and methodologic issues.

OBJECTIVES: The goal of this study was to validate the prognostic value of the drop in heart rate (HR) after exercise, compare it to other test responses, evaluate its diagnostic value and clarify some of the methodologic issues surrounding its use. BACKGROUND: Studies have highlighted the value of a new prognostic feature of the treadmill test-rate of recovery of HR after exercise. These studies have had differing as well as controversial results and did not consider diagnostic test characteristics. METHODS: All patients were referred for evaluation of chest pain at two university-affiliated Veterans Affairs Medical Centers who underwent treadmill tests and coronary angiography between 1987 and 1999 as predicted after a mean seven years of follow-up. All-cause mortality was the end point for follow-up, and coronary angiography was the diagnostic gold standard. RESULTS: There were 2,193 male patients who had treadmill tests and coronary angiography. Heart rate recovery at 2 min after exercise outperformed other time points in prediction of death; a decrease of <22 beats/min had a hazard ratio of 2.6 (2.4 to 2.8 95% confidence interval). This new measurement was ranked similarly to traditional variables including age and metabolic equivalents but failed to have diagnostic power for discriminating those who had angiographic disease. CONCLUSIONS: Heart rate at 1 or 2 min of recovery has been validated as a prognostic measurement and should be recorded as part of all treadmill tests. This new measurement does not replace, but is supplemental to, established scores.

Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis.

BACKGROUND: We explored the potential of early decompressive colonoscopy with intracolonic vancomycin administration as an adjunctive therapy for severe pseudomembranous Clostridium difficile colitis with ileus and toxic megacolon. METHODS: We reviewed the symptoms, signs, laboratory tests, radiographic findings, and outcomes from the medical records of seven patients who experienced eight episodes of severe pseudomembranous colitis with ileus and toxic megacolon. All seven patients underwent decompressive colonoscopy with intracolonic perfusion of vancomycin. RESULTS: Fever, abdominal pain, diarrhea, abdominal distention, and tenderness were present in all patients. Five of seven patients were comatose, obtunded, or confused, and six of the seven required ventilatory support. The white blood cell count was greater than 16,000 in seven cases (six patients). Colonoscopy showed left-side pseudomembranous colitis in one patient, right-side colitis in one patient, and diffuse pseudomembranous pancolitis in five patients. Two patients were discharged with improvement. Five patients had numerous medical problems leading to their death. Complete resolution of pseudomembranous colitis occurred in four patients. One patient had a partial response, and two patients failed therapy. CONCLUSION: Colonoscopic decompression and intracolonic vancomycin administration in the management of severe, acute, pseudomembranous colitis associated with ileus and toxic megacolon is feasible, safe, and effective in approximately 57% to 71% of cases.

Assessing patients with possible heart disease using scores.

Multivariable analysis of clinical and exercise test data has the potential to become a useful tool for assisting in the diagnosis of coronary artery disease, assessing prognosis, and reducing the cost of evaluating patients with suspected coronary disease. Since general practitioners are functioning as gatekeepers and decide which patients must be referred to the cardiologist, they need to use the basic tools they have available (i.e. history, physical examination and the exercise test), in an optimal fashion. Scores derived from multivariable statistical techniques considering clinical and exercise data have demonstrated superior discriminating power compared with simple classification of the ST response. In addition, by stratifying patients as to probability of disease and prognosis, they provide a management strategy. While computers, as part of information management systems, can run complicated equations and derive these scores, physicians are reluctant to trust them. Thus, these scores have been represented as nomograms or simple additive tables so physicians are comfortable with their application. Their results have also been compared with physician judgment and found to estimate the presence of coronary disease and prognosis as well as expert cardiologists and often better than nonspecialists. However, the discriminating power of specific variables from the medical history and exercise test remains unclear because of inadequate study design and differences in study populations. Should expired gases be substituted for estimated metabolic equivalents (METs)? Should ST/heart rate (HR) index be used instead of putting these measurements separately into the models? Should right-sided chest leads and HR in recovery be considered? There is a need for further evaluation of these routinely obtained variables to improve the accuracy of prediction algorithms especially in women. The portability and reliability of these equations must be demonstrated since access to specialised care must be safe-guarded. Hopefully, sequential assessment of the clinical and exercise test data and application of the newer generation of multivariable equations can empower the clinician to assure the cardiac patient access to appropriate and cost-effective cardiological care.

Simple treadmill score to diagnose coronary disease.

OBJECTIVE: Our aim was to derive and validate a simplified treadmill score for predicting the probability of angiographically confirmed coronary artery disease (CAD). BACKGROUND: The American College of Cardiology/American Heart Association guidelines for exercise testing recommend the use of multivariable equations to enhance the diagnostic characteristics of the standard treadmill test. Most of these equations use complicated statistical techniques to provide diagnostic estimates of CAD. Simplified scores derived from such equations that require physicians only to add points have been developed for pretest estimates of disease and for prognosis. However, no simplified score has been developed specifically for the diagnosis of CAD using exercise test results. METHODS: Consecutive patients referred for evaluation of chest pain who underwent standard treadmill testing followed by coronary angiography were studied. A logistic regression model was used to predict clinically significant (> or = 50% stenosis) CAD and then the variables and coefficients were used to derive a simplified score. The simplified score was calculated as follows: (6 x maximal heart rate code) + (5 x ST-segment depression code) + (4 x age code) + angina pectoris code + hypercholesterolemia code + diabetes code + treadmill angina index code. The simplified score had a range from 6 to 95, with < 40 designated as low probability, between 40 and 60 was intermediate probability, and > 60 was high probability for CAD. RESULTS: A total of 1,282 male patients without a prior myocardial infarction underwent exercise treadmill testing and coronary angiography in the derivation group, and there were 476 male patients in the validation group from another institution. The area under the receiver operating characteristic curve (+/- SE) for the ST-segment response alone was 0.67 as compared to 0.79 +/- 0.01 for the diagnostic score (p > 0.001). The prevalence of significant disease for the men was 27% in the low-probability group, 62% in the intermediate-probability group, and 92% in the high-probability group, which was similar to the prevalence in the validation group, with 22%, 58%, and 92% in low-, intermediate-, and high-probability groups, respectively. The low-probability group had < 4% prevalence of severe disease. In both populations, 7 more patients out of 100 were correctly classified than with the use of ST-segment criteria. When used as a clinical management strategy, the score has a sensitivity of 88% and a specificity of 96%. CONCLUSION: This simplified exercise score that estimates the probability of CAD can be easily applied without a calculator and is a useful and valid tool that can help physicians manage patients presenting with chest pain.

Leukocytosis as a harbinger and surrogate marker of Clostridium difficile infection in hospitalized patients with diarrhea.

OBJECTIVES: Clostridium difficile is the etiological agent of antibiotic-associated diarrhea and pseudomembranous colitis and is a leading cause of nosocomial diarrhea. The objective of the study was to examine if leukocytosis could be a harbinger and surrogate marker of C. difficile infection in hospitalized patients. METHODS: We retrospectively examined the medical records of 70 hospitalized patients who presented with diarrhea of variable severity and who underwent stool examination for enteric pathogens, including C. difficile. We specifically recorded the white blood cell count and the pattern and severity of leukocytosis in two groups of patients--those who were C. difficile-positive and those who were negative. RESULTS: Leukocytosis was common in C. difficile-positive patients, compared to in C. difficile-negative patients (mean 15,800/mm3 vs 7700/mm3, p < 0.01). Review of the 35 C. difficile-positive patients revealed three patterns: Pattern A) sudden WBC increase coinciding with the onset of symptoms suggestive of C. difficile; Pattern B) unexplained leukocytosis preceding the appearance of C. difficile-related diarrhea and serving as a harbinger of the infection; and Pattern C) worsening of pre-existing leukocytosis as a surrogate marker of C. difficile infection. Treatment with metronidazole led to amelioration of symptoms and normalization of the leukocyte count in all cases. CONCLUSIONS: Infection with C. difficile should be considered in the differential diagnosis of sudden onset of leukocytosis in hospitalized patients previously or concurrently treated with antibiotics. Doing so may obviate the need for expensive and time-consuming tests for other etiologies.