M. Mazen Jamal

Corpus gastritis is protective against reflux oesophagitis

BACKGROUND Gastric acid is important in the pathogenesis of reflux oesophagitis. Acid production by the gastric corpus is reduced in corpus gastritis. AIMS To determine whether corpus gastritis protects against reflux oesophagitis. METHODS Patients presenting for elective oesophagogastroduodenoscopy were studied. Two biopsy specimens were taken from the antrum, corpus, and cardia and stained with haematoxylin/eosin and Diff-Quick II stains. The presence and severity of gastritis were graded according to a modified updated Sydney classification. RESULTS Of 302 patients, 154 had endoscopic signs of reflux oesophagitis. There was no difference between patients with and controls without oesophagitis in the overall infection rates with Helicobacter pylori. Acute or chronic corpus gastritis occurred less often in patients with than those without reflux oesophagitis. Compared with controls, corpus gastritis was less severe in patients with reflux oesophagitis. The presence of acute or chronic gastritis in the corpus was significantly correlated with either type of gastritis in other areas of the stomach. In a multivariate logistic regression, age, sex, smoking status, and the presence of chronic corpus gastritis all exerted a significant influence on the presence of reflux oesophagitis. Chronic corpus gastritis was associated with a 54% reduced risk for reflux oesophagitis. CONCLUSIONS While infection withH pylori alone may not affect the occurrence of reflux oesophagitis, the development of chronic corpus gastritis seems to be protective.

A case-control study of risk factors for sporadic hepatitis C virus infection in the southwestern United States

Objective:We performed a case-control study to evaluate risk factors and possible modes of transmission for hepatitis C virus (HCV) infection in patients with no history of blood transfusion or injection drug use.Methods:Study subjects were selected from among patients seen in gastroenterology outpatient clinics at a university medical center in the southwestern United States. The study group consisted of 58 patients (12%) with chronic HCV infection who reported no history of transfusion or injection drug use, among a total of 477 patients evaluated for a positive HCV antibody test. These 58 patients were matched by age, ethnicity, and gender with 58 control patients diagnosed with gastroesophageal reflux attending the same clinics. Patients and controls were subjected to structured interviews and review of medical records.Results:A variety of variables were significantly associated with increased risk of sporadic HCV infection, including a history of tattoos, needlestick exposure, a history of sexually transmitted disease, intercourse with an injection drug user, five or more lifetime sexual partners, intercourse during menses (for women), lower income, and heavy alcohol intake (>60 g/day). Multivariate analysis identified a history of sexually transmitted disease, heavy alcohol intake, and the presence of a tattoo as independent risk factors for sporadic HCV. In addition, six cases and one control had a history of needlestick exposure. Of the cases, 88% had at least one of these four risk factors, as compared with 26% of controls (odds ratio = 16.5; 95% confidence interval = 4.0–68.8).Conclusions:A history of sexually transmitted disease, heavy alcohol intake, the presence of tattoos, and a history of needlestick exposure were identified as risk factors for sporadic hepatitis C in this case-control study. If we include all patients with a history of blood transfusion or injection drug use, only 2% of the total 477 HCV patients had no identified risk factors.

Trends in the Utilization of Endoscopic Retrograde Cholangiopancreatography (ERCP) in the United States

OBJECTIVES:To evaluate nationwide trends in the utilization of endoscopic retrograde cholangiopancreatography (ERCP) in relation to the advent of noninvasive methods of visualizing the biliary and pancreatic tree.METHODS:Retrospective cohort study. The Nationwide Inpatient Sample (NIS) database was used to calculate the age-adjusted rate for ERCPs performed from 1988 to 2002. The State Ambulatory Surgery Database (SASD) was used to evaluate trends in outpatient ERCPs from 1997 to 2003. Linear Poisson multivariate regression model was used to control for variations in age, gender, and ethnicity among the overall patient population.RESULTS:The NIS database contained 402,343 patients who had an ERCP performed from 1988 to 2002. The mean age for these patients was 60.21 ± 19.56 yr old. From 1988 to 1996; the age-adjusted rate for ERCPs increased by nearly threefold, from 25.66 per 100,000 in 1988 to 74.95 in 1996. The rate of 74.95 in 1996 declined to a rate of 59.70 by the year 2002. The rates of diagnostic ERCPs in men and women were 26.76 and 31.58 per 100,000 in 1988–1990, respectively. This rate then increased to 35.66 and 43.18 per 100,000 in 1994–1996, which then declined to 29.01 and 29.06 in 2000–2002. The age-adjusted rate for therapeutic ERCPs in men and women was 13.74 and 15.61 per 100,000 in 1988–1990, respectively, which continued to increase throughout the time span to 38.76 and 43.75 in 2000–2002. The SASD revealed a continual decline in outpatient ERCPs from 25.45 per 100,000 in 1997 down to 16.17 per 100,000 in the year 2003.CONCLUSION:The utilization of ERCP dramatically increased from 1988 to 1996; however, since the advent of noninvasive diagnostic techniques such as endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP), there has been a steady decline in the utilization of diagnostic ERCPs from 1996 to 2002.

Mesalamine Did Not Prevent Recurrent Diverticulitis in Phase 3 Controlled Trials

BACKGROUND & AIMS No therapy has been proven to prevent the recurrence of diverticulitis. Mesalamine has shown efficacy in preventing relapse in inflammatory bowel disease, and there is preliminary evidence that it might be effective for diverticular disease. We investigated the efficacy of mesalamine in preventing recurrence of diverticulitis in 2 identical but separate phase 3, randomized, double-blind, placebo-controlled, multicenter trials (identical confirmatory trials were conducted for regulatory reasons). METHODS We evaluated the efficacy and safety of multimatrix mesalamine vs placebo in the prevention of recurrent diverticulitis in 590 (PREVENT1) and 592 (PREVENT2) adult patients with ≥1 episodes of acute diverticulitis in the previous 24 months that resolved without surgery. Patients received mesalamine (1.2 g, 2.4 g, or 4.8 g) or placebo once daily for 104 weeks. The primary end point was the proportion of recurrence-free patients at week 104. Diverticulitis recurrence was defined as surgical intervention at any time for diverticular disease or presence of computed tomography scan results demonstrating bowel wall thickening (>5 mm) and/or fat stranding consistent with diverticulitis. For a portion of the study, recurrence also required the presence of abdominal pain and an increase in white blood cells. RESULTS Mesalamine did not reduce the rate of diverticulitis recurrence at week 104. Among patients in PREVENT1, 53%-63% did not have disease recurrence, compared with 65% of those given placebo. Among patients in PREVENT2, 59%-69% of patients did not have disease recurrence, compared with 68% of those given placebo. Mesalamine did not reduce time to recurrence, and the proportions of patients requiring surgery were comparable among treatment groups. No new adverse events were identified with mesalamine administration. CONCLUSIONS Mesalamine was not superior to placebo in preventing recurrent diverticulitis. Mesalamine is not recommended for this indication. ClinicalTrials.gov ID: NCT00545740 and NCT00545103.

A phase 2a, randomized, double‐blind 28‐day study of TZP‐102 a ghrelin receptor agonist for diabetic gastroparesis

Background  Gastroparesis causes significant morbidity and treatment options are limited. TZP‐102 a novel, macrocyclic, selective, oral ghrelin receptor agonist, was evaluated in a randomized, double‐blind, placebo‐controlled trial in patients with diabetic gastroparesis.

Characteristics of intestinal metaplasia in the gastric cardia

OBJECTIVE:Intestinal metaplasia of the gastroesophageal junction is frequently grouped together with Barretts esophagus. The area of the gastroesophageal junction is comprised of the distal esophagus and the gastric cardia. The aim of the present study was to assess whether intestinal metaplasia in the distal esophagus and gastric cardia represent two different entities with a different set of risk factors.METHODS:Patients presenting for elective upper endoscopy were enrolled into a prospective study. The presence of gastritis and intestinal metaplasia was evaluated in gastric biopsies taken from the antrum, corpus, and cardia. Barretts esophagus was defined by the presence of any length of columnar mucosa above the gastroesophageal junction.RESULTS:Of 302 patients, 50 patients had intestinal metaplasia of the gastric cardia, 73 Barretts esophagus, and 116 erosive esophagitis. Men were more prone than women to develop Barretts esophagus or erosive esophagitis. Both conditions were also more common among whites than nonwhites. Smoking was particularly common among patients with Barretts esophagus. Patients with cardiac intestinal metaplasia did not share these demographic characteristics. The prevalence of daily reflux symptoms, erosive esophagitis, and Barretts esophagus was similar among patients both with and without cardiac intestinal metaplasia. However, atrophy and intestinal metaplasia of the gastric antrum and corpus were found more frequently among patients with than without cardiac intestinal metaplasia.CONCLUSIONS:Intestinal metaplasia of the gastric cardia is different from Barretts esophagus. Although cardiac intestinal metaplasia is closely associated with signs of gastritis in other parts of the stomach, gastroesophageal reflux disease does not seem to be a risk factor. A diagnosis of Barretts esophagus should not be made based on the presence of intestinal metaplasia within the cardiac portion of the gastroesophageal junction.

Second-generation antipsychotic exposure and metabolic-related disorders in patients with schizophrenia : An observational pharmacoepidemiology study from 1988 to 2002

Patients with schizophrenia are at increased risk for cardiovascular disease as a consequence of lifestyle habits, impaired access to health care, and, increasingly, due to metabolic side effects ostensibly attributed to second-generation antipsychotics (SGAs). There is little evidence, however, on the extent and temporal patterns of SGA-associated metabolic side effects. We longitudinally examined the differential prevalence rates of obesity, diabetes mellitus, and diabetic ketoacidosis among inpatients with schizophrenia compared with control inpatients without schizophrenia. The data were derived from the National Inpatient Sample, the largest all-payer inpatient care database in the United States consisting of 5 to 8 million inpatient hospital stays per year sampled to approximate a 20% sample of community hospitals from 1988 to 2002. Overlaid on these observations was the market penetration data for SGAs. In 1988, the net difference from controls in obesity prevalence among inpatients with schizophrenia was +4.7%; by 2002, this difference had widened to +14.7%. Similarly, a significant increase in net prevalence of diabetes mellitus and diabetic ketoacidosis was observed from 1988 to 2002 among schizophrenic inpatients. In conclusion, after the introduction of SGAs, patients with schizophrenia in the United States have experienced a striking net increase in the prevalence of obesity and diabetes mellitus. This is likely to significantly add to an already elevated risk for cardiovascular disease in this population. Further investigations are urgently required so that health policy can be appropriately amended for preventive measures.

The Prevalence of Pulmonary Embolism and Pulmonary Hypertension in Patients With Type II Diabetes Mellitus

BACKGROUND Patients with diabetes mellitus (DM) have a hypercoagulable state that may increase their risk for thromboembolism. However, the data about this association are contradictory in the literature. The goal of this study was to evaluate the occurrence of pulmonary embolism (PE) and pulmonary hypertension (PHT) in patients with DM after adjusting for coronary artery disease (CAD), congestive heart failure (CHF), hypertension, and smoking using a large database. METHOD We used patient treatment file documents to inpatient hospital admissions containing discharge diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes) from Veterans Health Administration Hospitals. The patients were classified into two groups: a DM group with an ICD-9-CM code for DM (293,124), and a control group with an ICD-9-CM code for hypertension but no DM (552,623). The ICD-9-CM code for PE (415.19) and the ICD-9-CM code for PHT (416.0) were used to study prevalence of these diseases in DM patients vs control patients. We performed univariate and multivariate analyses adjusting for CAD, CHF, and smoking. Continuous variables were analyzed by unpaired t test. Binary variables were analyzed by chi(2) and Fisher exact tests. RESULTS PE was present in 2,011 patients with DM (0.7%) vs 2,759 patients (0.5%) in the control group. PHT was present in 3,356 patients with DM (1.1%) vs 3,357 patients (0.6%) in the control group. Using multivariate analysis, DM remained independently associated with PE (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.19 to 1.35; p < 0.001) and with PHT (OR, 1.53; 95% CI, 1.45 to 1.60; p < 0.001). CONCLUSION Patients with DM have significantly higher prevalence of PE and PHT independent of CAD, hypertension, CHF, or smoking. The pathogenesis of this association is not known at this time.

Trends in the age adjusted mortality from acute ST segment elevation myocardial infarction in the United States (1988-2004) based on race, gender, infarct location and comorbidities.

Treatment of acute ST-segment elevation myocardial infarction (STEMI) has dramatically changed over the past 2 decades. The goal of this study was to determine trends in the mortality of patients with acute STEMIs in the United States over a 16-year period (1988 to 2004) on the basis of gender, race, infarct location, and co-morbidities. The Nationwide Inpatient Sample database was used to analyze the age-adjusted mortality rates for STEMI from 1988 to 2004 for inpatients age >40. International Classification of Diseases, Ninth Revision, Clinical Modification codes consistent with acute STEMI were used. The Nationwide Inpatient Sample database contained a total of 1,316,216 patients who had diagnoses of acute STEMIs from 1988 to 2004. The mean age of these patients was 66.92 +/- 12.82 years. A total of 163,915 hospital deaths occurred during the study period. From 1988, the age-adjusted mortality rate decreased gradually for all acute STEMIs for the entire study period (in 1988, 406.86 per 100,000, 95% confidence interval 110.25 to 703.49; in 2004, 286.02 per 100,000, 95% confidence interval 45.21 to 526.84). Furthermore, unadjusted mortality decreased from 15% in 1988 to 10% in 2004 (p <0.01). This decrease was similar between the genders, among most ethnicities, and in patients with diabetes and those with congestive heart failure. However, women and African Americans had higher rates of acute STEMI-related mortality compared to men and Caucasians over the years studied. In conclusion, age-adjusted mortality from acute STEMIs has significantly decreased over the past 16 years, with persistent higher mortality rates in women and African Americans the study period.

A Randomized, Placebo-Controlled Trial of Lubiprostone for Opioid-Induced Constipation in Chronic Noncancer Pain

OBJECTIVES:This multicenter, phase 3 trial evaluated oral lubiprostone for constipation associated with non-methadone opioids in patients with chronic noncancer-related pain.METHODS:Adults with opioid-induced constipation (OIC; <3 spontaneous bowel movements [SBMs] per week) were randomized 1:1 to double-blind lubiprostone 24 μg or placebo twice daily for 12 weeks. The primary end point was the overall SBM response rate. Responders had at least moderate response (≥1 SBM improvement over baseline frequency) in all treatment weeks with available observed data, as well as full response (≥3 SBMs per week) for at least 9 of the 12 treatment weeks.RESULTS:In total, 431 patients were randomized; 212 each received lubiprostone and placebo, and 7 were not treated. Overall, the SBM response rate was significantly higher for patients treated with lubiprostone vs. placebo (27.1 vs. 18.9%, respectively; P=0.030). Overall mean change from baseline in SBM frequency was significantly greater with lubiprostone vs. placebo (3.2 vs. 2.4, respectively; P=0.001). The median time to first SBM was significantly shorter with lubiprostone vs. placebo (23.5 vs. 37.7 h, respectively; P=0.004). Compared with placebo, the patients treated with lubiprostone exhibited significant improvements in straining (P=0.004), stool consistency (P<0.001), and constipation severity (P=0.010). No significant differences were observed in quality-of-life measures or the use of rescue medication; however, the percentage of patients who used rescue medication was consistently lower in the lubiprostone group than in the placebo group at months 1 (34.9 vs. 37.7%), 2 (23.4 vs. 26.6%), and 3 (20.5 vs. 22.0%). Adverse events (AEs) >5% were diarrhea, nausea, vomiting, and abdominal pain (lubiprostone: 11.3, 9.9, 4.2, and 7.1%, respectively; placebo, 3.8, 4.7, 5.2, and 0%, respectively). None of the serious AEs (lubiprostone, 3.3%; placebo, 2.8%) were related to lubiprostone.CONCLUSIONS:Lubiprostone significantly improved symptoms of OIC and was well tolerated in patients with chronic noncancer pain.