Adverse Gastrointestinal Research Articles

Gastrointestinal Complications of Dual Antiplatelet Therapy

Case presentation: A 59-year-old man with a history of hypertension, dyslipidemia, and smoking was hospitalized with acute coronary syndrome requiring emergency percutaneous coronary intervention with 4 drug-eluting stents. His discharge medications included dual antiplatelet therapy with aspirin 325 mg/d and clopidogrel 75 mg/d. Three weeks after discharge, he returned to the Emergency Department with bloody stools and a hematocrit of 23% (previously 36%) and required 3 U of packed red blood cells. Endoscopy showed a bleeding duodenal ulcer with adherent clot (Figure). Endoscopic image of bleeding duodenal ulcer with clot on top. This image was taken in a patient with a history similar to that of our patient. Arrow points to the base of duodenal ulcer with active bleeding. Picture contributed by Sarathchandra Reddy, MD, and Edwin Chun Ouyang, MD, PhD, Division of Gastroenterology, Brigham and Women’s Hospital, Boston, Mass. We prescribe dual antiplatelet therapy with aspirin and clopidogrel to prevent and treat cardiovascular, cerebrovascular, and peripheral arterial disease. According to American Heart Association statistics, 700 000 patients had stroke, 13 million had coronary artery disease, and 8 to 12 million suffered from peripheral arterial disease in 2002. Each year, 1.2 million patients in the United States receive dual antiplatelet therapy with aspirin and clopidogrel after percutaneous coronary intervention with drug-eluting stents. The number of patients in the United States who receive dual antiplatelet therapy for various vascular conditions such as coronary artery disease, transient ischemic attack, thrombotic stroke, and peripheral vascular disease probably exceeds several million. The use of aspirin compared with placebo reduces the risk of myocardial infarction, stroke, or death from vascular causes by ≈25%.1 In the Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial, administration of clopidogrel decreased the relative risk of vascular events by 8.7% compared with aspirin.2 The …

Cyclo-Oxygenase-2 Inhibitors

The major goal of clinicians when treating acute musculoskeletal injuries is to return athletes to their pre-injury level of function, ideally in the shortest time possible and without compromising tissue-level healing. In this regard, a commonly used intervention is the taking of NSAIDs. These are used to limit the amount and duration of inflammation, and to control pain. While NSAIDs have become synonymous with the management of acute musculoskeletal injuries, their efficacy has yet to be proven. This is of particular concern in view of recent research investigating the latest class of NSAIDs - selective cyclo-oxygenase-2 inhibitors (COXIBs). COXIBs were developed to reduce the adverse gastrointestinal (GI) effects of traditional NSAIDs. While they have beneficial anti-inflammatory and analgesic properties, and appear to facilitate earlier return to function following acute injury, the effect of COXIBs on tissue-level healing is currently unknown. In experimental animal models of acute injury, COXIBs have been shown to be detrimental to tissue-level repair. Specifically, they have been shown to impair mechanical strength return following acute injury to bone, ligament and tendon. Clinically, this may have implications for ongoing morbidity and future injury susceptibility. However, the current animal studies have limited translation to the clinical setting, particularly because of significant limitations relating to drug use and dosage in these studies. There is currently no randomised, controlled trial evidence of the tissue-level effects of COXIBs on acute musculoskeletal injuries. In addition to questions relating to the effect of COXIBs on tissue-level healing, further questions regarding the use of these agents have been raised given a recent link being shown between one COXIB (rofecoxib) and an increased risk for adverse cardiovascular events. Whether this finding is related to the individual properties of rofecoxib or is a class phenomenon is the subject of ongoing investigation. However, in light of the potential risks associated with using COXIBs, an acceptable and possibly safer alternative in the management of acute musculoskeletal injuries may be to use traditional NSAIDs. Traditional NSAIDs do carry the potential for greater adverse GI effects and their clinical effects on tissue-level healing remain relatively unknown. However, they do not appear to be associated with adverse cardiovascular effects, and they are effective pain relievers and cheaper alternatives.

Autoimmunity in a Phase I Trial of a Fully Human Anti-Cytotoxic T-Lymphocyte Antigen-4 Monoclonal Antibody With Multiple Melanoma Peptides and Montanide ISA 51 for Patients With Resected Stages III and IV Melanoma

Nineteen patients with high-risk resected stage III and IV melanoma were immunized with three tumor antigen epitope peptides from gp100, MART-1, and tyrosinase emulsified with adjuvant Montanide ISA 51 and received a fully human anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibody MDX-010. Each of three cohorts received escalating doses of antibody with vaccine primarily to evaluate the toxicities and maximum-tolerated dose (MTD) of MDX-010 with vaccine. MDX-010 pharmacokinetics and immune responses were secondary end points. Peptide immunizations with MDX-010 were administered every 4 weeks for 6 months and then every 12 weeks for 6 months. A leukapheresis to obtain peripheral-blood mononuclear cells for immune analyses was performed before treatment and after the sixth vaccination. Patients were observed until relapse. Grade 3 gastrointestinal (GI) toxicity (diarrhea or abdominal pain) was observed in three patients in the highest dose cohort and one in the middle dose cohort who seemed to be autoimmune. That defined the MTD with vaccine on this schedule at 1 mg/kg. Of eight patients with evidence of autoimmunity, three have experienced disease relapse. Of 11 patients without autoimmune symptoms, nine have experienced disease relapse. Significant immune responses were measured by tetramer and enzyme-linked immunospot assays against gp100 and MART-1. Dose-related autoimmune adverse events, predominantly skin and GI toxicities, were reversible. Patients mounted an antigen-specific immune response to a peptide vaccine when combined with a human anti-CTLA-4 antibody.

Predicting the risk for gastrointestinal toxicity in patients taking NSAIDs: The Gastrointestinal Toxicity Survey

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs in the world, but their use is often associated with adverse gastrointestinal (GI) events that may be life threatening in some patients. Development of simple questionnaires for predicting GI events in individuals taking NSAIDs may help to prevent use of these drugs in high-risk patients. The present study was undertaken to test a new questionnaire designed to identify patients at high risk for NSAID-associated GI events--the Gastrointestinal Toxicity Survey (NSAID Induced) (GITS [NI]). In this study, results for GITS (NI) were compared with those for an established questionnaire, the Stanford Calculator of Risk for Events (SCORE), in a small cohort of 400 patients. Feasible generalized least squares (FGLS) and multinomial logistic (MNL) regression were used to perform the comparison. The overall correlation between results for GITS (NI) responses and the total score for the SCORE questionnaire was 0.962 (P < .0001). The agreement between the 2 instruments with respect to their ability to predict the same risk for NSAID-induced GI events was similar for both FGLS and MNL. For 4 levels of risk, the agreement was approximately 80% between the 2 instruments. For 3 levels of risk, the agreement was approximately 90%. This study showed that results obtained with GITS (NI) are highly correlated with those from SCORE and that GITS (NI) may provide physicians with information that will help them avoid administering NSAIDs to patients who are at high risk for adverse GI reactions.

Enteric-coated mycophenolate sodium: therapeutic equivalence to mycophenolate mofetil in de novo renal transplant patients

The introduction of mycophenolate mofetil (MMF)—the morpholino ester prodrug of mycophenolic acid (MPA)—has improved graft and patient survival, but its use has been linked with the occurrence of adverse events, particularly gastrointestinal (GI) side effects. These can be sufficiently severe to require dose reductions or discontinuation, which may lead to acute rejection episodes or graft failure. An enteric-coated formulation delivering mycophenolic acid—enteric-coated mycophenolate sodium (EC-MPS)—has been developed with the aim of improving upper GI tolerability. Therapeutic equivalence of EC-MPS 720 mg b.i.d. vs MMF 1000 mg b.i.d. has been established in a pivotal phase III, 12-month, international, randomized, double-blind, parallel group study, involving patients undergoing de novo renal transplantation. The incidence of efficacy failure (composite variable of biopsy-proven acute rejection [BPAR], graft loss, death or loss to follow-up) was similar between the two groups at 6 months (EC-MPS 25.8% vs MMF 26.2%; 95% CI [−8.7, +8.0]), demonstrating therapeutic equivalence. Efficacy failure remained similar between the two treatment groups at 12 months. The overall incidence of adverse events and GI side effects were also comparable between treatment groups throughout the 12-month study period, although fewer patients in the EC-MPS group experienced study drug discontinuations, interruptions, or dose reductions (12 months: EC-MPS 15.0% vs MMF 19.5%). Subgroup analysis revealed similar safety profiles for EC-MPS and MMF in elderly patients and patients with diabetes at baseline. The EC-MPS 720 mg b.i.d. and MMF 1000 mg b.i.d. show therapeutic equivalence in de novo renal transplant patients. Therefore, EC-MPS offers transplant physicians and their patients an alternative MPA therapy that is as effective and safe as MMF.

The Cost-Effectiveness of Acetaminophen, NSAIDs, and Selective COX-2 Inhibitors in the Treatment of Symptomatic Knee Osteoarthritis

Objective The objective of this study was to conduct an economic evaluation of rofecoxib and celecoxib compared with high-dose acetaminophen or ibuprofen with and without misoprostol for patients with symptomatic knee osteoarthritis (OA). Methods A decision analysis model was designed over 6 months using two measures of effectiveness: 1) number of upper gastrointestinal (GI) adverse events averted; and 2) number of patients who achieved perceptible pain relief. Separate analyses were conducted for all patients and for those who did not respond to acetaminophen. Outcome probabilities were obtained from a comprehensive review of randomized controlled trials and observational studies. Costs were derived from actual resource utilization of OA patients. Results In terms of averting GI events, acetaminophen dominates the other options for an average risk patient population. For patients who did not respond to acetaminophen, rofecoxib had the lowest incremental cost-effectiveness ratio (ICER) per GI event avoided ($32,000) relative to ibuprofen. In terms of pain control, ibuprofen had an ICER of $610.77 per additional patient achieving minimal perceptible clinical improvement (MPCI) relative to acetaminophen, while rofecoxib had an ICER of $12,000 relative to ibuprofen. For patients who did not respond to acetaminophen and who are at high risk of developing an adverse GI event, rofecoxib dominates ibuprofen as the preferred alternative for both measures of effectiveness. One-way, two-way, and probabilistic sensitivity analyses established that these results were generally robust. Conclusions Our results suggest that for average-risk knee OA patients, acetaminophen dominates the other therapies in terms of cost per GI event averted. In terms of pain relief, cost-effectiveness acceptability curves indicate that if one values pain relief below $275 per patient achieving MPCI, acetaminophen is the therapy most likely to be optimal; between $275 and $14,150, ibuprofen is most likely to be optimal; and above $14,150, rofecoxib is most likely to be optimal.

Gastrointestinal Effects of NSAIDs and Coxibs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in the world, but their use is limited because of their propensity to cause gastrointestinal (GI) injury. All patients are at risk of GI injury but certain risk factors increase the likelihood of adverse GI effects. The most important include a history of ulcer or GI complications, increasing age, concomitant anticoagulation, concomitant corticosteroid use, and high-dose NSAIDs or multiple NSAIDs (including an NSAID plus low-dose aspirin). Concurrent illness (e.g., severe rheumatoid arthritis, heart disease) has also been reported to increase the risk of GI events. NSAID-associated GI side effects markedly increase health care costs, with up to 31% of cost of managing arthritis patients accounted for through the management of GI side effects. The COX-2 specific inhibitors (coxibs) were developed with the aim of maintaining anti-inflammatory efficacy but improving gastrointestinal safety in comparison to non-selective NSAIDs. The use of COX-2 specific inhibitors significantly decreases the rate of endoscopic ulcers as compared to traditional NSAIDs. Prospective GI outcomes studies also indicate that these agents decrease clinical GI events as compared to non-selective NSAIDs. The number of patients needed to treat to avert one clinical event in one year is approximately 40–100. The cost-effectiveness of coxibs increases (the cost per GI event averted decreases) in patients with high-risk clinical features because they have higher rates of GI hospitalizations and greater use of expensive prophylactic co-therapy.

An approximate Bayesian risk-analysis for the gastro-intestinal safety of ibuprofen.

Although several studies on ibuprofen and its gastro-intestinal (GI) risk have been reported, the dose-response relationship was not clear due to the lack of information regarding high-dose exposure. Analysis using Bayesian methods is appropriate whenever data are sparse, although such methods are not easily implemented. A retrospective cohort study to assess this dose-response relationship was carried out using a record linkage database. A Bayesian risk-analysis was conducted using the Bayesian bootstrap approximation. Risks of GI events at different dose levels were compared using the posterior distributions and the number of events predicted to occur in the future was estimated. Risk factors such as age, gender and co-morbidity were adjusted for in the analysis. This approximation was compared with the full Bayesian approach using the usual but more computer-intensive tool of Markov Chain Monte Carlo simulation. There were 1, 5 and 10 complicated GI events during exposure to high, medium and low dose ibuprofen with 0.2, 1.8 and 7.0 thousand person-years (PY) exposure, respectively. After adjusting for other risk factors the relative risks of high versus low and medium versus low doses were 6.3 (95% CI = 0.21, 24.17) and 2.5 (95% CI = 0.71, 5.85), respectively. Using the approximate Bayesian method prediction of the number of events in a population of females aged 50-59 with no previous medical problems with 1000 PY drug exposure showed that the estimated probability of having more than five events was 0.048 for the medium-dose group and 0.14 for the high-dose group. High dose ibuprofen appears to have a considerably greater risk of having a larger number of adverse GI events than a medium dose. The approximate Bayesian bootstrap method was demonstrated to be a robust and easily implemented alternative to the full Bayesian approach to risk analysis whenever data are sparse.

Efficacy and tolerability of meloxicam in an observational, controlled cohort study in patients with rheumatic disease

Background Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase-2 without affecting platelet aggregation. Objective The goal of this study was to assess the efficacy and tolerability of meloxicam under natural prescribing conditions for up to 6 months. Methods This was a multicenter, prospective, observational cohort study. Participating centers were randomized to 1 of 2 groups: the meloxicam-only group, and the group who received comparator NSAIDs (ie, diclofenac, ibuprofen, piroxicam, or indomethacin). Results A total of 4526 patients received either meloxicam (n = 2530) or a comparator NSAID (n = 1996). Treatment groups were comparable in terms of observed efficacy measures. Meloxicam patients had significantly lower rates of reported gastrointestinal (GI) adverse drug reactions (1.80% vs 3.20%; P = 0.003), including dyspepsia (0.08% vs 0.35%; P = 0.049), abdominal pain (0.91% vs 1.90%; P = 0.006), gastritis (0.08% vs 0.60%; P = 0.002), and GI bleeding (0.08% vs 0.50%; P = 0.007), compared with those receiving comparator NSAIDs. Conclusion There was evidence that meloxicam was prescribed preferentially to patients who had not responded to NSAIDs previously, who had previously experienced NSAID-induced side effects (and so were at high risk for developing NSAID-induced GI toxicity), or who were more seriously impaired. The nonrandomized and unblinded nature of this study limits the conclusions that can be drawn concerning efficacy or tolerability. Nevertheless, the study results are consistent with the favorable GI tolerability seen with meloxicam in double-blind comparative trials.

Tolerability and efficacy of nabumetone and naproxen in the treatment of rheumatoid arthritis

The purpose of this study was to compare the tolerability and efficacy of nabumetone and naproxen in the treatment of patients with rheumatoid arthritis (RA). The occurrence of gastrointestinal (GI) adverse events was compared. Nonsteroidal anti-inflammatory drugs (NSAIDs) have similar efficacy at equipotent doses, but the therapeutic response to various NSAIDs often differs in individual patients. This was a 3-month, randomized, double-blind, multicenter, parallel-group study conducted in adult patients with RA. The study had 2 phases: a 3- to 14-day washout period and a 12-week treatment period. During the treatment phase, the tolerability and efficacy of nabumetone 2000 mg/d were compared with those of naproxen 1000 mg/d. The change from baseline in efficacy variables, including global assessments, number of tender or swollen joints, and pain, was evaluated. The study was sized to provide an 80% power to detect a 15% difference in the percentage improvement on the physician's global assessment (alpha = 0.05). GI safety was assessed by monitoring the occurrence of clinically important adverse GI events. A total of 346 RA patients at 31 US rheumatology centers were randomly assigned to treatment (173 patients per group). The study population was predominantly white (87.0%) and female (70.5%), with a mean age of 54 years. Both treatments improved the signs and symptoms of RA, with no statistically significant differences between groups for any efficacy variables. No serious GI adverse events occurred with either NSAID. The most frequent treatment-related adverse events in both groups were predominantly GI in origin, as were those that resulted in withdrawal from the study. Diarrhea with lower abdominal pain was the most common adverse event in the nabumetone group; upper abdominal pain was the most common adverse event in the naproxen group. The only significant difference between the 2 groups was a higher incidence of diarrhea (P < 0.01) in patients receiving nabumetone. Nabumetone 2000 mg/d was as effective as naproxen 1000 mg/d in relieving the signs and symptoms of RA. In this study, no serious GI adverse events were observed with either NSAID, but nabumetone was associated with a higher incidence of diarrhea.

Gastrointestinal safety profile of meloxicam: a meta-analysis and systematic review of randomized controlled trials

This article provides a systematic review of the frequency and severity of adverse gastrointestinal (GI) events among patients using meloxicam, a cyclooxygenase (COX)-2–selective nonsteroidal anti-inflammatory drug (NSAID). A MEDLINE search of English language articles from 1990–1998, a manual search of citations from primary trials and review articles, and a manual search of proceedings from international gastroenterology meetings were conducted. Randomized clinical trials comparing the frequency of GI adverse events for meloxicam versus non–COX-2–selective NSAIDs were selected. Specific data about the frequency of dyspepsia; perforations, ulcers, and bleeds (PUBs); and withdrawal of medication because of adverse GI events was also extracted. From a pool of 62 potentially relevant citations, 12 randomized trials were identified. All trials concerning symptomatic GI adverse events used the World Health Organization’s Adverse Reaction Terminology List (WHO-ARTL) to code adverse events. Patients using meloxicam had fewer GI adverse events compared with non–COX-2–selective NSAIDs (odds ratio = 0.64; 95% confidence interval [CI], 0.59–0.69). Patients using meloxicam experienced less dyspepsia (odds ratio = 0.73; 95% CI, 0.64–0.84), fewer PUBs (odds ratio = 0.52; 95% CI, 0.28–0.96), and less frequent discontinuation of NSAID because of adverse GI events (odds ratio = 0.59; 95% CI, 0.52–0.67) compared with non–COX-2 selective NSAIDs. Meloxicam, a COX-2–selective NSAID, appears to cause fewer adverse GI events than standard, non–COX-2–selective NSAIDs. However, the generalizability of these data may be limited by the low dose of meloxicam used in most trials and the use of the WHO-ARTL to code adverse events.

An endoscopic study of gastroduodenal lesions induced by nonsteroidal anti-inflammatory drugs

Rheumatoid arthritis (RA) and osteoarthritis (OA) are frequently treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Although NSAIDs are an effective therapy for the pain and inflammation of arthritis, they are associated with serious side effects, particularly ulceration, bleeding, and perforation of the gastrointestinal (GI) tract. In this study, 1826 OA or RA patients who either had been taking NSAIDS for ≥6 months or had been unable to tolerate continuous NSAID use because of adverse GI symptoms or suspected NSAID-related gastroduodenal lesions were examined endoscopically for gastroduodenal lesions and ulcers. At the same time, the patients were asked to rate the severity of any GI symptoms they had been experiencing. Of the total number of patients studied, 817 (44.7%) were OA patients with a mean (± SD) age of 55.8 ± 12.9 years, and 1009 (55.3%) were RA patients with a mean age of 53.1 ± 13.1 years. Clinically significant gastroduodenal lesions were found in 37.1% of patients (n = 678); of these, 24.0% (n = 439) had ulcers. Gastric ulcers were more frequent than duodenal ulcers (14.8% vs 10.2% of patients; P < 0.05), and most gastric ulcers (72.0%) were found in the antrum of the stomach. The prevalence of gastroduodenal ulcers increased with age ( P < 0.001), duration of OA ( P < 0.001), and duration of current NSAID use ( P = 0.019). The prevalence of gastroduodenal ulcers in patients taking NSAIDs for <1 year was 13.8%, compared with a nearly twofold higher prevalence (25.9%) in patients taking NSAIDs for periods of ≥1 year and up to 15 years. The prevalence of gastric ulcers was 32.6% in patients with a history of gastric ulcer but only 13.5% in patients with no GI history (previous gastric ulcer, duodenal ulcer, or upper GI hemorrhage). No relationship was found between the prevalence of gastroduodenal ulcers and sex (men, 22.4%; women, 24.9%) or prevalence of gastroduodenal ulcers and type of arthritic disease (RA, 23.6%; OA, 24.5%). The prevalence of gastroduodenal ulcers increased with the severity of GI symptoms ( P = 0.007). These results provide further endoscopic confirmation of the association between NSAID use and gastroduodenal lesions and ulcers and support the contention that safer treatment alternatives to conventional NSAIDs are required.

Nonsteroidal anti-inflammatory drug-induced gastrointestinal injury

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, are the most commonly used medications worldwide. They are effective analgesic and anti-inflammatory agents. A major drawback to their use is a high frequency of adverse gastrointestinal (GI) effects that cause significant morbidity, occasional mortality, and substantial increases in cost of therapy. In this review, mechanisms of NSAID-induced GI injury are presented, and a clinical approach to diagnosis, treatment, and prevention of these adverse GI effects is provided.

The potential of NSAIDs in the treatment of oesophagealcarcinoma

Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, exert a complex spectrum of harmful and beneficial effects in the gastrointestinal (GI) tract. In the stomach, the deleterious effects of NSAIDs have been well documented and include ulceration, complicated by haemorrhage, perforation and intestinal stricture. NSAIDs have also been associated with colorectal damage and the exacerbation of inflammatory colorectal disease. At the other end of the spectrum, there is a growing conviction that the regular use of NSAIDs reduces the risk of sporadic colorectal carcinoma. In recognition of this potential, a double-blind trial of aspirin and resistant starch is being conducted in familial adenomatous polyposis patients, t The biphasic properties of NSA1Ds in the GI tract are under intensive review. In the stomach, the deleterious NSAID effects appear to be related to cyclo-oxygenase (COX) inhibition thereby reducing the synthesis of protective prostaglandin E2 (PGE2) production. As a secondary effect, NSAIDs can augment the synthesis of damaging leukotrienes (LTs) by 'shunting' the PG precursor arachidonic acid (AA) into lipoxygenase metabolism. Paradoxically, it is these biochemical effects that appear to protect against colorectal carcinoma since excessive PGE2 production appears to contribute to carcinogenesis. The carcinostimulant role of PGE2 is unclear, but it may regulate the balance between colorectal mucosal proliferation and apoptosis. To complicate matters further, recent biochemical advances have demonstrated the existence of 2 COX enzymes. COX-I regulates physiological PG synthesis while COX-2 can be induced by mitogens during pathophysiological reactions. These observations have farreaching therapeutic/commercial implications since the development of COX-2 selective NSAIDs would allow the treatment of PG-related disease without the risk of adverse GI reactions. This new generation of NSAIDs may be particularly useful in colorectal cancer prevention since carcinostimulant PGE2 appears to originate from COX-2. In the oesophagus, there are also reports of harmful and beneficial NSAID effects. These reports have been reconciled- and the emerging message is that PGE2 exerts deleterious effects in oesophageal pathologies. These include pro-inflammatory, dysmotility and carcinostimulant effects. It therefore follows that NSAIDs have preventative potential in patients at risk of oesophageal carcinoma. 3 This potential deserves serious consideration since the incidence of oesophageal carcinoma has increased dramatically in recent decades. In extension of prevention, this paper illustrates the potential of NSAIDs in the treatment of established oesophageal carcinoma.

Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid-supplemented diet versus placebo in cancer patients

To evaluate the effect of early postoperative feeding with a nutritionally complete enteral diet supplemented with the nutrients arginine, ribonucleic acid (RNA), and omega-3 fatty acids on the immune function in patients undergoing surgery for upper gastrointestinal (GI) malignancies. Prospective, randomized, placebo-controlled, double-blind study. Surgical intensive care unit (ICU) in a German university hospital. Forty-two consecutive patients receiving an enteral diet via needle catheter jejunostomy after GI surgery for cancer. Patients were randomized to receive either the arginine, RNA, and omega-3 fatty acids supplemented diet or an isocaloric and isonitrogenous placebo diet. Early enteral nutrition was started on postoperative day 1 in the surgical ICU with 20 mL/hr and progressed to the optimal goal of 80 mL/hr by postoperative day 5. Clinical examination and adverse GI symptoms were recorded on a daily basis. Body weight was determined twice weekly. Immunoglobulin concentrations were determined by laser nephelometry. Interferon-gamma concentrations were measured with a modified enzyme-linked immunosorbent assay method. Fluorescence-activated cell scan flow cytometry was performed to analyze B cells, T lymphocytes and their subsets. Clinical patient characteristics and mean caloric intake were similar between the two groups and both formulas were well tolerated. The number of T lymphocytes and their subsets, helper T cells (CD4) and activated T cells (CD3, HLA-DR), were significantly higher in the supplemented diet group on postoperative days 10 and 16 (p < .05). Mean interferon-gamma concentration after phytohemagglutinin stimulation was higher in the supplemented diet group on postoperative day 16. In the supplemented diet group, mean immunoglobulin M concentrations were significantly higher on postoperative day 10 and mean immunoglobulin G concentrations were higher on postoperative day 16 (p < .05) compared with the results in the placebo group. B-lymphocyte indices were significantly higher in the supplemented vs. the placebo diet group on postoperative days 7 and 10 (p < .05). Supplementation of enteral diet with arginine, RNA, and omega-3 fatty acids in the early postoperative time period improves postoperative immunologic responses and helps to overcome more rapidly the immunologic depression after surgical trauma.

Epidemiology and economics of NSAID-induced gastropathy.

Nonsteroidal anti-inflammatory drug (NSAID) use and gastrointestinal (GI) injury and symptoms are associated in clinical practice, but the importance of this injury is debatable. Most rheumatologists and general practitioners view NSAIDs as extremely valuable and generally well-tolerated first-line agents in the treatment of arthritis and musculoskeletal disorders. Generally, gastroenterologists and surgeons, on the other hand, insist that NSAIDs are dangerous and potentially lethal irritants to the GI mucosa. More frequent NSAID-induced gastropathy may be related to general epidemiological trends in NSAID-using populations: longer life expectancy, multiple risk co-factors for peptic ulcer disease (ie, smoking, alcohol, diet, comedication), and the increased availability of endoscopic examinations. Based on endoscopic studies, the prevalence of NSAID-induced adverse GI events has been documented in published reports. The frequency of bleeding is related to dose and duration of NSAID therapy. Overall, the prevalence of ulcer complications is higher in patients who consume NSAIDs. Cost-benefit analyses indicate that preventing potential GI damage with agents such as misoprostol may reduce the expense of treating the GI side effects associated with NSAID therapy.

Psychopharmacology in Patients with Hepatic and Gastrointestinal Disease

Psychotropic drugs often need to be prescribed to patients who also have pre-existing gastrointestinal (GI) and/or hepatic disease. This paper addresses the effect of GI and hepatic disease on the pharmacokinetics of psychotropic drugs, the effect of psychotropic drugs on pre-existing GI and hepatic diseases, the adverse GI and hepatic effects of psychotropic medications, the effects of GI medications on mental status, and the potential drug interactions between commonly prescribed GI medications and psychotropic drugs. Drug selection and dosage modification based on these considerations should allow safe and effective psychotropic treatment for patients with pre-existing GI and/or hepatic disease.

Gastrointestinal Side Effects with Erythromycin Preparations

This study was designed to determine the incidence and severity of gastrointestinal (GI) side effects in patients taking erythromycin. More patients complained of GI side effects with the enteric-coated tablet (70.8 percent) than with the stearate (51.4 percent) or the ethylsuccinate (48.9 percent) salts. The enteric-coated tablet was associated with a higher incidence of individual adverse reactions; more patients discontinued it because of adverse GI effects. These data demonstrate a high incidence of GI side effects to erythromycin. Additionally, GI side-effect incidence appears to be higher with the enteric-coated tablet.