Subclinical candiduria in patients with gastrointestinal malignancies: a preliminary study on the protective effect of a natural phytocompound.

There is a great concern for the increasing incidence of candidiasis in cancer patients following immune-suppressive, cytostatic or antibiotic treatment. There are cancer patients with repeat asymptomatic recovery of candida in the urine in whom the choice of treatment, if any, is still a matter of debate. The aim of the study is to test the efficacy and tolerability of a natural anti-fungal phytocompound in patients with tumors of the gastrointestinal tract with prior or ongoing candiduria. Thirty-nine patients with operated gastrointestinal malignancies (18 still under current chemotherapy) with a history of repeated candiduria were enrolled. Eleven patients showed candiduria on enrolment and were treated with K-712, a natural antifungal phytocompound. Genomic analysis was carried out on blood samples of all patients on a monthly basis for 6 months. Within 3 weeks all 11 treated patients had negative cultures in the urine (10 patients after 2 weeks), 7 patients remained free of candiduria throughout the study period while 4 required a new treatment course. Three patients had positive genomic tests for systemic candidiasis and were treated with fluconazole. Eighteen (64 percent) out of the 28 patients who were free of candiduria on enrolment, developed a urinary candida infection during the 6-month follow-up and all cases were successfully treated with K-712. Seven (38 percent) of these cases presented a further recurrence at a later stage and all responded to a new course of K-172. No positive genomic tests were observed during the follow-up period. These data suggest that a consistent part of patients, mostly with gastrointestinal malignancies develop urinary candida infection when following chemotherapy treatment. A therapeutic approach with a natural antifungal phytocompound seems a safe and effective measure and a tentative prophylactic approach might also be envisaged.

Asia Pacific consensus recommendations for colorectal cancer screening.

Colorectal cancer (CRC) is rapidly increasing in Asia, but screening guidelines are lacking. Through reviewing the literature and regional data, and using the modified Delphi process, the Asia Pacific Working Group on Colorectal Cancer and international experts launch consensus recommendations aiming to improve the awareness of healthcare providers of the changing epidemiology and screening tests available. The incidence, anatomical distribution and mortality of CRC among Asian populations are not different compared with Western countries. There is a trend of proximal migration of colonic polyps. Flat or depressed lesions are not uncommon. Screening for CRC should be started at the age of 50 years. Male gender, smoking, obesity and family history are risk factors for colorectal neoplasia. Faecal occult blood test (FOBT, guaiac-based and immunochemical tests), flexible sigmoidoscopy and colonoscopy are recommended for CRC screening. Double-contrast barium enema and CT colonography are not preferred. In resource-limited countries, FOBT is the first choice for CRC screening. Polyps 5-9 mm in diameter should be removed endoscopically and, following a negative colonoscopy, a repeat examination should be performed in 10 years. Screening for CRC should be a national health priority in most Asian countries. Studies on barriers to CRC screening, education for the public and engagement of primary care physicians should be undertaken. There is no consensus on whether nurses should be trained to perform endoscopic procedures for screening of colorectal neoplasia.

Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models. METHODS: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922). RESULTS: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001). CONCLUSIONS: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update.

Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.

Treatment cost of non-small cell lung cancer in three European countries: comparisons across France, Germany, and England using administrative databases.

INTRODUCTION: Lung cancer is a highly prevalent condition with non-small cell lung cancer (NSCLC), representing ∼ 80%. Given its high prevalence and poor survival rates, it is important to understand costs associated with NSCLC treatment. OBJECTIVES: To carry out an incidence-based study in three European countries: France, Germany, and the UK, to estimate the cost of NSCLC treatment. METHODS: Three similar administrative databases were accessed; Hospital Episode Statistics (England), Gesundheitsforen Leipzig (Germany), French Hospital Discharge system (France), using ICD-9/10 codes and treatment/surgery algorithms to identify NSCLC patients. An incidence population of NSCLC patients was obtained using an index year (ranging from 2007-2008), ensuring the absence of prior lung cancer (12-months). Data were extracted on treatment information, patient characteristics, and disease staging. Average NSCLC treatment costs were estimated by age and severity. For England, 20,081 patients were identified, for France, 15,061, and for Germany, 1038. RESULTS: In-patient length of stay was 8.9, 8.7, and 10.1 days for France, England, and Germany, respectively, for the first year. Average total costs for the 2-year follow-up period for France, England, and Germany were €25,063, €17,777, and €32,500, respectively. Sub-group analyses showed higher costs for younger patients and those with metastatic disease. CONCLUSION: Considerable differences in average treatment costs were observed. In-patient costs dominate in the first year of treatment in all countries. The study highlights the costly nature of NSCLC.

Volume-outcome relationships in cardiovascular operations: New York State, 1990-1995.

BACKGROUND: It has been known for nearly 20 years that, in cardiovascular operations, a significant inverse relationship exists between clinical outcomes and the volume of procedures performed. Interestingly, this relationship persists 2 decades after it was recognized. OBJECTIVE: The purpose of this study was to examine the relationship between hospital volume and in-hospital deaths in 3 cardiovascular procedures: coronary artery bypass grafting, elective repair of abdominal aortic aneurysms, and repair of congenital cardiac defects. METHODS: The database includes all patients who were hospitalized in New York State during the years 1990 to 1995. Using standard logistic regression techniques, we analyzed the relationship between hospital volume and outcome. RESULTS: No correlation exists between hospital volume and in-hospital deaths in coronary artery bypass grafting. Statewide, 31 hospitals performed 97,137 operations over the 6-year period (overall mortality rate, 2. 75%). By contrast, most of the hospitals statewide (195 of 230 hospitals) performed 9847 elective abdominal aortic aneurysm repairs with an overall mortality rate of 5.5%. In abdominal aortic aneurysm operations, a significant inverse relationship between hospital volume and in-hospital deaths was determined. Sixteen hospitals performed 7199 repairs for congenital cardiac defects. A significant inverse relationship (which was most pronounced for neonates) was found between volume and death. CONCLUSIONS: The importance of these findings lies in the rather striking difference between the volume-outcome relationship found for operations for abdominal aortic aneurysms and congenital cardiac defects and the lack of such a relationship for coronary artery bypass grafting. This observation may be largely explained by the quality improvement program in New York State for bypass operations since 1989. If so, these results have important implications for expanding the scope of quality improvement efforts in New York State.

The REMATCH trial: rationale, design, and end points. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure.

BACKGROUND: Because left ventricular assist devices have recently been approved by the Food and Drug Administration to support the circulation of patients with end-stage heart failure awaiting cardiac transplantation, these devices are increasingly being considered as a potential alternative to biologic cardiac replacement. The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial is a multicenter study supported by the National Heart, Lung, and Blood Institute to compare long-term implantation of left ventricular assist devices with optimal medical management for patients with end-stage heart failure who require, but do not qualify to receive cardiac transplantation. METHODS: We discuss the rationale for conducting REMATCH, the obstacles to designing this and other randomized surgical trials, the lessons learned in conducting the multicenter pilot study, and the features of the REMATCH study design (objectives, target population, treatments, end points, analysis, and trial organization). CONCLUSIONS: We consider what will be learned from REMATCH, expectations for expanding the use of left ventricular assist devices, and future directions for assessing clinical procedures.

In vitro protective effect of Celergen, a bioactive marine compound, on interleukin-6-related invasiveness of pancreatic cancer.

The purpose of this study was to assess the effect of Celergen, a marine nutraceutical, against tumor cell invasion in human pancreatic cancer cell line (PSN-I). High invasive clone (HI) and low invasive clone (LI) were established from wild type PSN-l cell line after a repeated invasion assay test. The invasive ability of HI cells and the level of IL-6 in the conditioned medium of HI cells was significantly higher than that one of LI cells but both these parameters were significantly reduced by the addition of Celergen (p<0.01). Exogenous IL-6 administration induced a dose dependent enhancement of invasive ability in both cell populations. Moreover, IL-6 receptor expression was detected in 72% of HI cells whereas this occurred only in 37% of LI cells. When co-cultured with Celergen this parameter was significantly downregulated in both cellular subsets (p<0.05). The addition of conditioned medium derived from HI cells (HCM) and LI cells(LCM) enhanced the invasive ability in both cell populations without affecting cell proliferation. The effect of HCM on the invasive ability of HI cells was partially inhibited by the addition of Celergen (p<0.01). In summary, overexpression of IL-6 and its receptor may be one relevant factor contributing to the highly invasive characteristic of the pancreatic cancer cell line we used while a significantly beneficial modulation was obtained by applying this novel marine nutraceutical. This advices to further explore the possibility of marine compounds regulation of IL-6 ligand/receptor and other possible invasive factor interaction in the therapy of this malignancy while further studies are awaited in this setting.

The economics of drug discovery and the ultimate valuation of pharmacotherapies in the marketplace.

Although it is commonly believed that the innovation of new medicines is of paramount importance for improving the health and quality of life of patients, there is also a keen recognition regarding upward-spiraling costs of innovation, drug discovery, and drug development against a backdrop of dwindling successes in research and development (R&D) efforts. We propose a new model of valuation of pharmacotherapies that attempts to secure an adequate return on investment in innovation by ensuring optimal pricing and reimbursement.

Endoscopic hemostasis of bleeding peptic ulcers: 1:10000 adrenalin injection vs. 1:10000 adrenalin +1% aethoxysclerol injection vs. heater probe.

To evaluate the efficacy of three endoscopic methods which utilize different mechanisms of hemostasis to control bleeding peptic ulcers, we performed a prospective randomized study in 83 patients. Thirty-two patients were treated with 1:10000 adrenalin (Group I), 29 patients with 1:10000 adrenalin +1% aethoxysclerol (Group II), and 22 patients with the heater probe (Group III). Gastric ulcers were the source of bleeding in 14, 15 and 12 patients while duodenal ulcers were the source in 16, 13 and 10 patients in Groups I, II and III, respectively. Two stomal ulcers were noted in Group I and 1 in Group II. Two spurters were treated in Group I and 4 in Group II, while 22, 13 and 10 oozers were treated in Groups I, II and III, respectively. Definitive hemostasis was achieved in 94%, 100% and 95% in Groups I, II and III, respectively while the rebleeding rate was 6.25%, 6.9% and 9% respectively. 1:10000 adrenalin injection alone or when combined with subsequent instillation of a sclerosing agent and heater probe application have comparable efficacy in the endoscopic control of bleeding peptic ulcers.

An open trial on short-term omeprazole therapy for gastric and duodenal ulcers.

Omeprazole, a proton pump inhibitor, is a potent and long-acting gastric acid reducing agent. To assess its short-term efficacy and safety, 27 gastric ulcers (GU) and 40 duodenal ulcers (DU) in 64 patients were treated with 20 mg. Omeprazole was given once daily. At 2 weeks, the healing rate for gastric ulcers was 66% (18/27) and for duodenal ulcers, 78% (31/40). At 4 weeks, the healing rate was 85% and 95% for GU and DU, respectively. Pain relief was achieved after 2 weeks in 62% with GU and 61% in DU. There were no significant side effects noted during the treatment course. Omeprazole is effective and safe in the treatment of gastric and duodenal ulcers.

Ulcer recurrence among Filipino patients: clinical profile and risk factors.

Patients with endoscopic diagnosis of gastric and/or duodenal ulcers who eventually had endoscopic confirmation of ulcer healing after any anti-ulcer medication were entered in a 3 year study to determine ulcer recurrence rate, onset of ulcer recurrence and factors associated with ulcer recurrence. Patients from two participating centres who are not on any maintenance treatment had endoscopic examinations at 3, 6 and 12 months after ulcer healing or at any time of symptom recurrence. There were 144 patients entered into the study. The 1 year recurrence rate observed among 125 Filipino patients who completed the study was 73% wherein 71% occurred within the first six months. This was comparable with those reported in the world literature. Thirty-three per cent of those with recurrent ulcers were asymptomatic. The difference in the recurrence rate between gastric and duodenal ulcers was not statistically significant. The only risk factors found to be associated with ulcer relapse were history of smoking and alcohol intake. CLO test for Helicobacter pylori done in 45 patients with recurrent ulcers were all positive, suggesting a strong association between H. pylori and ulcer recurrence.

Direct detection of Mycobacterium tuberculosis using polymerase chain reaction assay among patients with hepatic granuloma.

BACKGROUND: In liver tuberculosis, demonstration of acid bacilli by conventional methods remains futile. Since the definitive diagnosis of liver tuberculosis is based on the histologic evidence of granulomatous process with caseation necrosis, seen in only a third of cases, the diagnosis is made retrospectively by response to empirical anti-tuberculous drug therapy. AIMS: Our objective is to establish a polymerase chain reaction assay for detection of Mycobacterium tuberculosis affecting the liver using the paraffin-embedded liver biopsy specimens obtained from patients with hepatic granulomas. METHODS: As positive control, patients having either "definitive" (n=8) or "presumptive" (n=9) tuberculosis on the basis of clinical, microbiological, histologic data and their positive response to empirical treatment of anti-tuberculous drugs were used. Patients with hepatic granulomas secondary to schistosomiasis (n=6), sarcoidosis (n=2) and other liver diseases (n=10) were used as negative control. RESULTS: Of those patients who were diagnosed as having "definitive" and "presumptive" liver tuberculosis, positivity by one-step polymerase chain reaction was 100% and 44%, respectively. Using the nested polymerase chain reaction, positivity increased to 78% with "presumptive" liver tuberculosis. In contrast, the polymerase chain reaction assays were negative among all patients with hepatic granuloma due to non-tuberculous-in-origin and other liver diseases. CONCLUSIONS: The overall positivity of this polymerase chain reaction assay (88%) compares favorably with that of other conventional methods (12%). Thus, this polymerase chain reaction assay may be a reliable diagnostic tool for liver tuberculosis in a patient population in which the prevalence of diseases associated with hepatic granuloma is common.

Sex differences in the management of coronary artery disease. Survival and Ventricular Enlargement Investigators.

BACKGROUND: Despite the fact that coronary artery disease is the leading cause of death among women, previous studies have suggested that physicians are less likely to pursue an aggressive approach to coronary artery disease in women than in men. To define this issue further, we compared the care previously received by men and women who were enrolled in a large postinfarction intervention trial. METHODS: We assessed the nature and severity of anginal symptoms and the use of antianginal and antiischemic interventions before enrollment in the 1842 men and 389 women with left ventricular ejection fractions less than or equal to 40 percent after an acute myocardial infarction who were randomized in the Survival and Ventricular Enlargement trial. RESULTS: Before their index infarction, women were as likely as men to have had angina and to have been treated with antianginal drugs. However, despite reports by women of symptoms consistent with greater functional disability from angina, fewer women had undergone cardiac catheterization (15.4 percent of women vs. 27.3 percent of men, P less than 0.001) or coronary bypass surgery (5.9 percent of women vs. 12.7 percent of men, P less than 0.001). When these differences were adjusted for important covariates, men were still twice as likely to undergo an invasive cardiac procedure as women, but bypass surgery was performed with equal frequency among the men and women who did undergo cardiac catheterization. CONCLUSIONS: Physicians pursue a less aggressive management approach to coronary disease in women than in men, despite greater cardiac disability in women.

Quality of life among patients post-myocardial infarction at baseline in the Survival and Ventricular Enlargement (SAVE) trial.

A quality of life ancillary study was incorporated into the Survival and Ventricular Enlargement (SAVE) trial of captopril versus placebo among patients who survived an acute myocardial infarction with compromised ventricular functioning, but no overt heart failure. Assessments included patient symptoms, health perceptions, emotional, cognitive, social and sexual levels of functioning, as well as potential covariates, such as life events and social support. The purpose of this study was to evaluate the psychometric properties of the quality of life measures in the SAVE at baseline, and provide a pre-randomization profile of the SAVE patients. One hundred and eighty-four patients participated in this aspect of the trial. Reliability alpha coefficients were adequate or better for all questionnaires, except for life events and sexual activities. Consistent with prior studies, the quality of life parameters were uncorrelated with ventricular ejection fraction. Despite experiencing a recent myocardial infarction with compromised ventricular functioning, patients at baseline generally neither appeared depressed nor focused on symptoms. The baseline findings support the inclusion of the quality of life ancillary study in the overall SAVE trial because of the independent contribution likely to be achieved in terms of evaluating both disease progression and treatment efficacy.

Long-term ciprofloxacin treatment for the prevention of biliary stent blockage: a prospective randomized study.

OBJECTIVE: In vitro experimental and animal studies have shown that quinolones reduce the adherence of bacteria on a polyethylene tube and prevent stent blockage. Our aim was to see whether ciprofloxacin prevents stent blockage in patients with malignant stricture of the biliary tract. METHODS: Patients with inoperable biliary or pancreatic tumor not involving the bifurcation of the common hepatic duct were recruited. They were randomized to receive either endoscopic stenting alone or stenting with prophylactic treatment of ciprofloxacin (200 mg i.v. before stenting, followed by 250 mg orally twice per day). In each follow-up visit, clinical symptoms of cholangitis were documented and blood samples taken for blood counts, serum levels of bilirubin, and alkaline phosphatase. Stent blockage was defined as clinical symptom(s) of cholangitis with biochemical or radiological evidence of stent dysfunction. RESULTS: Fifty-eight patients were recruited into the study. Three patients in the stenting group and three in the ciprofloxacin group were excluded after randomization. Eleven patients received stenting alone and five patients receiving ciprofloxacin had previous endoscopic stenting. Thirteen patients (50%) in the ciprofloxacin group and eight patients (31%) in the stenting group died before stent blockage. Ten patients (38%) in each group had stent blockage during the follow-up at 20 wk. The median stent patency was 11.6 wk and 11.9 wk in the ciprofloxacin group and the stenting group, respectively. Kaplan-Meier analysis of stent patency showed no difference between the two groups. Among patients who received endoscopic stenting for the first time, there was a trend favoring ciprofloxacin treatment, but the difference was not significant. The 30-day and 20-wk mortality between the groups were comparable. CONCLUSION: Long-term use of ciprofloxacin does not prevent blockage of polyethylene biliary stents.

Chronic hepatitis B virus infection in Asian countries.

Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5-10% of adults and up to 90% of infants will become chronically infected, 75% of these in Asia where hepatitis B is the leading cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). In Indonesia, 4.6% of the population was positive for HBsAg in 1994 and of these, 21% were positive for HBeAg and 73% for anti-HBe; 44% and 45% of Indonesian patients with cirrhosis and HCC, respectively, were HBsAg positive. In the Philippines, there appear to be two types of age-specific HBsAg prevalence, suggesting different modes of transmission. In Thailand, 8-10% of males and 6-8% of females are HBsAg positive, with HBsAg also found in 30% of patients with cirrhosis and 50-75% of those with HCC. In Taiwan, 75-80% of patients with chronic liver disease are HBsAg positive, and HBsAg is found in 34% and 72% of patients with cirrhosis and HCC, respectively. In China, 73% of patients with chronic hepatitis and 78% and 71% of those with cirrhosis and HCC, respectively, are HBsAg positive. In Singapore, the prevalence of HBsAg has dropped since the introduction of HBV vaccination and the HBsAg seroprevalence of unvaccinated individuals over 5 years of age is 4.5%. In Malaysia, 5.24% of healthy volunteers, with a mean age of 34 years, were positive for HBsAg in 1997. In the highly endemic countries in Asia, the majority of infections are contracted postnatally or perinatally. Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum and minimal hepatic inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better prognosis than patients who remain HBeAg-positive for prolonged periods of time. The outcome after anti-HBe seroconversion depends on the degree of pre-existing liver damage and any subsequent HBV reactivation. Without pre-existing cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with pre-existing cirrhosis, further complications may ensue. HBsAg-negative chronic hepatitis B is a phase of chronic HBV infection during which a mutation arises resulting in the inability of the virus to produce HBeAg. Such patients tend to have more severe liver disease and run a more rapidly progressive course. The annual probability of developing cirrhosis varies from 0.1 to 1.0% depending on the duration of HBV replication, the severity of disease and the presence of concomitant infections or drugs. The annual incidence of hepatic decompensation in HBV-related cirrhosis varies from 2 to 10% and in these patients the 5-year survival rate drops dramatically to 14-35%. The annual risk of developing HCC in patients with cirrhosis varies between 1 and 6%; the overall reported annual detection rate of HCC in surveillance studies, which included individuals with chronic hepatitis B and cirrhosis, is 0.8-4.1%. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. Prevention of HBV infection thorough vaccination is still, therefore, the best strategy for decreasing the incidence of hepatitis B-associated cirrhosis and HCC.

Cost-effectiveness of coronary artery bypass surgery in octogenarians.

OBJECTIVE: The objective of this retrospective cohort study was to determine whether coronary artery bypass graft (CABG) surgery is effective and cost-effective relative to medical management of coronary artery disease (CAD) in the elderly. SUMMARY BACKGROUND DATA: The aging of the U.S population and the improvements in surgical techniques have resulted in increasing numbers of elderly patients who undergo this surgery. The three randomized, controlled trials (RCTs) that established the efficacy of CABG surgery completed patient enrollment from 19 to 24 years ago excluded patients older than 65 years. Although information regarding outcomes of CABG in this population is mainly available in case series, a major lacuna exists with respect to information on quality of life and cost effectiveness of surgery as compared with medical management. METHODS: The authors retrospectively formed surgical and medically managed cohorts of octogenarians with significant multivessel CAD. More than 600 medical records of patients older than 80 years who underwent angiography at our institution were reviewed to identify 48 patients who were considered reasonable surgical candidates but had not undergone surgery. This cohort was compared with 176 patients who underwent surgery. RESULTS: The cost per quality-adjusted life year saved was $10,424. At 3 years, survival in the surgical group was 80% as compared with 64% in the entire medical cohort and 50% in a smaller subset of the medical cohort. Quality of life in patients who underwent surgery was measurably better than that of the medical cohort with utility index scores, as measured by the EuroQoL, (a seven-item quality of life questionnaire) of 0.84, 0.61, and 0.74, respectively. CONCLUSIONS: Performing CABG surgery in octogenarians is highly cost-effective. The quality of life of the elderly who elect to undergo CABG surgery is greater than that of their cohorts and equal to that of an average 55-year-old person in the general population.

Non-steroidal anti-inflammatory drug toxicity in the upper gastrointestinal tract.

Non-steroidal anti-inflammatory drug (NSAID) toxicity in the upper gastrointestinal tract is the most common serious drug-induced toxicity reported to drug regulatory authorities. In the last two decades, the rediscovery of H. pylori, development of potent ulcer-healing drugs and specific Cox-II inhibitors have opened new horizons in the management of NSAID toxicity. A Working Party composed of gastroenterologists and rheumatologists in the Asia-Pacific region met in Cairns, Australia, in 1999 to review the literature and develop appropriate guidelines. Recommendations were made based on the latest existing evidence. The importance of clinical events as study endpoints was emphasized. While differences exist between NSAIDs and aspirin, most studies have shown that advanced age, history of peptic ulcer disease, serious concomitant illnesses and coprescription of NSAID/aspirin with anticoagulants and steroids are high risk factors. These patients should be considered for prophylactic anti-ulcer therapy. Helicobacter pylori infection may aggravate the toxicity of NSAIDs and, in selected cases, should be treated before NSAID/aspirin is prescribed. Proton pump inhibitors and misoprostol are the most promising agents in preventing gastric and duodenal ulcers. When NSAID/aspirin needs to be continued in patients who develop an NSAID-related ulcer, proton pump inhibitors offer the best healing effect. With the discovery of cyclo-oxygenase isoforms (Cox-I and Cox-II), preferential and specific Cox-II inhibitors have been developed. While early clinical data have suggested promising antiinflammatory effects and improved safety profile in the gastrointestinal tract, several key issues on long-term safety remain unresolved. The use of potent anti-ulcer therapy, treatment of H. pylori infection and the development of Cox-II inhibitor will change the scenario of NSAID/aspirin-related gastrointestinal toxicity in the next millennium.