Duct-to-duct biliary reconstruction following liver transplantation for primary sclerosing cholangitis

BACKGROUND: Use of non-steroidal anti-inflammatory drugs (NSAIDs) is recognized as an important cause of peptic ulcer complications. The aim of this nested case-control study was to identify risk factors for NSAID-related ulcer complications. METHODS: Cases were consecutive NSAID users admitted with an ulcer complication (n = 118), and controls were a random sample of all NSAID users without ulcer complication identified by a pharmacoepidemiologic database (n = 540). RESULTS: Ninety-four of 118 cases were interviewed, and 324 of 540 controls answered the questionnaire. Analysis showed no difference between included and non-included subjects. Risk factors for patients at start of NSAID therapy were high age: 60-75 years (odds ratio (OR), 3.5 (95% confidence interval (Cl), 1.8-7.1); > 75 years (OR, 8.9 (4.3-18.3)); male sex (OR 1.7 (1.0-3.0)); ulcer history (OR 2.5 (1.2-5.1)); steroid treatment (OR 2.0 (0.8-4.6)); smoking (OR 1.6 (0.9-2.7)); and alcohol use (OR 1.8 (0.9-3.6)). Risk factors for patients receiving NSAID therapy were high age, male sex, ulcer history, smoking and, furthermore, dyspepsia (OR 2.0 (1.0-4.2)), especially NSAID-related dyspepsia (OR 8.7 (4.0-18.9)). Risk was lower for patients treated more than 3 months. CONCLUSION: Risk measured from this design can be shown to correlate strongly with the rate difference, a measure that is more clinically relevant than conventional relative risk estimates. Strong risk factors for NSAID-related ulcer complication are high age, male sex, ulcer history, and dyspepsia related to the NSAID therapy. Avoiding NSAID therapy in these high-risk patients, whenever possible, might prevent many adverse events.     

Possibility of improving postoperative QOL by selecting the gastroepiploic artery as a graft in coronary artery bypass

In patients with PG-dependent renal function, NSAID administration constantly reduces GFR and RBF in a dose-dependent fashion. In this situation, the risk of overt acute renal failure is high and should be taken into proper account. In contrast, the incidence of NSAID-related renal structural alterations appears to be very low, yet the absolute number of patients may be significant considering the wide use of such drugs. Concerning the antiproteinuric effect of NSAIDs, the unfavourable ratio risk/benefit does not seem to support their indication in proteinuric nephropathies. The development of PGHS-2 selective inhibitors is promising, and may open new therapeutical strategies in the treatment of the progression of renal disease.     

Polyamine-enhanced NMDA receptor activity: effect of ethanol

Gastrointestinal symptoms and lesions are often associated with the clinical use of non-steroidal antiinflammatory drugs (NSAIDs). An open-label, single arm multicenter Italian study evaluated if misoprostol, a prostaglandin E1 analogue with gastroduodenal mucosal protective activity, was effective in the prevention and treatment of NSAID-induced gastroduodenal lesions. Patients affected by rheumatoid arthritis (RA) or osteoarthritis (OA), in treatment with NSAIDs and suffering from gastric symptoms or gastroduodenal lesions related to NSAID use, were admitted to the study. Gastrointestinal and arthritic symptoms were assessed before and after 4 weeks co-administration of an NSAID (the most frequent was diclofenac, used in 35% of the RA and in 22% of the OA patients, followed by piroxicam and tenoxicam respectively) + misoprostol (200 mcg two times daily in 58% of the cases, 200 mcg three times daily in 39%, 200 mcg four times daily in 3%). On admission and after 4 weeks of therapy a gastrointestinal endoscopy was performed to evaluate the condition of the gastroduodenal mucosa. Final results showed that: (i) NSAID-related gastric lesions were more frequent than duodenal lesions; (ii) when patients were given misoprostol and NSAIDs, 96% of them did not develop gastric lesions and 97% did not develop duodenal lesions; (iii) even when NSAID therapy was continued, gastric or duodenal lesions induced by NSAIDs healed or in any case did not worsen in 92% and 91% respectively of the cases; (iv) during the period of coadministration of NSAIDs+misoprostol, NSAID-related UGI symptoms disappeared or improved in 77% of the cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mucin secretion in papillary (chromophil) renal cell carcinoma

BACKGROUND: In Canada, primary care physicians manage most musculoskeletal problems. However, their training in this area is limited, and some aspects of management may be suboptimal. This study was conducted to examine primary care physicians' management of 3 common musculoskeletal problems, ascertain the determinants of management and compare management with that recommended by a current practice panel. METHODS: A stratified computer-generated random sample of 798 Ontario members of the College of Family Physicians of Canada received a self-administered questionnaire by mail. Respondents selected various items in the management of 3 hypothetical patients: a 77-year-old woman with a shoulder problem, a 64-year-old man with osteoarthritis of the knee and a 30-year-old man with an acutely hot, swollen knee. Scores reflecting the proportion of recommended investigations, interventions and referrals selected for each scenario were calculated and examined for their association with physician and practice characteristics and physician attitudes. RESULTS: The response rate was 68.3% (529/775 eligible physicians). For the shoulder problem, all of the recommended items were chosen by the majority of respondents. However, of the items not recommended, ordering blood tests was selected by almost half (242 [45.7%]) as was prescribing an NSAID (236 [44.7%]). For the knee osteoarthritis the majority of respondents chose the recommended items except exercise (selected by only 175 [33.1%]). Of the items not recommended, tests were chosen by about half of the respondents and inappropriate referrals (chiefly for orthopedic surgery) were chosen by a quarter. For the acutely hot knee, the majority of physicians chose all of the recommended items except use of ice or heat (selected by only 188 [35.6%]). Although most (415 [78.5%]) of the respondents selected the recommended joint aspiration for this scenario, 84 (15.9%) omitted this investigation or referral to a specialist. The selection of recommended items was strongly associated with training in musculoskeletal specialties during medical school and residency. INTERPRETATION: Primary care physicians' management of 3 common musculoskeletal problems was for the most part in accord with panel recommendations. However, the unnecessary use of diagnostic tests, inappropriate prescribing of NSAIDs, low use of patient-centred options such as exercise, and lack of diagnostic suspicion of infectious arthritis are cause for concern. The results point to the need for increased exposure to musculoskeletal problems during undergraduate and residency training and in continuing medical education.     

Anti-inflammatory drugs and variceal bleeding: a case-control study

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) can have severe gastrointestinal effects and cause peptic ulcers to bleed. Acute bleeding from oesophageal varices is a major complication of cirrhosis of the liver. AIMS: To investigate the role, using a case-control study, of NSAIDs in first bleeding episodes associated with oesophageal or cardial varices in cirrhotic patients. Patients/METHODS: A structured interview was conducted of 125 cirrhotic patients with bleeding mainly related to oesophageal varices and 75 cirrhotic controls with oesophageal varices who had never bled. RESULTS: Cirrhotic patients who were admitted for bleeding related to portal hypertension were more likely to have used NSAIDs during the week before the index day (31 of 125 (25%)) than the cirrhotic controls (eight of 75 (11%); odds ratio = 2.8, p = 0.016). Use of aspirin alone or combined with other NSAIDs was also more prevalent in the cases (21 of 125 (17%)) than in the controls (three of 75 (4%); odds ratio = 4.9, p = 0.007). Logistic regression analysis showed that NSAID use (p = 0.022, odds ratio = 2. 9, 95% confidence interval = 1.8 to 4.7) and variceal size (p<0.001, odds ratio = 4.0, 95% confidence interval = 1.4 to 11.5) were the only variables independently associated with the risk of bleeding. CONCLUSIONS: Aspirin, used alone or combined with other NSAIDs, was associated with a first variceal bleeding episode in patients with cirrhosis. Given the life threatening nature of this complication, the possible benefit of this treatment should be weighed against the risk shown here. No firm conclusions could be drawn on non-aspirin NSAIDs used alone.     

Renal side-effects of non-steroidal antirheumatic drugs

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) are increasingly used for analgesia, as antirheumatics and to inhibit platelet aggregation. Renal side effects occur mainly in patients at risk, e.g. those with pre-existing renal insufficiency, or when used together with diuretics or a second NSAID. PATIENTS: In these patients, reversible impairment of renal function, disturbance of electrolyte homeostasis, edema and hypertension are quite common. Nephrotic syndrome with or without interstitial nephritis and renal failure is a rare complication of long-term NSAID therapy. Analgesic nephropathy may result from chronic NSAID use. These three renal complications are exemplified by case reports. CONCLUSIONS: Since side effects of NSAIDs are initially reversible, careful observation of patients can prevent chronic illness. Only rarely dialysis or treatment with glucocorticoids is indicated in patients with interstitial nephritis. Given the large number of patients taking NSAIDs, however, renal side effects are rare, and usually have no long-term consequences. Nevertheless, early detection of side effects is of importance for the prevention of long-term medical complications.     

Nonsteroidal antiinflammatory drug use and reduced risk of large bowel carcinoma

BACKGROUND: Animal experiments and epidemiologic data have suggested that the use of nonsteroidal antiinflammatory drugs (NSAIDs) may decrease the incidence of large bowel carcinoma. Our purpose was to assess the relation of the use of aspirin and nonaspirin NSAIDs with the risk of large bowel carcinoma. METHODS: A population-based case-control study of colon and rectal carcinoma was conducted in Massachusetts from 1992 to 1994. Data on NSAID use and risk factors for large bowel carcinoma were collected by interview from 1201 incident cases of large bowel carcinoma and 1201 controls matched by age, gender, and area of residence. RESULTS: Regular NSAID use that continued into the year before diagnosis was associated with a significantly decreased relative risk estimate overall (0.7; 95% confidence interval [CI], 0.5-0.8) and among Stage II-IV tumors (0.6; 95% CI, 0.4-0.7). There was no reduction in risk for discontinued use. The inverse association with regular continuing use was present across age and gender and for both colon and rectal carcinoma. Similar inverse associations were present for regular continuing use of aspirin and nonaspirin NSAIDs. There was no significant evidence of a trend for the relative risk to decrease as the duration of use increased, nor was there a trend across the dose of aspirin, which ranged from less than one-half of a 325 mg tablet per day to > or = 2 tablets per day. Discontinuation of use in response to symptoms of carcinoma did not appear to explain the inverse association, nor did bias related to diagnosis of the carcinoma. CONCLUSIONS: These data add to the growing body of evidence that suggests a protective effect of NSAIDs against large bowel carcinoma.     

Carbohydrate-deficient transferrin values in neonatal and umbilical cord blood

We set out to determine the extent to which two groups of patients reported having been informed about the adverse effects of NSAIDs. These consisted of 50 patients who had suffered an acute gastrointestinal bleed while taking a NSAID, and 100 age, sex and drug matched controls who had not. Eight (16%) of the index patients, and 41 (41%) of the control patients remembered having been informed of potential adverse effects, an odds ratio of 3.65 (95% CI 1.55-8.58, P < 0.002). Two (4%) of the index patients recalled having been advised what to do should adverse symptoms develop, whereas 21 (21%) of the control patients did so, an odds ratio of 6.38 (95% CI 1.4-28.4, P < 0.01). Eighteen (36%) of patients who bled had experienced gastrointestinal pain prior to the bleed, but of these only two (11%) admitted reduced compliance with NSAID therapy. In contrast, 10 (67%) of the 15 control patients who had suffered epigastric discomfort admitted reduced compliance, an odds ratio of 16.0 (95% CI 2.6-98.8, P < 0.001). Our results suggest that patients who report not having been informed of adverse effects of NSAIDs are less likely to reduce intake in response to epigastric pain than patients who report having received such information. If the patients who bled had reduced their intake of NSAIDs to the same extent as apparently better informed control patients in response to epigastric pain, it is possible that some episodes of acute gastrointestinal bleeding would have been avoided.     

Nonsteroidal anti-inflammatory drugs and corticosteroids for the management of canine osteoarthritis

Anti-inflammatory medications have long been prescribed for relief of the pain and discomfort associated with OA. This occurs despite the recognized side effects associated with use of NSAIDs and corticosteroids. Available evidence suggests that NSAIDs provide this relief through a combination of central and peripheral actions. Recent discovery of two isoforms of cyclooxygenase has increased our understanding of NSAID activity and may result in identification of drugs that potentially will have fewer side effects. A review of NSAIDs used in veterinary medicine indicates that relatively little is known regarding their role in treating OA, although controlled studies involving carprofen and etodolac have increased our knowledge of the efficacy of specific NSAIDs used for this purpose.     

Neutrophils, Helicobacter pylori, and nonsteroidal anti-inflammatory drug ulcers

BACKGROUND & AIMS: Gastric injury by nonsteroidal anti-inflammatory drugs (NSAIDs) is minimal in neutropenic animals. This study examined peptic ulcer development in the presence or absence of gastric neutrophils in patients requiring long-term use of NSAIDs. METHODS: Gastric histology, neutrophils, and Helicobacter pylori were assessed in 120 patients randomized to receive placebo or 20 or 40 mg famotidine twice daily as prophylaxis against NSAID-related ulcers and who underwent endoscopy at 0, 4, 12, and 24 weeks. RESULTS: In 43 patients without gastric neutrophils, ulcers developed in 1 of 14 (7.7%) taking placebo, 2 of 16 (12.5%) taking 20 mg famotidine, and none of 13 taking 40 mg famotidine. However, in 77 patients with neutrophils, ulcers developed in 13 of 28 (47. 4%) taking placebo (P < 0.001), 3 of 26 (12.6%) taking 20 mg famotidine, and 3 of 23 (13%) taking 40 mg famotidine. Eight of 46 patients (17%) without H. pylori had neutrophils compared with 69 of 74 (93%) with both H. pylori and neutrophils (P < 0.001). CONCLUSIONS: Gastric neutrophils increase the incidence of ulceration in long-term NSAID users. Because neutrophils exist with H. pylori, eradicating this infection might prevent NSAID-related peptic ulcers.     

Risk of severe periodontal disease in a Swedish adult population. A cross-sectional study

In this study, potential risk factors for severe periodontal disease were identified in a cross-sectional sample from the county of Jonkoping, Sweden. 547 adults 20-70 years of age were categorised clinically and radiographically by level of periodontal disease experience. These levels were used to divide the sample into groups--individuals without any reduction in periodontal bone level (60%) and those with severe periodontal bone loss (13%)--which were then used in univariate and multivariate logistic regression analyses as dependent variable. Demographic, socio-economic, general health, smoking habits, clinical, and dental care variables were used in the different regression analyses. In the univariate model, age (20-70 years) was found to be correlated with more severe periodontal disease experience (odds ratio: 1.13; 95% CI: 1.10-1.17). The association with periodontal disease was more pronounced for the older age groups (50, 60, and 70 years). A negative financial situation was also related to severe periodontal bone loss when regressed univariately (odds ratio 2.20 [95%: 1.04-4.68]). Moderate-heavy smoking (> or =10 cigarettes/day) appeared to be associated with severe periodontal destruction with an odds ratio of 9.78 (95% CI: 3.62-36.42). Of the clinical variables in the univariate model, higher mean levels of supragingival dental plaque and the presence of subgingival calculus were related to more severe periodontal disease with odds ratios of 1.02 (95%: 1.01-1.03) and 2.96 (95%: 1.50-5.88), respectively. When the same variables were regressed multivariately, age (continuous) (odds ratio 1.17 [95% CI: 1.12-1.22]), moderate-heavy smoking (odds ratio 11.84 [95% CI: 4.19-33.50]), and higher mean levels of plaque (odds ratio 1.02 [95% CI: 1.00-1.03]) remained significant. Light smoking (1-9 cigarettes/day) was not significantly associated with severe periodontal disease in the 2 regression models. The present study demonstrated that smoking, greater age, and higher mean levels of plaque are potential risk factors for severe periodontal disease in this specific population.     

Asthma, employment status, and disability among adults treated by pulmonary and allergy specialists

STUDY OBJECTIVE: Identify risk factors for work disability among adults with asthma treated by pulmonary and allergy specialists. DESIGN: Cross-sectional survey, including retrospective work history data. PARTICIPANTS: Sixty-eight pulmonary and 16 allergy internal medicine subspecialists maintaining a registry of patient visits for asthma; 698 registered patients aged 18 to 50 years, of whom 601 (86%) were studied. MEASURES: Computer-assisted, telephone-administered structured interview assessing asthma severity, perceived general health status, asthma quality of life, demographics, and work history. Complete work disability defined as total work cessation attributed to asthma; partial work disability defined as change in job, duties, or reduction in work hours attributed to asthma. RESULTS: Complete cessation of work due to asthma was reported by 40 (7%; 95% confidence interval [CI], 5 to 9%) and partial work disability by 53 (10%; 95% CI, 7 to 12%) of 550 subjects with a history of labor force participation. Severity of asthma score predicted both complete disability (odds ratio [OR], 7.9; 95% CI, 4.2 to 15 per 10-point increment) and partial disability (OR 2.6; 95% CI, 1.6 to 4.2). Taking illness severity into account, job conditions, occupation, and work exertion carried a combined disability OR of 3.9 (95% CI, 1.7 to 8.6). CONCLUSIONS: Work disability is common among adults with asthma receiving specialist care. Severity of disease is a powerful predictor, but not the sole predictor of disability in this group. Working conditions, including job-related exposures, are associated with added disability risk even after taking illness severity into account.     

Utilization of outpatient diagnostic imaging. Does the physician's gender play a role?

OBJECTIVE: To examine physician and patient characteristics related to the ordering of imaging studies in a general medicine practice and to determine whether physician gender influences ordering patterns. DESIGN: Retrospective cohort study. SETTING: Hospital-based academic general medicine practice of 29 attending physicians. PATIENTS: All 8,203 visits by 5,011 patients during a 6-month period. METHODS: For each visit the following variables were abstracted from the electronic patient record: patient age, patient gender, visit urgency, visit type, and physician seen. All diagnostic imaging studies performed within 30 days of each outpatient visit were identified from the hospital's Radiology Information System. Screening mammography was not included in the analysis. Physician variables included gender and years since medical school graduation. Logistic regression analysis was used to evaluate the effect of various patient, physician, and visit characteristics on the probability of a diagnostic imaging study being ordered. RESULTS: Patient age, urgent visits, visit frequency, and the gender of the physician were all significantly related to the ordering of an imaging study. Correcting for all other factors, the ordering of an imaging study during an outpatient medical visit was 40% more likely if the physician was female (odds ratio = 1.40; 95% confidence interval [CI] 1.01, 1.95). Female physicians were 62% more likely (95% CI 0.99, 2.64) than male physicians to order an imaging study for a male patient and 21% more likely (95% CI 0.87, 1.69) to order an imaging study for a female patient. CONCLUSIONS: Physician gender is a predictor of whether an outpatient medical visit generates an imaging study. Reasons for this observation are unclear, but may be the result of different practice styles of male and female physicians or unmeasured patient characteristics.     

Nonsteroidal anti-inflammatory drug-associated upper gastrointestinal lesions in rheumatoid arthritis patients. Relationships to gastric histology, Helicobacter pylori infection, and other risk factors for peptic ulcer

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are risk factors for peptic ulcer in rheumatoid arthritis (RA) patients, but the contribution of reactive gastritis, concomitant Helicobacter pylori infection, or RA activity to NSAID ulcer pathogenesis is unknown. METHODS: Ninety-six RA patients taking NSAIDs and dyspeptic sex- and age-matched control patients without NSAID use or an RA diagnosis were enrolled in the study. RESULTS: Gastric ulcer (GU) was detected in 29 (30%) RA patients and 3 control patients (P < 0.001). Sixteen RA patients and no control patient had an H. pylori-negative GU. The GUs of the RA patients were mainly located in the prepyloric region (28%) and antrum (62%). Nine of the 29 RA patients (31%) with GU had more than 1 ulcer. Erosive gastropathy was detected in 34 (71% H. pylori-negative) RA patients and in 13 (62% H. pylori-negative) control subjects (P < 0.001). Chronic gastritis was observed in 65 RA patients (48% H. pylori-negative) and in 58 control subjects (43% H. pylori-negative) (NS). whereas reactive gastritis was found in only 2 RA patients and in none of the controls. Corticosteroid use was the only independent risk factor for GU: odds ratio was 6.8 (95% confidence interval, 1.3-36.0). The prevalences of duodenal ulcer or esophagitis were not increased in RA patients. CONCLUSIONS: RA patients using NSAIDs continuously are at a greatly increased risk of developing both H. pylori-negative and -positive GUs, and corticosteroid use is an independent risk factor for ulcer development. Most RA patients have chronic gastritis, whereas reactive gastritis is rarely associated with continuous NSAID use in RA patients.     

Accelerated hyperfractionated radiotherapy combined with induction and concomitant chemotherapy for inoperable non-small-cell lung cancer--impact of total treatment time

PURPOSE: To determine the importance of fall characteristics, body habitus, function, and hip bone mineral density as independent risk factors for hip fracture in frail nursing home residents. SUBJECTS AND METHODS: In this prospective, case-control study of a single, long-term care facility, we enrolled 132 ambulatory residents (95 women and 37 men) aged 65 and older, including 32 cases (fallers with hip fracture) and 100 controls (fallers with no hip fracture). Principal risk factors included fall characteristics, body habitus, measures of functional assessment, and hip bone mineral density by dual-energy X-ray absorptiometry. RESULTS: In multivariate analysis, including only those with knowledge of the fall direction (n=100), those who fell and suffered a hip fracture were more likely to have fallen sideways (odds ratio 5.7, 95% confidence interval [CI] 1.7 to 18, P= 0.004) and have a low hip bone mineral density (odds ratio 1.9, 95% CI 0.97 to 3.7, P=0.06) than those who fell and did not fracture. When all participants were included (n=132) and subjects who did not know fall direction were coded as not having fallen to the side, a fall to the side (odds ratio 3.9, 95% CI 1.3 to 11, P=0.01), low hip bone density (odds ratio 1.8, 95% CI 1.03 to 3, P=0.04), and impaired mobility (odds ratios 6.4, 95% CI 1.9 to 21, P=0.002) were independently associated with hip fracture. Sixty-seven percent of subjects (87% with and 62% without hip fracture) had a total hip bone mineral density greater than 2.5 SD below adult peak bone mass and were therefore classified as having osteoporosis using World Health Organization criteria. CONCLUSIONS: Among frail elderly nursing home fallers, the preponderance of whom are osteoporotic, a fall to the side, a low hip bone density, and impairment in mobility are all important and independent risk factors for hip fracture. These data suggest that, among the frailest elderly, measures to reduce the severity of a sideways fall and improve mobility touch on new domains of risk, independent of bone mineral density, that need to be targeted for hip fracture prevention in this high-risk group.