Evidence on the safety and efficacy of methotrexate as a second- or third-line agent for treating patients with rheumatoid arthritis is reviewed. Four placebo-controlled clinical trials have documented short-term benefit from methotrexate; although true remission is rare, patients receiving methotrexate showed a 26% (95% confidence interval [CI], 17% to 35%) greater improvement in their inflamed joint count and a 39% (95% CI, 26% to 51.5%) greater improvement in pain than did controls receiving nonsteroidal anti-inflammatory agents with or without prednisone. With respect to long-term benefit, improvement usually occurs within 1 month, reaching a maximum at 6 and then leveling off for the duration of treatment; in some patients, the benefit may wane after an initial satisfactory response in the first 4 to 6 months. In one third of those given methotrexate, treatment had to be discontinued because of adverse effects, less than 1% of which were life threatening. Careful baseline and follow-up monitoring is recommended until more data on the safety of methotrexate are available.

To determine the efficacy of adenine arabinoside monophosphate (Ara-AMP vidarabine phosphate) with or without human leukocyte interferon in chronic hepatitis B.

We compared the safety and efficacy of diltiazem and propranolol, and examined demographic factors influencing responses to these agents. One hundred ninety-six patients with supine diastolic blood pressures of 95 to 114 mm Hg were treated with propranolol (80 to 240 mg twice a day) or a sustained-release preparation of diltiazem (60 to 180 mg twice a day) in a double-blind, randomized, parallel group protocol for 6 months. Hydrochlorothiazide was added for patients not achieving the treatment goal. Both agents produced nearly identical and highly significant (p less than 0.001) reductions in supine blood pressure. There were no significant differences at the end of the optional combination therapy phase, although additional reduction with hydrochlorothiazide was slightly greater in the propranolol group. Blood pressure responses in relation to age, gender, race, and smoking history showed that diltiazem produced greater changes in older subjects and women, whereas propranolol was less effective in blacks. However, these differences were not critical.

We used a meta-analysis protocol to evaluate the results of 18 controlled trials that measured the effectiveness of perioperative total parenteral nutrition. The pooled results of 11 trials that were randomized or quasi-randomized showed trends suggesting that total parenteral nutrition reduced the risk for complications from major surgery (p = 0.21) and fatalities (p = 0.21). Consideration of these pooled estimates of the effectiveness of this intervention must be offset by the poor quality of the trials' methodologies and the iatrogenic complications (pneumothorax, septicemia) that occurred at a pooled rate of 0.067. Alternately, other design flaws, such as the failure to exclude patients who were not malnourished from the trials, may have limited the ability of these trials to show the effectiveness of total parenteral nutrition. The evidence available up to August 1986 shows that the routine use of perioperative total parenteral nutrition in unselected patients having major surgery is not justified; however, this intervention may be helpful in subgroups of these patients who are at high risk.

To determine the efficacy and toxicity of brief chemotherapy and involved field radiation therapy for treatment of limited-stage, histologically aggressive malignant lymphoma.

To determine the prognostic value of the treadmill exercise test, we evaluated 2842 consecutive patients with chest pain who had both treadmill testing cardiac catheterization. The population was randomly divided into two equal-sized groups and the Cox regression model was used in one to form a treadmill score that was then validated in the other group. The final treadmill score was calculated as follows: exercise time--(5 X ST deviation)--(4 X treadmill angina index). Using this treadmill score, 13% of the patients were found to be at high risk; 53%, at moderate risk; and 34%, at low risk. The treadmill score added independent prognostic information to that provided by clinical data, coronary anatomy, and left ventricular ejection fraction: patients with three-vessel disease with a score of -11 or less had a 5-year survival rate of 67%, and those with a score of +7 or more had a 5-year survival rate of 93%. The treadmill score was useful for stratifying prognosis in patients with suspected coronary artery disease who were referred to us for catheterization, and may provide a useful adjunct to clinical decision making in the larger population of patients being evaluated for chest pain.

During the past 5 years, clinical trials in hairy cell leukemia have shown dramatic activity for alpha-interferon and 2'-deoxycoformycin (pentostatin). Responses can be induced in more than 80% of patients using either agent, although a greater number of complete pathologic remissions may be achieved with deoxycoformycin. Despite interesting preliminary data, the optimal dose, schedule, treatment duration, and impact of therapy on survival are unknown. Clinical trials comparing efficacy and toxicity of alpha-interferon and deoxycoformycin, the extent of cross-resistance, and relationship of activity to previous splenectomy are in progress. Additional studies are testing combinations of these agents. Although interferon is commercially available for treating hairy cell leukemia, considering such therapy routine is counterproductive. Long-term clinical trials of interferon and deoxycoformycin are essential to advance our biologic knowledge of this rare disease, and to ensure optimal therapy for a potentially curable malignancy.

To test the hypothesis that patients with asthma who develop cough and wheezing after the use of beclomethasone aerosol would have a better tolerance for triamcinolone aerosol.

To determine whether prolonging the duration of tamoxifen administration beyond the cessation of a combined chemotherapy regimen benefits patients with primary breast cancer with positive findings in axillary nodes who benefit initially from the combined regimen.

To determine the effect of concurrent chest radiation therapy on response rate, recurrence, and treatment toxicity among patients with limited stage small cell lung cancer who are receiving combination chemotherapy.

The combined data from 16 prospective trials (2133 patients) appear to suggest that antacids prevent stress ulcer bleeding more effectively than does cimetidine. However, the use of occult blood detection methods to diagnose stress ulcer bleeding may have led to the recognition of clinically insignificant bleeding. When the data from these trials are categorized according to the criteria used for the diagnoses of bleeding (either occult blood detection or clinically overt bleeding), there was no significant difference between antacids and cimetidine in the prevention of overt bleeding (3.3% of 458 compared with 2.7% of 402 patients who bled, respectively; p = 0.69). In addition, both agents were more effective (p less than 0.001) than placebo (15% of 720 patients who bled) in the prevention of overt bleeding. Cimetidine and antacids are equal in preventing significant stress ulcer bleeding.

to determine whether digoxin is effective in converting atrial fibrillation of recent onset to normal sinus rhythm.

to determine the efficacy of fish-oil dietary supplements in active rheumatoid arthritis and their effect on neutrophil leukotriene levels.

We compared the efficacy of orally administered ampicillin, 2 g/d, with that of trimethoprim-sulfamethoxazole, 320 mg/d-1600 mg/d, given for 2 or 6 weeks for outpatient management of acute uncomplicated renal infection in women. Of 98 women participating in the trial, 60 had renal infections with susceptible strains, complied with drug therapy, and completed 6 weeks of follow-up. Before treatment, 39 women had symptoms and signs of acute pyelonephritis; 21 had symptoms of cystitis but positive tests for antibody-coated bacteria. All 60 women had alleviation of symptoms and resolution of bacteriuria after 7 days of therapy. Subsequent recurrences occurred in 12 of 27 women given ampicillin, compared with 4 of 33 given trimethoprim-sulfamethoxazole (p = 0.008). Serotyping showed that most recurrences were reinfections with ampicillin-resistant strains. With each drug, a 2-week regimen of therapy proved as efficacious as a 6-week regimen, but the longer regimen was less well tolerated. We conclude that a 2-week treatment regimen is sufficient to manage acute pyelonephritis in outpatients and that trimethoprim-sulfamethoxazole is preferable to ampicillin therapy.

Nonsteroidal anti-inflammatory drugs are a frequent cause of gastric and duodenal mucosal injury. We examined the effect of indomethacin on duodenal mucosal bicarbonate secretion and prostaglandin output in healthy subjects. Subjects received either 50 mg of indomethacin or placebo orally 13 hours and 1 hour before study. A 4-cm segment of proximal (the duodenal bulb) or distal (10 to 14 cm beyond the pylorus) duodenum was isolated and perfused with 154 mM NaCl containing a nonabsorbable marker. In the proximal duodenum indomethacin reduced both basal and acid-stimulated bicarbonate secretion by approximately 65% (p less than 0.01); in the distal duodenum indomethacin decreased basal and acid-stimulated bicarbonate output by approximately 45% (p less than 0.01). Oral indomethacin inhibited basal and acid-stimulated duodenal prostaglandin E2 output in both the proximal and distal duodenum. We conclude that, by decreasing duodenal mucosal bicarbonate production and prostaglandin output in humans, oral indomethacin, in two doses of 50 mg each, impairs an important duodenal defense mechanism.