The effect of 2-mg nicotine chewing gum as an adjunct to group therapy for smoking cessation was studied in a placebo-controlled, double-blind, randomized trial. After one year, 29% of the 106 subjects treated with nicotine chewing gum had remained abstinent throughout the year compared with 16% of the 99 subjects treated with placebo. The results were confirmed by measurement of levels of expired CO. More subjects in the nicotine group (70/94 v 45/93) reported that the gum reduced the craving for smoking. The adverse effects were few and not serious. In the nicotine group, 3% were still using the nicotine gum after two years. No subjects in the placebo group used the chewing gum beyond six months. Nicotine chewing gum is effective in improving the success rates in smoking cessation based on group therapy.

Patients with many common tumors are treated with chemotherapy despite limited evidence of treatment effectiveness. To determine if chemotherapy trials reporting effectiveness actually demonstrated increased survival in treated patients, we reviewed trials published over a two-year period involving four common solid tumors. Of 80 studies, 95% reported response to chemotherapy as an end point. Of 38 studies demonstrating 15% or greater objective response, 76% reported significantly greater survival of responders than of nonresponders. Of 21 studies containing statements supporting treatment effectiveness, 95% based this claim at least in part on the superior survival of responders compared with nonresponders. Because responders may have lived longer without treatment, such comparisons are not valid and may lead to overly optimistic views of chemotherapy effectiveness. Journal editors should be wary of allowing survival comparisons between responders and nonresponders in published reports.

One hundred seven patients (77 women and 30 men) with migraine headache were given prophylactic treatment with timolol maleate, 20 to 30 mg/day, or matching placebo during a 20-week, double-blind crossover study. Among the 94 patients who completed the study, timolol was significantly better than placebo in terms of decrease in frequency of headaches from baseline, numbers of patients who had a 50% reduction in headache frequency, global response, and patient preference. Overall global response rates were 65% with timolol compared with 40% with placebo. The severity and duration of headaches that occurred were unchanged. Few side effects were reported with either timolol or placebo. The study demonstrates that the beta-blocker timolol is a safe and effective treatment in patients with frequent migraine headaches.

P6 an outpatient repeatedly sees the same practitioner, is his care influenced? This double-blind randomized trial examines the effects of outpatient health care provider continuity on the process and outcome of the medical care for 776 men aged 55 years and older. Participants were randomized to two different groups of provider care: provider discontinuity and provider continuity. The outcome of the continuity group was significantly different from that of the discontinuity group. During an 18-month period, patients who had been randomized to the continuity group had fewer emergent admissions (20% v 39%) and a shorter average length of stay (15.5 v 25.5 days). These patients also perceived that the providers were more knowledgeable, thorough, and interested in patient education. We conclude that continuity of outpatient provider care for men aged 55 years and older results in more patient satisfaction, shorter hospitalizations, and fewer emergent hospital admissions.

Moxalactam and ampicillin sodium therapy were compared with amikacin sulfate and ampicillin therapy for meningitis due to gram-negative enteric bacilli in 63 infants enrolled in the Third Neonatal Meningitis Cooperative Study. The population characteristics and causative organisms were comparable for the two treatment groups. Cultures of CSF were positive for approximately three days in both study groups. Case-fatality rates were 23% and 15% for moxalactam-treated infants and ampicillin- and amikacin-treated infants, respectively. Developmental or neurological abnormalities were found in about 40% of survivors, and the rates were comparable for both treatment groups. Computed tomograms in 44 infants were interpreted as normal in 13 (30%); hydrocephalus, abscesses, and low-density areas were the most frequent abnormalities. We conclude that moxalactam is a suitable alternative for treatment of meningitis due to gram-negative enteric bacilli.

In order to determine whether or not regular exercise could alter myocardial perfusion or function, we randomized 146 male volunteers with stable coronary heart disease to either a supervised exercise program (n = 72) or to a usual care program (n = 74). Subjects underwent exercise tests initially and one year later. Significant differences between the two groups included improved aerobic capacity, thallium ischemia scores, and ventricular function in the exercise intervention group. It was not possible to classify the conditions of patients as to the likelihood of improvement or deterioration. This study demonstrated changes in myocardial perfusion and function in a select group of middle-aged men with coronary heart disease who underwent a medically appropriate exercise program lasting one year, but these changes were relatively modest.

One hundred nineteen patients with primary and 31 patients with nonprimary first-episode genital herpes were treated for ten days with 200 mg of acyclovir capsules or placebo capsules orally five times daily. Among acyclovir recipients with primary genital herpes, the median duration of viral shedding (two days), time to crusting of all lesions (seven days), time to healing of all lesions (12 days), and duration of local pain (five days) and constitutional symptoms (three days) were shorter than among placebo recipients (9, 10, 16, 7, and 6 days, respectively). Among patients with nonprimary first-episode genital herpes, oral acyclovir shortened the median duration of viral shedding but had no significant effect on the duration of lesions or symptoms. The time to first recurrence and frequency of recurrences were similar in acyclovir- and placebo-treated patients. Oral acyclovir treatment of primary first-episode genital herpes shortens the duration of viral shedding and symptoms and accelerates healing, but it does not appear to influence subsequent genital recurrences.

The finding that high doses (160 mg) of zinc lowered high-density lipoprotein-cholesterol prompted us to study the effect of low-dose zinc supplementation on lipoprotein values in sedentary and endurance-trained men. Twenty-one endurance-trained and 23 sedentary men received either placebo or 50 mg of zinc sulfate daily for eight weeks. Despite the fact that plasma zinc increased 15%, fasting plasma high-density-lipoprotein cholesterol, total cholesterol, low-density-lipoprotein cholesterol, and triglyceride levels did not change in response to zinc ingestion. We conclude that low-dose zinc supplementation does not affect lipid or lipoprotein values in either endurance-trained or sedentary men.

A wide variety of therapies have been suggested for patients with painful esophageal motility disorders. In a prospective, double-blind, cross-over clinical trial, we evaluated the effectiveness of mercury bougienage ("placebo," 24 F; "therapeutic," 54 F) in eight symptomatic patients with the nutcracker esophagus (NE). There were no significant differences between the placebo or therapeutic dilators in relation to chest pain, dysphagia, lower esophageal sphincter pressure, or amplitude. Chest pain scores after completion of this trial were significantly lower than baseline scores, irrespective of the sequence of dilators used. No subjective or objective improvement could be demonstrated when "therapeutic bougienage" was compared with "placebo bougienage" in patients with the NE. The improvement in symptoms at the completion of the study may result from the close physician-patient interaction, suggesting that this may be more important than the actual size of the bougie.

Recent data from randomized trials have provided a clear understanding of the effectiveness and safety of differing long-term anticoagulant therapies for proximal vein thrombosis. An issue that has not been addressed is their cost-effectiveness. We have performed a cost-effectiveness analysis to rank alternative approaches for long-term therapy. Less intense oral anticoagulant therapy using warfarin sodium is the most cost-effective approach and is preferred in the majority of patients.

We performed a prospective randomized study of the effectiveness of repeated oral doses of activated charcoal in the treatment of phenobarbital overdose. Ten comatose patients who required intubation and mechanical ventilation completed the protocol. Five patients received repeated doses of activated charcoal and sorbitol. Five other patients who received a single dose of charcoal and cathartic served as control subjects. The serum half-life of phenobarbital (mean +/- SD, 36 +/- 13 hours) during repeated administration of charcoal and sorbitol was significantly shorter than that after charcoal administration was discontinued (93 +/- 7 hours) and shorter than the half-life in the single-dose group (93 +/- 52 hours). The length of time that patients in each group required mechanical ventilation, 39 +/- 24 hours (single-dose group) and 48 +/- 8 hours (repeated-dose group), did not differ significantly, nor did the time spent in the hospital. Although administration of repeated doses of activated charcoal to patients with phenobarbital overdose significantly increased the elimination of phenobarbital, it had no clear effects on the patients' clinical course.

In a large, prospective, multicenter investigation of the prophylaxis of deep vein thrombosis (DVT) in patients undergoing elective abdominal, pelvic, and thoracic surgery, 880 patients were randomized into five treatment groups: those receiving (1) dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 5,000 IU; (2) dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 2,500 IU; (3) heparin sodium, 5,000 IU alone; (4) dihydroergotamine mesylate, 0.5 mg alone; or (5) placebo. Treatment was initiated preoperatively and continued twice daily for five to seven days. Daily radiofibrinogen uptake tests revealed the following DVT rates: Dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 5,000 IU, 9.4%; dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 2,500 IU, 16.8%; heparin sodium, 5,000 IU alone, 16.8%; dihydroergotamine mesylate, 0.5 mg alone, 19.4%; and placebo, 24.4%. Dihydroergotamine mesylate, 0.5 mg, plus heparin sodium, 5,000 IU, was significantly superior to all other treatments. Adverse drug experiences did not differ significantly between groups and consisted primarily of postoperative bleeding (2% to 3%), injection site hematoma (6% to 12%), and wound hematoma (1% to 3%).

A vaccine formulated from hepatitis B surface antigen (HBsAg) produced by a recombinant strain of the yeast Saccharomyces cerevisiae was administered to two groups of human volunteers composed of 37 healthy, low-risk adults. Each subject received a 10-micrograms dose of HBsAg at 0, 1, and 6 months. By one month, 27% to 40% of the vaccinees had antibody to HBsAg, and by three months 80% to 100% were antibody positive. Large boosts in titer followed the third dose at six months. The antibody formed is predominantly specific for the a determinant of HBsAg. There have been no serious reactions attributable to the vaccine. The most frequent complaint has been transient soreness at the injection site. As far as we know, this is the first reported use in man of a vaccine prepared by recombinant DNA technology.

Using age-specific rates for multiple sclerosis (MS) based on a national survey, the number of "naturally occurring" new cases of MS among the 45 million swine flu vaccine recipients in the United States is estimated as 1,624 during the year after vaccination, or 31 cases per week. Information from available reports and publications indicates no excess over the expected frequencies. Analyses of admissions for MS before, during, and after the immunization program showed no increase to the US Army hospitals or to the Mayo Clinic. Three independent controlled clinical investigations performed on patients with MS showed no increase in the frequency of exacerbations among those receiving swine flu vaccine as compared with those receiving placebo. Epidemiologic features of MS do not implicate killed virus vaccine as an etiologic factor in onset or exacerbations of the disease. There is no indication from these analyses of any association or cause-and-effect relationship between swine flu vaccine and MS.