This study asks whether prolonged antihypertensive therapy will "cure" a substantial percent of rigorously treated hypertensive patients and whether nutritional change will add an antihypertensive effect and reduce the relapse rate. Of 584 eligible patients normotensive while receiving therapy, 496 were randomized into control and discontinued-medication groups with and without dietary intervention. At 56 weeks, 50% of those who were no longer receiving medication remained normotensive by study criteria. Randomization either to weight-loss group (mean loss of 4.5 kg [10 lb]) or to sodium-restriction group (mean reduction of 40 mEq/day) increased the likelihood of remaining without drug therapy, with an adjusted odds ratio of 2.17 for the sodium group and 3.43 for the weight group. Highest success rates were in the nonoverweight mild hypertensives with sodium restriction (78%) and the overweight mild hypertensives who were reducing their weight (72%). These data demonstrate that weight loss or sodium restriction, in hypertensives controlled for five years, more than doubles success in withdrawal of drug therapy.

A nicotine gum has been approved as a prescription drug to help smokers stop smoking. This article reviews the rationale, pharmacology, efficacy, adverse effects, and method of use of the gum. Several randomized trials, including double-blind placebo-controlled studies, indicate nicotine gum improves long-term quit rates. The efficacy of the gum seems to be due to its ability to relieve withdrawal symptoms. Successful use of the gum depends on appropriate instructions, expectancies, and adjunct therapies. How effective the gum will be when used in general medical practice, to whom it is best to prescribe the gum, and what proportion of smokers will become dependent on the gum are still unclear.

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.

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.

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%).

To determine the efficacy of rifampin prophylaxis in eradication of oropharyngeal carriage of Hemophilus influenzae type b and prevention of secondary H influenzae type b disease, we conducted a multicenter placebo-controlled trial among selected persons with invasive H influenzae type b disease. Households and day-care classrooms were randomized so that their members received either rifampin (initially at a dose of 10 mg/kg/dose for two to four days [rifampin-10], but subsequently at 20 mg/kg/dose for four days [rifampin-20]) or placebo. Pretherapy H influenzae type b colonization rates were similar in the treatment groups. Therapy with either rifampin regimen significantly reduced carriage (rifampin-20, 97%; rifampin-10, 63%; placebo, 28%). New acquisition of carriage was also significantly reduced by either rifampin regimen (rifampin-20 or rifampin-10, 2% v placebo, 6%). No rifampin-resistant H influenzae type b isolates emerged after treatment. Four of 765 placebo-treated contacts experienced secondary disease in contrast to zero of 1,112 rifampin-treated contacts. Because chemoprophylaxis of close contacts with rifampin seems to reduce significantly the risk of secondary H influenzae type b disease, we recommend the administration of prophylaxis in households or day-care classrooms where children younger than 4 years have been exposed to the disease.

Two hundred fifty patients were entered into a multicenter trial to evaluate the efficacy and toxicity of orally administered acyclovir for treatment of recurrent genital herpes. The study consisted of part A, in which patients entered the study within 48 hours of the onset of lesions, and part B, in which patients self-initiated therapy as soon as possible after the onset of a recurrent episode. In both parts, patients received either acyclovir (200 mg) or placebo, five times daily for five days. In both parts, the duration of virus shedding and the time to crusting and healing of lesions were shorter among acyclovir recipients than among placebo recipients. In part B, fewer acyclovir recipients formed new lesions during the study medication period than did placebo recipients. When parts A and B were compared directly, the duration of virus shedding and the times required for crusting and healing of lesions were significantly shorter among acyclovir recipients in part B than among acyclovir recipients in part A. No significant differences in the duration of itching and pain or in the times of subsequent recurrence were noted between acyclovir and placebo groups in either part A or part B. No significant toxic or adverse reactions were seen in acyclovir recipients. Oral acyclovir shortens the duration of virus shedding and the duration of lesions in patients with recurrent genital herpes. These effects are more pronounced when therapy is self-initiated by patients early in the course of a recurrent episode.

We compared the effect of rapid defibrillation by emergency medical technicians (EMTs) combined with paramedic care with that of standard EMT and paramedic care on survival from 540 witnessed episodes of out-of-hospital cardiac arrest caused by ventricular fibrillation. More than 400 EMTs were trained in the recognition of ventricular fibrillation and operation of a defibrillator. For a portion of the three-year study, emergency care for 179 cases was randomized between the two types of services. For randomized cases, when the time interval between EMT and paramedic arrival was greater than four minutes there was significantly improved survival with EMT defibrillation and paramedic care (42%) compared with basic EMT and paramedic care (19%). Similar findings occurred when all cases were considered (38% v 18%). Defibrillation by EMTs combined with paramedic services can enhance survival from ventricular fibrillation, compared with basic EMT and paramedic care.

Twelve patients with severe, painful diabetic neuropathy in the lower extremities were treated with imipramine and placebo in a fixed-dose, double-blind, crossover study of five plus five weeks. Seven patients experienced notable improvement while receiving imipramine and none while receiving placebo. The rating of specific symptoms at the end of each treatment period showed a beneficial effect of imipramine on pain, paresthesia, dysesthesia, numbness, and nocturnal aggravation. The plasma levels of imipramine and its metabolite desipramine were significantly higher in patients who benefited from imipramine treatment.

We conducted a randomized, double-blind, placebo-controlled study during a 30-month period to determine whether sulfamethoxazole and trimethoprim would decrease the incidence of infections occurring after ventriculoperitoneal shunt surgery. Of the 120 patients who completed the study according to protocol, 55 received sulfamethoxazole and trimethoprim and 65 received placebo. The incidence of CSF infection in the group receiving sulfamethoxazole and trimethoprim (4/55) was similar to that in the control group (5/65). There was a trend toward earlier identification of infections in the sulfamethoxazole and trimethoprim group (mean, 24.5 days) compared with the control group (mean, 47 days). There was no difference between infected and uninfected patients with respect to frequency of purported risk factors for infection, including history of shunt infection, history of recent myelomeningocele repair, and type and duration of shunt surgery. The incidence of shunt malfunction was similar in uninfected patients receiving antibiotic prophylaxis (18/51) compared with that of patients receiving placebo (23/60). We did not find that the perioperative use of sulfamethoxazole and trimethoprim reduced the incidence of shunt infection or malfunction.

Enthusiastic reports of the effectiveness of electrical stimulation of the outer ear for the relief of pain ("auriculotherapy") have led to increasing use of the procedure. In the present study, auriculotherapy was evaluated in 36 patients suffering from chronic pain, using a controlled crossover design. The first experiment compared the effects of stimulation of designated auriculotherapy points, and of control points unrelated to the painful area. A second experiment compared stimulation of designated points with a no-stimulation placebo control. Pain-relief scores obtained with the McGill Pain Questionnaire failed to show any differences in either experiment. It is concluded that auriculotherapy is not an effective therapeutic procedure for chronic pain.

These clinical trial results are the first, to our knowledge, from a prospective, randomized, and controlled experiment demonstrating that a reduction of smoking during pregnancy improves the birth weight of the infant. Nine hundred thirty-five pregnant smokers were randomly assigned to treatment and control groups; the former received smoking intervention. At the eighth month of pregnancy, differences between the two groups in salivary thiocyanate level and reported smoking were statistically significant. For single, live births, the treatment group infants had a mean birth weight that was 92 g heavier and were 0.6 cm greater in length than the control group infants. The decrement in weight related to smoking cannot be fully explained by gestational age. The findings suggest that some fetal growth retardation can be overcome by the provision of antismoking assistance to pregnant women.

We assessed the efficacy of periodic instillations of hydrogen peroxide into urinary drainage systems in the prevention of catheter-associated bacteriuria in a prospective and randomized clinical study of 668 patients with indwelling urethral catheters. Bacteriuria was documented in 68 (10%) of the 668 patients after a mean duration of four days of catheterization. There was no difference between the hydrogen peroxide group and the control group in the mean duration of catheterization before the onset of bacteriuria, in the attack rate for bacteriuria, or in the spectrum of etiologic agents recovered. Bag contamination with the same organism responsible for bacteriuria preceded infection in only five (7%) of the 68 patients, three patients using hydrogen peroxide and two in the control group. We conclude that infections arising intraluminally from contamination of the drainage bag are uncommon among catheterized patients and that the periodic instillation of disinfectants into closed sterile drainage systems is not effective in reducing the incidence of catheter-associated bacteriuria.