Systemic interferon has been advocated as an effective therapy for recurrent genital warts. A double-blind, placebo-controlled, multicenter international trial involving 172 patients with recurrent condylomata was conducted using systemic interferon alfa-2a in doses of 3 or 9 MIU three times per week for 4 weeks. The treatment period was followed by a treatment-free follow-up period of 2 months. Complete responders at month 3 were followed up to 9 months or until they had a recurrence, whichever occurred first. The combined rates of complete response (total disappearance of all lesions without appearance of new ones) and major incomplete response (at least a 75% reduction in total lesion area) at 3 months after the commencement of therapy were 34%, 25%, and 30%, respectively, in 166 patients receiving 3 and 9 MIU of interferon alfa-2a and placebo. The recurrence rates at the end of 9 months were 9% in the placebo and 3-MIU groups and 36% in the 9-MIU group. We conclude that systemic interferon alfa-2a administered three times weekly for 4 weeks at doses of 3 and 9 MIU is not effective as monotherapy for genital warts that have recurred after standard ablative therapy.

We report a prospective, randomized, controlled clinical trial to evaluate the efficacy of antibiotic-bonded catheters in reducing the incidence of intravascular catheter-related infections. Ninety-three central venous catheters and 85 arterial catheters were studied in the surgical intensive care unit. Study catheters were pretreated with the cationic surfactant tridodecylmethylammonium chloride. The anionic antibiotic, cefazolin, was bonded before insertion of the catheters by immersing them in a 50-mg/mL solution. Fourteen percent of the 81 catheters in the control group were infected, compared with 2% of the 97 antibiotic-bonded catheters. Staphylococcus epidermidis was the most common organism obtained. There was no significant difference in the number of colonized or clinically inflamed catheter insertion sites. None of the 100 antibiotic immersion solutions yielded anything on microbiologic culture. We conclude that antibiotic bonding is an efficient, safe, and cost-effective method of reducing intravascular catheter infection in patients who are in intensive care units.

Exposure of young children to group day-care settings increases the risk of illness and may result in higher use of medical care. These observations raise concerns that the use of such settings for early intervention programs for low-birth-weight infants may increase the already high burden of medical care costs incurred by these children and their families. To address the question of medical care use associated with center-based care, we examined the hospital-based and ambulatory care reported for participants of the Infant Health and Development Program. This project is a multisite randomized trial of an early intervention program for preterm low-birth-weight infants with an intervention including 2 years of center-based care. The Intervention group did not differ in hospital-based care and averaged only two more physicians' visits over the 3-year observation period than the comparison group. We conclude that early intervention programs involving high-quality group care are not accompanied by substantial increases in health care use.

A randomized controlled trial with 76 physicians in 16 community hospitals evaluated audit and feedback and local opinion leader education as methods of encouraging compliance with a guideline for the management of women with a previous cesarean section. The guideline recommended clinical actions to increase trial of labor and vaginal birth rates. Charts for all 3552 cases in the study groups were audited. After 24 months the trial of labor and vaginal birth rates in the audit and feedback group were no different from those in the control group, but rates were 46% and 85% higher, respectively, among physicians educated by an opinion leader. Duration of hospital stay was lower in the opinion leader education group than in the other two groups. The overall cesarean section rate was reduced only in the opinion leader education group. There were no adverse clinical outcomes attributable to the interventions. The use of opinion leaders improved the quality of care.

The continuous presence of a supportive companion (doula) during labor and delivery in two studies in Guatemala shortened labor and reduced the need for cesarean section and other interventions. In a US hospital with modern obstetric practices, 412 healthy nulliparous women in labor were randomly assigned to a supported group (n = 212) that received the continuous support of a doula or an observed group (n = 200) that was monitored by an inconspicuous observer. Two hundred four women were assigned to a control group after delivery. Continuous labor support significantly reduced the rate of cesarean section deliveries (supported group, 8%; observed group, 13%; and control group, 18%) and forceps deliveries. Epidural anesthesia for spontaneous vaginal deliveries varied across the three groups (supported group, 7.8%; observed group, 22.6%; and control group, 55.3%). Oxytocin use, duration of labor, prolonged infant hospitalization, and maternal fever followed a similar pattern. The beneficial effects of labor support underscore the need for a review of current obstetric practices.

Fecal coliform contamination of environmental surfaces and hands in the day-care center is common. This study evaluated the effect of two diaper types on fecal contamination. Ten rooms in four day-care centers containing 141 children were studied in a prospective, randomized, crossover study. A total of 2946 samples were cultured during the 9-week study. Fecal coliforms were isolated from 307 inanimate objects (15%), 73 toy balls (46%), and 131 hands (17%). The number of contaminated inanimate objects was significantly less in rooms where paper diapers were worn when compared with that in rooms where double cloth diapers with plastic overpants were worn and in rooms where clothes were worn over diapers. Inanimate object cultures had more contamination in rooms in which diarrhea had occurred. Containment of feces by overclothes and diaper type may be important in decreasing transmission of enteric pathogens in day-care environments.

Oat cereals rich in the water-soluble fiber beta-glucan have been studied as a dietary therapy for hypercholesterolemia. To determine the hypocholesterolemic response of beta-glucan in the diet, 156 adults with low-density lipoprotein cholesterol (LDL-C) levels above 4.14 mmol/L (160 mg/dL) or between 3.37 and 4.14 mmol/L (130 and 160 mg/dL) with multiple risk factors were randomized to one of seven groups. Six groups received either oatmeal or oat bran at doses (dry weight) of 28 g (1 oz), 56 g (2 oz), and 84 g (3 oz). A seventh group received 28 g of farina (beta-glucan control). At week 6 of treatment, significant differences were found for both total cholesterol and LDL-C levels among the farina control and the treatment groups who were receiving 84 g of oatmeal, 56 g of oat bran, and 84 g of oat bran, with decreases in LDL-C levels of 10.1%, 15.9%, and 11.5%, respectively. Fifty-six grams of oat bran resulted in significantly greater reductions in LDL-C levels than 56 g of oatmeal. Nutrient analysis shows no difference in dietary fat content between these treatment groups; therefore, the higher beta-glucan content of oat bran most likely explains the significantly greater LDL-C reductions. A dose-dependent reduction in LDL-C levels with oat cereals supports the independent hypocholesterolemic effects of beta-glucan.

Because the safety of withholding standard therapy and enrolling patients with stable angina in placebo-controlled trials is not known, we identified all events leading to dropout from trials of 12 antianginal drugs submitted in support of new drug applications to the US Food and Drug Administration. Persons who dropped out of the trials were classified as cause due to adverse cardiovascular events or other causes without knowledge of drug assignment. There were 3161 subjects who entered any randomized, double-blind phase of placebo-controlled protocols; 197 (6.2%) withdrew because of cardiovascular events. There was no difference in risk of adverse events between drug and placebo groups. A prospectively defined subgroup analysis showed that groups who received calcium antagonists were at an increased risk of dropout compared with placebo groups (P = .04), primarily because of a disproportionate number of adverse events in studies of one drug. In conclusion, there were few adverse experiences associated with short-term placebo use. Withholding active treatment does not increase the risk of serious cardiac events.

We randomized 389 symptomatic patients with human immunodeficiency virus (HIV) infection to ditiocarb sodium (400 mg/m2 orally for 24 weeks) or a placebo. Patients were well balanced according to Centers for Disease Control (CDC) group, CD4+ cell number, and duration of disease prior to entry. Ten new acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections occurred in the treated patients and 21 in the controls. Reduction of new opportunistic infections in the ditiocarb group was significant in all patients (relative risk [RR], 0.44) and in patients with AIDS (CDC groups IV-C1 and IV-D) (RR, 0.12). The size of the effect of ditiocarb was maintained when data were reanalyzed after exclusion of a patient who progressed to Pneumocystis carinii pneumonia who was not strictly CDC-defined (RR, 0.46), or when considering as new opportunistic infections three events, which were clinically active at entry, but for which the definitive diagnosis was made during study (RR, 0.49). The administration of ditiocarb did not induce any major adverse clinical or biological reactions. We conclude that, in this study, ditiocarb was safe and reduced the incidence of opportunistic infections in patients with symptomatic HIV infection.

Seventeen patients with congenital spastic cerebral palsy and six patients with other forms of spasticity were injected intrathecally with doses of placebo or baclofen, 25 micrograms, 50 micrograms, or 100 micrograms, in a randomized, double-blind manner. Muscle tone in the upper and lower extremities was assessed by Ashworth scores both before the injections and every 2 hours afterward for 8 hours. Function of the upper extremities was evaluated before the injections and 4 hours afterward. Muscle tone in the lower extremities was significantly decreased within 2 hours after baclofen injection and remained lower than baseline 8 hours afterward. Upper extremity tone and function were not significantly affected by these single doses. Confusion and drowsiness occurred in two of the youngest children in the study after the 50-micrograms dose, but cleared within 2 hours. Our findings indicate that intrathecal baclofen reduces spasticity in children with cerebral palsy, as it does in adults with spasticity of spinal origin.

In order to determine potential negative neurobehavioral effects of phenytoin given to prevent the development of posttraumatic seizures, 244 subjects were randomized to phenytoin or placebo. They received neurobehavioral assessments at 1 and 12 months postinjury while receiving their assigned drug and at 24 months while receiving no drugs. In the severely injured, phenytoin significantly impaired performance at 1 month. No significant differences were found as a function of phenytoin in the moderately injured patients at 1 month or in either severity group at 1 year. Patients who stopped receiving phenytoin according to protocol between 1 and 2 years improved more than corresponding placebo cases on several measures. We conclude that phenytoin has negative cognitive effects. This, combined with lack of evidence for its effectiveness in preventing posttraumatic seizures beyond the first week, raises questions regarding its use for long-term prophylaxis. Our findings do not negate phenytoin's proven efficacy in controlling established seizures nor do they indicate that its cognitive effects are worse than other anticonvulsant drugs.

We studied the effect of standard and high doses of epinephrine on coronary perfusion pressure during cardiopulmonary resuscitation in 32 patients whose cardiac arrest was refractory to advanced cardiac life support. Simultaneous aortic and right atrial pressures were measured and plasma epinephrine levels were sampled. Patients remaining in cardiac arrest after multiple 1-mg doses of epinephrine received a high dose of 0.2 mg/kg. The increase in the coronary perfusion pressures was 3.7 +/- 5.0 mm Hg following a standard dose, not a statistically significant change. The increase after a high dose was 11.3 +/- 10.0 mm Hg; this was both statistically different than before administration and larger than after a standard dose. High-dose epinephrine was more likely to raise the coronary perfusion pressure above the previously demonstrated critical value of 15 mm Hg. The highest arterial plasma epinephrine level after a standard dose was 152 +/- 162 ng/mL, and after a high dose, 393 +/- 289 ng/mL. Because coronary perfusion pressure is a good predictor of outcome in cardiac arrest, the increase after high-dose epinephrine may improve rates of return of spontaneous circulation.

The effectiveness of lovastatin was compared with both a high-fat vs low-fat diet. Hypercholesterolemic subjects were studied under metabolic ward conditions for diet periods of 3 weeks while receiving lovastatin (40 mg/d) or placebo. Multiple lipoprotein levels were measured during the final week of each diet period. Nineteen subjects completed the study on the high-fat (43% of kilojoules) diet and 16 on the low-fat (25% of kilojoules) diet. Lovastatin reduced total cholesterol by 23% and low-density lipoprotein cholesterol by 30%, compared with placebo on both diets, with no significant diet-drug interaction. High-density lipoprotein cholesterol was raised by 7% to 8% on the diet regimens. Addition of lovastatin to the low-fat diet permitted 80% of subjects on this diet, but less than 50% of those on the high-fat diet, to achieve current guidelines. Although lovastatin produces a comparable percentage reduction in lipoprotein profiles on either diet, the accompanying low-fat diet remains advisable for additional reduction of low-density lipoprotein cholesterol levels to specified goals.

In this 3-year study of suppressive acyclovir for recurrent genital herpes, patients with more than six recurrences per year were randomized initially to 400 mg of acyclovir or placebo orally two times per day, with recurrences treated with 200 mg of acyclovir five times per day for 5 days. In the second year of the study, all patients received acyclovir as a daily suppressive or intermittent acute therapy; in the third year, all received daily acyclovir. Among 525 patients completing 3 study years, 289 received 3 years of suppressive therapy and 236 received 1 year of acute therapy followed by 2 years of suppressive therapy. Of those who completed the third year, 61% were recurrence free that year; 25% of the suppressive therapy-only group were recurrence free for all 3 years. The annual recurrence rate dropped from more than 12 recurrences per year at baseline to 1.0 (suppressive therapy) and 1.4 (acute and suppressive therapy) recurrences during the third year. No significant toxic effects were detected. Daily suppressive acyclovir therapy was effective and well tolerated.

To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, we studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration. The patients were assigned randomly to receive continuous subcutaneous infusion of either octreotide, 300 micrograms/24 h (five patients) or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration rate and mean total kidney volume were not significantly different in the two groups. However, after 12 weeks of treatment, the mean glomerular filtration rate was significantly lower in the octreotide group (136 mL/min per 1.73 m2; range, 91 to 158 mL/min per 1.73 m2) than in the placebo group (157 mL/min per 1.73 m2; range, 138 to 184 mL/min per 1.73 m2). Furthermore, the mean total kidney volume was significantly lower after treatment in the octreotide group (379 mL/1.73 m2; range, 307 to 454 mL/1.73 m2) than in the placebo group (389 mL/1.73 m2; range, 347 to 465 mL/1.73 m2). Glycemic control did not change significantly in either group. We conclude that subcutaneous infusion of octreotide for 12 weeks reduces increased glomerular filtration rate and kidney size in patients with insulin-dependent diabetes mellitus despite the fact that glycemic control remains unchanged.

Decrease in the average duration of hemodialysis treatment time is a continuing phenomenon. We investigated the relationship of 3-year mortality to duration of dialysis in a 1984-1985 national random sample of 600 hemodialysis patients from 36 dialysis units. Mortality was negatively associated with duration of dialysis treatments, as shown by the Cox model, adjusted for other patient and dialysis unit covariates. With adjustment for other covariates, patients receiving an average dialysis treatment duration of less than 3.5 hours had relative mortality risks of 1.17 to 2.18 compared with those with treatments longer than 3.5 hours (mortality risk of 1.0). Reverse causation (the possibility that more seriously ill patients received dialysis for a shorter time) appears unlikely. We conclude that duration of the dialysis procedure is an important element in determining patient mortality as one of the factors determining the adequacy of dialysis.

The efficacy of bladder training was evaluated in a randomized clinical trial involving 123 noninstitutionalized women 55 years and older with urinary incontinence. Subjects were urodynamically categorized as those with urethral sphincteric incompetence (N = 88) and those with detrusor instability with or without concomitant sphincteric incompetence (N = 35). Bladder training reduced the number of incontinent episodes by 57%; the effect was similar for both urodynamic diagnostic groups. The quantity of fluid loss was reduced by 54%. This was greater for patients with detrusor instability than for those without it. Diurnal and nocturnal voluntary micturitions were also reduced. The effect on nocturnal micturition, however, was not observed in subjects with unstable detrusor function. It is recommended that bladder training be considered as an initial step in treatment of women with urinary incontinence. Provided prior comprehensive clinical evaluation is done, it can be prescribed without the need for urodynamic characterization.

The independent prognostic factors affecting survival were assessed in 240 men undergoing treatment for metastatic prostate cancer as part of a randomized clinical trial comparing the gonadotropin releasing hormone analogue Zoladex (goserelin acetate implant) with castration. In a multivariate analysis, the most highly significant predictors were the presence or absence of bone pain, serum testosterone levels, serum alkaline phosphatase levels, and performance status. Patients with all four factors favorable for survival had a 2-year survival rate of 84% as compared with only 8% for patients with none of the four factors favorable for survival. No other factors were significant. A separate analysis of serum testosterone levels revealed that the higher the pretreatment serum testosterone level, the greater the survival rate. Compared with patients with serum testosterone levels less than 6.9 nmol/L, significant differences in survival were observed for patients with serum testosterone levels of 10.4 to 13.9, 13.9 to 17.3, and over 17.3 nmol/L. These results have important implications for the design and analysis of future clinical trials of hormone therapy and for counseling patients regarding the short-term prognosis of their disease.

To measure the effectiveness and tolerance of long-term malaria prophylaxis with mefloquine, the incidence of Plasmodium falciparum malaria and of adverse reactions was compared in Peace Corps volunteers in West Africa who took mefloquine every 2 weeks and in volunteers who took chloroquine phosphate weekly. Mefloquine was only 63% more effective than chloroquine; the monthly incidence of P falciparum infections was one case per 100 volunteers who took mefloquine and 2.7 cases per 100 volunteers who took chloroquine. Using daily proguanil (chloroguanide) hydrochloride in addition to chloroquine did not provide additional protection. All mefloquine prophylaxis failures occurred during the second week of the every-2-weeks dosing regimen in volunteers who had used mefloquine for more than 2 months. Blood concentrations of mefloquine were lower during the second week of the alternate-week regimen than during the first week, suggesting that blood levels are too low during the second week to suppress parasitemia. No serious adverse reactions were observed. The results indicate that a dosing regimen of 250 mg of mefloquine weekly should be considered for travelers to areas with chloroquine-resistant P falciparum malaria.