A review of 150 published randomized trials on the treatment of lung cancer showed serious methodological drawbacks. Handling of withdrawals (only 7 trials had no dropouts), a priori estimates of sample size (only 9 trials specified the required number of patients), blinding of randomization (only 22 trials had a satisfactory procedure), and information on eligible nonrandomized patients (only 13 studies reported it precisely) were areas of major concern. Although trial quality improved over time both in design/execution (study size estimation and analysis by prognostic factors became more frequent) and reporting (information on patients' characteristics and side effects were more thoroughly reported), their evolution was inconsistent. For non-small-cell lung cancer-despite the persistent lack of proof of efficacy of any active treatment-an untreated control arm was prematurely abandoned and a wide variety of tested regimens prevailed even in better-quality studies. Slightly more promising is the picture for small-cell lung cancer, where research indicates somewhat more reliable-though limited-progress. While clinical research in lung cancer has contributed little to defining the best standard care, we conclude that its heterogeneity makes it unlikely that quantitative meta-analysis of existing trials will be constructive.

A 5-year trial involving 201 men and women with high-normal blood pressure at baseline demonstrated the ability to reduce the incidence of hypertension in participants randomized to nutritional-hygienic intervention compared with a control group. The incidence of hypertension was 8.8% among 102 intervention group participants vs 19.2% among 99 control group members. The odds ratio for the incidence of hypertension in the control group was 2.4. Mean trial blood pressure also was lower in the intervention compared with the control group (-1.2 and -1.9 mm Hg, respectively, for diastolic blood pressure at work-site and office visits and -1.3 and -2.0 mm Hg, respectively, for systolic blood pressure at the two sites). Net weight loss in the intervention group averaged 2.7 kg during the trial; sodium intake was reduced by 25% and reported alcohol intake decreased by 30%. The majority of intervention participants also reported an increase in physical activity. Effect on blood pressure was related particularly to degree of weight loss. Results indicate that even a moderate reduction in risk factors for hypertension among hypertension-prone individuals contributes to the primary prevention of the disease.

We assessed the efficacy of lithium carbonate in the treatment of 457 male alcoholics in a double-blind, placebo-controlled Department of Veterans Affairs Cooperative Study. Alcoholics either without depression or with a history of major depression, current major depression, or dysthymic disorder were studied. Two hundred eighty-six alcoholics without depression and 171 alcoholics with depression began the 52-week outpatient study; 172 alcoholics (60.1%) without depression and 108 alcoholics (63.2%) with depression completed the study. Among both all alcoholics who began the study and a subgroup who completed the study, no significant differences between alcoholics who took lithium and those who took placebo were found for the following outcome measures:number of alcoholics abstinent, number of days of drinking, number of alcohol-related hospitalizations, changes in rating of severity of alcoholism, and change in severity of depression. Similarly, no significant differences were found when only the 82 alcoholics compliant in taking lithium and the 89 alcoholics compliant in taking placebo were considered. In our study, lithium treatment did not affect the course of alcoholism in either depressed or nondepressed alcoholics.

Conventional nebulized beta-agonist therapy has met with disappointing results in an increasing number of moderate to severe asthmatics who may be characterized as "poor responders." Thirty-eight patients suffering from acute exacerbations of moderate to severe asthma were treated in an emergency department with an intravenous infusion of saline placebo or 1.2 g of magnesium sulfate after conventional beta-agonist therapy failed to produce significant improvement in peak expiratory flow rate. Nineteen patients were randomized into each of two groups in a placebo-controlled, double-blind clinical trial. The treatment group demonstrated an increase in peak expiratory flow rate from 225 to 297 L/min as compared with 208 to 216 L/min seen in the placebo group. In addition, the number admitted vs discharged was significantly better for the treatment group (7 vs 12) than the placebo group (15 vs 4). Intravenous magnesium sulfate may represent a beneficial adjunct therapy in patients with moderate to severe asthma who show little improvement with beta-agonists.

The effect of anemia (hematocrit less than or equal to 0.34) on subsequent preterm birth was prospectively studied in 35,423 pregnancies. The incidence of preterm birth among women with and without anemia at each week during the third trimester was compared. Early in the third trimester, there was a weak association between anemia and preterm delivery. However, anemia early in the third trimester did not account for the substantial increase in preterm birth seen among black women. Anemia after 30 weeks' gestation was not associated with preterm birth. Among women delivering term infants weighing 2500 g or more, the mean hematocrit rose 0.029 among black women and 0.021 among white women from 25 weeks to term. Compared with hematocrits at 40 weeks' gestation, the odds ratios for anemia reached a maximum at 28 weeks and fell sharply as term approached. When the hematocrits of women in term labor were compared with those of women in preterm labor, a spurious dose-response effect for anemia was created. We conclude that anemia is not a strong factor in the pathogenesis of preterm birth and that comparison of hematocrits from women who are in preterm and term labor produces biased results.

Using an enzyme-linked immunosorbent assay, we measured plasma levels of tumor necrosis factor (TNF) in 38 patients who were treated with either antilipid A antibody or a placebo for presumed gram-negative bacteremia. Sixteen of the 38 patients had positive blood cultures: 14 with gram-negative rods and 2 with Streptococcus pneumoniae. Initial serum samples for TNF determinations were obtained within 2 to 72 hours (mean, 18.8 hours) after the onset of clinical signs of sepsis. Six (16%) of 38 patients had detectable TNF levels: 4 of 14 with positive blood cultures for gram-negative rods but only 2 of 22 with negative blood cultures (odds ratio, 4; 95% confidence limits, 0.5 and 24.3). Of the 6 patients, 4 had received the placebo and 2 had received the antibody. Tumor necrosis factor levels did not predict adult respiratory distress syndrome, shock, disseminated intravascular coagulation, renal failure, or mortality. The highest TNF levels (500 and 250 pg/mL) were observed in 2 patients with Enterobacter cloacae bacteremia who had received the placebo and antilipid A antibody, respectively. The other 2 patients with bacteremia and detectable TNF levels had positive blood cultures for Haemophilus influenzae (50 pg/mL) and Bacteroides fragilis (120 pg/mL), respectively. Despite negative blood cultures, the remaining 2 patients repeatedly had detectable TNF levels and a clinical picture consistent with gram-negative sepsis.

Supplemental oxygen is currently widely utilized in conjunction with athletic competition. To assess the utility of this practice, 12 professional soccer players performed two bouts of exhaustive exercise separated by 5 minutes of rest ("recovery period"). During the recovery period, the subjects breathed either room air or 100% oxygen, assigned by randomized, double-blind design. The entire procedure was repeated on each subject using the opposite gas. The administration of enriched oxygen during the recovery period had no effect on plasma lactate levels or on performance during the second period of exercise. The subjects were unable to identify which gas they received. In conclusion, data from this study indicate that using 100% oxygen applied for short periods offers no advantage on recovery from exhaustive exercise or on subsequent exercise performance.

Accelerated atherosclerosis is a leading cause of death in long-term survivors of heart and renal transplantation and may be exacerbated by the frequent occurrence of posttransplant hyperlipidemia. Attempts to define the mechanism for hyperlipidemia in transplant recipients are confounded by dramatic changes in metabolism and nutritional status after transplantation, as well as by treatment with multiple immunosuppressive and antihypertensive drugs. To avoid these pitfalls and to determine if cyclosporine alone adversely affects lipid levels, we measured lipoprotein levels in a prospective, double-blind, randomized, placebo-controlled trial of cyclosporine in 36 men with amyotrophic lateral sclerosis. Plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol, and apolipoprotein B levels were measured at baseline, 2 weeks, 1 month, and 2 months. Significant increases of 21% in total cholesterol, 31% in low-density lipoprotein cholesterol, and 12% in apolipoprotein B levels occurred only in the cyclosporine group. Cyclosporine therapy alone adversely affects plasma lipoprotein levels by increasing total cholesterol levels, primarily due to an increase in low-density lipoprotein cholesterol level.

Twenty-four adults who were undergoing operations on the abdominal aorta were enrolled in a randomized, double-blind, placebo-controlled study in which epidural morphine sulfate (6 mg) was employed to attenuate the sympathoadrenal response to surgery to evaluate the possible contribution of sympathetic nervous system hyperactivity to postoperative hypertension. Patients who received epidural morphine required less parenteral morphine in the 24 hours following surgery, had lower analogue pain scores, and had markedly lower plasma norepinephrine levels when compared with patients in the control group who received an identical volume of saline in the epidural space. Epidural morphine had no effect on plasma epinephrine or arginine vasopressin levels. Fewer patients in the morphine group (4 of 12 vs 9 of 12 patients in the saline group) required treatment for hypertension (mean arterial blood pressure, greater than or equal to 110 mm Hg) in the 24 hours following surgery. In addition, patients in the morphine group had lower blood pressures in the 24 hours following surgery. These data suggest that sympathetic nervous system activity and not adrenal epinephrine or pituitary secretion of arginine vasopressin is responsible for the development of hypertension following aortic surgery. Furthermore, epidural narcotics appear to provide a means of attenuating this response.

Psyllium hydrophilic mucilloid was examined for its ability to lower serum cholesterol levels in hypercholesterolemic patients. Seventy-five patients with mild to moderate hypercholesterolemia were evaluated in this randomized, double-blind, placebo-controlled parallel study. Patients were treated with a Step I diet for 12 weeks before receiving placebo or 3.4 g of psyllium (equivalent to 1 teaspoon) three times per day for 8 weeks. Compared with placebo, psyllium achieved an additional 4.8% reduction in total cholesterol level, 8.2% reduction in low-density lipoprotein cholesterol level, and 8.8% reduction in apolipoprotein B level. Psyllium did not significantly affect blood pressure or levels of high-density cholesterol, triglycerides, serum glucose, or iron. Reported adherence to diet and treatment was excellent, and no significant adverse side effects were noted. These results indicate psyllium hydrophilic mucilloid is an effective and well-tolerated adjunct to diet in the management of mild to moderate hypercholesterolemia.

In a multicenter cohort study of homosexual men, the proportion of seropositives at enrollment who developed the acquired immunodeficiency syndrome (AIDS) during the following 18 months ranged from 5.5% to 8.2% in 1597 alcohol drinkers vs 9.2% in 109 nondrinkers with no clear trend according to use, and from 6.3% to 9.6% for 1662 users vs 7.2% for 83 nonusers of psychoactive drugs prior to enrollment. Among seropositive men with low initial T helper lymphocyte counts, those who continued to use drugs showed no significantly higher 18-month risk of AIDS than nonusers (13% vs 10%); the corresponding risks were 13% and 15%, respectively, for continued heavier vs continued lighter consumption of alcohol. No other manifestations of immunodeficiency were positively associated with substance use prior to enrollment. Prior use was not associated with low mean T helper cell counts at enrollment, and continued drug or alcohol use after enrollment was not associated with greater subsequent decline in counts. As used in a large cohort of homosexual men, psychoactive substances did not enhance the progression of human immunodeficiency virus infection.

The entire early adolescent population of the 15 communities that constitute the Kansas City (Kansas and Missouri) metropolitan area has participated in a community-based program for prevention of drug abuse since September 1984. The Kansas City area is the first of two major metropolitan sites being evaluated in the Midwestern Prevention Project, a longitudinal trial for primary prevention of cigarette, alcohol, and marijuana use in adolescents. The project includes mass media programming, a school-based educational program for youths, parent education and organization, community organization, and health policy components that are introduced sequentially into communities during a 6-year period. Effects of the program are determined through annual assessments of adolescent drug use in schools that are assigned to immediate intervention or delayed intervention control conditions. In the first 2 years of the project, 22,500 sixth- and seventh-grade adolescents received the school-based educational program component, with parental involvement in homework and mass media coverage. Analyses of 42 schools indicate that the prevalence rates of use for all three drugs are significantly lower at 1-year follow-up in the intervention condition relative to the delayed intervention condition, with or without controlling for race, grade, socioeconomic status, and urbanicity (17% vs 24% for cigarette smoking, 11% vs 16% for alcohol use, and 7% vs 10% for marijuana use in the last month), and the net increase in drug use prevalence among intervention schools is half that of delayed intervention schools.

Phenylpropanolamine (PPA) is frequently used in over-the-counter diet aids and cold medicines, In view of concern about the safety of this sympathomimetic agent, we undertook a double-blind, multicenter clinical trial to determine the factors that influence the pressor effect of short-term oral administration of PPA in healthy individuals. Eight hundred eighty-one healthy individuals in four categories of body weight were randomized to receive placebo capsules three times per day (n = 286), a 75-mg sustained-release PPA hydrochloride preparation once per day (n = 296) followed by two doses of placebo capsules, or a 25-mg immediate-release PPA hydrochloride preparation three times per day (n = 299). The median age of the study population was 28 years, 56% were men, 73% were white, and 47% were in excess of 30% above their ideal body weight. Measurements of pulse rate and supine and standing blood pressure were made 11 times during the day of PPA administration. A statistically significant but clinically unimportant pressor effect for the short-term administration of PPA was observed. The effect occurred in the first 6 hours after administration and was greater in the sustained-release group. Significant independent determinants of the pressor effect of PPA were baseline diastolic blood pressure, baseline body weight, and treatment.

We examined the cardiorespiratory responses of 16 patients with postpoliomyelitis sequelae to a 16-week aerobic exercise program. The patients exercised at 70% of maximal heart rate. Dependent variables were resting and maximal heart rates, systolic and diastolic blood pressures, maximum oxygen consumption, maximum carbon dioxide consumption, respiratory quotient, and maximum expired volume per unit time. The exercise group was superior to the control group in watts, exercise time, maximum expired volume per unit time, and maximum oxygen consumption. No untoward events or loss of leg strength occurred as a result of the exercise regimen. We conclude that the aerobic training program employed in this study is a safe, short-term procedure and that patients with postpolio sequelae respond to training in a manner similar to healthy adults.