We report on the treatment received by 217 patients in the community with a diagnosis of major depressive disorder of at least one month's duration. Only a low proportion of subjects received intensive treatment with antidepressant medication or electroconvulsive therapy, as judged by research standards and current clinical teaching. Specific associations emerge between treatment and several clinical, sociodemographic, and diagnostic variables; however, taken together these variables account for only a small fraction of the variance in treatment received. Even among patient subgroups based on severity and long duration of illness, high proportions did not receive adequate therapeutic trials. Substantial differences are found in treatment across community centers that are not attributable to variation in the clinical characteristics of patients. We conclude that more research is needed to determine how patients and practitioners contribute to this phenomenon of low intensity of somatic treatment.

Seventeen patients (15 women, two men) with progressive, erosive seropositive rheumatoid arthritis (RA) refractory to conventional therapy were treated with cyclophosphamide, azathioprine, and hydroxychloroquine sulfate for an average of 27 +/- 19 months (mean +/- SD throughout) (range, five to 60 months). Disease suppression began in 14 patients within three to 16 months (mean, seven months). Five patients achieved complete remission, two had activity in a single joint only, seven had partial disease suppression, and three showed no response. Prednisone dosage was decreased or administration discontinued in nine of ten patients (5.8 +/- 1.2 to 2.7 +/- 3 mg/day). Serial hand roentgenograms showed recortication of erosions in nine patients, with "filling in" of some erosions in three of these. No change was seen in the roentgenograms of five patients, while progressive disease occurred in three instances. Combined therapy with small doses of three drugs, each with proved antirheumatic activity when used separately in larger doses, may provide satisfactory long-term disease control in patients with intractable RA. This regimen is experimental. Proof of efficacy requires a controlled study. Until such data are obtained, this drug combination is not recommended for general use.

The Multiple Risk Factor Intervention Trial was a randomized primary prevention trial to test the effect of a multifactor intervention program on mortality from coronary heart disease (CHD) in 12,866 high-risk men aged 35 to 57 years. Men were randomly assigned either to a special intervention (SI) program consisting of stepped-care treatment for hypertension, counseling for cigarette smoking, and dietary advice for lowering blood cholesterol levels, or to their usual sources of health care in the community (UC). Over an average follow-up period of seven years, risk factor levels declined in both groups, but to a greater degree for the SI men. Mortality from CHD was 17.9 deaths per 1,000 in the SI group and 19.3 per 1,000 in the UC group, a statistically nonsignificant difference of 7.1% (90% confidence interval, -15% to 25). Total mortality rates were 41.2 per 1,000 (SI) and 40.4 per 1,000 (UC). Three possible explanations for these findings are considered: (1) the overall intervention program, under these circumstances, does not affect CHD mortality; (2) the intervention used does affect CHD mortality, but the benefit was not observed in this trial of seven years' average duration, with lower-than-expected mortality and with considerable risk factor change in the UC group; and (3) measures to reduce cigarette smoking and to lower blood cholesterol levels may have reduced CHD mortality within subgroups of the SI cohort, with a possibly unfavorable response to antihypertensive drug therapy in certain but not all hypertensive subjects. This last possibility was considered most likely, needs further investigation, and lends support to some preventive measures while requiring reassessment of others.

Four methods for calculating gentamicin sulfate dosage requirements were evaluated in 96 patients and compared with an individualized method. The pharmacokinetic parameters of gentamicin were determined from serum concentration time data and used to calculate individualized dosage regimens. Doses were determined in each patient using the "predictive methods" (Sarubbi-Hull, Dettli, "rule of eights," and Chan). Resultant serum concentrations were calculated from doses arrived at by each method. These dosing methods resulted in a large proportion of patients with subtherapeutic or potentially toxic concentrations, or both. The Dettli and Chan methods produced therapeutic concentrations in more patients than the Sarubbi-Hull and rule of eights methods. Desired therapeutic concentrations were attained in significantly more patients with the individualized method than with the predictive methods, and, in addition, larger doses were required. The use of predictive dosage methods should be followed with serum concentration determinations and dosage adjustment to ensure therapeutic concentrations early in treatment.

The efficacy and toxicity of topical applications of 30% idoxuridine in dimethyl sulfoxide, dimethyl sulfoxide alone, or saline in 96 recurrent and 39 first episodes of genital herpes simplex virus (HSV) infection were compared. Drug was applied to lesions four times daily for seven days. In recurrent episodes, the duration of viral shedding after beginning idoxuridine in dimethyl sulfoxide use was significantly shorter (0.6 days) than with dimethyl sulfoxide (1.4 days) or saline (2.0 days) (P less than .05). In primary episodes, viral shedding lasted 2.6 days with idoxuridine in dimethyl sulfoxide and 8.4 days with dimethyl sulfoxide or saline. Idoxuridine in dimethyl sulfoxide had no effect in recurrent or primary HSV on duration of symptoms, new lesion formation, healing time, or risk of subsequent recurrence. Complications in patients given idoxuridine in dimethyl sulfoxide included local burning, generalized contact dermatitis, and vulvar carcinoma in situ. Thirty percent idoxuridine in dimethyl sulfoxide has no effect on clinical manifestations of genital HSV infection and may be hazardous.

Nicotine chewing gum is designed to maintain plasma nicotine levels during a smoking cessation effort while the individual copes with the loss of the repetitive behavioral components of smoking. The plasma nicotine levels obtained with hourly gum chewing were compared with levels obtained with cigarette smoking in nine patients with lung disease. Chewing 2- and 4-mg nicotine gum hourly produced mean steady-state plasma nicotine levels of 11.8 and 23.2 ng/mL, respectively. This compares with a mean plasma nicotine trough level during usual smoking of 15.7 ng/mL and a mean trough level of 18.3 ng/mL with hourly smoking of a cigarette with a nicotine yield of 1.1 mg. Few side effects were seen with the use of either the 2- or 4-mg gum. In a short-term study, nicotine gum proved an acceptable source of nicotine for aiding smoking cessation.

The main evidence that tampons are an etiologic cofactor in the development of toxic shock syndrome (TSS) comes from epidemiologic case-control studies. The patients chosen as cases in those studies were assembled from reports submitted to health agencies in response to publicity that may have influenced physicians to diagnose TSS and to submit reports particularly in situations where the patient was a menstruating tampon user. When the submitted reports were checked for fulfillment of TSS diagnostic criteria, and when cases or controls were asked about antecedent tampon usage, suitable scientific precautions were not used to achieve "blinded" objective decisions. Since these biases would have distorted the statistical relationships, the etiologic role of tampons in TSS has not been scientifically proved.