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School pupils (mean age 17 years) were classified as convergers or divergers on the basis of their performance on the AH5 Intelligence Test and the Uses of Objects test. They were presented with a set of concrete and abstract sentences, followed immediately by a forced-choice recognition test. Considered the interaction between abstractness-concreteness and convergence-divergence. (Editor/RK)

We examined whether the study design of randomized clinical trials for medications against human immunodeficiency virus (HIV) may affect the results and whether the outcomes of these trials affect reporting and publication. We used a database of 71 published randomized HIV-related drug efficacy trials and considered the following study design factors: endpoint definition and method of analysis, masked design, sample size, and duration of follow-up. Large variation was noted in the methods of analysis for surrogate endpoints. Often statistical significance for a surrogate endpoint was not associated with statistical significance for the clinical endpoint or for survival in the same trial, although disagreements in the direction of the treatment effect for surrogate endpoints and survival within individual trials were uncommon. Open-label design seemed to affect the magnitude of the treatment effect for two treatments. The magnitude of the treatment effect in trials of zidovudine monotherapy was inversely related to their sample size, but this probably reflected the confounding effect of longer duration of follow-up in large trials (with a resulting loss of efficacy) rather than publication bias. There was, however, evidence for potential bias in reporting and publication of HIV-related trials. Meta-analyses of published trials for specific treatments demonstrated a sizable treatment benefit for all the examined medications regardless of whether these medications were officially approved, controversial, or abandoned, raising concerns about either publication bias or unjustifiable rejection of potentially useful medications. Compared with trials published in specialized journals, trials published in journals of wide readership were larger (p = 0.001) and 4.4 times more likely to report "positive" results (p = 0.01). We identified several examples of trials with "negative" results that have remained unpublished for a long time. In conclusion, study design factors may have an impact on the magnitude and significance of the treatment effect in HIV-related trials. Bias in reporting can further affect the information that these studies provide. Control Clin Trials

We studied predictors for losses to follow-up and the impact of such losses in the AIDS Clinical Trials Group 019 protocol, a long-term randomized trial of immediate versus deferred antiretroviral therapy in asymptomatic HIV-1-infected patients with >500 CD4 cells/mm3. The trial was selected because of its key importance in determining guidelines for antiretroviral therapy, and because it had the longest follow-up among all antiretroviral trials and the largest percentage of patients whose vital status was unknown at study end. Younger age, a history of parenteral drug use, and nonwhite race were associated with higher rates of loss to follow-up, but race was not an important predictor after adjusting for clinical site. There was large and statistically significant variability in the rates of losses among different clinical sites (p < 0.001). Patient retention was significantly better in clinical sites that enrolled many participants, with 25% of enrollees lost to follow-up in sites enrolling >100 patients and 44% in sites enrolling

OBJECTIVE: To model the predictive value of viral load measurements in asymptomatic patients with HIV-1 infection, who have CD4 cell counts > 500 x 10(6)/l and no prior antiretroviral therapy, when the time of seroconversion and the prior levels of viremia are unknown. DESIGN: A mathematical model was constructed for the changes in HIV RNA load over time based on data from cohorts of HIV-infected patients followed since the time of seroconversion. METHODS: For different values of viral load, the time to progression to AIDS or an equivalent state [progression to AIDS equivalent (PAE)] was calculated using a wide range of estimates for the time since seroconversion and the rate of change of the viral load over time. RESULTS: In the absence of antiretroviral treatment, patients with a viral load of 10(5) copies/ml serum are at risk for PAE in less than 3 years (0-3 years) and patients with a viral load half a log higher are at risk in less than 1 year. In contrast, patients with a viral load of 10(4.5) have at least 1.9 years and may have up to 8 years before risk of PAE. Patients with a viral load of 10(4) RNA copies/ml have at least 2.8 years and may have up to 19 years before risk of PAE. The rate of change of the viral load was an important predictor of outcome; the time since seroconversion had only a minor effect. CONCLUSIONS: The viral load in the plasma or serum has predictive value even if the time of seroconversion is unknown. The rate of change of viral load over time may also be an important predictive factor. Serial measurements of viral load over time may provide therapeutic guidance. AIDS

PURPOSE: To do a meta-analysis on the efficacy of early or deferred zidovudine monotherapy in patients with human immunodeficiency virus (HIV) infection but not the acquired immunodeficiency syndrome (AIDS). DATA SOURCES: Articles on zidovudine monotherapy published through May 1994. STUDY SELECTION: Double-blind, randomized, placebo-controlled trials addressing the efficacy of zidovudine monotherapy in HIV-infected persons without an AIDS-defining illness. DATA EXTRACTION: Progression to any primary trial end point; any clinical end point; and AIDS or death. Data were stratified according to disease stage at study entry and duration of follow-up (short-term, < 14 months; long-term, > 21 months). DATA SYNTHESIS: Early initiation of zidovudine therapy was of short-term benefit for all the end points evaluated (for example, the risk ratio for progression to any primary end point was 0.51; 95% CI, 0.41 to 0.64). Long-term trials showed a marginally significant trend of decreased progression to any primary end point (risk ratio, 0.73; CI, 0.52 to 1.03). The trend was not significant for other end points. With further stratification according to disease stage, progression to AIDS or death in the short term was significantly decreased for both symptomatic and asymptomatic patients with CD4 cell counts of less than 500 x 10(6)/L (risk ratios, 0.26 [CI, 0.13 to 0.56] and 0.43 [CI, 0.30 to 0.64], respectively). A regression analysis indicated a larger relative benefit in short-term trials and symptomatic patients than in long-term trials and asymptomatic patients. CONCLUSIONS: Early initiation of zidovudine therapy offers a benefit that decreases over time. Symptomatic patients experience a larger benefit than asymptomatic patients. The implications beyond 3 years of follow-up remain unknown. Ann Intern Med