THE MIDSESSION REVERSAL TASK WITH PIGEONS: EFFECTS OF A BRIEF DELAY BETWEEN CHOICE AND REINFORCEMENT

During a midsession reversal task, the session begins with a simple simultaneous discrimination in which one stimulus (S1) is correct and the alternate stimulus (S2) is incorrect (S1+/S2-). At the halfway point, the discrimination reverses and S2 becomes the correct choice (S2+/S1-). When choosing optimally, a pigeon should choose S1 until the first trial in which it is not reinforced and then shift to S2 (win-stay/lose-shift). With this task pigeons have been shown to respond suboptimally by anticipating the reversal (anticipatory errors) and continuing to choose S1 after the reversal (perseverative errors). This suboptimal behavior may result from a pigeon’s relative impulsivity due to the immediacy of reinforcement following choice. In other choice tasks, there is evidence that the introduction of a short delay between choice and reinforcement may decrease pigeons’ impulsivity. In the present experiment, a delay was introduced between stimulus selection and reinforcement in the midsession reversal task to assess whether anticipatory and perseverative errors decrease. The results showed a significant difference between the no-delay and delay groups for overall accuracy only during Sessions 11-20, with the no-delay group performing better than the delay group. There was no significant difference in overall accuracy during any other block of ten sessions. These results imply that the insertion of a delay may result in slower learning of this task

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570