Memory-guided force output is associated with self-reported ADHD symptoms in young adults

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed mental health disorder in childhood and persists into adulthood in up to 65 % of cases. ADHD is associated with adverse outcomes such as the ability to gain and maintain employment and is associated with an increased risk for substance abuse obesity workplace injuries and traffic accidents A majority of diagnosed children have motor deficits; however, few studies have examined motor deficits in young adults. This study provides a novel examination of visuomotor control of grip force in young adults with and without ADHD. Participants were instructed to maintain force production over a 20-second trial with and without real-time visual feedback about their performance. The results demonstrated that when visual feedback was available, adults with ADHD produced slightly higher grip force than controls. However, when visual feedback was removed, adults with ADHD had a faster rate of decay of force, which was associated with ADHD symptom severity and trait impulsivity. These findings suggest that there may be important differences in the way that adults with ADHD integrate visual feedback during continuous motor tasks. These may account for some of the motor impairments reported in children with ADHD. These deficits could result from (1) dysfunctional sensory motor integration and/or (2) deficits in short-term visuomotor memory

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

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

Sex Differences in the Prospective Association of Excessively Long Reaction Times and Hazardous Cannabis Use at Six Months

Objective: The neurocognitive risk mechanisms predicting divergent outcomes likely differ between men and women who use cannabis recreationally. Increasingly, the use of descriptive distributions including the ex-Gaussian has been applied to draw stronger inferences about neurocognitive health in clinical populations. The current project examines whether the long tail of reaction times (RTs) in a distribution, as characterized by the ex-Gaussian parameter tau which may represent difficulty with the regulation of arousal, predicts problematic cannabis use 6 months later in those who use cannabis recreationally, and whether sex moderates these prospective associations. Method: Young adults (ages 18-30, mean age 20.5 years, N =159, 57.2% women, 69.2% Caucasian) who recreationally used cannabis either occasionally (at least once per month) or frequently (three times or more per week) completed the Stroop Color-Word Task at baseline. Ex-Gaussian parameter tau was estimated for each participant. Self-report of hazardous cannabis use (CUDIT-R) and dysregulation of negative (DERS) and positive emotions (DERS-Positive) were obtained at baseline and 6-month follow-up. Results: For those with larger tau at baseline, being a man (but not a woman) was associated with increased difficulty regulating positive emotions concurrently (b = -0.01, F (1,159) = 5.48, p = 0.02), and with hazardous cannabis use six months later (b = -0.007, F (1,159) = 4.42, p = 0.037) after controlling for baseline hazardous cannabis use. Conclusions: Excessively long RTs during cognitive performance may help characterize men at risk for increased hazardous use, which contributes to understanding between-sex heterogeneity in pathways towards cannabis use disorders

Post-error slowing predicts rule-based but not information-integration category learning

We examine whether error monitoring, operationalized as the degree to which individuals slow down after committing an error (i.e, post-error slowing), is differentially important in the learning of rule-based vs. informationintegration category structures. Rule-based categories are most efficiently solved through the application of an explicit verbal strategy (e.g. sort by color). In contrast, information-integration categories are believed to be learned in a trial-by-trial associative manner. Results indicate that post-error slowing predicts enhanced rule-based but not information-integration category-learning. Implications for multiple category learning systems are discussed.

Sex differences in the prospective association of excessively long reaction times and hazardous cannabis use at six months

Objective: The neurocognitive risk mechanisms predicting divergent outcomes likely differ between men and women who use cannabis recreationally. Increasingly, the use of descriptive distributions including the ex-Gaussian has been applied to draw stronger inferences about neurocognitive health in clinical populations. The current project examines whether the long tail of reaction times (RTs) in a distribution, as characterized by the ex-Gaussian parameter tau which may represent difficulty with the regulation of arousal, predicts problematic cannabis use 6 months later in those who use cannabis recreationally, and whether sex moderates these prospective associations. Method: Young adults (ages 18–30, mean age 20.5 years, N =159, 57.2% women, 69.2% Caucasian) who recreationally used cannabis either occasionally (at least once per month) or frequently (three times or more per week) completed the Stroop Color-Word Task at baseline. Ex-Gaussian parameter tau was estimated for each participant. Self-report of hazardous cannabis use (CUDIT-R) and dysregulation of negative (DERS) and positive emotions (DERS-Positive) were obtained at baseline and 6-month follow-up. Results: For those with larger tau at baseline, being a man (but not a woman) was associated with increased difficulty regulating positive emotions concurrently (b = −0.01, F (1,159) = 5.48, p = 0.02), and with hazardous cannabis use six months later (b = −0.007, F (1,159) = 4.42, p = 0.037) after controlling for baseline hazardous cannabis use. Conclusions: Excessively long RTs during cognitive performance may help characterize men at risk for increased hazardous use, which contributes to understanding between-sex heterogeneity in pathways towards cannabis use disorders