Coronary Atherosclerotic Plaque Activity and Future Coronary Events.

Importance: Recurrent coronary events in patients with recent myocardial infarction remain a major clinical problem. Noninvasive measures of coronary atherosclerotic disease activity have the potential to identify individuals at greatest risk. Objective: To assess whether coronary atherosclerotic plaque activity as assessed by noninvasive imaging is associated with recurrent coronary events in patients with myocardial infarction. Design, Setting, and Participants: This prospective, longitudinal, international multicenter cohort study recruited participants aged 50 years or older with multivessel coronary artery disease and recent (within 21 days) myocardial infarction between September 2015 and February 2020, with a minimum 2 years' follow-up. Intervention: Coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography. Main Outcomes and Measures: Total coronary atherosclerotic plaque activity was assessed by 18F-sodium fluoride uptake. The primary end point was cardiac death or nonfatal myocardial infarction but was expanded during study conduct to include unscheduled coronary revascularization due to lower than anticipated primary event rates. Results: Among 2684 patients screened, 995 were eligible, 712 attended for imaging, and 704 completed an interpretable scan and comprised the study population. The mean (SD) age of participants was 63.8 (8.2) years, and most were male (601 [85%]). Total coronary atherosclerotic plaque activity was identified in 421 participants (60%). After a median follow-up of 4 years (IQR, 3-5 years), 141 participants (20%) experienced the primary end point: 9 had cardiac death, 49 had nonfatal myocardial infarction, and 83 had unscheduled coronary revascularizations. Increased coronary plaque activity was not associated with the primary end point (hazard ratio [HR], 1.25; 95% CI, 0.89-1.76; P = .20) or unscheduled revascularization (HR, 0.98; 95% CI, 0.64-1.49; P = .91) but was associated with the secondary end point of cardiac death or nonfatal myocardial infarction (47 of 421 patients with high plaque activity [11.2%] vs 19 of 283 with low plaque activity [6.7%]; HR, 1.82; 95% CI, 1.07-3.10; P = .03) and all-cause mortality (30 of 421 patients with high plaque activity [7.1%] vs 9 of 283 with low plaque activity [3.2%]; HR, 2.43; 95% CI, 1.15-5.12; P = .02). After adjustment for differences in baseline clinical characteristics, coronary angiography findings, and Global Registry of Acute Coronary Events score, high coronary plaque activity was associated with cardiac death or nonfatal myocardial infarction (HR, 1.76; 95% CI, 1.00-3.10; P = .05) but not with all-cause mortality (HR, 2.01; 95% CI, 0.90-4.49; P = .09). Conclusions and Relevance: In this cohort study of patients with recent myocardial infarction, coronary atherosclerotic plaque activity was not associated with the primary composite end point. The findings suggest that risk of cardiovascular death or myocardial infarction in patients with elevated plaque activity warrants further research to explore its incremental prognostic implications.

Parental experiences of caring for children who have learning disabilities and procedural anxiety in hospital: An interpretive phenomenological study.

BACKGROUND: Children with learning disabilities (LD) are more likely to have health conditions that require hospital attendance than children without LD. Like all children, they can experience fear and distress related to procedural anxiety. Parents play a key role in managing procedural anxiety in children with LD. No previous published qualitative studies have explored parental experiences of caring for a child with LD and procedural anxiety in hospital. OBJECTIVES: To explore how parents experienced caring for their child with LD and procedural anxiety in hospital. METHODS: A purposive sample of six participants were recruited through a Facebook group for parents of children with LD. Remote semi-structured interviews were conducted via telephone, Microsoft Teams or Whatsapp. Interviews were transcribed verbatim and analysed using interpretative phenomenological analysis. RESULTS: Five key themes were generated: (1) Emotional toll: parents characterized their experiences as highly emotional; reporting feeling stressed, anxious and worried. (2) Restraint and holding: parents spoke of their experiences of restraint which was largely viewed as negative and sometimes inappropriate. (3) Advocacy: parents articulated their responsibility as advocates for their children. (4) Going it alone: parents were extremely proactive in managing their child's anxieties but some also felt highly-pressurized and isolated. (5) Inconsistency and uncertainty: parents experienced inconsistency and uncertainty in their children's care from healthcare professionals which led to anxiety and frustration. CONCLUSION: Parents of children with both LD and procedural anxiety experienced many challenges. Parents' expertise must be utilized by clinicians when caring for children with LD and procedural anxiety whilst ensuring appropriate support for parents. Nurses require specific training in psychosocial interventions to enhance care for children with LD and procedural anxiety. Further research identifying effective nursing strategies to enhance parental experiences would be beneficial to improve care to this patient group.

Hippocampus, delay discounting, and vicarious trial-and-error.

In decision-making, an immediate reward is usually preferred to a delayed reward, even if the latter is larger. We tested whether the hippocampus is necessary for this form of temporal discounting, and for vicarious trial-and-error at the decision point. Rats were trained on a recently developed, adjustable delay-discounting task (Papale et al. (2012) Cogn Affect Behav Neurosci 12:513-526), which featured a choice between a small, nearly immediate reward, and a larger, delayed reward. Rats then received either hippocampus or sham lesions. Animals with hippocampus lesions adjusted the delay for the larger reward to a level similar to that of sham-lesioned animals, suggesting a similar valuation capacity. However, the hippocampus lesion group spent significantly longer investigating the small and large rewards in the first part of the sessions, and were less sensitive to changes in the amount of reward in the large reward maze arm. Both sham- and hippocampus-lesioned rats showed a greater amount of vicarious trial-and-error on trials in which the delay was adjusted. In a nonadjusting version of the delay discounting task, animals with hippocampus lesions showed more variability in their preference for a larger reward that was delayed by 10 s compared with sham-lesioned animals. To verify the lesion behaviorally, rat were subsequently trained on a water maze task, and rats with hippocampus lesions were significantly impaired compared with sham-lesioned animals. The findings on the delay discounting tasks suggest that damage to the hippocampus may impair the detection of reward magnitude.

The neural substrates of deliberative decision making: contrasting effects of hippocampus lesions on performance and vicarious trial-and-error behavior in a spatial memory task and a visual discrimination task.

Vicarious trial-and-errors (VTEs) are back-and-forth movements of the head exhibited by rodents and other animals when faced with a decision. These behaviors have recently been associated with prospective sweeps of hippocampal place cell firing, and thus may reflect a rodent model of deliberative decision-making. The aim of the current study was to test whether the hippocampus is essential for VTEs in a spatial memory task and in a simple visual discrimination (VD) task. We found that lesions of the hippocampus with ibotenic acid produced a significant impairment in the accuracy of choices in a serial spatial reversal (SR) task. In terms of VTEs, whereas sham-lesioned animals engaged in more VTE behavior prior to identifying the location of the reward as opposed to repeated trials after it had been located, the lesioned animals failed to show this difference. In contrast, damage to the hippocampus had no effect on acquisition of a VD or on the VTEs seen in this task. For both lesion and sham-lesion animals, adding an additional choice to the VD increased the number of VTEs and decreased the accuracy of choices. Together, these results suggest that the hippocampus may be specifically involved in VTE behavior during spatial decision making.