Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.

Utilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.

Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).

Across social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.

Our results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.

Hypotension is an adverse event that may be related to systemic exposure of milrinone; however, the true exposure–safety relationship is unknown.

Using the Pediatric Trials Network multicentre repository, we identified children ≤17 years treated with milrinone. Hypotension was defined according to age, using the Pediatric Advanced Life Support guidelines. Clinically significant hypotension was defined as hypotension with concomitant lactate >3 mg/dl. A prior population pharmacokinetic model was used to simulate milrinone exposures to evaluate exposure–safety relationships.

We included 399 children with a median (quarter 1, quarter 3) age of 1 year (0,5) who received 428 intravenous doses of milrinone (median infusion rate 0.31 mcg/kg/min [0.29,0.5]). Median maximum plasma milrinone concentration was 110.7 ng/ml (48.4,206.2). Median lowest systolic and diastolic blood pressures were 74 mmHg (60,85) and 35 mmHg (25,42), respectively. At least 1 episode of hypotension occurred in 178 (45%) subjects; clinically significant hypotension occurred in 10 (2%). The maximum simulated milrinone plasma concentrations were higher in subjects with clinically significant hypotension (251 ng/ml [129,329]) versus with hypotension alone (86 ng/ml [44, 173]) versus without hypotension (122 ng/ml [57, 208], p = 0.002); however, this relationship was not retained on multivariable analysis (odds ratio 1.01; 95% confidence interval 0.998, 1.01).

We successfully leveraged a population pharmacokinetic model and electronic health record data to evaluate the relationship between simulated plasma concentration of milrinone and systemic hypotension occurrence, respectively, supporting the broader applicability of our novel, efficient, and cost-effective study design for examining drug exposure–response and –safety relationships.

Targeted drug development efforts in patients with CHD are needed to standardise care, improve outcomes, and limit adverse events in the post-operative period. To identify major gaps in knowledge that can be addressed by drug development efforts and provide a rationale for current clinical practice, this review evaluates the evidence behind the most common medication classes used in the post-operative care of children with CHD undergoing cardiac surgery with cardiopulmonary bypass.

We systematically searched PubMed and EMBASE from 2000 to 2019 using a controlled vocabulary and keywords related to diuretics, vasoactives, sedatives, analgesics, pulmonary vasodilators, coagulation system medications, antiarrhythmics, steroids, and other endocrine drugs. We included studies of drugs given post-operatively to children with CHD undergoing repair or palliation with cardiopulmonary bypass.

We identified a total of 127 studies with 51,573 total children across medication classes. Most studies were retrospective cohorts at single centres. There is significant age- and disease-related variability in drug disposition, efficacy, and safety.

In this study, we discovered major gaps in knowledge for each medication class and identified areas for future research. Advances in data collection through electronic health records, novel trial methods, and collaboration can aid drug development efforts in standardising care, improving outcomes, and limiting adverse events in the post-operative period.

Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, ‘conventional’ meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis.

We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891).

We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies.

This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.

Extracorporeal membrane oxygenation (ECMO) has accelerated rapidly for patients in severe cardiac or respiratory failure. As a result, ECMO networks are being developed across the world using a “hub and spoke” model. Current guidelines call for all patients transported on ECMO to be accompanied by a physician during transport. However, as ECMO centers and networks grow, the increasing number of transports will be limited by this mandate.

The aim of this study was to compare rates of adverse events occurring during transport of ECMO patients with and without an additional clinician, defined as a physician, nurse practitioner (NP), or physician assistant (PA).

This is a retrospective cohort study of all adults transported while cannulated on ECMO from 2011-2018 via ground and air between 21 hospitals in the northeastern United States, comparing transports with and without additional clinicians. The primary outcome was the rate of major adverse events, and the secondary outcome was minor adverse events.

Over the seven-year study period, 93 patients on ECMO were transported. Twenty-three transports (24.7%) were accompanied by a physician or other additional clinician. Major adverse events occurred in 21.5% of all transports. There was no difference in the total rate of major adverse events between accompanied and unaccompanied transports (P = .91). Multivariate analysis did not demonstrate any parameter as being predictive of major adverse events.

In a retrospective cohort study of transports of ECMO patients, there was no association between the overall rate of major adverse events in transport and the accompaniment of an additional clinician. No variables were associated with major adverse events in either cohort.

The study describes the implementation of a prehospital treatment algorithm that included intravenous (IV) bolus (IVB) nitroglycerin (NTG) followed by maintenance infusion for the treatment of acute pulmonary edema (APE) in a single, high-volume Emergency Medical Services (EMS) system.

This is a retrospective chart review of patients who received IVB NTG for APE in a large EMS system in Minnesota and Wisconsin (USA). Inclusion criteria for treatment included a diagnosis of APE, systolic blood pressure ≥120mmHg, and oxygen saturation (SpO2) ≤93% following 800mcg of sublingual NTG. Patients received a 400mcg IVB of NTG, repeated every two minutes as needed, and subsequent infusion at 80mcg/min for transport times ≥10 minutes.

Forty-four patients were treated with IVB NTG. The median total bolus dose was 400mcg. Twenty patients were treated with NTG infusion following IVB NTG. The median infusion rate was 80mcg/min. For all patients, the initial median blood pressure was 191/113mmHg. Five minutes following IVB NTG, it was 160/94mmHg, and on arrival to the emergency department (ED) it was 152/90mmHg. Five minutes after the initial dose of IVB NTG, median SpO2 increased to 92% from an initial reading of 88% and was 94% at hospital arrival. One episode of transient hypotension occurred during EMS transport.

Patients treated with IVB NTG for APE had reduction in blood pressure and improvement in SpO2 compared to their original presentation. Prehospital treatment of APE with IVB appears to be feasible and safe. A randomized trial is needed to confirm these findings.