Some individuals with schizophrenia report similar feelings of positive affect "in the moment" compared to control participants but report decreased trait positive affect overall. One possible explanation for this disconnection between state and trait positive affect is the extent to which individuals with schizophrenia engage in elaborative processing of positive stimuli. To assess this, we examined evoked gamma band activity in response to positive words over several seconds in a group with schizophrenia, a group with major depressive disorder, and a healthy control group. From a pre-stimulus baseline to 2000 ms after onset of the stimulus (henceforth, "early period"), the schizophrenia group showed a reliable increase in gamma activity compared to both the control and depressed groups, who did not differ from each other. In contrast, the depressed group showed a reliable increase in gamma activity from 2001 to 8000 ms (henceforth, "late period") compared to the other groups, who did not differ from each other. At the same time, the schizophrenia group showed a reliable decrease from the early to late period while the depressed group showed the opposite pattern. In addition, self-reported depression and social anhedonia in the schizophrenia group were related to decreased gamma band activity over the entire processing window. Overall, these results suggest that schizophrenia is associated with increased initial reactivity but decreased sustained elaborative processing over time, which could be related to decreased trait positive affect. The results also highlight the importance of considering depressive symptomology and anhedonia when examining emotional abnormalities in schizophrenia.

Purpose

To describe the effect of tocilizumab in two patients with thyroid associated orbitopathy (TAO).

Observations

We present two patients with TAO who could not tolerate corticosteroids and had a reduction in clinical and laboratory markers of inflammatory activity with subsequent tocilizumab therapy.

Conclusions and importance

The IL-6 receptor antibody tocilizumab is a promising candidate for the treatment of TAO because it selectively targets a key inflammatory mediator and has a favorable side effect profile. Our report demonstrates that tocilizumab can achieve further reduction in inflammatory activity after treatment with corticosteroids. Importantly, we and others have observed a decrease in the level of thyroid stimulating immunoglobulin (TSI) with tocilizumab treatment. This suggests an upstream effect in the inflammatory cascade. Although the impact of tocilizumab on long-term outcome is unknown at this time, we believe that early disruption of the inflammatory process may prevent late complications and decrease the need for rehabilitative surgery.

Vitamin E is essential for neuromuscular function. The primary treatment, oral supplementation with natural ('RRR') α-tocopherol, is not effective in all horses. The objectives of this pilot study were to evaluate the safety and efficacy of a subcutaneously administered RRR-α-tocopherol preparation. Horses were randomly assigned in a cross-over design to initially receive RRR-α-tocopherol (5000 IU/450 kg of 600 IU/mL) subcutaneously (n = 3) or orally (n = 3) or were untreated sentinels (n = 2). Tissue reactions following injection in Phase I of the study necessitated adjustment of the preparation with reduction of the RRR-α-tocopherol concentration to 500 IU/mL in Phase 2. Following an 8-week washout period, horses received the reciprocal treatment route with the new preparation (5000 IU/450 kg of 500 IU/mL). Serum, CSF and muscle α-tocopherol concentrations were determined by high-performance liquid chromatography over a 14-day period during each phase. Serum and CSF α-tocopherol concentrations increased significantly postinjection only when the 500 IU/mL product was administered (P<0.0001). There was no significant difference in the muscle concentration of α-tocopherol following either treatment. All eight horses had marked tissue reaction to subcutaneous injection, regardless of product concentration. Whilst we have demonstrated that this route may be a useful alternative to oral supplementation, the marked tissue reaction makes use of such products limited at this time to only the most refractory of cases.

Purpose

Although demographic, clinicopathologic, and socioeconomic differences may affect treatment and outcomes of prostate cancer, the effect of mental health disorders remains unclear. We assessed the effect of previously diagnosed depression on outcomes of men with newly diagnosed prostate cancer.

Patients and methods

We performed a population-based observational cohort study using Surveillance, Epidemiology, and End Results-Medicare linked data of 41,275 men diagnosed with clinically localized prostate cancer from 2004 to 2007. We identified 1,894 men with a depressive disorder in the 2 years before the prostate cancer diagnosis and determined its effect on treatment and survival.

Results

Men with depressive disorder were older, white or Hispanic, unmarried, resided in nonmetropolitan areas and areas of lower median income, and had more comorbidities (P < .05 for all), but there was no variation in clinicopathologic characteristics. In adjusted analyses, men with depressive disorder were more likely to undergo expectant management for low-, intermediate-, and high-risk disease (P ≤ .05, respectively). Conversely, depressed men were less likely to undergo definitive therapy (surgery or radiation) across all risk strata (P < .01, respectively). Depressed men experienced worse overall mortality across risk strata (low: relative risk [RR], 1.86; 95% CI, 1.48 to 2.33; P < .001; intermediate: RR, 1.25; 95% CI, 1.06 to 1.49; P = .01; high: RR, 1.16; 95% CI, 1.03 to 1.32; P = .02).

Conclusion

Men with intermediate- or high-risk prostate cancer and a recent diagnosis of depression are less likely to undergo definitive treatment and experience worse overall survival. The effect of depression disorders on prostate cancer treatment and survivorship warrants further study, because both conditions are relatively common in men in the United States.

Ferroelectric materials exhibit spontaneous polarization that can be switched by electric field. Beyond traditional applications as nonvolatile capacitive elements, the interplay between polarization and electronic transport in ferroelectric thin films has enabled a path to neuromorphic device applications involving resistive switching. A fundamental challenge, however, is that finite electronic conductivity may introduce considerable power dissipation and perhaps destabilize ferroelectricity itself. Here, tunable microwave frequency electronic response of domain walls injected into ferroelectric lead zirconate titanate (PbZr0.2Ti0.8O3) on the level of a single nanodomain is revealed. Tunable microwave response is detected through first-order reversal curve spectroscopy combined with scanning microwave impedance microscopy measurements taken near 3 GHz. Contributions of film interfaces to the measured AC conduction through subtractive milling, where the film exhibited improved conduction properties after removal of surface layers, are investigated. Using statistical analysis and finite element modeling, we inferred that the mechanism of tunable microwave conductance is the variable area of the domain wall in the switching volume. These observations open the possibilities for ferroelectric memristors or volatile resistive switches, localized to several tens of nanometers and operating according to well-defined dynamics under an applied field.

Introduction

Decreasing unnecessary cranial computed tomography (CT) use in pediatric head trauma patients remains important for emergency departments (EDs) across the US. Our study evaluated CT use in children with minor blunt head trauma in 21 community EDs within an integrated health-care system.

Methods

We studied all children younger than 18 years old presenting to 21 community EDs between 2016 through 2018 with acute minor blunt head trauma, defined by an algorithm of ED chief complaints and diagnoses. We excluded patients with traumatic brain injuries diagnosed in the prior year, a CT within 24 hours prior to the ED visit, or an ED Glasgow Coma Scale score of less than 14.

Results

Among 39,792 pediatric minor head trauma ED visits, the aggregate CT use proportion across all EDs was 12.9% [95% confidence interval (CI), 12.6-13.3%; facility-level range, 5.4-21.6%]. The 7 facilities that had previously received a clinical decision support system intervention implementing the Pediatric Emergency Care Applied Research Network rules during 2013 through 2014 had an aggregate mean CT ordering rate of 11.2% (95% CI, 10.7-11.7%; facility-level range, 5.4-14.3%) compared to 14.1% (95% CI, 13.6-14.5%; facility-level range, 7.3-21.6%) for the nonintervention facilities.

Conclusion

CT use for children with minor blunt head trauma in the community EDs of an integrated health-care system was low and stable across facilities from 2016 through 2018. This may be indicative of the safe stewardship of resources in the system, including the absence of financial or medicolegal incentives to scan very low-risk patients as well the availability of resources for close patient follow-up.

Introduction

Relatively limited data are available regarding paediatric COVID-19. Although most children appear to have mild or asymptomatic infections, infants and those with comorbidities are at increased risk of experiencing more severe illness and requiring hospitalisation due to COVID-19. The recent but uncommon association of SARS-CoV-2 infection with development of a multisystem inflammatory syndrome has heightened the importance of understanding paediatric SARS-CoV-2 infection.

Methods and analysis

The Paediatric Emergency Research Network-COVID-19 cohort study is a rapid, global, prospective cohort study enrolling 12 500 children who are tested for acute SARS-CoV-2 infection. 47 emergency departments across 12 countries on four continents will participate. At enrolment, regardless of SARS-CoV-2 test results, all children will have the same information collected, including clinical, epidemiological, laboratory, imaging and outcome data. Interventions and outcome data will be collected for hospitalised children. For all children, follow-up at 14 and 90 days will collect information on further medical care received, and long-term sequelae, respectively. Statistical models will be designed to identify risk factors for infection and severe outcomes.

Ethics and dissemination

Sites will seek ethical approval locally, and informed consent will be obtained. There is no direct risk or benefit of study participation. Weekly interim analysis will allow for real-time data sharing with regional, national, and international policy makers. Harmonisation and sharing of investigation materials with WHO, will contribute to synergising global efforts for the clinical characterisation of paediatric COVID-19. Our findings will enable the implementation of countermeasures to reduce viral transmission and severe COVID-19 outcomes in children.

Trial registration number

NCT04330261.

Introduction

Pneumonia is a frequent and costly cause of emergency department (ED) visits and hospitalisations in children. There are no evidence-based, validated tools to assist physicians in management and disposition decisions for children presenting to the ED with community-acquired pneumonia (CAP). The objective of this study is to develop a clinical prediction model to accurately stratify children with CAP who are at risk for low, moderate and severe disease across a global network of EDs.

Methods and analysis

This study is a prospective cohort study enrolling up to 4700 children with CAP at EDs at ~80 member sites of the Pediatric Emergency Research Networks (PERN; https://pern-global.com/). We will include children aged 3 months to <14 years with a clinical diagnosis of CAP. We will exclude children with hospital admissions within 7 days prior to the study visit, hospital-acquired pneumonias or chronic complex conditions. Clinical, laboratory and imaging data from the ED visit and hospitalisations within 7 days will be collected. A follow-up telephone or text survey will be completed 7-14 days after the visit. The primary outcome is a three-tier composite of disease severity. Ordinal logistic regression, assuming a partial proportional odds specification, and recursive partitioning will be used to develop the risk stratification models.

Ethics and dissemination

This study will result in a clinical prediction model to accurately identify risk of severe disease on presentation to the ED. Ethics approval was obtained for all sites included in the study. Cincinnati Children's Hospital Institutional Review Board (IRB) serves as the central IRB for most US sites. Informed consent will be obtained from all participants. Results will be disseminated through international conferences and peer-reviewed publications. This study overcomes limitations of prior pneumonia severity scores by allowing for broad generalisability of findings, which can be actively implemented after model development and validation.

Background/aims

Despite evidence that preferential use of balanced/buffered fluids may improve outcomes compared with chloride-rich 0.9% saline, saline remains the most commonly used fluid for children with septic shock. We aim to determine if resuscitation with balanced/buffered fluids as part of usual care will improve outcomes, in part through reduced kidney injury and without an increase in adverse effects, compared to 0.9% saline for children with septic shock.

Methods

The Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) study is an international, open-label pragmatic interventional trial being conducted at > 40 sites in the USA, Canada, and Australia/New Zealand starting on August 25, 2020, and continuing for 5 years. Children > 6 months to < 18 years treated for suspected septic shock with abnormal perfusion in an emergency department will be randomized to receive either balanced/buffered crystalloids (intervention) or 0.9% saline (control) for initial resuscitation and maintenance fluids for up to 48 h. Eligible patients are enrolled and randomized using serially numbered, opaque envelopes concurrent with clinical care. Given the life-threatening nature of septic shock and narrow therapeutic window to start fluid resuscitation, patients may be enrolled under "exception from informed consent" in the USA or "deferred consent" in Canada and Australia/New Zealand. Other than fluid type, all decisions about timing, volume, and rate of fluid administration remain at the discretion of the treating clinicians. For pragmatic reasons, clinicians will not be blinded to study fluid type. Anticipated enrollment is 8800 patients. The primary outcome will be major adverse kidney events within 30 days (MAKE30), a composite of death, renal replacement therapy, and persistent kidney dysfunction. Additional effectiveness, safety, and biologic outcomes will also be analyzed.

Discussion

PRoMPT BOLUS will provide high-quality evidence for the comparative effectiveness of buffered/balanced crystalloids versus 0.9% saline for the initial fluid management of children with suspected septic shock in emergency settings.

Trial registration

PRoMPT BOLUS was first registered at ClinicalTrials.gov ( NCT04102371 ) on September 25, 2019. Enrollment started on August 25, 2020.