Pediatric Outcomes of Emergency Medical Services Non-Transport Before and During the COVID-19 Pandemic.

Introduction: Pediatric patients account for 6-10% of emergency medical services (EMS) activations in the United States. Approximately 30% of these children are not transported to an emergency department (ED). Adult data in the literature reports higher hospitalization and complications following non-transport. Few studies discuss epidemiology and characteristics of pediatric non-transport; however, data on outcome is limited. Our primary aim was to determine outcomes of non-transported children within our urban EMS system before and during the COVID-19 pandemic. Our secondary objective was to explore reasons for non-transport. Methods: This was a prospective, descriptive pilot study. We compared EMS data for September 2019 (pre-COVID-19) to September 2020 (pandemic). Included were children aged 0-17 years who activated EMS and did not receive transport to the primary hospital for the EMS capture area. We defined outcomes as repeat EMS activation, ED visits, and hospital admissions, all within 72 hours. Data was obtained via electronic capture. We used descriptive statistics to analyze our data, chi square for categorical data, stepwise logistic regression, and univariate logistic regression to test for association of covariates with non-transport. Results: There were 1,089 pediatric EMS activations in September 2019 and 780 in September 2020. Non-transport occurred in 633 (58%) in September 2019 and 412 (53%) in September 2020. Emergency medical services was reactivated within 72 hours in the following: 9/633 (1.4%) in 2019; and 5/412 (1.2%) in 2020 (P = 0.77). Visits to the ED occurred in 57/633 (9%) in 2019 and 42/412 (10%) in 2020 (P = 0.53). Hospital admissions occurred in 10/633 (1.5%) in 2019 and 4/412 (0.97%) in 2020 (P = 0.19). One non-transported patient was admitted to the intensive care unit in September 2020 (<1%) and survived. Hispanic ethnicity, age >12 years, and fever were associated with repeat EMS activation. The most common reason for non-transport in both study periods was that the parent felt an ambulance was not necessary (47%). Conclusion: In our system, non-transport of pediatric patients occurred in >50% of EMS activations with no significant adverse outcome. Age >12 years, fever, and Hispanic ethnicity were more common in repeated EMS activations. The most common reason for non-transport was parents feeling it was not necessary. Future studies are needed to develop reliable EMS guidelines for pediatric non-transport.

First measurements of radon-220 diffusion in mice tumors, towards treatment planning in diffusing alpha-emitters radiation therapy.

BACKGROUND: Diffusing alpha-emitters radiation therapy ("Alpha-DaRT") is a new method for treating solid tumors with alpha particles, relying on the release of the short-lived alpha-emitting daughter atoms of radium-224 from interstitial sources inserted into the tumor. Alpha-DaRT tumor dosimetry is governed by the spread of radium's progeny around the source, as described by an approximate framework called the "diffusion-leakage model". The most important model parameters are the diffusion lengths of radon-220 and lead-212, and their estimation is therefore essential for treatment planning. PURPOSE: Previous works have provided initial estimates for the dominant diffusion length, by measuring the activity spread inside mice-borne tumors several days after the insertion of an Alpha-DaRT source. The measurements, taken when lead-212 was in secular equilibrium with radium-224, were interpreted as representing the lead-212 diffusion length. The aim of this work is to provide first experimental estimates for the diffusion length of radon-220, using a new methodology. METHODS: The diffusion length of radon-220 was estimated from autoradiography measurements of histological sections taken from 24 mice-borne subcutaneous tumors of five different types. Unlike previous studies, the source dwell time inside the tumor was limited to 30 min, to prevent the buildup of lead-212. To investigate the contribution of potential non-diffusive processes, experiments were done in two sets: fourteen in vivo tumors, where during the treatment the tumors were still carried by the mice with active blood supply, and 10 ex-vivo tumors, where the tumors were excised before source insertion and kept in a medium at 37 ∘ C $37^\circ {\text{C}}$ with the source inside. RESULTS: The measured diffusion lengths of radon-220, extracted by fitting the recorded activity pattern up to 1.5 mm from the source, lie in the range 0.25 - 0.6 mm ${0.25-0.6}\nobreakspace {\text{mm}}$ , with no significant difference between the average values measured in in-vivo and ex-vivo tumors: L R n i n - v i v o = 0.40 ± 0.08 mm $L_{Rn}^{in-vivo}=0.40{\pm }0.08\nobreakspace {\text{mm}}$ versus L R n e x - v i v o = 0.39 ± 0.07 mm $L_{Rn}^{ex-vivo}=0.39{\pm }0.07\nobreakspace {\text{mm}}$ . However, in-vivo tumors display an enhanced spread of activity 2-3 mm away from the source. This effect is not explained by the current model and is much less pronounced in ex-vivo tumors. CONCLUSIONS: The average measured radon-220 diffusion lengths in both in-vivo and ex-vivo tumors are consistent with published data on the diffusion length of radon in water and lie close to the upper limit of the previously estimated range of 0.2 - 0.4 mm $0.2-0.4\nobreakspace {\text{mm}}$ . The observation that close to the source there is no apparent difference between in-vivo and ex-vivo tumors, and the good agreement with the theoretical model in this region suggest that the spread of radon-220 is predominantly diffusive in this region. The departure from the model prediction in in-vivo tumors at large radial distances may hint at potential vascular contribution, which will be the subject of future works.

Longitudinal study of insomnia, suicidal ideation, and psychopathology in schizophrenia.

OBJECTIVE: Insomnia is a common comorbidity in schizophrenia. Increasing cross-sectional evidence suggests an association between insomnia and suicidal ideation (SI) and symptom severity in schizophrenia. We investigated longitudinal associations over 3 months between insomnia, suicidal ideation, and symptom severity in a group of patients with chronic schizophrenia. METHOD: We performed a secondary analysis of data from n = 305 participants from the Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy (PROACTIVE) schizophrenia trial using regression models. RESULTS: The prevalence of moderate-to-severe insomnia was 17.7 % at baseline and 13.6 % at 3 months, respectively. The prevalence of SI was 22 % at baseline and 22.5 % at 3 months. After controlling for potential confounders, improved SI from baseline to 3 months was associated with both baseline moderate-to-severe insomnia (OR = 3.81, 95 % CI 1.11-13.12, p = 0.034) and improvement in insomnia (OR = 3.50, 95 % CI 1.23-9.92, p = 0.013). Worsening SI from baseline to 3 months was associated with worsening insomnia (OR = 3.50, 95 % CI 1.23-9.92, p = 0.013), but not baseline insomnia. Improvement in BPRS total score from baseline to 3 months was associated with improvement in insomnia (ß = 0.17, p = 0.029), but not baseline insomnia. CONCLUSION: Insomnia is common in patients with chronic schizophrenia and insomnia showed significant associations with SI and psychopathology. Clinicians should consider insomnia when assessing suicide risk in patients with schizophrenia.

Dominance Analysis of Bright and Dark Dispositional Predictors of Socially Desirable Responding.

Although the role of so-called dark traits in the prediction of maladaptive behavior has seen a large increase in interest by researchers, the Big Five still maintain their ubiquity in the prediction of most behaviors. This study uses measures of the Dark Tetrad and the Big Five personality traits to predict a very specific form of maladaptive behavior: the impression management form of socially desirable responding. In regression-based dominance analysis, results suggest that not all of the Big Five nor the Dark Tetrad provide statistically significant incremental validity but as a block, the Big Five dominate the Dark Tetrad in the prediction of the purposeful misrepresentation of one's self to others on self-report inventories. More specifically, four of the Big Five as well as the traits of Machiavellianism and sadism from the Dark Tetrad are significant predictors of impression management.

Taking identity-by-descent analysis into the wild: Estimating realized relatedness in free-ranging macaques.

Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent-offspring dyads, pedigrees capture relatedness imperfectly. The number and length of DNA segments that are identical-by-descent (IBD) yield the most precise estimates of relatedness. Here, we leverage novel methods for estimating locus-specific IBD from low coverage whole genome resequencing data to demonstrate the feasibility and value of resolving fine-scaled gradients of relatedness in free-living animals. Using primarily 4-6× coverage data from a rhesus macaque (Macaca mulatta) population with available long-term pedigree data, we show that we can call the number and length of IBD segments across the genome with high accuracy even at 0.5× coverage. The resulting estimates demonstrate substantial variation in genetic relatedness within kin classes, leading to overlapping distributions between kin classes. They identify cryptic genetic relatives that are not represented in the pedigree and reveal elevated recombination rates in females relative to males, which allows us to discriminate maternal and paternal kin using genotype data alone. Our findings represent a breakthrough in the ability to understand the predictors and consequences of genetic relatedness in natural populations, contributing to our understanding of a fundamental component of population structure in the wild.

Integrated Devices: A New Regulatory Pathway to Promote Revolutionary Innovation.

Policy Points Current medical device regulatory frameworks date back half a century and are ill suited for the next generation of medical devices that involve a significant software component. Existing Food and Drug Administration efforts are insufficient because of a lack of statutory authority, whereas international examples offer lessons for improving and harmonizing domestic medical device regulatory policy. A voluntary alternative pathway built upon two-stage review with individual component review followed by holistic review for integrated devices would provide regulators with new tools to address a changing medical device marketplace.

2D antiscatter grid and scatter sampling based CBCT method for online dose calculations during CBCT guided radiation therapy of pelvis.

BACKGROUND: Online dose calculations before the delivery of radiation treatments have applications in dose delivery verification, online adaptation of treatment plans, and simulation-free treatment planning. While dose calculations by directly utilizing CBCT images are desired, dosimetric accuracy can be compromised due to relatively lower HU accuracy in CBCT images. PURPOSE: In this work, we propose a novel CBCT imaging pipeline to enhance the accuracy of CBCT-based dose calculations in the pelvis region. Our approach aims to improve the HU accuracy in CBCT images, thereby improving the overall accuracy of CBCT-based dose calculations prior to radiation treatment delivery. METHODS: An in-house developed quantitative CBCT pipeline was implemented to address the CBCT raw data contamination problem. The pipeline combines algorithmic data correction strategies and 2D antiscatter grid-based scatter rejection to achieve high CT number accuracy. To evaluate the effect of the quantitative CBCT pipeline on CBCT-based dose calculations, phantoms mimicking pelvis anatomy were scanned using a linac-mounted CBCT system, and a gold standard multidetector CT used for treatment planning (pCT). A total of 20 intensity-modulated treatment plans were generated for five targets, using 6 and 10 MV flattening filter-free beams, and utilizing small and large pelvis phantom images. For each treatment plan, four different dose calculations were performed using pCT images and three CBCT imaging configurations: quantitative CBCT, clinical CBCT protocol, and a high-performance 1D antiscatter grid (1D ASG). Subsequently, dosimetric accuracy was evaluated for both targets and organs at risk as a function of patient size, target location, beam energy, and CBCT imaging configuration. RESULTS: When compared to the gold-standard pCT, dosimetric errors in quantitative CBCT-based dose calculations were not significant across all phantom sizes, beam energies, and treatment sites. The largest error observed was 0.6% among all dose volume histogram metrics and evaluated dose calculations. In contrast, dosimetric errors reached up to 7% and 97% in clinical CBCT and high-performance ASG CBCT-based treatment plans, respectively. The largest dosimetric errors were observed in bony targets in the large phantom treated with 6 MV beams. The trends of dosimetric errors in organs at risk were similar to those observed in the targets. CONCLUSIONS: The proposed quantitative CBCT pipeline has the potential to provide comparable dose calculation accuracy to the gold-standard planning CT in photon radiation therapy for the abdomen and pelvis. These robust dose calculations could eliminate the need for density overrides in CBCT images and enable direct utilization of CBCT images for dose delivery monitoring or online treatment plan adaptations before the delivery of radiation treatments.

Sleep Problems, Suicidal Ideation, and Psychopathology in First-Episode Psychosis.

BACKGROUND AND HYPOTHESIS: Insomnia occurs frequently in the clinical course of schizophrenia. A growing literature has found associations between insomnia, suicidal ideation and behavior, and psychopathology in schizophrenia. We explored associations between sleep problems, suicidal ideation, and psychopathology in a cohort of patients with first-episode psychosis. STUDY DESIGN: We performed a secondary analysis of data for n = 403 subjects with data from the Recovery After an Initial Schizophrenia Episode study using regression models. STUDY RESULTS: The prevalence of sleep problems and suicidal ideation at baseline was 57% and 15%, respectively. After controlling for potential confounders, in the study baseline sleep problems were associated with increased odds of suicidal ideation with evidence of a dose-dependent relationship (OR = 2.25, 95% CI 1.15-4.41, P = .018). Over 24 months, sleep problems at any time point were associated with an over 3-fold increased odds of concurrent suicidal ideation (OR = 3.21, 95% CI 1.45-7.14, P = .004). Subjects with persistent sleep problems were almost 14 times more likely to endorse suicidal ideation at least once over the study than those without sleep problems (OR = 13.8, 95% CI 6.5-53.4, P < .001). Sleep problems were also a predictor of higher Positive and Negative Syndrome Scale total (ß = 0.13-0.22), positive (ß = 0.14-0.25), and general (ß = 0.16-0.27) subscale scores at baseline and multiple follow-up visits (P < .01 for each). CONCLUSIONS: Sleep problems are highly prevalent and associated with suicidal ideation and greater psychopathology in first-episode psychosis. Formal assessment and treatment of insomnia appear relevant to the clinical care of patients with psychosis as a predictor of suicidal ideation and symptom severity.

Expansion of Telestroke Coverage in Community Hospitals: Unifying Stroke Care and Reducing Transfer Rate.

OBJECTIVE: Telestroke (TS) service has been shown to improve stroke diagnosis timing and accuracy, facilitate treatment decisions, and decrease interfacility transfers. Expanding TS service to inpatient units at the community hospital provides an opportunity to follow up on stroke patients and optimize medical management. This study examines the outcome of expanding TS coverage from acute emergency room triage to incorporate inpatient consultation. METHODS: We studied the effect of expanding TS to inpatient consultation service at 19 regional hospitals affiliated with Promedica Stroke Network. We analyzed data pre- and post-TS expansion. We reviewed changes in TS utilization, admission rate, thrombolytic therapy, patient transfer rate, and diagnosis accuracy. RESULTS: Between January 2018 and June 2022, a total of 9,756 patients were evaluated in our stroke network (4,705 in pre- and 5,051 in the post-TS expansion). In the post-TS expansion period, stroke patients' admission at the spoke hospital increased from 18/month to 40/month, and for TIA from 11/month to 16/month. TS cart use increased from 12% to 35.2%. Patient transfers to hub hospital decreased by 31%. TS service expansion did not affect intravenous thrombolytic therapy rate or door-to-needle time. There was no difference in length of stay or readmission rate, and the patients at the spoke hospitals had a higher rate of home discharge 57.38% compared with 52.58% at hub hospital. INTERPRETATION: Telestroke service expansion to inpatient units helped decrease transfers and retain patients in their communities, increased stroke and TIA diagnosis accuracy, and did not compromise patients' hospitalization or outcome. ANN NEUROL 2024;95:576-582.

Meta-analysis of a family history of diabetes in schizophrenia.

OBJECTIVE: Type 2 diabetes (T2DM) is common in patients with schizophrenia and non-affective psychosis. These patients also have an increased prevalence of a family history of T2DM. We performed a systematic review and meta-analysis of the association between a family history of T2DM and schizophrenia. METHOD: We searched electronic databases from inception until July 2022 for studies of a family history of T2DM or gestational diabetes in patients with schizophrenia and controls. We performed random effects meta-analysis, calculating odds ratios (ORs) and 95 % confidence intervals (CI) and meta-regression analyses. RESULTS: Nine studies were included, comprising 2953 patients with non-affective psychosis and 4484 controls. Schizophrenia was associated with an over two-fold increased odds of a family history of T2DM or gestational diabetes (OR = 2.18, 95 % CI 1.61-2.96, p < 0.01). In meta-regression analyses, age, sex, study quality score, and year of publication were all unrelated to the association. CONCLUSION: We found that patients with schizophrenia had a 2.2-fold increased odds of a family history of T2DM versus controls. This association may be relevant to both the pathophysiology of schizophrenia and the reported increased risk of development of diabetes with antipsychotic treatment.

Role of Patient Sorting in Avoidable Hospital Stays in Medicare Advantage vs Traditional Medicare.

Importance: Unlike traditional Medicare (TM), Medicare Advantage (MA) plans limit in-network care to a specific network of Medicare clinicians. MA plans thus play a role in sorting patients to a subset of clinicians. It is unknown whether the performance of physicians who treat MA and TM beneficiaries is different. Objective: To examine whether avoidable hospital stay differences between MA and TM can be explained by the primary care clinicians who treat MA and TM beneficiaries. Design, Setting, and Participants: This was a cross-sectional study of a nationally representative sample of MA and TM beneficiaries in 2019 with any of 5 chronic ambulatory care-sensitive conditions (ACSCs). The relative risk (RR) of avoidable hospital stays in MA compared with TM was estimated with inverse probability of treatment-weighted Poisson regression, both without and with clinician fixed effects. The degree to which the estimated MA vs TM difference could be explained by patient sorting was calculated by comparing the 2 RR estimates. Data were analyzed between February 2022 and April 2023. Exposure: Enrollment in MA. Main Outcome and Measures: Whether a beneficiary had avoidable hospital stays in 2019 due to any of the ACSCs. Avoidable hospital stays included both hospitalizations and observation stays. Results: The study sample comprised 1 323 481 MA beneficiaries (mean [SD] age, 75.4 [7.0] years; 56.9% women; 69.3% White) and 1 965 863 TM beneficiaries (mean [SD] age, 75.9 [7.4] years; 57.1% women; 82.5% White). When controlling for the primary care clinician, the RR of avoidable hospital stays in MA vs TM changed by 2.6 percentage points (95% CI, 1.72-3.50; P < .001), suggesting that compared with TM beneficiaries, MA beneficiaries saw clinicians with lower rates of avoidable hospital stays. This effect size was statistically significant to explain the 2% lower rate of avoidable hospital stays in MA than in TM. Conclusions and Relevance: In this cross-sectional study of MA and TM beneficiaries, the lower rate of avoidable hospital stays among MA beneficiaries than TM beneficiaries was attributable to MA beneficiaries visiting clinicians with lower rates of avoidable hospital stays. The patient sorting that occurs in MA plays a critical role in the lower rates of avoidable hospital stays compared with TM.

Applications of Artificial Intelligence in Health Care Delivery.

Health care costs now comprise nearly one-fifth of the United States' gross domestic product, with the last 25 years marked by rising administrative costs, a lack of labor productivity growth, and rising patient and physician dissatisfaction. Policy experts have responded with a series of reforms that have - ironically - increased patient and physician administrative burden with little meaningful effect on cost and quality. Artificial intelligence (AI), a topic of great consternation, can serve as the "wheat thresher" for health care delivery, empowering and freeing both patients and physicians by decreasing administrative burden and improving labor productivity. In this Viewpoint, we discuss three principal areas where AI poses an unprecedented opportunity to reduce cost, improve care, and markedly enhance the patient and physician experience: (1) automation of administrative process, (2) augmentation of clinical practice, and (3) automation of elements of clinical practice.

The neuropsychological presentation of women with epilepsy: clinical considerations and future directions.

Objective: Cognitive, mood, and behavioral changes are common among persons with epilepsy (PWE), resulting in a complex neuropsychological presentation. Women with epilepsy (WWE) represent a distinct cohort within the broader epilepsy population due to sex and gender-specific factors impacting epilepsy semiology and treatment. However, unique neuropsychological profiles among WWE have not been established. This narrative review aims to further define neuropsychological correlates in WWE and promote meaningful discussion related to enhancing the provision of neuropsychological care within this clinical population. Method: Current literature in PWE examining differences in cognitive function, mental health, and quality of life (QoL) between women and men was critically reviewed, emphasizing considerations for neuropsychological practice. Results: WWE demonstrate a preservation of verbal learning and memory compared to men both pre- and post-surgically, with sex-based, neurobiological mechanisms likely contributing to this association. WWE also have elevated risk for affective disorder psychopathology, suicidality, and traumatic experiences. Epidemiology related to psychotic and bipolar spectrum disorders is less clear, and findings are mixed regarding sex-specific behavioral side effects of antiseizure and psychotropic medication. Finally, hormonal and obstetric factors are highlighted as important contributors to neuropsychological symptoms in WWE, with elevated risk for low QoL and increased stigma associated with greater medical and psychiatric comorbidities compared to men. Conclusions: While emerging literature has begun to characterize the neuropsychological presentation of WWE, future research is needed to define sex and gender differences in neuropsychological sequalae among PWE to ensure consistency and quality of care for WWE.

A review of clinical studies of electrodermal activity and transcranial magnetic stimulation.

There is a growing body of evidence indicative of changes in autonomic nervous system (ANS) activity in patients with disorders of the central nervous system (CNS). Non-invasive measures of the ANS, including heart rate variability (HRV), electrodermal activity (EDA), and pupillary light reflex (PLR) may have value as markers of symptom severity, subtype, risk profile, and/or treatment response. In this paper we provide an introduction into the anatomy and physiology of EDA and review the literature published after 2007 in which EDA was an outcome measure of cortical stimulation with transcranial magnetic stimulation (TMS). Eleven studies were included and considered regarding the potential of EDA as an outcome measure reflecting ANS activity in TMS research and treatment. These studies are summarized according to study population, experimental methodology, cortical region targeted, and correlation with other measures of ANS activity. Results indicate that EDA changes vary with the frequency and target of TMS. Inhibitory TMS to the dorsolateral prefrontal cortex (dlPFC) was the most common paradigm in these studies, consistently resulting in decreased EDA.

A 2D antiscatter grid and scatter sampling based CBCT method for online dose calculations during CBCT guided radiation therapy of pelvis.

Online dose calculations before radiation treatment have applications in dose delivery verification, plan adaptation, and treatment planning. We propose a novel CBCT imaging pipeline to enhance accuracy. Our approach aims to improve HU accuracy in CBCT images for more precise dose calculations. A quantitative CBCT pipeline was implemented, combining data correction strategies and scatter rejection, achieving high CT number accuracy. We evaluated the pipeline's effect using pelvis anatomy phantoms and found that dosimetric errors in quantitative CBCT-based dose calculations were minimal. In contrast, clinical CBCT and high-performance ASG CBCT-based plans showed significant errors. The proposed quantitative CBCT pipeline offers comparable dose calculation accuracy to the gold-standard planning CT, eliminating the need for density overrides and enabling precise dose delivery monitoring or online plan adaptations in radiation therapy.

Recruitment of a Middling Promiscuous Enzyme Drives Adaptive Metabolic Evolution in Escherichia coli.

A key step in metabolic pathway evolution is the recruitment of promiscuous enzymes to perform new functions. Despite the recognition that promiscuity is widespread in biology, factors dictating the preferential recruitment of one promiscuous enzyme over other candidates are unknown. Escherichia coli contains four sugar kinases that are candidates for recruitment when the native glucokinase machinery is deleted-allokinase (AlsK), manno(fructo)kinase (Mak), N-acetylmannosamine kinase (NanK), and N-acetylglucosamine kinase (NagK). The catalytic efficiencies of these enzymes are 103- to 105-fold lower than native glucokinases, ranging from 2,400 M-1 s-1 for the most active candidate, NagK, to 15 M-1 s-1 for the least active candidate, AlsK. To investigate the relationship between catalytic activities of promiscuous enzymes and their recruitment, we performed adaptive evolution of a glucokinase-deficient E. coli strain to restore glycolytic metabolism. We observed preferential recruitment of NanK via a trajectory involving early mutations that facilitate glucose uptake and amplify nanK transcription, followed by nonsynonymous substitutions in NanK that enhance the enzyme's promiscuous glucokinase activity. These substitutions reduced the native activity of NanK and reduced organismal fitness during growth on an N-acetylated carbon source, indicating that enzyme recruitment comes at a cost for growth on other substrates. Notably, the two most active candidates, NagK and Mak, were not recruited, suggesting that catalytic activity alone does not dictate evolutionary outcomes. The results highlight our lack of knowledge regarding biological drivers of enzyme recruitment and emphasize the need for a systems-wide approach to identify factors facilitating or constraining this important adaptive process.

Improving Health Care Quality Measurement to Combat Clinician Burnout.

This Viewpoint explores a critical source of administrative burden and physician frustration­the explosive growth of health care quality metrics­and how improving these metrics could combat clinician burnout.

Cognitive "success" in the setting of performance validity test failure.

BACKGROUND: Although studies have shown unique variance contributions from performance invalidity, it is difficult to interpret the meaning of cognitive data in the setting of performance validity test (PVT) failure. The current study aimed to examine cognitive outcomes in this context. METHOD: Two hundred and twenty-two veterans with a history of mild traumatic brain injury referred for clinical evaluation completed cognitive and performance validity measures. Standardized scores were characterized as Within Normal Limits (≥16th normative percentile) and Below Normal Limits (<16th percentile). Cognitive outcomes are examined across four commonly used PVTs. Self-reported employment and student status were used as indicators of "productivity" to assess potential functional differences related to lower cognitive performance. RESULTS: Among participants who performed in the invalid range on Test of Memory Malingering trial 1, Word Memory Test, Wechsler Adult Intelligence Scale-Fourth Edition Digit Span aged corrected scaled score, and the California Verbal Learning Test-Second Edition Forced Choice index, 16-88% earned broadly within normal limits scores across cognitive testing. Depending on which PVT measure was applied, the average number of cognitive performances below the 16th percentile ranged from 5 to 7 of 14 tasks. There were no differences in the total number of below normal limits performances on cognitive measures between "productive" and "non-productive" participants (T = 1.65, p = 1.00). CONCLUSIONS: Results of the current study suggest that the range of within normal limits cognitive performance in the context of failed PVTs varies greatly. Importantly, our findings indicate that neurocognitive data may still provide important practical information regarding cognitive abilities, despite poor PVT outcomes. Further, given that rates of below normal limits cognitive performance did not differ among "productivity" groups, results have important implications for functional abilities and recommendations in a clinical setting.

The Role of the Autonomic Nervous System in the Mediation of the Resolution of Suicidal Ideation With Electroconvulsive Therapy: A Hypothesis and Review of Heart Rate Variability Over a Course of Electroconvulsive Therapy.

ABSTRACT: Longitudinal observational studies have shown a meaningful decrease in suicidal thinking and suicidal behavior after receipt of electroconvulsive therapy (ECT). The antisuicide effect of ECT may be related to success in the global relief of the presenting syndrome such as depressive or psychotic illness. However, it is possible that the antisuicide effect is specific to ECT per se, over and above the relief of the clinical syndrome. Electroconvulsive therapy is associated with many observable neurochemical and physiologic effects, and some of these may plausibly be specifically linked to an antisuicide effect. The phenomenon of physiologic hyperarousal has been named as a candidate mechanism driving the risk for suicide. Hyperarousal is associated with decreased neuropsychological executive function responsible for response inhibition and can lead to impulsive action. The level of arousal within the autonomic nervous system (ANS) can be assayed with the pupillary light reflex, electrodermal activity, or with heart rate variability (HRV). This article summarizes the literature on the effects of ECT on HRV 24 to 72 hours after a course of ECT and finds evidence for increases in HRV, which indicates lower levels of arousal in the ANS. This finding suggests that ECT-related reductions in ANS arousal, presumably with corresponding improvements in response inhibition, may be one mechanism whereby ECT reduces risk for suicide.

The 510(k) Third Party Review Program: Promise and Potential.

Every year, the Food and Drug Administration (FDA) clears approximately 3,000 medical devices for marketing via the 510(k) pathway. These constitute 99% of all devices approved for human use and includes the premarket review of many devices incorporating newer technology such as artificial intelligence (AI), machine learning (ML), and other software. As the complexity of these novel technologies and the number of applications is expected to increase in the coming years, statutory changes such as the 2016 21st Century Cures Act, regulations, and guidance documents have increased both the volume and complexity of device review. Thus, the ability to streamline the review of less complex, low-to-moderate risk devices through the 510(k) pathway will maximize the FDA's capability to address other important, future-oriented regulatory questions. For over twenty five years, third party review organizations have served a defined function to assist with the review of 510(k) applications for a set of enumerated device classes. This paper reviews the history of FDA device regulation, the evolution of the 510(k) review pathway, and the recent history of the 510(k) third party review program. Finally, the paper addresses policy concerns from all stakeholders - including the FDA - along with policy suggestions to improve the third party review program and FDA device regulation writ large.