Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with thrombotic complications in adults, but the incidence of COVID-19-related thrombosis in children and adolescents is unclear. Most children with acute COVID-19 have mild disease, but coagulopathy has been associated with multisystem inflammatory syndrome in children (MIS-C), a postinfectious complication. We conducted a multicenter retrospective cohort study to determine the incidence of thrombosis in children hospitalized with COVID-19 or MIS-C and evaluate associated risk factors. We classified patients into 1 of 3 groups for analysis: COVID-19, MIS-C, or asymptomatic SARS-CoV-2. Among a total of 853 admissions (COVID-19, n = 426; MIS-C, n = 138; and asymptomatic SARS-CoV-2, n = 289) in 814 patients, there were 20 patients with thrombotic events (TEs; including 1 stroke). Patients with MIS-C had the highest incidence (9 [6.5%] of 138) vs COVID-19 (9 [2.1%] of 426) or asymptomatic SARS-CoV-2 (2 [0.7%] of 289). In patients with COVID-19 or MIS-C, a majority of TEs (89%) occurred in patients age ≥12 years. Patients age ≥12 years with MIS-C had the highest rate of thrombosis at 19% (9 of 48). Notably, 71% of TEs that were not present on admission occurred despite thromboprophylaxis. Multivariable analysis identified the following as significantly associated with thrombosis: age ≥12 years, cancer, presence of a central venous catheter, and MIS-C. In patients with COVID-19 or MIS-C, hospital mortality was 2.3% (13 of 564), but it was 28% (5 of 18) in patients with TEs. Our findings may help inform pediatric thromboprophylaxis strategies.

Effectiveness of Switching to Subcutaneous Infliximab in Pediatric Inflammatory Bowel Disease Patients on Intravenous Maintenance Therapy.

No real-world data are available on subcutaneous infliximab (SC-IFX) in pediatric inflammatory bowel disease (PIBD). We report a single-center cohort experience of an elective switching program from biosimilar intravenous infliximab to SC-IFX, 120 mg fortnightly, as maintenance. Clinical and laboratory data were collected for 7 patients with infliximab trough levels collected prior and at 6 and 40 weeks after the switch. High treatment persistence was registered with a single patient discontinuing the treatment due to high IFX antibodies, already present before switching. All patients remained in clinical remission with no significant changes in laboratory markers and median infliximab trough levels (12.3 µg/mL at baseline; 13.9 and 14.0 µg/mL at 6 and 40 weeks respectively). No newly-developed IFX antibodies were detected and no adverse reactions or rescue therapies were recorded. Our real-world data support the feasibility of an elective switch to SC-IFX in PIBD as maintenance with potential advantages concerning medical resources and patient satisfaction.

Chemotherapy-induced thrombocytopenia in pediatric oncology: Scope of the problem and opportunities for intervention.

BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a known hematologic complication of oncology treatment. This single-institution study examines the degree with which CIT impacts specific pediatric solid tumor cohorts reflected by platelet transfusion burden and treatment modifications. PROCEDURE: Data regarding clinically relevant CIT were obtained via a retrospective chart review of pediatric solid tumor patients treated at Memorial Sloan Kettering Cancer Center from 2013 to 2020. Patients were stratified based on histologic diagnoses as well as chemotherapy regimen. CIT impact was assessed through platelet transfusion means, chemotherapy dose reductions, and treatment delays. RESULTS: A total of 150 patients were included with mean age 10.3 [0.2-21.0]. Patients receiving therapy for high-risk neuroblastoma and localized Ewing sarcoma, both of which included high-dose cyclophosphamide and doxorubicin, required the most platelet transfusions over the treatment course, with a mean of 13 and 9, respectively. Reduced relative dose intensity (RDI), due in part to CIT, was greatest for the patients receiving therapy for high-risk and intermediate-risk rhabdomyosarcoma. Fifty-six percent of high-risk patients experienced a reduced RDI during the final two cycles of treatment and 69% of intermediate-risk patients experienced one during the final four cycles of treatment. CONCLUSIONS: The impact of CIT varied by the administered chemotherapy regimens and dose intensity of chemotherapy agents. This study demonstrated that CIT causes both marked platelet transfusion burden as well as treatment reduction and delay within certain solid tumor cohorts. This can lend to future studies aimed at reducing the burden of CIT and targeting the most at-risk populations.

Recognising and Treating Complicated Fissuring Perianal Crohn Disease: A South-East Scotland Cohort Study.

ABSTRACT: Fissuring perianal Crohn disease (CD) is not recognised as a perianal phenotype in Montreal/Paris inflammatory bowel disease classifications; however, can occasionally present as complicated disease with severe perianal pain driving increasingly intensive medical therapy despite well controlled luminal disease. We identified a regional cohort of prospectively acquired incident cases of paediatric CD diagnosed <16 years of age in South-East Scotland over a 19-year period (1999-2018), and conducted a retrospective review of complicated fissuring perianal CD causing severe pain related to anal sphincter complex spasm at defecation. Two hundred forty-seven new cases of paediatric CD were diagnosed with complicated fissuring perianal disease identified in 4 described cases (cumulative incidence 1.6%). These patients with marked fissuring and refractory anal sphincter complex spasm required neurostimulation-guided, 4-quadrant, anal intrasphincteric botulinum toxin (BT). All experienced immediate success, measured by cessation of spasms, with variable ongoing symptom relief after median (range) 3 (2-5) BT injections.

Red-Hot Reactance: Color Cues Moderate the Freedom Threatening Characteristics of Health PSAs.

This study investigated whether color cues in health PSAs affect people's experience of psychological reactance to health recommendations. By integrating psychological reactance theory and color-in-context theory, we predicted that reactance would be greater after viewing a threatening health PSA conveyed in red compared to other colors. Using a 3 (color: gray, green, red) × 2 (freedom threatening language: low, high) experimental design in the context of oral health, we found that red exacerbated the degree to which freedom threatening language elicited perceived freedom threat and reactance, and this effect further decreased attitude and intention toward using a firm-bristled toothbrush. These findings show the importance of considering visual communication like color cues when developing successful health campaigns.

Frailty Interdisciplinary Pathway: Compliance and Sustainability in a Level I Trauma Center.

BACKGROUND: Frailty is a state of physiological vulnerability that predisposes many older adult trauma patients to poor health outcomes. Specialized care pathways for frail trauma patients have been shown to improve outcomes, but the compliance and sustainability of these pathways have not been reported (Bryant et al., 2019; Engelhardt et al., 2018). METHODS: We retrospectively measured compliance and sustainability during the first 2 years of a frailty pathway for patients 65 years or older at an urban Level I trauma center. Compliance to 19 pathway elements was collected for 279 pathway patients between October 1, 2016, and September 30, 2018. Compliance was analyzed and reported as a percentage of the total possible times each element could have been completed per pathway guidelines. Benchmark compliance was 75% or more. RESULTS: Retrospective 2-year mean overall compliance to all pathway elements was 68.2% and improved from Year 1 (65.0%) to Year 2 (71.4%). Seven elements achieved a mean 75% or more compliance over the 2-year period: frailty screening on admission (92.8%), consultation requests for physical therapy (97.9%), geriatrics (96.2%), and nutrition (92.3%), consultant care within 72 hr of admission (78.0%), delirium screening 3 times daily (76.3%), and daily senna administration (76.0%). Compliance to 10 elements significantly improved from Year 1 to Year 2 and significantly worsened in 2 elements. CONCLUSION: Many standardized geriatric care processes for frail older adult trauma patients can be successfully integrated into routine daily inpatient practice and sustained over time. Multicenter studies are needed to demonstrate how to improve compliance and to understand better which pathway elements are most effective.

Does 20-min rounding reduce falls in an aged-care setting? A pilot intervention study.

BACKGROUND: This study investigated if implementation of a 20-min rounding intervention can reduce falls in aged care settings. METHODS: Participants (aged 66-99 years) from five aged care facilities were randomly allocated to intervention (n = 20) or control groups (n = 21). The intervention consisted of 20-min rounding observations over a six month period. The number of falls for all residents of each aged care facility was also collected. RESULTS: For participants of the intervention study, there were no differences for number of falls in the intervention compared to the control group (mean(95%CI) control:2.3(0.8-3.7), intervention:4.0(2.5-5.5), p = 0.108). There was a trend for a decreased average number of falls across all aged care sites (mean±SD, 60.4 ± 35.7 falls occurred prior vs. 53.4 ± 37.4 during the intervention, p = 0.056). There were no fall related fractures in the intervention group during the study. CONCLUSIONS: This study suggests that 20-min rounding may decrease falls for all residents of aged care sites.

Quantitative description of 1H SQ and DQ coherences for the hydroxyl disorder within hydrous ringwoodite.

Proton-containing point defects in solid materials are important for a variety of properties ranging from ionic transport over thermal conductivity up to compressibility. Ultrafast magic-angle spinning techniques nowadays offer high-resolution solid-state NMR spectra, even for 1H, and thus open up possibilities to study the underlying defect chemistry. Nevertheless, disorder within such defects again leads to heavy spectral overlap of 1H resonances, which prevents quantitative analysis of defect concentrations, if several defect types are present. Here, we present a strategy to overcome this limitation by simulating the 1H lineshape as well as 1H-1H double-quantum buildup curves, which we then validate against the experimental data in a joint cost function. To mimic the local structural disorder, we use molecular dynamics simulations at the DFT level. It turned out to be advantageous for the joint refinement to put the computational effort into the structural optimisation to derive accurate proton positions and to use empirical correlations for the relation between isotropic and anisotropic 1H chemical shifts and structural elements. The expressiveness of this approach is demonstrated on ringwoodite's (γ-Mg2SiO4) OH defect chemistry containing four different defect types in octahedral and tetrahedral voids with both pure Mg and mixed Si and Mg cation environments. Still, we determine the ratio for each defect type with an accuracy of about 5% as a result of the minimization of the joint cost function. We expect that our approach is generally applicable for local proton disorder and might prove to be a valuable alternative to the established AIRSS and Monte Carlo methods, respectively.

Hidden Oceans? Unraveling the Structure of Hydrous Defects in the Earth's Deep Interior.

High-pressure silicates making up the main proportion of the earth's interior can incorporate a significant amount of water in the form of OH defects. Generally, they are charge balanced by removing low-valent cations such as Mg2+. By combining high-resolution multidimensional single- and double-quantum 1H solid-state NMR spectroscopy with density functional theory calculations, we show that, for ringwoodite (γ-Mg2SiO4), additionally, Si4+ vacancies are formed, even at a water content as low as 0.1 wt %. They are charge balanced by either four protons or one Mg2+ and two protons. Surprisingly, also a significant proportion of coupled Mg and Si vacancies are present. Furthermore, all defect types feature a pronounced orientational disorder of the OH groups, which results in a significant range of OH···O bond distributions. As such, we are able to present unique insight into the defect chemistry of ringwoodite's spinel structure, which not only accounts for a potentially large fraction of the earth's entire water budget, but will also control transport properties in the mantle. We expect that our results will even impact other hydrous spinel-type materials, helping to understand properties such as ion conduction and heterogeneous catalysis.

Effect of vaginal estrogen on pessary use.

INTRODUCTION AND HYPOTHESIS: Many providers recommend concurrent estrogen therapy with pessary use to limit complications; however, limited data exist to support this practice. We hypothesized that vaginal estrogen supplementation decreases incidence of pessary-related complications and discontinuation. METHODS: We performed a retrospective cohort study of women who underwent a pessary fitting from 1 January 2007 through 1 September 2013 at one institution; participants were identified by billing code and were eligible if they were postmenopausal and had at least 3 months of pessary use and 6 months of follow-up. All tests were two sided, and P values < 0.05 were considered statistically significant. RESULTS: Data from 199 women were included; 134 used vaginal estrogen and 65 did not. Women who used vaginal estrogen had a longer median follow-up time (29.5 months) compared with women who did not (15.4 months) and were more likely to have at least one pessary check (98.5 % vs 86.2 %, P < 0.001). Those in the estrogen group were less likely to discontinue using their pessary (30.6 % vs 58.5 %, P < 0.001) and less likely to develop increased vaginal discharge than women who did not [hazard ratio (HR) 0.31, 95 % confidence interval (CI) 0.17-0.58]. Vaginal estrogen was not protective against erosions (HR 0.93, 95 % CI 0.54-1.6) or vaginal bleeding (HR 0.78, 95 % CI 0.36-1.7). CONCLUSIONS: Women who used vaginal estrogen exhibited a higher incidence of continued pessary use and lower incidence of increased vaginal discharge than women who did not.

Novel Use of Ultrasound Elastography to Quantify Muscle Tissue Changes After Dry Needling of Myofascial Trigger Points in Patients With Chronic Myofascial Pain.

OBJECTIVES: To compare a mechanical heterogeneity index derived from ultrasound vibration elastography with physical findings before and after dry-needling treatment of spontaneously painful active myofascial trigger points in the upper trapezius muscle. METHODS: Forty-eight patients with chronic myofascial pain enrolled in a prospective interventional trial of 3 weekly dry-needling treatments for active myofascial trigger points. Trigger points were evaluated at baseline and at treatment completion using palpation, the pressure-pain threshold, and the mechanical heterogeneity index. Thirty patients were reevaluated at 8 weeks. Trigger points that "responded" changed to tissue that was no longer spontaneously painful, with or without the presence of a palpable nodule. Trigger points that "resolved" changed to tissue without a palpable nodule. The mechanical heterogeneity index was defined as the proportion of the upper trapezius muscle that appeared mechanically stiffer on elastography. Statistical significance for comparisons was determined at P < .05. RESULTS: Following 3 dry needle treatments, the mechanical heterogeneity index decreased significantly for the 38 myofascial trigger points (79% of 48) that responded to treatment. Among these, the baseline mechanical heterogeneity index was significantly lower for the 13 trigger points (27% of 38) that resolved, but the decrease after 3 dry needle treatments did not reach significance. The pressure-pain threshold improved significantly for both groups. At 8 weeks, the mechanical heterogeneity index decreased significantly for the 22 trigger points (73% of 30) that responded and for the 10 (45% of 22) that resolved. The pressure-pain threshold improvement was significant for trigger points that responded but did not reach significance for resolved trigger points. CONCLUSIONS: The mechanical heterogeneity index identifies changes in muscle tissue properties that correlate with changes in the myofascial trigger point status after dry needling.

Long-term sobriety strategies for men with co-occurring disorders.

OBJECTIVE: Roughly half of people with severe mental disorders also experience a co-occurring substance use disorder, and recovery from both is a critical objective for health care services. While understanding of abstinence initiation has grown, the strategies people with co-occurring disorders use to maintain sobriety are largely unknown. This article reports strategies for relapse prevention as described by men with co-occurring disorders who achieved one or more years of sobriety. METHODS: We analyzed semi-structured interviews conducted with a sample of 12 men with co-occurring psychosis and substance use disorder who achieved and maintained sobriety for at least one year, supplemented with demographic and diagnostic clinical record data. These men were participating in residential or outpatient treatment at a private, nonprofit integrated treatment clinic. RESULTS: The 12 men were primarily Caucasian (91.7%) and unmarried (100%), and their ages ranged from 23 to 42 years. The two most common psychiatric disorders were schizoaffective disorder (n = 4, 33.3%) and bipolar disorder (n = 4, 33.3%), while the two most commonly misused substances were alcohol and cannabis. Qualitative analyses showed that participants maintained sobriety for at least one year by building a supportive community, engaging in productive activities, and carefully monitoring their own attitudes toward substances, mental health, and responsibility. Alcoholics Anonymous might act as a catalyst for building skills. CONCLUSIONS: People with co-occurring disorders who achieve sobriety use a variety of self-management strategies to prevent relapse-seeking support, activities, and a healthy mindset. The findings suggest a relapse prevention model that focuses on social networks, role functioning, and self-monitoring and conceptualizes self-care as critical to extending periods of wellness.

Dissociation of response variability from firing rate effects in frontal eye field neurons during visual stimulation, working memory, and attention.

Recent studies suggest that trial-to-trial variability of neuronal spiking responses may provide important information about behavioral state. Observed changes in variability during sensory stimulation, attention, motor preparation, and visual discrimination suggest that variability may reflect the engagement of neurons in a behavioral task. We examined changes in spiking variability of frontal eye field (FEF) neurons in a change detection task requiring monkeys to remember a visually cued location and direct attention to that location while ignoring distracters elsewhere. In this task, the firing rates (FRs) of FEF neurons not only continuously reflect the location of the remembered cue and select targets, but also predict detection performance on a trial-by-trial basis. Changes in FEF response variability, as measured by the Fano factor (FF), showed clear dissociations from changes in FR. The FF declined in response to visual stimulation at all tested locations, even in the opposite hemifield, indicating much broader spatial tuning of the FF compared with the FR. Furthermore, despite robust spatial modulation of the FR throughout all epochs of the task, spatial tuning of the FF did not persist throughout the delay period, nor did it show attentional modulation. These results indicate that changes in variability, at least in the FEF, are most effectively driven by visual stimulation, while behavioral engagement is not sufficient. Instead, changes in variability may reflect shifts in the balance between feedforward and recurrent sources of excitatory drive.

Current practices in pediatric hospital-acquired thromboembolism: Survey of the Children's Hospital Acquired Thrombosis (CHAT) Consortium.

Background: A rise in hospital-acquired venous thromboembolism (HA-VTE) in children has led to increased awareness regarding VTE prophylaxis and risk assessment. Despite no consensus exists regarding these practices in pediatrics. Objective: To describe common practices in VTE prophylaxis, VTE risk assessment models, and anticoagulation dosing strategies in pediatric hospitals that are members of the Children's Hospital Acquired Thrombosis (CHAT) Consortium. Methods: An electronic survey of 44 questions evaluating practices surrounding pediatric HA-VTE risk assessment and prevention was distributed between August 9, 2021, and August 30, 2021, to the primary investigators from the 32 institutions within the CHAT Consortium. Results: The survey response rate was 100% (n = 32). In total, 85% (n = 27) of the institutions assess HA-VTE, but only 63% (n = 20) have formal hospital guidelines. Within the institutions with formal guidelines, 100% (n = 20) include acute systemic inflammation or infection and presence of a central venous catheter (CVC) as risk factors for VTE. Pharmacologic prophylaxis is prescribed at 87% (28) of institutions, with enoxaparin being the most frequent (96%, n = 27). Variability in responses persisted regarding risk factors, risk assessment, thromboprophylaxis, dosing of prophylactic anticoagulation or anticoagulant drug monitoring. A majority of providers were comfortable providing thromboprophylaxis across all age groups. In addition, the global coronavirus disease 2019 increased the providers' use of prophylactic anticoagulation 78% (n = 25). Conclusion: Practices among institutions are variable in regard to use of HA-VTE prophylaxis, risk assessment, or guideline implementation, highlighting the need for further research and a validated risk assessment model through groups like the CHAT Consortium.

Probing neural circuitry and function with electrical microstimulation.

Since the discovery of the nervous system's electrical excitability more than 200 years ago, neuroscientists have used electrical stimulation to manipulate brain activity in order to study its function. Microstimulation has been a valuable technique for probing neural circuitry and identifying networks of neurons that underlie perception, movement and cognition. In this review, we focus on the use of stimulation in behaving primates, an experimental system that permits causal inferences to be made about the effect of stimulation-induced activity on the resulting behaviour or neural signals elsewhere in the brain.

Laparoscopic Cerclage Sacrohysteropexy: Comparing a Novel Technique for Sacrohysteropexy to Traditional Supracervical Hysterectomy and Sacrocervicopexy.

OBJECTIVE: The objective of this study was to compare outcomes of laparoscopic cerclage sacrohysteropexy (LCSH), a novel technique used to perform sacrohysteropexy, which requires significantly less suturing and knot tying, to traditional laparoscopic supracervical hysterectomy (LSH) with sacrocervicopexy for the treatment of uterine prolapse. METHODS: This is a retrospective cohort study of all patients who underwent LCSH between March 3, 2016, and October 30, 2018, and patients who underwent LSH with sacrocervicopexy between September 1, 2013, and October 30, 2018. Medical records were reviewed to obtain information on baseline demographics, preoperative pelvic organ prolapse quantification (POP-Q), baseline Pelvic Floor Distress Inventory score, and intraoperative and postoperative outcomes. Apical failure was defined as descent of the cervix beyond the midvagina (C > -TVL/2). Subjective failure was defined as reporting of bulge symptoms, reoperation, or use of a vaginal pessary. RESULTS: Seventy-seven patients who underwent the LCSH procedure and 88 who underwent LSH with sacrocervicopexy were identified. Baseline demographic data were similar between the 2 groups. Operating time was significantly decreased in the LCSH group with median time of 129 minutes (interquartile range, 121-153) versus 199 minutes (interquartile range, 178.5-222.5; P < 0.001) in the traditional cohort. Six weeks after surgery, patients had equivalent POP-Q examinations and Pelvic Floor Distress Inventory scores. At 6 months after surgery, patients similarly had no significant difference in POP-Q examination or scores on standardized questionnaires between the 2 groups. There were no mesh or suture erosions noted in either cohort at any time point. CONCLUSIONS: Laparoscopic cerclage sacrohysteropexy is a novel variation of traditional sacrohysteropexy and an alternative to LSH with sacrocervicopexy that minimizes the dissection and suturing required. This procedure appears to offer equivalent anatomic and subjective outcomes to traditional LSH with sacrocervicopexy with significantly decreased intraoperative time.

Changes in visual receptive fields with microstimulation of frontal cortex.

The influence of attention on visual cortical neurons has been described in terms of its effect on the structure of receptive fields (RFs), where multiple stimuli compete to drive neural responses and ultimately behavior. We stimulated the frontal eye field (FEF) of passively fixating monkeys and produced changes in V4 responses similar to known effects of voluntary attention. Subthreshold FEF stimulation enhanced visual responses at particular locations within the RF and altered the interaction between pairs of RF stimuli to favor those aligned with the activated FEF site. Thus, we could influence which stimulus drove the responses of individual V4 neurons. These results suggest that spatial signals involved in saccade preparation are used to covertly select among multiple stimuli appearing within the RFs of visual cortical neurons.

Selection and maintenance of spatial information by frontal eye field neurons.

Voluntary attention is often allocated according to internally maintained goals. Recent evidence indicates that the frontal eye field (FEF) participates in the deployment of spatial attention, even in the absence of saccadic eye movements. In addition, many FEF neurons maintain persistent representations of impending saccades. However, the role of persistent activity in the general maintenance of spatial information, and its relationship to spatial attention, has not been explored. We recorded the responses of single FEF neurons in monkeys trained to remember cued locations in order to detect changes in targets embedded among distracters in a task that did not involve saccades. We found that FEF neurons persistently encoded the cued location throughout the trial during the delay period, when no visual stimuli were present, and during visual discrimination. Furthermore, FEF activity reliably predicted whether monkeys would detect the target change. Population analyses revealed that FEF neurons with persistent activity were more effective at selecting the target from among distracters than neurons lacking persistent activity. These results demonstrate that FEF neurons maintain spatial information in the absence of saccade preparation and suggest that this maintenance contributes to the selection of relevant visual stimuli.

Deep magma ocean formation set the oxidation state of Earth's mantle.

The composition of Earth's atmosphere depends on the redox state of the mantle, which became more oxidizing at some stage after Earth's core started to form. Through high-pressure experiments, we found that Fe2+ in a deep magma ocean would disproportionate to Fe3+ plus metallic iron at high pressures. The separation of this metallic iron to the core raised the oxidation state of the upper mantle, changing the chemistry of degassing volatiles that formed the atmosphere to more oxidized species. Additionally, the resulting gradient in redox state of the magma ocean allowed dissolved CO2 from the atmosphere to precipitate as diamond at depth. This explains Earth's carbon-rich interior and suggests that redox evolution during accretion was an important variable in determining the composition of the terrestrial atmosphere.