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.

Physical activity in children at risk of postthrombotic sequelae: a pilot randomized controlled trial.

Increased physical activity is protective against worsening of postthrombotic syndrome (PTS) in adults. We assessed patient eligibility, consent, adherence, and retention rates in a pilot trial of prescribed physical activity following venous thromboembolism (VTE) in children. Secondary objectives were to describe the within-subject changes in PTS, quality of life, and coagulation biomarkers before and after the intervention in each group. We enrolled and randomized patients between 7 and 21 years of age to the physical activity group or the standard care (education-only) group in a 1:1 allocation ratio. The physical activity group wore a Fitbit for 4 weeks to determine habitual activity and then increased activity over an 8-week "active" period, followed by a 4-week "do-as-you-wish" period. Two hundred thirty-five children were diagnosed with VTE; 111 patients were screened, of whom 40 (36%) met study eligibility criteria. Of these, 23 (57%) consented to participate and were randomized (Fitbit,11; standard group, 12). The trial was of greater interest to overweight and obese children, as they comprised 83% of consented patients. Only 33% adhered to the activity prescription, and 65% (15/23) completed the trial. The PTS scores (P = .001) improved in the physical activity group compared with the education-only group. It is feasible to enroll and randomize pediatric VTE patients to a prescribed physical activity regimen 3 months following VTE. Metrics for adherence to enhanced physical activity and retention were not met. These results provide the rationale to explore low adherence and retention rates before moving forward with a larger trial of exercise training following VTE. This trial was registered at www.clinicaltrials.gov as #NCT03075761.

Prospective evaluation of ISTH-BAT as a predictor of bleeding disorder in adolescents presenting with heavy menstrual bleeding in a multidisciplinary hematology clinic.

BACKGROUND: Heavy menstrual bleeding (HMB) can be the first manifestation of an undiagnosed bleeding disorder (BD). Identifying a BD can be challenging in the adolescent age group. The utility of bleeding assessment tools (BAT) remains elusive in this population. AIM: We evaluated the ability of the International Society on Thrombosis and Haemostasis-BAT (ISTH-BAT) in predicting a BD in adolescents referred for HMB to a multidisciplinary hematology clinic. METHODS: Two hundred adolescents with HMB underwent a standardized evaluation for BD. The clinical characteristics, laboratory data, and bleeding scores (BS) assessed using ISTH-BAT were prospectively collected. Comparisons were made between patients based on the diagnosis of BD receiver operating characteristic (ROC) curve analyses of ISTH-BAT were performed to assess its value for predicting BD. RESULTS: Overall, 33% (n = 67) of adolescents were diagnosed with a BD. The mean ISTH-BAT BS was higher in BD as compared to those without (4.1 versus 3.1, P < .0001), but the mean menorrhagia-specific scores did not differ (2.9 in both groups). The ISTH-BAT demonstrated a modest discriminative ability as a screening tool to identify BD in girls with HMB with an area under the curve (AUC) of 0.71. The ROC analysis demonstrated that with increasing BS, the sensitivity decreased, but the specificity increased. At BS = 3, sensitivity was 88%, specificity 31%, and accuracy 50%; at BS = 5, sensitivity was 37%, specificity 94%, and accuracy was 75%. There was no change thereafter. CONCLUSION: In adolescents with HMB, an ISTH-BAT BS of >4 instead of the established cut-off of >2 in children is highly specific in predicting a BD.

A randomized trial of an NMDA receptor antagonist for reversing corticosteroid effects on the human hippocampus.

Preclinical and clinical research indicates that excess corticosteroid is associated with adverse effects on the hippocampus. Animal model data suggest that N-methyl-D-aspartate (NMDA) receptor antagonists may block corticosteroid effect on the hippocampus. This translational clinical trial investigated the effect of memantine vs. placebo on hippocampal subfield volume in humans receiving chronic corticosteroid therapy. Men and women (N = 46) receiving chronic prescription corticosteroid therapy were randomized to memantine or placebo in a double-blind, crossover design (two 24-week treatment periods, separated by a 4-week washout) for 52 weeks. Structural magnetic resonance imaging was obtained at baseline and after each treatment. Data were analyzed using repeated measures analysis of variance. Mean corticosteroid dose was 7.69 ± 6.41 mg/day and mean duration 4.90 ± 5.61 years. Controlling for baseline volumes, the left DG/CA3 region was significantly larger following memantine than placebo (p = .011). The findings suggest that an NMDA receptor antagonist attenuates corticosteroid effect in the same hippocampal subfields in humans as in animal models. This finding has both mechanistic and clinical implications. Attenuation of the effect of corticosteroids on the human DG/CA3 region implicates the NMDA receptor in human hippocampal volume losses with corticosteroids. In addition, by suggesting a drug class that may, at least in part, block the effects of corticosteroids on the human DG/CA3 subfield, these results may have clinical relevance for people receiving prescription corticosteroids, as well as to those with cortisol elevations due to medical or psychiatric conditions.

Markers of coagulation activation, inflammation and fibrinolysis as predictors of poor outcomes after pediatric venous thromboembolism: A systematic review and meta-analysis.

BACKGROUND: Sequelae of venous thromboembolism (VTE) in children include recurrence, development of post thrombotic syndrome (PTS) when venous return from a limb is affected and chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism. Identification of laboratory-based risk factors may be useful for individualized risk assessment for VTE sequelae. Coagulation activation and inflammation may contribute to their pathophysiology. We performed a systematic review to investigate the association between biomarkers of coagulation activation, inflammation and fibrinolysis and adverse VTE outcomes in children and young adults. METHODS: A systematic search of electronic databases, PubMed (NIH), EMBASE (Ovid), Web of Science (Thompson Reuters), and SCOPUS (Elsevier) for studies published through November 2016 was conducted using "VTE" including MeSH terms for "coagulation activation," "inflammation" and "fibrinolysis," with no limit on publication date. A study was eligible for inclusion when it evaluated patients (< 21years) with VTE and biomarkers of coagulation activation, inflammation, and fibrinolysis and assessed for their association with development of adverse thrombotic outcomes. A modified Newcastle Ottawa Scale was applied to examine the quality of included studies. RESULTS: Our search strategy yielded 200 references. A total of 3 cohort studies representing 220 patients with VTE were included. Two authors independently assessed all references for inclusion. Three studies (2 prospective cohort and one mixed cohort study) were identified that reported on biomarkers of coagulation activation, inflammation and fibrinolysis, checked at least once after VTE diagnosis and assessed association with primary outcomes of recurrent VTE, PTS and CTEPH. Studies varied with regards to definition of outcomes, the type of biomarkers measured and time point of measurement. We were unable to meta-analyze results due to marked clinical heterogeneity and <3 studies available for each biomarker. Descriptively, a significant association was found for elevated plasma levels of FVIII and D-dimer for a compound outcome of PTS, recurrence and progression in one study, and positive lupus anticoagulant at DVT diagnosis and subsequent PTS by another study. No studies were found for CTEPH. CONCLUSIONS: Elevated D-dimer, FVIII and lupus anticoagulant show promise for predicting recurrent VTE and PTS in children and young adults. Further research is needed to elucidate whether these markers might be useful to predict development of adverse outcomes after VTE in children.

Suicide risk and mental health co-morbidities in a probationer population.

Mental health problems are disproportionately represented in the community corrections system with limited information on the epidemiology of mental health and correlated factors such as suicide among probationers. This study recruited 2,077 probationers who completed screeners for mental health and substance disorders and suicide risk. Results found 13% of probationers were at high risk of suicide. Those who screened positive for a mental health condition were between 2 and 8 times more likely to screen positive for suicide risk. Allocation of additional resources to mental health in the criminal justice system and to effectively coordinate existing mental health services is needed.

Incidental computer tomography radiologic findings through research participation in the North Texas Healthy Heart Study.

BACKGROUND: Although variation exists in the classification and practice of managing clinical findings in research, emerging views suggest that researchers bear some responsibility in the management of incidental findings. This study contributes to the documentation of the population characteristics and prevalence of medical findings incidental to research participation, specifically findings related to coronary calcium scores and computed tomography (CT) scans that investigated cardiovascular disparities in an asymptomatic population. METHODS: A total of 571 asymptomatic adult participants were recruited in the North Texas Healthy Heart Study. Participants completed a 16-slice CT scan of the heart and abdomen. Findings of radiology reports and 3 years of follow-up documentation were reviewed. RESULTS: A total of 246 clinically apparent findings were identified in 169 asymptomatic participants (32.9% of participants who completed a CT scan). Another 245 participants (48%) had findings of unknown significance, a total of 307 findings. At least 4 cases in this study led to a clinically significant intervention. CONCLUSION: Although CT scans were completed for research purposes, study procedures resulted in the diagnosis and treatment of individuals who were previously asymptomatic. Potential clinical benefits in imaging research are moderated by considerations regarding possible harm and costs resulting from uncertain findings and the use of CT scans for nonclinical purposes. The continued development of protocols for the handling of incidental findings in research and the establishment of guidelines are needed to ensure that research procedures mirror the best interests of participants.