Risk factors for pediatric ischemic stroke and intracranial hemorrhage: A national electronic health record based study.

Background: Stroke is an important cause of morbidity in pediatrics. Large studies are needed to better understand the epidemiology, pathogenesis and risk factors associated with pediatric stroke. Large administrative datasets can provide information on risk factors in perinatal and childhood stroke at low cost. The aim of this hypothesis-generating study was to use a large administrative dataset to assess for prevalence and odds-ratios of rare exposures associated with pediatric stroke. Methods: The data for patients aged 0-18 with a diagnosis of either ischemic stroke or intracranial hemorrhage were extracted from the Cerner Health Facts EMR Database from 2000 to 2018. Prevalence of various possible risk factors for pediatric and adult stroke was assessed using ICD 9 and 10 codes. Odds ratios were calculated using a control group of patients without stroke. Results: 10,688 children were identified with stroke. 6339 (59 %) were ischemic and 4349 (41 %) were hemorrhagic. The most frequently identified risk factors for ischemic stroke across age groups were hypertension (29-44 %), trauma (19-33 %), and malignancy (11-24 %). The most common risk factors seen with hemorrhagic stroke were trauma (32-64 %), malignancy (5-19 %) and arrhythmia (9-12 %). Odds ratios across all age groups for dyslipidemia (17-64), hypertension (20-63), and tobacco exposure (3-59) were high in the ischemic stroke cohort. Conclusion: This is the largest retrospective study of pediatric stroke of its kind from hospitals across the US in both academic and non-academic clinical settings. Much of our data was consistent with prior studies. ICD codes for tobacco exposure, hyperlipidemia, diabetes, and hypertension all had high odds ratios for stroke in children, which suggest a relationship between these conditions and pediatric stroke. However, ascertainment bias is a major concern with electronic health record-based studies. More focused study is needed into the role of these exposures into the pathogenesis of pediatric stroke.

A National, Electronic Health Record-Based Study of Perinatal Hemorrhagic and Ischemic Stroke.

BACKGROUND: Perinatal stroke occurs in approximately 1 in 1100 live births. Large electronic health record (EHR) data can provide information on exposures associated with perinatal stroke in a larger number of patients than is achievable through traditional clinical studies. The objective of this study is to assess prevalence and odds ratios of known and theorized comorbidities with perinatal ischemic and hemorrhagic stroke. METHODS: The data for patients aged 0-28 days with a diagnosis of either ischemic or hemorrhagic stroke were extracted from the Cerner Health Facts Electronic Medical Record (EMR) database. Incidence of birth demographics and perinatal complications were recorded. Odds ratios were calculated against a control group. RESULTS: A total of 535 (63%) neonates were identified with ischemic stroke and 312 (37%) with hemorrhagic stroke. The most common exposures for ischemic stroke were sepsis (n = 82, 15.33%), hypoxic injury (n = 61, 11.4%), and prematurity (n = 49, 9.16%). The most common comorbidities for hemorrhagic stroke were prematurity (n = 81, 26%) and sepsis (n = 63, 20%). No perinatal ischemic stroke patients had diagnosis codes for cytomegalovirus disease. Procedure and diagnosis codes related to critical illness, including intubation and resuscitation, were prominent in both hemorrhagic (n = 46, 15%) and ischemic stroke (n = 45, 8%). CONCLUSION: This electronic health record-based study of perinatal stroke, the largest of its kind, demonstrated a wide variety of comorbid conditions with ischemic and hemorrhagic stroke. Sepsis, prematurity, and hypoxic injury are associated with perinatal hemorrhagic and ischemic stroke, though prevalence varies between types. Much of our data were similar to prior studies, which lends validity to the electronic health record database in studying perinatal stroke.

Familial caregiving following stroke: findings from the comprehensive post-acute stroke services (COMPASS) pragmatic cluster-randomized transitional care study.

BACKGROUND: Stroke patients discharged home often require prolonged assistance from caregivers. Little is known about the real-world effectiveness of a comprehensive stroke transitional care intervention on relieving caregiver strain. OBJECTIVES: To describe the effect of the COMPASS transitional care (COMPASS-TC) intervention on caregiver strain and characterize the types, duration, and intensity of caregiving. METHODS: The cluster-randomized COMPASS pragmatic trial evaluated the effectiveness of COMPASS-TC versus usual care with patients with mild stroke and TIA at 40 hospitals in North Carolina, USA. Of 5882 patients enrolled, 4208 (71%) identified a familial caregiver. A follow-up Caregiver Questionnaire, including the Modified Caregiver Strain Index, was administered at approximately three months post-discharge. Demographics and frequency, duration, and intensity of caregiving were compared between groups. RESULTS: 1228 caregivers (29%) completed the questionnaire. Completion was positively associated with older patient age, white race, and spousal relationship. One-third of the caregivers provided ≥30 hours of care per week and 889 (79%) provided care ≥9 weeks. Average standardized caregiver strain was 21.9 (0-100), increasing with stroke severity and comorbidity burden. Women caregivers reported higher strain than men. Treatment allocation was not associated with caregiver strain. CONCLUSIONS: This sample of mild stroke and TIA survivors received significant assistance from familial caregivers. However, caregiver strain was relatively low. Findings support the importance of familial caregiving in stroke, the continued disproportionate burden on women within the family, and the need for future research on caregiver support.

Global reach of ageism on older persons' health: A systematic review.

OBJECTIVE: Although there is anecdotal evidence of ageism occurring at both the structural level (in which societal institutions reinforce systematic bias against older persons) and individual level (in which older persons take in the negative views of aging of their culture), previous systematic reviews have not examined how both levels simultaneously influence health. Thus, the impact of ageism may be underestimated. We hypothesized that a comprehensive systematic review would reveal that these ageism levels adversely impact the health of older persons across geography, health outcomes, and time. METHOD: A literature search was performed using 14 databases with no restrictions on region, language, and publication type. The systematic search yielded 13,691 papers for screening, 638 for full review, and 422 studies for analyses. Sensitivity analyses that adjusted for sample size and study quality were conducted using standardized tools. The study protocol is registered (PROSPERO CRD42018090857). RESULTS: Ageism led to significantly worse health outcomes in 95.5% of the studies and 74.0% of the 1,159 ageism-health associations examined. The studies reported ageism effects in all 45 countries, 11 health domains, and 25 years studied, with the prevalence of significant findings increasing over time (p < .0001). A greater prevalence of significant ageism-health findings was found in less-developed countries than more-developed countries (p = .0002). Older persons who were less educated were particularly likely to experience adverse health effects of ageism. Evidence of ageism was found across the age, sex, and race/ethnicity of the targeters (i.e., persons perpetrating ageism). CONCLUSION: The current analysis which included over 7 million participants is the most comprehensive review of health consequences of ageism to date. Considering that the analysis revealed that the detrimental impact of ageism on older persons' health has been occurring simultaneously at the structural and individual level in five continents, our systematic review demonstrates the pernicious reach of ageism.

Implementation of a billable transitional care model for stroke patients: the COMPASS study.

BACKGROUND: The COMprehensive Post-Acute Stroke Services (COMPASS) pragmatic trial compared the effectiveness of comprehensive transitional care (COMPASS-TC) versus usual care among stroke and transient ischemic attack (TIA) patients discharged home from North Carolina hospitals. We evaluated implementation of COMPASS-TC in 20 hospitals randomized to the intervention using the RE-AIM framework. METHODS: We evaluated hospital-level Adoption of COMPASS-TC; patient Reach (meeting transitional care management requirements of timely telephone and face-to-face follow-up); Implementation using hospital quality measures (concurrent enrollment, two-day telephone follow-up, 14-day clinic visit scheduling); and hospital-level sustainability (Maintenance). Effectiveness compared 90-day physical function (Stroke Impact Scale-16), between patients receiving COMPASS-TC versus not. Associations between hospital and patient characteristics with Implementation and Reach measures were estimated with mixed logistic regression models. RESULTS: Adoption: Of 95 eligible hospitals, 41 (43%) participated in the trial. Of the 20 hospitals randomized to the intervention, 19 (95%) initiated COMPASS-TC. Reach: A total of 24% (656/2751) of patients enrolled received a billable TC intervention, ranging from 6 to 66% across hospitals. IMPLEMENTATION: Of eligible patients enrolled, 75.9% received two-day calls (or two attempts) and 77.5% were scheduled/offered clinic visits. Most completed visits (78% of 975) occurred within 14 days. Effectiveness: Physical function was better among patients who attended a 14-day visit versus those who did not (adjusted mean difference: 3.84, 95% CI 1.42-6.27, p = 0.002). Maintenance: Of the 19 adopting hospitals, 14 (74%) sustained COMPASS-TC. CONCLUSIONS: COMPASS-TC implementation varied widely. The greatest challenge was reaching patients because of system difficulties maintaining consistent delivery of follow-up visits and patient preferences to pursue alternate post-acute care. Receiving COMPASS-TC was associated with better functional status. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02588664. Registered 28 October 2015.

Predicting Cellular Rejection With a Cell-Based Assay: Preclinical Evaluation in Children.

BACKGROUND: Allospecific CD154+T-cytotoxic memory cells (CD154+TcM) predict acute cellular rejection after liver transplantation (LTx) or intestine transplantation (ITx) in small cohorts of children and can enhance immunosuppression management, but await validation and clinical implementation. METHODS: To establish safety and probable benefit, CD154+TcM were measured in cryopreserved samples from 214 children younger than 21 years (National Clinical Trial 1163578). Training set samples (n = 158) were tested with research-grade reagents and 122 independent validation set samples were tested with current good manufacturing practices-manufactured reagents after assay standardization and reproducibility testing. Recipient CD154+TcM induced by stimulation with donor cells were expressed as a fraction of those induced by HLA nonidentical cells in parallel cultures. The resulting immunoreactivity index (IR) if greater than 1 implies increased rejection-risk. RESULTS: Training and validation set subjects were demographically similar. Mean coefficient of test variation was less than 10% under several conditions. Logistic regression incorporating several confounding variables identified separate pretransplant and posttransplant IR thresholds for prediction of rejection in the respective training set samples. An IR of 1.1 or greater in posttransplant training samples and IR of 1.23 or greater in pretransplant training samples predicted LTx or ITx rejection in corresponding validation set samples in the 60-day postsampling period with sensitivity, specificity, positive, and negative predictive values of 84%, 80%, 64%, and 92%, respectively (area under the receiver operator characteristic curve, 0.792), and 57%, 89%, 78%, and 74%, respectively (area under the receiver operator characteristic curve, 0.848). No adverse events were encountered due to phlebotomy. CONCLUSIONS: Allospecific CD154+T-cytotoxic memory cells predict acute cellular rejection after LTx or ITx in children. Adjunctive use can enhance clinical outcomes.

Profile of the Pleximmune blood test for transplant rejection risk prediction.

The Pleximmune™ test (Plexision Inc., Pittsburgh, PA, USA) is the first cell-based test approved by the US FDA, which predicts acute cellular rejection in children with liver- or intestine transplantation. The test addresses an unmet need to improve management of immunosuppression, which incurs greater risks of opportunistic infections and Epstein-Barr virus-induced malignancy during childhood. High-dose immunosuppression and recurrent rejection after intestine transplantation also result in a 5-year graft loss rate of up to 50%. Such outcomes seem increasingly unacceptable because children can experience rejection-free survival with reduced immunosuppression. Pleximmune test sensitivity and specificity for predicting acute cellular rejection is 84% and 80% respectively in training set-validation set testing of 214 children. Among existing gold standards, the biopsy detects but cannot predict rejection. Anti-donor antibodies, which presage antibody-mediated injury, reflect late-stage allosensitization as a downstream effect of engagement between recipient and donor cells. Therefore, durable graft and patient outcomes also require accurate management of cellular immune responses in clinical practice.

Alloreactive CD154-expressing T-cell subsets with differential sensitivity to the immunosuppressant, belatacept: potential targets of novel belatacept-based regimens.

Belatacept blocks CD28-mediated T-cell costimulation and prevents renal transplant rejection. Understanding T-cell subset sensitivity to belatacept may identify cellular markers for immunosuppression failure to better guide treatment selection. Here, we evaluate the belatacept sensitivity of allo-antigen-specific CD154-expressing-T-cells, whose T-cytotoxic memory (TcM) subset predicts rejection with high sensitivity after non-renal transplantation. The belatacept concentration associated with half-maximal reduction (EC50) of CD154 expression was calculated for 36 T-cell subsets defined by combinations of T-helper (Th), Tc, T-memory and CD28 receptors, following allostimulation of peripheral blood leukocytes from 20 normal healthy subjects. Subsets were ranked by median EC50, and by whether subset EC50 was correlated with and therefore could be represented by the frequency of other subsets. No single subset frequency emerged as the significant correlate of EC50 for a given subset. Most (n = 25) T-cell subsets were sensitive to belatacept. Less sensitive subsets demonstrated a memory phenotype and absence of CD28 receptor. Potential drug-resistance markers for future validation include the low frequency highly differentiated, Th-memory-CD28-negative T-cells with the highest median EC50, and the least differentiated, high-frequency Tc subset, with the most CD28-negative T-cells, the third highest median EC50, and significant correlations with frequencies of the highest number of CD28-negative and memory subsets.

A phase I study on the feasibility and acceptability of an acupuncture/hypnosis intervention for chronic pediatric pain.

The purpose of the present study was to conduct a Phase I investigation examining the feasibility and acceptability of a complementary and alternative medicine (CAM) package combining acupuncture and hypnosis for chronic pediatric pain. Thirty-three sequentially referred children (21 girls) aged 6-18 years were offered 6 weekly sessions consisting of individually tailored acupuncture treatment together with a 20-minute hypnosis session (conducted while the needles were in place). Parent and child ratings of pain and pain-related interferences in functioning, as well as child ratings of anxiety and depression, were obtained at pre- and post-treatment. The treatment was highly acceptable (only 2 patients refused; > or = 90% completed treatment) and there were no adverse effects. Both parents and children reported significant improvements in children's pain and interference following treatment. Children's anticipatory anxiety declined significantly across treatment sessions. Our results support the feasibility and acceptability of a combined acupuncture/hypnosis intervention for chronic pediatric pain.