Real-world experience of direct oral anticoagulant use in a single pediatric center.

BACKGROUND: Pediatric venous thromboembolism has increased by 130%-200%, specifically in hospitalized children, and direct oral anticoagulants (DOACs) offer several therapeutic advantages. METHODS: This study aims to evaluate the real-world epidemiological and outcome data from a retrospective review of pediatric patients treated with DOACs from January 1, 2013 to December 31, 2022. In this single-center, IRB-approved study, 65 patients were identified and analyzed using SPSS statistical software, and a descriptive statistical analysis was conducted. RESULTS: Of the 65 patients, 37% were on apixaban, 61.5% were on rivaroxaban, and 1.5% were on dabigatran. Per the 2023 ISTH outcome definitions, one (2%) patient had a major bleeding episode, six (9%) had clinically relevant non-major bleeding, three (5%) patients had patient-important heavy menstrual bleeding (HMB), and one (1.5%) patient had minor bleeding. Seven (19%) of 37 postmenarchal patients had evidence of HMB. Six (9.2%) patients had recurrent venous thromboembolism while on a DOAC (one was on apixaban, and five were on rivaroxaban) and were transitioned to other forms of anticoagulation. CONCLUSION: Thus, bleeding rates after DOAC therapy are comparable to previous DOAC trials, as well as other anticoagulants in pediatrics. HMB is an important outcome measure and should continue to be investigated. This study reports a higher rate of recurrent thrombosis (9.2%) compared to other trials. However, this observation may be attributed to patients who had ongoing risk factors, as well as a longer duration of study follow-up. Additional multicentered outcome studies evaluating DOAC use in children are needed to determine long-term recurrence and HMB risks.

Recombinant Von Willebrand factor concentrate in 2A Von Willebrand disease: comparison to plasma-derived Von Willebrand factor concentrate therapy.

: Type 2A sub-type of Von Willebrand disease (VWD) is characterized by the loss of high molecular weight multimers. Several plasma-derived Von Willebrand factor concentrates (PD-VWFC) are available for treatment and recently a recombinant VWF concentrate (rVWFC) has been approved for use in VWD for adults in the United States. We describe a patient with Type 2A VWD who had persistent refractory epistaxis despite treatment with PD-VWFC. We describe differences in VWF multimeric composition and Factor VIII (FVIII) levels after plasma-derived and rVWF concentrates. Despite similar VWF levels, VWF multimeric composition after PD-VWFC remained abnormal while it corrected with rVWFC. Post-PD-VWFC, high levels of FVIII were seen, which were not observed after rVWFC. Recombinant VWFC may offer some advantages over PD-VWFC. This finding needs to be confirmed in larger studies.

Effects of Curtailed Juvenile State on Cardiac Structure and Function in Adulthood: The Fels Longitudinal Study.

OBJECTIVE: Previous studies have shown associations between body mass index and cardiac structure in both childhood and adulthood. Using Fels Longitudinal Study measurements, we investigate the relationships between a curtailed juvenile state and both adult cardiac structure and function. METHODS: A linear mixed-effect repeated measure analysis of variance model is used to test if there is a relationship between juvenile state and each echocardiographic measurement. RESULTS: The curtailed juvenile state is significantly associated with adult left ventricular mass index for both males and females. It is also significantly associated with the interventricular septal wall thickness index and relative wall thickness index for females. In both cases, early juvenile states led to more abnormal structural estimates in adulthood than did late juvenile states. Among cardiac function measurements such as left ventricular ejection fraction and left ventricular shortening fraction, left ventricular ejection fraction is significantly associated with the juvenile state for females. CONCLUSION: The curtailed juvenile state at the childhood may have a long-term adverse effect on adult cardiac structure and function abnormalities.

Age variation and sexual dimorphism in the sixteen diagnostic clusters of risk factors for the metabolic syndrome.

OBJECTIVE: To document age- and sex-related differences in the 16 phenotypes of risk factors for the metabolic syndrome (MS) among adults in the Fels Longitudinal Study (FLS). METHODS: Data on risk factors for the MS were analyzed in 471 white men and 503 white women in the FLS. We used the Cochran-Armitage test to compare age- and sex-related differences in the prevalence of the 16 diagnostic clusters of positive risk factors. RESULTS: Of the 974 subjects, 238 were found to meet diagnostic criteria for 15 of a possible 16 phenotypes of the MS. The prevalence of the MS was four times greater in subjects older than 40 years than in subjects 20-40 years old. Older subjects had more risk factors exceeding criterion values than younger subjects. Among those who met three-to-five criteria for the MS, younger subjects were more likely to have dyslipidemia, less likely to have high blood pressure (HBP), and two times less likely to have impaired fasting plasma glucose (IFG) than subjects 40+ years old. Older men were more likely than older women to have HBP and IFG. . We found that if one of the five risk factors reaches a criterion value, the values for the other four risk factors move closer to their own diagnostic criterion values in apparent synchrony. CONCLUSIONS: Subjects 40+ years old are four times likelier to have the MS than younger subjects, and older men are at higher risk than older women. The mean values for each of the five risk factors get progressively worse as the number of risk factors meeting diagnostic criteria increases. Therefore, when one factor is found to meet its diagnostic criterion, levels of the other four risk factors should be measured. The different phenotypic patterns that comprise the MS should prompt clinicians to target specific risk factors for prevention or treatment. Certain phenotypes were found more commonly in women and certain others more commonly in men. Similarly, certain phenotypes were found more commonly in older than in younger age groups. These age- and sex-specific phenotypes should help clinicians to identify subjects at highest risk for certain risk factors and to initiate specifically tailored preventive and therapeutic interventions. Our observations should also stimulate clinical investigators and epidemiologists to ascertain what factors determine the sex and age specificity of certain phenotypes of the MS.

Secular trends in body composition for children and young adults: the Fels Longitudinal Study.

OBJECTIVES: To determine secular trends by birth decade in body mass index (BMI), waist circumference/height (W/Ht), percent body fat (PBF), and fat-free mass adjusted for height squared (FFM/Ht(2) ) in children and adolescents aged 8-18 years. METHODS: Serial data were analyzed from 628 boys and 591 girls aged 8-18 years who participated in the Fels Longitudinal Study. Subjects were stratified by birth decade from 1960 to 1999. Means and standard deviations were computed for all measurements by birth decade, age, and sex. A repeated-measures analysis of variance was used data to ascertain secular trends separately for boys and girls. RESULTS: Boys and girls born in the 1990s had significantly higher mean BMI, W/Ht, and PBF than did children born in previous decades. Mean FFM/Ht(2) was significantly smaller in boys born in the 1990s than boys of the same age born in earlier decades. No secular trend was noted in FFM/Ht(2) in girls by decade of birth. CONCLUSION: Our analysis of serial data collected over 4 decades confirms the secular trend in childhood BMI previously observed in successive cross-sectional studies. Our analysis discloses significant positive secular trends in W/Ht and PBF in both boys and girls and a significant negative secular trend in FFM/Ht(2) in boys over the last 4 decades of the 20th century. The secular changes presage increases in the prevalence of conditions associated with childhood and adolescent obesity-such as hypertension, glucose intolerance, and dyslipidemia-that may appear as early as the second decade of life.

Challenges and opportunities for promoting booster seat use: progressive dissemination of a high-threat message.

Motivating parents to take certain safety precautions when traveling with their children remains challenging for advocates. Caregivers of booster-aged children are particularly difficult to reach because they do not consider their children to be of "safety-seat" age and have inherently low perceptions of vulnerability to crash injury. Unfortunately, most booster seat programs fail to adequately motivate their intended population because they are primarily informational in nature and rely on caregivers to seek out and attend to the information. In this article, interventions using threat appeal tactics and progressive dissemination methods are recommended to effectively target participation and perceptions of vulnerability among this population. Recent research on risk communication indicates that threat appeals are supported when they contain high threat and high efficacy components. Threat appeal tactics are particularly desirable when perception of vulnerability is low, as is the case with parents of booster-aged children. In addition to theoretical arguments for more aggressive intervention approaches, a case example is presented wherein such techniques were used to promote booster seat use. The intervention resulted in significant increases in knowledge, risk-reduction attitudes, sense of efficacy, and observed booster seat use. Through use of progressive dissemination methods, the intervention has reached an audience of 431,600 people and counting.

Plasma homocysteine levels, methylene tetrahydrofolate reductase polymorphisms, and the risk of thromboembolism in children.

INTRODUCTION: Hyperhomocystenemia (HHcy) is a risk factor for thrombosis in adults. Polymorphisms in methylene tetrahydrofolate reductase (MTHFR) enzyme may cause HHcy. Data on their role in pediatric thromboembolism (TE) are sparse. MATERIALS AND METHODS: Charts of patients from 1989 to 2007, with documented TE, were reviewed. Homocysteine (Hcy) levels were defined both as per the adult normal range and the age-specific normal ranges from literature. RESULTS: A total of 141 patients (67 females, 74 males) were identified. With age-specific normal ranges for Hcy, 15 patients were found to have HHcy: 6 had CT, 9 patients had CC, and none had TT MTHFR genotype. When adult normal range was used, HHcy (>12 µmol/L) was seen in 7 patients: 4 had CT and 3 had the CC genotype. Again, none had TT genotype. In addition, the mean Hcy levels were unaffected by sex and ethnicities, but universal folic acid supplementation (post 1996) lowered the mean. CONCLUSIONS: (1) Age-specific ranges for Hcy should be used in pediatrics for accurate diagnosis of HHcy. (2) MTHFR C677T polymorphism is not a risk factor in pediatric TE. (3) Folic acid supplementation could play a role in lowering the prevalence of HHcy.

Measuring injury risk perceptions: feasibility of a Risk Estimation Scale.

OBJECTIVES: To develop a scale for measuring parental perceptions of childhood injury risk. METHODS: The Worry Assessment and Risk Estimation (WARE) Scale was administered to 256 parents/guardians to examine reliability, factor structure, and perception of risk. RESULTS: The WARE Scale has high internal consistency reliability (alpha = .89). Parents underestimated scenarios with high injury/death rates and overestimated scenarios with low injury/death rates. CONCLUSIONS: Risk estimation measures such as the WARE Scale have great potential as research tools and may be modified to suit researchers' needs.

Evaluation of the Boost 'em in the Back Seat Program: using fear and efficacy to increase booster seat use.

OBJECTIVES: Recent research supports the use of high-threat messages when they are targeted appropriately and designed to promote high efficacy as well as fear. This research examined the effectiveness of using a novel threat-appeal approach to encourage parents to place their children in booster seats and rear seats of vehicles. METHOD: A 6-min video-intervention was created and evaluated at after-school/daycare centers via an interrupted time series design with similar control sites for comparison. Caregivers (N=226) completed knowledge and practice surveys and fear and efficacy estimations related to childhood motor vehicle hazards. Researchers observed booster-seat and rear-seat use in study site parking lots. RESULTS: Compared to baseline and control assessments, the treatment groups' child passenger safety knowledge, risk-reduction attitudes, behavioral intentions, sense of fear related to the hazard, and sense of efficacy related to the recommended behaviors increased significantly. Further, observed overall restraint use and booster-seat use increased significantly following the intervention. CONCLUSIONS: Applying high-threat messages to child passenger safety interventions is promising and has the potential to be adapted to other health risk areas.

Pulmonary embolism-experience at a single children's hospital.

INTRODUCTION: Pulmonary embolism in children is a rare, potentially life threatening condition. The clinical characteristics of pediatric pulmonary embolism have not been well studied and the exact incidence in children is not known. We report a case series of fourteen patients with pulmonary embolism and describe their clinical characteristics. MATERIALS AND METHODS: Inpatient and outpatient clinic charts of patients with proven pulmonary embolism (PE) followed at the Hemostasis and Thrombosis Center at Children's Hospital of Michigan were reviewed for relevant clinical and laboratory information. RESULTS: All patients with PE were symptomatic but accurate diagnosis of PE was often delayed in the outpatient setting. Screening testing with D-dimer was normal in 40% of patients. Acquired risk factors and lower extremity clots were more common in patients analyzed. Treatment regimens differed but most patients had resolution of pulmonary emboli on follow-up. CONCLUSIONS: A high index of suspicion is needed for the diagnosis of pediatric PE. D-Dimer may be normal in some children with PE. Pediatric multicenter trials are needed to evaluate clinical characteristics, risk factors, long-term outcome and effects of PE on pulmonary and cardiac function.