Karen Rychlik

The course of childhood‐onset epilepsy over the first two decades: A prospective, longitudinal study

Determine frequency of remissions, relapses, and pharmacoresistance over two decades. Develop a composite measure of seizure control over that time.

Complete remission of childhood-onset epilepsy: stability and prediction over two decades

The ultimate seizure outcome of childhood epilepsy is complete resolution of all seizures without further treatment. How often this happens and how well it can be predicted early in the course of epilepsy could be valuable in helping families understand the nature of childhood epilepsy and what to expect over time. In the Connecticut study of epilepsy, a prospective cohort of 613 children with newly-diagnosed epilepsy (onset age 0-15 years), complete remission, ≥5 years both seizure-free and medication-free, was examined as a proxy of complete seizure resolution. Predictors at initial diagnosis were tested. Information about seizure outcomes within 2 years and from 2-5 years after diagnosis was sequentially added in a proportional hazards model. The predictive value of the models was determined with logistic regression. Five hundred and sixteen subjects were followed ≥10 years. Three hundred and twenty-eight (63%) achieved complete remission; 23 relapsed. The relapse rate was 8.2 per 1000 person-years and decreased over time: 10.7, 6.7, and 0 during first 5 years, the next 5 years, and then >10 years after complete remission (P=0.06 for trend). Six participants regained complete remission; 311 (60%) were in complete remission at last contact. Baseline factors predicting against complete remission at last contact included onset age≥10 years (hazard ratio=0.55, P=0.0009) and early school or developmental problems (hazard ratio=0.74, P=0.01). Factors predicting for complete remission were uncomplicated epilepsy presentation (hazard ratio=2.23, P<0.0001), focal self-limited epilepsy syndrome (hazard ratio=2.13, P<0.0001), and uncharacterized epilepsy (hazard ratio=1.61, P=0.04). Remission (hazard ratio=1.95, P<0.0001) and pharmaco-resistance (hazard ratio=0.33, P<0.0001) by 2 years respectfully predicted in favour and against complete remission. From 2 to 5 years after diagnosis, relapse (hazard ratio=0.21, P<0.0001) and late pharmaco-resistance (hazard ratio=0.21, P=0.008) decreased and late remission (hazard ratio=2.40, P<0.0001) increased chances of entering complete remission. The overall accuracy of the models increased from 72% (baseline information only), to 77% and 85% with addition of 2-year and 5-year outcomes. Relapses after complete remission are rare making this an acceptable proxy for complete seizure resolution. Complete remission after nearly 20 years is reasonably well predicted within 5 years of initial diagnosis.

The Use of Family Conferences in the Pediatric Intensive Care Unit

BACKGROUND Data about pediatric intensive care unit (PICU) family conferences (FCs) are needed to enhance our understanding of the role of FCs in patient care and build a foundation for future research on PICU communication and decision making. OBJECTIVE The studys objective was to describe the use and content of PICU FCs. DESIGN The study design was a prospective chart review comparing patients who had conferences with those who did not, and a sub-analysis of patients with chronic care conditions (CCCs). SETTING/SUBJECTS The study setting was an academic PICU from January 2011 through June 2011. MEASUREMENTS Medical events under consideration were placement of tracheostomy or gastrostomy tube; initiation of chronic ventilation; palliative care involvement; use of extracorporeal membrane oxygenation, continuous renal replacement, or cardiopulmonary resuscitation; care limitation orders; death; length of stay; and discharge to a new environment. RESULTS From 661 admissions, we identified 74 conferences involving 49 patients. Sixty-four conferences (86%) were held about 40 patients with CCCs. Having a conference was associated with (p<0.05): length of PICU admission; palliative care involvement; initiation of chronic ventilation; extracorporeal membrane oxygenation; cardiopulmonary resuscitation; death; discharge to a new environment; and care limitation orders. Twenty-nine percent of patients who had a new tracheostomy or gastrostomy tube placed had a conference. We identified two categories of discussion topics: information exchange and future management. CONCLUSIONS Most identified FCs involved complex patients or patients who faced decisions affecting the childs quality of life or dying. For many patients who faced life changing decisions we did not identify a FC. Further research is needed to understand how to best utilize FCs and less formal conversations.

Metabolic alterations in children with obstructive sleep apnea

IMPORTANCE The incidence of obesity is rising in the United States and has been linked to Obstructive Sleep Apnea (OSA) even in young children. Understanding the role that obesity and OSA play in alterations in metabolic variables that can lead to serious health issues is essential to the care and counseling of affected children. OBJECTIVES To evaluate the association of alterations in metabolic variables, including insulin resistance, to OSA in young, obese children. DESIGN Retrospective, case-control series. SETTING Tertiary care childrens hospital. PARTICIPANTS Obese children aged 2-12 years who had undergone overnight polysomography and routine laboratory testing for lipid levels, fasting glucose, and insulin from January 1, 2006 to December 31, 2012 were identified from a TransMed Bio-Integration Suite and Epics clarity database search. RESULTS A total of 76 patients were included for analysis. Forty-three (56.6%) were male, and the mean age was 8.3±2.5 years (range, 2.4-11.9 years). The mean body mass index (BMI) z score was 2.8±0.75 (range, 1.7-6.3), and all patients were obese (BMI z score>95th percentile). Twenty two patients (28.9%) had an apnea-hypopnea index (AHI) <1/h (no OSA), 27 (35.5%) an AHI≥1<5/h, 12 (15.8%) had an AHI ≥5<9.99/h, and 15 (19.7%) had an AHI≥10/h. There was no significant difference in total cholesterol, triglycerides, high and low density lipoprotein levels, systolic and diastolic blood pressure in those patients with or without OSA. Fasting insulin, blood glucose, and homeostasis model assessment (HOMA) were significantly higher in patients with OSA compared to those with no OSA (p<0.01). AHI correlated to alterations in insulin as well as glucose homeostasis on multivariate analysis. Results from logistic regression analysis showed that fasting insulin (p<0.01), and HOMA (p<0.01) predicted severe OSA independent of age, gender, and BMI z score in these patients. CONCLUSION Metabolic alterations in glucose and insulin levels, known to be associated with obesity and increased risk for cardiovascular disease, appear to relate to the severity of OSA in young children.

Health-related quality of life and adherence to hydroxyurea in adolescents and young adults with sickle cell disease

Complications related to sickle cell disease (SCD) result in significant declines in health‐related quality of life (HRQOL). While hydroxyurea reduces SCD complications, adherence remains suboptimal. The studys objectives were to assess the feasibility of Internet‐based electronic assessment of HRQOL in SCD clinic and to examine the relationship between HRQOL and hydroxyurea adherence in adolescents and young adults (AYAs) with SCD.

Nausea Predicts Delayed Gastric Emptying in Children

OBJECTIVES To assess whether the gastroparesis cardinal symptom index (GCSI), or any individual symptom, is associated with delayed gastric emptying in children, and to assess understanding of symptoms associated with delayed gastric emptying. STUDY DESIGN Fifty children (36 F), 5-18 years of age, undergoing gastric emptying scintigraphy (GES) at Lurie Childrens Hospital in Chicago, Illinois, completed Likert-type GCSI and symptom comprehension questionnaires. Correlation of GES results (normal or abnormal) with questionnaire results using the Wilcoxon rank sum test. RESULTS Seventy percent of subjects had a normal GES. Children reported understanding most terms of GCSI (average score 2.59, range 0-3). The GCSI was not associated with delayed gastric emptying. Nausea was associated with delayed gastric emptying only (numerical P = .04, word P = .02). Results were not altered when poorly understood terms were excluded. CONCLUSIONS The GCSI is not associated with delayed gastric emptying in children. Lack of association does not seem to be related to lack of understanding. Nausea alone was the only symptom that showed an association with delayed gastric emptying on GES.

Barriers to hydroxyurea adherence and health-related quality of life in adolescents and young adults with sickle cell disease

To identify barriers to hydroxyurea adherence (negative beliefs, access, and/or recall barriers), and their relationship to adherence rates and health‐related quality of life (HRQOL) among adolescents and young adults (AYA) with sickle cell disease (SCD).

Determinants of Social Outcomes in Adults With Childhood-onset Epilepsy.

BACKGROUND: Adults with childhood-onset epilepsy experience poorer adult social outcomes than their peers. The relative roles of seizures over time versus learning and psychiatric problems are unclear. METHODS: We examined independent influences of psychiatric and learning disorders and of seizure course in 241 young adults (22–35 years old) with uncomplicated epilepsy in a longitudinal community-based cohort study. Social outcomes were ascertained throughout the study. A history of psychiatric and learning problems was ascertained ∼9 years after study entry. Seizure course was: “Excellent,” no seizures after the first year, in complete remission at last contact (N = 95, 39%); “Good,” seizures occurred 1 to 5 years after diagnosis, in complete remission at last contact (N = 56, 23%); “Fluctuating,” more complicated trajectories, but never pharmacoresistant (N = 70, 29%); “Pharmacoresistant,” long-term pharmacoresistant (N = 20, 8%). Multiple logistic regression was used to identify contributors to each social outcome. RESULTS: Better seizure course predicted college completion, being either employed or pursuing a degree, and driving, but was not substantially associated with other social outcomes. Poorer seizure course was associated with a greater likelihood of having offspring, particularly in women without partners. Learning problems, psychiatric disorders, or both negatively influenced all but 2 of the social outcomes. CONCLUSIONS: In young adults with uncomplicated epilepsy, the course of seizures contributed primarily to education, employment, and driving. A history of learning problems and psychiatric disorders adversely influenced most adult outcomes. These findings identify potential reasons for vocational and social difficulties encountered by young adults with childhood epilepsy and areas to target for counseling and transition planning.

Prevalence of BK polyomavirus infection and association with renal dysfunction in pediatric heart transplant recipients

BACKGROUND BK polyomavirus (BKV) infection and nephropathy complicate renal allografts; however, their effect in the native kidneys of pediatric heart transplant (HTx) recipients is unknown. We assessed the prevalence of BKV infection and its association with kidney dysfunction in survivors of pediatric HTx. METHODS A single-center retrospective study compared pediatric (aged <18 years ) HTx recipients, with and without BKV (controls), who received an allograft from May 1989 to July 2013. Screening of urine for BKV was performed in patients with chronic kidney disease (CKD) stage ≥2 since 2006, and since April 2012 in all HTx recipients at least at an annual evaluation. Serum for BKV DNA was assayed if BK viruria was present. Data collected included recipient and donor demographics, the immunosuppressive regimen, and history of Epstein-Bar virus (EBV) and cytomegalovirus infection. Statistics included Fishers exact test, chi-square test, Students t-test, and multivariate logistic regression. RESULTS Of 98 eligible recipients, 83 (85%) were screened: 28 (34%) had BK viruria, and 7 had BK viremia. One viremic patient had biopsy-proven BKV nephropathy that progressed to end-stage renal disease. Risk factors for BK viruria were (1) longer duration since HTx (6.02 vs 2.95 years; p = 0.01), (2) worsening estimated glomerular filtration rate (71.3 vs 86.3 ml/min/1.73 m(2), p = 0.03), (3) history of EBV infection (p = 0.0002), and (4) use of sirolimus (p = 0.0003). After multivariate logistic-regression, only history of EBV infection remained associated with BKV infection (p = 0.015). CONCLUSIONS BKV may lead to BK viremia and BK nephropathy in pediatric HTx patients. Routine screening for BK viruria should be considered.

Growth and Obesity Among Older Single Ventricle Patients Presenting for Fontan Conversion.

Introduction: Long-term growth outcomes and the prevalence of obesity among older single ventricle (SV) patients have not been well characterized. We investigated these parameters, as well as the impact of obesity on survival, in an older cohort of SV patients presenting for Fontan conversion. Methods: We analyzed preoperative height, weight, and body mass index (BMI) of patients who underwent Fontan conversion. Overweight and obese were defined as BMI ≥85 percentile and ≥95 percentile for patients <20 years and BMI 25 to 30 kg/m2 and ≥30 kg/m2 for patients ≥20 years, respectively. Postoperative transplant-free survival was assessed among obese, overweight, and normal weight patients. Results: We evaluated 139 patients presenting for Fontan conversion at a median age of 23.2 years. Patients had shorter stature compared to the normal population (mean Z score −0.6, P < .001). Younger patients had lower BMI compared to the normal population (<20 years: mean Z score −0.5, P = .02), while older patients had elevated BMI (≥20 years: mean Z score +0.4, P < .001). The mean BMI among older patients approached overweight at 24.6 kg/m2. The prevalence of obesity increased with advancing age, with 36% overweight and 14% obese at >30 years. At a median of 8.2 years following Fontan conversion, obesity and overweight status were not associated with transplant-free survival. Conclusion: Older SV patients presenting for Fontan conversion had shorter stature compared to the normal population as well as a high prevalence of overweight and obesity. Although there was no relationship between weight status and early postoperative survival, further investigation of long-term outcomes is warranted.