Crisis In Children Research Articles

Candidate Gene Associations with Vaso-Occlusive Crisis in Children with Sickle Cell Anemia Enrolled in the Multinational DOVE Trial

Introduction: Sickle cell disease (SCD) is complex, with marked inter-individual variability in disease severity. The clinical heterogeneity of SCD is largely influenced by genetic factors, including several well-established modifiers of fetal hemoglobin (HbF) levels within the beta globin locus, BCL11A, and HBS1L-MYB genes. However, little is known about genetic factors that may influence variability in treatment response, particularly in clinical trials assessing potential therapeutic agents for SCD. The DOVE (Determining Effects of Platelet Inhibition on Vaso-Occlusive Events) study was a multinational, phase 3, randomized, double-blinded, placebo-controlled trial evaluating the efficacy and safety of the antiplatelet agent prasugrel for the reduction of vaso-occlusive crisis (VOC) in children with sickle cell anemia (NCT01794000). Although the primary endpoint of reduction of rate of VOC did not reach statistical significance in the DOVE trial in the ITT population, a treatment effect of prasugrel was suggested in certain subgroups. The objective of this study was to evaluate candidate genetic variants with SCD severity and to assess impact of these variants on response to prasugrel, as measured by the frequency of VOC (composite of painful crisis and acute chest syndrome events) during the study period of up to 24 months.Methods: De-identified dried blood spot samples were collected for genetic analyses as per informed consent and study protocol. Genomic DNA was extracted from a 3 mm Whatman FTA card punch using Qiagen QIAamp DNA kit. A total of 313 (92%) DOVE patients (Hb SS or Hb S/β0 thalassemia) were genotyped using the TaqMan assay. After quality control, 253 patients and 28 variants were considered for genetic evaluation. These variants have been reported to be associated with SCD and/or its related comorbidities. All variants were analyzed for VOC in the prasugrel and placebo groups separately and for treatment by variant interactions in the overall study population. Variants were also assessed in the overall study population for associations with a hemolytic score, derived from 5 biomarkers of hemolysis and baseline hematologic markers including leukocyte, neutrophil, and platelet counts, and red cell mean corpuscular volume. All analyses were conducted using additive multivariate regression framework as the main model and were adjusted for age, race, geographic region, and hydroxyurea (HU) use at baseline. In addition, genotypic, dominant, and recessive models were evaluated as supportive analyses.Results: Two variants, rs7482144, located in the 5'- HBG2 gene promoter (-158 Xmn1) on chr 11 and rs1427407, located in the BCL11A gene on chr 2, were associated with VOC and a treatment interaction effect of prasugrel. HBG2 rs7482144, was associated with a significant decrease in frequency of VOC in prasugrel-treated patients relative to placebo (adjusted p=0.0065). The BCL11A rs1427407 variant was associated with an increase in VOC in prasugrel-treated patients relative to placebo (adjusted p=0.0205).No genetic associations were found with baseline composite hemolytic score in the overall population. However, significant associations with KLF-1, HBG2, and HBE variants were observed with individual hematologic markers. The KLF-1 variant (rs112631212) was associated with lower leukocyte (p<0.0001) and neutrophil (p=0.0002) counts in the subgroup of participants on HU; whereas the HBG2 (rs2070972; p=0.0116) and HBE (rs3834466 and rs7130110; p=0.0274 and p=0.0340 respectively) variants were associated with elevated platelet counts in the overall group.Conclusions: Given the study sample size, this study highlights the significance of HBG2 and BCL11A variants for the frequency of VOC in prasugrel-treated patients versus placebo. These variants have been reported in association with HbF/F-cells, an ameliorating factor for VOC that is only partly explained by endogenous levels of HbF. Our findings suggest that these variants may have contributed to the treatment-related effects of prasugrel on VOC outcomes in the DOVE trial. Identifying such genetic variants that are associated with differential response to treatment may help guide selection of patients for clinical trials based on predicted risk of VOC. DisclosuresHoppe:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Jakubowski:Eli Lilly and Company: Employment, Equity Ownership, Other: Former employee and minor shareholder of Eli Lilly and Company. Foster:Eli Lilly and Company: Employment, Equity Ownership, Other: Employee and minor shareholder of Eli Lilly and Company. Heath:Eli Lilly and Company: Employment, Equity Ownership, Other: Employee and minor shareholder of Eli Lilly and Company. Pillai:Eli Lilly and Company: Employment, Equity Ownership, Other: Employee and minor shareholder of Eli Lilly and Company. Pallav:Eli Lilly and Company: Employment, Equity Ownership, Other: Employee and minor shareholder of Eli Lilly and Company.

Topiramate in the treatment of Prader-Willi syndrome: A case report.

Prader-Willi syndrome (PWS), a neurologic disorder caused by a mutation of chromosome 15, is characterized by such symptoms as hypotonia, hypogonadism, hyperphagia, cognitive impairment, and difficult behaviors. One of the most concerning symptoms is hyperphagia, which can lead to uncontrolled obesity. Obesity is a major cause of increased morbidity and mortality in patients with PWS; however, diagnosing PWS early in life improves the prognosis. An 11-year-old African American boy with a past medical history significant for PWS, attention deficit/hyperactivity disorder, oppositional defiant disorder, obesity, and asthma was admitted after he became violent and destructive at his foster home while trying to get food. The patient had a 28-day stay on the children's crisis intervention unit where quetiapine was discontinued and he was maintained on clonidine 0.1 mg 3 times daily, hydroxyzine 25 mg in the morning and 50 mg at bedtime, montelukast 5 mg daily and titrated on methylphenidate 10 mg in the morning and 5 mg in the afternoon, topiramate 100 mg twice daily, and aripiprazole 10 mg twice daily. The patient displayed improved behavior control and less food-related aggression; he denied any side effects of medications. This case demonstrates the positive effects of topiramate for reducing aggression and demand for food in a child with PWS most likely due to an increase in satiety. It is hard to definitively attribute the positive response directly to topiramate. Further research should be conducted to determine if topiramate is an effective treatment option in these individuals.

Lactate Dehydrogenase: A Marker of the Severity of Vaso-Occlusive Crisis in Children with Sickle Cell Disease Presenting at the Emergency Department

The aim of this study was to describe the characteristics of vaso-occlusive crises (VOC) in children with sickle cell disease and to identify factors associated with greater severity. We performed a prospective observational study from August 2012 to January 2014. The study population comprised patients with sickle cell disease who consulted at the emergency department (ED) for VOC. We recorded demographic variables, history of complications related to the disease, and data on usual treatment. We also assessed pain, analgesia at home, need for admission, length of stay, and analgesia during admission. Analytical parameters were collected. A total of 29 patients with VOC were included. The patient’s usual treatment was hydroxyurea (HU) in 69.0%, and 7.0% required chronic transfusions. In the ED, 90.0% had moderate or severe pain, even though 86.0% had received analgesia at home (41.4% minor opioids). Overall, 27 of the 29 patients were admitted, and 56.0% needed major opioids. Higher lactate dehydrogenase (LDH) levels were related to the use of major opioids during admission (p = 0.038). A significant difference was recorded between the median number of days of admission for patients receiving non-steroidal anti-inflammatory drugs and for those requiring intravenous opioids (p = 0.005). Most patients with VOC were admitted to hospital. Lactate dehydrogenase level in the ED was a predictor of severity and was associated with the need for major opioids during admission and more days of admission.

Single Nucleotide Polymorphisms at +191 and +292 of Galectin-3 Gene (LGALS3) Related to Lower GAL-3 Serum Levels Are Associated with Frequent Respiratory Tract Infection and Vaso-Occlusive Crisis in Children with Sickle Cell Anemia.

IntroductionPatients with sickle cell anemia (SCA) may present chronic hemolytic anemia, vaso-occlusion and respiratory tract infection (RTI) episodes. Galectin-3 (GAL-3) is a multifunctional protein involved in inflammation, apoptosis, adhesion and resistance to reactive oxygen species. Studies point to a dual role for GAL-3 as both a circulation damage-associated molecular pattern and a cell membrane associated pattern recognition receptor.ObjectiveTo investigate associations between the SNPs of GAL-3 gene (LGALS3) and serum levels with RTI and vaso-occlusive crisis (VOC) in children with SCA.Materials and MethodsSNPs +191 and +292 in LGALS3 were studied using the TaqMan real-time PCR system; GAL-3 serum levels were measured by ELISA. The study included 79 children with SCA ranging from 2 to 12 years old.ResultsGAL-3 serum levels were associated with LGALS3 +191 and +292 genotypes (p <0.0001; p = 0.0169, respectively). LGALS3 +191, AA genotype was associated with low and CC with higher levels of GAL-3. For LGALS3 +292, the CC genotype was associated with lower GAL-3 and AA with higher levels. Patients with Frequency of RTI (FRTI) ≥1 presented higher frequency of +191AA (p = 0.0263) and +292AC/CC genotypes (p = 0.0320). SNP +292 was associated with Frequency of VOC (FVOC) (p = 0.0347), whereas no association was shown with SNP +191 and FVOC. However, CA/AC and AA/CC genotypes with lower GAL-3 levels showed a higher frequency in patients with FRTI ≥1 (p = 0.0170; p = 0.0138, respectively). Also, patients with FVOC ≥1 presented association with CA/AC (p = 0.0228). LGALS3 +191 and +292 combined genotypes related to low (p = 0.0263) and intermediate expression (p = 0.0245) were associated with FRTI ≥1. Lower GAL-3 serum levels were associated with FRTI ≥1 (p = 0.0426) and FVOC ≥1 (p = 0.0012).ConclusionVariation of GAL-3 serum levels related to SNPs at +191 and +292 may constitute a susceptibility factor for RTI and VOC frequency.

Embracing Comprehensive Mental Health and Social Services Programs to Serve Children Under California's Mental Health Services Act.

Authorized under California's Mental Health Services Act (MHSA) of 2004, full service partnership (FSP) programs address social welfare and other human service needs of seriously mentally ill adults and children who are especially socially and economically vulnerable or who are untreated or insufficiently treated. Because FSP enrollment should reflect greater individual and community distress, we investigated whether counties' enrollment of children into FSPs came from mental health system caseloads with higher crisis use, assessed trauma and substance abuse problems; and from counties which had more foster care placement, more child poverty, lower median household incomes and more unemployment. We addressed these questions in 36 counties over 34 quarters after MHSA's onset. Results indicated greater FSP enrollment for children was associated with higher county unemployment and foster care placement rates and with mental health systems which had increasing children's crisis rates over the study period. These findings suggest that underservice and community adversity prompt officials to adopt and make greater use of children's FSP programming, in keeping with MHSA's intensions.

A Multi-Center Randomized Controlled Trial of Intravenous Magnesium for Sickle Cell Pain Crisis in Children

Introduction: There are approximately 18,000 hospitalizations and 75,000 hospitalization days annually in the United States for children experiencing sickle cell vasoocclusive crises. Despite advances in the management of other comorbidities of sickle cell disease, little has changed in the management of sickle cell pain crises. Magnesium, a known vasodilator, anti-inflammatory and pain reliever, has the potential to alter the pathophysiology of pain crises, shortening length of stay and decreasing opioid use. A previous pilot study showed IV magnesium shortened length of stay compared to historical controls. A randomized trial conducted in Canada showed no decrease in length of stay with the use of intravenous magnesium. In the MAGiC (MAGnesium for children in Crisis) study, we hypothesized that the addition of intravenous (IV) magnesium to standard therapy would shorten hospital length of stay, result in decreased opioid use and improve quality of life for pediatric patients hospitalized with sickle cell pain crises.Methods: The MAGiC study was a multi-center, randomized, double-blind, placebo-controlled trial of IV magnesium versus normal saline for the treatment of pediatric sickle cell pain crisis conducted at 8 sites. Participating sites were members of the Pediatric Emergency Care Applied Research Network (PECARN), and collaborations between Pediatric Emergency Medicine physicians and Pediatric sickle cell experts facilitated enrollment. Children aged 4 to 21 years, with hemoglobin SS or hemoglobin SB° thalassemia were eligible if they required inpatient hospitalization after failing emergency department (ED) management for pain. Enrollment occurred at 8 sites between December 2010 and December 2013, with a total of 217 eligible site enrollment months. Children received 40 mg/kg of IV magnesium every eight hours for a total of 6 doses or normal saline placebo of equivalent volume (1 ml/kg). Randomization was stratified by site, age and hydroxyurea use. The primary outcome was length of stay from the time of first drug infusion until 12 hours after the last IV opioid dose or time of discharge, whichever occurred first. Secondary outcomes included opioid use, recorded as morphine equivalents, and quality of life, as measured using the PedsQL Sickle cell disease specific module, fatigue module and generic module. Side effects, specifically hypotension, weakness, warmth on infusion, or the development of acute chest syndrome (ACS) were documented. Using an intention-to-treat analysis, we compared length of stay using a Van Elteren test, stratified by the same factors used to stratify randomization.Results: 208 children were enrolled. Four children were excluded prior to receipt of any study drug, resulting in 101 children receiving magnesium and 103 receiving placebo. The 2 groups were similar with respect to age, sex ,genotype, weight, history of ACS or asthma, previous hospitalizations within the past three years and days of pain prior to arrival. The median time from first ED opioid to first study drug infusion was 7.4 hours, similar between the two groups. The median (interquartile range) length of stay was 56.0 (27.0 - 109.0) hours in the magnesium group compared to 47.0 (24.0 - 99.0) hours in the placebo group, p = 0.264. Patients who received magnesium received 1.46 mg/kg of morphine equivalents compared to 1.28 mg/kg in the placebo group (p=0.11). Quality of life scores were similar between the two groups after 48 hours on study drug and one week after discharge (p > 0.10 at both time points). Safety analysis revealed no differences in hypotension (3% for magnesium versus 1% for placebo) or weakness (7% versus 4%) between the 2 groups. Of those who received magnesium, 26% reported warmth on infusion compared to 2% of children who received placebo, p < .0001. Other adverse events, serious adverse events, and rehospitalizations within 7 days were similar between the groups.Conclusion: Intravenous magnesium does not shorten length of stay, lessen opioid use or improve quality of life in children who require hospitalization for sickle cell pain crisis. Close collaboration between Pediatric Emergency Medicine physicians and Pediatric Hematologists allows for the successful enrollment of large numbers of children in an acute intervention trial for children with sickle cell disease. DisclosuresOff Label Use: magnesium for sickle cell pain crisis.

Predictive Value of Pain Intensity in the Clinical Severity of Painful Crises in Children and Adolescents with Sickle Cell Diseases

Objectives: Painful crisis is a significant problem for patients with sickle cell diseases (SCD). We tried to understand whether or not there is an association between severity of pain and complication rate in hospitalized children and adolescents with SCD in the present study. Methods: All hospitalized SCD patients with painful crisis between September 2012 and September 2013 were included into the study. The intensity of pain was assessed at the first visit. Pain scores were obtained using the Faces Pain scale and Verbal Descriptor Scale. Severity of pain was divided into three groups as mild, moderate, and severe according to the scales. Results: Seventy-nine patients under the age of 18 years-old with SCD and 146 episodes of painful crisis were evaluated. Forty-five (57%) patients were women and mean age was 11.5 years. The white blood cell counts, aspartate aminotransferase and C-reactive protein (CRP) were significantly higher while erythrocytes, hemoglobin, hematocrit and albumin levels were significantly lower in the severe pain episodes group (p<0.05 for all). The number of patients transfused was significantly high in the severe pain episodes group than the other two groups (p=0.006, p=0.001). Most of severe pain episodes group had complicated vaso-occlusive crisis (acute chest syndrome 41.6 %, Hepatic sequestration crisis 6.7%), (p<0.05). Conclusion: There may be an direct relationship between prevalence of complicated vaso-occlusive crisis and pain intensity of SCD. Patients with sickle cell anemia should be classified according to their pain scores during hospitalization, and patients with high pain scores should be closely monitored for complications.

G186(P) An Audit of Management of Pain Crises in Children with Sickle Cell Disease

AimsSickle cell disease (SCD) is a lifelong haematological disorder resulting in anaemia and pain crisis. Specialist centres use experienced staff and accredited protocols to manage pain crises in affected children....

Does Time-to-Opioid Administration in the Emergency Department Affect Outcomes for Uncomplicated Acute Pain Crises in Children with Sickle Cell Disease?.

Abstract 2111▪▪This icon denotes a clinically relevant abstract Background:The acute painful crisis is the clinical hallmark of sickle cell disease (SCD). Recently, time-to-opioid administration (TTO) has been suggested as quality-of-care (QOC) measure for SCD patients with an acute painful crisis (Wang,Pediatrics,128:484,2011). We sought to determine whether TTO was associated with outcomes of emergency department (ED) visits for acute painful crisis. Methods:We conducted a retrospective cohort study of ED visits for acute painful crisis to Children’s Medical Center Dallas between 1/1/2008 and 12/31/2010. Potential subjects were identified by query of hospital administrative records using all ICD-9CM codes for SCD (282.41, 282.42, and 282.6x) as either the primary or a secondary diagnosis. We included patients with any SCD genotype between 5 and 18 years of age. Records of all potential subjects were reviewed to determine whether the episode represented an acute painful crisis, defined as the recent onset of acute pain not explained by other mechanisms. We excluded patients with confounding sources of pain (e.g., headache and gallstones), patients transferred from other medical centers, and patients who had a surgical procedure within 2 weeks of presentation. We also excluded patients who received a simple transfusion in the preceding 30 days or were part of a chronic transfusion program in the preceding 6 months. The primary predictor variable was TTO in minutes, analyzed continuously and in quartiles. The primary outcome variable was hospital admission with secondary outcomes of change in pain scores 1 & 2, area under the curve (AUC) for pain scores at 4 hours (pain score AUC), and length of stay in the ED (ED LOS) in minutes. Univariate mixed regression (logistic for admission, linear for other outcome variables), including patient random effects, was used to test for association between TTO and other relevant covariates with the outcome variables. Variables with P-values <0.10 in the univariate regression models were subsequently evaluated in multivariate mixed models. Results:From 2,866 ED visits in 2008–2010, 177 subjects were identified with 416 presentations for acute painful crisis treated with IV opioids. 47% of subjects were female and 65% had HbSS/HbSβ0. The primary outcome, inpatient admission, occurred in 53% of ED visits. The median TTO was 86 minutes (intraquartile range (IQR) 54 – 130 minutes) and was not different between those admitted and not admitted to the hospital (not admitted - 86.5 minutes, (IQR 56.5, 126.5); admitted - 85.5 minutes, (IQR 50.5, 130)). TTO (both as a continuous and categorical variable) was not associated with inpatient admission in either univariate or multivariate analyses. In multivariate analyses with secondary outcomes, TTO was associated with change in pain scores 1 & 2, pain score AUC at 4 hours, and ED LOS. After adjusting for age and initial pain score, decreased TTO was independently associated with a decrease in pain scores 1 & 2 (referent - TTO Quartile 4 (>131 minutes) vs Quartile1 (<56 minutes), β coefficient = 0.49, 95% Confidence Interval (CI) [0.08, 0.89], p=0.019). After adjusting for age, decreased TTO was independently associated with a decreased pain score AUC (referent - TTO Quartile 4 vs Quartile 1, β coefficient = −81, 95% CI [−153, −9], p=0.027). Finally, after adjusting for admission status, decreased TTO was independently associated with decreased ED LOS (referent – TTO Quartile 4 vs Quartile 1, β coefficient = −131, 95% CI [−191, −72], p=<0.001). Conclusions:For acute painful crisis, TTO in the ED setting has been suggested as a QOC measure. While TTO is not associated with our primary outcome, inpatient admission, it is independently associated three other important outcomes: change in pain scores 1 & 2, pain score AUC, and ED LOS. The association of the process measure, TTO, with these outcomes increases the appeal for its use in broader sickle cell populations and should lead to necessary steps to reduce TTO in the ED setting. Subsequent studies should investigate TTO in other SCD populations including adults, examine determinants of prolonged TTO, and study interventions designed to reduce TTO in various ED settings. Disclosures:No relevant conflicts of interest to declare.

Trivalent Inactivated Influenza Vaccine Is Not Associated With Sickle Cell Crises in Children

Children with sickle cell disease are considered at high risk for complications from influenza infection and are recommended to receive annual influenza vaccination. However, data on the safety of influenza vaccination in children with sickle cell anemia are sparse. Using a retrospective cohort of children aged 6 months to 17 years in 8 managed care organizations that comprise the Vaccine Safety Datalink and who had a diagnosis of sickle cell anemia from 1999 to 2006, we conducted matched case-control and self-controlled case series studies to examine the association of trivalent inactivated influenza vaccination with hospitalization for sickle cell crisis in the 2 weeks after vaccination. From an original pool of 1085 pediatric subjects with a diagnosis of sickle cell anemia, we identified 179 children with at least 1 sickle cell crisis during any influenza season (October 1-March 31). In the matched case-control study (matching on age category, gender, Vaccine Safety Datalink site, and season), the odds ratio of hospitalization for a crisis in vaccinated compared with unvaccinated children was not significant: 1.3 (95% confidence interval 0.8-2.2). In the self-controlled case series study of hospitalized cases, the incident rate ratio for hospitalization with sickle cell crisis in the 2 weeks after trivalent inactivated influenza vaccination was also not significant: 1.2 (95% confidence interval 0.75-1.95). This large cohort study did not find an association of influenza vaccination and hospitalization for sickle cell crises in children with sickle cell anemia.

Trivalent Inactivated Influenza Vaccine Is Not Associated With Sickle Cell Crises in Children

Trivalent Inactivated Influenza Vaccine Is Not Associated With Sickle Cell Crises in Children

Drug Treatment of Hypertensive Crisis in Children

Hypertensive crisis is a relatively rare event and is associated with significant morbidity and mortality in adults and pediatric patients alike. Rapid, safe, and effective treatment is imperative to alleviate immediate presenting clinical symptoms, prevent devastating morbidity, preserve long-term quality of life, and prevent mortality. Many medications in the hypertensive crisis arsenal have been used for nearly half a century. Nearly all treatment options have been utilized in children for decades, yet reliable data and sound clinical literature remain elusive. Every agent considered to be a first-line, second-line, or adjunctive option has yet to be evaluated in a randomized controlled trial in pediatric patients. With a paucity of clinical data to form evidence-based decisions, the clinician must rely entirely on the extrapolation from adult data and small retrospective studies, case series, and case reports of medication use in pediatric patients. Although more research in the treatment of pediatric hypertensive crisis is desperately needed, current practice demands a sharp knowledge of the pediatric clinical literature and pharmacology in this area as an essential tool to consistently improve patient outcomes with respect to morbidity and mortality.

Promoting Children's Well‐being: Policy Lessons from Past and Present Economic Crises

This article reviews evidence from historical crisis episodes from four geographical regions to identify patterns in how economic crises shape dimensions of child wellbeing. The analysis is motivated by a concern to identify possible policy lessons of relevance to the 2007‐ financial crisis and its impacts on children and their caregivers. We conclude that while broad counter‐cyclical economic and social policy responses are key to minimising vulnerability in both the short and longer terms, unless such responses are informed by an understanding of age‐ and gender‐specific vulnerabilities they are unlikely to adequately address the multi‐dimensionality of children's crisis experiences. This is especially the case with child protection and mental and emotional well‐being deficits.

Responding to the Crisis in Children's Mental Health: Potential Roles for the Counseling Profession

Mental health concerns pose a substantial threat to the immediate and future health of children and their functioning at home, at school, and in the community. Research indicates that 1 in 5 children has a diagnosable mental or addictive disorder and 1 in 10 has a serious emotional disturbance. This review considers emerging trends, national initiatives, and the roles of related professions in responding to the crisis in children's mental health. Recommendations are offered for counseling practice, training, leadership, and research.

Table of Contents

AbstractThe Tricky Balance of Ethics and Treatment: A Case ExampleAn Asperger's Diagnosis and Success in Individual TherapyAACAP Responds to ADHD Follow‐Up StudyRoutine Depression Screening for TeensPTSD and Increased Risk for Suicidal EventsSuicidal Events During Early Antidepressant TreatmentAnger Control Training for Teens with Tourette's SyndromeIntelligence in PDD‐NOS, ADHD or a Combined DiagnosisThe Economic Crisis is Our Children's Crisis Too

A Study to Overcome the Crisis of Children's Art Making through Small Group Project

A Study to Overcome the Crisis of Children's Art Making through Small Group Project

Day Hospital Approach to Uncomplicated Vaso-Occlusive Crises in Children with Sickle Cell Disease.

Day hospital management for patients with sickle cell disease experiencing uncomplicated vaso-occlusive pain crises has been described in adult populations as an alternative care delivery system. To date, there are no published studies addressing the utility of this model in pediatric populations. We retrospectively studied all admissions to the Day Hospital at the Texas Children's Sickle Cell Center since its inception in 2000. A Day Hospital admission was defined as a minimum of two consecutive days of aggressive pain management as an outpatient, including intravenous hydration and analgesics, supported by home treatment over night with oral analgesic and anti-inflammatory agents. We gathered data on demographics, sickle cell genotype, incoming pain scale, provider type (physician versus nurse practitioner), home treatment with narcotics prior to presentation, average daily dose of narcotics administered during admission, length of stay, admission charges, return rate to the emergency department within 48 hrs, and transfer rate from Day Hospital to inpatient care. A total of 35 patients accounted for 80 visits during the study period (2000–2006). Approximately 83% of patients had sickle cell anemia (HbSS). The mean baseline hemoglobin for patients was 9.1 g/dl. Patients were seen equally by physicians and nurse practitioners. Approximately 93% of visits were preceded by home narcotic use within 24hrs of presentation. The mean incoming pain score was 7.9 on a scale from 1 to 10. The mean length of stay was 2.4 days. The return rate for emergency care within 48 hours was 6%. Approximately 40% of patients admitted to the Day Hospital were transferred to inpatient care for unresolved pain or increasing medical needs. We conclude that a dedicated Day Hospital facility has the potential to provide patient-centered, effective, and timely management of vaso-occlusive crises in children as well as adults. It may serve as an alternative to emergency and inpatient care for children with mild to moderate pain. Future studies should compare day hospital care to inpatient hospitalization for differences in length of stay, cost, patient satisfaction, and quality of life.

Decline of Acute Encephalopathic Crises in Children with Glutaryl-CoA Dehydrogenase Deficiency Identified by Newborn Screening in Germany

Glutaryl-CoA dehydrogenase (GCDH) deficiency is a rare neurometabolic disorder that is considered treatable if patients are identified before the onset of acute encephalopathic crises. To allow early identification of affected individuals, tandem mass spectrometry-based newborn screening for GCDH deficiency has been started in Germany in 1999. We prospectively followed neonatally screened patients (n=38) and compared the neurologic outcome with patients from a historical cohort (n=62). In the majority of neonatally screened children, the onset of encephalopathic crises has been prevented (89%), whereas acute encephalopathic crises or progressive neurologic impairment was common in the historical cohort. Neonatal screening in combination with intensive management is effective--even assuming ascertainment bias in the historical cohort. Similar proportions of commonest mutations and biochemical phenotypes (high and low excretors) were found in neonatally screened and historical patients. However, potential predictor variables for mild clinical phenotypes are not yet known and thus a selection of these patients by newborn screening is not excluded. No patient was known to be missed by newborn screening from 1999 to 2005. In conclusion, this study confirms that newborn screening for GCDH deficiency in combination with intensive management is beneficial.

Inefficacy of Piracetam in the Prevention of Painful Crises in Children and Adolescents with Sickle Cell Disease

Analgesia and hydration remain the only safe treatment for painful crises of sickle cell disease; hydroxyurea is effective, but the toxicity is still a problem. Piracetam is a nootropic drug that has reportedly been effective and non-toxic in sickle cell patients, but most studies were not placebo-controlled and included a small number of patients. The present study evaluated the drug in a double-blind crossed placebo-controlled clinical trial in 73 children and adolescents suffering from moderate to severe painful crises for 13 months. Information regarding frequency and severity of pain was acquired through monthly clinical evaluation, visits and house calls, and 4,300 weekly questionnaires filled out by the patients in their domiciles. A monthly pain score was calculated for each patient. Pain was the most frequent adverse manifestation of the disease stressing its significant bio-psycho-social impact. Although nearly all patients and relatives reported a better clinical course throughout the whole study, the drug was ineffective in the prevention of painful crises. This placebo effect may be ascribed to an unplanned and unsystematic ‘cognitive-behavioural’ management of the children. The pain score in the second semester of the study – both in the experimental and in the control groups – was significantly smaller than that in the first semester. In conclusion, piracetam was found to be ineffective in the prevention of painful crises; a powerful placebo effect due to adequate patient care was demonstrated.

Acute Hepatic Crisis in Children With Sickle Cell Disease

Acute Hepatic Crisis in Children With Sickle Cell Disease