Impact of individualized pain plan on the emergency management of children with sickle cell disease.

BACKGROUND: Vaso-occlusive crisis (VOC) the hallmark of sickle cell disease (SCD) is often treated inadequately in the emergency department (ED). We hypothesized that pain management plans individualized for each patient can improve pain management and lead to high levels of patient satisfaction. PROCEDURE: Starting in 2002, we treated all patients with SCD reporting to Children's Hospital of Pittsburgh (CHP) ED with VOC using a structured algorithm. We recorded regimens used successfully for each patient as an "individualized pain plan" and implemented it during subsequent VOC visits and adjusted it to patient response. We compared rates of hospitalization following an ED visit with VOC and readmission within 1 week after discharge for CHP with that of four comparable hospitals from Pediatric Health Information (PHIS) database. Patients and parents completed surveys of satisfaction with pain management and with care. RESULTS: Between 2002 and 2008 there was a greater decline in the rate of admission of patients presenting to the ED at CHP (78% to 52%) as compared to PHIS (71% to 68%), (P < 0.05) and readmission rates at CHP (7.3% to 3.2%) as compared to PHIS (6.5% to 5.1%) (P < 0.05). Improvement in pain score during ED management was 2.0 or more on a Wong Baker scale of 0-5 (P < 0.01). Participants on average, rated quality of pain management as very good or higher. CONCLUSION: Individualized pain management plans in the ED are effective in delivering high quality management of VOC and are associated with a high level of patient satisfaction and decreased avoidable hospitalizations.

An assessment of time involved in pre-test case review and counseling for a whole genome sequencing clinical research program.

Whole genome sequencing (WGS) is being used for evaluation of individuals with undiagnosed disease of suspected genetic origin. Implementing WGS into clinical practice will place an increased burden upon care teams with regard to pre-test patient education and counseling about results. To quantitate the time needed for appropriate pre-test evaluation of participants in WGS testing, we documented the time spent by our clinical research group on various activities related to program preparation, participant screening, and consent prior to WGS. Participants were children or young adults with autism, intellectual or developmental disability, and/or congenital anomalies, who have remained undiagnosed despite previous evaluation, and their biologic parents. Results showed that significant time was spent in securing allocation of clinical research space to counsel participants and families, and in acquisition and review of participant's medical records. Pre-enrollment chart review identified two individuals with existing diagnoses resulting in savings of $30,000 for the genome sequencing alone, as well as saving hours of personnel time for genome interpretation and communication of WGS results. New WGS programs should plan for costs associated with additional pre-test administrative planning and patient evaluation time that will be required to provide high quality care.

Towards a Universal Clinical Genomics Database: the 2012 International Standards for Cytogenomic Arrays Consortium Meeting.

The 2012 International Standards for Cytogenomic Arrays (ISCA) Consortium Meeting, "Towards a Universal Clinical Genomic Database," was held in Bethesda, Maryland, May 21-22, 2012, and was attended by over 200 individuals from around the world representing clinical genetic testing laboratories, clinicians, academia, industry, research, and regulatory agencies. The scientific program centered on expanding the current focus of the ISCA Consortium to include the collection and curation of both structural and sequence-level variation into a unified clinical genomics database, available to the public through resources such as the National Center for Biotechnology Information's ClinVar database. Here, we provide an overview of the conference, with summaries of the topics presented for discussion by over 25 different speakers. Presentations are available online at www.iscaconsortium.org.

Girls with Seizures Due to the c.320A>G Variant in ALG13 Do Not Show Abnormal Glycosylation Pattern on Standard Testing.

A girl with early onset severe epilepsy, developmental delay, intellectual disability, visual maturation delays, and feeding problems was without a diagnosis despite an extensive genetic and metabolic evaluation. She initially manifested infantile spasms which responded to high-dose ACTH. Seizures seemed to resolve, but then at age 5, she developed complex partial seizures resistant to antiepileptics that responded to a ketogenic diet. Additional features included visual impairment, hypotonia, reflux, and severe feeding problems requiring a G-tube. She was referred to the Geisinger Health System whole-genome sequencing clinical research program. A variant in the X-linked gene ALG13 (c.320A->G p. 107 N->S) was identified. Four additional girls from three published exome sequencing studies were found to have the identical c.320A>G variant in ALG13. All presented with early onset severe epilepsy and intellectual disability. Three of the five exhibited visual impairment and possible developmental regression. A boy with a variant in ALG13 presented with a severe congenital disorder of glycosylation type Is. Glycosylation studies in the case reported here were normal; none of the other girls reported in the literature have had glycosylation studies. X-inactivation studies have not been done. The N107 residue and the surrounding region - MNNHQ - are highly conserved across species and are found in a presumed functional domain of this glycotransferase superfamily. The consistent clinical presentation of a severe phenotype in girls coupled with identical variants in an X-linked gene strongly suggests a critical position effect. Negative glycosylation studies in one individual suggest the possibility of a new mechanism requiring investigation.