Defining Natural History: Assessment of the Ability of College Students to Aid in Characterizing Clinical Progression of Niemann-Pick Disease, Type C

Niemann-Pick Disease, type C (NPC) is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease

Improving Pediatric Procedural Skills for EMS Clinicians: A Longitudinal Simulation-Based Curriculum with Novel, Remote, First-Person-View Video-Based Outcome Measurement

Objective Emergency medical services (EMS) clinicians are expected to provide expert care to all patients, but face obstacles in maintaining skillsets required in the care of critically ill or injured children. The objectives of this study were to describe and assess the effectiveness of a pediatric-focused, simulation-based, procedural training program for EMS clinicians, delivered on-site by a pediatric simulation education team. We also describe a novel, remote, asynchronous performance outcome measurement system using first-person-view video review. Methods This was a prospective study of simulation-based training and procedural outcomes. The study population involved EMS clinicians at three fire-based EMS agencies stratified as urban, suburban, and rural sites. The primary outcome was performance of intraosseous catheterization (IO), bag-valve-mask ventilation (BVM), and supraglottic device placement (SGD), measured across three time points. Secondary outcomes were identification of differences across EMS agencies and participant survey responses. Results We obtained video data from 122 clinicians, totalling 561 videos, with survey response rates of 89.0-91.3%. Pre-intervention scores were high: least-square means (95% confident-intervals) 9.5 (8.9, 10.2) for IO; 9.6 (9.3, 9.9) for BVM; and 11.6 (10.9, 12.2) for SGD. There was significant improvement post-intervention: 11.5 (10.7, 12.3) for IO; 11.0 (10.7, 11.4) for BVM; and 13.6 (12.8, 14.4) for SGD. Improvement was maintained at follow-up after a median of 9.5 months: 10.5 (9.8, 11.2) for IO; 10.2 (9.9, 10.6) for BVM; and 12.4 (11.7, 13.1) for SGD. There were no statistical differences between sites. Of survey respondents, half had not cared for a critically ill or injured child in at least a year, the vast majority had not had hands-on pediatric training in over 6 months, and the majority felt that training should occur at least every 6 months. Conclusions Our pediatric-focused, simulation-based procedural training program was associated with improvement and maintenance of high-baseline procedural performance for EMS clinicians over the study period. Findings were consistent across sites. Remote assessment was feasible. Participant surveys emphasized a desire for more pediatric-focused training and highlighted the low frequency of clinical exposure to procedures potentially needed in the care of critically ill or injured pediatric patients.</p

Gray Platelet Syndrome: Natural History Of A Large Patient Cohort And Locus Assignment To Chromosome 3P

Gray platelet syndrome (GPS) is an inherited bleeding disorder characterized by macrothrombocytopenia and absence of platelet alpha-granules resulting in typical gray platelets on peripheral smears. GPS is associated with a bleeding tendency, myelofibrosis, and splenomegaly. Reports on GPS are limited to case presentations. The causative gene and underlying pathophysiology are largely unknown. We present the results of molecular genetic analysis of 116 individuals including 25 GPS patients from 14 independent families as well as novel clinical data on the natural history of the disease. The mode of inheritance was autosomal recessive (AR) in 11 and indeterminate in 3 families. Using genome-wide linkage analysis, we mapped the AR-GPS gene to a 9.4-Mb interval on 3p21.1-3p22.1, containing 197 protein-coding genes. Sequencing of 1423 (69%) of the 2075 exons in the interval did not identify the GPS gene. Long-term follow-up data demonstrated the progressive nature of the thrombocytopenia and myelofibrosis of GPS resulting in fatal hemorrhages in some patients. We identified high serum vitamin B(12) as a consistent, novel finding in GPS. Chromosome 3p21.1-3p22.1 has not been previously linked to a platelet disorder; identification of the GPS gene will likely lead to the discovery of novel components of platelet organelle biogenesis. This study is registered at www.clinicaltrials.gov as NCT00069680 and NCT00369421. (Blood. 2010;116(23):4990-5001)WoSScopu