Micro RNAs comprise a large family of small, functional RNAs with important roles in the regulation of protein coding genes in animals and plants. Here we show that human and mouse miRNA22 precursor molecules are subject to posttranscriptional modification by A-to-I RNA editing in vivo. The observed editing events are predicted to have significant implications for the biogenesis and function of miRNA22 and might point toward a more general role for RNA editing in the regulation of miRNA gene expression.

Single nucleotide polymorphisms (SNPs) are DNA sequence variations that can affect the expression or function of genes. As a result, they may lead to phenotypic differences between individuals, such as susceptibility to disease, response to medications, and disease progression. Millions of SNPs have been mapped within the human genome providing a rich resource for genetic variation studies. Adenosine-to-inosine RNA editing also leads to the production of RNA and protein sequence variants, but it acts on the level of primary gene transcripts. Sequence variations due to RNA editing may be misannotated as SNPs when relying solely on expressed sequence data instead of genomic material. In this study, we screened the human SNP database for potential cases of A-to-I RNA editing that cause amino acid changes in the encoded protein. Our search strategy applies five molecular features to score candidate sites. It identifies all previously known cases of editing present in the SNP database and successfully uncovers novel, bona fide targets of adenosine deamination editing. Our approach sets the stage for effective and comprehensive genome-wide screens for A-to-I editing targets.

This study aimed to quantify the indirect costs of sickle cell disease in the United States.Methods: Adult patients from a sickle cell disease clinic at an urban academic healthcare system completed an adapted Institute for Medical Technology Assessment Productivity Cost Questionnaire related to the impact of their disorder on absenteeism, presenteeism, ability to contribute through unpaid work outside of employment, and other aspects of life. Additional data were collected from patient records about each participant's genotype, total hemoglobin level, and pain level.Results: Of the 192 individuals, 187 who completed the survey reported experiencing vaso-occlusive crisis pain events during the last year that negatively affected their productivity at work and in daily roles. Three-fourths of respondents reported impairment in their ability to complete everyday tasks, such as caring for children, running errands, doing housework, shopping for groceries, and volunteer (unpaid) work. Only 30% of respondents reported being employed or self-employed. Of those employed, estimated costs of absenteeism and presenteeism attributable to pain events averaged $15 103 per person annually. Estimated total annual losses in unpaid work productivity averaged $3 145 862 for the study respondents and another $2 870 652 for their caregivers.Conclusions: Sickle cell disease affected the work productivity, nonwork productivity, and the daily lives of adults seen with the disorder in an academic medical center.

Spontaneous haemorrhage in patients with haemophilia is generally considered to occur randomly and without a predictable temporal or seasonal pattern; however, there is a lack of evidence in the literature on the effects of weather, temperature and atmosphere on bleeding episodes. This post hoc analysis of a multicentre, open-label crossover study examined the influence of seasonality on bleeding frequency and patient-assessed pain in patients with moderately severe and severe (FIX C ≤ 2%) haemophilia B. Fifty patients were enrolled and treated on-demand for 16 weeks; 47 were subsequently randomized to one of two prophylactic regimens (nonacog alfa 100 IU kg−1 once weekly or 50 IU kg−1 twice weekly) for 16 weeks. Patients then underwent an 8-week washout period of on-demand therapy before being crossed over to the other prophylactic regimen for 16 weeks. Bleeding episodes during the on-demand treatment periods were analysed. To assess for temporal trends, data were graphed as scatter plots. The primary end point was the annualized bleeding rate (ABR). Additional measures included raw and median pain scores during every joint bleeding event (spontaneous or traumatic), with pain scored using the Brief Pain Inventory (0 = ‘no pain’ to 10 = ‘pain as bad as you can imagine’). The observed ABRs during the on-demand periods showed no distinguishable trend over time. Analysis of pain associated with joint bleeding episodes also did not demonstrate any discernible temporal trend. No apparent seasonal variation in bleeding pattern or patient-reported pain was observed in this analysis of patients with haemophilia B.

4699 Background Retrospective data analysis is relatively inexpensive & allows evaluation of rare conditions such as Vaso Occlusive Crisis (VOC) of Sickle Cell Disease (SCD) with ease, as compared to conducting actual prospective studies. A particularly useful application of a retrospective data analysis is to act as a pilot study that can be completed in anticipation of a prospective study. The analysis can help to identify feasibility issues & factors which affect study outcomes that need to be adjusted for in prospective studies. Objective To identify health outcome measures employed in retrospective database analysis of individuals suffering from VOC of SCD, from reviewed literature. Method Potentially relevant articles were searched electronically using terms related to VOC & pain crisis in SCD, across PubMed, COCHRANE & CINAHL databases. Dissertations, guidelines to management of VOC, abstracts, conference proceedings & case reports were excluded for lack of sufficient information. Reference lists of prior literature reviews, as well as reference lists of studies included in this review, served to identify additional articles. However, review articles were not included for further analyses. Studies analyzing retrospective databases such as chart reviews, hospital records, electronic medical records (EMR), claims data, health care cost & utilization project database (HCUP) were included for further analyses. Studies qualifying for full review were searched for relevant clinical, humanistic, economic outcomes & clinical endpoints, which have previously been defined elsewhere. Result 1,917 potentially relevant study abstracts were reviewed. Of which, 13 studies qualified for further analyses. 8 clinical outcomes, 6 humanistic outcomes, 3 economic outcomes & 1 clinical endpoint were found. Codes used to identify patients with VOC of SCD in claims databases were (282.42), (282.60), (282.62), (282.64) & (282.69). Four studies used HCUP database, 3 studies used EMRs, & 2 studies each used Medicaid claims data, chart reviews & hospital records for retrospective assessment of a VOC event. Majority of the studies captured length of stay (LOS) (8 studies) & readmission rates (5 studies) as clinical outcomes measure while Wong-Baker Faces scale in children (2 studies) & Numeric Rating scale (2 studies) in adults, were most common measures recorded. Type of hospital admission, type of SCD admission, severity of pain, age, hemoglobin count & polymorphonuclear leukocyte count, associated significantly with length of stay in patients with VOC of SCD (Table 1). Disease severity, severity of pain, use of steroids, age, type of visits & having co-morbid history of asthma associated significantly with 14- & 30-day readmission rates. Number of pain episodes, intensity of pain, LOS, presence of Human Platelet Alloantigen polymorph (HPA-3), amount of analgesic administered, cost of healthcare & 14- & 30-day readmission rates were found to be significant predictors of severity of a VOC (Table 2). Conclusion Research evidence available, while scarce, is applicable, in population of all ages with VOC of SCD. Findings suggest using LOS & readmission rates for assessment of a VOC event in a retrospective database as well as prospective studies aimed to assess treatment efficacies. Care should be taken during design of pilot & retrospective studies to ensure collection & adjustment for variables known to associate significantly with LOS & readmission rate before reaching a clinical conclusion. Further research is necessary to support the use of suggested retrospective indicators of a VOC event. Disclosures: Shafer: Pfizer: Employment. Sivamurthy:Pfizer: Employment. Kollmer:Pfizer: Employment, Equity Ownership. Vendetti:Pfizer: Employment.