Adenosine-to-inosine (A-to-I) editing of RNA transcripts is an increasingly recognized cellular strategy to modulate the function of proteins involved in neuronal excitability. We have characterized the editing of transcripts encoding the ␣3 subunit of heteromeric GABA A receptors (Gabra3), in which a genomically encoded isoleucine codon (ATA) is converted to a methionine codon (ATI) in a region encoding the predicted third transmembrane domain of this subunit. Editing at this position (I/M site) was regulated in a spatiotemporal manner with ϳ90% of the Gabra3 transcripts edited in most regions of adult mouse brain, but with lower levels of editing in the hippocampus. Editing was low in whole-mouse brain at embryonic day 15 and increased during development, reaching maximal levels by postnatal day 7. GABA-evoked current in transfected cells expressing nonedited ␣3(I)␤3␥2L GABA A receptors activated more rapidly and deactivated much more slowly than edited ␣3(M)␤3␥2L receptors. Furthermore, currents from nonedited ␣3(I)␤3␥2L receptors were strongly outwardly rectifying (corresponding to chloride ion influx), whereas currents from edited ␣3(M)␤3␥2L receptors had a more linear current/voltage relationship. These studies suggest that increased expression of the nonedited ␣3(I) subunit during brain development, when GABA is depolarizing, may allow the robust excitatory responses that are critical for normal synapse formation. However, the strong chloride ion influx conducted by receptors containing the nonedited ␣3(I) subunit could act as a shunt to prevent excessive excitation, providing the delicate balance necessary for normal neuronal development.

Recurrent hospitalizations are responsible for considerable health care spending, although prior studies have shown that a substantial proportion of readmissions are preventable through effective discharge planning and patient follow-up after the initial hospital visit. This retrospective cohort study was undertaken to determine whether telephonic outreach to ensure patient understanding of and adherence to discharge orders following a hospitalization is effective at reducing hospital readmissions within 30 days after discharge. Claims data were analyzed from 30,272 members of a commercial health plan who were discharged from a hospital in 2008 to determine the impact of telephonic intervention on the reduction of 30-day readmissions. Members who received a telephone call within 14 days of discharge and were not readmitted prior to that call comprised the intervention group; all other members formed the comparison group. Multiple logistic regression was used to determine the impact of the intervention on 30-day readmissions, after adjusting for covariates. Results demonstrated that older age, male sex, and increased initial hospitalization length of stay were associated with an increased likelihood of readmission (P < 0.001). Receipt of a discharge call was associated with reduced rates of readmission; intervention group members were 23.1% less likely than the comparison group to be readmitted within 30 days of hospital discharge (P ¼ 0.043). These findings indicate that timely discharge follow-up by telephone to supplement standard care is effective at reducing near-term hospital readmissions and, thus, provides a means of reducing costs for health plans and their members. (Population Health Management

Escalating health care expenditures highlight the need to identify modifiable predictors of short-term utilization and cost. Thus, the predictive value of individual well-being scores was explored with respect to 1-year health care expenditures and hospital utilization among 2245 employees and members of a health plan who completed the Well-Being Assessment (WBA). The relationship between well-being scores and hospital admissions, emergency room (ER) visits, and medical and prescription expenditures 12-months post WBA was evaluated using multivariate statistical models controlling for participant characteristics and prior cost and utilization. An inverse relationship existed between well-being scores and all measured outcomes (P≤0.01). For every point increase in well-being on a 100-point scale, respondents were 2.2% less likely to have an admission, 1.7% less likely to have an ER visit, and 1.0% less likely to incur any health care costs. Among those who did incur cost, each point increase in well-being was associated with 1% less cost, and individuals with low well-being scores (≤50) had 2.7 times the median annual expenditure of individuals with high well-being (>75) ($5172 and $1885, respectively). Also, well-being proved lowest among respondents who incurred more than $20,000, and was highest among those who incurred ≤$5000, with median scores of 71.1 and 80.3, respectively. These results indicate that individual well-being is a strong predictor of important near-term health care outcomes. Thus, well-being improvement efforts represent a promising approach to decrease future health care utilization and expenditures.

Building upon extensive research from 2 validated well-being instruments, the objective of this research was to develop and validate a comprehensive and actionable well-being instrument that informs and facilitates improvement of well-being for individuals, communities, and nations. The goals of the measure were comprehensiveness, validity and reliability, significant relationships with health and performance outcomes, and diagnostic capability for intervention. For measure development and validation, questions from the Well-being Assessment and Wellbeing Finder were simultaneously administered as a test item pool to over 13,000 individuals across 3 independent samples. Exploratory factor analysis was conducted on a random selection from the first sample and confirmed in the other samples. Further evidence of validity was established through correlations to the established well-being scores from the Well-Being Assessment and Wellbeing Finder, and individual outcomes capturing health care utilization and productivity. Results showed the Well-Being 5 score comprehensively captures the known constructs within well-being, demonstrates good reliability and validity, significantly relates to health and performance outcomes, is diagnostic and informative for intervention, and can track and compare well-being over time and across groups. With this tool, well-being deficiencies within a population can be effectively identified, prioritized, and addressed, yielding the potential for substantial improvements to the health status, performance, and quality of life for individuals and cost savings for stakeholders. (Population Health Management 2014;17:357-365)

Tailored behavior change programs have proven effective at decreasing health risk factors, but the impact of such programs on participant well-being has not been tested. This randomized trial evaluated the impact of tailored telephone coaching and Internet interventions on health risk behaviors and individual well-being. Exercise and stress management were the primary health risks of interest; improvements in other health risk behaviors were secondary outcomes. A sample of 3391 individuals who reported health risk in the areas of exercise and stress management were randomly assigned to 3 groups: telephonic coaching that applied Transtheoretical Model (TTM) tailoring for exercise and minimal tailoring (stage of change) for stress management; an Internet program that applied TTM tailoring for stress management and minimal tailoring for exercise; or a control group that received an assessment only. Participants were administered the Well-Being Assessment and, at baseline, had relatively low well-being scores (mean, 60.9 out of 100 across all groups). At 6 months, a significantly higher percentage of both treatment groups progressed to the Action stage for exercise, stress management, healthy diet, and total number of health risks, compared to the control group. Both treatment groups also demonstrated significantly greater improvements on overall well-being and the domains of emotional health, physical health, life evaluation, and healthy behaviors. There were no differences between the groups for 2 well-being domains: basic access to needs and work environment. These results indicate that scalable, tailored behavior change programs can effectively reduce health risk and accrue to improved well-being for participants.