Ethanol-Induced Behavioral Sensitization Alters the Synaptic Transcriptome and Exon Utilization in DBA/2J Mice.

Alcoholism is a complex behavioral disorder characterized by loss of control in limiting intake, and progressive compulsion to seek and consume ethanol. Prior studies have suggested that the characteristic behaviors associated with escalation of drug use are caused, at least in part, by ethanol-evoked changes in gene expression affecting synaptic plasticity. Implicit in this hypothesis is a dependence on new protein synthesis and remodeling at the synapse. It is well established that mRNA can be transported to distal dendritic processes, where it can undergo localized translation. It is unknown whether such modulation of the synaptic transcriptome might contribute to ethanol-induced synaptic plasticity. Using ethanol-induced behavioral sensitization as a model of neuroplasticity, we investigated whether repeated exposure to ethanol altered the synaptic transcriptome, contributing to mechanisms underlying subsequent increases in ethanol-evoked locomotor activity. RNAseq profiling of DBA/2J mice subjected to acute ethanol or ethanol-induced behavioral sensitization was performed on frontal pole synaptoneurosomes to enrich for synaptic mRNA. Genomic profiling showed distinct functional classes of mRNA enriched in the synaptic vs. cytosolic fractions, consistent with their role in synaptic function. Ethanol sensitization regulated more than twice the number of synaptic localized genes compared to acute ethanol exposure. Synaptic biological processes selectively perturbed by ethanol sensitization included protein folding and modification as well as and mitochondrial respiratory function, suggesting repeated ethanol exposure alters synaptic energy production and the processing of newly translated proteins. Additionally, marked differential exon usage followed ethanol sensitization in both synaptic and non-synaptic cellular fractions, with little to no perturbation following acute ethanol exposure. Altered synaptic exon usage following ethanol sensitization strongly affected genes related to RNA processing and stability, translational regulation, and synaptic function. These genes were also enriched for targets of the FMRP RNA-binding protein and contained consensus sequence motifs related to other known RNA binding proteins, suggesting that ethanol sensitization altered selective mRNA trafficking mechanisms. This study provides a foundation for investigating the role of ethanol in modifying the synaptic transcriptome and inducing changes in synaptic plasticity.

Vaccine Coverage for United States Infants at Milestone Ages: Missed Opportunities for Vaccination.

We used a claims database to assess coverage for rotavirus (RV), diphtheria-tetanus-acellular pertussis, and pneumococcal conjugate vaccines among infants in the United States. Similar coverage was seen until 7 months of age, after which RV coverage lagged. Missed opportunities for vaccination at well-child visits were found to vary by age.

Family impact of Rotavirus Gastroenteritis in Taiwan and Vietnam: an Ethnographic Study.

BACKGROUND: Prior to the introduction of rotavirus vaccines, rotavirus was the leading cause of severe gastroenteritis in infants and young children, and it continues to be the leading cause in countries without vaccination programs. Rotavirus gastroenteritis results in substantial economic burden and has a pronounced effect on the family of those who are ill. Both in Taiwan and in Vietnam, rotavirus illness is viewed as a priority disease. This study assessed, in Taiwan and Vietnam, the impact of rotavirus gastroenteritis on the family among a group of parents whose children had recently been hospitalized for this illness. METHODS: In the first half of 2013, parents of children who had been hospitalized due to rotavirus infection were recruited from hospitals in Taiwan (n = 12) and Vietnam (n = 22), and participated in focus group sessions or in-depth ethnographic interviews. RESULTS: In both countries, the results point to a substantial burden on the parents concerning emotions and logistics of daily tasks, and to considerable disruptions of the family routine. Taiwanese parents reported satisfaction with the health care system, a great deal of effort to suppress emotions, a fair amount of knowledge about rotavirus, and little extra costs related to the illness. On the other hand, parents in Vietnam expressed concern about the emotional well-being of and the health care treatments for their children, were less knowledgeable regarding rotavirus infection, and experienced a substantial financial burden due to indirect costs that were related to accessing treatment. CONCLUSIONS: Families in Taiwan and Vietnam suffer from a considerable economic and emotional burden related to rotavirus gastroenteritis. One way to substantially reduce this burden is to provide universal and affordable rotavirus vaccination to susceptible children, especially since cost-effectiveness studies have demonstrated that universal vaccination would be safe and efficacious against severe rotavirus gastroenteritis in these countries.

Applying the new genomics to alcohol dependence.

This review summarizes the proceedings of a symposium presented at the "Alcoholism and Stress: A Framework for Future Treatment Strategies" conference held in Volterra, Italy on May 6-9, 2014. The overall goal of the symposium titled "Applying the New Genomics to Alcohol Dependence", chaired by Dr. Adron Harris, was to highlight recent genomic discoveries and applications for profiling alcohol use disorder (AUD). Dr. Sean Farris discussed the gene expression networks related to lifetime consumption of alcohol within human prefrontal cortex. Dr. Andrzej Pietrzykowski presented the effects of alcohol on microRNAs in humans and animal models. Alcohol-induced alterations in the synaptic transcriptome were discussed by Dr. Michael Miles. Dr. Pietro Sanna examined methods to probe the gene regulatory networks that drive excessive alcohol drinking, and Dr. Samir Zakhari served as a panel discussant and summarized the proceedings. Collectively, the presentations emphasized the power of integrating multiple levels of genetics and transcriptomics with convergent biological processes and phenotypic behaviors to determine causal factors of AUD. The combined use of diverse data types demonstrates how unique approaches and applications can help categorize genetic complexities into relevant biological networks using a systems-level model of disease.

Cost effectiveness of a pentavalent rotavirus vaccine in Oman.

BACKGROUND: Rotavirus gastroenteritis (RGE) is the leading cause of diarrhea in young children in Oman, incurring substantial healthcare and economic burden. We propose to formally assess the potential cost effectiveness of implementing universal vaccination with a pentavalent rotavirus vaccine (RV5) on reducing the health care burden and costs associated with rotavirus gastroenteritis (RGE) in Oman METHODS: A Markov model was used to compare two birth cohorts, including children who were administered the RV5 vaccination versus those who were not, in a hypothetical group of 65,500 children followed for their first 5 years of life in Oman. The efficacy of the vaccine in reducing RGE-related hospitalizations, emergency department (ED) and office visits, and days of parental work loss for children receiving the vaccine was based on the results of the Rotavirus Efficacy and Safety Trial (REST). The outcome of interest was cost per quality-adjusted life year (QALY) gained from health care system and societal perspectives. RESULTS: A universal RV5 vaccination program is projected to reduce, hospitalizations, ED visits, outpatient visits and parental work days lost due to rotavirus infections by 89%, 80%, 67% and 74%, respectively. In the absence of RV5 vaccination, RGE-related societal costs are projected to be 2,023,038 Omani Rial (OMR) (5,259,899 United States dollars [USD]), including 1,338,977 OMR (3,481,340 USD) in direct medical costs. However, with the introduction of RV5, direct medical costs are projected to be 216,646 OMR (563,280 USD). Costs per QALY saved would be 1,140 OMR (2,964 USD) from the health care payer perspective. An RV5 vaccination program would be considered cost saving, from the societal perspective. CONCLUSIONS: Universal RV5 vaccination in Oman is likely to significantly reduce the health care burden and costs associated with rotavirus gastroenteritis and may be cost-effective from the payer perspective and cost saving from the societal perspective.

Cost-effectiveness of pneumococcal vaccines for adults in the United States.

INTRODUCTION: In 2012, the Advisory Committee on Immunization Practices (ACIP) revised recommendations for adult pneumococcal vaccination to include a sequential regimen of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) for certain high-risk adults with immunocompromising conditions. This study, from a payer perspective, examined: (1) the cost-effectiveness of the new 2012 ACIP vaccine policy recommendation relative to the 1997 ACIP recommendation; (2) the cost-effectiveness of potential future pneumococcal vaccination policies; and (3) key assumptions that influence study results. METHODS: A static cohort model that incorporated costs, health outcomes, and quality-adjusted life-year (QALY) losses associated with invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia (NBPP) was developed to evaluate seven pneumococcal vaccination strategies for a 50-year-old adult cohort over a 50-year period using incremental cost-effectiveness ratios (ICERs). RESULTS: For objective 1, the 2012 ACIP recommendation is the more economically efficient strategy (ICER was $25,841 per QALY gained vs. no vaccination). For objective 2, the most efficient vaccination policy would be to maintain the 2012 recommendation for PPSV23 for healthy and immunocompetent adults with comorbidities, and to modify the recommendation for adults with immunocompromising conditions by replacing PPSV23 with a sequential regimen of PCV13 and PPSV23 at age 65 (ICER was $23,416 per QALY gained vs. no vaccination). For objective 3, cost-effectiveness ratios for alternative pneumococcal vaccine policies were highly influenced by assumptions used for vaccine effectiveness against NBPP and accounting for the herd protection effects of pediatric PCV13 vaccination on adult pneumococcal disease. CONCLUSION: Modifying the 2012 recommendation to include an additional dose of PCV13 at age 65, followed by PPSV23, for adults with immunocompromising conditions appears to be a cost-effective vaccine policy. Given the uncertainty in the available data and the absence of key influential data, comprehensive sensitivity analyses should be conducted by policy-makers when evaluating new adult pneumococcal vaccine strategies.

Differential expression of the alternatively spliced OPRM1 isoform µ-opioid receptor-1K in HIV-infected individuals.

OBJECTIVE: We previously examined the expression of specific C-terminal µ-opioid receptor (MOR) splice variants in human central nervous system cell types and HIV-infected brain tissue from individuals with neurocognitive impairment ±â€ŠHIV encephalitis (HIVE). In the present study, we examined the N-terminal splice variant MOR-1K, which mediates excitatory cellular signaling. METHODS AND RESULTS: We found segregation of expression ranging from undetectable to seemingly exclusive across nervous system cell types compared to the pool of C-terminal MOR splice variants using the real-time polymerase chain reaction (RT-PCR). Expression of MOR-1K mRNA was also increased in HIV-infected individuals with combined neurocognitive impairment and HIVE compared with the other groups. MOR-1K expression correlated with the level of patient neurocognitive impairment, whereas the pool of C-terminal MOR splice variants did not. HIVE was also associated with increased expression of the inflammatory mediators MCP-1, MCP-2, and RANTES, but not the host HIV coreceptors CXCR4 and CCR5 or the CD4 receptor using qRT-PCR. Network analysis of microarray data from these same patients revealed filamin A (FLNA) as a possible interaction partner with MOR-1K, and FLNA gene expression was also found to be upregulated in HIVE using qRT-PCR. Overexpression of FLNA in HEK293 cells redistributed MOR-1K from intracellular compartments to the cell surface. CONCLUSION: These results suggest that HIVE, and neurocognitive impairment depending on its severity, are associated with enhanced MOR-1K signaling through both increased expression and trafficking to the cell surface, which may alter the contribution of MOR receptor isoforms and exacerbate the effects of MOR activation in neuroAIDS.

Mitochondrial genome sequences and comparative genomics of Achlya hypogyna and Thraustotheca clavata.

As a lineage, oomycetes have adapted to a wide range of lifestyles. Although the common ancestor of the group was likely a marine pathogen, extant members inhabit a spectrum from free-living saprobes to obligate biotrophs. The mitochondrial genomes of Achlya hypogyna and Thraustotheca clavata were sequenced to directly compare a facultative parasitic species (A. hypogyna) to a closely related free living saprobe (T. clavata). Both sequenced mitochondrial genomes are circular, with sizes of 46,869 bp for A. hypogyna and 47,381 bp for T. clavata. They share 63 common genes, indicating little influence of lifestyle on gene content, but small differences in total number and order of genes. Achlya hypogyna has a single copy of nad2, whereas T. clavata has one pseudogene (rps7) and two duplicated genes (nad5 and nad2), each with one full and one truncated copy. The genomes encode a total of 29 or 30 tRNAs (A. hypogyna and T. clavata, respectively) for 19 amino acids. Three unidentified open reading frames are conserved, and one is unique to T. clavata. Comparisons of these genomes with published sequences of the closely related Saprolegnia ferax mitochondrial genome, and four other more distantly related oomycetes, reveals no correlation in genome content or architecture with lifestyle.

Cost-effectiveness of a pentavalent rotavirus vaccine in Japan.

OBJECTIVE: To evaluate the impact of universal vaccination with a pentavalent rotavirus vaccine (RV5) on the healthcare burden and costs associated with rotavirus gastroenteritis (RGE) in Japan. METHODS: The model included a hypothetical cohort of 1,091,156 children followed for their first 5 years of life. In the absence of universal vaccination, there were 19 deaths, 78,000 hospitalizations, and 678,000 outpatient visits due to RGE. The efficacy of RV5 is based on international clinical trial data, which was similar to the efficacy observed in clinical trials conducted in Japan. The primary outcome measure is the cost per quality-adjusted-life-year (QALY) gained. In the base case, the QALY loss per 1000 RGE episodes included 2.2 for children and 1.8 per parent. RESULTS: Universal vaccination is projected to reduce hospitalizations by 92%, outpatient visits by 74%, and work-loss days by 73%. For the base case analysis, the total vaccination cost was ¥26 billion. The estimated reduction in medical costs was ¥16 billion. Of 2500 QALYs gained with the vaccination program, approximately half are directly attributed to the child. In the base case analysis, the incremental cost-effectiveness ratio (ICER) for vaccination vs. no vaccination is ¥4 million and ¥2 million per quality-adjusted life year (QALY) gained from the healthcare payer and societal perspectives, respectively. The ICERs are ¥8 million and ¥4 million if parental disutilities are excluded. KEY LIMITATION: The QALY decrements for children and parents were evaluated using different instruments, and the QALY decrements do not vary based on episode severity. Given the interdependence between children and their parents, excluding parental disutilities may under-estimate the impact of RGE. CONCLUSION: Universal vaccination with RV5 in Japan is projected to have a substantial public health impact and may be cost-effective from both the payer and societal perspectives if parental disutilities are included in the cost-effectiveness ratios.

Factors associated with receipt of two doses of varicella vaccine among adolescents in the United States.

BACKGROUND: In 2006, routine two-dose varicella vaccination for all children was recommended, including a second dose catch-up program for older children and adolescents. Recent studies have shown that a second dose of the vaccine provides incremental protection against varicella disease. METHODS: This study is a cross-sectional analysis of data collected in the National Immunization Survey-Teen 2010 combined with publicly available data related to state immunization requirements. Bivariate and multivariable logistic regression analyses were performed to examine individual-level and state-level factors associated with receipt of two doses of varicella vaccine among 10,542 adolescents 13 to 17 years of age with no history of varicella. RESULTS: Overall, 58.1% of adolescents without any history of varicella had received two doses of varicella vaccine. Coverage varied widely among states, ranging from 19.7% in South Dakota to 85.3% in Rhode Island. In the multivariable model, receipt of two doses of varicella vaccine was significantly associated with younger age, higher maternal education level, private health insurance, more frequent health care visits, receipt of both quadrivalent meningococcal conjugate and tetanus, diphtheria, and acellular pertussis vaccinations, and residing in a state with two-dose policies for middle school entry. Vaccines for Children program-eligible adolescents were less likely to have received two doses. CONCLUSION: Two-dose varicella vaccination coverage remained low among adolescents in 2010, despite the universal recommendation. Programs that are aimed specifically at Vaccines for Children program-eligible adolescents, state policies requiring two doses for middle school entry, and broad education and implementation of the adolescent vaccination platform may help to improve varicella vaccination coverage.

Burden of rotavirus gastroenteritis and distribution of rotavirus strains in Asia: a systematic review.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea in children worldwide. We systematically reviewed the burden of rotavirus gastroenteritis (RVGE) and distribution of rotavirus strains in Asia. METHODS: We searched MEDLINE, EMBASE and the World Health Organization (WHO) website for the term "rotavirus" and the name of each country. We included studies that were conducted in children between 2000 and 2011 and that examined the epidemiology, health and/or economic burden of RVGE, and G and P-type distribution in Eastern, South East, Southern and Central Asia. Random effects models were used to pool the proportions of RVGE. We also estimated child mortality due to RVGE using the updated WHO and United Nations Children's Fund's mortality estimates in 2008. RESULTS: The search identified 113 eligible articles. The incidence rates of rotavirus-related hospitalizations in children under 5 years of age ranged from 2.1 to 20.0 cases per 1000 children per year with the highest rates reported in Bangladesh, South Korea, Taiwan, Thailand, and Vietnam. Rotavirus accounted for 37.5% of year-round hospitalized gastroenteritis cases, with higher proportions reported in South East Asia. Rotavirus was associated with approximately 145,000 deaths every year in Asia, with the greatest numbers occurring in India, Pakistan, and Indonesia. The highest annual societal costs of treating RVGE were reported in China (US$365 million), followed by Japan (US$254 million) and India (US$41-72 million). A diversity of rotavirus G and P-types was observed across Asia and the distribution of strains differed by country and year. The most common strains were G1P[8] (23.6%), G2P[4] (11.8%), G3P[8] (18.9%), and G9P[8] (7.4%). CONCLUSIONS: Rotavirus is associated with substantial hospitalizations and deaths among children and causes large healthcare expenditures throughout Asia. Safe and effective rotavirus vaccines could substantially reduce the burden of disease.

Genetic structure and the North American postglacial expansion of the barnacle, Semibalanus balanoides.

Population genetic characteristics are shaped by the life-history traits of organisms and the geologic history of their habitat. This study provides a neutral framework for understanding the population dynamics and opportunities for selection in Semibalanus balanoides, a species that figures prominently in ecological and evolutionary studies in the Atlantic intertidal. We used mitochondrial DNA (mtDNA) control region (N = 131) and microsatellite markers (∼40 individuals/site/locus) to survey populations of the broadly dispersing acorn barnacle from 8 sites spanning 800 km of North American coast and 1 site in Europe. Patterns of mtDNA sequence evolution were consistent with larger population sizes in Europe and population expansion at the conclusion of the last ice age, approximately 20 000 years ago, in North America. A significant portion of mitochondrial diversity was partitioned between the continents (ϕ(ST) = 0.281), but there was only weak structure observed from mtDNA within North America. Microsatellites showed significant structuring between the continents (F(ST) = 0.021) as well as within North America (F(ST) = 0.013). Isolation by distance in North America was largely driven by a split between populations south of Cape Cod and all others (P < 10(-4)). The glacial events responsible for generating allelic diversity at mtDNA and microsatellites may also be responsible for generating selectable variation at metabolic enzymes in S. balanoides.

Cost-effectiveness of stockpiling 23-valent pneumococcal polysaccharide vaccine to prevent secondary pneumococcal infections among a high-risk population in the United States during an influenza pandemic.

BACKGROUND: Secondary bacterial infections (especially pneumococcal infections) were a major cause of death during prior influenza pandemics. One strategy to prevent pneumococcal infections in adults during a future pandemic is to stockpile 23-valent pneumococcal polysaccharide vaccine (PPSV23). Stockpiling a pneumococcal vaccine can ensure that it is available when needed most-that is, at the onset of a pandemic. OBJECTIVE: The purpose of this article was to project the health and economic impact of stockpiling PPSV23 to prevent secondary pneumococcal infections among high-risk adults aged 18 to 64 years during an influenza pandemic within the United States. METHODS: A cost-effectiveness model was developed to evaluate the health and economic effects of stockpiling PPSV23 versus not stockpiling this vaccine for preventing secondary pneumococcal infections among 20 million high-risk US adults aged 18 to 64 years during an influenza pandemic. The model was used to project the number of pneumococcal cases, hospitalizations, deaths, and days of work loss averted. Three health outcomes (deaths, hospitalizations, and outpatient care) were estimated from secondary pneumococcal infections. To assess the overall effectiveness of the different strategies, the quality-adjusted life-year (QALY) was used as a measure of these 3 health outcomes. The results are presented for 3 scenarios based on the pandemic severity and anticipated prepandemic influenza vaccine availability: base case, more-severe case, and less-severe case. RESULTS: In the base-case scenario, vaccinating 20 million high-risk adults with PPSV23 avoided 2858 deaths, 878 hospitalizations, 41,881 pneumococcal pneumonia cases, and 232,891 days of work loss during a pandemic. Under the more-severe case scenario, vaccination avoided 21,921 deaths, 10,280 hospitalizations, 70,345 pneumococcal cases, and approximately 1.12 million days of work loss. Under the less-severe case scenario, pneumococcal vaccination avoided 715 deaths, 219 hospitalizations, 10,470 pneumococcal cases, and 58,235 days of work loss. The incremental cost-effectiveness ratio for stockpiling PPSV23 versus no stockpiling for the base-case and less-severe case scenarios was $39,946 and $198,653 per QALY, respectively. For the more-severe case scenario, stockpiling PPSV23 was cost saving. Probabilistic sensitivity analyses found that the range of incremental cost-effectiveness ratio values was broad due to the large uncertainty regarding the timing and impact of the next pandemic. In addition, the shelf life of PPSV23 and stockpile management substantially influenced the cost-effectiveness ratio. CONCLUSIONS: For severe pandemics or pandemics in which prepandemic influenza vaccine is unavailable, stockpiling of PPSV23 can be a cost-effective strategy for reducing the health and economic burden associated with secondary pneumococcal infections in a high-risk US population. However, for a mildly severe pandemic in which prepandemic influenza vaccine is available, stockpiling of PPSV23 may not be cost-effective.

New vaccines against otitis media: projected benefits and cost-effectiveness.

OBJECTIVE: New vaccines that offer protection against otitis media caused by nontypeable Haemophilus influenzae and by Moraxella catarrhalis are under development. However, the potential health benefits and economic effects of such candidate vaccines have not been systematically assessed. METHODS: We created a computerized model to compare the projected benefits and costs of (1) the currently available 7-valent pneumococcal conjugate vaccine, (2) a candidate pneumococcal-nontypeable H influenzae vaccine that has been tested in Europe, (3) a hypothetical pneumococcal-nontypeable H influenzae-Moraxella vaccine, and (4) no vaccination. The clinical probabilities of acute otitis media and of otitis media with effusion were generated from multivariate analyses of data from 2 large health maintenance organizations and from the Pittsburgh Child Development/Otitis Media Study cohort. Other probabilities, costs, and quality-of-life values were derived from published and unpublished sources. The base-case analysis assumed vaccine dose costs of $65 for the 7-valent pneumococcal conjugate vaccine, $100 for the pneumococcal-nontypeable H influenzae vaccine, and $125 for the pneumococcal-nontypeable H influenzae-Moraxella vaccine. RESULTS: With no vaccination, we projected that 13.7 million episodes of acute otitis media would occur annually in US children aged 0 to 4 years, at an annual cost of $3.8 billion. The 7-valent pneumococcal conjugate vaccine was projected to prevent 878,000 acute otitis media episodes, or 6.4% of those that would occur with no vaccination; the corresponding value for the pneumococcal-nontypeable H influenzae vaccine was 3.7 million (27%) and for the pneumococcal-nontypeable H influenzae-Moraxella vaccine was 4.2 million (31%). Using the base-case vaccine costs, pneumococcal-nontypeable H influenzae vaccine use would result in net savings compared with nontypeable 7-valent pneumococcal conjugate use. Conversely, pneumococcal-nontypeable H influenzae-Moraxella vaccine use would not result in savings compared with pneumococcal-nontypeable H influenzae vaccine use, but would cost $48 000 more per quality-adjusted life-year saved. The results were sensitive to variations in assumptions on vaccine effectiveness and vaccine dose costs but not to variations in other assumptions. CONCLUSIONS: New candidate vaccines against otitis media have the potential to prevent millions of disease episodes in the United States annually. If priced comparably with other recently introduced vaccines, these new otitis vaccines could achieve cost-effectiveness comparable with or more favorable than that of the 7-valent pneumococcal conjugate vaccine.

Non-traditional settings for influenza vaccination of adults: costs and cost effectiveness.

OBJECTIVE: Influenza vaccination rates remain far below national goals in the US. Expanding influenza vaccination in non-traditional settings such as worksites and pharmacies may be a way to enhance vaccination coverage for adults, but scant data exist on the cost effectiveness of this strategy. The aims of this study were to (i) describe the costs of vaccination in non-traditional settings such as pharmacies and mass vaccination clinics; and (ii) evaluate the projected health benefits, costs and cost effectiveness of delivering influenza vaccination to adults of varying ages and risk groups in non-traditional settings compared with scheduled doctor's office visits. All analyses are from the US societal perspective. METHODS: We evaluated the costs of influenza vaccination in non-traditional settings via detailed telephone interviews with representatives of organizations that conduct mass vaccination clinics and pharmacies that use pharmacists to deliver vaccinations. Next, we constructed a decision tree to compare the projected health benefits and costs of influenza vaccination delivered via non-traditional settings or during scheduled doctor's office visits with no vaccination. The target population was stratified by age (18-49, 50-64 and >or=65 years) and risk status (high or low risk for influenza-related complications). Probabilities and costs (direct and opportunity) for uncomplicated influenza illness, outpatient visits, hospitalizations, deaths, vaccination and vaccine adverse events were derived from primary data and from published and unpublished sources. RESULTS: The mean cost (year 2004 values) of vaccination was lower in mass vaccination (dollars US 17.04) and pharmacy (dollars US 11.57) settings than in scheduled doctor's office visits (dollars US 28.67). Vaccination in non-traditional settings was projected to be cost saving for healthy adults aged >or=50 years, and for high-risk adults of all ages. For healthy adults aged 18-49 years, preventing an episode of influenza would cost dollars US 90 if vaccination were delivered via the pharmacy setting, dollars US 210 via the mass vaccination setting and dollars US 870 via a scheduled doctor's office visit. Results were sensitive to assumptions on the incidence of influenza illness, the costs of vaccination (including recipient time costs) and vaccine effectiveness. CONCLUSION: Using non-traditional settings to deliver routine influenza vaccination to adults is likely to be cost saving for healthy adults aged 50-64 years and relatively cost effective for healthy adults aged 18-49 years when preferences for averted morbidity are included.

Using electronic medical records to enhance detection and reporting of vaccine adverse events.

We implemented an automated vaccine adverse event surveillance and reporting system based in an ambulatory electronic medical record to improve underreporting and incomplete reporting that prevails in spontaneous systems. This automated system flags potential vaccine adverse events for the clinician when a diagnosis is entered, prompts clinicians to consider the vaccine as a cause of the condition, and facilitates reporting of suspected adverse events to the Vaccine Adverse Event Reporting System (VAERS). During five months, a total of 33,420 vaccinations were administered during 14,466 encounters. There were 5,914 follow-up contacts by vaccinees within 14 days of the vaccination visits; 686 (11.6%) generated an alert. Clinicians submitted VAERS reports for 23 of these (0.69 per 1,000 vaccine doses), which is almost 6 times the dose-based reporting rate to VAERS. (1) Clinician surveys indicated that it took a minimal amount of time to respond to the alerts. Of those who felt that an alert corresponded to an actual vaccine adverse event, the majority used the reporting feature to file a VAERS report. We believe that elicited surveillance via real time prompts to clinicians holds substantial promise. By coupling simplified reporting with the initial prompt, clinicians can consider and report a vaccine adverse event electronically in a few moments during the office visit.

Incidence of outpatient visits and hospitalizations related to influenza in infants and young children.

OBJECTIVE: The Advisory Committee on Immunization Practices currently encourages influenza vaccination for all children aged 6 to 23 months when feasible, based on studies that have demonstrated that young children have high hospitalization rates attributable to influenza. The Advisory Committee on Immunization Practices recently voted to recommend influenza vaccination for all children beginning during the 2004-2005 influenza season; information on the rate of outpatient visits due to influenza is needed to better evaluate the potential health impact and cost-effectiveness of the recommendation. We estimated the incidence of outpatient visits as well as hospitalizations for specific acute respiratory illnesses and for influenza-associated outpatient-visit and hospitalization rates among healthy infants and children in a Massachusetts health maintenance organization. DESIGN/METHODS: Surveillance data were used to identify when influenza viruses, respiratory syncytial viruses, and parainfluenza viruses were circulating in the greater Boston area during 1994-2000. Using computerized medical records, we identified outpatient visits and hospitalizations for selected respiratory illnesses. Outpatient-visit rates and hospitalizations attributed to influenza were calculated by subtracting the rate of visits during the periseasonal period from the rate of visits during the influenza period. Rates were stratified by age and risk for complications from influenza. RESULTS: Between 1994 and 2000, there were 188 139 outpatient visits and 885 hospitalizations for respiratory illnesses in the study population. Among healthy children aged 6 to 23 months, the rate per 100 person-months for outpatient visits during influenza periods was 14.5 (95% confidence interval [CI]: 13.9 to 15.1), and the excess rate that could be attributed to influenza compared with the periseasonal period was 1.8 (95% CI: 1.1 to 2.4). Among healthy children, the rate of hospitalizations for acute respiratory disease was 10.4 per 10 000 person-months (95% CI: 6.0 to 17.0), and the rate that could be attributed to influenza when compared with the periseasonal baseline period was 3.9 (95% CI: -2.0 to 0.0). Among children who were at high risk for complications from influenza, the rate of outpatient visits per 100 person-months was 28.7 (95% CI: 26.6 to 30.9) during influenza periods. The rate of hospitalizations among high-risk children was 44.6 per 10 000 person-months (95% CI: 19.0 to 17.0). CONCLUSION: Influenza season is associated with a substantial increase in outpatient visits by healthy children. These estimates of outpatient visits for influenza will help quantify the potential health benefits and cost savings from influenza vaccination of healthy children aged 6 to 23 months.

Adoption of reminder and recall messages for immunizations by pediatricians and public health clinics.

OBJECTIVE: Strong scientific evidence and national recommendations support the use of reminder and recall messages to improve immunization coverage rates, yet reports have suggested that only a minority of pediatric practices use such messages. Our aims were to 1) determine the proportions of pediatric practices and public clinics that currently use practice-based reminder or recall messages and routinely undergo immunization assessment efforts, 2) evaluate barriers and supports to implementing these practices, and 3) identify predictors of either current use or plans for future adoption of these practices. METHODS: This study combined qualitative and quantitative methods in sequential phases. In the qualitative phase, we conducted semistructured, open-ended interviews with a convenience sample of 18 clinician-administrators representing adopters and nonadopters of these messages in both private practices and public health clinics. In the subsequent quantitative phase, we mailed a structured, closed-ended survey to national samples of randomly selected pediatricians (n = 600) and public clinics (n = 600). RESULTS: Response rates were 75% for pediatricians and 77% for public clinics. Among pediatricians, 38% were conducting regular assessments of immunization coverage but only 16% were currently using routine reminder or recall messages. Among public clinics, 85% were conducting regular assessments and 51% were using reminder or recall messages. Among pediatricians' practices, the most commonly reported barriers to the adoption of reminder or recall messages were lack of time and funding and the inability to identify children at specified ages. For pediatricians' practices, the strongest predictors of current use of reminder or recall messages were having a champion who led efforts to improve immunization delivery (odds ratio: 1.85; 95% confidence interval: 1.08-3.18) and current use of regular immunization assessments (odds ratio: 2.30; 95% confidence interval: 1.33-3.84). Likewise, for public health clinics, having a champion to lead immunization improvement efforts and believing that their current system needed improvement was associated with current use of reminder or recall messages. CONCLUSIONS: Reminder and recall messages remain underused by both pediatricians and public health clinics. Promising strategies to promote adoption of these approaches in both the private and the public sectors include identifying and training champions to promote immunization delivery improvement efforts and helping practices develop methods to identify children at specific ages.