Sean O’Leary - Academia.edu (original) (raw)

Papers by Sean O’Leary

Vaccine, 2011

Background: Less than half of adults for whom seasonal influenza vaccine is recommended receive t... more Background: Less than half of adults for whom seasonal influenza vaccine is recommended receive the vaccine. Little is known about physician willingness to collaborate with community vaccinators to improve delivery of vaccine. Objectives: To assess among general internists and family medicine physicians: (1) seasonal influenza vaccination practices, (2) willingness to collaborate with community vaccinators, (3) barriers to collaboration, and (4) characteristics associated with unwillingness to refer patients to community sites for vaccination. Design: Mail and Internet-based survey. Setting: National survey conducted during July-October 2009. Participants: General internists and family medicine physicians. Measurements: Survey responses on vaccination practices, willingness to collaborate to deliver vaccine and barriers to collaboration. Results: Response rates were 78% (337/432 general internists) and 70% (298/424 family medicine physicians). Ninety-eight percent of physicians reported giving influenza vaccine in their practice during the 2008-2009 season. Most physicians reported willingness to refer certain patients to other community vaccinators such as public clinics or pharmacies (79%); to collaborate with public health entities in holding community vaccination clinics (76%); and set up vaccination clinics with other practices (69%). The most frequently reported barriers to collaboration included concerns about record transfer (24%) and the time and effort collaboration would take (21%). Reporting loss of income (RR 1.40, 95% CI 1.03-1.89) and losing opportunities to provide important medical services to patients with chronic medical conditions (RR 1.77, 95% CI 1.25-2.78) were associated with unwillingness to refer patients outside of the practice for vaccination. Limitations: Surveyed physicians may not be representative of all physicians. Conclusions: The majority of physicians report willingness to collaborate with other community vaccinators to increase influenza vaccination rates although some will need assurance that collaboration will be financially feasible and will not compromise care. Successful collaboration will require reliable record transfer and must not be time consuming.

Reproduction, Fertility and Development, 2005

Journal of Reproductive Immunology, 2010

The Journal of Pediatrics, 2012

To assess practices regarding the expanded Advisory Committee on Immunization Practices (ACIP) re... more To assess practices regarding the expanded Advisory Committee on Immunization Practices (ACIP) recommendations for influenza vaccination in children among US pediatricians and family medicine physicians (FMs) and strategies to promote vaccination. We administered a survey between July and October 2009 to 416 pediatricians and 424 FMs from nationally representative networks. The response rate was 75% (79% pediatricians, 70% FMs). FMs were less likely than pediatricians to report adherence to ACIP recommendations (35% vs 65%; adjusted risk ratio [RR], 0.60; 95% CI, 0.50-0.72). Most physicians (89% pediatricians and 89% FMs) reported using posters or pamphlets to encourage influenza vaccination, and 57% pediatricians and 41% FMs reported offering after hours dedicated influenza vaccination clinics. Only 23% pediatricians and 14% FMs reported providing written, telephone, or e-mail reminders to all children. Having dedicated influenza vaccination clinics after hours or weekends was associated with routine vaccination of all children (adjusted RR, 1.33; 95% CI, 1.15-1.57). In the first year of the expanded ACIP recommendations to immunize all eligible children against influenza, two-thirds of pediatricians and one-half of FMs reported adherence, although less than one-quarter were actively engaging in reminder/recall efforts. Practices that adhered to the ACIP recommendations were more likely to put a substantial effort into promoting vaccination opportunities.

Journal of Autoimmunity, 2010

Antibodies reactive with the ovarian glycoprotein zona pellucida (ZP) have been linked with human... more Antibodies reactive with the ovarian glycoprotein zona pellucida (ZP) have been linked with human female infertility. Anti-fertility vaccines that target ZP antigens have been utilized to restrict pest animal populations and their efficacy is associated with ovary-specific antibody induction. However, the necessity for zona pellucida-specific antibody in mediating infertility has not been examined in vivo. A recombinant mouse cytomegalovirus vaccine encoding murine zona pellucida 3 that induces rapid and complete infertility in BALB/c mice has been produced. The onset of infertility is temporally related to the presence of antibody sequestered into ovarian follicles and binding to the ZP of infected mice and the loss of mature follicles. When this vaccine was inoculated into immunoglobulin-deficient BALB/c mice with a null mutation in the immunoglobulin mu chain gene Igh-6, fertility was unaffected. Passive transfer of serum containing ZP3 antibodies also elicited transient infertility. Electron microscopy of ovarian tissue collected from ZP3-immunized immunocompetent mice demonstrated significant focal thinning of the zona pellucida (ZP) with reduced length and concentration of transzonal processes and many oocytes displayed evidence of injury. None of these changes were found in vaccinated immunoglobulin-deficient mice. These data confirm that ZP3-reactive antibody is necessary and sufficient to induce autoimmunemediated follicular depletion and fertility suppression following the inoculation of this vaccine, and suggest that this is due to impaired zona pellucida formation. These findings have relevance in understanding the etiology of autoimmune ovarian disease in woman where anti-ZP antibodies are likely to have a causal role in infertility.

Biology of Reproduction, 2008

Zona pellucida (ZP) glycoproteins are promising candidate antigens for use in immunocontraceptive... more Zona pellucida (ZP) glycoproteins are promising candidate antigens for use in immunocontraceptive vaccines because of their crucial role in mammalian fertilization. A single intraperitoneal immunization with recombinant murine cytomegalovirus engineered to express murine ZP3 (rMCMV-mZP3) induces permanent infertility with no evident systemic illness in female BALB/c mice. To investigate the mechanisms underpinning reproductive failure elicited by rMCMV-mZP3, ovarian parameters and reproductive function were evaluated at time points spanning 10 days to 5 wk after virus inoculation. Fertility was substantially impaired by 14 days after inoculation with rMCMV-mZP3 and was fully ablated by 21 days. Pregnancies established after inoculation but before complete infertility showed no adverse effects on fetal viability assessed at Day 17.5 post coitum (pc). Infertile mice retained estrous cycling activity and remained receptive to mating; however, at Day 3.5 pc there were fewer developing embryos and corpora lutea, plasma progesterone content was reduced, and there was no evidence of excess unfertilized oocytes. Consistent with this, profound ovarian pathology was evident from 10 days after rMCMV-mZP3 inoculation, with a decline first in mature ovarian follicles and then in immature ovarian follicles and with diminished expression of genes regulating follicle development, including Nobox, Gdf9, and Gja1 (connexin43). Follicle loss was associated with mild focal oophoritis and with recruitment of inflammatory leukocytes, predominantly CD4(+) and CD8(+) T cells evident from 10 days after virus inoculation. These data indicate that vaccination with rMCMV-mZP3 causes permanent infertility in BALB/c mice principally due to induction of ovarian autoimmune pathology leading to progressive oocyte depletion and eventual ovulation failure.

Annals of Internal Medicine, 2014

Adults are at substantial risk for vaccine-preventable disease, but their vaccination rates remai... more Adults are at substantial risk for vaccine-preventable disease, but their vaccination rates remain low. To assess practices for assessing vaccination status and stocking recommended vaccines, barriers to vaccination, characteristics associated with reporting financial barriers to delivering vaccines, and practices regarding vaccination by alternate vaccinators. Mail and Internet-based survey. Survey conducted from March to June 2012. General internists and family physicians throughout the United States. A financial barriers scale was created. Multivariable linear modeling for each specialty was performed to assess associations between a financial barrier score and physician and practice characteristics. Response rates were 79% (352 of 443) for general internists and 62% (255 of 409) for family physicians. Twenty-nine percent of general internists and 32% of family physicians reported assessing vaccination status at every visit. A minority used immunization information systems (8% and 36%, respectively). Almost all respondents reported assessing need for and stocking seasonal influenza; pneumococcal; tetanus and diphtheria; and tetanus, diphtheria, and acellular pertussis vaccines. However, fewer assessed and stocked other recommended vaccines. The most commonly reported barriers were financial. Characteristics significantly associated with reporting greater financial barriers included private practice setting, fewer than 5 providers in the practice, and, for general internists only, having more patients with Medicare Part D. The most commonly reported reasons for referring patients elsewhere included lack of insurance coverage for the vaccine (55% for general internists and 62% for family physicians) or inadequate reimbursement (36% and 41%, respectively). Patients were most often referred to pharmacies/retail stores and public health departments. Surveyed physicians may not be representative of all physicians. Improving adult vaccination delivery will require increased use of evidence-based methods for vaccination delivery and concerted efforts to resolve financial barriers, especially for smaller practices and for general internists who see more patients with Medicare Part D. Centers for Disease Control and Prevention.

Reproduction, Fertility and Development, 2004

ABSTRACT A recombinant mouse virus, murine cytomegalovirus, that has been engineered to encode th... more ABSTRACT A recombinant mouse virus, murine cytomegalovirus, that has been engineered to encode the fertility antigen murine zona pellucida 3 (mZP3), is being developed for fertility control in mice. A single inoculation of the recombinant virus induces complete infertility in female BALB/c mice which persists for the breeding life of the animal. The extent of this autoimmune response was unexpected especially as the incorporation of mZP3 appears to have immunologically attenuated the growth of the recombinant virus. The histological features of the infection are an initial depletion in tertiary follicles by 21 days post inoculation followed by a progressive depletion of primordial follicles, leading to an almost complete absence of follicles by 150 days post-infection. High titre, long lasting, zona pellucida-specific antibody is present in infertile BALB/c mice although infertility has not been linked with either a critical titre or a dominant immunoglobulin isotype. However, our evidence suggests that anti-ZP3 antibody plays a primary role in infertility since antibodies are detected in vivo bound to the zona pellucida of ovaries from recombinant virus-infected mice, and passively transferred antibody from infected animals induces infertility in the absence of recombinant virus. In addition, an experiment in which immunoglobulin-deficient mice remained fertile after inoculation with the recombinant virus indicates that antibody is crucial for the immunocontraceptive effect to occur. Other immune mechanisms are also being explored.