Prophylactic Left Atrial Appendage Exclusion in Cardiac Surgery Patients With Elevated CHA2DS2-VASc Score: Results of the Randomized ATLAS Trial.

OBJECTIVE: Patients with elevated CHA2DS2-VASc scores are at high risk for atrial fibrillation (AF) and thromboembolic events (TE) after cardiac surgery. Left atrial appendage exclusion (LAAE) is a permanent, continuous approach to stroke prevention in AF, overcoming limitations of oral anticoagulation (OAC). We report ATLAS trial results focused on LAAE technical success and perioperative safety and TE rates with and without LAAE in cardiac surgery patients who developed postoperative AF (POAF). METHODS: ATLAS (NCT02701062) was a prospective, multicenter, feasibility trial. Patients age ≥18 years, undergoing structural heart procedure, with no preoperative AF, CHA2DS2-VASc ≥2, and HAS-BLED ≥2 were randomized 2:1 to LAAE or no LAAE. Patients who developed POAF and/or received LAAE were followed for 1 year. LAAE was evaluated with intraoperative transesophageal echocardiography. RESULTS: A total of 562 patients were randomized to LAAE (n = 376) or no LAAE (n = 186). Mean CHA2DS2-VASc (3.4 vs 3.4) and HAS-BLED (2.8 vs 2.9) scores were similar for LAAE and no LAAE groups. LAAE success (no flow nor residual stump >10 mm) was 99%. One LAAE-related serious adverse event (0.27%) occurred and was resolved without sequelae. There were 44.3% of patients who developed POAF. Through 1 year, 3.4% of LAAE patients and 5.6% of no LAAE patients had TE. OAC was used by 32.5% of POAF patients. Bleeding was higher with OAC than without (16.1% vs 5.4%, P = 0.008). CONCLUSIONS: ATLAS demonstrated a high rate of successful LAAE with low LAAE-related serious adverse events in cardiac surgery patients. Study results should be considered in future trial design to further evaluate prophylactic LAAE for stroke prevention in cardiac surgery patients with elevated stroke risk.

Prevention of pertussis, tetanus, and diphtheria among pregnant, postpartum women, and infants.

Pertussis disease in the United States has been increasing since 1976 and many states are reporting epidemics. Pertussis is more severe in infants less than 3 months of age and is characterized by high hospital admission rates, apnea of the infant. The CDC recommends that Tdap be administered to all pregnant women after the 20th week of gestation to provide pertussis antibodies to the fetus which will offer protection against pertussis disease. Tdap is highly immunogenetic in the pregnant women and has an excellent safety profile. Tdap given to the postpartum patient and her cocoon family is an alternative strategy.

Maternal immunization with tetanus-diphtheria-pertussis vaccine: effect on maternal and neonatal serum antibody levels.

OBJECTIVE: We sought to determine whether tetanus-diphtheria-pertussis vaccination (Tdap) in pregnancy provides newborns antibodies against pertussis when compared to mothers who did not receive Tdap. STUDY DESIGN: Paired maternal and umbilical cord blood samples were collected at the time of delivery and the serum stored at -86°C. For each paired sample of maternal and cord blood, the medical chart and vaccine history was reviewed to determine whether Tdap was received or not. RESULTS: Newborns born from mothers who received Tdap during pregnancy had significantly higher concentrations of diphtheria antitoxin (P < .001), tetanus antitoxin (P = .004), and antibodies to pertussis toxin (P < .001), filamentous hemagglutinin (P = .002), pertactin (P < .001), and fimbriae 2/3 (P < .001) when compared to newborns from mothers who did not receive Tdap. There was a significant increase in the odds that newborns from mothers who received Tdap during pregnancy have antibodies that may provide protection against diphtheria (P = .0141), pertussis toxin (P < .0001), and fimbriae 2/3 (P = .0146). CONCLUSION: Administering Tdap during pregnancy increases antibody titers against diphtheria and pertussis antigens. Maternal Tdap may prevent neonatal pertussis infection.

Pregnancy and infant outcomes in the clinical trials of a human papillomavirus type 6/11/16/18 vaccine: a combined analysis of five randomized controlled trials.

OBJECTIVE: To present a combined analysis of the pregnancy outcomes for women aged up to 45 years enrolled in five phase III clinical studies of the prophylactic quadrivalent human papillomavirus 6/11/16/18 vaccine. METHODS: Twenty thousand five hundred fifty-one women aged 15-45 years received quadrivalent HPV vaccine or placebo at day 1 and months 2 and 6. Urine pregnancy tests were performed immediately before each injection; participants testing positive were not vaccinated. Women who became pregnant after enrollment were discontinued from further vaccination until resolution of pregnancy. All pregnancies were followed for outcomes. RESULTS: During the studies, 1,796 vaccine and 1,824 placebo recipients became pregnant, resulting in 2,008 and 2,029 pregnancies with known outcomes. No significant differences were noted overall for the proportions of pregnancies resulting in live birth, fetal loss, or spontaneous abortion. A total of 40 neonates born to vaccinated women and 30 neonates born to women given placebo had one or more congenital anomalies (P=.20). The anomalies were diverse and consistent with those most commonly observed in the general population. The vaccine was well tolerated among women who became pregnant. CONCLUSION: Administration of quadrivalent human papillomavirus vaccine to women who became pregnant during the phase III clinical trials did not appear to negatively affect pregnancy outcomes. The vaccine is a U.S. Food and Drug Administration pregnancy category B medication (animal studies revealed no evidence of fetal harm, but there are no adequate and well-controlled studies in pregnant women); however, vaccination is not recommended during pregnancy. Postlicensure surveillance is ongoing. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00092521, NCT00092534, NCT00092495, NCT00092547 and NCT00090220. LEVEL OF EVIDENCE: II.

Immunization programs for infants, children, adolescents, and adults: clinical practice guidelines by the Infectious Diseases Society of America.

Evidence-based guidelines for immunization of infants, children, adolescents, and adults have been prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). These updated guidelines replace the previous immunization guidelines published in 2002. These guidelines are prepared for health care professionals who care for either immunocompetent or immunocompromised people of all ages. Since 2002, the capacity to prevent more infectious diseases has increased markedly for several reasons: new vaccines have been licensed (human papillomavirus vaccine; live, attenuated influenza vaccine; meningococcal conjugate vaccine; rotavirus vaccine; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis [Tdap] vaccine; and zoster vaccine), new combination vaccines have become available (measles, mumps, rubella and varicella vaccine; tetanus, diphtheria, and pertussis and inactivated polio vaccine; and tetanus, diphtheria, and pertussis and inactivated polio/Haemophilus influenzae type b vaccine), hepatitis A vaccines are now recommended universally for young children, influenza vaccines are recommended annually for all children aged 6 months through 18 years and for adults aged > or = 50 years, and a second dose of varicella vaccine has been added to the routine childhood and adolescent immunization schedule. Many of these changes have resulted in expansion of the adolescent and adult immunization schedules. In addition, increased emphasis has been placed on removing barriers to immunization, eliminating racial/ethnic disparities, addressing vaccine safety issues, financing recommended vaccines, and immunizing specific groups, including health care providers, immunocompromised people, pregnant women, international travelers, and internationally adopted children. This document includes 46 standards that, if followed, should lead to optimal disease prevention through vaccination in multiple population groups while maintaining high levels of safety.

Obstetrician-gynecologists' practices and perceived knowledge regarding immunization.

BACKGROUND: Obstetrician-gynecologists can play a key role in providing appropriate vaccinations to women of childbearing age. PURPOSE: This study investigated immunization knowledge and practices, and opinions concerning potential barriers to immunization, among obstetrician-gynecologists. METHODS: In 2007, surveys were sent to Collaborative Ambulatory Research Network members, a representative sample of practicing Fellows of the American College of Obstetricians and Gynecologists; 394 responded (51.2%). Data analysis was completed in 2008. RESULTS: Most responding obstetrician-gynecologists disagreed that "routine screening for vaccine-preventable diseases falls outside of the routine practice of an ob/gyn." A majority (78.7%) stock and administer at least some vaccines. Among those who stock vaccines, 91.0% stock the human papillomavirus vaccine, and 66.8% stock the influenza vaccine. All other vaccines were stocked by <30% of practices that stock vaccines. A majority of physicians agreed that financial factors (e.g., inadequate reimbursement) were barriers to vaccine administration. Most were aware that the influenza (89.8%); hepatitis B (64.0%); and tetanus, diptheria, pertussis (58.6%) vaccines are safe to administer during pregnancy, and that the measles, mumps, rubella (97.5%); and varicella (92.9%) vaccines are not. Most (84.5%) were in concordance with recommendations that all pregnant women should receive the influenza vaccine. A majority believed their immunization training was less than adequate and believed their practice would benefit from continuing medical education courses. CONCLUSIONS: Immunization is an important part of women's health care and has been, at least partially, incorporated into obstetrician-gynecologist practice. Financial burdens and knowledge regarding vaccine recommendations remain barriers to vaccine administration. Additional training and professional information may benefit obstetric-gynecologic practice.

Vaccines for pertussis and influenza: recommendations for use in pregnancy.

The active immunization of pregnant women during pregnancy to protect them from disease and protect their neonate with passive antibodies is a biologic fact. Fortunately, many infectious diseases occur infrequently due to excellent pediatric vaccine programs. However, most adults and many physicians are unaware of the risks of not administering vaccines especially to pregnant women. Influenza vaccine (trivalent inactivated influenza vaccine) is recommended by (Advisory Committee on Immunization Practices (ACIP) for pregnant women in any trimester of pregnancy and Tetanus, reduced diphtheria, and pertussis (TdaP) vaccine is recommended by the ACIP to be given before pregnancy, during pregnancy, or in the immediate postpartum period. Only 2% of the adult US population is protected against pertussis and it is estimated that only 25% of pregnant women receive influenza vaccine during the influenza season. This chapter discusses trivalent inactivated influenza vaccine and TdaP use during pregnancy, the diseases they prevent, and the benefit to the neonate.

Maternal immunization to protect the mother and neonate.

The concept of maternal immunization to protect the mother against vaccine-preventable disease and the neonate against illness for the first 3-6 months of life is one that is simple, straightforward and safe. Neonatal immunization is largely unsuccessful due to immaturity of the infant's immune system. Therefore, appropriate maternal immunization and passive transferred antibodies to the fetus can protect the neonate until infant vaccination is more efficacious.

Expanding the use of hepatitis vaccines in obstetrics and gynecology.

Current pediatric vaccination schedules in the United States are based on age. In contrast, adults are vaccinated against most infectious diseases, including hepatitis A and B, only when they are identified as at high risk or after a known exposure. There are multiple risk factors for hepatitis A and B of which clinicians often are not aware. Consequently, many persons at high risk are never vaccinated. Universal vaccination against hepatitis A and B is recommended for adults to halt transmission of the virus and prevent long-term sequelae. Women and their offspring are an especially important population to consider in efforts to reduce the incidence of hepatitis. The following recommendations for expanding the use of hepatitis vaccines in obstetrics and gynecology are made in this article: all older adolescents and adults should be vaccinated regardless of risk factors, and greater efforts should be made to educate physicians about the need to vaccinate their patients against hepatitis.

Maternal immunization.

Maternal immunization embraces the concepts that vaccines given to pregnant women enhance their resistance to vaccine-preventable diseases and passive antibodies that cross the placenta protect the neonate for the first 3 to 6 months of life. It is a great public health move to get excellent protection at a small cost. Because all recommended vaccines for use in pregnancy are safe, it makes good sense to bring patients up to date on vaccines.