Functional analysis and consequences of Mdm2 E3 ligase inhibition in human tumor cells.

Mdm2 is the major negative regulator of p53 tumor-suppressor activity. This oncoprotein is overexpressed in many human tumors that retain the wild-type p53 allele. As such, targeted inhibition of Mdm2 is being considered as a therapeutic anticancer strategy. The N-terminal hydrophobic pocket of Mdm2 binds to p53 and thereby inhibits the transcription of p53 target genes. Additionally, the C-terminus of Mdm2 contains a RING domain with intrinsic ubiquitin E3 ligase activity. By recruiting E2 ubiquitin-conjugating enzyme(s), Mdm2 acts as a molecular scaffold to facilitate p53 ubiquitination and proteasome-dependent degradation. Mdmx (Mdm4), an Mdm2 homolog, also has a RING domain and hetero-oligomerizes with Mdm2 to stimulate its E3 ligase activity. Recent studies have shown that C-terminal residues adjacent to the RING domain of both Mdm2 and Mdmx contribute to Mdm2 E3 ligase activity. However, the molecular mechanisms mediating this process remain unclear, and the biological consequences of inhibiting Mdm2/Mdmx co-operation or blocking Mdm2 ligase function are relatively unexplored. This study presents biochemical and cell biological data that further elucidate the mechanisms by which Mdm2 and Mdmx co-operate to regulate p53 level and activity. We use chemical and genetic approaches to demonstrate that functional inhibition of Mdm2 ubiquitin ligase activity is insufficient for p53 activation. This unexpected result suggests that concomitant treatment with Mdm2/Mdmx antagonists may be needed to achieve therapeutic benefit.

Interventions aimed at improving immunization rates.

BACKGROUND: Immunization rates for children and adults are rising, but coverage levels have not reached national goals. As a result of low immunization rates, vaccine-preventable diseases still occur. In an era of increasing complexity of immunization schedules, rising expectations about the performance of primary care, and large demands on primary care physicians, it is important to understand and promote interventions that work in primary care settings to increase immunization coverage. A common theme across immunization programs in all nations involves the challenge of determining the denominator of eligible recipients (e.g., all children who should receive the measles vaccine), and identifying the best strategy to ensure high vaccination rates. Strategies have focused on patient-oriented interventions (e.g., patient reminders), provider interventions, and system interventions. One intervention strategy involves patient reminder/recall systems. OBJECTIVES: Assess the effectiveness of patient reminder/recall systems in improving immunization rates, and compare the effects of various types of reminders in different settings or patient populations. SEARCH STRATEGY: A systematic search was performed using MEDLINE (1966-1998) and 4 other bibliographic databases: EMBASE, PsychINFO, Sociological Abstracts, and CAB Abstracts. Authors also performed a search of EPOC in April 2001 to update the review. Two authors reviewed the lists of titles and abstracts, and used the inclusion criteria to mark potentially relevant articles for full review. The reference lists of all relevant articles and reviews were back searched for additional studies. Publications of abstracts, proceedings from scientific meetings, and files of study collaborators were also searched for references. STUDY DESIGN: Randomized controlled trials (RCT), controlled before and after studies (CBA), and interrupted time series (ITS) studies written in English. TYPES OF PARTICIPANTS: Health care personnel who deliver immunizations and children (birth to 18 years) or adults (18 years and up) who receive immunizations in any setting. Types of interventions: Any intervention that falls within the Effective Practice and Organization of Care Group (EPOC) scope and that includes patient reminder and/or recall in at least one arm of the study. Types of outcome measures: Immunization rates, or the proportion of the target population up-to-date on recommended immunizations. Outcomes were acceptable for either individual vaccinations (e.g., influenza vaccination) or standard combinations of recommended vaccinations (e.g., all recommended vaccinations by a specific date or age). DATA COLLECTION: Each study was read independently by two reviewers. Disagreements between reviewers were resolved by a formal reconciliation process to achieve consensus. ANALYSIS: Results are presented for individual studies as relative rates for randomized controlled trials, and as absolute changes in percentage points for controlled before and after studies. Pooled results were presented using the random effects model. MAIN RESULTS: Patient reminder/recall systems were effective in improving immunization rates in 33 of 41 included studies, irrespective of baseline immunization rates, patient ages, type of setting, or type of vaccination. Increases in immunization rates due to reminders were in the range of 5 to 20 percentage points. Reminders were effective for childhood vaccinations (OR=2.02, 95% CI =1.49,2.72), childhood influenza vaccinations (OR=4.19, 95% CI =2.07,8.49), adult pneumococcus or tetanus (OR=5.14, 95%CI = 1.21, 21.8), and adult influenza vaccinations (OR=2.29, 95%CI = 1.69, 3.10). While reminders were most effective in academic settings (OR = 3.33, 95% CI = 1.98, 5.58), they were also highly effective in private practice settings (OR=1.79, 95% CI = 1.45, 2.22) and public health clinics (OR = 2.09, 95% CI = 1.42, 3.07). All types of reminders were effective (postcards, letters, telephone or autodialer calls), with telephone being the most effective but most costly. REVIEWER'S CONCLUSIONS: Patient reminder/recall systems in primary care settings are effective in improving immunization rates.

Attitudes, practices, and preferences of pediatricians regarding initiation of hepatitis B immunization at birth.

OBJECTIVES: To explore practices and attitudes of pediatricians toward administration of the first dose of hepatitis B vaccine to infants, and to identify factors influencing the decision of pediatricians to initiate immunization at birth versus at 1 to 2 months of age. METHODS: A random sample of 600 pediatricians obtained from the American Academy of Pediatrics membership database was surveyed by mail. RESULTS: Three hundred eighty (68%) of the 563 pediatricians who were located responded to the survey. Of these 380 pediatricians, 279 provided routine immunizations to children. Of the 270 pediatricians who vaccinated children with hepatitis B vaccine and indicated their practice regarding the birth dose, 50% offered the first dose of hepatitis B vaccine at birth to all infants; the rest either offered the vaccine at birth only to infants of hepatitis B surface antigen-positive mothers and mothers whose serostatus is unknown, or did not offer the birth dose to any infants at all. Practicing in the inner city, working for a medical school or government hospital, and living in a state with universal immunization supply policies were associated with the respondent giving the birth dose. The strongest perceived barriers to giving the birth dose in the hospital were the difficulty tracking these vaccines (39%), the increased cost (27%), and the lack of reimbursement from insurance companies (26%). If a combination vaccine that includes hepatitis B; diphtheria, tetanus, pertussis (diphtheria and tetanus toxoids and acellular pertussis vaccine); and polio (inactivated poliovirus vaccine) antigens become available in the near future, then 38% of physicians who currently give the birth dose to all infants would prefer to wait until 2 months of age to initiate hepatitis B immunization. CONCLUSIONS: Efforts to achieve high implementation of hepatitis B birth dose administration may falter once a hepatitis B-containing pentavalent combination vaccine becomes available. Programmatic efforts should ensure prevention of perinatal hepatitis B virus transmission through universal prenatal hepatitis B surface antigen screening and immunoprophylaxis of high-risk newborn infants.

Impact of multiple injections on immunization rates among vulnerable children.

BACKGROUND: In 1997, the Advisory Committee on Immunization Practices (ACIP) recommended a switch from oral polio vaccine (OPV) to inactivated polio vaccine (IPV) for the first two infant doses. The ACIP also recommended use of diphtheria, tetanus, and acellular pertussis vaccine (DTaP) for infants. These recommendations resulted in two additional injections at the 2- and 4-month immunization visits. This study evaluates the implementation of new IPV and DTaP immunization recommendations and their impact on immunization coverage levels. METHODS: Immunization coverage was assessed in public clinics in three urban areas before and after the recommendations. One pre- and three post-recommendation cohorts were followed to 12 months of age. RESULTS: Almost all (> or = 88%) infants in the pre-recommendation cohort received OPV, DTP, and only one or two injections. Almost all (> or = 78%) infants in the post-recommendation cohorts received IPV, DTaP, and three or four injections. The percentage of infants in the post-recommendation cohorts up-to-date for immunizations at 12 months of age was slightly higher than those in the pre-recommendation cohort. CONCLUSIONS: Providers rapidly switched from OPV and DTP to IPV and DTaP. Coverage at 12 months of age was higher among IPV/DTaP recipients than among OPV/DTP recipients. Provider and parent acceptance of four injections at a visit was high. The recent pneumococcal conjugate vaccine recommendations potentially add a fifth injection at 2 and 4 months of age. Acceptance or rejection of five injections by providers and parents needs early assessment.

Impact of the change in polio vaccination schedule on immunization coverage rates: a study in two large health maintenance organizations.

OBJECTIVE: In January 1997, one of the most significant changes to United States vaccine policy occurred when polio immunization guidelines changed to recommend a schedule containing inactivated polio vaccine (IPV). There were concerns that parent or physician reluctance to accept IPV into the routine childhood immunization schedule would lead to lowered coverage. We determined whether adoption of an IPV schedule had a negative impact on immunization coverage. DESIGN: A cohort study of 2 large health maintenance organizations (HMOs), Group Health Cooperative and Kaiser Permanente Northern California, was conducted. For analysis at 12 months of age, children who were born between October 1, 1996, and December 31, 1997, and were commercially insured and covered by Medicaid were continuously enrolled; for analysis at 24 months of age, children who were born between October 1, 1996, and June 30, 1997, and were commercially insured and covered by Medicaid were continuously enrolled. The 3 measures of immunization status at 12 and 24 months of age were up-to-date status, cumulative time spent up-to-date, and the number of missed opportunity visits. RESULTS: At both HMOs, children who received IPV were as likely to be up to date at 12 months as were children who received oral poliovirus vaccine (OPV), whereas at Group Health, children who received IPV were slightly more likely to be up to date at 24 months (relative risk: 1.12; 95% confidence interval [CI]: 1.05, 1.19). These findings were consistent for children who were covered by Medicaid. At Kaiser Permanente, children who received IPV spent ~3 fewer days up to date in the first year of life, but this difference did not persist at 2 years of age. At Group Health, children who received IPV were no different from those who received OPV in terms of days spent up to date by 1 or 2 years of age. At Group Health, children who received IPV were less likely to have a missed opportunity by 12 months old (odds ratio [OR] 0.46; 95% CI: 0.31, 0.70), but this finding did not persist at 24 months of age. At Kaiser Permanente, children who received IPV were more likely to have a missed opportunity by 12 months (OR 2.06; 95% CI: 1.84, 2.30), and 24 months of age (OR 1.50; 95% CI: 1.36, 1.67). CONCLUSIONS: The changeover from an all-OPV schedule to one containing IPV had little if any negative impact on vaccine coverage. Use of IPV was associated with a small increase in the likelihood of being up to date at 2 years of age at one of the HMOs and conversely was associated with a small increase in the likelihood of having a missed-opportunity visit in the other HMO.polio, poliomyelitis, vaccination, immunization coverage.

Variation in clinician recommendations for multiple injections during adoption of inactivated polio vaccine.

OBJECTIVES: To describe variation in clinician recommendations for multiple injections during the adoption of inactivated poliovirus vaccine (IPV) in 2 large health maintenance organizations (HMOs), and to test the hypothesis that variation in recommendations would be associated with variation in immunization coverage rates. DESIGN: Cross-sectional study based on a survey of clinician practices 1 year after IPV was recommended and computerized immunization data from these clinicians' patients. STUDY SETTINGS: Two large West Coast HMOs: Kaiser Permanente in Northern California and Group Health Cooperative of Puget Sound. OUTCOME MEASURES: Immunization status of 8-month-olds and 24-month-olds cared for by the clinicians during the study. RESULTS: More clinicians at Group Health (82%), where a central guideline was issued, had adopted the IPV/oral poliovirus vaccine (OPV) sequential schedule than at Kaiser (65%), where no central guideline was issued. Clinicians at both HMOs said that if multiple injections fell due at a visit and they elected to defer some vaccines, they would be most likely to defer the hepatitis B vaccine (HBV) for infants (40%). At Kaiser, IPV users were more likely than OPV users to recommend the first HBV at birth (64% vs 28%) or if they did not, to defer the third HBV to 8 months or later (62% vs 39%). In multivariate analyses, patients whose clinicians used IPV were as likely to be fully immunized at 8 months old as those whose clinicians used all OPV. At Kaiser, where there was variability in the maximum number of injections clinicians recommended at infant visits, providers who routinely recommended 3 or 4 injections at a visit had similar immunization coverage rates as those who recommended 1 or 2. At both HMOs, clinicians who strongly recommended all possible injections at a visit had higher immunization coverage rates at 8 months than those who offered parents the choice of deferring some vaccines to a subsequent visit (at Kaiser, odds ratio [OR]: 1.2; 95% confidence interval [CI]: 1.0-1.5; at Group Health, OR: 1.8; 95% CI: 1.1-2.8). CONCLUSIONS: Neither IPV adoption nor the use of multiple injections at infant visits were associated with reductions in immunization coverage. However, at the HMO without centralized immunization guidelines, IPV adoption was associated with changes in the timing of the first and third HBV. Clinical policymakers should continue to monitor practice variation as future vaccines are added to the infant immunization schedule.

Health department clinics as pediatric immunization providers: a national survey.

OBJECTIVE: To describe a national sample of health department immunization clinics in terms of populations served, patient volume trends, services offered, and immunization practices. METHODS: Telephone survey conducted with health departments sampled from a national database, using probability proportional to population size. RESULTS: All (100%) 166 sampled and eligible clinics completed the survey. The majority of pediatric patients were uninsured (42%) or enrolled in Medicaid (34%). Most children (69%) and adolescents (70%) were referred to the health department, with only 12% using these clinics as a medical home. A number of clinics (72%) reported recent increases in adolescents served. Less than 25% of clinics offered comprehensive care, 47% conducted semiannual coverage assessments, and 76% and 38% operated recall systems for children and adolescents. Storage of records in an electronic database was common (83%). CONCLUSIONS: Although the majority of these clinics do not provide comprehensive care, they continue to serve vulnerable children, including adolescents, Medicaid enrollees, and the uninsured, and may represent the main contact with the healthcare system for such patients. Because assuring the immunization of these children is essential to their health and the health of our nation as a whole, this immunization safety net must be preserved. Experience implementing key recommendations such as coverage assessment and feedback as well as reminder or recall may enable health department staff to assist private provider colleagues. Further research is needed to investigate how patient populations, services offered, and immunization practices vary by different clinic characteristics.

Vaccination status of children in the Women, Infants, and Children (WIC) Program: are we doing enough to improve coverage?

BACKGROUND: Vaccination-promoting strategies in the Supplemental Nutrition Program for Women, Infants, and Children (WIC) have been shown to produce dramatic improvements in coverage and other health outcomes. OBJECTIVES: To determine national and state-specific population-based vaccine coverage rates among preschool children who participate in the WIC program, and to describe the strategies for promoting vaccination in WIC. DESIGN/METHODS: Demographic data, WIC participation, and vaccination histories for children aged 24 to 35 months in 1999 were collected from parents through the National Immunization Survey. The healthcare providers for the children in the survey were contacted to verify and complete vaccination information. We defined children as up-to-date (UTD) if they had received four doses of diphtheria and tetanus toxoids and pertussis vaccine (DPT), three doses of poliovirus vaccine, one dose of measles-mumps-rubella vaccine (MMR), and three doses of Haemophilus influenzae type b vaccine (Hib) by 24 months. Description of state-level vaccination-promoting activities in WIC was collected through an annual survey completed by the state WIC and immunization program directors. RESULTS: Complete data were collected on 15,766 children, of whom 7783 (49%) participated in WIC sometime in their lives. Nationally, children who had ever participated in WIC were less well-immunized at 24 months compared to children who had not: 72.9% UTD (95% CI, 71.3-74.5) versus 80.8% UTD (95% CI, 79.5-82.1), respectively. In 42 states, 24-month coverage among WIC participants was less than among non-WIC participants, including 13 states where the difference was > or = 10%. Vaccination activities linked with WIC were reported from 76% of 8287 WIC sites nationwide. States conducting more-frequent interventions and reaching a higher proportion of WIC participants had 40% higher vaccination coverage levels for the WIC participants in that state (p<0.05). CONCLUSIONS: Children served by WIC remain less well-immunized than the nation's more-affluent children who do not participate in WIC. Thus, WIC remains a good place to target these children. This study provides evidence that fully implemented WIC linkage works to improve vaccination rates. Strategies that have been shown to improve the vaccination coverage levels of WIC participants should be expanded and adequately funded to protect these children.

Processes for obtaining nonmedical exemptions to state immunization laws.

OBJECTIVES: This study sought to determine the specific processes required for obtaining religious and philosophical exemptions to school immunization laws. METHODS: State health department immunization program managers in the 48 states that offer nonmedical exemptions were surveyed. Categories were assigned to reflect the complexity of the procedure within a state for obtaining an exemption. RESULTS: Sixteen of the states delegated sole authority for processing exemptions to school officials. Nine states had written policies informing parents who seek an exemption of the risks of not immunizing. The complexity of the exemption process, in terms of paperwork or effort required, was inversely associated with the proportion of exemptions field. CONCLUSIONS: In many states, the process of claiming a nonmedical exemption requires less effort than fulfilling immunization requirements.

The impact of record scattering on the measurement of immunization coverage.

BACKGROUND: Lack of a consolidated immunization record may lead to problems with determining individual immunization needs at office visits as well as measuring vaccination coverage levels of a clinician's practice or a community's population. OBJECTIVES: For children with multiple immunization providers, evaluate the difference in coverage levels using data from all responding immunization providers compared with: 1) the most recent immunization provider's records, 2) the first immunization provider's records, and 3) a randomly selected immunization provider's records. Identify characteristics of the most recent provider that may be associated with reporting incomplete immunization histories. METHODS: Data from the 1995 National Immunization Provider Record Check Study (NIPRCS) were used for analysis. The NIPRCS is a provider validation study of the household reported immunization histories of all children 19 to 35 months of age included in the National Health Interview Survey (NHIS). Providers identified by the child's parent during the NHIS interview are mailed a 2-page survey to report all immunizations (type and date) the child received, regardless of the provider who administered the shots, and child's first and most recent visit dates to the practice. RESULTS: Of the 1352 children with provider data, 304 (22%) had received immunizations from more than one provider. Compared with information from all providers and depending on the vaccine, the most recent provider records underestimated coverage by 9.6 to 13.4 percentage points; the initial provider records underestimated coverage by 15.6 to 34.6 percentage points; and the randomly selected provider records underestimated coverage by 10.0 to 20.7 percentage points. Public facilities and having an immunization summary sheet in the patient's chart were associated with having complete records. CONCLUSION: Scattered immunization records significantly compromise the ability of clinicians to determine the immunization status of their patients who received immunizations at other sites of health care. Routinely assessing immunization coverage levels at the practice level, implementing a recall system, and developing community-wide immunization registries are some strategies to reduce the problem of scattered immunization records.immunization, assessment, provider validation, record scattering.

National, state and urban-area vaccination-coverage levels among children aged 19-35 months, United States, 1999.

BACKGROUND: Assessment of vaccination coverage is an important component of the U.S. vaccination program and is primarily measured by the National Immunization Survey (NIS). METHODS: The 1999 NIS is a nationally representative sample of children aged 19 to 35 months, verified by provider records, that is conducted to obtain estimates of vaccination coverage rates. Coverage estimates are calculated for the nation, states, and selected urban areas for recommended vaccines and selected vaccine series. RESULTS: Coverage estimates are presented by a variety of demographic and healthcare-related factors: overall, by poverty status, race/ethnicity, selected milestone ages, participation in WIC, level of urbanicity, provider participation in VFC, and by provider facility type. In 1999, national coverage estimates were high for most vaccines and among most demographic groups. State and urban-area level estimates varied.

Immunization pockets of need: science and practice.

Despite high overall immunization coverage levels among U.S. preschool children, areas of underimmunization, called pockets of need, remain. These areas, which pose both a personal health and a public health risk, are typically poor, crowded, urban areas in which barriers to immunization are difficult to overcome and health care resources are limited. The purpose of this report is to review barriers to immunization of preschool children living in pockets of need and to discuss current issues in the identification of and implementation of interventions within these areas. The Centers for Disease Control and Prevention administers a federal grants program that funds state and metropolitan immunization programs. This program promotes a three-pronged approach for addressing pockets of need: (1) identification of target areas, (2) selection and implementation of programmatic strategies to improve immunization coverage, and (3) evaluation of progress or impact. At each step, scientific evidence can guide programmatic efforts. While there is evidence that state and metropolitan immunization programs are currently making efforts to address pockets of need, much work remains to be done to improve immunization coverage levels in pockets of need. Public health agencies must take on a broadened role of accountability, new partnerships must be forged, and it may be necessary to strengthen the oversight authority of public health. These tasks will require a concentration and redirection of resources to support the development of an immunization delivery infrastructure capable of ensuring the timely delivery of immunizations to the most vulnerable of America's children.

Effect of patient reminder/recall interventions on immunization rates: A review.

CONTEXT: Immunization rates for children and adults remain below national goals. While experts recommend that health care professionals remind patients of needed immunizations, few practitioners actually use reminders. Little is known about the effectiveness of reminders in different settings or patient populations. OBJECTIVES: To assess the effectiveness of patient reminder systems in improving immunization rates, and to compare the effectiveness of different types of reminders for a variety of patient populations. DATA SOURCES: A search was performed using MEDLINE, EMBASE, PsychINFO, Sociological Abstracts, and CAB Health Abstracts. Relevant articles, as well as published abstracts, conference proceedings, and files of study collaborators, were searched for relevant references. STUDY SELECTION AND DATA EXTRACTION: English-language studies involving patient reminder/recall interventions (using criteria established by the Cochrane Collaboration) were eligible for review if they involved randomized controlled trials, controlled before-after studies, or interrupted time series, and measured immunization rates. Of 109 studies identified, 41 met eligibility criteria. Studies were reviewed independently by 2 reviewers using a standardized checklist. Results of studies are expressed as absolute percentage-point changes in immunization rates and as odds ratios (ORs). Studies with similar characteristics of patients or interventions were pooled (random effects model). DATA SYNTHESIS: Patient reminder systems were effective in improving immunization rates in 33 (80%) of the 41 studies, irrespective of baseline immunization rates, patient age, setting, or vaccination type. Increases in immunization rates due to reminders ranged from 5 to 20 percentage points. Reminders were effective for childhood vaccinations (OR, 2.02; 95% confidence interval [CI], 1.49-2.72), childhood influenza vaccinations (OR, 4. 25; 95% CI, 2.10-8.60), adult pneumococcus or tetanus vaccinations (OR, 5.14; 95% CI, 1.21-21.78), and adult influenza vaccinations (OR, 2.29; 95% CI, 1.69-3.10). While reminders were most effective in academic settings (OR, 3.33; 95% CI, 1.98-5.58), they were also highly effective in private practice settings (OR, 1.79; 95% CI, 1. 45-2.22) and public health clinics (OR, 2.09; 95% CI, 1.42-3.07). All types of reminders were effective (postcards, letters, and telephone or autodialer calls), with telephone reminders being most effective but costliest. CONCLUSIONS: Patient reminder systems in primary care settings are effective in improving immunization rates. Primary care physicians should use patient reminders to improve immunization delivery. JAMA. 2000;284:1820-1827.

Association between administration of hepatitis B vaccine at birth and completion of the hepatitis B and 4:3:1:3 vaccine series.

CONTEXT: The association between infant age at initiation of hepatitis B vaccination and completion of the 3-dose hepatitis B vaccination series is unclear. OBJECTIVE: To assess the association between administration of the first dose of hepatitis B vaccine within 7 days of birth and completion of the hepatitis B vaccine series and the 4:3:1:3 vaccine series (4 doses of diphtheria-tetanus-pertussis vaccine, 3 doses of polio vaccine, 1 dose of measles-containing vaccine, and 3 doses of Haemophilus influenzae type b vaccine). DESIGN, SETTING, AND PARTICIPANTS: Analysis of data from the 1998 National Immunization Survey, a random-digit-dialing telephone survey (n = 34,480 completed interviews) of parents of children aged 19 to 35 months from 50 states and 28 selected urban areas in the United States that included a provider record check mail survey. MAIN OUTCOME MEASURES: Percentage of infants who received at least 3 doses of hepatitis B vaccine and percentage who received the 4:3:1:3 vaccine series, by age at receipt of the first dose of hepatitis B vaccine. RESULTS: Overall, 86.9% of children 19 to 35 months of age in 1998 received 3 or more doses of hepatitis B vaccine, and 79.9% completed the 4:3:1:3 vaccine series. Multivariate analysis indicated that, compared with children who received the first hepatitis B vaccine dose within 7 days of birth, odds ratios (ORs) for not completing the 3-dose hepatitis B vaccine series among children who received the first dose at 8 to 41 days, 42 to 91 days, 92 to 182 days, 183 to 273 days, and 274 or more days of age were 2.4 (95% confidence interval [CI], 2.0-3.0), 7.8 (95% CI, 6.5-9.3), 9.6 (95% CI, 7.0-13. 3), 18.3 (95% CI, 12.0-28.0), and 46.6 (95% CI, 33.7-64.5), respectively; ORs for not completing the 4:3:1:3 vaccine series among these same groups were 1.0 (95% CI, 0.8-1.1), 1.0 (95% CI, 0. 8-1.1), 1.7 (95% CI, 1.3-2.3), 3.8 (95% CI, 2.6-5.6), and 4.0 (95% CI, 2.9-5.5), respectively. CONCLUSION: Administration of the first dose of hepatitis B vaccine at birth is associated with increased likelihood of completion of the hepatitis B vaccination series. JAMA. 2000;284:978-983