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COVID-19 vaccines are critical for ending the COVID-19 pandemic; however, current data about vaccination coverage and safety in pregnant women are limited. Pregnant women are at increased risk for severe illness and death from COVID-19 compared with nonpregnant women of reproductive age, and are at risk for adverse pregnancy outcomes, such as preterm birth (1-4). Pregnant women are eligible for and can receive any of the three COVID-19 vaccines available in the United States via Emergency Use Authorization.* Data from Vaccine Safety Datalink (VSD), a collaboration between CDC and multiple integrated health systems, were analyzed to assess receipt of ≥1 dose (first or second dose of the Pfizer-BioNTech or Moderna vaccines or a single dose of the Janssen [Johnson & Johnson] vaccine) of any COVID-19 vaccine during pregnancy, receipt of first dose of a 2-dose COVID-19 vaccine (initiation), or completion of a 1- or 2-dose COVID-19 vaccination series. During December 14, 2020-May 8, 2021, a total of 135,968 pregnant women were identified, 22,197 (16.3%) of whom had received ≥1 dose of a vaccine during pregnancy. Among these 135,968 women, 7,154 (5.3%) had initiated and 15,043 (11.1%) had completed vaccination during pregnancy. Receipt of ≥1 dose of COVID-19 vaccine during pregnancy was highest among women aged 35-49 years (22.7%) and lowest among those aged 18-24 years (5.5%), and higher among non-Hispanic Asian (Asian) (24.7%) and non-Hispanic White (White) women (19.7%) than among Hispanic (11.9%) and non-Hispanic Black (Black) women (6.0%). Vaccination coverage increased among all racial and ethnic groups over the analytic period, likely because of increased eligibility for vaccination† and increased availability of vaccine over time. These findings indicate the need for improved outreach to and engagement with pregnant women, especially those from racial and ethnic minority groups who might be at higher risk for severe health outcomes because of COVID-19 (4). In addition, providing accurate and timely information about COVID-19 vaccination to health care providers, pregnant women, and women of reproductive age can improve vaccine confidence and coverage by ensuring optimal shared clinical decision-making.

OBJECTIVES: Influenza vaccination coverage among pregnant women in the United States is suboptimal. We surveyed women who were pregnant during the 2016–17 influenza season to assess knowledge and attitudes regarding influenza vaccination. METHODS: We identified and sampled pregnant women to include approximately equal numbers of vaccinated and unvaccinated women from strata defined by vaccination status and trimester from four integrated health systems in the Vaccine Safety Datalink (VSD). Potential participants were contacted via mail and telephone to complete a standardized survey. Characteristics and responses of women vaccinated and unvaccinated during pregnancy were compared. RESULTS: The survey was completed by 510 (48%) of 1062 contacted women; 500 were included in the analysis. Vaccine receipt while pregnant was associated with primigravida status (p = 0.02), college degree (p = 0.01), employment in health care (p < 0.01), and history of routine annual influenza vaccination (p < 0.01). Among 330 vaccinated women, the primary reasons for vaccination included protection of self and baby from influenza (n = 233, 71%), and medical professional recommendation (n = 46, 14%). Multiple reasons were given for nonvaccination, but concern about ‘negative effects’ was cited most often (n = 44, 29%). Vaccinated women were significantly more likely to believe that influenza vaccines are safe and effective, and to recognize the potential for harm from influenza infection. Nearly all women reported receiving at least one influenza vaccination recommendation from a healthcare provider. CONCLUSIONS: Vaccinated pregnant women were more likely to receive routine annual influenza vaccine compared to those not vaccinated. Recommendations by obstetric providers should be supplemented with efforts to encourage women of childbearing age to receive annual vaccination.

Introduction A recent study reported an association between inactivated influenza vaccine (IIV) and spontaneous abortion (SAB), but only among women who had also been vaccinated in the previous influenza season. We sought to estimate the association between IIV administered in three recent influenza seasons and SAB among women who were and were not vaccinated in the previous influenza season. Methods We conducted a case-control study over three influenza seasons (2012–13, 2013–14, 2014–15) in the Vaccine Safety Datalink (VSD). Cases (women with SAB) and controls (women with live births) were matched on VSD site, date of last menstrual period, age group, and influenza vaccination status in the previous influenza season. Of 1908 presumptive cases identified from the electronic record, 1236 were included in the main analysis. Administration of IIV was documented in several risk windows, including 1–28, 29–56, and >56 days before the SAB date. Results Among 627 matched pairs vaccinated in the previous season, no association was found between vaccination in the 1–28 day risk window and SAB (adjusted odds ratio (aOR) 0.9; 95% confidence interval (CI) 0.6–1.5). The season-specific aOR ranged from 0.5 to 1.7 with all CIs including the null value of 1.0. Similarly, no association was found among women who were not vaccinated in the previous season; the season-specific aOR in the 1–28 day risk window ranged from 0.6 to 0.7 and the 95% CI included 1.0 in each season. There was no association found between SAB and influenza vaccination in the other risk windows, or when vaccine receipt was analyzed relative to date of conception. Conclusion During these seasons we found no association between IIV and SAB, including among women vaccinated in the previous season. These findings lend support to current recommendations for influenza vaccination at any time during pregnancy, including the first trimester.

This cohort study examines the risks for spontaneous abortion, preterm birth, small-for-gestational age birth, and major structural birth defects among female teenagers and adults who received the human papillomavirus vaccine., Key Points Question Is exposure to the 9-valent human papillomavirus (9vHPV) vaccine in pregnancy associated with adverse pregnancy or birth outcomes? Findings In this cohort study of 1493 pregnancies, in adjusted analyses, during-pregnancy or peripregnancy exposures to 9vHPV vaccine were not associated with spontaneous abortion. Among live births, 9vHPV vaccine exposures during or around the time of pregnancy were not associated with adverse birth outcomes. Meaning Results of this study suggest that, in an insured population, adverse events after exposure to 9vHPV vaccine during or around the time of pregnancy were uncommon; these findings can inform counseling after inadvertent 9vHPV vaccine exposures., Importance The 9-valent human papillomavirus (9vHPV) vaccine is recommended for individuals through age 26 years and may be administered to women up to age 45 years. Data on 9vHPV vaccine exposures during pregnancy are limited. Objective To evaluate the associations between 9vHPV vaccine exposures during pregnancy or peripregnancy and selected pregnancy and birth outcomes (spontaneous abortion [SAB], preterm birth, small-for-gestational age [SGA] birth, and major structural birth defect). Design, Setting, and Participants This cohort study analyzed data from 7 participating health systems in the Vaccine Safety Datalink. The cohort comprised pregnancies among girls and women aged 12 to 28 years that ended between October 26, 2015, and November 15, 2018. Singleton pregnancies that ended in a live birth, stillbirth, or SAB were included. Exposures Vaccine exposure windows were distal (9vHPV or 4vHPV vaccine administered from 22 to 16 weeks before last menstrual period [LMP]), peripregnancy (9vHPV vaccine administered from 42 days before LMP until LMP), and during pregnancy (9vHPV vaccine administered from LMP to 19 completed weeks’ gestation). Primary comparisons were (1) girls and women with 9vHPV vaccine exposures during pregnancy vs those with 4vHPV or 9vHPV distal vaccine exposures, (2) girls and women with vaccine exposures peripregnancy vs those with 4vHPV or 9vHPV distal vaccine exposures, and (3) girls and women with 9vHPV vaccine exposures during pregnancy or peripregnancy vs those with 4vHPV or 9vHPV distal vaccine exposure. Main Outcomes and Measures Spontaneous abortions were confirmed based on medical record review and adjudication. Preterm and SGA births were identified from electronic health record and birth data. Major structural birth defects were based on diagnostic codes using a validated algorithm. Inverse probability weighting was used to balance the covariates. Time-dependent covariate Cox proportional hazards regression models and Poisson regression were used to estimate the associations between 9vHPV vaccine exposures and pregnancy and birth outcomes. Results The final cohort included 1493 pregnancies among girls and women with a mean (SD) maternal age of 23.9 (2.9) years. Of these pregnancies, 445 (29.8%) had exposures to the 9vHPV vaccine during pregnancy, 496 (33.2%) had exposures to the 9vHPV vaccine peripregnancy, and 552 (37.0%) had 4vHPV or 9vHPV distal vaccine exposures. The 9vHPV vaccine administered during pregnancy was not associated with increased risk for SAB (hazard ratio, 1.12; 95% CI, 0.66-1.93) compared with distal vaccine exposures. Findings were similar for 9vHPV vaccine exposures peripregnancy (relative risk [RR], 0.72; 95% CI, 0.42-1.24). Among live births (n = 1409), 9vHPV vaccine exposures during pregnancy were not associated with increased risks for preterm birth (RR, 0.73; 95% CI, 0.44-1.20) or SGA birth (RR, 1.31; 95% CI, 0.78-2.20). Results were similar regarding the association between 9vHPV vaccine exposures peripregnancy and preterm birth (RR, 0.72; 95% CI, 0.45-1.17) and SGA birth (RR, 1.10; 95% CI, 0.65-1.88). Birth defects were rare in all exposure groups, occurring in about 1% of live births with available infant data. Conclusions and Relevance This study found that 9vHPV vaccine exposures during or around the time of pregnancy were uncommon and not associated with SABs or selected adverse birth outcomes. These findings can inform counseling for inadvertent 9vHPV vaccine exposures.

Seven to ten days after a first dose of a measles-containing vaccine (MCV; i.e., MMR or MMRV), children have elevated fever risk which can be associated with febrile seizures. This study investigated individual and familial factors associated with fever 7-10days after MCV.Retrospective cohort study among children who were36months of age at receipt of MCV in six sites of the Vaccine Safety Datalink from 1/1/2000 to 12/31/2012. We evaluated medically-attended clinic or emergency department visits with a code for fever 7-10days after any MCV ("MCV- associated"). We evaluated factors associated with MCV-associated fever using χAmong 946,806 children vaccinated with MCV, we identified 7480 (0.8%) MCV-associated fever visits. Compared with children without fever after MCV, children with MCV-associated fever were more likely to have received MMRV than MMR (OR 1.3 95% CI 1.2, 1.5), have had medically attended fever both following previous vaccines (OR 1.3 95% CI 1.1, 1.6) and at any other previous time (OR 1.7 95% CI 1.6, 1.8), have had at least 1 prior seizure (OR 2.2 95% CI 1.7, 2.7), and have had3 medical visits within the 6months before MCV (OR 1.7 95% CI 1.6, 1.8). In families with multiple MCV-immunized children, after adjusting for healthcare seeking behavior care for fever, those whose siblings had MCV-associated fever were more likely to also have MCV-associated fever (OR 3.5 95% CI 2.5, 4.8).Children who received MMRV vaccine or who had prior medically-attended fevers and seizures during the first year of life had increased risk of fever after a first dose of measles vaccine. After adjusting for familial propensity to seek care, MCV-associated fever still clustered within families, suggesting a possible genetic basis for susceptibility to developing fever due to measles vaccines.

BACKGROUND AND OBJECTIVES: Human papillomavirus is the most common sexually transmitted infection in the United States and causes certain anogenital and oropharyngeal cancers. The 9-valent human papillomavirus vaccine (9vHPV) provides protection against additional types not included in the quadrivalent vaccine. We conducted near real-time vaccine safety surveillance for 24 months after the vaccine became available in the Vaccine Safety Datalink. METHODS: Immunizations and adverse events were extracted weekly from October 2015 to October 2017 from standardized data files for persons 9 to 26 years old at 6 Vaccine Safety Datalink sites. Prespecified adverse events included anaphylaxis, allergic reaction, appendicitis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, injection site reaction, pancreatitis, seizure, stroke, syncope, and venous thromboembolism. The observed and expected numbers of events after 9vHPV were compared weekly by using sequential methods. Both historical and concurrent comparison groups were used to identify statistical signals for adverse events. Unexpected signals were investigated by medical record review and/or additional analyses. RESULTS: During 105 weeks of surveillance, 838 991 doses of 9vHPV were administered. We identified unexpected statistical signals for 4 adverse events: appendicitis among boys 9 to 17 years old after dose 3; pancreatitis among men 18 to 26 years old; and allergic reactions among girls 9 to 17 years old and women 18 to 26 years old after dose 2. On further evaluation, which included medical record review, temporal scan analysis, and additional epidemiological analyses, we did not confirm signals for any adverse events. CONCLUSIONS: After 2 years of near real-time surveillance of 9vHPV and several prespecified adverse events, no new safety concerns were identified.

Background Some parents, especially those of children with autism spectrum disorders (ASD), are uncertain about the safety of childhood immunization. We compared rates of fever, febrile seizure and emergency room (ER) visits following measles and pertussis-containing vaccines recommended between ages 4–6 years among children with and without ASD. Methods The study included children who were born between 1995–2012, aged 4–7 years at vaccination, and members of six integrated healthcare delivery systems within the Vaccine Safety Datalink. Children with ASD were defined based on receipt of two separate International Classification of Diseases (ICD)-9 or 10 codes. Outcomes (fever, febrile seizures, and ER visits) were identified in electronic health records. To minimize confounding by unmeasured factors related both to avoidance of vaccination and to outcomes of interest, we compared rates of each outcome between children with and without ASD, in risk and control intervals, by estimating the difference-in-differences on a log scale (i.e. the ratio of rate ratios) using logistic regressions. We also conducted risk interval analyses comparing rates of outcomes in risk intervals and control intervals within each group. Results The study included 14,947 children with ASD and 1,650,041 children without ASD. After measles or pertussis-containing vaccination, there were no differences in association between the two groups for fever or ER visits (Table). There were no febrile seizures identified among children with ASD. Within the ASD group, rates of fever, seizure or ER visits did not differ significantly between the risk and control intervals after vaccination. However, among the non-ASD group, measles and pertussis-containing vaccines were associated with higher rates of fever and seizure in risk intervals compared to controls intervals. Pertussis-containing vaccines were associated with increased risk of ER visits in risk interval compared to control interval (Table). Conclusion We found no difference in the risk of fever, and ER visits comparing children with autism to children without autism after measles or pertussis-containing vaccines. The study provides some reassurance that these vaccines are not less safe in children with ASD. Disclosures Lei Qian, PhD, GlaxoSmithKlein (Research Grant or Support) Nicola P. Klein, MD, PhD, GSK group of companies (Research Grant or Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support)Protein Science (now SP) (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)

OBJECTIVE: To evaluate the risk of spontaneous abortion after quadrivalent human papillomavirus (4vHPV) vaccination before and during pregnancy across seven integrated health systems within the Vaccine Safety Datalink. METHODS: Within a retrospective observational cohort, we compared risks for spontaneous abortion after 4vHPV in three exposure windows: distal (16–22 weeks prior to last menstrual period (LMP)), peripregnancy (within 6 weeks prior to LMP) and during pregnancy (LMP through 19 weeks of gestation). Women 12–27 years of age with a pregnancy between 2008 and 2014, with continuous insurance enrollment 8 months prior to and through pregnancy end, and with a live birth, stillbirth, or spontaneous abortion were included. Pregnancies were identified through validated algorithms. Spontaneous abortions and stillbirths were verified via chart review, with spontaneous abortions adjudicated by clinical experts. We excluded multiple gestations, spontaneous abortions before 6 weeks of gestation, and women using medications increasing risk for spontaneous abortion. Spontaneous abortion risk after 4vHPV during pregnancy was compared to distal vaccination using time dependent covariate Cox models. Spontaneous abortion risk for peri-pregnancy versus distal vaccination was evaluated with standard Cox models. RESULTS: We identified 2,800 pregnancies with 4vHPV exposure in specified risk windows: 919 (33%) distal, 986 (35%) peripregnancy and 895 (32%) during pregnancy. Mean age was 22.4 years in distal and peripregnancy groups versus 21.4 years among women vaccinated during pregnancy. Among women with distal 4vHPV exposure, 96 (10.4%) experienced a spontaneous abortion. For peripregnancy and during pregnancy exposures, spontaneous abortions occurred in 110 (11.2%) and 77 (8.6%), respectively. The risk of spontaneous abortion was not increased among women who received 4vHPV during pregnancy (adjusted hazard ratio 1.10 (95% CI: 0.81–1.51)) or peripregnancy 1.07 (0.81–1.41). CONCLUSION: Inadvertent 4vHPV exposure during or peripregnancy was not significantly associated with an increased risk for spontaneous abortion.

In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, maintaining protection may require repeated Tdap vaccination. We evaluated the safety of repeated doses of tetanus-containing vaccine in 68 915 nonpregnant adolescents and adults in the Vaccine Safety Datalink population who had received an initial dose of Tdap. Compared with 7521 subjects who received a subsequent dose of tetanus toxoid, reduced diphtheria (Td) vaccine, the 61 394 subjects who received a subsequent dose of Tdap did not have significantly elevated risk of medical visits for seizure, cranial nerve disorders, limb swelling, pain in limb, cellulitis, paralytic syndromes, or encephalopathy/encephalitis/meningitis. These results suggest that repeated Tdap vaccination has acceptable safety relative to Tdap vaccination followed by Td vaccination.

Introduction Infection with hepatitis A virus (HAV) during pregnancy, although uncommon, is associated with gestational complications and pre-term labor. Hepatitis A vaccine (HepA) is recommended for anyone at increased risk for contracting hepatitis A, including women at risk who are also pregnant. Limited data are available on the safety of maternal HepA vaccination. Objectives Assess the frequency of maternal HepA receipt and evaluate the potential association between maternal vaccination and pre-specified maternal and infant safety outcomes. Methods A retrospective cohort of pregnancies in the Vaccine Safety Datalink (VSD) resulting in live births from 2004 through 2015 was included. Pregnancies with HepA exposure were compared to those with other vaccine exposures, and to those with no vaccine exposures. Risk factors for contracting hepatitis A were identified up to one-year prior to or during the pregnancy using ICD-9 codes. Maternal and fetal adverse events were evaluated according to maternal HepA exposure status. Adjusted odds ratio (OR) were used to describe the association. Results Among 666,233 pregnancies in the study period, HepA was administered at a rate of 1.7 per 1000 (n = 1140), most commonly within the first six weeks of pregnancy. Less than 3% of those exposed to HepA during pregnancy had an ICD-confirmed risk factor. There were no significant associations between HepA exposure during pregnancy and gestational hypertension, gestational diabetes, pre-eclampsia/eclampsia, cesarean delivery, pre-term delivery, and low birthweight. There was a statistically significant association between HepA exposure during pregnancy and small-for-gestational age (SGA) infants (aOR 1.32, [95% CI 1.09, 1.60], p = 0.004). Conclusions The rate of maternal HepA vaccination was low and rarely due to documented risk factors for vaccination. HepA vaccination during pregnancy was not associated with an increased risk for a range of adverse events examined among pregnancies resulting in live births, but an identified association between maternal HepA and SGA infant outcomes, while likely due to unmeasured confounding, warrants further exploration.

Background The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was recommended for use in adolescents in 2005. Soon after, case reports of Guillain-Barre syndrome (GBS) following vaccination prompted subsequent studies, with a meta-analysis concluding that the attributable risk of GBS after MenACWY-D is unlikely to exceed 1 case per million vaccinations. We conducted a retrospective cohort study in the Vaccine Safety Datalink to assess the risk of 10 outcomes, including GBS, following MenACWY-D. Methods We included adolescents (aged 11–18 years) vaccinated with MenACWY-D during the years 2005–2014. We identified pre-specified outcomes using ICD-9 (International Classification of Disease, version 9) codes. We used automated data only for Bell’s palsy, fever, seizure and syncope, and we confirmed incident cases by medical record review for acute disseminated encephalomyelitis (ADEM), acute transverse myelitis (ATM), anaphylaxis, chronic inflammatory demyelinating polyneuropathy (CIDP), GBS and Henoch-Schönlein purpura (HSP). We used a self-controlled risk interval design to estimate relative risk (RR). Results Following 1.4 million doses of MenACWY-D, we detected increased risks for fever in the 1–6 days following vaccination (RR 1.5, 95% confidence interval [CI] 1.3–1.7) and syncope on the day of vaccination (RR 5.8, 95% CI 4.1–8.3), but not for seizures (RR 1.1, 95% CI 0.7–1.9) or Bell’s palsy (RR 1.1, 95% CI 0.8–1.5). We detected no cases in the post-vaccination risk intervals for CIDP, ADEM or ATM. We detected few cases of the other outcomes resulting in relatively unstable RR estimates: anaphylaxis (RR 1.9, 95% CI 0.5–7.1), GBS (RR 2.5, 95% CI 0.6–10.0) and HSP (RR 1.6, 95% CI 0.7–3.3). We estimated that the attributable risk of GBS was 1.5 cases per million vaccinations (upper bound of one-sided 95% CI, 4.9). Conclusion In a large retrospective cohort, we detected increased risks for syncope and fever, but not seizures or Bell’s palsy, following vaccination with MenACWY-D. Other outcomes were rare. Our findings, consistent with previous studies, suggest that the increased risk of GBS, if any, is likely small (

Introduction The Vaccine Safety Datalink (VSD) is a collaborative project whose infrastructure provides comprehensive medical and immunization histories for more than 9 million adults and children annually, a predominantly insured population. This study provides the coverage rates of recommended vaccines among children 19–35 months in the VSD from 2005 through 2010. We examine the consistency in vaccine coverage levels, detect possible trends, and evaluate any effect of vaccine shortages on coverage in the VSD. Methods We included data from all 10 VSD sites, and examined each year independently. Coverage rates were defined as the percentage of children in the VSD aged 19, 24, or 35 months in a given study year who had received the specified Advisory Committee on Immunization Practices (ACIP) recommended vaccine(s). Results We assessed coverage on 658,154 children. The overall coverage rate for children receiving all of the specified ACIP recommended vaccines was 73%, 80%, and 78% at ages 19, 24, and 35 months respectively. The range of coverage across all ages and years was 95–97% for polio vaccine, 91–97%, for MMR vaccine, 94–97% for HepB vaccine, 81–95% for DTaP vaccine, 90–95% for varicella vaccine, 66–91% for PCV, and 93–98% for Hib vaccine. Coverage rates of 4 or more doses of PCV were relatively low in 2005 possibly due to a vaccine shortage, and increased sharply in 2007. Hib vaccine coverage was relatively stable among all ages until 2009 when rates declined among children aged 19 and 24 months also during a vaccine shortage. Conclusions Vaccine coverage in the VSD is high, but there is a decline from 2005 to 2010. The results of this study provide benchmark data for future studies, and describe how vaccine supply shortages and resulting changes in ACIP recommendations may have affected vaccine coverage rates in the VSD.

OBJECTIVE: Our objective was to assess whether the occurrence of medically attended local reactions to intramuscularly administered vaccines varies by injection site (arm versus thigh) in children 1 to 6 years of age. METHODS: This is a retrospective cohort study of children in the Vaccine Safety Datalink population from 2002 to 2009. Site of injection and the outcome of medically attended local reactions were identified from administrative data. RESULTS: The study cohort of 1.4 million children received 6.0 million intramuscular (IM) vaccines during the study period. The primary analyses evaluated the IM vaccines most commonly administered alone, which included inactivated influenza, hepatitis A, and diphtheria-tetanus-acellular pertussis (DTaP) vaccines. For inactivated influenza and hepatitis A vaccines, local reactions were relatively uncommon, and there was no difference in risk of these events with arm versus thigh injections. The rate of local reactions after DTaP vaccines was higher, and vaccination in the arm was associated with a significantly greater risk of this outcome compared with vaccination in the thigh, both for children 12 to 35 months (relative risk: 1.88 [95% confidence interval: 1.34–2.65]) and 3 to 6 years of age (relative risk: 1.41 [95% confidence interval: 0.84–2.34]), although this difference was not statistically significant in the older age group. CONCLUSIONS: Injection in the thigh is associated with a significantly lower risk of a medically attended local reaction to a DTaP vaccination among children 12 to 35 months of age, supporting current recommendations to administer IM vaccinations in the thigh for children younger than 3 years of age.

BACKGROUND Published data on the safety of tetanus-diphtheria-acellular pertussis vaccine (Tdap) in persons aged ≥65 years are limited. This study aims to examine a large cohort of Tdap users ≥65 years for evidence of increased risk of adverse events following vaccination. METHODS A matched cohort study design and a self-controlled case series (SCCS) design were used. The study population was adults aged ≥65 years who received the Tdap or tetanus and diphtheria (Td) vaccine during 1 January 2006-31 December 2010 at 7 health maintenance organizations in the United States. Seven major groups of prespecified events were identified electronically by diagnostic codes. RESULTS The study included 119 573 Tdap vaccinees and the same number of Td vaccinees. The results indicated that the risk of the prespecified events following Tdap was comparable to that following Td vaccination in this elderly population. There was a small increased rate of codes suggesting medically attended inflammatory or allergic events in 1-6 days following Tdap in the SCCS analysis (incidence rate ratio, 1.59 [95% confidence interval, 1.40-1.81]). CONCLUSION Although there is a small increased risk of medically attended inflammatory or allergic events in 1-6 days following Tdap compared to other time periods, it is no more common than that following Td. This study provides empirical safety data suggesting that immunizing adults aged ≥65 years with Tdap to reduce the risk of pertussis in the elderly and their contacts should not have untoward safety consequences.

The continuing epizootic of H5N1 avian influenza (AI) in Asia and subsequent zoonotic transmission has led to heightened concerns about a pandemic and the demand for improved surveillance of poultry in all sectors, including backyard poultry. We conducted a 15-month prospective study to determine the prevalence of AI in backyard poultry and extent of transmission to flock handlers.Starting July 2007, registered poultry owners in six counties in central Wisconsin were mailed invitations to participate; household members with poultry exposure were also invited. Premises with1000 birds were eligible. Participants completed a baseline interview to characterize poultry exposures. Illness in flocks and flock handlers was monitored using semimonthly telephone interviews and self-report of acute influenza-like symptoms by flock handlers. Participants provided blood at baseline and at the end of the surveillance period for serology and, if ill, nasopharyngeal, eye, and throat swabs for viral testing. Blood was also collected at baseline from a convenience sample of adult poultry.We enrolled 87 flocks and 128 persons who had regular contact with poultry. Influenza-like symptoms were reported by 77 (65%) persons. Swabs were collected from 53 persons at 88 illness episodes. AI was not isolated, but five persons were positive for human influenza. Twenty-one participants (20%) seroconverted to at least one human influenza strain, but there were no seroconversions to AI. Blood samples from all 717 birds tested were seronegative for influenza.Despite limited biosecurity there was no evidence of AI infection in participating backyard flocks or flock handlers.

Mass vaccination campaigns during which new vaccines may be administered to many millions of people in a short period of time call for timely and accurate post-licensure surveillance to monitor vaccine safety. To address the need for timely H1N1 influenza vaccine safety information during the 2009-2010 H1N1 influenza pandemic, the Vaccine Safety Datalink (VSD) project assessed the feasibility and potential mechanisms for utilizing data from state and local immunization registries to capture vaccinations that would not otherwise be captured by the data systems of the participating VSD managed care organizations (MCOs). Three of the eight VSD sites were able to capture H1N1 immunization data electronically from the state and local registries, and one site was able to capture the immunizations through a paper-based system; however, the remaining four sites encountered various obstacles that prevented capture of such data. Additional work will be required at these sites to overcome the barriers, which included privacy and confidentiality laws, time constraints brought on by the pandemic, as well as data quality concerns.

Please cite this paper as: Irving et al. (2012) Comparison of clinical features and outcomes of medically attended influenza A and influenza B in a defined population over four seasons: 2004–2005 through 2007–2008. Influenza and Other Respiratory Viruses 6(1), 37–43. Background There are few prospectively collected data comparing illnesses caused by different subtypes of influenza. We compared the clinical presentation and outcomes of subjects with primarily outpatient‐attended influenza A and B infections during four consecutive influenza seasons (2004–2005 through 2007–2008). Methods Patients were prospectively enrolled and tested for influenza following an encounter for acute respiratory illness. Influenza infections were confirmed by culture or reverse transcription polymerase chain reaction; subtype was determined for a sample of influenza A isolates each season. Clinical characteristics of influenza A and B infections were compared across and within individual seasons. Results We identified 901 cases of influenza A and 284 cases of influenza B; 98% of cases were identified through an outpatient medical encounter. Thirty‐six percent of patients with each strain had received seasonal influenza vaccine prior to illness onset. There were no consistent differences in symptoms associated with influenza A and B. Influenza A infection was associated with earlier care seeking compared with influenza B during the 2005–2006 and 2007–2008 seasons, when H3N2 was the dominant type A virus, and in a combined analysis that included all seasons. Twenty‐six (2·2%) of 1185 cases were diagnosed with radiographically confirmed pneumonia, and 59 (5%) of 1185 patients were hospitalized within 30 days of illness onset. Conclusions Over four influenza seasons, aside from shorter intervals from illness onset to clinical encounter for infections with the A(H3N2) subtype, clinical symptoms and outcomes were similar for patients with predominantly outpatient‐attended influenza A and B infections.

Importance In recent years, rates of vaccination have been declining. Whether this phenomenon disproportionately affects children with autism spectrum disorder (ASD) or their younger siblings is unknown. Objectives To investigate if children after receiving an ASD diagnosis obtain their remaining scheduled vaccines according to the Advisory Committee on Immunization Practices (ACIP) recommendations and to compare the vaccination patterns of younger siblings of children with ASD with the vaccination patterns of younger siblings of children without ASD. Design, Setting, and Participants This investigation was a retrospective matched cohort study. The setting was 6 integrated health care delivery systems across the United States within the Vaccine Safety Datalink. Participants were children born between January 1, 1995, and September 30, 2010, and their younger siblings born between January 1, 1997, and September 30, 2014. The end of follow-up was September 30, 2015. Exposures Recommended childhood vaccines between ages 1 month and 12 years. Main Outcome and Measure The proportion of children who received all of their vaccine doses according to ACIP recommendations. Results The study included 3729 children with ASD (676 [18.1%] female), 592 907 children without ASD, and their respective younger siblings. Among children without ASD, 250 193 (42.2%) were female. For vaccines recommended between ages 4 and 6 years, children with ASD were significantly less likely to be fully vaccinated compared with children without ASD (adjusted rate ratio, 0.87; 95% CI, 0.85-0.88). Within each age category, vaccination rates were significantly lower among younger siblings of children with ASD compared with younger siblings of children without ASD. The adjusted rate ratios varied from 0.86 for siblings younger than 1 year to 0.96 for those 11 to 12 years old. Parents who had a child with ASD were more likely to refuse at least 1 recommended vaccine for that child’s younger sibling and to limit the number of vaccines administered during the younger sibling’s first year of life. Conclusions and Relevance Children with ASD and their younger siblings were undervaccinated compared with the general population. The results of this study suggest that children with ASD and their younger siblings are at increased risk of vaccine-preventable diseases.

Several case reports have described immune hemolytic anemia (IHA) following vaccination in children. We examined the risk of IHA in the 42 days following vaccination exposure using a self-controlled case series study design. In our population-based cohort of nearly 4.5 million children in the Vaccine Safety Datalink, we identified 55 confirmed cases of new-onset IHA from 1991 through 2000. We found no association between IHA and diphtheria-pertussis-tetanus vaccination (incidence rate ratio (IRR)=0.65, 95% CI: 0.19-2.24), hepatitis B vaccination (IRR=1.73, 95% CI: 0.59-5.01), or any vaccination (IRR=1.04, 95% CI: 0.46-2.32).

Summary Objectives: To assess how well selected ICD-9-CM diagnosis codes predict adverse events; to model bias and power loss when vaccine safety analyses rely on unverified codes. Methods: We extracted chart verification data for ICD-9-CM diagnosis codes from six Vaccine Safety Datalink (VSD) publications and modeled biases and power losses using positive predictive value (PPV) estimates and ranges of code sensitivity. Results: Positive predictive values were high for type 1 diabetes (80%) in children, relative to WHO criteria, and intussusception (81%) in young children, relative to a standard published case definition. PPVs were moderate (65%) for inpatient and emergency department childhood seizures and low (21%) for outpatient childhood seizures, both relative to physician investigator judgment. Codes for incident central nervous system demyelinating disease in adults had high PPV for inpatient codes (80%) and low PPV for outpatient codes (42%) relative to physicians’ diagnoses. Modeled biases were modest, but large increases in frequencies of adverse events are required to achieve adequate power if unverified ICD-9-CM codes are used, especially when vaccine associations are weak. Conclusions: ICD-9-CM codes for type 1 diabetes in children, intussusception in young children, childhood seizures in inpatient and emergency care settings, and inpatient demyelinating disease in adults were sufficiently predictive for vaccine safety analyses to rely on unverified diagnosis codes. Adverse event misclassification should be accounted for in statistical power calculations.

Bioterrorism surveillance systems can be assessed using modeling to simulate real-world attacks., We measured sensitivity and timeliness of a syndromic surveillance system to detect bioterrorism events. A hypothetical anthrax release was modeled by using zip code population data, mall customer surveys, and membership information from HealthPartners Medical Group, which covers 9% of a metropolitan area population in Minnesota. For each infection level, 1,000 releases were simulated. Timing of increases in use of medical care was based on data from the Sverdlovsk, Russia, anthrax release. Cases from the simulated outbreak were added to actual respiratory visits recorded for those dates in HealthPartners Medical Group data. Analysis was done by using the space-time scan statistic. We evaluated the proportion of attacks detected at different attack rates and timeliness to detection. Timeliness and completeness of detection of events varied by rate of infection. First detection of events ranged from days 3 to 6. Similar modeling may be possible with other surveillance systems and should be a part of their evaluation.

Objective—To identify factors significantly associated with an epidemic of fibrinous pericarditis during spring 2001 among horses in central Kentucky. Design—Case-control study. Animals—38 horses with fibrinous pericarditis and 30 control horses examined for other reasons. Procedure—A questionnaire was developed to solicit information regarding a wide range of management practices and environmental exposures from farm owners or managers. Results—The following factors were found in bivariate analyses to be significantly associated with an increased risk of pericarditis: being from a farm with mares and foals affected by mare reproductive loss syndrome, exposure to Eastern tent caterpillars in or around horse pastures, younger age, shorter duration of residence in Kentucky and at the farm of current residence, being fed hay grown outside Kentucky, a lack of access to pond water, access to orchard grass for grazing, and a lack of direct contact with cattle. In multivariate logistic regression analyses, only variables related to caterpillar exposure and age were significantly associated with fibrinous pericarditis. Conclusions and Clinical Relevance—Results suggest that fibrinous pericarditis in horses may be associated with mare reproductive loss syndrome. Exposure to Eastern tent caterpillars was the greatest risk factor for development of fibrinous pericarditis. The distribution of times of diagnosis of fibrinous pericarditis was consistent with a point-source epidemic. (J Am Vet Med Assoc 2003;223:832–838)

The automated health plan data and data from medical chart abstractions from eight large health maintenance organizations were used to evaluate the positive predictive values (PPVs) of the International Classification of Diseases, 9th revision (ICD-9) codes for cases of peptic ulcers and upper gastrointestinal bleeding. Overall, 207 of 884 cases of peptic ulcers and upper gastrointestinal bleeding (23%) were confirmed by surgery, endoscopy, X-ray, or autopsy. The PPVs were 66% for hospitalizations with codes for duodenal ulcer (ICD-9-CM 532), 61% for gastric/gastrojejunal ulcer (ICD-9-CM 531, 534), 1% for peptic ulcer (ICD-9-CM 533), and 9% for gastrointestinal hemorrhage (ICD-9-CM578). The overall and diagnostic category-specific PPVs were generally similar for the various HMOs. This study, using data from a large number of health plans located in different geographical regions, underscores the importance of evaluating the accuracy of the diagnoses from automated health plan databases.

Background: Asthma is the most common chronic disease among children and the most frequent cause of hospitalization. Appropriate pharmacotherapy is a cornerstone of published national guidelines for the care of children with asthma. Objective: The goal was to compare the baseline pharmacotherapy and health care utilization from 1996 to 1997 in children with asthma at managed care organizations (MCOs). Methods: A common protocol was used to extract the study sample from 3 MCOs with automated claims and pharmacy databases. Children were selected if they were 3 to 15 years old as of June 1997 with 1 or more encounters (outpatient, emergency department visit, hospitalization) with an asthma diagnosis in the previous year. Results: Of the 13,352 children studied, less than 40% were given controllers during the 12-month interval, with ranges of 15% to 77% by level of bronchodilator use, 31% to 44% by age, and 38% to 42% by MCO. Among children given 6 or more bronchodilators, controller dispensing ranged from 73% to 89% among the 3 MCOs. Variability was most evident for inhaled corticosteroids, for which dispensing ranged from 51% to 70%. Rates of asthma hospitalization and emergency department visits also differed among the MCOs, ranging from 21 to 37 per 1000 person-years and 37 to 142 per 1000 person-years, respectively. Conclusion: Five years after dissemination of national guidelines for care, the pattern of asthma therapy does not reflect guideline recommendations. Variation among health care organizations with respect to asthma therapy and utilization of health services exists. In addition, controller medications may not be used by all children who could benefit from them. (J Allergy Clin Immunol 2000;106:1108-14.)

Summary Background Inhibitors of hydroxymethylglutaryl-coenzyme A reductase (statins) increase new bone formation in rodents and in human cells in vitro. Statin use is associated with increased bone mineral density of the femoral neck. We undertook a population-based case-control study at six health-maintenance organisations in the USA to investigate further the relation between statin use and fracture risk among older women. Methods We investigated women aged 60 years or older. Exposure, outcome, and confounder information was obtained from automated claims and pharmacy data from October, 1994, to September, 1997. Cases had an incident diagnosis of non-pathological fracture of the hip, humerus, distal tibia, wrist, or vertebrae between October, 1996, and September, 1997. Controls had no fracture during this period. We excluded women with records of dispensing of drugs to treat osteoporosis. Findings There were 928 cases and 2747 controls. Compared with women who had no record of statin dispensing during the previous 2 years, women with 13 or more statin dispensings during this period had a decreased risk of non-pathological fracture (odds ratio 0·48 [95% CI 0·27–0·83]) after adjustment for age, number of hospital admissions during the previous year, chronic disease score, and use of non-statin lipid-lowering drugs. No association was found between fracture risk and fewer than 13 dispensings of statins or between fracture risk and use of non-statin lipid-lowering drugs. Interpretation Statins seem to be protective against non pathological fracture among older women. These findings are compatible with the hypothesis that statins increase bone mineral density in human beings and thereby decrease the risk of osteoporotic fractures.

Although pregnant women are a high-priority group for influenza vaccination, vaccination rates in this population remain below recommended levels. This prospective cohort study followed a group of pregnant women during the 2010-2011 influenza season to determine possible predictors of vaccination.Participants were 552 pregnant women who had not already received the influenza vaccine at the time of enrollment. Women completed a survey assessing knowledge, attitudes, and beliefs about vaccination (based on the Health Belief Model) by telephone and were then followed to determine vaccination status by the end of the 2010-2011 influenza season.Forty-six percent (n=252) of the women were vaccinated, and 54% (n=300) remained unvaccinated after enrollment in the study. Few baseline characteristics, with the exception of study site, month of enrollment, and maternal ethnicity, were predictive of vaccination status. Even after adjusting for significant baseline characteristics, we found that at least one item from each domain of the Health Beliefs Model was predictive of subsequent vaccination. Specifically, women who perceived they were susceptible to influenza, that they were at risk of getting seriously ill from influenza, that they would regret not getting vaccinated, and who trusted recommended guidelines about influenza vaccination during pregnancy were more likely to get vaccinated. Women who were concerned about vaccine side effects were less likely to get vaccinated.Trust in recommendations, perceived susceptibility to and seriousness of influenza, perceived regret about not getting vaccinated, and vaccine safety concerns predict vaccination in pregnant women.II.

The automated records of over 250,000 members of a health maintenance organization were analyzed to assess the epidemiology of varicella and its complications between 1 July 1990 and 30 June 1992. All complications were verified by review of full-text medical records. The incidence rates of varicella in persons15 years of age were 20%-50% lower than published figures, probably reflecting underreporting. The rates in thoseor = 15 years old, however, were greater than those reported for 1972-1978 (607 vs. 291/10(5) years, 15-19 years old; 175 vs. 33/10(5) years,or = 20 years old). The rates of hospitalization for uncomplicated varicella, skin superinfections, and pneumonia in children were, respectively, 15, 11, and 4 times higher than previous estimates. Hospitalization rates for adults with pneumonia and uncomplicated varicella were5 times higher than prior figures. Thus, varicella in adults and varicella complications in general may be more frequent than previously estimated.

Epidemiological and pathological findings of 433 late-term abortions associated with the mare reproductive loss syndrome (MRLS) in central Kentucky were identified by reviewing the records of the University of Kentucky Livestock Diseases Diagnostic Center. The distribution of dates of abortion was clustered during a brief period of time, presumably from a simultaneous environmental exposure. The most common pathological findings were microscopic pulmonary lesions consisting of squamous epithelial cells present in alveoli with or without concurrent infiltration of inflammatory cells (neutrophils, macrophages, or monocytes) in the interstitium or within alveoli. Isolation of a non–β-hemolytic Streptococcus (52% of fetuses) or an Actinobacillus sp. (19% of fetuses) was common. Placentitis or funisitis was identified in 44% of fetuses. No single pathological finding, however, was pathognomonic for MRLS-associated late-term abortion. This report describes the pathological findings characterizing the MRLS-associated abortion. A cause of MRLS could not be determined from necropsy findings.

To estimate the association between spontaneous abortion and influenza vaccine receipt with a case-control study utilizing data from six health care organizations in the Vaccine Safety Datalink.Women aged 18-44 years with spontaneous abortion during the autumn of 2005 or 2006 were identified using International Classification of Diseases, 9th Revision, Clinical Modification codes. Cases of spontaneous abortion at 5-16 weeks of gestation were confirmed by medical record review; date of fetal demise was based on ultrasound information when available. Control group individuals with a live birth were individually matched to case group individuals by health care organization and date of last menstrual period (LMP). The primary exposure of interest was influenza vaccination during the 28 days preceding the date of spontaneous abortion of the matched pair. Conditional logistic regression models adjusted for maternal age, health care utilization, maternal diabetes, and parity.Our final analysis included 243 women with spontaneous abortion and 243 matched control group women; 82% of women with spontaneous abortion had ultrasound confirmation of fetal demise. Using clinical diagnosis and ultrasound data, the mean gestational age at fetal demise was 7.8 weeks. Mean ages at LMP of case group women and control group women were 31.7 and 29.3 years, respectively (P.001). Sixteen women with spontaneous abortion (7%) and 15 (6%) matched control group women received influenza vaccine within the 28-day exposure window. There was no association between spontaneous abortion and influenza vaccination in the 28-day exposure window (adjusted matched odds ratio 1.23, 95% confidence interval 0.53-2.89; P=.63).There was no statistically significant increase in the risk of pregnancy loss in the 4 weeks after seasonal inactivated influenza vaccination.II.

Large observational vaccine safety studies often use automated diagnoses extracted from medical care databases to identify pre-specified potential adverse events following immunization (AEFI). We assessed the secular trends and variability in the number of diagnoses per encounter regardless of immunization status referred as diagnostic code density, by healthcare setting, age, and pre-specified condition in eight large health care systems of the Vaccine Safety Datalink project during 2001–2009. An increasing trend in diagnostic code density was observed in all healthcare settings and age groups, with variations across the sites. Sudden increases in diagnostic code density were observed at certain sites when changes in coding policies or data inclusion criteria took place. When vaccine safety studies use an historical comparator, the increased diagnostic code density over time may generate low expected rates (based on historical data) and high observed rates (based on current data), suggesting a false positive association between a vaccine and AEFI. The ongoing monitoring of the diagnostic code density can provide guidance on study design and choice of appropriate comparison groups. It can also be used to ensure data quality and allow timely correction of errors in an active safety surveillance system.

Background. The most common serious complication of blood transfusion is post-transfusion hepatitis from the hepatitis C virus (HCV). Blood banks now screen blood donors for surrogate markers of non-A, non-B hepatitis and antibodies to HCV, but the current risk of post-transfusion hepatitis C is unknown. Methods. From 1985 through 1991, blood samples and medical information were obtained prospectively from patients before and at least six months after cardiac surgery. The stored serum samples were tested for antibodies to HCV by enzyme immunoassay, and by recombinant immunoblotting if positive. Results. Of the 912 patients who received transfusions before donors were screened for surrogate markers, 35 seroconverted to HCV, for a risk of 3.84 percent per patient (0.45 percent per unit transfused). For the 976 patients who received transfusions after October 1986 with blood screened for surrogate markers, the risk of seroconversion was 1.54 percent per patient (0.19 percent per unit). For the 522 p...

Objectives. We studied compliance with multiple-dose vaccine schedules, assessed factors associated with noncompliance, and examined timeliness of series completion among older children, adolescents, and adults. Methods. We conducted a large, multisite, retrospective cohort study of older children, adolescents, and adults in the Vaccine Safety Datalink population from 1996 through 2004. We quantified the rates of completion of all required doses for varicella, hepatitis A, and hepatitis B vaccines according to their recommended schedules. Results. Among those who received a first dose of varicella (n = 16 075), hepatitis A (n = 594 917), and hepatitis B (n = 590 445) vaccine, relatively few completed the series (55%–65% for hepatitis B vaccine and 40%–50% for hepatitis A and varicella vaccines in most age groups). Compliance was lowest among adolescents (35.9%) and Medicaid recipients (29.7%) who received varicella vaccine and among younger adult age groups who received hepatitis A vaccine (25%–35% across those age groups). Even among series completers, there was a relatively long interval of undervaccination between the first and last doses. Conclusions. Compliance with multiple-dose vaccine series among older children, adolescents, and adults is suboptimal. Further evaluations of strategies to improve compliance in these populations are needed.

BACKGROUND. Ischemic stroke is a known complication of varicella disease. Although there have been case reports of ischemic stroke after varicella vaccination, the existence and magnitude of any vaccine-associated risk has not been determined. OBJECTIVE. The purpose of this work was to determine whether varicella vaccination is associated with an increased risk of ischemic stroke and encephalitis in children within 12 months after vaccination. PATIENTS AND METHODS. We conducted a retrospective cohort study based on computerized data from children 11 months through 17 years old enrolled for ≥12 months in the Vaccine Safety DataLink from 1991 through 2004. International Classification of Disease codes identified cases of ischemic stroke (433–436, 437.1, 437.4, 437.6, 437.8–437.9) and encephalitis (052.0, 323.5, 323.8–9). Cox regression was used to model the risk in the 12 months after vaccination relative to all other person-time. Covariates included calendar time, gender, and stroke risk factors (eg, sickle cell disease). RESULTS. Varicella vaccine was administered to 35.3% of the 3.2 million children in the cohort. There were 203 new inpatient ischemic stroke diagnoses, including 8 that occurred within 12 months after vaccination; there was no temporal clustering. The adjusted stroke hazard ratio was not elevated during any of the time periods in the 12 months after vaccination. Stroke was strongly associated with known risk factors such as sickle cell disease and cardiac disease. None of the 243 encephalitis cases occurred during the first 30 days after vaccination, and there was no association between encephalitis and varicella vaccination at any time in the 12 months after vaccination. CONCLUSION. Our retrospective cohort study of >3 million children found no association between varicella vaccine and ischemic stroke.

In order to define the risk factors for infection with hepatitis C virus, the authors determined the prevalence and incidence of antibodies to hepatitis C in three cohorts in Baltimore, Maryland, enrolled in prospective studies of human immunodeficiency virus (HIV-1) infection. Among 500 multi-transfused patients who underwent cardiac surgery in 1985 and 1986, 12 (2.4%) were hepatitis C seropositive before surgery while 19 (3.9%) developed antibodies in the 8-12 months after surgery. The seroprevalence of hepatitis C virus among 225 intravenous drug users followed since 1988 was 85%, which did not vary by HIV-1 status. Longer duration of intravenous drug use was significantly associated with hepatitis C seropositivity. Among 926 homosexual/bisexual men followed since 1984, 15 (1.6%) were hepatitis C seropositive; only intravenous drug use and a history of hepatitis A were marginally associated with hepatitis C in this population. No association was found between hepatitis C virus and HIV-1 or sexual behavior variables in this population. These data suggest that hepatitis C is readily transmitted by blood exposure, but is transmitted inefficiently by sexual means.

Lamotrigine is an important new addition to the drugs used to treat people with seizure disorders, but disconcerting are reports of a higher than expected incidence of severe skin reaction among children. Using automated data from three HMOs, we conducted a retrospective investigation of children (

Purpose The Food and Drug Administration currently requires the labeling of HMG-CoA reductase inhibitors to recommend liver function tests (LFTs) before the start of therapy and at various intervals during therapy, depending on the specific agent. We sought to determine the frequency and patterns of LFT screening in patients receiving HMG-CoA reductase inhibitors. Methods A retrospective study was conducted at a staff-model health maintenance organization among 4178 new users of HMG-CoA reductase inhibitors during the period 1 January 1991 through 31 December 1996. The number and proportions of HMG-CoA reductase inhibitor therapy courses with baseline LFTs (within 180 days prior to dispensing), follow-up LFTs and LFT abnormalities were calculated. Results For the initial HMG-CoA reductase inhibitor dispensed, 1947 patients (47%) had at least one screening LFT at baseline and 3063 (73%) had at least one follow-up LFT. Twenty-seven (0.9%) patients with at least one follow-up LFT performed had a level greater than 3 times the upper limit of normal. In a random sample of 100 discontinued patients, none discontinued due to elevated LFTs or liver disease. Conclusions A large proportion of patients dispensed HMG-CoA reductase inhibitors in this managed care setting did not have baseline and follow-up LFTs performed. Modest LFT abnormalities were common among users of HMG-CoA reductase inhibitors; however, in this population, serious abnormalities were rare. Copyright © 2003 John Wiley & Sons, Ltd.

Objective—To identify factors associated with abortions of mares during late gestation attributed to mare reproductive loss syndrome (MRLS). Design—Case-control study. Animals—282 broodmares from 62 farms in central Kentucky, including 137 mares that had late-term abortions (LTAs) associated with MRLS, 98 mares from the same farms that did not abort, and 48 mares that aborted from causes other than MRLS. Procedure—Farm managers were interviewed to obtain data on a wide range of management practices and environmental exposures for the mares. Data for case and control horses were compared to identify risk factors for a mare having a MRLS-associated LTA (MRLS-LTA). Results—Several factors increased the risk of mares having MRLS-LTAs, including increased amount of time at pasture, less time in a stall, feeding concentrate on the ground, higher proportion of diet derived from grazing pasture, being fed in pasture exclusively during the 4-week period prior to abortion, access to pasture after midnight during the 4-week period prior to abortion, and drinking from a water trough or not having access to water buckets or automatic waterers. Conclusions and Clinical Relevance—Analysis indicates that exposure to pasture predisposed mares to having MRLS-LTAs and stillborn foals. Methods for limiting exposure to pasture (keeping mares in stalls longer) during environmental conditions similar to those seen in 2001 should reduce the risk of mares having MRLS-LTAs. (J Am Vet Med Assoc 2003;222:199–209)

Objective—To identify factors associated with abortions during early gestation classified as mare reproductive loss syndrome (MRLS). Design—Case-control study. Animals—324 broodmares from 43 farms in central Kentucky, including 121 mares from 25 farms that had early-term abortions (ETAs) associated with MRLS (case horses), 120 mares from the same farms but that did not abort, and 83 mares from 18 farms that were not severely impacted by MRLS. Procedure—Farm managers were interviewed to obtain data on various management practices and environmental exposures for the mares. Data for case and control horses were compared to identify risk factors for mares having MRLS-associated ETAs. Results—Several factors increased the risk of MRLS-associated ETAs, including feeding hay in pasture, greater than usual amounts of white clover in pastures, more eastern tent caterpillars in pastures, abortion during a previous pregnancy, and sighting deer or elk on the premises. Conclusions and Clinical Relevance—Analysis indicates that certain characteristics of pastures predisposed mares to MRLS-associated ETAs. Methods for limiting exposure to pasture (keeping mares in stalls longer) during environmental conditions similar to those of 2001 (ie, sudden freezing in mid-April following warmer-than-usual springtime temperatures and larger-than-usual numbers of eastern tent caterpillars in and around pastures) should reduce the risk of mares having MRLS-associated ETAs. It was not possible to determine whether exposure to white clover or caterpillars were causal factors for MRLS or were merely indicators of unusual environmental conditions that resulted in exposure of mares to a toxic or infectious agent. (J Am Vet Med Assoc 2003;222:210–217)

Objective To compare ambulatory visit patterns, rates of medication use, and emergency department and hospital utilization for children with asthma covered under Medicaid and commercial payers within the same health maintenance organization (HMO). Design Retrospective cohort study. Setting Eleven staff-model pediatric departments of an HMO. Patients A total of 1928 Medicaid and 11,007 non-Medicaid children aged 2 to 18 years with at least 1 encounter with a diagnosis of asthma between October 1, 1991, and September 30, 1996. Methods We linked patient-level data from the HMO's automated medical record system for ambulatory encounters, a claims system for emergency department and hospital care, and an automated pharmacy dispensing database. Medicaid and non-Medicaid patients were compared for all encounter types and for prescribing and dispensing of β-agonist and controller medications (inhaled corticosteroids and cromolyn sodium). Incidence rate ratios were calculated from Poisson regression models to control for age, sex, and, when appropriate, β-agonist dispensing rate. The number of refills authorized on each prescription and the fraction of medications dispensed as refills compared with new prescriptions were compared for Medicaid and non-Medicaid patients. Results Medicaid-insured children in the HMO were 1.4 times (95% confidence interval, 1.2-1.5) more likely to receive care in emergency departments and 1.3 times (95% confidence interval, 1.1-1.5) more likely to be hospitalized for their asthma compared with non-Medicaid members. Medicaid and non-Medicaid enrollees had similar yearly rates of nonurgent (1.32 vs 1.17) and urgent (0.38 vs 0.31) ambulatory visits. β-Agonists were dispensed roughly equally to Medicaid and non-Medicaid members. Although Medicaid patients were less likely to have controller medications dispensed (relative risk, 0.72; 95% confidence interval, 0.69-0.74), they were equally likely to have them prescribed. Conclusions Differences in ambulatory contact for Medicaid members do not explain the higher rates of emergency department visits and hospitalization in this population. Reasons for lower rates of dispensing of controller medications should continue to be investigated as one cause of increased morbidity for low-income children with asthma.

Summary Background Inhibitors of hydroxymethylglutaryl-coenzyme A reductase (statins) increase new bone formation in rodents and in human cells in vitro. Statin use is associated with increased bone mineral density of the femoral neck. We undertook a population-based case-control study at six health-maintenance organisations in the USA to investigate further the relation between statin use and fracture risk among older women. Methods We investigated women aged 60 years or older. Exposure, outcome, and confounder information was obtained from automated claims and pharmacy data from October, 1994, to September, 1997. Cases had an incident diagnosis of non-pathological fracture of the hip, humerus, distal tibia, wrist, or vertebrae between October, 1996, and September, 1997. Controls had no fracture during this period. We excluded women with records of dispensing of drugs to treat osteoporosis. Findings There were 928 cases and 2747 controls. Compared with women who had no record of statin dispensing during the previous 2 years, women with 13 or more statin dispensings during this period had a decreased risk of non-pathological fracture (odds ratio 0·48 [95% CI 0·27–0·83]) after adjustment for age, number of hospital admissions during the previous year, chronic disease score, and use of non-statin lipid-lowering drugs. No association was found between fracture risk and fewer than 13 dispensings of statins or between fracture risk and use of non-statin lipid-lowering drugs. Interpretation Statins seem to be protective against non pathological fracture among older women. These findings are compatible with the hypothesis that statins increase bone mineral density in human beings and thereby decrease the risk of osteoporotic fractures.

Background Allergic rhinitis and asthma are important sources of morbidity among adults and children. Although immunotherapy is sometimes used to treat these conditions, there is little information on its use, adherence, or cost in the general population. Objective We sought to characterize the recipients of immunotherapy for allergic rhinitis and/or asthma with respect to their immunotherapy and utilization of health care services. Methods A combination of automated and manually extracted data was used to identify HMO members with diagnoses of allergic rhinitis or asthma who were treated with immunotherapy. Costs associated with immunotherapy and related care were examined by linear regression. Proportional hazards and Kaplan-Meier plots were used to evaluate duration of therapy. Results Of the 122,196 persons with a diagnosis of asthma or rhinitis, 2,667 were also treated with immunotherapy. Eligibility criteria were satisfied by 603 individuals who had 28,266 encounters for immunotherapy (median 48). Most patients (>80%) were treated with multiple allergens; ragweed was the most common single allergen administered. Thirty-three percent of patients with sufficient observation time completed the intended course of 61 immunotherapy treatments. Females and younger patients had shorter durations of immunotherapy. The most common reason for discontinuation of therapy was patient's decision (54%). Immunotherapy costs were related most strongly to costs for care of rhinitis and asthma. Prescription drugs accounted for more than 50% of the non-immunotherapy costs; hospitalizations accounted for less than 20%. Conclusions Approximately 2% of HMO members with an asthma or rhinitis diagnosis received immunotherapy. Although screened to optimize compliance, most patients did not complete immunotherapy. Costs of non-immunotherapy care were higher for individuals who completed immunotherapy which is consistent with more severe disease in this group.

PURPOSE: To investigate the possible association between ibuprofen use and dermatologic superinfections among children with recent varicella infection. METHODS: A retrospective cohort study of children in Harvard Pilgrim Health Care, a health maintenance organization in New England, was conducted. Outcomes and exposures of interest were identified from automated medical and pharmacy records. Exposure was defined by dispensing of ibuprofen before varicella to avoid potential confounding by indication. RESULTS: Between July 1, 1990 and September 30, 1994, 89 superinfections developed among 7,013 cases of varicella. The 30-day risk of superinfection was 7.2/10 3 cases (95% CI = 5.8 – 8.8/10 3 cases). Four of 169 children dispensed ibuprofen within 180 days of varicella developed superinfection. Relative to children without prior use, children with ibuprofen dispensed in the month prior to varicella were 3.1 times more likely to be diagnosed with a superinfection (95% CI = 0.1–19.7; P -value: 0.31). Restriction of outcomes to superinfections treated with systemic antibiotics increased the odds ratio to 5.1 (95% CI = 0.1–32.5; P -value: 0.22). CONCLUSIONS: The results of this study are consistent with a broad range of effects including no association and suggest that further study is needed.

Automated medical records systems are used to study clinical outcomes and quality of care, but this requires accurate disease identification and assessment of severity. We sought to determine the reliability of identifying asthmatics through automated medical and pharmacy records, and the adequacy of such data for severity assessment. All adult health maintenance organization (HMO) members who received at least one asthma drug and an asthma diagnosis between April 1988 and September 1991 were identified. Records of a random sample were reviewed to validate the diagnosis and extract clinical information. Asthma drugs were dispensed to 15,491 individuals; 7583 (49%) also received an asthma diagnosis. Asthma drug use was three times greater for persons with diagnosed asthma compared to those with no diagnosis. Record review revealed that a coded asthma diagnosis had a positive predictive value of 86%. Nearly 4000 ambulatory encounters were reviewed, 10% of which were for asthma; the median number of encounters was two. Asthma symptoms were mentioned in 9% of all encounters; wheezing was most common. Peak flow and spirometry were measured in 4% and 1% of encounters, respectively. Records from recipients of asthma drugs who lacked an asthma diagnosis showed that 79% did not have asthma. Automated medical and pharmacy records from an HMO were relatively accurate when used to identify individuals with asthma. Similarly, most asthma drug recipients who lacked a coded diagnosis of asthma did not have asthma. However, conventional full-text records usually do not contain sufficient information to assess asthma severity, limiting the utility of such records for research and quality improvement.

Background: Telangiectasia macularis eruptiva perstans, a rare form of cutaneous mastocytosis associated with elevated histamine excretion, has not previously been reported to complicate pregnancy. Case: A woman presented in the late second trimester with an anaphylactoid reaction, rash, uterine contractions, and vaginal bleeding. Skin biopsy revealed perivascular mast-cell infiltration. Her urinary histamine excretion was markedly elevated. She was treated successfully with tocolytics and antihistamines. Conclusion: Elevated histamine excretion in biopsyproven cutaneous mastocytosis may be associated with preterm labor.

Background/Aims Trivalent influenza vaccine (TIV) is the only vaccine recommended by the Advisory Committee on Immunization Practices (ACIP) for routine administration during pregnancy. The ACIP categorizes remaining vaccines as, “should be considered if indicated”, “contraindicated”, or with “special/conditional recommendation.” The objective of this study was to describe rates of vaccination during pregnancy in seven Vaccine Safety Datalink (VSD) sites.

Background: The risk factors for postherpetic neuralgia (PHN), the most common complication of herpes zoster, have not been well established. Objective: To elucidate the risk factors for PHN. Methods: Automated medical, claims, and pharmacy records of a health maintenance organization were used to identify cases of PHN and obtain data on risk factors. A case-base design was used to assess the impact of various patient, disease, and treatment factors on the prevalence of PHN 1 and 2 months after developing zoster. Results: There were 821 cases of herpes zoster that met all eligibility criteria. The prevalence of PHN more than 30 days after onset of zoster was 8.0% (95% confidence interval [CI], 6.3%-10.1%) and 4.5% (95% CI, 3.2%6.2%) after 60 days. Compared with patients younger than 50 years, individuals aged 50 years or older had a 14.7-fold higher prevalence (95% CI, 6.8-32.0) 30 days and a 27.4-fold higher prevalence (95% CI, 8.8-85.4) 60 days after developing zoster. Prodromal sensory symptoms and certain conditions associated with compromised immunity were also associated with PHN. Systemic corticosteroids before zoster and treatment of zoster with acyclovir or corticosteroids did not significantly affect the prevalence of PHN. Conclusions: Increased age and prodromal symptoms are associated with higher prevalence of PHN 1 and 2 months after onset of zoster. Overall, systemic acyclovir appears not to confer any protection against PHN, although benefit among elderly patients cannot be excluded. Arch Intern Med. 1997;157:1217-1224

Objective. —To determine if anti-inflammatory treatment for asthma reduces the risk of asthma hospitalization. Design. —Retrospective cohort study. Setting. —A health maintenance organization (HMO) in eastern Massachusetts. Participants. —Members of the HMO who were identified during the period October 1991 through September 1994 as having a diagnosis of asthma using a computerized medical record system. Main Outcome. —Hospitalization for asthma. Results. —Of the 16 941 eligible persons, 742 (4.4%) were hospitalized for asthma. The overall relative risk (RR) of hospitalization among those who received inhaled steroids was 0.5 (95% confidence interval [CI], 0.4-0.6) after adjustment for β-agonist dispensing. Additional adjustment for age, race, other asthma medications, and amount and type of ambulatory care for asthma did not substantially affect the inverse relationship between use of inhaled steroids and hospitalization. Cromolyn was similarly associated with reduced risk, especially among children (RR,0.8;95%CI,0.7-0.9). In contrast, increasing β-agonist use was associated with increasing hospitalization risk even after adjustment for other factors and medications. The steroid-associated protection was most marked among individuals who received the largest amount of β-agonist. Conclusions. —Inhaled steroids and, to a lesser extent, cromolyn confer significant protection against exacerbations of asthma leading to hospitalization. These results support the use of inhaled steroids by individuals who require more than occasional β-agonist use to control asthma symptoms.

Using the vector tick, Ixodes dammini, we described the reservoir competence of the white-footed mouse, Peromyscus leucopus, for the Lyme disease spirochete, Borrelia burgdorferi. Nymphal I. dammini were used to infect mammals, and larval ticks were used to diagnose infection (a form of xenodiagnosis). One tick was nearly as efficient as more than 1 in transmitting the spirochete to mice. The duration of the prepatent period was about 1 week. Prevalence of infection approached 100% in ticks that fed as larvae on mice infected 2 or 3 weeks previously. Thereafter, infectivity gradually decreased, but duration exceeded 200 days. Hamsters, too, became infectious for larval I. dammini. This report formally demonstrates the life cycle of B. burgdorferi as it seems to occur in nature. We conclude that the white-footed mouse is a competent reservoir for the Lyme disease spirochete.

We determined the rates of seroconversion to human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus Type I (HTLV-I) in a cohort of patients receiving transfusions of blood components screened for antibody to HIV-1. Preoperative and postoperative serum samples were collected from 4163 adults undergoing cardiac surgery who received 36,282 transfusions of blood components. The postoperative samples from all patients were tested for serologic evidence of HIV-1 infection, and those that were positive were compared with the corresponding preoperative samples. One case of HIV-1 transmission by transfusion of screened blood components was identified; two preexisting HIV-1 infections were found. Samples from 2749 patients were tested similarly for serologic evidence of HTLV-I infection; these patients received 20,963 units of blood components. Five new cases and two preexisting cases of HTLV-I infection were detected. The observed risk of HIV-1 transmission by transfusion was 0.003 percent per unit; the risk of HTLV-I transmission was 0.024 percent per unit. We conclude that there is a very small risk of HTLV-I infection from transfused blood products that have been screened for antibodies to HIV-1, but that it is nearly 10-fold higher than the risk of HIV-1 infection.