Clinical Epidemiology and Risk Factors for Critical Outcomes Among Vaccinated and Unvaccinated Adults Hospitalized With COVID-19-VISION Network, 10 States, June 2021-March 2023.

BACKGROUND: The epidemiology of coronavirus disease 2019 (COVID-19) continues to develop with emerging variants, expanding population-level immunity, and advances in clinical care. We describe changes in the clinical epidemiology of COVID-19 hospitalizations and risk factors for critical outcomes over time. METHODS: We included adults aged ≥18 years from 10 states hospitalized with COVID-19 June 2021-March 2023. We evaluated changes in demographics, clinical characteristics, and critical outcomes (intensive care unit admission and/or death) and evaluated critical outcomes risk factors (risk ratios [RRs]), stratified by COVID-19 vaccination status. RESULTS: A total of 60 488 COVID-19-associated hospitalizations were included in the analysis. Among those hospitalized, median age increased from 60 to 75 years, proportion vaccinated increased from 18.2% to 70.1%, and critical outcomes declined from 24.8% to 19.4% (all P < .001) between the Delta (June-December, 2021) and post-BA.4/BA.5 (September 2022-March 2023) periods. Hospitalization events with critical outcomes had a higher proportion of ≥4 categories of medical condition categories assessed (32.8%) compared to all hospitalizations (23.0%). Critical outcome risk factors were similar for unvaccinated and vaccinated populations; presence of ≥4 medical condition categories was most strongly associated with risk of critical outcomes regardless of vaccine status (unvaccinated: adjusted RR, 2.27 [95% confidence interval {CI}, 2.14-2.41]; vaccinated: adjusted RR, 1.73 [95% CI, 1.56-1.92]) across periods. CONCLUSIONS: The proportion of adults hospitalized with COVID-19 who experienced critical outcomes decreased with time, and median patient age increased with time. Multimorbidity was most strongly associated with critical outcomes.

Impact of the COVID-19 Pandemic on Health Care Utilization in the Vaccine Safety Datalink: Retrospective Cohort Study.

BACKGROUND: Understanding the long-term impact of the COVID-19 pandemic on health care utilization is important to health care organizations and policy makers for strategic planning, as well as to researchers when designing studies that use observational electronic health record data during the pandemic period. OBJECTIVE: This study aimed to evaluate the changes in health care utilization across all care settings among a large, diverse, and insured population in the United States during the COVID-19 pandemic. METHODS: We conducted a retrospective cohort study within 8 health care organizations participating in the Vaccine Safety Datalink Project using electronic health record data from members of all ages from January 1, 2017, to December 31, 2021. The visit rates per person-year were calculated monthly during the study period for 4 health care settings combined as well as by inpatient, emergency department (ED), outpatient, and telehealth settings, both among all members and members without COVID-19. Difference-in-difference analysis and interrupted time series analysis were performed to assess the changes in visit rates from the prepandemic period (January 2017 to February 2020) to the early pandemic period (April-December 2020) and the later pandemic period (July-December 2021), respectively. An exploratory analysis was also conducted to assess trends through June 2023 at one of the largest sites, Kaiser Permanente Southern California. RESULTS: The study included more than 11 million members from 2017 to 2021. Compared with the prepandemic period, we found reductions in visit rates during the early pandemic period for all in-person care settings. During the later pandemic period, overall use reached 8.36 visits per person-year, exceeding the prepandemic level of 7.49 visits per person-year in 2019 (adjusted percent change 5.1%, 95% CI 0.6%-9.9%); inpatient and ED visits returned to prepandemic levels among all members, although they remained low at 0.095 and 0.241 visits per person-year, indicating a 7.5% and 8% decrease compared to pre-pandemic levels among members without COVID-19, respectively. Telehealth visits, which were approximately 42% of the volume of outpatient visits during the later pandemic period, were increased by 97.5% (95% CI 86.0%-109.7%) from 0.865 visits per person-year in 2019 to 2.35 visits per person-year in the later pandemic period. The trends in Kaiser Permanente Southern California were similar to those of the entire study population. Visit rates from January 2022 to June 2023 were stable and appeared to be a continuation of the use levels observed at the end of 2021. CONCLUSIONS: Telehealth services became a mainstay of the health care system during the late COVID-19 pandemic period. Inpatient and ED visits returned to prepandemic levels, although they remained low among members without evidence of COVID-19. Our findings provide valuable information for strategic resource allocation for postpandemic patient care and for designing observational studies involving the pandemic period.

Influenza vaccination coverage among persons ages six months and older in the Vaccine Safety Datalink in the 2017-18 through 2022-23 influenza seasons.

BACKGROUND: In the United States, annual vaccination against seasonal influenza is recommended for all people ages ≥ 6 months. Vaccination coverage assessments can identify populations less protected from influenza morbidity and mortality and help to tailor vaccination efforts. Within the Vaccine Safety Datalink population ages ≥ 6 months, we report influenza vaccination coverage for the 2017-18 through 2022-23 seasons. METHODS: Across eight health systems, we identified influenza vaccines administered from August 1 through March 31 for each season using electronic health records linked to immunization registries. Crude vaccination coverage was described for each season, overall and by self-reported sex; age group; self-reported race and ethnicity; and number of separate categories of diagnoses associated with increased risk of severe illness and complications from influenza (hereafter referred to as high-risk conditions). High-risk conditions were assessed using ICD-10-CM diagnosis codes assigned in the year preceding each influenza season. RESULTS: Among individual cohorts of more than 12 million individuals each season, overall influenza vaccination coverage increased from 41.9 % in the 2017-18 season to a peak of 46.2 % in 2019-20, prior to declaration of the COVID-19 pandemic. Coverage declined over the next three seasons, coincident with widespread SARS-CoV-2 circulation, to a low of 40.3 % in the 2022-23 season. In each of the six seasons, coverage was lowest among males, 18-49-year-olds, non-Hispanic Black people, and those with no high-risk conditions. While decreases in coverage were present in all age groups, the declines were most substantial among children: 2022-23 season coverage for children ages six months through 8 years and 9-17 years was 24.5 % and 22.4 % (14 and 10 absolute percentage points), respectively, less than peak coverage achieved in the 2019-20 season. CONCLUSIONS: Crude influenza vaccination coverage increased from 2017 to 18 through 2019-20, then decreased to the lowest level in the 2022-23 season. In this insured population, we identified persistent disparities in influenza vaccination coverage by sex, age, and race and ethnicity. The overall low coverage, disparities in coverage, and recent decreases in coverage are significant public health concerns.

Simultaneous administration of mRNA COVID-19 bivalent booster and influenza vaccines.

The U.S. Food and Drug Administration authorized use of mRNA COVID-19 bivalent booster vaccines on August 31, 2022. Currently, CDC's clinical guidance states that COVID-19 and other vaccines may be administered simultaneously. At time of authorization and recommendations, limited data existed describing simultaneous administration of COVID-19 bivalent booster and other vaccines. We describe simultaneous influenza and mRNA COVID-19 bivalent booster vaccine administration between August 31-December 31, 2022, among persons aged ≥6 months in the Vaccine Safety Datalink (VSD) by COVID-19 bivalent booster vaccine type, influenza vaccine type, age group, sex, and race and ethnicity. Of 2,301,876 persons who received a COVID-19 bivalent booster vaccine, 737,992 (32.1%) received simultaneous influenza vaccine, majority were female (53.1%), aged ≥18 years (91.4%), and non-Hispanic White (55.7%). These findings can inform future VSD studies on simultaneous influenza and COVID-19 bivalent booster vaccine safety and coverage, which may have implications for immunization service delivery.

Influenza Vaccination Among Pregnant People Before and During the Coronavirus Disease 2019 (COVID-19) Pandemic.

There are limited data on influenza vaccination coverage among pregnant people in the United States during the coronavirus disease 2019 (COVID-19) pandemic. Within the Vaccine Safety Datalink, we conducted a retrospective cohort study to examine influenza vaccination coverage during the 2016-2017 through the 2021-2022 influenza seasons among pregnant people aged 18-49 years. Using influenza vaccines administered through March each season, we assessed crude coverage by demographic and clinical characteristics. Annual influenza vaccination coverage increased from the 2016-2017 season (63.0%) to a high of 71.0% in the 2019-2020 season. After the start of the COVID-19 pandemic, it decreased to a low of 56.4% (2021-2022). In each of the six seasons, coverage was lowest among pregnant people aged 18-24 years and among non-Hispanic Black pregnant people. The 2021-2022 season had the lowest coverage across all age and race and ethnicity groups. The recent decreases highlight the need for continued efforts to improve coverage among pregnant people.

Epidemiology of Upper Limb Complex Regional Pain Syndrome in a Retrospective Cohort of Persons Aged 9-30 Years, 2002-2017.

Introduction This paper describes the epidemiology and clinical presentation of complex regional pain syndrome (CRPS) in a large, integrated health care delivery system; and CRPS incidence rates (IRs) over a time period spanning human papillomavirus (HPV) vaccine licensure and published case reports of CRPS following HPV vaccination. Methods The authors examined CRPS diagnoses in patients aged 9-30 years between January 2002 and December 2017 using electronic medical records, excluding patients with lower limb diagnoses only. Medical record abstraction and adjudication were conducted to verify diagnoses and describe clinical characteristics. CRPS IRs were calculated for 3 periods: Period 1 (2002-2006: before HPV vaccine licensure), Period 2 (2007-2012: after licensure but before published case reports), and Period 3 (2013-2017: after published case reports). Results A total of 231 individuals received an upper limb or unspecified CRPS diagnosis code during the study period; 113 cases were verified through abstraction and adjudication. Most verified cases (73%) were associated with a clear precipitating event (eg, non-vaccine-related injury, surgical procedure). The authors identified only 1 case in which a practitioner attributed CRPS onset to HPV vaccination. Twenty-five incident cases occurred in Period 1 (IR = 4.35/100,000 person-years (PY), 95% confidence interval (CI) = 2.94-6.44), 42 in Period 2 (IR = 5.94/100,000 PY, 95% CI = 4.39-8.04), and 29 in Period 3 (IR = 4.53/100,000 PY, 95% CI = 3.15-6.52); differences between periods were not statistically significant. Conclusion These data provide a comprehensive assessment of the epidemiology and characteristics of CRPS in children and young adults and provide further reassurance about the safety of HPV vaccination.

Changes in incidence rates of outcomes of interest in vaccine safety studies during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic caused an abrupt drop in in-person health care (inpatient, Emergency Department, outpatient) and an increase in telehealth care, which poses challenges in vaccine safety studies that identify outcomes from in-person encounters. We examined the changes in incidence rates of selected encounter-based outcomes during the COVID-19 pandemic. METHODS: We assembled a cohort of members from 8 Vaccine Safety Datalink sites from January 1, 2017 through December 31, 2020. Using ICD-10 diagnosis codes or laboratory criteria, we identified 21 incident outcomes in traditional in-person settings and all settings. We defined 4 periods in 2020: January-February (pre-pandemic), April-June (early pandemic), July-September (middle pandemic), and October-December (late pandemic). We defined four corresponding periods in each year during 2017-2019. We calculated incidence rates, conducted difference in difference (DiD) analyses, and reported ratios of incidence rate ratios (RRR) to examine changes in rates from pre-pandemic to early, middle, and late pandemic in 2020, after adjusting for changes across similar periods in 2017-2019. RESULTS: Among > 10 million members, regardless of setting and after adjusting for changes during 2017-2019, we found that incidence rates of acute disseminated encephalomyelitis, encephalitis/myelitis/encephalomyelitis/meningoencephalitis, and thrombotic thrombocytopenic purpura did not significantly change from the pre-pandemic to early, middle or late pandemic periods (p-values ≥ 0.05). Incidence rates decreased from the pre-pandemic to early pandemic period during 2020 for acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, convulsions/seizures, Guillain-Barré syndrome, immune thrombocytopenia (ITP), narcolepsy/cataplexy, hemorrhagic stroke, ischemic stroke, and venous thromboembolism (p-values < 0.05). Incidence rates of Bell's palsy, ITP, and narcolepsy/cataplexy were higher in all settings than in traditional in-person settings during the three pandemic periods (p-values < 0.05). CONCLUSION: Rates of some clinical outcomes during the pandemic changed and should not be used as historical background rates in vaccine safety studies. Inclusion of telehealth visits should be considered for vaccine studies involving Bell's palsy, ITP, and narcolepsy/cataplexy.

Changes in Cervical Cytology Results and Human Papillomavirus Types Among Persons Screened for Cervical Cancer, 2007 and 2015-2017.

OBJECTIVES: Since 2006, the US human papillomavirus (HPV) vaccination program has led to decreases in HPV infections caused by high-risk vaccine-targeted HPV types (HPV 16/18). We assessed differences in high-risk HPV prevalence by cervical cytology result among 20- to 24-year-old persons participating in routine cervical cancer screening in 2015-2017 compared with 2007. MATERIALS AND METHODS: Residual routine cervical cancer screening specimens were collected from 20- to 24-year-old members of 2 integrated healthcare delivery systems as part of a cross-sectional study and were tested for 37 HPV types. Cytology results and vaccination status (≥1 dose) were extracted from medical records. Cytology categories were normal, atypical squamous cells of undefined significance, low-grade squamous intraepithelial lesions (SIL), or high-grade SIL/atypical squamous cells cannot exclude high-grade SIL. Prevalences of HPV categories (HPV 16/18, HPV 31/33/45/52/58, HPV 35/39/51/56/59/66/68) were estimated by cytology result for 2007 and 2015-2017. RESULTS: Specimens from 2007 (n = 4046) were from unvaccinated participants; 4574 of 8442 specimens (54.2%) from 2015-2017 were from vaccinated participants. Overall, HPV 16/18 positivity was lower in 2015-2017 compared with 2007 in all groups: high-grade SIL/atypical squamous cells cannot exclude high-grade SIL, 16.0% vs 69.2%; low-grade SIL, 5.4% vs 40.1%; atypical squamous cells of undefined significance, 5.0% vs 25.6%; and normal, 1.3% vs 8.1%. Human papillomavirus 31/33/45/52/58 prevalence was stable for all cytology groups; HPV 35/39/51/56/59/66/68 prevalence increased among low-grade SIL specimens (53.9% to 65.2%) but remained stable in other groups. CONCLUSIONS: Prevalence of vaccine-targeted high-risk HPV types 16/18 was dramatically lower in 2015-2017 than 2007 across all cytology result groups while prevalence of other high-risk HPV types was mainly stable, supporting vaccine impact with no evidence of type replacement.

Monitoring vaccine safety using the vaccine safety Datalink: Assessing capacity to integrate data from Immunization Information systems.

BACKGROUND: The Vaccine Safety Datalink (VSD) uses vaccination data from electronic health records (EHR) at eight integrated health systems to monitor vaccine safety. Accurate capture of data from vaccines administered outside of the health system is critical for vaccine safety research, especially for COVID-19 vaccines, where many are administered in non-traditional settings. However, timely access and inclusion of data from Immunization Information Systems (IIS) into VSD safety assessments is not well understood. METHODS: We surveyed the eight data-contributing VSD sites to assess: 1) status of sending data to IIS; 2) status of receiving data from IIS; and 3) integration of IIS data into the site EHR. Sites reported separately for COVID-19 vaccination to capture any differences in capacity to receive and integrate data on COVID-19 vaccines versus other vaccines. RESULTS: All VSD sites send data to and receive data from their state IIS. All eight sites (100%) routinely integrate IIS data for COVID-19 vaccines into VSD research studies. Six sites (75%) also routinely integrate all other vaccination data; two sites integrate data from IIS following a reconciliation process, which can result in delays to integration into VSD datasets. CONCLUSIONS: COVID-19 vaccines are being administered in a variety of non-traditional settings, where IIS are commonly used as centralized reporting systems. All eight VSD sites receive and integrate COVID-19 vaccine data from IIS, which positions the VSD well for conducting quality assessments of vaccine safety. Efforts to improve the timely receipt of all vaccination data will improve capacity to conduct vaccine safety assessments within the VSD.

Vaccine Safety Datalink infrastructure enhancements for evaluating the safety of maternal vaccination.

BACKGROUND: Identifying pregnancy episodes and accurately estimating their beginning and end dates are imperative for observational maternal vaccine safety studies using electronic health record (EHR) data. METHODS: We modified the Vaccine Safety Datalink (VSD) Pregnancy Episode Algorithm (PEA) to include both the International Classification of Disease, ninth revision (ICD-9 system) and ICD-10 diagnosis codes, incorporated additional gestational age data, and validated this enhanced algorithm with manual medical record review. We also developed the new Dynamic Pregnancy Algorithm (DPA) to identify pregnancy episodes in real time. RESULTS: Around 75% of the pregnancy episodes identified by the enhanced VSD PEA were live births, 12% were spontaneous abortions (SABs), 10% were induced abortions (IABs), and 0.4% were stillbirths (SBs). Gestational age was identified for 99% of live births, 89% of SBs, 69% of SABs, and 42% of IABs. Agreement between the PEA-assigned and abstractor-identified pregnancy outcome and outcome date was 100% for live births, but was lower for pregnancy losses. When gestational age was available in the medical record, the agreement was higher for live births (97%), but lower for pregnancy losses (75%). The DPA demonstrated strong concordance with the PEA and identified pregnancy episodes ⩾6 months prior to the outcome date for 89% of live births. CONCLUSION: The enhanced VSD PEA is a useful tool for identifying pregnancy episodes in EHR databases. The DPA improves the timeliness of pregnancy identification and can be used for near real-time maternal vaccine safety studies. PLAIN LANGUAGE SUMMARY: Improving identification of pregnancies in the Vaccine Safety Datalink electronic medical record databases to allow for better and faster monitoring of vaccination safety during pregnancy Introduction: It is important to monitor of the safety of vaccines after they have been approved and licensed by the Food and Drug Administration, especially among women vaccinated during pregnancy. The Vaccine Safety Datalink (VSD) monitors vaccine safety through observational studies within large databases of electronic medical records. Since 2012, VSD researchers have used an algorithm called the Pregnancy Episode Algorithm (PEA) to identify the medical records of women who have been pregnant. Researchers then use these medical records to study whether receiving a particular vaccine is linked to any negative outcomes for the woman or her child.Methods: The goal of this study was to update and enhance the PEA to include the full set of medical record diagnostic codes [both from the older International Classification of Disease, ninth revision (ICD-9 system) and the newer ICD-10 system] and to incorporate additional sources of data about gestational age. To ensure the validity of the PEA following these enhancements, we manually reviewed medical records and compared the results with the algorithm. We also developed a new algorithm, the Dynamic Pregnancy Algorithm (DPA), to identify women earlier in pregnancy, allowing us to conduct more timely vaccine safety assessments.Results: The new version of the PEA identified 2,485,410 pregnancies in the VSD database. The enhanced algorithm more precisely estimated the beginning of pregnancies, especially those that did not result in live births, due to the new sources of gestational age data.Conclusion: Our new algorithm, the DPA, was successful at identifying pregnancies earlier in gestation than the PEA. The enhanced PEA and the new DPA will allow us to better evaluate the safety of current and future vaccinations administered during or around the time of pregnancy.

COVID-19 Vaccination Coverage Among Pregnant Women During Pregnancy - Eight Integrated Health Care Organizations, United States, December 14, 2020-May 8, 2021.

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.

Temporal Trends in the Incidence of Anogenital Warts: Impact of Human Papillomavirus Vaccination.

BACKGROUND: Studies in countries with high human papillomavirus (HPV) vaccination coverage have demonstrated marked reductions in anogenital wart (AGW) incidence. Our goal was to assess the impact of HPV vaccination in a population with suboptimal coverage by comparing AGW incidence trends in the years before and after vaccine introduction. METHODS: We conducted a retrospective analysis of AGW incidence trends using an ecologic study design among 11- through 39-year-olds enrolled at Kaiser Permanente Northwest. We defined incidence as the proportion of persons who had a new AGW diagnosis for each calendar year in the prevaccine periods (2000 through 2006 for female individuals, 2000 through 2010 for male individuals) and the postvaccine periods (2007 through 2016 for female individuals, 2011 through 2016 for male individuals). We also described cumulative HPV vaccination coverage. RESULTS: The average annual AGW incidence rates in the prevaccine periods were 27.8 per 10,000 in female individuals and 26.9 per 10,000 in male individuals. In the postvaccine periods, AGW incidence rates decreased by 31% (P < 0.001) in female individuals and 10% (P = 0.006) in male individuals; the largest reductions were observed in 15- to 19-year-old female individuals (67%, P < 0.001) and male individuals (45%, P < 0.001). Three dose HPV coverage rates were less than 50% in all age groups and both sexes. CONCLUSIONS: In a population of young adults with moderate HPV vaccination coverage, we observed declines in AGW incidence among both female and male year after the introduction of HPV vaccination. The largest incidence reductions were observed in 15- to 19-year-olds who were most likely to have been vaccinated.

Declines in HPV vaccine type prevalence in women screened for cervical cancer in the United States: Evidence of direct and herd effects of vaccination.

BACKGROUND: Human papillomavirus (HPV) vaccine has been recommended in the United States since 2006 for routine vaccination of girls at age 11-12 years and through age 26 years for women not previously vaccinated. Changes in vaccine-type HPV (VT) prevalence can be used to evaluate vaccine impact, including herd effects. METHODS: We determined type-specific HPV in cytology specimens from women aged 20-29 years screened for cervical cancer at Kaiser Permanente Northwest in 2007 and in two vaccine era periods: 2012-2013 and 2015-2016. Detection and typing used L1 consensus PCR with hybridization for 37 types, including quadrivalent vaccine types (HPV 6/11/16/18). RESULTS: Among 20-24 year-olds in 2012-2013 and 2015-2016, 44% and 64% had a history of ≥1-dose vaccination. VT prevalence decreased from 13.1% in 2007 to 2.9% in 2015-2016 (prevalence ratio [PR] = 0.22; 95% confidence interval [CI] 0.17-0.29). HPV 31 prevalence was also lower in the vaccine periods compared with 2007. VT prevalence in 2015-2016 among 20-24 year-olds was lower in both vaccinated, 1.3% (PR = 0.10; 95% CI 0.06-0.16), and unvaccinated women, 5.8% (PR = 0.45; 95% CI 0.33-0.61). Among 25-29 year-olds, 21% and 32% had a history of ≥1-dose vaccination. VT prevalence decreased from 8.1% in 2007 to 5.0% in 2015-2016 (PR = 0.62; 95% CI 0.50-0.78). Non-VT high risk prevalence was higher in the vaccine periods compared with the pre-vaccine era in both age groups, however, not in 2015-2016 compared with 2012-2013. CONCLUSION: Within 9-10 years of vaccine introduction, VT prevalence decreased 78% among 20-24 year-olds and 38% in 25-29 year-olds. There were declines in both vaccinated and unvaccinated women, showing evidence of direct and herd protection.

Primary Ovarian Insufficiency and Adolescent Vaccination.

BACKGROUND: Published case series have suggested a potential association between human papillomavirus (HPV) vaccination and primary ovarian insufficiency (POI). We describe POI incidence and estimate POI risk after HPV; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis, adsorbed (Tdap); inactivated influenza (II); and meningococcal conjugate (MenACWY) vaccination. METHODS: We searched Kaiser Permanente Northwest electronic health records for outpatient diagnoses suggestive of POI in female patients aged 11 to 34 years between 2006 and 2014. We reviewed and adjudicated the medical record to confirm diagnoses and estimate symptom onset dates. We excluded cases with known causes and calculated the incidence of idiopathic POI. We estimated risk by calculating hazard ratios and 95% confidence intervals (CIs). RESULTS: From a cohort of 199 078 female patients, we identified 120 with diagnoses suggestive of POI. After adjudication and exclusion of 26 POI cases with known causes, we confirmed 46 idiopathic POI cases. POI incidence was low in 11- to 14-year-olds (0.87 per 1 000 000 person-months) and increased with age. One confirmed case patient received the HPV vaccine 23 months before the first clinical evaluation for delayed menarche. The adjusted hazard ratio was 0.30 (95% CI: 0.07-1.36) after HPV, 0.88 (95% CI: 0.37-2.10) after Tdap, 1.42 (95% CI: 0.59-3.41) after II, and 0.94 (95% CI: 0.27-3.23) after MenACWY vaccination. CONCLUSIONS: We did not find a statistically significant elevated risk of POI after HPV, Tdap, II, or MenACWY vaccination in this population-based retrospective cohort study. These findings should lessen concern about POI risk after adolescent vaccination.

Myocarditis and pericarditis are rare following live viral vaccinations in adults.

Reports of myocarditis and pericarditis following smallpox vaccination in adults suggested a need to assess inflammatory cardiac disease risk among adults who receive live viral vaccinations. From 1996 through 2007, among 416,629 vaccinated adults in the Vaccine Safety Datalink, we identified one probable pericarditis case and no cases of myocarditis in the 42 days following a live viral vaccination. Our self-controlled risk interval analysis found that, based on one case identified during the risk interval and 10 cases during the control interval, there is no increased risk of myopericarditis in the 42 days following vaccination (IRR, 0.57; 95% CI, 0.07, 4.51). Our study suggests that the occurrence of myopericarditis following live viral vaccination is rare with an estimated incidence of 0.24 per 100,000 vaccinated, which is not higher than the background rate and is much lower than the incidence rates reported following smallpox vaccination.

Human Papillomavirus Vaccine Effectiveness Against Incident Genital Warts Among Female Health-Plan Enrollees, United States.

We examined the effectiveness of human papillomavirus vaccination by dose number and spacing against incident genital warts in a cohort of 64,517 female health-plan enrollees in the United States during 2006-2012. Eligible recipients were classified into groups by regimen: 0, 1, 2 (<6 months apart), 2 (≥6 months apart), or 3 doses. They were followed until a genital wart diagnosis, loss to follow-up, or the end of study. Propensity score weights were used to balance baseline differences across groups. To account for latent genital warts before vaccination, we applied 6- and 12-month buffer periods from last and first vaccine dose, respectively. Incidence rates and hazard ratios were calculated using Poisson regression and Cox models. The propensity score-weighted incidence rate per 100,000 person-years was 762 among unvaccinated participants. Using 6- and 12-month buffer periods, respectively, incidence rates were 641 and 257 for 1 dose, 760 and 577 for the 2-dose (<6-month interval) regimen, 313 and 194 for the 2-dose (≥6-month interval) regimen, and 199 and 162 among 3-dose vaccinees; vaccine effectiveness was 68% and 76% for the 2-dose (≥6-month interval) regimen and 77% and 80% in 3-dose vaccinees compared with unvaccinated participants. Vaccine effectiveness was not significant among vaccinees receiving 1-dose and 2-dose (<6-month interval) regimens compared with unvaccinated participants. Our findings contribute to a better understanding of the real-world effectiveness of HPV vaccination.

Reduction in Human Papillomavirus Vaccine Type Prevalence Among Young Women Screened for Cervical Cancer in an Integrated US Healthcare Delivery System in 2007 and 2012-2013.

BACKGROUND: In the United States, human papillomavirus (HPV) vaccine is recommended for 11- or 12-year-olds, and for young adults not previously vaccinated. Early vaccine impact can be measured by reductions in vaccine-type (VT) HPV prevalence. METHODS: Consecutive residual cervical specimens were retained from women aged 20-29 years at Kaiser Permanente Northwest in 2007, 2012, and 2013. HPV genotypes were determined using L1 consensus polymerase chain reaction with type-specific hybridization to detect 37 types, including VT HPV (HPV type 6, 11, 16, and 18). We compared HPV prevalence in 2007 and 2012-2013, and we evaluated predictors of VT HPV and any-HPV prevalence in 2012-2013. RESULTS: In 2012-2013, 31.9% of 4181 women had initiated HPV vaccination. VT HPV prevalence decreased from 10.6% in 2007 to 6.2% in 2012-2013 (P < .001). In 2012-2013, VT HPV prevalence was significantly lower among those who initiated vaccination <19 years (adjusted prevalence ratio, 0.1; 95% confidence interval, .1-.3) than among those who were not vaccinated, and higher among those who had chlamydia, human immunodeficiency virus, or pregnancy testing in the past year than among those who did not (adjusted prevalence ratio, 1.4; 95% confidence interval, 1.1-1.8). CONCLUSIONS: Reduction in VT HPV was found in young women in an integrated healthcare delivery system within 6 years of vaccine introduction, indicating early HPV vaccine impact.

Predictors of seasonal influenza vaccination during pregnancy.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: II.