Use of Recommended Neurodiagnostic Evaluation Among Patients With Drug-Resistant Epilepsy.

Importance: Interdisciplinary practice parameters recommend that patients with drug-resistant epilepsy (DRE) undergo comprehensive neurodiagnostic evaluation, including presurgical assessment. Reporting from specialized centers suggests long delays to referral and underuse of surgery; however, longitudinal data are limited to characterize neurodiagnostic evaluation among patients with DRE in more diverse US settings and populations. Objective: To examine the rate and factors associated with neurodiagnostic studies and comprehensive evaluation among patients with DRE within 3 US cohorts. Design, Setting, and Participants: A retrospective cross-sectional study was conducted using the Observational Medical Outcomes Partnership Common Data Model including US multistate Medicaid data, commercial claims data, and Columbia University Medical Center (CUMC) electronic health record data. Patients meeting a validated computable phenotype algorithm for DRE between January 1, 2015, and April 1, 2020, were included. No eligible participants were excluded. Exposure: Demographic and clinical variables were queried. Main Outcomes and Measures: The proportion of patients receiving a composite proxy for comprehensive neurodiagnostic evaluation, including (1) magnetic resonance or other advanced brain imaging, (2) video electroencephalography, and (3) neuropsychological evaluation within 2 years of meeting the inclusion criteria. Results: A total of 33 542 patients with DRE were included in the Medicaid cohort, 22 496 in the commercial insurance cohort, and 2741 in the CUMC database. A total of 31 516 patients (53.6%) were women. The proportion of patients meeting the comprehensive evaluation main outcome in the Medicaid cohort was 4.5% (n = 1520); in the commercial insurance cohort, 8.0% (n = 1796); and in the CUMC cohort, 14.3% (n = 393). Video electroencephalography (24.9% Medicaid, 28.4% commercial, 63.2% CUMC) and magnetic resonance imaging of the brain (35.6% Medicaid, 43.4% commercial, 52.6% CUMC) were performed more regularly than neuropsychological evaluation (13.0% Medicaid, 16.6% commercial, 19.2% CUMC) or advanced imaging (3.2% Medicaid, 5.4% commercial, 13.1% CUMC). Factors independently associated with greater odds of evaluation across all 3 data sets included the number of inpatient and outpatient nonemergency epilepsy visits and focal rather than generalized epilepsy. Conclusions and Relevance: The findings of this study suggest there is a gap in the use of diagnostic studies to evaluate patients with DRE. Care setting, insurance type, frequency of nonemergency visits, and epilepsy type are all associated with evaluation. A common data model can be used to measure adherence with best practices across a variety of observational data sources.

The All of Us Research Program: Data quality, utility, and diversity.

The All of Us Research Program seeks to engage at least one million diverse participants to advance precision medicine and improve human health. We describe here the cloud-based Researcher Workbench that uses a data passport model to democratize access to analytical tools and participant information including survey, physical measurement, and electronic health record (EHR) data. We also present validation study findings for several common complex diseases to demonstrate use of this novel platform in 315,000 participants, 78% of whom are from groups historically underrepresented in biomedical research, including 49% self-reporting non-White races. Replication findings include medication usage pattern differences by race in depression and type 2 diabetes, validation of known cancer associations with smoking, and calculation of cardiovascular risk scores by reported race effects. The cloud-based Researcher Workbench represents an important advance in enabling secure access for a broad range of researchers to this large resource and analytical tools.

Comparing medical history data derived from electronic health records and survey answers in the All of Us Research Program.

OBJECTIVE: A participant's medical history is important in clinical research and can be captured from electronic health records (EHRs) and self-reported surveys. Both can be incomplete, EHR due to documentation gaps or lack of interoperability and surveys due to recall bias or limited health literacy. This analysis compares medical history collected in the All of Us Research Program through both surveys and EHRs. MATERIALS AND METHODS: The All of Us medical history survey includes self-report questionnaire that asks about diagnoses to over 150 medical conditions organized into 12 disease categories. In each category, we identified the 3 most and least frequent self-reported diagnoses and retrieved their analogues from EHRs. We calculated agreement scores and extracted participant demographic characteristics for each comparison set. RESULTS: The 4th All of Us dataset release includes data from 314 994 participants; 28.3% of whom completed medical history surveys, and 65.5% of whom had EHR data. Hearing and vision category within the survey had the highest number of responses, but the second lowest positive agreement with the EHR (0.21). The Infectious disease category had the lowest positive agreement (0.12). Cancer conditions had the highest positive agreement (0.45) between the 2 data sources. DISCUSSION AND CONCLUSION: Our study quantified the agreement of medical history between 2 sources-EHRs and self-reported surveys. Conditions that are usually undocumented in EHRs had low agreement scores, demonstrating that survey data can supplement EHR data. Disagreement between EHR and survey can help identify possible missing records and guide researchers to adjust for biases.

Risk Factors Associated With SARS-CoV-2 Breakthrough Infections in Fully mRNA-Vaccinated Individuals: Retrospective Analysis.

BACKGROUND: COVID-19 messenger RNA (mRNA) vaccines have demonstrated efficacy and effectiveness in preventing symptomatic COVID-19, while being relatively safe in trial studies. However, vaccine breakthrough infections have been reported. OBJECTIVE: This study aims to identify risk factors associated with COVID-19 breakthrough infections among fully mRNA-vaccinated individuals. METHODS: We conducted a series of observational retrospective analyses using the electronic health records (EHRs) of the Columbia University Irving Medical Center/New York Presbyterian (CUIMC/NYP) up to September 21, 2021. New York City (NYC) adult residences with at least 1 polymerase chain reaction (PCR) record were included in this analysis. Poisson regression was performed to assess the association between the breakthrough infection rate in vaccinated individuals and multiple risk factors-including vaccine brand, demographics, and underlying conditions-while adjusting for calendar month, prior number of visits, and observational days in the EHR. RESULTS: The overall estimated breakthrough infection rate was 0.16 (95% CI 0.14-0.18). Individuals who were vaccinated with Pfizer/BNT162b2 (incidence rate ratio [IRR] against Moderna/mRNA-1273=1.66, 95% CI 1.17-2.35) were male (IRR against female=1.47, 95% CI 1.11-1.94) and had compromised immune systems (IRR=1.48, 95% CI 1.09-2.00) were at the highest risk for breakthrough infections. Among all underlying conditions, those with primary immunodeficiency, a history of organ transplant, an active tumor, use of immunosuppressant medications, or Alzheimer disease were at the highest risk. CONCLUSIONS: Although we found both mRNA vaccines were effective, Moderna/mRNA-1273 had a lower incidence rate of breakthrough infections. Immunocompromised and male individuals were among the highest risk groups experiencing breakthrough infections. Given the rapidly changing nature of the SARS-CoV-2 pandemic, continued monitoring and a generalizable analysis pipeline are warranted to inform quick updates on vaccine effectiveness in real time.

Effectiveness of Homologous and Heterologous COVID-19 Booster Doses Following 1 Ad.26.COV2.S (Janssen [Johnson & Johnson]) Vaccine Dose Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults - VISION Network, 10 States, December 2021-March 2022.

CDC recommends that all persons aged ≥18 years receive a single COVID-19 vaccine booster dose ≥2 months after receipt of an Ad.26.COV2.S (Janssen [Johnson & Johnson]) adenovirus vector-based primary series vaccine; a heterologous COVID-19 mRNA vaccine is preferred over a homologous (matching) Janssen vaccine for booster vaccination. This recommendation was made in light of the risks for rare but serious adverse events following receipt of a Janssen vaccine, including thrombosis with thrombocytopenia syndrome and Guillain-Barré syndrome† (1), and clinical trial data indicating similar or higher neutralizing antibody response following heterologous boosting compared with homologous boosting (2). Data on real-world vaccine effectiveness (VE) of different booster strategies following a primary Janssen vaccine dose are limited, particularly during the period of Omicron variant predominance. The VISION Network§ determined real-world VE of 1 Janssen vaccine dose and 2 alternative booster dose strategies: 1) a homologous booster (i.e., 2 Janssen doses) and 2) a heterologous mRNA booster (i.e., 1 Janssen dose/1 mRNA dose). In addition, VE of these booster strategies was compared with VE of a homologous booster following mRNA primary series vaccination (i.e., 3 mRNA doses). The study examined 80,287 emergency department/urgent care (ED/UC) visits¶ and 25,244 hospitalizations across 10 states during December 16, 2021-March 7, 2022, when Omicron was the predominant circulating variant.** VE against laboratory-confirmed COVID-19-associated ED/UC encounters was 24% after 1 Janssen dose, 54% after 2 Janssen doses, 79% after 1 Janssen/1 mRNA dose, and 83% after 3 mRNA doses. VE for the same vaccination strategies against laboratory-confirmed COVID-19-associated hospitalizations were 31%, 67%, 78%, and 90%, respectively. All booster strategies provided higher protection than a single Janssen dose against ED/UC visits and hospitalizations during Omicron variant predominance. Vaccination with 1 Janssen/1 mRNA dose provided higher protection than did 2 Janssen doses against COVID-19-associated ED/UC visits and was comparable to protection provided by 3 mRNA doses during the first 120 days after a booster dose. However, 3 mRNA doses provided higher protection against COVID-19-associated hospitalizations than did other booster strategies during the same time interval since booster dose. All adults who have received mRNA vaccines for their COVID-19 primary series vaccination should receive an mRNA booster dose when eligible. Adults who received a primary Janssen vaccine dose should preferentially receive a heterologous mRNA vaccine booster dose ≥2 months later, or a homologous Janssen vaccine booster dose if mRNA vaccine is contraindicated or unavailable. Further investigation of the durability of protection afforded by different booster strategies is warranted.

Feasibility of Linking Area Deprivation Index Data to the OMOP Common Data Model.

Linking Area Deprivation Index (ADI) scores to observational data offers the opportunity to characterize healthcare treatment and outcomes that are driven by socioeconomic deprivation. The current study aims to assess the feasibility of creating an analysis package to link ADI rankings to multiple patient-level EHR datasets transformed into the OMOP CDM. Patients within two cancer cohorts (breast cancer and multiple myeloma) were identified within two OMOP datasets and their records were linked with ADI scores using address information in the OMOP location table. With ADI linked to patient addresses, we generated visualizations showing the geographic distribution of each cohort based on ADI scores. Additionally, further assessment showed that over 89% of patient addresses could successfully be linked with ADI rankings. In conducting this assessment, we have demonstrated that developing a package to link ADI scores with multiple OMOP datasets is feasible.

Characteristics and Outcomes of Over 300,000 Patients with COVID-19 and History of Cancer in the United States and Spain.

BACKGROUND: We described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza. METHODS: We conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes. RESULTS: We included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%-18% and 1%-14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events. CONCLUSIONS: Patients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent. IMPACT: This study provides epidemiologic characteristics that can inform clinical care and etiologic studies.

Association between procurement biopsy findings and deceased donor kidney outcomes: a paired kidney analysis.

Unfavourable procurement biopsy findings are the most common reason for deceased donor kidney discard in the United States. We sought to assess the association between biopsy findings and post-transplant outcomes when donor characteristics are accounted for. We used registry data to identify 1566 deceased donors of 3132 transplanted kidneys (2015-2020) with discordant right/left procurement biopsy classification and performed time-to-event analyses to determine the association between optimal histology and hazard of death-censored graft failure or death. We then repeated all analyses using a local cohort of 147 donors of kidney pairs with detailed procurement histology data available (2006-2016). Among transplanted kidney pairs in the national cohort, there were no significant differences in incidence of delayed graft function or primary nonfunction. Time to death-censored graft failure was not significantly different between recipients of optimal versus suboptimal kidneys. Results were similar in analyses using the local cohort. Regarding recipient survival, analysis of the national, but not local, cohort showed optimal kidneys were associated with a lower hazard of death (adjusted HR 0.68, 95% CI 0.52-0.90, P = 0.006). In conclusion, in a large national cohort of deceased donor kidney pairs with discordant right/left procurement biopsy findings, we found no association between histology and death-censored graft survival.

Impact of Deceased Donor Kidney Procurement Biopsy Technique on Histologic Accuracy.

INTRODUCTION: The factors that influence deceased donor kidney procurement biopsy reliability are not well established. We examined the impact of biopsy technique and pathologist training on procurement biopsy accuracy. METHODS: We retrospectively identified all deceased donor kidney-only transplants at our center from 2006 to 2016 with both procurement and reperfusion biopsies performed and information available on procurement biopsy technique and pathologist (n = 392). Biopsies were scored using a previously validated system, classifying "suboptimal" histology as the presence of at least 1 of the following: glomerulosclerosis ≥11%, moderate/severe interstitial fibrosis/tubular atrophy, or moderate/severe vascular disease. We calculated relative risk ratios (RRR) to determine the influence of technique (core vs. wedge) and pathologist (renal vs. nonrenal) on concordance between procurement and reperfusion biopsy histologic classification. RESULTS: A total of 171 (44%) procurement biopsies used wedge technique, and 221 (56%) used core technique. Results of only 36 biopsies (9%) were interpreted by renal pathologists. Correlation between procurement and reperfusion glomerulosclerosis was poor for both wedge (r 2 = 0.11) and core (r 2 = 0.14) biopsies. Overall, 34% of kidneys had discordant classification on procurement versus reperfusion biopsy. Neither biopsy technique nor pathologist training was associated with concordance between procurement and reperfusion histology, but a larger number of sampled glomeruli was associated with a higher likelihood of concordance (adjusted RRR = 1.12 per 10 glomeruli, 95% confidence interval = 1.04-1.22). CONCLUSIONS: Biopsy technique and pathologist training were not associated with procurement biopsy histologic accuracy in this retrospective study. Prospective trials are needed to determine how to optimize procurement biopsy practices.

Treatment Patterns for Chronic Comorbid Conditions in Patients With Cancer Using a Large-Scale Observational Data Network.

PURPOSE: Patients with cancer are predisposed to developing chronic, comorbid conditions that affect prognosis, quality of life, and mortality. While treatment guidelines and care variations for these comorbidities have been described for the general noncancer population, less is known about real-world treatment patterns in patients with cancer. We sought to characterize the prevalence and distribution of initial treatment patterns across a large-scale data network for depression, hypertension, and type II diabetes mellitus (T2DM) among patients with cancer. METHODS: We used the Observational Health Data Sciences and Informatics network, an international collaborative implementing the Observational Medical Outcomes Partnership Common Data Model to standardize more than 2 billion patient records. For this study, we used 8 databases across 3 countries-the United States, France, and Germany-with 295,529,655 patient records. We identified patients with cancer using SNOMED (Systematized Nomenclature of Medicine) codes validated via manual review. We then characterized the treatment patterns of these patients initiating treatment of depression, hypertension, or T2DM with persistent treatment and at least 365 days of observation. RESULTS: Across databases, wide variations exist in treatment patterns for depression (n = 1,145,510), hypertension (n = 3,178,944), and T2DM (n = 886,766). When limited to 6-node (6-drug) sequences, we identified 61,052 unique sequences for depression, 346,067 sequences for hypertension, and 40,629 sequences for T2DM. These variations persisted across sites, databases, countries, and conditions, with the exception of metformin (73.8%) being the most common initial T2DM treatment. The most common initial medications were sertraline (17.5%) and escitalopram (17.5%) for depression and hydrochlorothiazide (20.5%) and lisinopril (19.6%) for hypertension. CONCLUSION: We identified wide variations in the treatment of common comorbidities in patients with cancer, similar to the general population, and demonstrate the feasibility of conducting research on patients with cancer across a large-scale observational data network using a common data model.

Reproducibility of Deceased Donor Kidney Procurement Biopsies.

BACKGROUND AND OBJECTIVES: Unfavorable histology on procurement biopsies is the most common reason for deceased donor kidney discard. We sought to assess the reproducibility of procurement biopsy findings. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compiled a continuous cohort of deceased donor kidneys transplanted at our institution from 1/1/2006 to 12/31/2016 that had at least one procurement biopsy performed, and excluded cases with missing biopsy reports and those used in multiorgan transplants. Suboptimal histology was defined as the presence of advanced sclerosis in greater than or equal to one biopsy compartment (glomeruli, tubules/interstitium, vessels). We calculated κ coefficients to assess agreement in optimal versus suboptimal classification between sequential biopsy reports for kidneys that underwent multiple procurement biopsies and used time-to-event analysis to evaluate the association between first versus second biopsies and patient and allograft survival. RESULTS: Of the 1011 kidneys included in our cohort, 606 (60%) had multiple procurement biopsies; 98% had first biopsy performed at another organ procurement organization and their second biopsy performed locally. Categorical agreement was highest for vascular disease (κ=0.17) followed by interstitial fibrosis and tubular atrophy (κ=0.12) and glomerulosclerosis (κ=0.12). Overall histologic agreement (optimal versus suboptimal) was κ=0.15. First biopsy histology had no association with allograft survival in unadjusted or adjusted analyses. However, second biopsy optimal histology was associated with a higher probability of death-censored allograft survival, even after adjusting for donor and recipient factors (adjusted hazard ratio, 0.50; 95% confidence interval, 0.34 to 0.75; P=0.001). CONCLUSIONS: Deceased donor kidneys that underwent multiple procurement biopsies often displayed substantial differences in histologic categorization in sequential biopsies, and there was no association between first biopsy findings and post-transplant outcomes.

Relative Risk of Cervical Neoplasms Among Copper and Levonorgestrel-Releasing Intrauterine System Users.

OBJECTIVE: To evaluate the relative risk of cervical neoplasms among copper intrauterine device (Cu IUD) and levonorgestrel-releasing intrauterine system (LNG-IUS) users. METHODS: We performed a retrospective cohort analysis of 10,674 patients who received IUDs at Columbia University Medical Center. Our data were transformed to a common data model and are part of the Observational Health Data Sciences and Informatics network. The cohort patients and outcomes were identified by a combination of procedure codes, condition codes, and medication exposures in billing and claims data. We adjusted for confounding with propensity score stratification and propensity score 1:1 matching. RESULTS: Before propensity score adjustment, the Cu IUD cohort included 8,274 patients and the LNG-IUS cohort included 2,400 patients. The median age for both cohorts was 29 years at IUD placement. More than 95% of the LNG-IUS cohort used a device with 52 mg LNG. Before propensity score adjustment, we identified 114 cervical neoplasm outcomes. Seventy-seven (0.9%) cervical neoplasms were in the Cu IUD cohort and 37 (1.5%) were in the LNG-IUS cohort. The propensity score matching analysis identified 7,114 Cu IUD and 2,174 LNG-IUS users, with covariate balance achieved over 16,827 covariates. The diagnosis of high-grade cervical neoplasia was 0.7% in the Cu IUD cohort and 1.8% in the LNG-IUS cohort (2.4 [95% CI 1.5-4.0] cases/1,000 person-years and 5.2 [95% CI 3.7-7.1] cases/1,000 person-years, respectively). The relative risk of high-grade cervical neoplasms among Cu IUD users was 0.38 (95% CI 0.16-0.78, P<.02) compared with LNG-IUS users. By inspection, the Kaplan-Meier curves for each cohort diverged over time. CONCLUSION: Copper IUD users have a lower risk of high-grade cervical neoplasms compared with LNG-IUS users. The relative risk of cervical neoplasms of LNG-IUS users compared with the general population is unknown.

The Young Myocardial Infarction Study of the Western Indians: YOUTH Registry.

BACKGROUND: Myocardial infarction is among the leading causes of morbidity and mortality in young adults around the world. OBJECTIVES: In the YOUTH (Young Myocardial Infarction Study of the Western Indians) registry, we aimed to evaluate risk factor profile and angiographic outcomes of reperfusion therapies of infarct-related artery in young western Indians (≤40 years) having ST-segment elevation myocardial infarction. METHODS: A total of 1,179 consecutive patients aged ≤40 years who presented with ischemic heart disease from June 2012 to December 2014 were enrolled in the YOUTH registry. A total of 787 patients with ST-segment elevation myocardial infarction were further evaluated. Categorical data was assessed using chi-square test, whereas continuous data was assessed using Student's t test. Regression analysis was performed to investigate the strength of association. RESULTS: In the YOUTH registry, the study population was predominantly male (93%) with tobacco consumption as major prevalent risk factor (49.7%). Of 787 patients, 451 (57.31%) were thrombolyzed, 326 (41.42%) did not receive any reperfusion therapy, and 10 patients (1.27%) underwent primary angioplasty. Younger age, window period <6 h, and lower lipoprotein (a) level were observed in patients with a recanalized infarct-related artery. Regression analysis showed window period of thrombolysis as strongest predictor (odds ratio: 1.790, 95% confidence interval: 1.144-2.802; p < 0.011) of successful reperfusion. Patients (n = 235) being thrombolyzed in a window period of <6 h, had higher rate of infarct-related artery recanalization (77%) as compared to those with ≥6 h window period (23%). In-hospital mortality was 0.38% (n = 3), whereas bleeding complication was noted only in 1 patient. CONCLUSIONS: We herewith conclude that acute short-term outcome is favorable in young ST-segment elevation myocardial infarction patients, particularly in those who had received timely thrombolytic therapy. Though tobacco consumption was a major contributor of risk in young adults, prevalence of other risk factors was low in young Western Indians.

Vaccination Coverage of Adolescents With Chronic Medical Conditions.

INTRODUCTION: Adolescents with chronic medical conditions (CMCs) are at increased risk of vaccine-preventable infections. Little is known about their vaccine uptake. METHODS: This retrospective cohort study included 3,989 adolescents aged 11-17 years receiving care at academically affiliated pediatric clinics between August 2011 and June 2013. Data were abstracted from the medical center's electronic health record and immunization registry in 2014. Vaccination coverage, timeliness, and missed opportunities were evaluated and analyzed in 2015-2016. RESULTS: Adolescents with CMCs had lower human papillomavirus vaccination initiation than those without CMCs (81.3% vs 85.0%), although this difference was only observed in stratified analysis among males (adjusted relative risk=0.90, 95% CI=0.85, 0.96), aged 13-17 years (adjusted relative risk=0.94, 95% CI=0.91, 0.98), and those with more primary care visits (adjusted relative risk=0.94, 95% CI=0.91, 0.98). Adolescents with CMCs had greater influenza vaccination coverage and timeliness than those without CMCs (2011-2012 season: 66.9% vs 50.1%; adjusted hazards ratio=1.27, 95% CI=1.15, 1.40; 2012-2013 season: 73.8% vs 64.5%; adjusted hazards ratio=1.20, 95% CI=1.10, 1.31). Only 32.1% and 18.2% of eligible adolescents had received pneumococcal polysaccharide and 13-valent pneumococcal conjugate vaccines, respectively. Missed opportunities were higher among adolescents with versus without CMCs for human papillomavirus vaccination initiation (4.2 vs 2.7, p<0.001), meningococcal vaccination (4.0 vs 2.9, p<0.001), and influenza vaccination (2011-2012 season: 2.1 vs 1.7, p<0.001; 2012-2013 season: 2.0 vs 1.6, p<0.001). Missed opportunities for pneumococcal vaccination were common. CONCLUSIONS: Pockets of undervaccination and missed opportunities exist among adolescents with CMCs. Greater, more timely influenza vaccination suggests that optimal vaccination of high-risk adolescents is possible.

HPV vaccination: are we initiating too late?

BACKGROUND: Human papillomavirus (HPV) vaccination is recommended in early adolescence. While limited data suggest that patients frequently delay initiation of the three-dose series, age-based variability in initiation of HPV vaccination and its clinical relevance are not well described. Thus, this study aims to characterize HPV vaccination delay among adolescent and young adult females. METHODS: This retrospective cohort study examined age at HPV vaccination initiation and missed opportunities for receipt of the first vaccine dose (HPV1) among 11-26 year-old females (n=22,900) receiving care at 16 urban academically-affiliated ambulatory care clinics between 2007 and 2011. Predictors of timely vaccination and post-licensure trends in age at HPV1 receipt were assessed using multivariable logistic regression and a generalized linear mixed model, respectively. Chlamydia trachomatis and Papanicolaou screening before HPV vaccination initiation, as markers of prior sexual experience and associated morbidity, were examined in a subcohort of subjects (n=15,049). RESULTS: The proportion of 11-12 year-olds who initiated HPV vaccination increased over time (44.4% [2007] vs. 74.5% [2011], p<0.01). Initiation rates also improved among 13-26 year-olds. Thus, the mean age at HPV1 receipt remained unchanged between 2007 and 2011 (16.0 ± 2.7 vs. 15.9 ± 4.0 years, p=0.45). Spanish language was a positive predictor (AOR 1.62, 95% CI 1.05-2.48) of HPV vaccination initiation among 11-12 year-olds in 2011. The majority (70.8-76.4%) of unvaccinated subjects experienced missed vaccination opportunities. Of the subcohort, 36.9% underwent Chlamydia screening before HPV1 receipt (19.1% with ≥ 1 positive result). Of those with prior Papanicolaou screening (16.6%), 32.1% had ≥ 1 abnormal result. CONCLUSIONS: These low-income, minority females frequently delayed initiation of HPV vaccination. Many had evidence of prior sexual experience and associated morbidity, placing them at risk of HPV-related complications. Promoting timely HPV vaccination and reducing missed vaccination opportunities are crucial.