Near real-time surveillance of safety outcomes in US COVID-19 vaccine recipients aged 12 to 64 years.

BACKGROUND: Active monitoring of safety outcomes following COVID-19 vaccination is critical to understand vaccine safety and can provide early detection of rare outcomes not identified in pre-licensure trials. We present findings from an early warning rapid surveillance system in three large commercial insurance databases including more than 16 million vaccinated individuals. METHODS: We evaluated 17 outcomes of interest following COVID-19 vaccination among individuals aged 12-64 years in Optum, HealthCore, and CVS Health databases from December 11, 2020, through January 22, 2022, January 7, 2022, and December 31, 2021, respectively. We conducted biweekly or monthly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. FINDINGS: Among 17 outcomes evaluated, 15 did not meet the threshold for statistical signal in any of the three databases. Myocarditis/pericarditis met the statistical threshold for a signal following BNT162b2 in two of three databases (RRs: 1.83-2.47). Anaphylaxis met the statistical threshold for a signal in all three databases following BNT162b2 vaccination (RRs: 4.48-10.86) and mRNA-1273 vaccination (RRs: 7.64-12.40). DISCUSSION: Consistent with published literature, our near-real time monitoring of 17 adverse outcomes following COVID-19 vaccinations identified signals for myocarditis/pericarditis and anaphylaxis following mRNA COVID-19 vaccinations. The method is intended for early detection of safety signals, and results do not imply a causal effect. Results of this study should be interpreted in the context of the method's utility and limitations, and the validity of detected signals must be evaluated in fully adjusted epidemiologic studies.

The risk of febrile seizures following influenza and 13-valent pneumococcal conjugate vaccines.

BACKGROUND: Evidence on the risk of febrile seizures after inactivated influenza vaccine (IIV) and 13-valent pneumococcal conjugate vaccine (PCV13) is mixed. In the FDA-sponsored Sentinel Initiative, we examined risk of febrile seizures after IIV and PCV13 in children 6-23 months of age during the 2013-14 and 2014-15 influenza seasons. METHODS: Using claims data and a self-controlled risk interval design, we compared the febrile seizure rate in a risk interval (0-1 days) versus control interval (14-20 days). In exploratory analyses, we assessed whether the effect of IIV was modified by concomitant PCV13 administration. RESULTS: Adjusted for age, calendar time and concomitant administration of the other vaccine, the incidence rate ratio (IRR) for risk of febrile seizures following IIV was 1.12 (95% CI 0.80, 1.56) and following PCV13 was 1.80 (95% CI 1.29, 2.52). The attributable risk for febrile seizures following PCV13 ranged from 0.33 to 5.16 per 100,000 doses by week of age. The age and calendar-time adjusted IRR comparing exposed to unexposed time was numerically larger for concomitant IIV and PCV13 (IRR 2.80, 95% CI 1.63, 4.83), as compared to PCV13 without concomitant IIV (IRR 1.54, 95% CI 1.04, 2.28), and the IRR for IIV without concomitant PCV13 suggested no independent effects of IIV (IRR 0.94, 95% CI 0.63, 1.42). Taken together, this suggests a possible interaction between IIV and PCV13, though our study was not sufficiently powered to provide a precise estimate of the interaction. CONCLUSIONS: We found an elevated risk of febrile seizures after PCV13 vaccine but not after IIV. The risk of febrile seizures after PCV13 is low compared to the overall risk in this population of children, and the risk should be interpreted in the context of the importance of preventing pneumococcal infections.

Validation of febrile seizures identified in the Sentinel Post-Licensure Rapid Immunization Safety Monitoring Program.

BACKGROUND: The Sentinel Initiative was established in 2008 to monitor the safety of FDA-regulated medical products. We evaluated the positive predictive value (PPV) of ICD-9 codes for post-vaccination febrile seizures to identify optimal algorithms for use in post-market safety surveillance. METHODS: We identified ICD-9 diagnosis codes for fever and seizures in the emergency department or inpatient setting after vaccinations of interest from July 1, 2010 to June 30, 2011. Medical record review was conducted to verify febrile seizure events. RESULTS: Of 216 potential febrile seizures identified with one or more seizure codes (the broadest algorithm), 152 were chart-confirmed (i.e., documentation of fever within 24 h of seizure or clinician diagnosis of febrile seizure; PPV 70%, 95% CI 64, 76%). Two codes specific for febrile seizures produced the highest PPV (PPV 91%, 95% CI 85, 95%) and accounted for 140 confirmed febrile seizures. In the absence of febrile seizure codes, other seizure codes yielded much lower PPVs, regardless of the presence of fever codes. CONCLUSIONS: Our results indicate that ICD-9 diagnosis codes in the inpatient and emergency department settings have high predictive value for identifying febrile seizures within the Sentinel Distributed Database. While the PPV of the algorithm based on any diagnosis code for seizure is moderate, the algorithm limited to febrile seizure codes has a high PPV (>90%) and captures the vast majority of confirmed cases identified by the broadest algorithm, suggesting that the narrower algorithm limited to febrile seizure codes may be preferred.

Do FDA label changes work? Assessment of the 2010 class label change for proton pump inhibitors using the Sentinel System's analytic tools.

PURPOSE: To pilot use of the US Food and Drug Administration's (FDA's) Sentinel System data and analytic tools by a non-FDA stakeholder through the Innovation in Medical Evidence Development and Surveillance system of the Reagan Udall Foundation. We evaluated the US FDA 2010 proton pump inhibitor (PPI) class label change that warned of increased risk of bone fracture, to use PPIs for the lowest dose and shortest duration, and to manage bone status for those at risk for osteoporosis. METHODS: The cohort consisted of adults aged 18 years or older prescribed PPIs without fracture risk factors. We evaluated incident and prevalent uses of the 8 PPIs noted in the label change. Outcomes evaluated before and after label change were PPI dispensing patterns, incident fractures, and osteoporosis screening or interventions. Consistent with FDA use of descriptive tools, we did not include direct comparisons or statistical testing. RESULTS: There were 1 488 869 and 2 224 420 incident PPI users in the before [PRE] and after [POST] periods, respectively. Users with 1 year or more of exposure decreased (8.4% vs 7.5%), as did mean days supplied/user (130.4 to 113.7 d among all users and 830.8 to 645.4 d among users with 1 y or more of exposure). Osteoporosis screening and interventions did not appear to increase, but the proportion of patients with fractures decreased (4.4% vs 3.1%). Prevalent user results were similar. CONCLUSIONS: This analysis demonstrated the ability to use Sentinel tools to assess the effectiveness of a label change and accompanying communication at the population level and suggests an influence on subsequent dispensing behavior.

Occurrence of hemolytic reactions on the same day as immune globulin product administrations during 2008 to 2014.

BACKGROUND: Hemolytic reactions (HRs) are rare serious adverse events after immune globulin (IG) use. Our large claims-based study evaluated occurrence of same-day hemolysis after administration of different IG products and potential risk factors, during the 2008 to 2014 study period. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study using a large commercial administrative database. The study included individuals exposed to IG products as identified by procedure codes. HRs were ascertained using ICD-9-CM diagnosis codes. Unadjusted same-day hemolysis rates (per 1000 persons) were estimated overall, by age, sex, and IG products. Multivariable regression analyses were used to evaluate potential risk factors. RESULTS: Of 20,440 persons exposed, 211 (10.3 per 1000) had same-day HRs. The median numbers of doses for IG users with versus without same-day hemolysis were one and six, respectively. The unadjusted product-specific HR rates ranged from 1.92 for subcutaneous product Hizentra to 17.99 for intravenous Octagam. The multivariable regression analyses showed significantly increased same-day HR risk in males and in IG users with histories of hemolysis, pneumonia, and hereditary hemolytic anemias. Compared to Gammagard Liquid, significantly elevated overall hemolysis risk was identified with Octagam (odds ratio, 2.36; 95% confidence interval, 1.04-5.35), using Firth's method to account for small sample size bias. CONCLUSION: The study showed variation in the same-day IG-related hemolysis by age, sex, and IG products administered. The results suggest importance of underlying health conditions, especially prior hemolysis, and first IG product dose. Differences in HR occurrence may also be explained by product manufacturing processes, indications, routes, and rates of administration, which warrant further investigation.

Occurrence of acute renal failure on the same day as immune globulin product administrations during 2008 to 2014.

BACKGROUND: Acute renal failure (ARF) is a rare serious adverse event after immune globulin (IG) use. Our large claims-based study evaluated occurrence of same-day ARF after administration of different IGs and ascertained potential risk factors, during the 2008 to 2014 study period. STUDY DESIGN AND METHODS: A retrospective cohort study was conducted using a large commercial administrative database. The cohort included individuals exposed to IG products as identified by procedure codes. ARF was ascertained using ICD-9-CM diagnoses. Unadjusted same-day ARF rates (per 1000 persons exposed) were estimated overall and by age, sex, and IG products. Regression analyses were conducted to control for confounding and assess potential risk factors. RESULTS: Of 20,440 persons exposed, 163 (7.97 per 1000) had a recorded same-day ARF. The unadjusted nonzero same-day ARF rates (per 1000) ranged from 1.92 (95% confidence interval [CI], 0.05-10.69) for Hizentra to 16.97 (95% CI, 11.36-24.37) for Privigen and differed by sex. In multivariate analyses, compared to Gammagard Liquid, no significantly elevated ARF risks were identified with any IGs. A significantly lower odds ratio was identified with Gamunex, 0.53 (95% CI, 0.30-0.93). Age 45 and over, prior renal impairment, hypertension, and other factors were associated with increased risk of same-day ARF. CONCLUSION: The study showed variation in the risk of IG-related ARF by age, sex, and IG products. The study results suggest the importance of recipient factors, such as older age and underlying health conditions. Variations in ARF occurrence may also be explained by product dosage, administration route and rate, and manufacturing processes, which warrant further evaluation.

Aggressive End-of-Life Care for Metastatic Cancer Patients Younger Than Age 65 Years.

Background: Aggressive medical care at the end of life can be harmful to patients and families, but its prevalence in use among younger cancer patients is unknown. The goal of the study was to report on the use of aggressive care and hospice services for patients younger than age 65 years. Methods: Using the HealthCore Integrated Research Database, we analyzed patients who died between 2007 and 2014 with metastatic lung (n = 12 764), colorectal (n = 5207), breast (n = 5855), pancreatic (n = 3397), or prostate (n = 1508) cancer. Based on published quality measures, we assessed uses of chemotherapy, intensive care, emergency room visits, and hospice care at the end of life. We examined additional items including radiotherapy, invasive procedures, hospitalization, and in-hospital deaths. Multivariable modified Poisson regression models were used to adjust for age, sex, geographic region, rural/urban location, year of death, and regional education and income measures. Results: Across the five cancers, 10.1% to 14.1% of patients received chemotherapy within the last 14 days of life, 15.9% to 20.6% received intensive care in last 30 days, and 1.5% to 2.5% went to the emergency room two or more times in last 30 days. Hospice enrollment at least three days before death was 54.4% to 59.6%. However, 55.3% to 59.3% of patients had a hospital admission in the last 30 days, and one-third died (30.3%-35.4%) in the hospital. Conclusions: There was low use of cancer-directed treatment at the end of life for younger cancer patients, and hospice use was higher than 50%. However, there was a relatively high utilization of hospital-based care. These results demonstrate an opportunity for continued improvements in the provision of high-value, patient-centered care at the end of life.

Initiation of Trastuzumab by Women Younger Than 64 Years for Adjuvant Treatment of Stage I-III Breast Cancer.

Purpose: Studies have reported disparities by age and race in the initiation of adjuvant trastuzumab for the initial treatment of older women with early-stage breast cancer, but less is known about its initiation in younger patients. Therefore, we assessed temporal trends and clinical and demographic factors associated with trastuzumab initiation in a large, population-based cohort of patients aged <64 years in 5 states. Methods: Using a cancer registry and claims-linked data set of 13,398 women with incident invasive breast cancer from 2006 to 2011, we identified 934 patients aged <64 years with HER2-positive stage I-III breast cancer. We assessed trastuzumab initiation within the first 9 months after diagnosis and conducted logistic regression analyses to assess sociodemographic and clinical factors associated with trastuzumab initiation. Results: From 2006 to 2011, trastuzumab initiation steadily increased in patients with node-positive (from 65% to 91%) and node-negative (from 39% to 75%) breast cancers. Several tumor-related factors were associated with trastuzumab initiation, including high histologic grades (adjusted odds ratio [aOR], 6.43; 95% CI, 3.27-12.65; and aOR, 3.25; 95% CI, 1.66-6.36, for grades 3 and 2, respectively), node-positive status (aOR, 1.88; 95% CI, 1.28-2.78; P=.001), tumor size >2 cm (aOR, 1.50; 95% CI, 1.04-2.16; P=.03), and hormone receptor-negative status (aOR, 1.51; 95% CI, 1.01-2.26; P=.04). We found a null effect of race. Conclusions: Adjuvant trastuzumab therapy for early-stage breast cancer has been widely disseminated among women aged <64 years. The initiation of this targeted therapy was associated with higher-risk features, consistent with practice guidelines.

Evaluation of optic neuritis following human papillomavirus vaccination.

To assess the relationship between human papillomavirus (HPV) vaccination and occurrence of optic neuritis (ON) and to evaluate a claims-based algorithm for identification of ON. Females of 9-26 year olds in the HealthCore's Integrated Research Database (HIRDSM) with and without claims evidence of HPV vaccination between 2007 and 2012 were included in this study. Potential ON cases were identified using the claims-based algorithm, positive predictive value (PPV) was determined using medical chart review. For the claims analysis, two study designs, a self-controlled temporal scan statistic and a retrospective matched cohort analysis, were used. ON was defined based on an algorithm developed using diagnosis and procedure codes from the medical claims. The PPV for ON cases using charts that had enough information for reviewers to make a determination was 62.5% (95% CI: 49.5%-74.3%). With the self-controlled temporal scan statistic, the primary analysis restricting on recommended vaccination schedule timing showed an increased risk of potential ON after second dose (RR = 3.39; p = 0.03), this finding was not confirmed for any of the additional analyses performed for individual or combined doses. With the cohort design, there was no increased risk of potential ON following vaccination in either individual or combined dose analyses. The risk of potential ON was higher among participants with a history of prior autoimmune diseases. In conclusion, identifying confirmed ON cases through administrative claims data proved challenging. The claims-based analysis in this study did not provide evidence for an association of ON with HPV vaccination.

Endocrine therapy initiation, discontinuation and adherence and breast imaging among 21-gene recurrence score assay-eligible women under age 65.

BACKGROUND: Aside from chemotherapy utilization, limited data are available on the relationship between gene expression profiling (GEP) testing and breast cancer care. We assessed the relationship between GEP testing and additional variables and the outcomes of endocrine therapy initiation, discontinuation and adherence, and breast imaging exams in women under age 65 years. METHODS: Data from five state cancer registries were linked with claims data and GEP results. We assessed variables associated with survivorship care outcomes in an incident cohort of 5014 commercially insured women under age 65 years, newly diagnosed with stage I or II hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2) non-positive breast cancer from 2006 to 2010. RESULTS: Among tested women, those with high Oncotype DX® Breast Recurrence Score® (RS) were significantly less likely to initiate endocrine therapy than women with low RS tumors (OR 0.40 (95% CI 0.20 to 0.81); P = 0.01). Among all test-eligible women, receipt of Oncotype DX testing was associated with a greater likelihood of endocrine therapy initiation (OR 2.48 (95% CI 2.03 to 3.04); P <0.0001). The odds of initiation were also significantly higher for tested vs. untested women among women who did not initiate chemotherapy within six months of diagnosis (OR 3.25 (95% CI 2.53 to 4.16)), with no effect in women who received chemotherapy. Discontinuation and adherence and breast imaging exams were unrelated to tested status or RS. CONCLUSIONS: Lower endocrine therapy initiation rates among women with high RS tumors and among untested women not receiving chemotherapy are concerning, given its established efficacy. Additional research is needed to suggest mechanisms to close this gap.

Use of Quantile Regression to Determine the Impact on Total Health Care Costs of Surgical Site Infections Following Common Ambulatory Procedures.

OBJECTIVE: To determine the impact of surgical site infections (SSIs) on health care costs following common ambulatory surgical procedures throughout the cost distribution. BACKGROUND: Data on costs of SSIs following ambulatory surgery are sparse, particularly variation beyond just mean costs. METHODS: We performed a retrospective cohort study of persons undergoing cholecystectomy, breast-conserving surgery, anterior cruciate ligament reconstruction, and hernia repair from December 31, 2004 to December 31, 2010 using commercial insurer claims data. SSIs within 90 days post-procedure were identified; infections during a hospitalization or requiring surgery were considered serious. We used quantile regression, controlling for patient, operative, and postoperative factors to examine the impact of SSIs on 180-day health care costs throughout the cost distribution. RESULTS: The incidence of serious and nonserious SSIs was 0.8% and 0.2%, respectively, after 21,062 anterior cruciate ligament reconstruction, 0.5% and 0.3% after 57,750 cholecystectomy, 0.6% and 0.5% after 60,681 hernia, and 0.8% and 0.8% after 42,489 breast-conserving surgery procedures. Serious SSIs were associated with significantly higher costs than nonserious SSIs for all 4 procedures throughout the cost distribution. The attributable cost of serious SSIs increased for both cholecystectomy and hernia repair as the quantile of total costs increased ($38,410 for cholecystectomy with serious SSI vs no SSI at the 70th percentile of costs, up to $89,371 at the 90th percentile). CONCLUSIONS: SSIs, particularly serious infections resulting in hospitalization or surgical treatment, were associated with significantly increased health care costs after 4 common surgical procedures. Quantile regression illustrated the differential effect of serious SSIs on health care costs at the upper end of the cost distribution.

Quality of Care Provided by Board-Certified Versus Non-Board-Certified Psychiatrists and Neurologists.

PURPOSE: To examine associations between board certification of psychiatrists and neurologists and quality-of-care measures, using multilevel models controlling for physician and patient characteristics, and to assess feasibility of linking physician information with patient records to construct quality measures from electronic claims data. METHOD: The authors identified quality measures and matched claims data from 2006 to 2012 with 942 board-certified (BC) psychiatrists, 868 non-board-certified (nBC) psychiatrists, 963 BC neurologists, and 328 nBC neurologists. Using the matched data, they identified psychiatrists who treated at least one patient with a schizophrenia diagnosis, and neurologists attending patients discharged with a principal diagnosis of ischemic stroke, and analyzed claims from these patients. For patients with schizophrenia who were prescribed an atypical antipsychotic, quality measures were claims for glucose and lipid tests, duration of any antipsychotic treatment, and concurrent prescription of multiple antipsychotics. For patients with ischemic stroke, quality measures were dysphagia evaluation; speech/language evaluation; and prescription of clopidogrel, low-molecular-weight heparin, intravenous heparin, and warfarin (for patients with co-occurring atrial fibrillation). RESULTS: Overall, multilevel models (patients nested within physicians) showed no statistically significant differences in quality measures between BC and nBC psychiatrists and neurologists. CONCLUSIONS: The authors demonstrated the feasibility of linking physician information with patient records to construct quality measures from electronic claims data, but there may be only minimal differences in the quality of care between BC and nBC psychiatrists and neurologists, or there may be a difference that could not be measured with the quality measures used.

Bidirectional Data Collaborations in Distributed Research.

INTRODUCTION: The need for collaborations with bidirectional data exchange within and across distributed research networks has increased. CURRENTLY EXISTING ACTIVITIES: This commentary will present currently publically available activities including the Sentinel Initiative, the Patient-Centered Outcomes Research Network (PCORnet), and the NIH Research Collaboratory. CURRENT TECHNICAL AND GOVERNANCE CHALLENGES: Even with the advances made in this arena, several technical and governance challenges remain including the evolution of clinically rich data sources and modes of care, availability of longitudinal data resources through data linkage, and the processes to share data and link data resources while ensuring privacy and proprietary control of data. PERSPECTIVE: These activities will require enhanced levels of trust between entities involved in the delivery of healthcare (Trust 2.0) in addition to the trust health plans and health systems have with patients (Trust 1.0). Recent public funding announcements and public access to data resources will likely improve the landscape of bidirectional data collaborations in distributed research.

Evaluation of the risk of venous thromboembolism after quadrivalent human papillomavirus vaccination among US females.

After the Food and Drug Administration (FDA) licensed quadrivalent human papillomavirus vaccine (HPV4) in 2006, reports suggesting a possible association with venous thromboembolism (VTE) emerged from the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink. Our objective was to determine whether HPV4 increased VTE risk. The subjects were 9-26-year-old female members of five data partners in the FDA's Mini-Sentinel pilot project receiving HPV4 during 2006-2013. The outcome was radiologically confirmed first-ever VTE among potential cases identified by diagnosis codes in administrative data during Days 1-77 after HPV4 vaccination. With a self-controlled risk interval design, we compared counts of first-ever VTE in risk intervals (Days 1-28 and Days 1-7 post-vaccination) and control intervals (Days 36-56 for Dose 1 and Days 36-63 for Doses 2 and 3). Combined hormonal contraceptive use was treated as a potential confounder. The main analyses were: (1) unadjusted for time-varying VTE risk from contraceptive use, (2) unadjusted but restricted to cases without such time-varying risk, and (3) adjusted by incorporating the modeled risk of VTE by week of contraceptive use in the analysis. Of 279 potential VTE cases identified following 1,423,399 HPV4 doses administered, 225 had obtainable charts, and 53 were confirmed first-ever VTE. All 30 with onsets in risk or control intervals had known risk factors for VTE. VTE risk was not elevated in the first 7 or 28 days following any dose of HPV in any analysis (e.g. relative risk estimate (95% CI) from both unrestricted analyses, for all-doses, 28-day risk interval: 0.7 (0.3-1.4)). Temporal scan statistics found no clustering of VTE onsets after any dose. Thus, we found no evidence of an increased risk of VTE associated with HPV4 among 9-26-year-old females. A particular strength of this evaluation was its control for both time-invariant and contraceptive-related time-varying potential confounding.

Provider Patient-Sharing Networks and Multiple-Provider Prescribing of Benzodiazepines.

BACKGROUND: Prescription benzodiazepine overdose continues to cause significant morbidity and mortality in the US. Multiple-provider prescribing, due to either fragmented care or "doctor-shopping," contributes to the problem. OBJECTIVE: To elucidate the effect of provider professional relationships on multiple-provider prescribing of benzodiazepines, using social network analytics. DESIGN: A retrospective analysis of commercial healthcare claims spanning the years 2008 through 2011. Provider patient-sharing networks were modelled using social network analytics. Care team cohesion was measured using care density, defined as the ratio between the total number of patients shared by provider pairs within a patient's care team and the total number of provider pairs in the care team. Relationships within provider pairs were further quantified using a range of network metrics, including the number and proportion of patients or collaborators shared. MAIN MEASURES: The relationship between patient-sharing network metrics and the likelihood of multiple prescribing of benzodiazepines. PARTICIPANTS: Patients between the ages of 18 and 64 years who received two or more benzodiazepine prescriptions from multiple providers, with overlapping coverage of more than 14 days. RESULTS: A total of 5659 patients and 1448 provider pairs were included in our study. Among these, 1028 patients (18.2 %) received multiple prescriptions of benzodiazepines, involving 445 provider pairs (30.7 %). Patients whose providers rarely shared patients had a higher risk of being prescribed overlapping benzodiazepines; the median care density was 8.1 for patients who were prescribed overlapping benzodiazepines and 10.1 for those who were not (p < 0.0001). Provider pairs who shared a greater number of patients and collaborators were less likely to co-prescribe overlapping benzodiazepines. CONCLUSIONS: Our findings demonstrate the importance of care team cohesion in addressing multiple-provider prescribing of controlled substances. Furthermore, we illustrate the potential of the provider network as a surveillance tool to detect and prevent adverse events that could arise due to fragmentation of care.

Adoption of Gene Expression Profiling for Breast Cancer in US Oncology Practice for Women Younger Than 65 Years.

BACKGROUND: A number of practice guidelines incorporate the use of gene expression profiling (GEP) tests for early-stage, hormone receptor-positive, HER2-negative breast tumors. Few studies describe factors associated with GEP testing in US oncology practice. We assessed the relationship between clinical, demographic, and group-level socioeconomic variables and test use in women younger than 65 years. PATIENTS AND METHODS: Data from 5 state cancer registries were linked with insurance claims data and GEP test results. We assessed rates of testing and variables associated with test use in an incident cohort of 9,444 commercially insured women younger than 65 years, newly diagnosed with stage I or II hormone receptor-positive breast cancer from 2006 through 2012. RESULTS: Rates of testing for women with N0 disease increased from 20.4% in 2006 to 35.2% in 2011. Variables associated with higher rates of testing, beyond clinical factors such as nodal status (P<.001), included being diagnosed from 2008 through 2012 versus 2006 through 2007 (adjusted odds ratio [OR], 1.67; 95% CI, 1.47-1.90), having preexisting comorbidities (adjusted OR, 1.35; 95% CI, 1.14-1.59), and higher out-of-pocket pharmacy costs (adjusted OR, 1.66; 95% CI, 1.40-1.97). Women younger than 50 years were more likely to be tested if they had stage I versus stage II disease (P<.0001). CONCLUSIONS: In an insured population of women younger than 65 years, GEP testing increased after its inclusion in clinical practice guidelines and mounting evidence. Additional research is needed to better understand oncologists' decision not to order GEP testing for their patients who are otherwise eligible.

Febrile Seizures After 2010-2011 Trivalent Inactivated Influenza Vaccine.

OBJECTIVES: In the Post-Licensure Rapid Immunization Safety Monitoring Program, we examined risk of febrile seizures (FS) after trivalent inactivated influenza vaccine (TIV) and 13-valent pneumococcal conjugate vaccine (PCV13) during the 2010-2011 influenza season, adjusted for concomitant diphtheria tetanus acellular pertussis-containing vaccines (DTaP). Assuming children would receive both vaccines, we examined whether same-day TIV and PCV13 vaccination was associated with greater FS risk when compared with separate-day vaccination. METHODS: We used a self-controlled risk interval design, comparing the FS rate in a risk interval (0-1 days) versus control interval (14-20 days). Vaccinations were identified in claims and immunization registry data. FS were confirmed with medical records. RESULTS: No statistically significant TIV-FS associations were found in unadjusted or adjusted models (incidence rate ratio [IRR] adjusted for age, seasonality, and concomitant PCV13 and DTaP: 1.36, 95% confidence interval [CI] 0.78 to 2.39). Adjusted for age and seasonality, PCV13 was significantly associated with FS (IRR 1.74, 95% CI 1.06 to 2.86), but not when further adjusting for concomitant TIV and DTaP (IRR 1.61, 95% CI 0.91 to 2.82). Same-day TIV and PCV13 vaccination was not associated with excess risk of FS when compared with separate-day vaccination (1.08 fewer FS per 100 000 with same day administration, 95% CI -5.68 to 6.09). CONCLUSIONS: No statistically significant increased risk of FS was found for 2010-2011 TIV or PCV13, when adjusting for concomitant vaccines. Same-day TIV and PCV13 vaccination was not associated with more FS compared with separate-day vaccination.

Population-based study of the effect of gene expression profiling on adjuvant chemotherapy use in breast cancer patients under the age of 65 years.

BACKGROUND: Gene expression profiling (GEP) testing can help to predict the risk of cancer recurrence and guide decisions about adjuvant chemotherapy for breast cancer (BC). However, no prior US studies have evaluated the relation between GEP testing and the use of adjuvant chemotherapy by women treated in a general oncology practice. METHODS: Eligible patients were women under the age 65 of years who were newly diagnosed with their first stage I or II, hormone receptor-positive BC between 2006 and 2011 (n = 9405). This retrospective study was conducted with a data set consisting of registry data, health claims data, and GEP testing results. The distribution of GEP test results was reported in terms of the risk of recurrence predicted, and logistic regression was used to assess the association of test results with chemotherapy use, with adjustments made for multiple patient characteristics. RESULTS: The proportions of tested women with low, intermediate, and high recurrence score results were 51%, 39%, and 10%, respectively. Among these women, 11%, 47%, and 88%, respectively, received adjuvant chemotherapy. There was a significant, positive linear relation of assay scores with chemotherapy use within the low and intermediate subgroups after adjustments for all other factors (adjusted odds ratios, 1.17 and 1.20, respectively). CONCLUSIONS: Adjuvant chemotherapy use after GEP testing is generally consistent with the recommended test interpretation for women with a high or low predicted risk of recurrence. Chemotherapy use in the intermediate-risk group increased with Recurrence Score values, and evidence from ongoing randomized trials may help to clarify whether this finding reflects optimal interpretation of GEP test results. These results demonstrate the principle that genomic testing, on the basis of research establishing its utility, can be applied appropriately in general practice in accordance with guideline recommendations.

Identification of Stevens-Johnson syndrome and toxic epidermal necrolysis in electronic health record databases.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) carry a high mortality risk. While identifying clinical and genetic risk factors for these conditions has been hindered by their rarity, large electronic health databases hold promise for identifying large numbers of cases for study, especially with the introduction in 2008 of ICD-9 codes more specific for these conditions. OBJECTIVE: The objective of this study is to estimate the validity of ICD-9 codes for ascertaining SJS/TEN in 12 collaborating research units in the USA, covering almost 60 million lives. METHODS: From the electronic databases at each site, we ascertained potential cases of SJS/TEN using ICD-9 codes. At five sites, a subset of medical records was abstracted and standardized criteria applied by board-certified dermatologists to adjudicate diagnoses. Multivariate logistic regression was used to identify factors independently associated with validated SJS/TEN cases. RESULTS: A total of 56 591 potential cases of SJS/TEN were identified. A subset of 276 charts was selected for adjudication and 39 (of the 276) were confirmed as SJS/TEN. Patients with the ICD-9 codes introduced after 2008 were more likely to be confirmed as cases (OR 3.32; 95%CI 0.82, 13.47) than those identified in earlier years. Likelihood of case status increased with length of hospitalization. Applying the probability of case status to the 56 591 potential cases, we estimated 475-875 to be valid SJS/TEN cases. CONCLUSION: Newer ICD-9 codes, along with length of hospitalization, identified patients with a high likelihood of SJS/TEN. This is important for identification of subjects for future pharmacogenomics studies.