Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-27 (of 27 Records) |
Query Trace: Flagg EW[original query] |
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Can diagnostic codes in health-care claims data identify confirmed chlamydial and gonococcal infections A retrospective cohort study, 2003-2017
Mauk KC , Torrone EA , Flagg EW . Sex Transm Dis 2021 48 S26-S31 BACKGROUND: Because most sources of administrative claims data do not contain laboratory result data, researchers rely on diagnosis codes to identify cases of disease. The validity of using diagnosis codes to identify chlamydial and gonococcal infections in administrative claims data remains largely uninvestigated. METHODS: We conducted a retrospective cohort analysis using OptumLabs® Data Warehouse, which includes de-identified medical (inpatient and outpatient) claims and laboratory test results. Among males and females aged 15-39 years during 2003-2017, we identified chlamydia and gonorrhea test results and corresponding diagnosis codes. Using test results as the gold standard, we calculated the sensitivity and specificity of chlamydia and gonorrhea diagnosis codes to identify laboratory confirmed infections. RESULTS: We identified 9.7 million chlamydia and gonorrhea test results among 3.1 million enrollees. Of the 176,241 positive chlamydia test results, only 11,515 had a corresponding diagnosis code, for a sensitivity of 6.5 (95% confidence interval [CI]: 6.4-6.7) and a specificity of 99.5 (95% CI: 99.5-99.5). Corresponding diagnosis codes were identified for 8,056 of the 31,766 positive gonorrhea test results for a sensitivity of 25.4 (95% CI: 24.9-25.8) and a specificity of 99.7 (95% CI: 99.7-99.7). CONCLUSIONS: Our findings indicate that using only ICD-CM diagnosis codes to identify chlamydial and gonococcal infections substantially underestimates the burden of these diseases and inaccurately classifies laboratory confirmed infections. |
Incidence and prevalence of Trichomonas vaginalis infection among persons aged 15-59: United States, 2018
Lewis FMT , Spicknall IH , Flagg EW , Papp JR , Kreisel KM . Sex Transm Dis 2021 48 (4) 232-237 BACKGROUND: Trichomonas vaginalis (TV) is a sexually transmitted parasite associated with multiple adverse outcomes in women. Estimating TV incidence is challenging due to its largely asymptomatic presentation. METHODS: Per capita prevalence was estimated using the National Health and Nutrition Examination Survey, 2013-2018. Incidence was estimated using ordinary differential equations assuming static incidence at steady state and fit using Bayesian techniques. Model inputs included estimates of: proportion of asymptomatic cases, natural clearance, and time to symptomatic treatment seeking. Posterior distributions were drawn, and uncertainty reported, from 25th (Q1) to 75th (Q3) percentiles. Aggregated measures were estimated by combining component distributions. RESULTS: Among 15-59 year-olds in 2018, the number of prevalent TV infections was 2.5 (Q1=2.4, Q3=2.7) million overall, 435,000 (Q1=382,000, Q3=492,000) among men, and 2.1 (Q1=2.0, Q3=2.2) million among women; the number of incident infections was 7.4 (Q1=6.6, Q3=8.3) million, 4.1 (Q1=3.5, Q3=4.9) million, and 3.2 (Q1=2.7, Q3=3.7) million among all persons, men, and women, respectively. Persons aged 15-24 years comprised 15.7% and 17.6% of all prevalent and incident infections, respectively; prevalence and incidence in both sexes increased with age. Incidence in both sexes were highly dependent upon estimates of natural clearance, which were based on little data. CONCLUSIONS: Prevalence and incidence of TV are substantial in the United States, particularly among those aged ≥25 years. Though estimated prevalence is higher in women, estimated incidence is higher in men. Data on key parameters of TV infection are limited; future research should focus on clarifying the natural history of TV. |
Estimates of the Prevalence and Incidence of Genital Herpes, United States, 2018.
Spicknall IH , Flagg EW , Torrone EA . Sex Transm Dis 2021 48 (4) 260-265 BACKGROUND: Although there are more recent estimate of genital herpes prevalence, incidence estimates in the United States (US) have not been updated since 2008. METHODS: We estimated genital herpes prevalence and incidence for 2018 among adults aged 18-49 years. We estimated prevalence using 2015-2018 NHANES herpes simplex virus (HSV) type 2 (HSV-2) seroprevalence data among the non-institutionalized civilian population and extrapolated this prevalence to the full US population using 2018 American Community Survey data. We estimated incidence using 2011-2018 NHANES HSV-2 data as inputs to a simple mathematical model. We used Monte Carlo simulation to generate 10,000 input parameter sets for age and sex subpopulations and summarized our estimates by their median; uncertainty intervals for these estimates are characterized by their first (Q1) and third (Q3) quartiles. We conducted sensitivity analyses investigating the impact of HSV type 1 (HSV-1) infection on estimates of genital herpes burden. RESULTS: In 2018, there were an estimated 18.6 (Q1=18.1, Q3=19.0) million prevalent and 572,000 (Q1=479,000, Q3=673,000) incident genital herpes infections among 18-49-year-olds. Women accounted for two-thirds of prevalent infections with an estimated 12.1 (Q1=11.9, Q3=12.5) million infections. Incidence was highest among 18-24-year-olds with an estimated 242,000 (Q1=210,000, Q3= 274,000) infections. Sensitivity analyses indicated that HSV-1 could be responsible for millions more prevalent genital herpes infections, and tens of thousands of additional incident genital herpes infections, depending on the percentage of HSV-1 infections that are genital. DISCUSSION: Genital herpes is a common sexually transmitted disease in the United States. Future research to understand the burden of genital infections attributable to HSV-1 would refine estimates of genital herpes burden. |
Can machine learning help identify patients at risk for recurrent sexually transmitted infections
Elder HR , Gruber S , Willis SJ , Cocoros N , Callahan M , Flagg EW , Klompas M , Hsu KK . Sex Transm Dis 2020 48 (1) 56-62 BACKGROUND: A substantial fraction of sexually transmitted infections (STIs) occur in patients who have previously been treated for an STI. We assessed whether routine electronic health record (EHR) data can predict which patients presenting with an incident STI are at greatest risk for additional STIs in the next 1-2 years. METHODS: We used structured EHR data on patients aged ≥15 years who acquired an incident STI diagnosis during 2008-2015 in eastern Massachusetts. We applied machine learning algorithms to model risk of acquiring ≥1 or ≥2 additional STIs diagnoses within 365 or 730 days following the initial diagnosis using over 180 different EHR variables. We performed sensitivity analysis incorporating state health department surveillance data to assess whether improving the accuracy of identifying STI cases improved algorithm performance. RESULTS: We identified 8,723 incident episodes of laboratory-confirmed gonorrhea, chlamydia, or syphilis. Bayesian Additive Regression Trees, the best performing algorithm of any single method, had a cross-validated area under the receiver operating curve (cv-AUC) of 0.75. Receiver-operator curves for this algorithm showed a poor balance between sensitivity and positive predictive value (PPV). A predictive probability threshold with a sensitivity of 91.5% had a corresponding PPV of 3.9%. A higher threshold with PPV of 29.5% had sensitivity of 11.7%. Attempting to improve classification of patients with and without repeat STIs diagnoses by incorporating health department surveillance data had minimal impact on cv-AUC. CONCLUSIONS: Machine algorithms using structured EHR data did not differentiate well between patients with and without repeat STIs diagnosis. Alternative strategies, able to account for socio-behavioral characteristics, could be explored. |
More screening or more disease Gonorrhea testing and positivity patterns among men in three large clinical practices in Massachusetts, 2010-2017
Willis SJ , Elder H , Cocoros N , Young J , Marcus JL , Eberhardt K , Callahan M , Herrick B , Weiss M , Hafer E , Erani D , Josephson M , Llata E , Flagg EW , Hsu KK , Klompas M . Clin Infect Dis 2020 71 (9) e399-e405 BACKGROUND: Gonorrhea diagnosis rates in the U.S. increased by 75% during 2009-2017, predominantly in men. It is unclear whether the increase among men is being driven by more screening, an increase in the prevalence of disease, or both. We sought to evaluate changes in gonorrhea testing patterns and positivity among men in Massachusetts. METHODS: The analysis included men >/=15 years who received care during 2010-2017 in three clinical practice groups. We calculated annual percentages of men who received a gonorrhea test and men with at least one positive result, among men tested. Log-binomial regression models were used to examine trends in these outcomes. We adjusted for clinical and demographic characteristics that may influence predilection to test and probability of gonorrhea disease. RESULTS: On average 306,348 men had encounters each year. There was a significant increase in men with at least one gonorrhea test from 2010 (3.1%) to 2017 (6.4%; adjusted annual RR: 1.12, 95% CI 1.12,1.13). There was a significant, albeit lesser, increase in the percentage of tested men with at least one positive result (1.0% in 2010 to 1.5% in 2017; adjusted annual RR: 1.07, 95% CI 1.04,1.09). CONCLUSIONS: We estimated significant increases in the proportion of men tested at least once in a year for gonorrhea and the proportion of tested men with at least one positive gonorrhea result between 2010 and 2017. These results suggest that observed increases in gonorrhea rates could be explained by both increases in screening and the prevalence of gonorrhea. |
Prevalence of Trichomonas vaginalis among civilian, noninstitutionalized male and female population aged 14 to 59 years: United States, 2013 to 2016
Flagg EW , Meites E , Phillips C , Papp J , Torrone EA . Sex Transm Dis 2019 46 (10) e93-e96 Among the US civilian noninstitutionalized population aged 14 to 59 years in 2013 to 2016, prevalence of Trichomonas vaginalis infection in urine was 1.3% overall. Prevalence was 2.1% among females, 0.5% among males, and highest at 9.6% among non-Hispanic black females. Estimate instability limited analysis of factors beyond sex, age, and race/Hispanic ethnicity. |
Trends in the prevalence of anogenital warts among patients at sexually transmitted disease clinics - Sexually Transmitted Disease Surveillance Network, United States, 2010-2016
Mann LM , Llata E , Flagg EW , Hong J , Asbel L , Carlos-Henderson J , Kerani RP , Kohn R , Pathela P , Schumacher C , Torrone EA . J Infect Dis 2019 219 (9) 1389-1397 BACKGROUND: Approximately 90% of genital warts are caused by human papillomavirus (HPV) types 6 and 11. In the United States, HPV vaccination has been recommended for girls and women aged </=26 years, and since 2011, for boys and men aged </=21 years and for gay, bisexual, and other men who have sex with men (MSM) aged </=26 years. METHODS: Data were obtained from 27 clinics participating in the STD Surveillance Network. Trends in the annual prevalence of anogenital warts (AGW) from 2010-2016 were described by sex and by the sex of sex partners. RESULTS: During 2010-2016, significant declines in the prevalence of AGW were observed in women aged <40 years, men who have sex with women only (MSW) aged <40 years, and MSM of all age categories. An inflection in trend in 2012 was noted for MSW aged 20-24 or 25-29 years and for MSM aged 20-24 years. CONCLUSIONS: The observed declines in the prevalence of AGW suggest that HPV morbidity is declining among populations attending STD clinics, including MSW, MSM, and women. Declines in younger age groups are consistent with what would be expected following the implementation of HPV vaccination. However, declines were also observed in older age groups and are not likely to be the result of vaccination. |
Temporal patterns in chlamydia repeat testing in Massachusetts
Dee EC , Hsu KK , Kruskal BA , Menchaca JT , Zambarano B , Cocoros N , Herrick B , Weiss MDP , Hafer E , Erani D , Josephson M , Young J , Torrone EA , Flagg EW , Klompas M . Am J Prev Med 2019 56 (3) 458-463 Introduction: National guidelines recommend test-of-cure for pregnant women and test-of-reinfection for all patients with chlamydia infections in order to interrupt transmission and prevent adverse sequelae for patients, partners, and newborns. Little is known about retesting and positivity rates, and whether they are changing over time, particularly in private sector practices. Methods: Electronic health record data on patients with chlamydia tests were extracted from three independent clinical practice groups serving ≅20% of the Massachusetts population. Records were extracted using the Electronic medical record Support for Public Health platform (esphealth.org). These data were analyzed for temporal trends in annual repeat testing rates by using generalized estimating equations after index positive chlamydia tests between 2010 and 2015 and for differences in intervals to first repeat tests among pregnant females, non-pregnant females, and males. Data extraction and analysis were performed during calendar years 2017 and 2018. Results: An index positive C. trachomatis result was identified for 972 pregnant female cases, 10,309 non-pregnant female cases, and 4,973 male cases. Test-of-cure 3–5 weeks after an index positive test occurred in 37% of pregnant females. Test-of-reinfection 8–16 weeks after an index positive test occurred in 39% of pregnant females, 18% of non-pregnant females, and 9% of males. There were no significant increases in test-of-cure or test-of-reinfection rates from 2010 to 2015. Among cases with repeat tests, 16% of pregnant females, 15% of non-pregnant females, and 16% of males had positive results. Conclusions: Chlamydia test-of-cure and test-of-reinfection rates are low, with no evidence of improvement over time. There are substantial opportunities to improve adherence to chlamydia repeat testing recommendations. |
Incidence and characteristics of neonatal herpes: Comparison of two population-based data sources, New York City, 2006-2015
Lao S , Flagg EW , Schillinger JA . Sex Transm Dis 2019 46 (2) 125-131 BACKGROUND: Neonatal herpes (nHSV) is a potentially fatal disease caused by herpes simplex virus (HSV) infection during the neonatal period. Neonatal herpes simplex virus infections are not nationally notifiable, and varying incidence rates have been reported. Beginning in 2006, New York City (NYC) required reporting of nHSV infections and conducted case investigations. We compared the use of administrative hospital data with active surveillance to monitor trends in nHSV infection. METHODS: We compared the incidence and characteristics of nHSV cases as measured using population-based surveillance and administrative hospital discharge data collected between 2006 and 2015. Surveillance cases were defined as laboratory-confirmed HSV infections in NYC-resident infants aged 60 days or younger at diagnosis. Administrative cases were defined as NYC-resident infants aged 60 days or younger at hospital admission whose records included an HSV diagnosis. Neonatal herpes cases after ritual Jewish circumcision with direct orogenital suction were excluded. RESULTS: There were 107 surveillance cases (9.9 per 100,000 live births) and 131 administrative cases (12.1 per 100,000 live births). Incidence was highest in infants born to non-Hispanic black mothers aged 20 years or younger (surveillance, 57.2 per 100,000 live births; administrative data, 31.2 per 100,000 live births). The distribution of cases by year did not significantly differ across data sources. Surveillance cases had a higher case-fatality rate (18.7%) compared with administrative cases (8.4%; P = 0.019). CONCLUSIONS: Administrative hospital data can be used to measure the incidence of nHSV infection and describe disease burden across population subgroups in jurisdictions where nHSV reporting is not required. However, administrative data may underascertain nHSV case fatality. |
Men Who Have Sex With Men-Identification Criteria and Characteristics From the National Health and Nutrition Examination Survey, 1999 to 2014
Esie P , Kang J , Flagg EW , Hong J , Chen T , Bernstein K . Sex Transm Dis 2018 45 (5) 337-342 OBJECTIVES: This study aimed to provide identification criteria for men who have sex with men (MSM), estimate the prevalence of MSM behavior, and compare sociodemographics and sexually transmitted disease risk behaviors between non-MSM and MSM groups using data from a nationally representative, population-based survey. METHODS: Using data from men aged 18 to 59 years who took part in the National Health and Nutrition Examination Survey (NHANES), 1999 to 2014, detailed criteria were developed to estimate MSM behavior-at least one lifetime same-sex partner (MSM-ever), at least one same-sex partner in the past 12 months (MSM-current), and at least one lifetime and zero same-sex partners in the past 12 months (MSM-past). RESULTS: The estimated prevalence of MSM-ever was 5.5%-of these, 52.4% were MSM-current and 47.1% were MSM-past. Furthermore, MSM-ever are a nonhomogenous subpopulation, for example, 70.4% of MSM-current identified as homosexual and 71.2% of MSM-past identified as heterosexual (P < 0.001). CONCLUSIONS: The prevalence of MSM behavior identified here is similar to other published estimates. This is also the first article, to our knowledge, to use National Health and Nutrition Examination Survey data to compare MSM by 2 recall periods (recent vs. lifetime) of last same-sex sexual behavior. |
Assessment of trends in cervical cancer screening rates using healthcare claims data: United States, 2003-2014
Watson M , Benard V , Flagg EW . Prev Med Rep 2018 9 124-130 Improved understanding of the natural history of cervical cancer has led to changes in screening recommendations, including the addition of the human papillomavirus (HPV) testing as an option in routine screening. Most studies of screening trends have used national self-reported survey data. To better understand recent trends in cervical cancer screening, including cytology (Papanicolaou, or Pap, tests) and human papillomavirus co-tests (HPV+Pap test), we used healthcare claims data to examine screening practices and trends. We analyzed screening among commercially-insured females ages 18-65 during 2005-2014 who were continuously enrolled during three or more contiguous calendar years, to identify those who received cervical cancer screening with a Pap test or co-test. We examined screening prevalence by age group and year. During the latter years of our study period, screening prevalence (regardless of screening method) declined significantly for women in all age groups examined. Despite declines in overall screening, the prevalence of co-testing increased in all age groups except those aged 18-20. In 2014, women aged 30-39 had the highest overall screening uptake (77.5%) and the highest use of co-testing (44.4%); this group also had the lowest overall declines in screening over the time period (-4.5%). These screening measures from healthcare claims were lower than self-reported screening from national surveys of the general population. More research to explore the reasons for these differences is needed to ensure that women are receiving appropriate screening, and to better understand why screening prevalence is declining among this population of commercially insured women. |
Declines in anogenital warts among age groups most likely to be impacted by human papillomavirus vaccination, United States, 2006-2014
Flagg EW , Torrone EA . Am J Public Health 2017 108 (1) e1-e8 OBJECTIVES: To detect decreases in anogenital warts (AGW) among sex and age groups likely to be affected by human papillomavirus vaccination. METHODS: We estimated annual AGW prevalence during 2006 to 2014 using health care claims among US private health insurance enrollees aged 15 to 39 years. We derived AGW diagnoses using 1 of the following: (1) condylomata acuminata diagnosis, (2) viral wart diagnosis combined with a benign anogenital neoplasm diagnosis or destruction or excision of an anogenital lesion, or (3) AGW medication combined with a benign anogenital neoplasm diagnosis or destruction or excision of an anogenital lesion. RESULTS: Prevalence decreased during 2008 to 2014 among females aged 15 to 19 years (annual percentage change [APC] = -14.1%; P < .001) and during 2009 to 2014 among women aged 20 to 24 years (APC = -12.9%; P < .001) and among women aged 25 to 29 years (APC = -6.0%; P = .001). We observed significant declines among men aged 20 to 24 years (APC = -6.5%; P = .005). Prevalence increased or was stable in all other sex and age groups. CONCLUSIONS: We observed AGW decreases among females in the age groups most likely to be affected by human papillomavirus vaccination and decreases in men aged 20 to 24 years. Decreased prevalence in young men is likely attributable to herd protection from vaccination among females. (Am J Public Health. Published online ahead of print November 21, 2017: e1-e8. doi:10.2105/AJPH.2017.304119). |
Trends in pelvic inflammatory disease emergency department visits, United States, 2006-2013
Kreisel K , Flagg EW , Torrone E . Am J Obstet Gynecol 2017 218 (1) 117 e1-117 e10 BACKGROUND: Pelvic inflammatory disease is a female genital tract disorder with severe reproductive sequelae. Due to difficulties in diagnosing pelvic inflammatory disease, it is not a reportable condition in many states. Females seeking care in emergency departments are a sentinel population for pelvic inflammatory disease surveillance. OBJECTIVE: To determine trends in diagnoses of acute pelvic inflammatory disease in a nationally representative sample of emergency departments. STUDY DESIGN: All emergency department visits among females aged 15-44 years with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code indicating pelvic inflammatory disease during 2006-2013 were assessed from the HealthCare Utilization Project Nationwide Emergency Department Sample. Total and annual percent changes in the proportion of pelvic inflammatory disease emergency department visits were estimated using trend analyses. RESULTS: While the number of emergency department visits among females aged 15-44 years during 2006-2013 increased (6.5 to 7.4 million), the percent of visits due to pelvic inflammatory disease decreased from 0.57% in 2006 to 0.41% in 2013 (total percent change: -28.1%; annual percent change: -4.3%; 95% CI: -5.7%, -2.9%). The largest decreases were among those aged 15-19 years (total percent change: -40.6%; annual percent change: -6.6%; 95% CI: -8.6%, -4.4%) and living in the South (total percent change: -38.0%; annual percent change: -6.2%; 95% CI: -7.8%, -4.6%). Females aged 15-19 years who lived in the South had a 47.9% decrease in visits due to pelvic inflammatory disease (APC: -8.4%, 95% CI: -10.4, -6.5). Patients living in zip codes with the lowest median income (<$38,000) had the highest percent of visits with a pelvic inflammatory disease diagnosis; the smallest declines over time were in patients living in zip codes with the highest median income (i.e., >$64,000, total percent change: -24.4%; annual percent change: -3.8%; 95% CI: -5.2%, -2.4%). The percent of emergency department visits due to pelvic inflammatory disease was highest among patients not charged for their visit, self-paying, or those covered by Medicaid, with total percent changes in these three groups of -27.8%, -30.7%, and -35.1%, respectively. Patients with Medicaid coverage had the largest decrease in visits with a diagnosis of pelvic inflammatory disease (total percent change: -35.1%; annual percent change: -5.8%; 95% CI: -7.2%, -4.3%). CONCLUSIONS: Nationally representative data indicate the percent of emergency department visits with a pelvic inflammatory disease diagnosis decreased during 2006-2013 among females aged 15-44 years, primarily driven by decreased diagnoses of pelvic inflammatory disease among females aged 15-19 years and among women living in the Southern United States. Despite declines, a large number of females of reproductive age are receiving care for pelvic inflammatory disease in emergency departments. Patients with lower median income and no or public health insurance status, which may decrease access to and use of healthcare services, consistently had the highest percent of emergency department visits due to pelvic inflammatory disease. Future research should focus on obtaining a better understanding of factors influencing trends in pelvic inflammatory disease diagnoses and ways to address the challenges surrounding surveillance for this condition. |
Surveillance of high-grade cervical cancer precursors (CIN III/AIS) in four population-based cancer registries, United States, 2009-2012
Watson M , Soman A , Flagg EW , Unger E , Deapen D , Chen VW , Peres LC , Copeland G , Tucker TC , Garnett E , Saraiya M . Prev Med 2017 103 60-65 Surveillance of cervical intraepithelial neoplasia grade III (CIN III) and adenocarcinoma in situ (AIS) is important for determining the burden of a preventable disease, identifying effects of vaccination on future diagnoses, and developing targeted programs. We analyzed population-based rates of high-grade cervical cancer precursor lesions using data from four central cancer registries (diagnosis years 2009-2012 from Louisiana, Kentucky, Michigan, and diagnosis years 2011-2012 from Los Angeles) by age, race, and histology. We also compared rates of precursors to invasive cancers. With 4 complete years of data from Michigan, we were able to conduct a trend analysis for that state. Data analysis was conducted in Atlanta during 2016. Kentucky reported the highest rate of CIN III/AIS (69.8), followed by Michigan (55.4), Louisiana (42.3), and Los Angeles (19.2). CIN III/AIS rates declined among women in Michigan by 37% each year for women aged 15-19, 14% for those aged 20-24, and 7% for those aged 25-29. Rates of CIN III/AIS vary by registry, and were higher than invasive cancer. In Michigan, declines in CIN III/AIS among women aged 15-29 are likely related in part to updated screening recommendations, and to the impact of human papillomavirus vaccination. |
Ecological association of human papillomavirus vaccination with cervical dysplasia prevalence in the United States, 2007-2014
Flagg EW , Torrone EA , Weinstock H . Am J Public Health 2016 106 (12) e1-e8 OBJECTIVES: To examine prevalence of low- and high-grade cervical lesions over time in a large cohort of US female adolescents and women. METHODS: We used health care claims data from 9 million privately insured female patients aged 15 to 39 years to estimate annual prevalence of cytologically detected cervical low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and high-grade histologically detected cervical intraepithelial neoplasia grades 2 and 3 (CIN2+) during 2007 through 2014. We restricted analyses to those who received cervical cancer screening in a given calendar year. RESULTS: Prevalence of HSIL and CIN2+ decreased significantly for those aged 15 to 19 years. Average annual percent change in prevalence in this group during 2007 through 2014 for HSIL and CIN2+ was -8.3% and -14.4%, respectively (P < .001 for both estimates). Prevalence of HSIL and CIN2+ also decreased significantly for women aged 20 to 24 years. No decreases were seen in women aged 30 to 39 years. CONCLUSIONS: Decreases in high-grade lesions reflected their greater association with human papillomavirus types 16 and 18, compared with low-grade lesions, providing ecological evidence of population effectiveness of human papillomavirus vaccination among young, privately insured women. |
Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis
Drolet M , Benard E , Boily MC , Ali H , Baandrup L , Bauer H , Beddows S , Brisson J , Brotherton JM , Cummings T , Donovan B , Fairley CK , Flagg EW , Johnson AM , Kahn JA , Kavanagh K , Kjaer SK , Kliewer EV , Lemieux-Mellouki P , Markowitz L , Mboup A , Mesher D , Niccolai L , Oliphant J , Pollock KG , Soldan K , Sonnenberg P , Tabrizi SN , Tanton C , Brisson M . Lancet Infect Dis 2015 15 (5) 565-80 BACKGROUND: Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations. METHODS: We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I2 and chi2 statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure. FINDINGS: We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0.32, 95% CI 0.19-0.52) and anogenital warts decreased significantly by 61% (0.39, 0.22-0.71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0.72, 95% CI 0.54-0.96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0.66 [95% CI 0.47-0.91]) and in women 20-39 years of age (0.68 [95% CI 0.51-0.89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0.50, 95% CI 0.34-0.74]) and in anogenital warts (0.86 [95% CI 0.79-0.94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects. INTERPRETATION: Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement. FUNDING: The Canadian Institutes of Health Research. |
Bacterial sexually transmitted infections among HIV-infected patients in the United States: estimates from the Medical Monitoring Project
Flagg EW , Weinstock HS , Frazier EL , Valverde EE , Heffelfinger JD , Skarbinski J . Sex Transm Dis 2015 42 (4) 171-9 BACKGROUND: Bacterial sexually transmitted infections may facilitate HIV transmission. Bacterial sexually transmitted infection testing is recommended for sexually active HIV-infected patients annually and more frequently for those at elevated sexual risk. We estimated percentages of HIV-infected patients in the United States receiving at least one syphilis, gonorrhea, or chlamydia test, and repeat (≥2 tests, ≥3 months apart) tests for any of these sexually transmitted infections from mid-2008 through mid-2010. DESIGN: The Medical Monitoring Project collects behavioral and clinical characteristics of HIV-infected adults receiving medical care in the United States using nationally representative sampling. METHODS: Sexual activity included self-reported oral, vaginal, or anal sex in the past 12 months. Participants reporting more than 1 sexual partner or illicit drug use before/during sex in the past year were classified as having elevated sexual risk. Among participants with only 1 sex partner and no drug use before/during sex, those reporting consistent condom use were classified as low risk; those reporting sex without a condom (or for whom this was unknown) were classified as at elevated sexual risk only if they considered their sex partner to be a casual partner, or if their partner was HIV-negative or partner HIV status was unknown. Bacterial sexually transmitted infection testing was ascertained through medical record abstraction. RESULTS: Among sexually active patients, 55% were tested at least once in 12 months for syphilis, whereas 23% and 24% received at least one gonorrhea and chlamydia test, respectively. Syphilis testing did not vary by sex/sexual orientation. Receipt of at least 3 CD4+ T-lymphocyte cell counts and/or HIV viral load tests in 12 months was associated with syphilis testing in men who have sex with men (MSM), men who have sex with women only, and women. Chlamydia testing was significantly higher in sexually active women (30%) compared with men who have sex with women only (19%), but not compared with MSM (22%). Forty-six percent of MSM were at elevated sexual risk; 26% of these MSM received repeat syphilis testing, whereas repeat testing for gonorrhea and chlamydia was only 7% for each infection. CONCLUSIONS: Bacterial sexually transmitted infection testing among sexually active HIV-infected patients was low, particularly for those at elevated sexual risk. Patient encounters in which CD4+ T-lymphocyte cell counts and/or HIV viral load testing occurs present opportunities for increased bacterial sexually transmitted infection testing. |
Monitoring the impact of human papillomavirus vaccines on high-grade pre-invasive cervical lesions: designing a framework of linked immunization information system and cancer registry data in Michigan
Potter RC , Flagg EW , Datta SD , Saraiya M , Copeland G . Vaccine 2015 33 (11) 1400-5 State immunization and cancer registries contain data that, if linked, could be used to monitor the impact of human papillomavirus (HPV) vaccine on cervical cancer and precancer. Michigan is uniquely positioned to examine these outcomes using two population-based resources: the state-wide cancer registry and immunization information system (IIS). We assessed the feasibility of identifying females in the IIS who had continuous Michigan residence and linking them to the cancer registry. We considered continuous residence necessary for future studies of vaccine impact to avoid misclassifying those who may have been immunized while residing out-of-state and whose immunization therefore may not have been reported in Michigan. We identified females with 1976-1996 birthdates in the IIS and used probabilistic linkage software to match them with Michigan birth records. A stratified random sample of IIS-birth matches was provided to a commercial locator service to identify females with continuous Michigan residence. Cervical carcinoma in situ cases diagnosed in 2006 among females aged 10 through 30 years were also matched with the birth records; cancer registry-birth matches were merged with the IIS-birth matches using the birth record identifier. Overall, 68% of the 1274,282 IIS and 61% of the 1358 cancer registry records could be matched with birth records. Among the sample of IIS-birth matches, most (86%) were continuous residents. Seventy percent or more of cancer registry-birth matches merged with IIS-birth matches for cases born after 1984. This is the first effort in the U.S. to show that linking records across IIS and cancer registries is practical and reasonably efficient. The increasing proportion of matches between the registries and live birth file with birth year, and the use of population-based data, strengthen the utility of this approach. Future steps include use of this method to examine incidence of cervical cancer precursors in HPV immunization-eligible females. |
Hospitalization cost per case of neonatal herpes simplex virus infection from claims data
Owusu-Edusei K Jr , Flagg EW , Gift TL . J Pediatr Nurs 2014 30 (2) 346-52 The purpose of this study was to estimate the average excess inpatient cost of neonatal herpes simplex virus (NHSV) infection from 2005 to 2009 insurance claims data. The estimated adjusted average excess inpatient cost for neonate admissions with HSV diagnosis and >7days of hospitalization was $40,044 [95% confidence interval (CI), $33,529-$47,775]. When disaggregated by the days of admission, cost estimates were: 8-13days, $23,918 [CI, $19,490-$29,282]; 14-21days, $44,358 [CI, $34,654-$56,673]; >21days, $68,916 [CI, $49,905-$94,967]). Although these estimates are not representative of the entire US, they can inform future economic evaluation studies on NHSV interventions. |
Population-based surveillance for cervical cancer precursors in three central cancer registries, United States 2009
Flagg EW , Datta SD , Saraiya M , Unger ER , Peters E , Cole L , Chen VW , Tucker T , Byrne MJ , Copeland G , Silva W , Watson M , Weinstock H . Cancer Causes Control 2014 25 (5) 571-81 PURPOSE: The USA has a well-established network of central cancer registries (CCRs) that collect data using standardized definitions and protocols to provide population-based estimates of cancer incidence. The addition of cervical cancer precursors in select CCR operations would facilitate future studies measuring the population-level impact of human papillomavirus (HPV) vaccine. To assess the feasibility of collecting data on cervical cancer precursors, we conducted a multi-site surveillance study in three state-wide CCRs, to obtain annual case counts and compare rates of precursor lesions to those for invasive cervical cancer. METHODS: We developed standardized methods for case identification, data collection and transmission, training and quality assurance, while allowing for registry-specific strategies to accomplish surveillance objectives. We then conducted population-based surveillance for precancerous cervical lesions in three states using the protocols. RESULTS: We identified 5,718 cases of cervical cancer precursors during 2009. Age-adjusted incidence of cervical cancer precursors was 77 (Kentucky), 60 (Michigan), and 54 (Louisiana) per 100,000 women. Highest rates were observed in those aged 20-29 years: 274 (Kentucky), 202 (Michigan), and 196 (Louisiana) per 100,000. The variable with the most missing data was race/ethnicity, which was missing for 13 % of cases in Kentucky, 18 % in Michigan, and 1 % in Louisiana. Overall rates of cervical cancer precursors were over sixfold higher than invasive cervical cancer rates [rate ratios: 8.6 (Kentucky), 8.3 (Michigan), and 6.2 (Louisiana)]. CONCLUSIONS: Incorporating surveillance of cervical cancer precursors using existing CCR infrastructure is feasible and results in collection of population-based incidence data. Standardized collection of these data in high-quality registry systems will be useful in future activities monitoring the impact of HPV vaccination across states. As a result of this study, ongoing surveillance of these lesions has now been conducted in four CCRs since 2010. |
Would young women attending sexually transmitted disease clinics benefit from human papillomavirus vaccination? An assessment of human papillomavirus DNA and seropositivity from human papillomavirus sentinel surveillance, 2003-2005
Dunne EF , Flagg EW , Unger ER , Hsu K , Ghanen K , Kerndt P , Shlay JC , Koutsky LA , Datta DS , Panicker G , Zaidi A , Weinstock H , Markowitz LE . Sex Transm Dis 2014 41 (1) 46-9 BACKGROUND: There are limited data on the proportion who have been exposed to vaccine-type human papillomavirus (HPV) among women attending sexually transmitted disease (STD) clinics; this information could inform the potential benefits of HPV vaccination for women attending this venue. METHODS: Human papillomavirus surveillance was conducted in STD clinics in Baltimore, MD; Boston, MA; Denver, CO; Los Angeles, CA; and Seattle, WA, among women receiving cervical cancer screening from January 2003 to December 2005. The women had specimens collected for cervical cytology HPV testing by L1 consensus polymerase chain reaction testing and serologic assessment for HPV 6, 11, 16, and 18 using the competitive Luminex immunoassay. Results from 880 women with adequate specimens were included. Women were HPV naive if they were both HPV DNA negative and seronegative for a specific HPV type. RESULTS: One hundred seventy women (19.3%) had HPV 16, 18, 6, or 11 DNA, and 418 (47.5%) were HPV 16, 18, 6, or 11 seropositive. Four hundred ten (46.6%) women were naive to all 4 types, 570 (64.8%) were naive to both HPV 16 and 18, and 545 (61.9%) were naive to both HPV 6 and 11. Almost all (99.3%) women were naive to at least 1 vaccine HPV type. CONCLUSIONS: Almost half of young women age eligible for HPV vaccine and attending STD clinics were naive to all 4 HPV types, and more than half were naive to both HPV 16 and 18. This assessment suggests that most young women attending this venue might benefit from HPV vaccination. |
Prevalence of anogenital warts among participants in private health plans in the United States, 2003-2010: potential impact of human papillomavirus vaccination
Flagg EW , Schwartz R , Weinstock H . Am J Public Health 2013 103 (8) 1428-35 OBJECTIVES: We estimated anogenital wart prevalence from 2003 to 2010 by gender and age group in a large US cohort with private insurance to detect potential decreases among people most likely to be affected by human papillomavirus (HPV) vaccination. METHODS: We restricted health care claims to those from individuals aged 10 to 39 years with continuous insurance within a given year. We derived anogenital wart diagnoses from a diagnosis of condyloma acuminata, or either a less specific viral wart diagnosis or genital wart medication combined with either a benign anogenital neoplasm or destruction or excision of a noncervical anogenital lesion. RESULTS: Prevalence increased slightly in 2003 to 2006, then significantly declined in 2007 to 2010 among girls aged 15 to 19 years; increased in 2003 to 2007, remained level through 2009, and declined in 2010 among women aged 20 to 24 years; and increased through 2009 but not in 2010 for women aged 25 to 39 years. For males aged 15 to 39 years, prevalence for each 5-year age group increased in 2003 to 2009, but no increases were observed for 2010. CONCLUSIONS: These data indicate reductions in anogenital warts among US females aged 15 to 24 years, the age group most likely to be affected by introduction of the HPV vaccine. (Am J Public Health. Published online ahead of print June 13, 2013: e1-e8. doi:10.2105/AJPH.2012.301182). |
Modeling the impact of quadrivalent HPV vaccination on the incidence of Pap test abnormalities in the United States
Chesson HW , Flagg EW , Koutsky L , Hsu K , Unger ER , Shlay JC , Kerndt P , Ghanem KG , Zenilman JM , Hagensee M , Weinstock H , Datta SD . Vaccine 2013 31 (29) 3019-24 BACKGROUND: We present data on Pap test results and HPV prevalence from the HPV Sentinel Surveillance project, a multiyear surveillance project enrolling women from a diverse set of 26 clinics throughout the US from 2003 to 2005. We use mathematical modeling to illustrate the potential timing and magnitude of decreases in Pap test abnormalities in sexually transmitted disease (STD), family planning, and primary care clinics in the US as a result of HPV vaccination. METHODS: The probability of an abnormal Pap result was based on three factors: (1) infection with HPV 16/18, or both; (2) infection with high-risk HPV types other than HPV 16/18; and (3) infection with HPV 6/11, or both. We estimated the relative reduction in the probability of an abnormal Pap result over the first 25 years of a female-only, quadrivalent HPV vaccination program, compared to a scenario of no HPV vaccination in which the probability of abnormal Pap results was assumed constant. RESULTS: The probability of an abnormal Pap result ranged from 7.0% for the lowest risk group (those without any high-risk HPV types and without HPV 6/11) to 45.2% for the highest risk group (those with HPV 16/18 and at least one other high-risk HPV type). Estimated reductions in abnormal Pap results among women in the 21- to 29-year age group were 0.8%, 10.2%, and 11.3% in years 5, 15, and 25 of the vaccine program respectively, in the lower vaccine coverage scenario, and 7.4%, 21.4%, and 22.2%, respectively, in the higher coverage scenario. CONCLUSIONS: Our results suggest that HPV vaccination will have a discernable impact on the probability of Pap abnormalities, but the timing and magnitude of the reduction will depend substantially on vaccine coverage and the degree of cross-protection against high risk HPV types other than HPV 16/18. |
Monitoring HPV type-specific prevalence over time through clinic-based surveillance: a perspective on vaccine effectiveness.
Gaffga NH , Flagg EW , Weinstock HS , Shlay JC , Ghanem KG , Koutsky LA , Kerndt PR , Hsu KK , Unger ER , Datta SD . Vaccine 2012 30 (11) 1959-64 We investigated the feasibility of monitoring trends in prevalence of vaccine-preventable human papillomavirus (HPV) types in different clinic populations. We collected cervical specimens from women presenting to family planning, primary care, and sexually transmitted disease (STD) clinics for routine pap smears in five US cities during 2003-2005. We performed HPV genotyping and calculated annual type-specific prevalences; pre-vaccine era prevalence was highest for HPV 16 (6.0; 95% confidence interval [CI] 5.5-6.6%) and annual prevalences for vaccine-preventable types were stable, with few exceptions, after controlling for clinic type, age group, and city. With sufficient sample size and stable population characteristics, clinic-based surveillance systems can contribute to monitoring HPV vaccine impact in the cervical screening population. |
Genome-wide copy number alterations in subtypes of invasive breast cancers in young white and African American women.
Loo LW , Wang Y , Flynn EM , Lund MJ , Bowles EJ , Buist DS , Liff JM , Flagg EW , Coates RJ , Eley JW , Hsu L , Porter PL . Breast Cancer Res Treat 2011 127 (1) 297-308 Genomic copy number alterations (CNA) are common in breast cancer. Identifying characteristic CNAs associated with specific breast cancer subtypes is a critical step in defining potential mechanisms of disease initiation and progression. We used genome-wide array comparative genomic hybridization to identify distinctive CNAs in breast cancer subtypes from 259 young (diagnosed with breast cancer at <55 years) African American (AA) and Caucasian American (CA) women originally enrolled in a larger population-based study. We compared the average frequency of CNAs across the whole genome for each breast tumor subtype and found that estrogen receptor (ER)-negative tumors had a higher average frequency of genome-wide gain (P < 0.0001) and loss (P = 0.02) compared to ER-positive tumors. Triple-negative (TN) tumors had a higher average frequency of genome-wide gain (P < 0.0001) and loss (P = 0.003) than non-TN tumors. No significant difference in CNA frequency was observed between HER2-positive and -negative tumors. We also identified previously unreported recurrent CNAs (frequency >40%) for TN breast tumors at 10q, 11p, 11q, 16q, 20p, and 20q. In addition, we report CNAs that differ in frequency between TN breast tumors of AA and CA women. This is of particular relevance because TN breast cancer is associated with higher mortality and young AA women have higher rates of TN breast tumors compared to CA women. These data support the possibility that higher overall frequency of genomic alteration events as well as specific focal CNAs in TN breast tumors might contribute in part to the poor breast cancer prognosis for young AA women. |
Incidence of neonatal herpes simplex virus infections in the United States, 2006
Flagg EW , Weinstock H . Pediatrics 2010 127 (1) e1-8 OBJECTIVES: Neonatal herpes simplex virus (nHSV) infections, although relatively rare, cause significant morbidity and mortality. Estimates of nHSV incidence across the United States vary widely and have been derived by using a variety of methods. We estimated the incidence of nHSV infections for the United States during 2006, as well as demographic-specific rates, by using nationally and regionally weighted estimates from a population-based sample of inpatient data. METHODS: We examined inpatient records of infants aged 60 days or younger at admission using the Healthcare Cost and Utilization Project Kids' Inpatient Database. Patients with a length of stay that exceeded 7 days (or deceased during hospitalization) were identified at discharge from the International Classification of Diseases, Ninth Revision, Clinical Modification codes for herpes simplex (054.0-054.9). Cases for which patients had been transferred from another hospital or readmitted were excluded from case counts. RESULTS: We found an overall US incidence of 9.6 per 100 000 births in 2006. Rates per 100 000 births among US regions were 8.2 in the Northeast, 12.9 in the Midwest, 8.9 in the South, and 8.8 in the West. Rates of 13.8, 9.9, and 7.5 were observed for black, white, and Hispanic newborns, respectively; these differences were not statistically significant. Rates were significantly higher among cases for which the expected primary payer was Medicaid (15.1) compared with private insurance or managed health care (5.4). Median age at admission was 10 days; 25% of admissions were on the day of birth. CONCLUSIONS: This description of regional and demographic-specific nHSV incidence rates for the United States provides important new information on the extent of this potentially devastating disease. |
The epidemiology of triple-negative breast cancer, including race
Trivers KF , Lund MJ , Porter PL , Liff JM , Flagg EW , Coates RJ , Eley JW . Cancer Causes Control 2009 20 (7) 1071-82 OBJECTIVE: Predictors of intrinsic breast cancer subtypes, including the triple-negative (TN) subtype, are largely unknown. We evaluated whether anthropometrics, demographics, and reproductive history were associated with distinct breast cancer subtypes. METHODS: Invasive breast tumors from a population-based case-control study of 476 (116 black and 360 white) Atlanta women aged 20-54, diagnosed between 1990 and 1992, were centrally reviewed and immunohistochemically analyzed for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2); then grouped [TN (ER-PR-HER2-); ER-PR-HER2+; ER/PR+HER2+; ER/PR+HER2- (case-only reference group)]. Data were from interviews and anthropometric measurements; adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression, including both case-only and case-control comparisons. RESULTS: From the case-only analyses and compared with the ER/PR+HER2- subtype, women with TN tumors were more likely to be obese than normal/underweight [OR = 1.89 (95% CI = 1.22, 2.92)]. Regardless of HER2 status, ER-PR- tumors were associated with black race, young age at first birth, having a recent birth, and being overweight. CONCLUSIONS: Distinct breast cancer subtypes have unique sociodemographic, anthropometric and reproductive characteristics and possibly different pathways for development. |
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