BACKGROUND: The Ministry of Health in Côte d'Ivoire and the International Training and Education Center for Health at the University of Washington, funded by the United States President's Emergency Plan for AIDS Relief, have been collaborating to develop and implement the Open-Source Enterprise-Level Laboratory Information System (OpenELIS). The system is designed to improve HIV-related laboratory data management and strengthen quality management and capacity at clinical laboratories across the nation. OBJECTIVE: This evaluation aimed to quantify the effects of implementing OpenELIS on data quality for laboratory tests related to HIV care and treatment. METHODS: This evaluation used a quasi-experimental design to perform an interrupted time-series analysis to estimate the changes in the level and slope of 3 data quality indicators (timeliness, completeness, and validity) after OpenELIS implementation. We collected paper and electronic records on clusters of differentiation 4 (CD4) testing for 48 weeks before OpenELIS adoption until 72 weeks after. Data collection took place at 21 laboratories in 13 health regions that started using OpenELIS between 2014 and 2020. We analyzed the data at the laboratory level. We estimated odds ratios (ORs) by comparing the observed outcomes with modeled counterfactual ones when the laboratories did not adopt OpenELIS. RESULTS: There was an immediate 5-fold increase in timeliness (OR 5.27, 95% CI 4.33-6.41; P<.001) and an immediate 3.6-fold increase in completeness (OR 3.59, 95% CI 2.40-5.37; P<.001). These immediate improvements were observed starting after OpenELIS installation and then maintained until 72 weeks after OpenELIS adoption. The weekly improvement in the postimplementation trend of completeness was significant (OR 1.03, 95% CI 1.02-1.05; P<.001). The improvement in validity was not statistically significant (OR 1.34, 95% CI 0.69-2.60; P=.38), but validity did not fall below pre-OpenELIS levels. CONCLUSIONS: These results demonstrate the value of electronic laboratory information systems in improving laboratory data quality and supporting evidence-based decision-making in health care. These findings highlight the importance of OpenELIS in Côte d'Ivoire and the potential for adoption in other low- and middle-income countries with similar health systems.

In 2021, the U.S. Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), and state and local health and regulatory partners investigated an outbreak of Salmonella enterica serovar Oranienburg infections linked to bulb onions from Mexico, resulting in 1040 illnesses and 260 hospitalizations across 39 states, the District of Columbia, and Puerto Rico. The Kansas Department of Agriculture recovered the outbreak strain of Salmonella Oranienburg from a sample of condiment collected from an ill person's home. The condiment was made with cilantro, lime, and onions, but, at the time of collection, there were no onions remaining in it. FDA conducted traceback investigations for white, yellow, and red bulb onions, cilantro, limes, tomatoes, and jalapeño peppers. Growers in the state of Chihuahua, Mexico, were identified as supplying the implicated onions that could account for exposure to onions for all illnesses included in the traceback investigation, but investigators could not determine a single source or route of contamination. FDA collected product and environmental samples across the domestic supply chain but did not recover the outbreak strain of Salmonella. Binational collaboration and information sharing supported Mexican authorities in collecting environmental samples from two packing plants and onion, water, and environmental samples from 15 farms and firms in Chihuahua, Mexico identified through FDA's traceback investigation, but did not recover the outbreak strain. Distributors of the implicated onions issued voluntary recalls of red, yellow, and white whole, fresh onions imported from the state of Chihuahua, Mexico. This outbreak showcased how investigators overcame significant traceback and epidemiologic challenges, the need for strengthening the ongoing collaboration between U.S. and Mexican authorities and highlighted the need for identifying practices across the supply chain that can help improve the safety of onions. © 2024

Attractive Targeted Sugar Baits (ATSB) have been demonstrated to result in significant reductions in malaria vector numbers in areas of scarce vegetation cover such as in Mali and Israel, but it is not clear whether such an effect can be replicated in environments where mosquitoes have a wide range of options for sugar resources. The current study evaluated the attractiveness of the predominant flowering plants of Asembo Siaya County, western Kenya in comparison to an ATSB developed by Westham Co. Sixteen of the most common flowering plants in the study area were selected and evaluated for relative attractiveness to malaria vectors in semi-field structures. Six of the most attractive flowers were compared to determine the most attractive to local Anopheles mosquitoes. The most attractive plant was then compared to different versions of ATSB. In total, 56,600 Anopheles mosquitoes were released in the semi-field structures. From these, 5150 mosquitoes (2621 males and 2529 females) of An. arabiensis, An. funestus and An. gambiae were recaptured on the attractancy traps. Mangifera indica was the most attractive sugar source for all three species while Hyptis suaveolens and Tephrosia vogelii were the least attractive plants to the mosquitoes. Overall, ATSB version 1.2 was significantly more attractive compared to both ATSB version 1.1 and Mangifera indica. Mosquitoes were differentially attracted to various natural plants in western Kenya and ATSB. The observation that ATSB v1.2 was more attractive to local Anopheles mosquitoes than the most attractive natural sugar source indicates that this product may be able to compete with natural sugar sources in western Kenya and suggests this product may have the potential to impact mosquito populations in the field.

BACKGROUND: Repeat HIV testing during pregnancy and breastfeeding identifies women with incident infections, those living with HIV who have been lost to care, and infants at risk for HIV infection. We report data from repeat testing for women in maternal and child health (MCH) services at 10 health facilities in Mozambique. METHODS: Routinely collected data from health facility registers are reported from April-November 2019. From antenatal care (ANC), we report numbers and proportions of women eligible for retesting; returned for care when retesting eligible; retested; and HIV-positive (HIV+) at retesting. From child welfare clinics (CWC), we report mothers retested; tested HIV-positive; HIV+ mothers linked to ART services; HIV-exposed infants (HEI) tested for HIV with polymerase chain reaction (PCR) tests; HEI testing PCR positive; PCR-positive infants linked to care. RESULTS: In ANC, 28,233 pregnant women tested HIV-negative at first ANC visit, 40.7% had a follow-up visit when retesting eligible, among whom 84.8% were retested and 0.3%(N = 26) tested HIV+. In CWC, 26,503 women were tested; 0.8%(N = 212) tested HIV+ and 74.1%(N = 157) of HIV+ women were linked to care. Among 157 HEI identified in CWC, 68.4%(N = 145) received PCR testing and 19.3%(N = 28) tested positive. CONCLUSION: In ANC, less than half of pregnant women eligible for retesting returned for follow-up visits, and test positivity was low among women retested in ANC and CWC. In CWC, linkage to infant testing was poor and almost 20% of HEI were PCR-positive. Implementing retesting for pregnant and breastfeeding women is challenging due to high numbers of women and low testing yield.

Introduction: Pregnant and lactating people (PLP) experience heightened risk of acquiring HIV, which adversely impacts their health and increases the risk for vertical HIV transmission. Preexposure prophylaxis (PrEP), as part of a combination prevention package, including condoms, sexually transmitted infection prevention, and regular HIV testing, is a safe, efficacious method to prevent HIV infections among PLP and their infants. This article examines the evolution of strategies and guidance on PrEP services for PLP from 18 countries supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR).

PURPOSE: Cte d'Ivoire has a tiered public health laboratory system of 9 reference laboratories, 77 laboratories at regional and general hospitals, and 100 laboratories among 1,486 district health centers. Prior to 2009, nearly all of these laboratories used paper registers and reports to collect and report laboratory data to clinicians and national disease monitoring programs. PROJECT: Since 2009 the Ministry of Health (MOH) in Cte d'Ivoire has sought to implement a comprehensive set of activities aimed at strengthening the laboratory system. One of these activities is the sustainable development, expansion, and technical support of an open-source electronic laboratory information system (OpenELIS), with the long-term goal of Ivorian technical support and managerial sustainment of the system. This project has addressed the need for a comprehensive, customizable, low- to no-cost, open-source LIS to serve the public health systems with initial attention to HIV clients and later expansion to cover the general population. This descriptive case study presents the first published summary of original work which has been ongoing since 2009 in Cte d'Ivoire to transform the laboratory information management systems and processes nationally. IMPACT: OpenELIS is now in use at 106 laboratories across Cte d'Ivoire. This article describes the iterative planning, design, and implementation process of OpenELIS in Cte d'Ivoire, and the evolving leadership, ownership, and capacity of the Ivorian MOH in sustaining the system. This original work synthesizes lessons learned from this 13-year experience towards strengthening laboratory information systems in other low resource settings.

The USA National Phenology Network (USA-NPN) hosts the largest volunteer-contributed collection of plant phenology observations in the USA. The potential contributions of these spatially and temporally explicit observations of flowers and pollen cones to the field of aerobiology remain largely unexplored. Here, we introduce this freely available dataset and demonstrate its prospective applications for modeling airborne pollen in a case study. Specifically, we compare the timing of 4265 observations of flowering for oak (Quercus) trees in the eastern USA to winter–spring temperatures. We then use this relationship to predict the day of peak flowering at 15 pollen monitoring stations in 15 years and compare the predicted day of peak flowering to the peak day of measured pollen (n = 111 station-years). There was a strong association between winter–spring temperature and the presence of open flowers (r2 = 0.66, p &lt; 0.0001) and the predicted peak flowering was strongly correlated with peak airborne pollen concentrations (r2 = 0.81, p &lt; 0.0001). These results demonstrate the potential for the USA-NPN’s phenological observations to underpin source-based models of airborne pollen. We also highlight opportunities for leveraging and enhancing this near real-time dataset for aerobiological applications. © 2022, The Author(s), under exclusive licence to Springer Nature B.V.

BACKGROUND: Long-term persistence of Ebola virus (EBOV) in immunologically-privileged sites has been implicated in recent outbreaks of Ebola Virus Disease (EVD) in Guinea and the Democratic Republic of Congo. This study was designed to understand how the acute course of EVD, convalescence, and host immune and genetic factors may play a role in prolonged viral persistence in semen. METHODS: A cohort of 131 male EVD survivors in Liberia were enrolled in a case-case study. "Early clearers" were defined as those with two consecutive negative EBOV semen tests by real-time reverse transcriptase polymerase chain reaction (rRT-PCR) at least two weeks apart within 1 year after discharge from the Ebola Treatment Unit (ETU) or acute EVD. "Late clearers" had detectable EBOV RNA by rRT-PCR over one year following ETU discharge or acute EVD. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical exams and blood work. RESULTS: Compared to early clearers, late clearers were older (median 42.5 years, p = 0.0001) and experienced fewer severe clinical symptoms (median 2, p = 0.006). Late clearers had more lens opacifications (OR 3.9, 95%CI 1.1-13.3, p = 0.03), after accounting for age, higher total serum IgG3 titers (p = 0.007) and increased expression of the HLA-C*03:04 allele (OR 0.14, 95% CI 0.02-0.70, p = 0.007). CONCLUSIONS: Older age, decreased illness severity, elevated total serum IgG3 and HLA-C*03:04 allele expression may be risk factors for the persistence of EBOV in the semen of EVD survivors. EBOV persistence in semen may also be associated with its persistence in other immunologically protected sites, such as the eye.

INTRODUCTION: Our study describes changes in HIV care service delivery and continuity of HIV antiretroviral therapy (ART) for people living with HIV (PLHIV) during the 8 weeks before and after diagnosis of the first coronavirus disease 2019 (COVID-19) cases in Haiti on March 19, 2020. METHODS: Using data from 96 out of 167 health facilities offering ART services, we compared four ART program indicators: (1) count of HIV visits; (2) proportion of ART dispenses in community-based settings (DAC); (3) proportion of multi-month dispensing of ART medications > 6 months (> 6 m MMD); and (4) proportion of timely ART refills. We used uncontrolled interrupted time series (ITS) models to estimate slope and level changes in each indicator with the arrival of COVID-19. RESULTS AND DISCUSSION: From week 1 to week 16, the average number of HIV visits fell from 121.5 to 92.5 visits, the proportion of DAC rose from 22.7% to 36.7%, the proportion of > 6 m MMD rose from 29.4% to 48.4%, and the proportion of timely ART refills fell from 51.9% to 43.8%. The ITS models estimated abrupt increases of 36% in > 6 m MMD (p < 0.001) and 37% in DAC (p < 0.001) at the time of COVID-19 arrival, and no change after arrival of COVID-19. The was an abrupt decline of 18% in timely ART refills with the arrival of COVID-19 and a decline of 1% per week thereafter, both non-statistically significant changes. CONCLUSIONS: The sudden changes in HIV service utilization represent dramatic adaptations needed to mitigate primary and secondary effects of the COVID-19 pandemic on PLHIV. This study underscores the urgency of optimizing ART delivery models in Haiti and beyond, in order to maintain progress toward HIV epidemic control.

INTRODUCTION: Voluntary medical male circumcision (VMMC), an effective HIV prevention programme for men, is implemented in East and Southern Africa. Approximately 50% of VMMC clients are aged below 15 years. More targeted interventions to reach older men and others at higher short-term HIV risk are needed. METHODS: We implemented a quality improvement project testing the effectiveness of an active referral-based VMMC recruitment approach, targeting men attending STI clinics and those escorting partners to antenatal care (ANC) clinics, at Bwaila Hospital in Lilongwe, Malawi. We compared the proportions aged older than 15 years among men who received VMMC following referral from STI and ANC clinics with those among men referred from standard community mobilisation. We also analysed referral cascades to VMMC. RESULTS: In total, 330 clients were circumcised after referral from STI (242) and ANC (88) clinics, as compared with 3839 other clients attributed to standard community mobilisation. All clients from ANC and STI clinics were aged over 15 years, as compared with 69% from standard community mobilisation. STI clinics had a higher conversion rate from counselling to VMMC than ANC (12% vs 9%) and a higher contribution to total circumcisions performed at the VMMC clinic (6% vs 2%). CONCLUSIONS: Integrating VMMC recruitment and follow-up in STI and ANC clinics co-located with VMMC services can augment demand creation and targeting of men at risk of HIV, based on age and STI history. This approach can be replicated at least in similar health facilities with ANC and STI services in close proximity to VMMC service delivery.

Terpenes are a class of volatile organic hydrocarbons commonly produced by vegetation and released into the atmosphere. These compounds are responsible for the scents of pine forests, citrus fruits, and some flowers. Human terpene exposure can come from inhalation, diet, smoking, and more recently, using e-cigarettes. Terpenes are present in tobacco smoke and are used as flavor chemicals in e-liquids. The health effects of terpenes are not widely known, though several studies have suggested that they may prove useful in future medical applications. We have developed a novel, high-throughput method of quantifying seven terpenes (α-pinene, β-pinene, β-myrcene, 3-carene, limonene, β-caryophyllene, and α-humulene) in human serum to aid human-exposure investigations. This method employs headspace sampling using solid-phase microextraction (SPME) coupled to gas chromatography-tandem mass spectrometry to detect and quantify five monoterpenes and two sesquiterpenes in the low parts-per-trillion to low parts-per-billion range. The intraday and interday variability (percent error) of the method are ≤2 and ≤11%, respectively. In addition, this method showed excellent recovery in human serum (between 80 and 120% for all analytes). The assay precision ranges between 4.0 and 11%. Limits of detection ranged between 0.032 and 0.162 μg/L. Using serum cotinine values to classify tobacco use showed that smokers have higher serum concentrations of six terpenes compared to nonusers. Terpene concentrations were 14-78% higher in smokers than nonusers. Our method can provide essential biomonitoring data to establish baseline exposure levels for terpenes in humans.

INTRODUCTION: Ebola virus (EBOV), species Zaire ebolavirus, may persist in the semen of male survivors of Ebola Virus Disease (EVD). We conducted a study of male survivors of the 2014-2016 EVD outbreak in Liberia and evaluated their immune responses to EBOV. We report here findings from the serologic testing of blood for EBOV-specific antibodies, molecular testing for EBOV in blood and semen, and serologic testing of peripheral blood mononuclear cells (PBMCs) in a subset of study participants. METHODS: We tested for EBOV RNA in blood by qRT-PCR, and for anti-EBOV-specific IgM and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) for 126 study participants. We performed peripheral blood mononuclear cell (PBMC) analysis on a subgroup of 26 IgG-negative participants. RESULTS: All 126 participants tested negative for EBOV RNA in blood by qRT-PCR. The blood of 26 participants tested negative for EBOV-specific IgG antibodies by ELISA. PBMCs were collected from 23/26 EBOV IgG-negative participants. Of these, 1/23 participants had PBMCs which produced anti-EBOV-specific IgG antibodies upon stimulation with EBOV-specific GP and NP antigens. DISCUSSION: The blood of EVD survivors, collected when they did not have symptoms meeting the case definition for acute or relapsed EVD, is unlikely to pose a risk for EBOV transmission. We identified one IgM/IgG negative participant who had PBMCs which produced anti-EBOV-specific antibodies upon stimulation. Immunogenicity following acute EBOV infection may exist along a spectrum and absence of antibody response should not be exclusionary in determining an individual's status as a survivor of EVD.

BACKGROUND: In response to reported COVID-19 outbreaks among people experiencing homelessness (PEH) in other U.S. cities, we conducted multiple, proactive, facility-wide testing events for PEH living sheltered and unsheltered and homelessness service staff in Atlanta, Georgia. We describe SARS-CoV-2 prevalence and associated symptoms and review shelter infection prevention and control (IPC) policies. METHODS: PEH and staff were tested for SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) during April 7-May 6, 2020. A subset of PEH and staff was screened for symptoms. Shelter assessments were conducted concurrently at a convenience sample of shelters using a standardized questionnaire. RESULTS: Overall, 2,875 individuals at 24 shelters and nine unsheltered outreach events underwent SARS-CoV-2 testing and 2,860 (99.5%) had conclusive test results. SARS-CoV-2 prevalence was 2.1% (36/1,684) among PEH living sheltered, 0.5% (3/628) among PEH living unsheltered, and 1.3% (7/548) among staff. Reporting fever, cough, or shortness of breath in the last week during symptom screening was 14% sensitive and 89% specific for identifying COVID-19 cases compared with RT-PCR. Prevalence by shelter ranged 0%-27.6%. Repeat testing 3-4 weeks later at four shelters documented decreased SARS-CoV-2 prevalence (0%-3.9%). Nine of 24 shelters completed shelter assessments and implemented IPC measures as part of the COVID-19 response. CONCLUSIONS: PEH living in shelters experienced higher SARS-CoV-2 prevalence compared with PEH living unsheltered. Facility-wide testing in congregate settings allowed for identification and isolation of COVID-19 cases and is an important strategy to interrupt SARS-CoV-2 transmission.

BACKGROUND: Anal cancer rates have increased, particularly in HIV-positive (HIV+) women. We assessed factors associated with anal precancer in HIV+ and at-risk HIV-negative (ARHIVN) women from the Atlanta Women's Interagency HIV Study Cohort. METHODS: All participants underwent high resolution anoscopy, anal cytology (AC) and had anal (AS) and cervical (CS) samples collected. Specimens were tested for 37 HPV types and for FAM19A4 and microRNA124-2 promoter methylation. Binary logistic regression and multivariate analysis were conducted with histologic anal high grade squamous intraepithelial lesion (A-HSIL) as the dependent variable. RESULTS: Seventy-five women enrolled: 52(69%) were HIV+ with three-fourths having undetectable viral load, 64(86%) were black, with mean age 49+/-8 years. Forty-nine (65%) AC samples were abnormal, and 38(51%) of AS were positive for at least one of 13 high-risk HPV (hrHPV) types. Thirteen (18%) anal biopsies identified A-HSIL. Hypermethylation of FAM19A4 and/or microRNA124-2 was found in 69 (95%) AS and 19(26%) CS. In multivariate analyses, the odds of having A-HSIL were over 6 times higher in women with anal hrHPV (aOR 6.08, 95% CI 1.27-29.18, p=0.02) and with positive cervical methylation (aOR 6.49, 95% CI 1.66-25.35, p=0.007), but not significantly higher in women with positive anal methylation. CONCLUSIONS: Anal hrHPV and promoter hypermethylation in the cervix show promise as biomarkers for anal cancer screening in HIV+ and ARHIVN women. Greater understanding of gene silencing by promoter hypermethylation in anal carcinogenesis is needed.

OBJECTIVES: To assess potentially missed sexually transmitted infections (STIs), we compared clinically diagnosed STIs to laboratory-confirmed diagnoses of gonorrhoea (GC), chlamydia (CT) and trichomonas (Tvag). DESIGN: Secondary analysis of a randomised controlled trial. SETTING: We used data and specimens previously collected for the Sino-Implant Study in Kingston, Jamaica. PARTICIPANTS: The Sino-Implant Study randomised 414 women to receive a levonorgestrel implant at either baseline or 3 months post-enrolment to evaluate unprotected sex after implant initiation. This analysis used 254 available vaginal swab samples. OUTCOME MEASURES: Clinically diagnosed STIs were determined from medical records by assessing clinical impressions and prescriptions. Laboratory-confirmed STIs included GC, CT and Tvag tested by Aptima Combo 2 for CT/GC and Aptima Tvag assays (Hologic, San Diego, California, USA). Log-binomial regression models fit with generalised estimating equations were used to estimate associations of clinically diagnosed STIs with laboratory-confirmed diagnoses and demographic and behavioural characteristics. RESULTS: Overall, 195 (76.8%) women had laboratory-confirmed STI (CT, GC or Tvag) while only 65 (25.6%) women had clinically diagnosed cervicitis and/or vaginitis during the study period. Clinical diagnosis missed 79.7% of laboratory-confirmed STIs: 85% of GC (n=17/20), 78.8% of CT (n=141/179) and 80.0% of Tvag (n=180/225). Hormonal contraceptive use in the month prior to the study visit was significantly associated with clinical diagnosis at any time point (prevalence ratio (PR): 1.65, 95% CI 1.07 to 2.54). As age increased, clinically missed infections significantly decreased (PR: 0.98 per year increase, 95% CI 0.97 to 1.00). CONCLUSIONS: The prevalence of laboratory-confirmed STIs was much higher than what was captured by clinical diagnosis. GC, CT and Tvag were not accurately detected without lab confirmation. Missed diagnoses decreased with older age. Increased laboratory capacity and refinement of the syndromic approach are needed to protect the health of sexually active Jamaican women. TRIAL REGISTRATION NUMBER: NCT01684358.

BACKGROUND: There is limited information on rates of STIs in Jamaica due to syndromic management and limited aetiological surveillance. We examined the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) and characteristics associated with STIs among sexually active women who participated in a randomised trial of a progestin implant initiation in Jamaica (the Sino-Implant Study (SIS)). METHODS: SIS was a randomised trial conducted in Kingston, Jamaica, from 2012 to 2014 to evaluate whether initiation of the Sino-Implant (II) led to more unprotected sex among women ages 18-44 years. Data collected included self-reported demographic, sexual behaviour information; and vaginal swabs collected at baseline, 1-month and 3-month follow-up visits for a biomarker of recent semen exposure (prostate-specific antigen (PSA)) and for STIs. We examined associations between STIs and PSA, demographics, sexual behaviour and insertion of an implant, with a repeated-measures analysis using generalised estimating equations (SAS Institute, V.9.3). RESULTS: Remnant vaginal swabs from 254 of 414 study participants were tested for STIs. At baseline, 29% of participants tested for STIs (n=247) had laboratory-confirmed CT, 5% NG, 23% TV and 45% any STI. In a repeated-measures analysis adjusted for study arm (immediate vs delayed implant insertion), those with PSA detected did not have an increased prevalence of any STI (prevalence ratio (PR)=1.04 (95% CI 0.89 to 1.21)), whereas prevalence decreased for each 1-year increase in age (PR=0.98 (95% CI 0.97 to 0.99)). Immediate implant insertion was not associated with increases in any STI in subsequent visits (PR=1.09 (95% CI 0.94 to 1.27)). CONCLUSIONS: Although the prevalence of laboratory-confirmed STIs was high, the immediate initiation of a contraceptive implant was not associated with higher STI prevalence rates over 3 months. TRIAL REGISTRATION NUMBER: NCT01684358.

From the initial task of getting "50 deployers within 30 days" into the field to support the 2014-2016 Ebola virus disease (Ebola) epidemic response in West Africa to maintaining well over 200 staff per day in the most affected countries (Guinea, Liberia, and Sierra Leone) during the peak of the response, ensuring the safe and effective deployment of international responders was an unprecedented accomplishment by CDC. Response experiences shared by CDC deployed staff returning from West Africa were quickly incorporated into lessons learned and resulted in new activities to better protect the health, safety, security, and resiliency of responding personnel. Enhanced screening of personnel to better match skill sets and experience with deployment needs was developed as a staffing strategy. The mandatory predeployment briefings were periodically updated with these lessons to ensure that staff were aware of what to expect before, during, and after their deployments. Medical clearance, security awareness, and resiliency programs became a standard part of both predeployment and postdeployment activities. Response experience also led to the identification and provision of more appropriate equipment for the environment. Supporting the social and emotional needs of deployed staff and their families also became an agency focus for care and communication. These enhancements set a precedent as a new standard for future CDC responses, regardless of size or complexity.The activities summarized in this report would not have been possible without collaboration with many U.S and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).

BACKGROUND: With the development and widespread use of combination antiretroviral therapy, HIV-infected women live longer, healthier lives. Previous research has shown that, since the adoption of combination antiretroviral therapy in the U.S., rates of morbidity and adverse obstetric outcomes remained higher for HIV-infected pregnant women compared with HIV-uninfected pregnant women. Monitoring trends in the outcomes these women experience is essential, as recommendations for this special population continue to evolve with the progress of HIV treatment and prevention options. OBJECTIVE(S): We conducted an analysis comparing rates of hospitalizations and associated outcomes among HIV-infected and uninfected pregnant women in the United States from 2004-2011. STUDY DESIGN: We used cross-sectional hospital discharge data from the 2004, 2007, and 2011 Nationwide Inpatient Sample, a nationally representative sample of US hospital discharges. Demographic characteristics, morbidity outcomes, and time trends were compared using chi2 tests and multivariate logistic regression. Analyses were weighted to produce national estimates. RESULTS: In 2011, there were 4,751 estimated pregnancy hospitalizations and 3,855 delivery hospitalizations for HIV-infected pregnant women; neither increased since 2004. Compared with those of HIV-uninfected women, pregnancy hospitalizations of HIV-infected women were more likely to be longer, in the South and Northeast, covered by public insurance, and to incur higher charges (all p < 0.005). Hospitalizations among pregnant women who were HIV-infected had higher rates for many adverse outcomes. Compared to 2004, hospitalizations of HIV-infected pregnant women in 2011 had higher odds of gestational diabetes (1.81 [1.16, 2.84]), pre-eclampsia/hypertensive disorders of pregnancy (1.58 [1.12, 2.24]), viral/mycotic/parasitic infections (1.90 [1.69, 2.14]), and bacterial infections (2.54 [1.53, 4.20]). Bacterial infections did not increase among hospitalizations of HIV-uninfected pregnant women. CONCLUSIONS: The numbers of hospitalizations during pregnancy and delivery have not increased for HIV-infected women since 2004, a departure from previously estimated trends. Pregnancy hospitalizations of HIV-infected women remain more medically complex than those of uninfected women. An increasing trend in infections among the delivery hospitalizations of HIV-infected pregnant women warrant further attention.

BACKGROUND: Studies describing the incidence of Crohn's disease (CD) and ulcerative colitis (UC) are uncommon in the United States. We sought to determine the incidence of CD and UC in the state of Rhode Island. METHODS: The Ocean State Crohn's and Colitis Area Registry is a state-based inception cohort of patients newly diagnosed with inflammatory bowel disease (IBD) in Rhode Island. To confirm a diagnosis of CD, UC, or IBD unclassified (IBDU), the National Institute of Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium criteria were applied in a review of medical records from gastroenterology practices located in the state of Rhode Island and adjacent to the Rhode Island border in Massachusetts and Connecticut. Using population-based data, we determined the statewide incidence of IBD in Rhode Island from 2008 to 2010. RESULTS: A total of 971 Rhode Island residents were diagnosed with IBD, including 444 with CD, 486 with UC, and 41 with IBD unclassified from 2008 to 2010. The overall age- and sex-adjusted IBD incidence was 30.2 (95% confidence interval, 28.3-32.1) per 100,000 persons in this time frame with 13.9, 15.1, and 1.3 per 100,000 diagnosed with CD, UC, and IBD unclassified, respectively. Of the total incident cases in Rhode Island, 30% (n = 291) were enrolled in Ocean State Crohn's and Colitis Area Registry for follow-up. CONCLUSIONS: The incidence of IBD in Rhode Island is higher than that previously reported by other population-based cohorts in the United States. Prospective follow-up of individuals enrolled in the community-based Ocean State Crohn's and Colitis Area Registry cohort is ongoing.

OBJECTIVE: To assess the characteristics of IVF cycles for which preimplantation genetic diagnosis (PGD) was used and to evaluate indications for PGD and treatment outcomes associated with this procedure as compared with cycles without PGD with the data from the U.S. National ART Surveillance System. DESIGN: Retrospective cohort study. SETTING: None. PATIENT(S): Fresh autologous cycles that involved transfer of at least one embryo at blastocyst when available. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): PGD indications and age-specific reproductive outcomes. RESULT(S): There were a total of 97,069 non-PGD cycles and 9,833 PGD cycles: 55.6% were performed for aneuploidy screening (PGD Aneuploidy), 29.1% for other reasons (PGD Other), and 15.3% for genetic testing (PGD Genetic). In comparison to non-PGD cycles, PGD Aneuploidy cycles showed a decreased odds of miscarriage among women 35-37 years (adjusted odds ratio [aOR] 0.62; 95% CI, 0.45-0.87) and women >37 years (aOR 0.55; 95% CI, 0.43-0.70); and an increased odds of clinical pregnancy (aOR 1.18; 95% CI, 1.05-1.34), live-birth delivery (aOR 1.43; 95% CI, 1.26-1.62), and multiple-birth delivery (aOR 1.98; 95% CI, 1.52-2.57) among women >37 years. CONCLUSION(S): Aneuploidy screening was the most common indication for PGD. Use of PGD was not observed to be associated with an increased odds of clinical pregnancy or live birth for women <35 years. PGD for aneuploidy was associated with a decreased odds of miscarriage for women >35 years, but an increased odds of a live-birth and a multiple live-birth delivery among women >37 years.

OBJECTIVE: To compare rates of complications associated with cesarean delivery in HIV-infected and HIV-uninfected women in the United States and to investigate trends in such complications across four study cycles spanning the implementation of HAART in the United States (1995-1996, 2000-2001, 2005-2006, 2010-2011). DESIGN: The Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project is the largest all-payer hospital inpatient care database in the United States; when weighted to account for the complex sampling design, nationally representative estimates are derived. After restricting the study sample to women aged 15-49 years, our study sample consisted of approximately 1 090 000 cesarean delivery hospitalizations annually. METHODS: Complications associated with cesarean deliveries were categorized as infection, hemorrhage, or surgical trauma, based on groups of specific International Classification of Diseases 9th revision codes. Length of hospitalization, hospital charges, and in-hospital deaths were also examined. RESULTS: The rate of complications significantly decreased during the study periods for HIV-infected and HIV-uninfected women. However, rates of infectious complications and surgical trauma associated with cesarean deliveries remained higher among HIV-infected, compared with HIV-uninfected women in 2010-2011, as did prolonged hospital stay and in-hospital deaths. Length of hospitalization decreased over time for cesarean deliveries of HIV-infected women to a greater extent compared with HIV-uninfected women. CONCLUSION: In the United States, rates of cesarean delivery complications decreased from 1995 to 2011. However, rates of infection, surgical trauma, hospital deaths, and prolonged hospitalization are still higher among HIV-infected women. Clinicians should remain alert to this persistently increased risk of cesarean delivery complications among HIV-infected women.

OBJECTIVE: While pregnancy-related severe liver disorders are rare, when they occur morbidity and mortality rates are increased for mothers and infants. The objective of this study was to examine the prevalence and trends of hepatic diseases during pregnancy hospitalizations from 2002 through 2010 in the United States. STUDY DESIGN: Hospital discharge data were obtained from the Nationwide Inpatient Sample, the largest all-payer hospital inpatient care database in the United States that provides nationally representative estimates. Pregnancy hospitalizations with the following diagnoses were identified: hepatitis B, hepatitis C, gallbladder disease/cholelithiasis, liver disorders of pregnancy, chronic/alcohol-related liver disease, biliary tract disease, and HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome. Age, insurance status, hospital location, and hospital region were compared among women with and without hepatic diseases using a chi2 test. Trends in rates of pregnancy hospitalizations and mean charges were analyzed using multivariable logistic and linear regression, respectively. RESULTS: From 2002 through 2010 there were an estimated 41,479,358 pregnancy hospitalizations in the United States. Gallbladder disease and liver disorders of pregnancy were the most common hepatic diseases (rates = 7.18 and 4.65/1000 pregnancy hospitalizations, respectively). Adjusted rates and mean charges significantly increased for all hepatic diseases during pregnancy over the study period. All hepatic diseases were associated with significantly higher charges compared to all pregnancy hospitalizations. HELLP syndrome was associated with the highest mean charges. CONCLUSION: This large study among a representative sample of the US population provides valuable information that can aid policy planning and management of these hepatic diseases during pregnancy in the United States.

BACKGROUND: Fatigue is common in Crohn's disease (CD) and ulcerative colitis (UC). Data on fatigue in newly diagnosed patients are unavailable. AIM: To report prevalence of fatigue in newly diagnosed CD and UC patients and examine its association with health-related quality of life (HRQOL), depression and disability. METHODS: The Ocean State Crohn's and Colitis Area Registry (OSCCAR) is a statewide cohort of newly diagnosed inflammatory bowel disease patients in Rhode Island. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue Scale. Patients were administered instruments measuring HRQOL, overall disability and work impairment, and depression. RESULTS: Fatigue was prevalent in 26.4% of 220 subjects. Cohen's d effect sizes for fatigue were large: Short-Form 36 Health Survey mental health component (CD 1.5, UC 1.4) and physical health component (CD 1.4, UC 1.4), EuroQol-5D valuation of current health state (CD 1.2, UC 1.0), Inflammatory Bowel Disease Questionnaire (CD 1.9, UC 1.6) and Patient Health Questionnaire depression scale (CD 1.8, UC 1.7). Fatigued patients reported more work impairment (Score difference: CD 29.5%, UC 23.8%) and activity impairment (score difference: CD 32.3%, UC 25.7%) on the Work Productivity and Activity Impairment Questionnaire. Fatigue's association with all scores remained highly significant despite controlling for disease activity. CONCLUSIONS: Fatigue is strongly associated with poor HRQOL, disability and depression similarly in CD and UC even when controlling for disease activity. Fatigue's association with a wide range of patient-reported outcome measures suggests that monitoring fatigue is a simple way to screen for overall disruption in patient life.

BACKGROUND: Current knowledge of racial disparities in healthcare utilization and disease outcomes for ulcerative colitis (UC) is limited. We sought to investigate these differences among Caucasian, African American, Asian, and Hispanic patients with ulcerative colitis in Kaiser Permanente, a large integrated health-care system in Northern California. METHODS: This retrospective cohort study used computerized clinical data from 5,196 Caucasians, 387 African-Americans, 550 Asians, and 801 Hispanics with prevalent UC identified between 1996 and 2007. Healthcare utilization and outcomes were compared at one and five-year follow-up by use of multivariate logistic regression analysis. RESULTS: Compared with whites, the male-to-female ratio differed for African-Americans (0.68 vs. 0.91, p < 0.01) and Asians (1.3 vs. 0.91, p < 0.01). Asians had fewer co-morbid conditions (p < 0.01) than whites, whereas more African-Americans had hypertension and asthma (p < 0.01). Use of immunomodulators did not differ significantly among race and/or ethnic groups. Among Asians, 5-ASA use was highest (p < 0.05) and the incidence of surgery was lowest (p < 0.01). Prolonged steroid exposure was more common among Hispanics (p < 0.05 at 1-year) who also had more UC-related surgery (p < 0.01 at 5-year) and hospitalization (<0.05 at 5-year), although these differences were not significant in multivariate analysis. CONCLUSIONS: In this population of UC patients with good access to care, overall health-care utilization patterns and clinical outcomes were similar across races and ethnicity. Asians may have milder disease than other races whereas Hispanics had a trend toward more aggressive disease, although the differences we observed were modest. These differences may be related to biological factors or different treatment preferences.

BACKGROUND: The effect of the inflammatory bowel diseases (IBD) on menstrual function is largely unknown. The aims of this study were to determine whether changes in menstrual function occur in the year before IBD diagnosis or in the initial years after diagnosis. METHODS: Women aged 18 years and older in the Ocean State Crohn's and Colitis Area Registry with at least 2 years of follow-up were eligible for this study. All patients were enrolled within 6 months of IBD diagnosis and followed prospectively. Menstrual cycle characteristics were retrospectively assessed. To assess for changes over time, general linear models for correlated data were used for continuous outcomes, and generalized estimating equations were used for discrete outcomes. RESULTS: One hundred twenty-one patients were studied. Twenty-five percent of patients experienced a change in cycle interval in the year before IBD diagnosis and 21% experienced a change in the duration of flow. Among women with dysmenorrhea, 40% experienced a change in the intensity of their menstrual pain and 31% experienced a change in its duration. Overall cycle regularity increased over time. Quality of life was significantly lower in women without regular cycles across all time points. CONCLUSIONS: Changes in menstrual function occur frequently in the year before IBD diagnosis; therefore, screening for menstrual irregularities should be considered in women with newly diagnosed IBD. Patients can be reassured that cycles typically become more regular over time.

Cervical cancer is a leading cause of cancer death among women in Bolivia, where cytology based screening has not performed well due to health-systems constraints. In response, the Centers for Disease Control and Prevention and the Pan American Health Organization partnered with the Bolivian Ministry of Health and the Peruvian Cancer Institute (INEN) to build capacity in Bolivia for the use of visual inspection of the cervix with acetic acid (VIA) and cryotherapy. Four 5-day courses on basic clinical skills to perform these procedures, provide related counseling, and manage side effects and infections were conducted from September 2010 to December 2012 for 61 Bolivian nurses and physicians. Of these courses, two were conducted by Bolivian trainers that were certified through a Training-of-Trainers course taught by the INEN. Classroom didactic sessions included lectures and practice with anatomic models followed by clinical practice sessions to provide trainees with practical experience in VIA and cryotherapy. Pre- and post-training evaluations were administered to ascertain knowledge gained. Evaluation of competency was conducted during simulation exercises in the classroom and during supervised performances of procedures in clinical settings. This report summarizes findings and lessons learned that will be useful for planning the supervision and monitoring phase of this project as well as for future partnerships in the Latin American and the Caribbean region.

PROBLEM/CONDITION: Since the birth of the first U.S. infant conceived with Assisted Reproductive Technology (ART) in 1981, use of advanced technologies to overcome the problem of infertility has increased steadily, as has the number of fertility clinics providing ART services in the United States. ART includes fertility treatments in which both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo ART procedures are more likely to deliver multiple-birth infants than those who conceive naturally. Multiple births pose substantial risks to both mothers and infants, including pregnancy complications, preterm delivery, and low birthweight infants. This report presents the most recent data on ART use and birth outcomes for U.S. states and territories. REPORTING PERIOD COVERED: 2009. DESCRIPTION OF SYSTEM: In 1996, CDC began collecting data on all ART procedures performed in the United States, as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). ART data for 1995-2003 were obtained from the Society of Assisted Reproductive Technology (SART) through its proprietary Clinical Outcomes Reporting System data base (SART CORS). Since 2004, CDC has contracted with Westat, Inc., a statistical survey research organization, to obtain data from fertility clinics in the United States through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. RESULTS: In 2009, a total of 146,244 ART procedures were reported to CDC. These procedures resulted in 45,870 live-birth deliveries and 60,190 infants. The largest numbers of ART procedures were performed among residents of California (18,405), New York (14,539), Illinois (10,192), Massachusetts (9,845), New Jersey (9,146), and Texas (8,244). Together, these six states reported the highest number of live-birth deliveries as a result of ART and accounted for 48% of all ART procedures initiated, 46% of all infants born from ART, and 45% of all ART multiple-birth deliveries but only 34% of all births in the United States. Nationally, the average number of ART procedures performed per 1 million women of reproductive age (15-44 years), which is a proxy indicator of ART utilization, was 2,361. In four states (Massachusetts, New York, New Jersey, and Connecticut) and the District of Columbia, this proxy measure of ART use exceeded twice the national average. Nationally, the average number of embryos transferred was 2.1 among women aged <35 years, 2.5 among women aged 35-40 years, and 3.0 among women aged >40 years (and varied most in this age group from 1.7 in Maine to 3.5 in Missouri). Age-specific elective single-embryo transfer (eSET) rates were approximately 7% among women aged <35 years, 3% among women aged 35-40 years, and 0.5% among women aged >40 years. The highest rates of eSET were observed among women aged <35 years (41% in Delaware, 20% in Iowa, and 17% Massachusetts). Overall, ART contributed to 1.4% of U.S. births (ranging from 0.2% in Puerto Rico to 4.3 % in Massachusetts). The proportion of ART to total infants born in the state or territory, which is another measure of ART utilization, was highest in Massachusetts (>4%) with high rates also observed in New Jersey, New York, Connecticut, and the District of Columbia (>3% of all infants born). Infants conceived with ART accounted for 20% of all multiple-birth infants (ranging from 4% in Maine to 41% in New York), 19% of all twin births (ranging from 4% in Maine to 42% in New York) and 34% of triplet or higher order births (ranging from 0 in several states to 61.5% in New Jersey). Among infants conceived with ART, 47% were born as multiple-birth infants (ranging from 35% in Delaware to 60.8% in Wyoming), compared with only 3% of infants among the general birth population (ranging from 1% in New York to 5% in Connecticut). Nationally, infants conceived with ART contributed to approximately 6% of all low birthweight (<2,500 grams) infants, ranging from 1.3% in Mississippi to 15% in Massachusetts and to 6% of all very low birthweight (<1,500 grams) infants, ranging from 1% in Alaska to 15% in New Jersey. Overall, among ART-conceived infants, 32% were low birthweight (ranging from 20% in Alaska to 48% in Puerto Rico), compared with 8% among the general birth population (ranging from 5.8% in South Dakota to 12.2% in Mississippi), and 6% of ART infants were very low birthweight (ranging from 1.5% in Alaska to 13% in South Dakota), compared with 1% among the general birth population (ranging from 1% in Alaska to 2% in Mississippi and District of Columbia). Finally, ART-conceived infants accounted for 3.9% of all preterm (<37 weeks; range: 0.5% in Puerto Rico to 11.1% in Massachusetts) and 4.5% of all very preterm births (<32 weeks; range: 0.5% in Puerto Rico to 12% in New York). Overall, among infants conceived with ART, 33.4% were born preterm (ranging from 21.3% in Vermont to 47.1% in Wyoming), compared with 12.2% of the general birth population (ranging from 9.3% in Vermont to 18.0% in Mississippi), and 6.1% of ART infants were very preterm births (ranging from 1.5% in Alaska to 14.7% in South Dakota), compared with 2% among the general birth population (ranging from 1.4% in Alaska, Oregon, Utah, and Washington to 3% in Mississippi). INTERPRETATION: The proportion of births from ART varied considerably by state and territory (ranging from 0.2% to 4.3%) with substantial impact on perinatal outcomes in some states. In most states, multiple births from ART accounted for substantial proportions of twins and triplets and higher order infants, and the rates of low birthweight and preterm births were disproportionately higher among ART infants than in the general birth population. More than one embryo was transferred per procedure in most states and territories for all age groups, influencing the overall multiple birth rates in the United States. ART use was represented disproportionately in the United States, with only 13 states having above-average ART use. High rates of ART utilization were observed in Massachusetts and New Jersey, which have comprehensive statewide-mandated health insurance coverage for ART procedures. Insurance mandates might influence ART utilization and ART-related birth outcomes. PUBLIC HEALTH ACTIONS: Promotion of single-embryo transfer, where feasible, is needed to reduce multiple births and related adverse consequences of ART. Nevertheless, because ART accounts for a relatively small fraction of total births in most states and territories, the overall prevalence of low birthweight and preterm births cannot be explained solely by the use of ART, and therefore non-ART causes of these adverse outcomes must be examined. Monitoring the use of non-ART infertility treatments (e.g., ovulation stimulation medications without ART) in the general population might be useful because these treatments also might be associated with high rates of multiple births and adverse outcomes such as preterm delivery and infants born with low birthweight.

BACKGROUND: Progress has been made recently in estimating ambient PM(2.5) (particulate matter with aerodynamic diameter < 2.5 mcm) and ozone concentrations using various data sources and advanced modeling techniques, which resulted in gridded surfaces. However, epidemiologic and health impact studies often require population exposures to ambient air pollutants to be presented at an appropriate census geographic unit (CGU), where health data are usually available to maintain confidentiality of individual health data. We aim to generate estimates of population exposures to ambient PM(2.5) and ozone for U.S. CGUs. METHODS: We converted 2001-2006 gridded data, generated by the U.S. Environmental Protection Agency (EPA) for CDC's (Centers for Disease Control and Prevention) Environmental Public Health Tracking Network (EPHTN), to census block group (BG) based on spatial proximities between BG and its four nearest grids. We used a bottom-up (fine to coarse) strategy to generate population exposure estimates for larger CGUs by aggregating BG estimates weighted by population distribution. RESULTS: The BG daily estimates were comparable to monitoring data. On average, the estimates deviated by 2 mcg/m(3) (for PM(2.5)) and 3 ppb (for ozone) from their corresponding observed values. Population exposures to ambient PM(2.5) and ozone varied greatly across the U.S. In 2006, estimates for daily potential population exposure to ambient PM(2.5) in west coast states, the northwest and a few areas in the east and estimates for daily potential population exposure to ambient ozone in most of California and a few areas in the east/southeast exceeded the National Ambient Air Quality Standards (NAAQS) for at least 7 days. CONCLUSIONS: These estimates may be useful in assessing health impacts through linkage studies and in communicating with the public and policy makers for potential intervention.

Allergy to marijuana is generally considered to be rare. Cannabis sativa is an annual plant in the Cannabaceae family that pollinates during the summer months. Various parts of this plant are used for both commercial and recreational purposes. Psychoactive cannabinoid compounds, mainly Δ9-tetrahydrocannabinol (THC), are present in the flowers and, to a lesser extent, in the leaves, stems, and seeds of the plant. When derived as dried preparations of the plant parts (marijuana), the cannabinoids are consumed by smoking, vaporizing, and oral ingestion. Teas and ointments are also common preparations. | The first report of allergic reaction to C sativa was in 1971, when a 29-year-old woman, after smoking a marijuana cigarette for the first time, had symptoms consistent with an anaphylactic response.1 Hypersensitivity was confirmed via skin prick testing (SPT) and passive transfer studies, suggesting an immunologic response to the THC component of the marijuana plant.1 Since then, several case reports have been published describing allergic reactions to C sativa after exposures through inhalation, ingestion, or skin contact.[2], [3], [4] Reactions, including rhinoconjunctivitis, urticaria, and angioedema, have been reported.

BACKGROUND: Recommendations for high risk human papillomavirus (HR-HPV) testing as an adjunct to cytology for cervical cancer screening differ by age group, because HR-HPV tests lack adequate specificity in women aged <30. Here, we assess age-group differences in HPV types and other risk factors for cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) versus CIN0-2 in women from four colposcopy clinics. METHODS: Women ages 18-69 (n=1658) were enrolled and completed structured interviews to elicit data on behavioral risk factors prior to their examinations. HPV genotyping was performed on exfoliated cervical cell samples. We estimated relative risks (RR) for HPV types and cofactors for CIN3+, overall and stratified by age group. RESULTS: After 2 years of follow-up, we identified 178 CIN3+, 1305 CIN0-2, and 175 indeterminate outcomes. Non-vaccine HR-HPV types were only associated with CIN3+ among women ≥30 (RR=2.3, 95% CI 1.5-3.4; <30: RR=0.9). Among all HR-HPV positive women, adjusting for age, significant cofactors for CIN3+ included current smoking (RR=1.5), former smoking (RR=1.8), regular Pap screening (RR=0.7), current regular condom use (RR=0.5), and parity ≥5 (RR=1.6, p-trend for increasing parity=.07). However, the parity association differed by age group (≥30: RR=1.8, p-trend=.008; <30: RR=0.9, p-trend=.55). CONCLUSIONS: Subgroup variation by age in the risk of CIN3+ points to the importance of the timing of exposures in relation to CIN3+ detection. IMPACT: Future screening strategies need to consider natural history and secular trends in cofactor prevalence in the pursuit of appropriately sensitive and specific screening tools applied to appropriate age groups.