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Multiparametric imaging is a critical tool in the noninvasive study and assessment of cancer. Imaging methods have evolved over the past several decades to provide quantitative measures of tumor and healthy tissue characteristics related to, for example, cell number, blood volume fraction, blood flow, hypoxia, and metabolism. Mechanistic models of tumor growth also have matured to a point where the incorporation of patient-specific measures could provide clinically relevant predictions of tumor growth and response. In this review, we identify and discuss approaches that use multiparametric imaging data, including diffusion-weighted magnetic resonance imaging, dynamic contrast-enhanced magnetic resonance imaging, diffusion tensor imaging, contrast-enhanced computed tomography, [18F]fluorodeoxyglucose positron emission tomography, and [18F]fluoromisonidazole positron emission tomography to initialize and calibrate mechanistic models of tumor growth and response. We focus the discussion on brain and breast cancers; however, we also identify three emerging areas of application in kidney, pancreatic, and lung cancers. We conclude with a discussion of the future directions for incorporating multiparametric imaging data and mechanistic modeling into clinical decision making for patients with cancer.

Doxorubicin is a chemotherapy widely used to treat several types of cancer, including triple-negative breast cancer. In this work, we use a Bayesian framework to rigorously assess the ability of ten different mathematical models to describe the dynamics of four TNBC cell lines (SUM-149PT, MDA-MB-231, MDA-MB-453, and MDA-MB-468) in response to treatment with doxorubicin at concentrations ranging from 10 to 2500 nM. Each cell line was plated and serially imaged via fluorescence microscopy for 30 days following 6, 12, or 24 h of in vitro drug exposure. We use the resulting data sets to estimate the parameters of the ten pharmacodynamic models using a Bayesian approach, which accounts for uncertainties in the models, parameters, and observational data. The ten candidate models describe the growth patterns and degree of response to doxorubicin for each cell line by incorporating exponential or logistic tumor growth, and distinct forms of cell death. Cell line and treatment specific model parameters are then estimated from the experimental data for each model. We analyze all competing models using the Bayesian Information Criterion (BIC), and the selection of the best model is made according to the model probabilities (BIC weights). We show that the best model among the candidate set of models depends on the TNBC cell line and the treatment scenario, though, in most cases, there is great uncertainty in choosing the best model. However, we show that the probability of being the best model can be increased by combining treatment data with the same total drug exposure. Our analysis points to the importance of considering multiple models, built on different biological assumptions, to capture the observed variations in tumor growth and treatment response.

BACKGROUND: Historically, foreign-born individuals in the US have had an elevated risk of dying from gastric cancer when compared to US-born individuals. This is primarily due to factors that occur prior to their immigration to the US, including diet and underlying risk of H. pylori infection. METHODS: National mortality data from 2005 to 2014 were obtained from the CDC’s National Center for Health Statistics. Annual population estimates were obtained from the US Census Bureau’s American Community Survey for foreign-born and US-born persons. Age-adjusted gastric cancer mortality rates and rate ratios (RR) were calculated stratified by birth place, age, race/ethnicity, and geographic location. RESULTS: From 2005 to 2014, 111,718 deaths from malignant gastric cancer occurred in the US, of which 24,583 (22%) occurred among foreign-born individuals. Overall, foreign-born individuals had higher mortality rates compared with US- born individuals (RR 1.82; 95% CI 1.80, 1.85) and this difference remained after stratifying by sex, age, and geographic location. However, this finding was primarily driven by the low rate of gastric cancer mortality among US-born whites, with similar mortality rates observed among all other foreign-born and US-born groups. Gastric cancer mortality rates significantly decreased during the study period overall (AAPC − 2.50; 95% CI − 3.21, − 1.79) with significant declines observed among US-born (AAPC − 2.81; 95% CI − 3.55, − 2.07) and the foreign-born (AAPC − 2.53; 95% CI − 3.20, − 1.86) population. CONCLUSIONS: Efforts directed at reducing the prevalence of gastric cancer risk factors could help reduce the elevated burden observed among foreign-born individuals and US-born minority groups.

Purpose: Deep learning is a promising technique for spleen segmentation. Our study aims to validate the reproducibility of deep learning-based spleen volume estimation by performing spleen segmentation on clinically acquired computed tomography (CT) scans from patients with myeloproliferative neoplasms. Approach: As approved by the institutional review board, we obtained 138 de-identified abdominal CT scans. A sum of voxel volume on an expert annotator’s segmentations establishes the ground truth (estimation 1). We used our deep convolutional neural network (estimation 2) alongside traditional linear estimations (estimation 3 and 4) to estimate spleen volumes independently. Dice coefficient, Hausdorff distance, [Formula: see text] coefficient, Pearson [Formula: see text] coefficient, the absolute difference in volume, and the relative difference in volume were calculated for 2 to 4 against the ground truth to compare and assess methods’ performances. We re-labeled on scan–rescan on a subset of 40 studies to evaluate method reproducibility. Results: Calculated against the ground truth, the [Formula: see text] coefficients for our method (estimation 2) and linear method (estimation 3 and 4) are 0.998, 0.954, and 0.973, respectively. The Pearson [Formula: see text] coefficients for the estimations against the ground truth are 0.999, 0.963, and 0.978, respectively (paired [Formula: see text]-tests produced [Formula: see text] between 2 and 3, and 2 and 4). Conclusion: The deep convolutional neural network algorithm shows excellent potential in rendering more precise spleen volume estimations. Our computer-aided segmentation exhibits reasonable improvements in splenic volume estimation accuracy.

INTRODUCTION: A defining hallmark of cancer is aberrant cell proliferation. Efforts to understand the generative properties of cancer cells span all biological scales: from genetic deviations and alterations of metabolic pathways, to physical stresses due to overcrowding, as well as the effects of therapeutics and the immune system. While these factors have long been studied in the laboratory, mathematical and computational techniques are being increasingly applied to help understand and forecast tumor growth and treatment response. Advantages of mathematical modeling of proliferation include the ability to simulate and predict the spatiotemporal development of tumors across multiple experimental scales. Central to proliferation modeling is the incorporation of available biological data and validation with experimental data. AREAS COVERED: We present an overview of past and current mathematical strategies directed at understanding tumor cell proliferation. We identify areas for mathematical development as motivated by available experimental and clinical evidence, with a particular emphasis on emerging, non-invasive imaging technologies. EXPERT COMMENTARY: The data required to legitimize mathematical models are often difficult or (currently) impossible to obtain. We suggest areas for further investigation to establish mathematical models that more effectively utilize available data to make informed predictions on tumor cell proliferation.

Medical oncology is in need of a mathematical modeling toolkit that can leverage clinically-available measurements to optimize treatment selection and schedules for patients. Just as the therapeutic choice has been optimized to match tumor genetics, the delivery of those therapeutics should be optimized based on patient-specific pharmacokinetic/pharmacodynamic properties. Under the current approach to treatment response planning and assessment, there does not exist an efficient method to consolidate biomarker changes into a holistic understanding of treatment response. While the majority of research on chemotherapies focus on cellular and genetic mechanisms of resistance, there are numerous patient-specific and tumor-specific measures that contribute to treatment response. New approaches that consolidate multimodal information into actionable data are needed. Mathematical modeling offers a solution to this problem. In this perspective, we first focus on the particular case of breast cancer to highlight how mathematical models have shaped the current approaches to treatment. Then we compare chemotherapy to radiation therapy. Finally, we identify opportunities to improve chemotherapy treatments using the model of radiation therapy. We posit that mathematical models can improve the application of anticancer therapeutics in the era of precision medicine. By highlighting a number of historical examples of the contributions of mathematical models to cancer therapy, we hope that this contribution serves to engage investigators who may not have previously considered how mathematical modeling can provide real insights into breast cancer therapy.

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average-risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;68:250-281. © 2018 American Cancer Society.

We develop a combined experimental-mathematical framework to investigate heterogeneity in the context of breast cancer treated with doxorubicin. We engineer a cell line to over-express the multi-drug resistance 1 protein (MDR1), an ATP-dependent pump that effluxes intracellular drug. Co-culture experiments mixing the MDR1-overexpressing line with its parental line are evaluated via fluorescence microscopy. To quantify the impact of population heterogeneity on therapy response, these data are analyzed with a coupled pharmacokinetics/pharmacodynamics model. The proliferation and death rates of each line vary with co-culture condition (the relative fraction of each cell line at the time of seeding). For example, the death rate in the parental line under low-dose doxorubicin treatment is increased from 0.64 (±0.22) × 10(−2) hr(−1) to 1.46 (±0.58) × 10(−2) hr(−1) with increasing fractions of MDR1-overexpressing cells. The growth rate of the MDR1-overexpressing line increases 29% as its relative fraction is decreased. Simulations of the pharmacokinetics/pharmacodynamics model suggest increased efflux from MDR1-overexpressing cells contributes to the increased death rate in the parental cells. Experimentally, the death rate of parental cells is constant across co-culture conditions under co-treatment with an MDR1 inhibitor. These data indicate that intercellular pharmacokinetic variability should be considered in analyzing treatment response in heterogeneous populations.

Doxorubicin forms the basis of chemotherapy regimens for several malignancies, including triple negative breast cancer (TNBC). Here, we present a coupled experimental/modeling approach to establish an in vitro pharmacokinetic/pharmacodynamic model to describe how the concentration and duration of doxorubicin therapy shape subsequent cell population dynamics. This work features a series of longitudinal fluorescence microscopy experiments that characterize (1) doxorubicin uptake dynamics in a panel of TNBC cell lines, and (2) cell population response to doxorubicin over 30 days. We propose a treatment response model, fully parameterized with experimental imaging data, to describe doxorubicin uptake and predict subsequent population dynamics. We found that a three compartment model can describe doxorubicin pharmacokinetics, and pharmacokinetic parameters vary significantly among the cell lines investigated. The proposed model effectively captures population dynamics and translates well to a predictive framework. In a representative cell line (SUM-149PT) treated for 12 hours with doxorubicin, the mean percent errors of the best-fit and predicted models were 14% (±10%) and 16% (±12%), which are notable considering these statistics represent errors over 30 days following treatment. More generally, this work provides both a template for studies quantitatively investigating treatment response and a scalable approach toward predictions of tumor response in vivo.

The goal of this study is to experimentally and computationally investigate combination trastuzumab-paclitaxel therapies and identify potential synergistic effects due to sequencing of the therapies with in vitro imaging and mathematical modeling. Longitudinal alterations in cell confluence are reported for an in vitro model of BT474 HER2+ breast cancer cells following various dosages and timings of paclitaxel and trastuzumab combination regimens. Results of combination drug regimens are evaluated for drug interaction relationships based on order, timing, and quantity of dose of the drugs. Altering the order of treatments, with the same total therapeutic dose, provided significant changes in overall cell confluence (p in vitro data to simulate the tumor cell response to the individual therapies. A collective model merging the two individual drug response models was designed to investigate the potential mechanisms of synergy for paclitaxel-trastuzumab combinations. This collective model shows increased synergy for regimens where trastuzumab is administered prior to paclitaxel and suggests trastuzumab accelerates the cytotoxic effects of paclitaxel. The synergy derived from the model is found to be in agreement with the combination index, where both indicate a spectrum of additive and synergistic interactions between the two drugs dependent on their dose order. The combined in vitro results and development of a mathematical model of drug synergy has potential to evaluate and improve standard-of-care combination therapies in cancer.

From 1970 to 2010 the foreign-born population in the United States has rapidly increased from 9.6 to 40.0 million individuals. Historically, differences in cancer rates have been observed between US-born and foreign-born individuals. However, comprehensive and up-to-date data on US cancer rates by birth place is lacking. To compare cancer mortality rates among foreign and US-born individuals, population-based cancer mortality data were obtained from the CDC's National Center for Health Statistics. Utilizing data recorded on death certificates, individuals were categorized as US-born or foreign-born. Annual population estimates were obtained from the American Community Survey. Age-adjusted mortality rates and rate ratios (RRs) for all cancer sites were calculated using SEER*Stat. A total of 5,670,535 deaths from malignant cancers were recorded in the US from 2005 to 2014 and 9% of deaths occurred among foreign-born individuals. Overall, foreign-born individuals had a 31% lower cancer mortality rate when compared to US-born individuals (Rate Ratio (RR): 0.69 (95% CI: 0.68-0.69)), and similar results were observed when stratifying by sex, race/ethnicity, age, and geographic region. However, foreign-born individuals did have significantly elevated cancer mortality rates for seven cancers sites, of which five were infection-related, including: nasopharynx (RR: 2.01), Kaposi Sarcoma (RR: 1.94), stomach (RR: 1.82), gallbladder (RR: 1.47), acute lymphocytic leukemia (RR: 1.27), liver and intrahepatic bile duct (RR: 1.24), and thyroid (RR: 1.22) cancers. Many of these deaths could be avoided through improved access to prevention, screening, and treatment services for immigrant populations in the US or in their country of origin.

Introduction Historically, foreign-born women in the U.S. are less likely to be screened and are more likely to die from cervical cancer when compared with their U.S.-born counterparts. In order to inform prevention efforts and reduce this health disparity, mortality data were obtained from the National Center for Health Statistics to describe cervical cancer mortality among U.S.- and foreign-born women. Methods Annual population estimates were obtained from the U.S. Census Bureau's American Community Survey from 2005 to 2014. From 2017 to 2018, age-adjusted mortality rates and rate ratios were calculated by nativity status, race/ethnicity, age, geographic region, and country of birth. Results From 2005 to 2014, a total of 5,924 deaths from cervical cancer were recorded among the foreign-born population, compared with 33,893 deaths among U.S.-born women. Overall, foreign-born women had a lower cervical cancer mortality rate when compared with the U.S.-born women (rate ratio=0.95, 95% CI=0.92, 0.97). However, older foreign-born women had significantly higher mortality rates compared with U.S.-born women: aged 65–79 years (rate ratio=1.15, 95% CI=1.09, 1.22) and ≥80 years (rate ratio=1.43, 95% CI=1.32, 1.55). Women born in Mexico had significantly elevated rates of cervical cancer mortality (rate ratio=1.35, 95% CI=1.27, 1.42) when compared with U.S.-born women. Conclusions Efforts that work to increase cervical cancer screening access and guideline compliance might further reduce the cervical cancer deaths in the U.S., and the excess burden observed among older foreign-born women.

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average-risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;68:250-281. © 2018 American Cancer Society.

In a large, population based cohort study, Alexander and colleagues report that a diagnosis of non-alcoholic fatty liver disease (NAFLD) does not confer an increased risk of ischaemic heart disease or stroke.1 To translate these findings into clinical practice, we must appreciate the spectrum of NAFLD severity, especially as patients with advanced fibrosis have …

Tobacco use is one of the leading preventable causes of morbidity and mortality worldwide. Given that country-specific international data on tobacco use were limited or nonexistent, in 1998, the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and the Canadian Public Health Association (CPHA) initiated the Global Tobacco Surveillance System (GTSS) to assist countries in establishing tobacco control surveillance and monitoring programs. GTSS includes collection of data through three school-based surveys: the Global Youth Tobacco Survey (GYTS) for youth; the Global School Personnel Survey (GSPS), and the Global Health Professions Student Survey (GHPSS) for adults; and one household survey: the Global Adult Tobacco Survey (GATS) for adults. The GTSS provides a globally implemented and consistent framework for conducting surveillance including standard sampling procedures, core questionnaire items, training in field procedures and analysis of data consistent across all GTSS countries. The GTSS also enhances the role of the nongovernmental sector by supporting participation of civil society agencies in surveillance, monitoring, and policy and program development. The synergy between countries passing tobacco control laws, regulations or decrees, ratifying and complying with the WHO Framework Convention on Tobacco Control, and conducting GTSS surveys offers a unique opportunity to develop, implement, and evaluate comprehensive tobacco control policy that can be helpful to each country document the development, growth, and collaboration in sustaining the GTSS. The report highlights countries’ involvement in tobacco control measures and the establishment of comprehensive tobacco control programs worldwide. This report can assist countries in prioritizing and developing tobacco control programs, including surveillance, evaluation, and policy development. (Global Health Promotion, 2009; Supp (2): pp. 04-37)

BACKGROUND: Implementation of sensitive screening methods for human immunodeficiency virus (HIV) and hepatitis viruses prompts the question of what quantitative risks may result from altered deferral strategies for donation of blood by men who have had sex with men (MSM). STUDY DESIGN AND METHODS: Quantitative probabilistic models were developed to assess changes in the residual risk of transfusion-transmitted HIV and hepatitis B virus (HBV) associated with blood testing and quarantine release errors (QREs) in the initial year of two hypothetical policy scenarios that would allow donations from donors who have abstained from MSM behavior for at least 5 years (MSM5) or at least 1 year (MSM1). RESULTS: The MSM5 and MSM1 models, respectively, predicted annual increases in units of HIV-infected blood of 0.5% (0.03 mean additional units; 95% confidence interval [CI], 0-1) and 3.0% (0.18 mean additional units; 95% CI, 0-1) over current estimated HIV residual risk using recent, nationwide biologic product deviation reports to estimate QRE rates. These estimates are approximately 10-fold lower than estimates based on New York State QRE data from the previous decade. The models predicted smaller increases in infectious HBV donations. CONCLUSIONS: QREs remain the most significant preventable source of risk. More accurate inputs, including the percentage of MSM in the population, the percentage of MSM who have abstained from MSM activity for 1 or 5 years, the prevalence of HIV and HBV in MSM who have abstained from MSM activity for 1 or 5 years, the rate of self-deferral, and QRE rates, are required before making more precise predictions.

SUMMARY The human immunodeficiency virus (HIV) epidemic emerged in the early 1980s with HIV infection as a highly lethal disease among men who have sex with men and among frequent recipients of blood product transfusions. Advances in the treatment of HIV infection have resulted in a fundamental shift in its epidemiology, to a potentially chronic and manageable condition. However, challenges in the prevention of this infection remain. In particular, increasing evidence suggests that transmission of drug-resistant virus is becoming more common and that the epidemic is having a profound impact on morbidity and mortality in ethnic and racial minority subgroups in the United States. New population-based data collection systems designed to describe trends in behaviors associated with HIV transmission and better methods for measuring the true incidence of transmission will better elucidate the characteristics of HIV infection in the United States and inform future public health policies.

Since the height of HIV incidence in the mid-1980s, advances in treatment have delayed progression of HIV infection. As a result, surveillance of AIDS cases alone is no longer sufficient to monitor the current status of the HIV epidemic. At the national level, new HIV diagnoses and progression of these cases to AIDS are used to describe the epidemic. The capacity to monitor the national HIV epidemic has consistently improved over the last several years. An increasing number of states report diagnosed HIV cases to the national surveillance system, allowing data from this system to better represent the national picture. Monitoring the national HIV epidemic depends on a nationwide system using standardized methods of data collection, and establishing such a comprehensive system remains one of the highest priorities for national HIV case surveillance.

Ascertainment of risk factors for HIV transmission is critical to monitoring the HIV epidemic. Since 1993, there has been an increase in the proportion of HIV/AIDS cases that are reported to the Centers for Disease Control and Prevention (CDC) without an identified risk factor for HIV. About this time many areas implemented laboratory reporting, which generates an initial report with little to no HIV risk factor information. In 2001, the CDC convened a group of experts who recommended changes to the presentation of HIV risk factor data. The CDC subsequently funded two projects to improve the collection of HIV risk factors by surveillance staff. Since 2004, the CDC and state surveillance coordinators revised surveillance guidance to recommend prioritization of follow-up and provider training, and to monitor key variables while providing feedback to reporters. The CDC also began an evaluation of provider-targeted educational materials. The CDC has also been working with professional associations to incorporate methods for documenting HIV risk factors into existing training modules. CDC and state surveillance coordinators will need to continue efforts to educate, train, and identify barriers for providers in order to improve the completeness of HIV risk factor documentation and reporting.

The objective of the study is to identify opportunities to improve cervical cancer screening among privately insured women. From MedStat's Marketscan database, we identified 735,181 women aged 21-64 years who remained in the same insurance plan during the entire period of 2000-2002. We obtained the percentages of women who had a Papanicolaou (Pap)-test reimbursement claim and any health-related claim during the 3-year period. For women without a Pap-test claim, we obtained information about the frequency of insurance claims, type of health-care provider, and type of insurance plan in which the women were enrolled. The multivariate logistic regression model was used to identify factors independently associated with not having a Pap test. Of the total sample, in the 3-year period, 96% had at least one health insurance reimbursement claim and 69% had at least one claim for a Pap test. Approximately, 87% of the women who had no Pap-test claim had a health claim; 44% of such claims were from primary care providers. In the multiple logistic regression model, factors that were independently associated with having no Pap test were old age, being dependents of employees, and enrollment in comprehensive insurance plans. Efforts to increase the use of cervical cancer screening service should consider additional risk factors besides lack of insurance coverage. Concerted efforts by insurance and health-care providers are needed to improve adherence to the recommended cervical cancer screening guidelines, both by consumers and service providers.

Background The burden of HIV/AIDS has not been described for certain rural areas of the United States (Appalachia, the Southeast Region, the Mississippi Delta, and the US-Mexico Border), where barriers to receiving HIV services include rural residence, poverty, unemployment, and lack of education. Methods We used data from Centers for Disease Control and Prevention (CDC) HIV/AIDS Reporting System to determine the rates of HIV (data from 29 states) and AIDS diagnoses (data from 50 states and the District of Columbia) in 2000 for the 4 regions by demographic and residential (rural and economic indicators of county of residence) characteristics. Results The rate of HIV diagnoses in 2000 was lower in rural areas (7.3 per 100,000) than in suburban (8.6 per 100,000) or urban areas (22.7 per 100,000). The highest race-adjusted rate was observed for the US-Mexico Border (21.1 per 100,000), followed by the Mississippi Delta (17.3 per 100,000), Southeast Region (14.7 per 100,000), and Appalachia (10.4 per 100,000). Heterosexually acquired HIV was more common in the Southeast Region and the Mississippi Delta than elsewhere. The Mississippi Delta had the highest proportion of HIV diagnoses among young people aged 13-24 years (18.4%). More than three quarters of people diagnosed with HIV in the Mississippi Delta and the Southeast Region were black, and diagnosis rates were higher among blacks and Hispanics than whites in all regions. The distribution of demographic and residential characteristics among people with AIDS was similar to that of all people with a diagnosis of HIV. Conclusion Strategies are needed to reach the populations of these areas to reduce transmission of HIV.

Purpose We examined the demographic and risk characteristics of persons with HIV using traditional AIDS case reporting and the more recent system that includes HIV diagnoses without AIDS. Methods Using data from 25 states with HIV reporting of HIV/AIDS cases diagnosed from 1994 through 2001, we calculated percentage distributions, annual diagnosis rates, and estimated annual percent change (EAPC) for persons with HIV (all HIV diagnoses with or without AIDS) and persons with AIDS. Results The age at diagnosis of persons with all stages of HIV tended to be younger than that of the subset of persons with AIDS. Annual diagnosis rates decreased more among AIDS cases (men: EAPC, − 9.76; 95% CI, − 12.00, − 7.45; women: EAPC, − 3.40; 95% CI − 5.72, − 1.02) than for persons with HIV (men: EAPC, − 6.14; 95% CI, − 7.66, − 4.60; women: EAPC, − 2.99; 95% CI, − 4.15, − 1.82), except among women and black non-Hispanics, for whom the difference in the decreases in rates for both disease groups were small. Injection drug use was a more common mode of exposure for women with AIDS than for women with HIV. Conclusions The epidemiology of HIV differs for certain key population groups from that of AIDS.

Background & Aims: Estimates of the current number of endoscopic colorectal cancer screening and follow-up examinations being performed are limited. A national study was therefore conducted among US physician practices. Methods: Approximately 1800 medical practices were surveyed from a list of all practices known to have purchased or leased lower endoscopic equipment between 1996 and 2000. Questions were asked regarding the current number of lower endoscopic procedures performed and the potential maximum number that could be performed. Results: In 2002, a total of 8207 practices reported performing flexible sigmoidoscopy or colonoscopy in the United States. Gastroenterologists performed 43.7% (95% confidence interval [CI], 37.2–50.2) of all sigmoidoscopies and 82.5% (95% CI, 80.3–84.7) of all colonoscopies. Primary care physicians performed 24.9% (95% CI, 20.3–29.5) of all sigmoidoscopies and 2.0% (95% CI, 1.4–2.6) of all colonoscopies. All physicians combined performed approximately 2.8 million (95% CI, 2.4–3.1) flexible sigmoidoscopies and 14.2 million (95% CI, 12.1–16.4) colonoscopies but reported that they could increase to approximately 9.5 million flexible sigmoidoscopies (95% CI, 8.4–10.5) and 22.4 million colonoscopies (95% CI, 20.1–24.8) in 1 year. Conclusions: Approximately 2.8 million flexible sigmoidoscopies and 14.2 million colonoscopies were estimated to have been performed in 2002. Physicians reported that they could perform an additional 6.7 million flexible sigmoidoscopies and 8.2 million colonoscopies in 1 year. These additional procedures could be used for the unscreened population and should be considered in the estimate of the national capacity to provide colorectal cancer screening to all eligible persons in the United States.

To determine the recent trends in AIDS-defining cancers in Western Europe, we analyzed the June 2002 European Non-Aggregate AIDS Data Set. We obtained the percentage of people with AIDS aged 15 years or older (n = 125,691; males, 99,560, females, 26,131) who had cancers as the initial AIDS-defining illness in 17 European countries. Overall, from 1994 through 2001, declines were noted in the number of people with AIDS (25,324 to 8929), the proportion of people with AIDS who were homosexual/bisexuals (38.8% to 26.6%) or intravenous drug users (male, 41.7% to 34.8%; female, 50.2% to 26.4%). Among males, between 1994 and 2001, the percentage with any AIDS-defining, cancers declined (14.4% to 13.1%, p for trend = 0.091) because of a decline in Kaposi's sarcoma (KS; 10.7% to 7.9%) mostly among homosexual/bisexual men (22.7% to 18.8%) (p for trends < 0.05). Between 1994 and 2001, the percentage of males with all types of lymphomas increased (3.8% to 5.2%, p for trend = 0.012). Among females, AIDS-defining cancers increased (7.3% to 8.5%) due to increase in lymphomas (all types, 2.6% to 4.0%) (p for trend = 0.05). Cervical cancer remained the most common cancer among females, the percentage of which declined between 1994 and 2001 (2.8% to 2.0%, p for trend = 0.37) mostly among women who were 15 to 29 years old, most of whom acquired HIV heterosexually. In summary, declines were noted for the two leading AIDS-defining cancers at initial AIDS diagnosis among certain population groups. KS declined among men who had sexually transmitted HIV infection. Cervical cancer declined among young females and heterosexuals.

BACKGROUND: Pooled NAT and donor screening have reduced the diagnostic window period for HIV in the blood donor population to approximately 10 to 15 days. This report describes two cases of transfusion-acquired HIV infection and verification of transmission from the donor to the recipients, and attempts to identify how the 18-year-old donor acquired her infection. STUDY DESIGN AND METHODS: After a repeat donor had a positive HIV test result, two recipients of the donor's previous donation were identified and tested. The donor and recipients were interviewed and blood samples were obtained for HIV DNA sequencing and phylogenetic analysis. RESULTS: The two recipients had positive HIV test results. Phylogenetic analysis showed a high genetic similarity among the viruses (bootstrap 100%), consistent with transmission from the donor to the recipients. Four of five men with whom the donor had sexual contact during the critical time period when infection most likely occurred were located and tested; results were negative for HIV. CONCLUSIONS: Pooled NAT of blood donations has not eliminated the window period for HIV identification during seroconversion.

Escalating healthcare costs have led employers to identify ways to assess the actual burden of disease among their employees. One such measure is the use of disability-adjusted life-years (DALYs). DALYs were calculated for the General Motors (GM) population for 1994 through 1998 using data from GM's Mortality Registry, published life tables, and age- and sex-specific disease incidence and disability data from the U.S. Burden of Disease Study. Chronic diseases accounted for 45% (245,844 of 540,450) of total DALYs lost. Ischemic heart disease, stroke, lung cancer, and chronic obstructive pulmonary disease led the list for both men and women and accounted for 39% and 31%, respectively, of the top 10 DALYs lost. Disease burden among employees could be reduced through targeted interventions aimed at the risk factors associated with the leading causes of DALYs.

Background Societal cost-effectiveness analysis and its variants help decision makers achieve an efficient allocation of resources across the set of all possible health interventions. Sometimes, however, decision makers are focused instead on the efficient allocation of resources within a particular intervention program that has already been implemented. This is especially true when the intervention is being delivered at several different sites. An analysis of average cost across program sites may help program officials to maximize the health benefits that can be achieved with limited resources. In this article, the authors present such an analysis, with special attention paid to the possible existence and implications of economies of scale. Methods Focusing on federally sponsored, state-organized cancer detection programs, the authors modeled 19 state programs as productive processes and examined their average costs over a 2- to 5-year period of operation. They considered 3 alternative definitions of output: women served, screens performed, and conditions detected. Average federal costs and average total costs were estimated for each grant period. Multivariate regression analysis was used to help explain the variation in average costs. Results The average cost estimates were distributed in a skewed pattern with the majority of observations falling close to the median and substantially below the mean. For all measures considered, average cost decreased as output expanded. This inverse relationship between average cost and output level persisted even after controlling for the effects of other predictors, suggesting the possible existence of economies of scale. Discussion The potential existence of economies of scale calls into question the assumption of a constant average cost frequently made in economic analyses of proposed public health programs. It also implies that a) differences in output level should be taken into account when comparing operating efficiency across program sites; b) conclusions from societal cost-effectiveness analyses may depend on the level of output at which the programs are evaluated; c) cost projections could be inaccurate if they do not take into account the decrease in average cost that occurs as output expands; and d) gains might be possible if similar programs with limited output potential are integrated, perhaps through cost sharing.

Introduction: We aim to use clinical imaging data to initialize and constrain tumor-specific biophysical models of in situ cell proliferation, motility, and therapy response. Towards this goal, we have developed a 3D in vitro cell culture system that can be non-invasively interrogated by both microscopy and magnetic resonance imaging (MRI). The system supports long-term cell growth and allows for control over microenvironmental factors such as drug delivery and extracellular matrix. Cellular and subcellular level data obtained from confocal microscopy define the cell state and local environment and improve interpretation of the lower resolution, clinically relevant information provided by MRI. Here, we report system design and initial data collection. Apparatus Design: The system consists of the bioreactor body, a reservoir with a filter enabling CO2 equilibration in the incubator, and a peristaltic pump to drive media flow throughout the tubing and bioreactor. The bioreactor body has a cavity for cells embedded in extracellular matrix, a hollow-fiber for delivery of nutrients (FiberCell Systems, Frederick, MD), and is sealed using a gasket and lid with a confocal microscopy window. The removable lid makes the bioreactor reusable after sterilization. Data Collection: As a simplified model of 3D tumor growth, we selected the triple negative breast cancer cell line MDA-MB-231 embedded in 0.4% agarose. MDA-MB-231 cells were labeled with H2B-RFP and FUCCI-GFP to image cell nuclei and entry into the cell cycle, respectively, enabling measurements of cell number and cell division. Fluorescence microscopy images were collected on a Zeiss spinning disk confocal microscope using a 20x objective. Sixty 200 μm z -stacks using the green and red channels can be collected in approximately 90 minutes. The bioreactor is secured into a custom microscope mount using screws, ensuring it is placed in the same location every time. A reference point is marked on the first imaging day, to enable longitudinal alignment at subsequent imaging sessions. The bioreactor was also designed for use on a 9.4 T Agilent Technologies (Palo Alto, CA) MRI scanner equipped with a 38-mm quadrature RF coil, which is conventionally used for small animal studies. Diffusion-weighted (DW) images have been acquired using a standard pulsed gradient spin echo sequence with four b values (67, 200, 400, and 800 s/mm2) and gradients applied simultaneously along three orthogonal directions (x , y , and z ). The apparent diffusion coefficient obtained from the DW-MRI data provides an indirect measure of cell number. Images were acquired at a resolution of 100x100x1000 μm3. Conclusion: Overall, we have designed and fabricated a multi-modal imaging compatible bioreactor that supports long-term 3D cell growth under controlled conditions. We have successfully collected both MRI and confocal microscopy data on the bioreactor system at multiple time points. Currently, we are working towards co-registering these two imaging data types and extending the life of the bioreactor. Our novel multi-modal imaging compatible bioreactor is ideal for iterative biophysical tumor model refinement, providing a bridge to predictive models exclusively populated with non-invasive clinical imaging data. Citation Format: Abigail M. Searfoss, Matthew T. McKenna, Vito Quaranta, Thomas E. Yankeelov, Erin C. Rericha. A window into 3D culture: A multi-modal imaging compatible bioreactor for developing tumor growth models. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A22.

Summary As the fifth, and final, report in this Lancet series on health economics, we discuss how economic analyses in public health, with cancer screening as the example, differ depending on the perspective taken. We identify nine different, but related, decision makers at various levels, from the individual patient to society as a whole, and discuss how their different viewpoints affect their ultimate decisions. Central to our discussion is the identification of seven distinct components of perspective, each potentially important in the screening decision. In many fields of healthcare, decisions about the use of resources, such as time, wealth, or energy, are made by weighing up the positive and negative consequences of the alternatives under consideration and are thus based on an economic analysis of the situation (although sometimes this process is subconscious). For simplicity, we restrict our report to the effect of perspective on cancer screening decisions and show how the costs (negative consequences) and benefits (positive consequences) vary depending on the decision maker.

Background: Tuberculosis (TB) control activities are contingent on the timely identification and reporting of cases to public health authorities to ensure complete assessment and appropriate treatment of contacts and identification of secondary cases. We report the results of a multistate evaluation of completeness and timeliness of reporting of TB cases in the United States during 1993 and 1994. Methods: To determine completeness of TB reporting, laboratory log books, death certificates, hospital discharge, Medicaid databases, and pharmacy databases were reviewed in seven states to identify possible unreported cases. Timeliness of TB reporting was calculated using the number of days between date of TB diagnosis and date of report to the local or state health department. Cases reported >7 days after diagnosis were considered to have delayed reporting. Results: Of 2711 cases identified through review of secondary data sources, 14 (0.5%) were previously unreported to public health. The largest yield of unreported cases was identified through review of laboratory records; 13 of the 14 unreported cases were identified, of which eight were found only through this method. Timeliness of reporting varied between sites from a median of 7 days to a median of 38 days. The number of cases with delayed reporting varied from 5% to 53% between sites. Factors associated with delayed reporting included infectiousness, type of provider, diagnosing provider, and reporting source. Conclusions: Through a review of several different secondary data sources, few unreported TB cases were detected; however, timeliness of reporting was poor among the reported cases.

Use of rifampin is required for short-course treatment regimens for tuberculosis. Tuberculosis caused by isolates of M. tuberculosis with resistance to rifampin and susceptibility to isoniazid is unusual, but it has been recognized through surveillance. Patients with tuberculosis (cases) with rifampin monoresistance were compared with HIV-matched controls with tuberculosis caused by a drug-susceptible isolate. A total of 77 cases of rifampin mono-resistant tuberculosis were identified in this multicenter study. Three were determined to be laboratory contaminants, and 10 cases had an epidemiologic link to a case with rifampin mono-resistant tuberculosis, suggesting primary acquisition of rifampin-resistant isolates. Of the remaining 64 cases and 126 controls, there was no difference between cases and controls with regard to age, sex, race, foreign birth, homelessness, or history of incarceration. Cases were more likely to have a history of prior tuberculosis than were controls. Of the 38 cases and 74 controls with HIV infection, there was no difference between cases and controls with regard to age, sex, race, foreign birth, homelessness, history of incarceration, or prior tuberculosis. Cases were more likely to have histories of diarrhea, rifabutin use, or antifungal therapy. Laboratory analysis of available isolates showed that there was no evidence of spread of a single clone of M. tuberculosis. Further studies are needed to identify the causes of the development of rifampin resistance in HIV-infected persons with tuberculosis and to develop strategies to prevent its emergence. Ridzon R, Whitney CG, McKenna MT, Taylor JP, Ashkar SH, Nitta AT, Harvey SM, Valway S, Woodley C, Cooksey R, Onorato IM. Risk factors for rifampin mono-resistant tuberculosis. AM J RESPIR CRIT CARE MED 1998;157:1881‐1884.

Despite the long-standing observation that tuberculosis (TB) case rates are higher among racial and ethnic minorities than whites in the United States (U.S.), the proportion of this increased risk attributable to socioeconomic status (SES) has not been determined. Values for six SES indicators (crowding, income, poverty, public assistance, unemployment, and education) were assigned to U.S. TB cases reported from 1987-1993 by ZIP code- and demographic-specific matching to 1990 U.S. Census data. TB risk between racial/ethnic groups was then evaluated by quartile for each SES indicator utilizing univariate and Poisson multivariate analyses. Relative risk (RR) of TB increased with lower SES quartile for all six SES indicators on univariate analysis (RRs 2.6-5.6 in the lowest versus highest quartiles). The same trend was observed in multivariate models containing individual SES indicators (RRs 1.8-2.5) and for three SES indicators (crowding, poverty, and education) in the model containing all six indicators. Tuberculosis risk increased uniformly between SES quartile for each indicator except crowding, where risk was concentrated in the lowest quartile. Adjusting for SES accounted for approximately half of the increased risk of TB associated with race/ethnicity among U.S.-born blacks, Hispanics, and Native Americans. Even more of this increased risk was accounted for in the final model, which also adjusted for interaction between crowding and race/ethnicity. SES impacts TB incidence via both a strong direct effect of crowding, manifested predominantly in overcrowded settings, and a TB-SES health gradient, manifested at all SES levels. SES accounts for much of the increased risk of TB previously associated with race/ethnicity.

Introduction The goal of this study is to establish a predictive model of cytotoxic therapy that incorporates in vitro drug pharmacokinetics and cell-scale therapy response data, on a cell-line specific basis. We report on a series of time-resolved fluorescence microscopy experiments to characterize the uptake of doxorubicin and its effect on the population dynamics of MDA-MB-231 cells, a model of triple negative breast cancer. Experimental Design We leveraged the intrinsic fluorescence of doxorubicin to measure its uptake by MDA-MB-231 cells. Cells, labeled with a fluorescent nuclear marker, were seeded in microtiter plates and incubated with doxorubicin concentrations ranging from 10 nM to 10 μM for 6, 12, or 24 hours. These plates were imaged daily via bright field and fluorescent microscopy after addition of doxorubicin. Nuclei were segmented and automatically counted to quantify cell population size. Counts were normalized to population size at time of treatment and converted to population doublings. On a separate channel, extracellular, cytoplasmic, and nuclear doxorubicin fluorescence were quantified. A compartment model describing the movement of doxorubicin from the extracellular space into cells was fit to these data. We then constructed a cell treatment response model and fit it, coupled with the compartment model, to the population data using MATLAB. Results MDA-MB-231 cellular response to doxorubicin was tightly linked to both drug concentration and exposure time. Higher doses (> 1 μM) invariably induced rapid cell death. Smaller doses (< 1 μM) induced a concentration-dependent nonlinear response defined by an initial increase in population size that, depending on exposure time, was followed by a protracted decrease in cell number. For example, when treated with 156 nM for 6, 12, and 24 hours, we observed, respectively, an average of 2.6, 2.1, and 0.67 population doublings over the first 150 hours after treatment (p < 0.05 among groups). These populations then either held stable or receded out to 400 hours, when we observed net population doublings of 2.6, 1.7, and 0.037, respectively (p < 0.05). Untreated cells followed a logistic growth pattern, with an average total of 4.4 population doublings. Conclusion These time-resolved treatment protocols replicate clinically observed pharmacokinetics of cytotoxic therapies more closely than the constant concentrations in previous dose-response assays. By explicitly considering both drug and population dynamics, our mathematical model enables exploration, in silico, of treatment protocols intractable experimentally. Predictions from model simulations can then be tested experimentally, hopefully allowing for computationally-optimized and experimentally validated treatment regimens that maximize cytotoxic effects of doxorubicin. Citation Format: Matthew T. McKenna, Stephanie L. Barnes, Abigail Searfoss, Darren R. Tyson, Erin Rericha, Vito Quaranta, Thomas E. Yankeelov. Multiscale treatment response model for triple-negative breast cancer linking drug pharmacokinetics to tumor cell population dynamics. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 776.

As part of a larger cervical cancer study, we tried to verify the Pap smear histories for 125 black women with cervical cancer. For 105 of the patients, we identified all possible providers for the five-year period before the calendar year of diagnosis. Agreement between the medical records and the patient reports was poor to fair (kappa = 0.34) for whether the patient had a Pap smear in the three-year period before diagnosis. Patients tended to report far more Pap smears than medical records confirmed. Important determinants of agreement were the number of Pap smears reported during the five-year period and the age of the patient. The older the patient and the more Pap smears reported, the larger the discrepancy between the medical record and her self-report. The medical records did not contain enough data for us to complete an investigation of the possible reasons for this disagreement. Our results suggest these implications: (1) clinicians should strongly consider performing Pap smears if they doubt a patient's screening history, and (2) Pap smear registries are required for reliable and efficient evaluations of cervical cancer control programs because neither the patient report nor medical records are adequate.

Tobacco use is the leading preventable cause of death and disease in the world; yet little is known about the levels or patterns of youth tobacco use on a global basis. The purpose of this paper is to focus on change in youth tobacco use using data from 100 sites that have conducted repeat Global Youth Tobacco Surveys (GYTS). The GYTS is a school-based survey that collects data from students aged 13–15 years using a standardized methodology for constructing the sample frame, selecting schools and classes, and processing data. GYTS is conducted in school classes using self-administered anonymous data collection. The GYTS sample produces representative, independent, cross-sectional estimates for each sampling frame. Of the 100 sites surveyed, 61 reported no change over time in prevalence of cigarette smoking, likewise in 50 of the 97 sites with data on use of other tobacco products there was no change. However, 34 sites reported an increase in other tobacco use. This appears to be attributed to waterpipe, an emerging trend in tobacco use. Evidence was found supporting the idea that tobacco use among adolescent girls is likely increasing. The global tobacco control effort continues to face many challenges in reversing the tobacco epidemic. Few countries have implemented comprehensive tobacco control legislation laid out by the World Health Organization. The few countries that have adopted some of these proven policies can serve as examples in achieving positive results in curbing the tobacco epidemic. (Global Health Promotion, 2009; Supp (2): pp. 38–90)

For adults and adolescents (i.e., persons aged/=13 years), the human immunodeficiency virus (HIV) infection classification system and the surveillance case definitions for HIV infection and acquired immunodeficiency syndrome (AIDS) have been revised and combined into a single case definition for HIV infection. In addition, the HIV infection case definition for children aged13 years and the AIDS case definition for children aged 18 months to13 years have been revised. No changes have been made to the HIV infection classification system, the 24 AIDS-defining conditions for children aged13 years, or the AIDS case definition for children aged18 months. These case definitions are intended for public health surveillance only and not as a guide for clinical diagnosis. Public health surveillance data are used primarily for monitoring the HIV epidemic and for planning on a population level, not for making clinical decisions for individual patients. CDC and the Council of State and Territorial Epidemiologists recommend that all states and territories conduct case surveillance of HIV infection and AIDS using the 2008 surveillance case definitions, effective immediately.

Purpose To review the history and challenges of "burden of disease" studies, how these are dependent on robust epidemiologic data as well as complex conceptual constructions, and to identify the public health policy issues these studies can most usefully inform. Methods The emergence of the concept of the "burden of disease" in the public health literature is reviewed, with a focus on the results of an analysis of data from the United States that used the methodology presented in the Global Burden of Disease Study. Results The systematic analysis of public health mortality data to identify major health problems was conducted by Graunt in 16th-century London. He found that many of the predominant sources of mortality were not the focus of public attention. Today, despite refinements in epidemiologic measurement methods designed to capture the impact of non-fatal health conditions, there are similar incongruities between the major public health problems and expenditures on prevention interventions. Conclusions Controversies surrounding the interpretation of "burden of disease" studies are not new. Particularly in developed countries, these studies appear more useful for setting research priorities rather than allocating resources to support prevention efforts. Such investigations are not possible without ongoing support for systematic collection and analysis of descriptive epidemiologic data.

Context Incidence of human immunodeficiency virus (HIV) in the United States has not been directly measured. New assays that differentiate recent vs long-standing HIV infections allow improved estimation of HIV incidence. Objective To estimate HIV incidence in the United States. Design, Setting, and Patients Remnant diagnostic serum specimens from patients 13 years or older and newly diagnosed with HIV during 2006 in 22 states were tested with the BED HIV-1 capture enzyme immunoassay to classify infections as recent or long-standing. Information on HIV cases was reported to the Centers for Disease Control and Prevention through June 2007. Incidence of HIV in the 22 states during 2006 was estimated using a statistical approach with adjustment for testing frequency and extrapolated to the United States. Results were corroborated with back-calculation of HIV incidence for 1977-2006 based on HIV diagnoses from 40 states and AIDS incidence from 50 states and the District of Columbia. Main Outcome Measure Estimated HIV incidence. Results An estimated 39 400 persons were diagnosed with HIV in 2006 in the 22 states. Of 6864 diagnostic specimens tested using the BED assay, 2133 (31%) were classified as recent infections. Based on extrapolations from these data, the estimated number of new infections for the United States in 2006 was 56 300 (95% confidence interval [CI], 48 200-64 500); the estimated incidence rate was 22.8 per 100 000 population (95% CI, 19.5-26.1). Forty-five percent of infections were among black individuals and 53% among men who have sex with men. The back-calculation (n = 1.230 million HIV/AIDS cases reported by the end of 2006) yielded an estimate of 55 400 (95% CI, 50 000-60 800) new infections per year for 2003-2006 and indicated that HIV incidence increased in the mid-1990s, then slightly declined after 1999 and has been stable thereafter. Conclusions This study provides the first direct estimates of HIV incidence in the United States using laboratory technologies previously implemented only in clinic-based settings. New HIV infections in the United States remain concentrated among men who have sex with men and among black individuals.

Public health surveillance is the basis for evidence-based action. Case surveillance for AIDS was critical in the early 1980s to understand the scope and impact of the epidemic, and multiple systems to monitor the epidemic have evolved during the past 25 years.1 The changes in surveillance systems and practices have occurred in response to improved understanding of the pathogenesis and treatment of HIV infection, and to emerging needs for data to monitor the epidemic and to direct prevention, care, and research programs. In 2000, the Centers for Disease Control and Prevention (CDC) described a strategy for the development of an integrated approach to HIV surveillance, to respond to changes in the epidemic and associated data needs.2 This approach envisioned a basic platform of HIV case surveillance in all U.S. states, with supplemental surveillance projects in states and cities more heavily impacted by the HIV epidemic. In this issue of Public Health Reports, a series of reports describes progress toward the implementation of multiple new surveillance approaches that will provide information on the leading edge of the epidemic. These new systems focus on earlier events in the natural history of HIV; recognize the critical contributions of therapy, both for the health of the individual and as part of an integrated prevention approach; and relate to new prevention initiatives being conducted by CDC's prevention partners. New HIV surveillance systems focus on earlier events in the natural history of HIV than historical systems. AIDS case surveillance was implemented by all U.S. states by the early 1980s;3 before the availability of highly active antiretroviral therapy (HAART), AIDS diagnosis bore a predictable, though distant, relationship to earlier HIV infection.4 The broad availability of HAART has fortunately resulted in a disruption of the predictable progression from early HIV infection to AIDS by vastly increasing the interval between these two stages of the disease for those who enter care and receive therapy.5 Thus, HIV public health surveillance systems must collect information on earlier events in the course of an HIV infection: behaviors that put uninfected people at risk for HIV infection, incident HIV infections, first diagnoses of HIV infection, and entry into medical care. In response to these needs, new systems for monitoring behaviors6 and HIV incidence7 are currently underway, and CDC has recently recommended that all states collect data on first HIV diagnoses by use of named identifiers.8,9 Effective therapy for HIV infection has changed the characteristics of the epidemic in the United States. As HAART has become broadly available, the number of persons living with HIV infection in the U.S. has increased steadily.10 Benefits of appropriate therapy accrue to people living with HIV infection, and also the greater community, because risk of transmission of HIV infection is greatly lowered in the setting of undetectable viral load.11 Accordingly, effective surveillance systems require data on access to and quality of care and prevention services for the increasing number of people living with HIV infection. In response, CDC and state surveillance partners are deploying a new system—the Medical Monitoring Project (MMP)—to describe needs for and use of care and prevention services for people who are in care for HIV infection.12 This system builds on the history of population-based clinical outcomes evaluation established by the Health Care Services and Utilization Survey (HCSUS),13,14 and on pilot studies of population-based approaches to clinical outcomes surveillance conducted by CDC and the Health Resources and Services Administration (HRSA).15 A complementary surveillance system will help provide an understanding of the characteristics of those HIV-infected people who have never received care for their HIV infection, and barriers to entry into care.16 A new surveillance system for drug resistance will provide information about prevalent resistance patterns that may threaten the long-term benefits of antiretroviral therapy in the population.17 Finally, CDC has launched new prevention approaches, and has developed new surveillance systems to help determine the impact of these approaches in communities. For example, the Advancing HIV Prevention (AHP) initiative calls for increased access to and use of HIV testing.18 The National HIV Behavioral Surveillance System will provide a means to describe HIV testing behaviors among the highest-risk populations in major U.S. cities,19,20 and a new post-marketing surveillance system has provided data on the uptake of rapid HIV tests by HIV prevention providers, and on field performance of rapid HIV tests.21 AHP also brings focus to the provision of prevention services as part of medical care to people living with HIV infection. MMP will collect data on the needs and receipt of prevention services for people living with HIV infection.12 Finally, CDC continues to focus on the dissemination of prevention interventions of proven efficacy.22,23 It is critical to determine whether these proven effective interventions are reaching those at highest risk for HIV infection. The National HIV Behavioral Surveillance System allows state public health officials to understand the extent to which effective prevention interventions are reaching those people with the greatest behavioral risks.20 The collection and use of public health surveillance data is a public trust. For HIV and AIDS case surveillance, the collection of data for the purposes of disease control does not require consent, and the Health Insurance Portability and Privacy Act specifically allows for the collection of such data.24 For other supplemental surveillance projects, such as interview studies, consent is obtained, and mechanisms to assure ethics oversight and the protection of human subject are in place.25 In either case, it is incumbent on those who work in these diverse HIV surveillance activities to protect the confidentiality of data collected; to ensure that data collected are most relevant for use in local prevention planning and resource planning; to ensure that the data are available to the community for these purposes; and to ensure that personally identifiable data are protected, and used only for public health purposes.26 The surveillance systems described in this special issue of Public Health Reports will be the systems that inform prevention and care planning into the fourth decade of the AIDS epidemic in the U.S. CDC continues to work with public health partners to implement systems that will paint a picture of the cutting edge of the epidemic, and that honor the public trust to use these data to achieve greater control of the HIV epidemic.

We analyzed national surveillance data that had been reported to the Centers for Disease Control and Prevention to elucidate the impact of recent clinical and public health efforts to further decrease the number of human immunodeficiency virus (HIV) infections and resulting morbidity caused by perinatal transmission. Long-term trends in pediatric (ages, 0-13 years), perinatal acquired immune deficiency syndrome (AIDS) cases were analyzed by log-linear Poisson regression for the period 1992-2004. Estimates for the number of perinatal HIV infections that occurred during the more recent period of 2001-2004 were developed by extrapolation from the 33 states with ongoing HIV (non-AIDS) reporting to the entire United States with the use of a probabilistic model. The number of pediatric perinatal AIDS cases that were identified decreased from 858 in 1992 to only 41 in 2004. These declines were consistent across demographic and regional subgroups. Data on the number of perinatal HIV infections suggests ongoing declines throughout the early years of the 21st century from 277 (95% CI, 224-346) in 2001 to 138 (95% CI, 96-186) in 2004. The incidence and morbidity associated with perinatal HIV infection continue to decline. To ensure that existing prevention efforts continue to achieve control of these infections, consistent methods of public health surveillance must be instituted throughout the entire United States.

Background Burden of disease studies have been implemented in many countries using the Disability-Adjusted Life Year (DALY) to assess major health problems. Important objectives of the study were to quantify intra-country differentials in health outcomes and to place the United States situation in the international context. Methods We applied methods developed for the Global Burden of Disease (GBD) to data specific to the United States to compute Disability-Adjusted Life Years. Estimates are provided by age and gender for the general population of the United States and for each of the four official race groups: White; Black; American Indian or Alaskan Native; and Asian or Pacific Islander. Several adjustments of GBD methods were made: the inclusion of race; a revised list of causes; and a revised algorithm to allocate cardiovascular disease garbage codes to ischaemic heart disease. We compared the results of this analysis to international estimates published by the World Health Organization for developed and developing regions of the world. Results In the mid-1990s the leading sources of premature death and disability in the United States, as measured by DALYs, were: cardiovascular conditions, breast and lung cancers, depression, osteoarthritis, diabetes mellitus, and alcohol use and abuse. In addition, motor vehicle-related injuries and the HIV epidemic exacted a substantial toll on the health status of the US population, particularly among racial minorities. The major sources of death and disability in these latter populations were more similar to patterns of burden in developing rather than developed countries. Conclusion Estimating DALYs specifically for the United States provides a comprehensive assessment of health problems for this country compared to what is available using mortality data alone.