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Toshihiko Kaise,1 Eishin Sakihara,2 Kentaro Tamaki,3 Hiroaki Miyata,4 Norimichi Hirahara,4 Oksana Kirichek,5 Ryosuke Tawara,1 Shoko Akiyama,1 Masayuki Katsumata,1 Mei Haruya,6 Takeo Ishii,7 Edgar P Simard,8 Bruce E Miller,8 Ruth Tal-Singer8 1Japan Development, GSK, Tokyo, Japan; 2Lifestyle Related Disease Medical Center, Naha Medical Association, Okinawa, Japan; 3Department of Breast Surgery, Nahanishi Clinic, Okinawa, Japan; 4Health Policy and Management, School of Medicine, Keio University, Tokyo, Japan; 5Value Evidence and Outcomes, GSK, Stockley Park, UK; 6Government Affairs and Market Access, GSK, Tokyo, Japan; 7Medical Japan, GSK, Tokyo, Japan; 8Value Evidence and Outcomes, GSK, Collegeville, PA, USACorrespondence: Toshihiko KaiseJapan Development, GSK, Tokyo, JapanTel +81 80 5927 9500Fax +81 3 4231 5993Email toshihiko.kaise@gsk.comPurpose: Many individuals with obstructive airway disease (OAD), including chronic obstructive pulmonary disease (COPD) and asthma, remain undiagnosed, despite the potential for reducing disease burden through early detection and treatment. OCEAN aimed to determine the prevalence of, and characteristics associated with, impaired lung function in a Japanese population, with the goal of improving strategies for early OAD detection.Methods: OCEAN was an observational, cross-sectional study in sequentially recruited Japanese individuals ≥ 40 years of age undergoing routine health examinations. Participants completed screening questionnaires and spirometry testing. Airflow limitation was defined as forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 0.7 by pre-bronchodilator spirometry. Preserved ratio impaired spirometry (PRISm) was defined as FEV1/FVC ≥ 0.7 and FEV1 < 80% predicted. The primary endpoint was prevalence of spirometry-based airflow limitation and PRISm. The characteristics of study participants were reported as secondary endpoints.Results: Overall, 2518 individuals were included; 79% were < 60 years of age (mean 52.0 years). Airflow limitation and PRISm were observed in 52 (2.1%) and 420 (16.7%) participants, respectively. FEV1 in the PRISm group was between that in the no airflow limitation/PRISm and airflow limitation groups, FVC was similar in the PRISm and airflow limitation groups. The PRISm group had higher mean body mass index and a higher proportion of comorbid metabolic disease compared with the airflow limitation group. The prevalence of airflow limitation and PRISm was highest among current smokers (3.9% and 21.3%, respectively) versus former or never smokers.Conclusion: A significant proportion of Japanese individuals < 60 years of age attending their annual health examination had impaired lung function (airflow limitation and PRISm); prevalence was highest among current smokers. These findings support screening of current or former smokers ≥ 40 years of age using patient-reported questionnaires to inform the need for spirometry to confirm an OAD diagnosis.Keywords: CAPTURE, CAAT, PRISm, COPD-Q, Japan, airflow limitation

Hana Müllerová,1 Beth Hahn,2 Edgar P Simard,3 George Mu,3 Umur Hatipoğlu4 1Real-World Evidence, GSK, Stockley Park, Uxbridge, Middlesex, UK; 2US Medical Affairs, GSK, Research Triangle Park, NC, USA; 3Real-World Data and Analytics, GSK, Upper Providence, PA, USA; 4Center for Comprehensive Care in Chronic Obstructive Pulmonary Disease, Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA Purpose: Current understanding of the relationship between COPD phenotype and health care resource utilization (HCRU) is limited. This real-world study evaluated disease burden and HCRU for COPD subgroups prone to exacerbation as defined by blood eosinophil (EOS) count and multiple inhaler triple therapy (MITT) use.Methods: This was a large-scale, retrospective, longitudinal, observational cohort study using data from the US IBM Watson Explorys real-world database (GSK Study HO-17-18395). The population of interest comprised patients with COPD ≥40 years of age with ≥2 moderate or ≥1 severe exacerbations (prior year) while on inhaled maintenance therapy, with ≥1 blood EOS count. Data were analyzed during the year prior to index date (last COPD encounter between January 1, 2011 and December 31, 2016). Four subgroups were analyzed based on a combination of EOS counts (

Background: The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updates on cancer incidence and death rates and trends in these outcomes for the United States. This year's report includes incidence trends for human papillomavirus (HPV)-associated cancers and HPV vaccination (recommended for adolescents aged 11-12 years).Methods: Data on cancer incidence were obtained from the CDC, NCI, and NAACCR, and data on mortality were obtained from the CDC. Long- (1975/1992-2009) and short-term (2000-2009) trends in age-standardized incidence and death rates for all cancers combined and for the leading cancers among men and among women were examined by joinpoint analysis. Prevalence of HPV vaccination coverage during 2008 and 2010 and of Papanicolaou (Pap) testing during 2010 were obtained from national surveys.Results: Death rates continued to decline for all cancers combined for men and women of all major racial and ethnic groups and for most major cancer sites; rates for both sexes combined decreased by 1.5% per year from 2000 to 2009. Overall incidence rates decreased in men but stabilized in women. Incidence rates increased for two HPV-associated cancers (oropharynx, anus) and some cancers not associated with HPV (eg, liver, kidney, thyroid). Nationally, 32.0% (95% confidence interval [CI] = 30.3% to 33.6%) of girls aged 13 to 17 years in 2010 had received three doses of the HPV vaccine, and coverage was statistically significantly lower among the uninsured (14.1%, 95% CI = 9.4% to 20.6%) and in some Southern states (eg, 20.0% in Alabama [95% CI = 13.9% to 27.9%] and Mississippi [95% CI = 13.8% to 28.2%]), where cervical cancer rates were highest and recent Pap testing prevalence was the lowest.Conclusions: The overall trends in declining cancer death rates continue. However, increases in incidence rates for some HPV-associated cancers and low vaccination coverage among adolescents underscore the need for additional prevention efforts for HPV-associated cancers, including efforts to increase vaccination coverage. [ABSTRACT FROM AUTHOR]

Objectives: To support development of a robust postmarket device evaluation system using real-world data (RWD) from electronic health records (EHRs) and other sources, employing unique device identifiers (UDIs) to link to device information., Methods: To create consistent device-related EHR RWD across 3 institutions, we established a distributed data network and created UDI-enriched research databases (UDIRs) employing a common data model comprised of 24 tables and 472 fields. To test the system, patients receiving coronary stents between 2010 and 2019 were loaded into each institution's UDIR to support distributed queries without sharing identifiable patient information. The ability of the system to execute queries was tested with 3 quality assurance checks. To demonstrate face validity of the data, a retrospective survival study of patients receiving zotarolimus or everolimus stents from 2012 to 2017 was performed using distributed analysis. Propensity score matching was used to compare risk of 6 cardiovascular outcomes within 12 months postimplantation., Results: The test queries established network functionality. In the analysis, we identified 9141 patients (Mercy = 4905, Geisinger = 4109, Intermountain = 127); mean age 65 ± 12 years, 69% males, 23% zotarolimus. Separate matched analyses at the 3 institutions showed hazard ratio estimates (zotarolimus vs everolimus) of 0.85-1.59 for subsequent percutaneous coronary intervention ( P  = .14-.52), 1.06-2.03 for death ( P  = .16-.78) and 0.94-1.40 for the composite endpoint ( P  = .16-.62)., Discussion: The analysis results are consistent with clinical studies comparing these devices., Conclusion: This project shows that multi-institutional data networks can provide clinically relevant real-world evidence via distributed analysis while maintaining data privacy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Use of existing data in electronic health records (EHRs) could be used more extensively to better leverage real world data for clinical studies, but only if standard, reliable processes are developed. Numerous computable phenotypes have been validated against manual chart review, and common data models (CDMs) exist to aid implementation of such phenotypes across platforms and sites. Our objective was to measure consistency between data that had previously been manually collected for an implantable cardiac device registry and CDM-based phenotypes for the condition of heart failure (HF)., Methods: Patients enrolled in an implantable cardiac device registry at two hospitals from 2013 to 2018 contributed to this analysis wherein registry data were compared to PCORnet CDM-formatted EHR data. Seven different phenotype algorithms were used to search for the presence of HF and compare the results with the registry. Sensitivity, specificity, predictive value and congruence were calculated for each phenotype., Results: In the registry, 176 of 319 (55%) patients had history of HF, compared with different phenotypes estimating between 96 (30%) and 188 (59%). The least-restrictive phenotypes (any diagnosis) had high sensitivity and specificity (90%/80%), but more restrictive phenotypes had higher specificity (e.g., code present in problem list, 94%). Differences were observed using time-based criteria (e.g., days between visit diagnoses) and between participating hospitals., Conclusions: Consistency between manually-collected registry data and CDM-based phenotypes for history of HF was high overall, but use of different phenotypes impacted sensitivity and specificity, and results may differ depending on the medical condition of interest., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Several authors (AI, JM, KW, KS, KS, ES) are employed by and own shares in Medtronic plc.]., (© 2022 The Authors.)

Purpose: A considerable proportion of patients with chronic obstructive pulmonary disease (COPD) remain undiagnosed and untreated even though they may have a burden of respiratory symptoms that impact quality of life. The OCEAN study assessed the ability of screening questionnaires to identify individuals with, or at risk of, COPD by comparing questionnaire outcomes with spirometric measures of lung function., Methods: This observational study included participants ≥40 years of age presenting for their annual health examination at a single medical center in Okinawa, Japan. Participants completed COPD screening questionnaires (CAPTURE and COPD-Q), the Chronic Airways Assessment Test (CAAT), and general demographic and health-related questionnaires. The performance characteristics of CAPTURE and COPD-Q were compared with spirometry-based airflow limitation by calculating the area under the receiver operating characteristic (ROC-AUC) curve., Results: A total of 2518 participants were included in the study; 79% of whom were <60 years of age (mean 52.0 years). A total of 52 (2.1%) participants had airflow limitation defined as forced expiratory volume in 1 second (FEV 1 )/forced vital capacity (FVC) <0.7, and 420 (16.7%) participants were classified as Preserved Ratio Impaired Spirometry (PRISm). Among participants with PRISm, 75 (17.9%) had a CAAT total score ≥10. Airflow limitation and PRISm were more prevalent in current smokers versus past smokers. For the CAPTURE questionnaire, ROC-AUC for screening airflow limitation, PRISm, and PRISm with a CAAT total score ≥10 were 0.59, 0.55, and 0.69, respectively; for COPD-Q, these three clinical features were 0.67, 0.58 and 0.68, respectively., Conclusion: This study demonstrated that CAPTURE and COPD-Q appear to be effective screening tools for identifying symptomatic individuals with undiagnosed, or at risk of developing COPD in adults ≥40 years of age in Okinawa. Furthermore, early diagnosis and management of PRISm is important to improve future outcomes and the societal burden of disease., Competing Interests: Kentaro Tamaki, Eishin Sakihara, Hiroaki Miyata, and Norimichi Hirahara belong to the association/institution that received funding for this study from GSK. Takeo Ishii, Shoko Akiyama, Toshihiko Kaise, Masayuki Katsumata and Ryosuke Tawara are employees of GSK and hold shares in GSK. Mei Haruya, Oksana Kirichek and Edgar P. Simard are former employees of GSK. Bruce E. Miller and Ruth Tal-Singer are former employees of GSK and hold shares in GSK. Ruth Tal-Singer reports personal fees from Ena Respiratory, Immunomet, Vocalis Health, and Teva. The authors report no other conflicts of interest in this work., (© 2021 Tamaki et al.)

Background: Highly active antiretroviral therapy (HAART) has extended the life expectancy of patients with HIV/AIDS to approach that of the general population. However, it remains unclear whether HIV infection affects the survival of patients with lymphoma in the HAART era. Methods: Patients diagnosed with Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, peripheral T-cell lymphoma (PTCL), or follicular lymphoma during 2004-2011 were identified from the National Cancer Database. Survival analyses were conducted, where each HIV-infected patient was propensity score matched to a HIV-uninfected patient on the basis of demographic factors, clinical features, and treatment characteristics. Results: Among 179,520 patients, the prevalence of HIV-infection ranged from 1.0% for follicular lymphoma, 3.3% for PTCL, 4.7% for Hodgkin lymphoma, 5.4% for DLBCL, to 29% for Burkitt lymphoma. HIV infection was significantly associated with inferior overall survival for patients with each lymphoma subtype: Hodgkin lymphoma [HR, 1.47; 95% confidence interval (CI), 1.25-1.74], DLBCL (HR, 1.95; 95% CI, 1.80-2.11), Burkitt lymphoma (HR, 1.46; 95% CI, 1.24-1.73), PTCL (HR, 1.43; 95% CI, 1.14-1.79), and follicular lymphoma (HR, 1.44; 95% CI, 1.04-2.00). Conclusions: HIV/AIDS continues to be independently associated with increased risk of death among patients with lymphoma in the HAART era in the United States, and the association varies by lymphoma histologic subtype. Impact: Examination of effective management strategies for patients with HIV/AIDS-associated lymphoma and enrollment of patients in prospective clinical trials are needed to improve patient outcomes. Cancer Epidemiol Biomarkers Prev; 26(3); 303-11. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Background: Little data exists regarding the effectiveness and safety of rivaroxaban or apixaban versus warfarin in nonvalvular atrial fibrillation (NVAF) patients treated outside of clinical trials., Methods: This was a retrospective study using MarketScan claims from January 2012 to October 2014. We included adults, newly initiated on rivaroxaban, apixaban or warfarin, with a baseline CHA 2 DS 2 -VASc score ≥2, ≥2 diagnosis codes for NVAF and ≥180 days of continuous medical and prescription benefits. Patients with a prior stroke, systemic embolism or intracranial hemorrhage (ICH) were excluded. Eligible rivaroxaban or apixaban users were 1:1 propensity-score matched individually to warfarin users. Cox regression was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for rivaroxaban and apixaban versus warfarin for the combined endpoint of ischemic stroke or ICH and each endpoint individually., Results: Upon matching 11,411 rivaroxaban to 11,411 warfarin users, rivaroxaban was associated with a significant reduction of the combined endpoint of ischemic stroke or ICH versus warfarin (HR = 0.61, 95% CI = 0.45-0.82). ICH was significantly (HR = 0.53, 95% CI = 0.35-0.79) and ischemic stroke nonsignificantly reduced (HR = 0.71, 95% CI = 0.47-1.07) by rivaroxaban versus warfarin. After matching 4083 apixaban and 4083 warfarin users, apixaban was found to nonsignificantly reduce the combined endpoint of ischemic stroke or ICH versus warfarin (HR = 0.63, 95% CI = 0.35-1.12) and to reduce ICH risk (HR = 0.38, 95% CI = 0.17-0.88). Ischemic stroke risk was nonsignificantly increased with apixaban (HR = 1.13, 95% CI = 0.49-2.63) versus warfarin., Limitations: Sample size and number of combined events observed were relatively small. Residual confounding could not be ruled out., Conclusions: Rivaroxaban and apixaban were associated with less ICH than warfarin and both are likely associated with reductions in the combined endpoint. Further investigation to validate the numerically higher rate of ischemic stroke with apixaban versus warfarin is required.

Background: Patients with cancer who are infected with the human immunodeficiency virus (HIV) are less likely to receive cancer treatment compared with HIV-uninfected individuals. However, to the authors' knowledge, the impact of insurance status and comorbidities is unknown., Methods: Data from the National Cancer Data Base were used to study nonelderly adults diagnosed with several common cancers from 2003 to 2011. Cancer treatment was defined as chemotherapy, surgery, radiotherapy, or any combination during the first course of treatment. Multivariate logistic regression was used to examine associations between HIV status and lack of cancer treatment, and identify predictors for lack of treatment among HIV-infected patients., Results: A total of 10,265 HIV-infected and 2,219,232 HIV-uninfected cases were included. In multivariate analysis, HIV-infected patients with cancer were found to be more likely to lack cancer treatment for cancers of the head and neck (adjusted odds ratio [aOR], 1.48; 95% confidence interval [95% CI], 1.09-2.01), upper gastrointestinal tract (aOR, 2.62; 95% CI, 2.04-3.37), colorectum (aOR, 1.70; 95% CI, 1.17-2.48), lung (aOR, 2.46; 95% CI, 2.19-2.76), breast (aOR, 2.14; 95% CI, 1.16-3.98), cervix (aOR, 2.81; 95% CI, 1.77-4.45), prostate (aOR, 2.16; 95% CI, 1.69-2.76), Hodgkin lymphoma (aOR, 1.92; 95% CI, 1.66-2.22), and diffuse large B-cell lymphoma (aOR, 1.82; 95% CI, 1.65-2.00). Predictors of a lack of cancer treatment among HIV-infected individuals varied by tumor type (solid tumor vs lymphoma), but black race and a lack of private insurance were found to be predictors for both groups., Conclusions: In the United States, HIV-infected patients with cancer appear to be less likely to receive cancer treatment regardless of insurance and comorbidities. To the authors' knowledge, the current study is the largest study of cancer treatment in HIV-infected patients with cancer in the United States and provides evidence of cancer treatment disparities even after controlling for differences with regard to insurance status and comorbidities. Further work should focus on addressing differential cancer treatment. Cancer 2016;122:2399-2407. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Objective: Non-AIDS-defining cancers (NADCs) have emerged as significant contributors to cancer mortality and morbidity among persons living with HIV (PLWH). Because NADCs are also associated with many social and behavioural risk factors that underlie HIV, determining the extent to which each of these factors contributes to NADC risk is difficult. We examined cancer incidence and mortality among persons with a history of incarceration, because distributions of other cancer risk factors are likely similar between prisoners living with HIV and non-infected prisoners., Design: Registry-based retrospective cohort study., Participants: Cohort of 22,422 persons incarcerated in Georgia, USA, prisons on 30 June 1991, and still alive in 1998., Outcome Measures: Cancer incidence and mortality were assessed between 1998 and 2009, using cancer and death registry data matched to prison administrative records. Age, race and sex-adjusted standardised mortality and incidence ratios, relative to the general population, were calculated for AIDS-defining cancers, viral-associated NADCs and non-infection-associated NADCs, stratified by HIV status., Results: There were no significant differences in cancer mortality relative to the general population in the cohort, regardless of HIV status. In contrast, cancer incidence was elevated among the PLWH. Furthermore, incidence of viral-associated NADCs was significantly higher among PLWH versus those without HIV infection (standardised incidence ratio=6.1, 95% CI 3.0 to 11.7, p<0.001)., Conclusions: Among PLWH with a history of incarceration, cancer incidence was elevated relative to the general population, likely related to increased prevalence of oncogenic viral co-infections. Cancer prevention and screening programmes within prisons may help to reduce the cancer burden in this high-risk population., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution., Methods: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol., Findings: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa., Interpretation: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks., Funding: Bill & Melinda Gates Foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development., Methods: We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time., Findings: Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries., Interpretation: Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions., Funding: Bill & Melinda Gates Foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: HIV-infected people are at increased risk of cancers of infectious origin. We estimated the burden of cancer attributable to infections among HIV-infected people in the United States in 2008., Design: Incidence rates for cancer sites associated with infections were estimated from record linkage between HIV/AIDS registries and cancer registries., Methods: Rates were applied to estimates of the population living with diagnosed HIV in the United States in 2008 to obtain the number of incident cancer cases. Site-specific attributable fractions and corresponding 95% confidence intervals (CIs) were estimated from infection prevalence among cancer cases. Infection prevalence data were derived from literature review of case series., Results: Of an estimated 6200 incident cancer cases (95% CI 6000-6500), 2500 (95% CI 2400-2700) were attributable to infection (attributable fraction = 40%, 95% CI 39-42). The most important infections were Kaposi sarcoma herpes virus, Epstein-Barr virus, and human papillomavirus, which together were responsible for 2200 new cancer cases (95% CI 2100-2400), mainly Kaposi sarcoma, lymphomas, and ano-genital cancers. The attributable fraction in HIV-infected people was highest in the age group 20-29 years (69%, 95% CI 65-72). MSM were the HIV transmission group with the highest attributable fraction (48%, 95% CI 46-50), due to the high incidence of both Kaposi sarcoma and anal cancer., Conclusion: The very high fraction of cancer attributable to infection in HIV-infected people points to special opportunities to prevent these cancers, that is, avoidance, detection, and early treatment of cancer-associated infections, and universal early detection and uninterrupted treatment of HIV infection to avoid immunosuppression.

Background: A positive association between recent Papanicolaou (Pap) test uptake and initiation of HPV vaccination among U.S. women has been reported. However, it is unknown whether recent Pap testing by HPV vaccination status varies by race/ethnicity. Discerning racial/ethnic variations is important given the higher prevalence of HPV types other than 16 and 18 in some racial/ethnic groups. We assessed whether uptake of recent Pap testing differed among women aged 21-30 years who had not initiated the HPV vaccination series versus those who had and whether this pattern differed by sociodemographic factors., Methods: 2008, 2010, and 2013 National Health Interview Survey data were used to generate weighted prevalence estimates and 95% confidence intervals (CIs) (n=7095). Adjusted predicted marginal models were used to generate adjusted prevalence ratios (aPRs) to assess the relationship between recent Pap test uptake and HPV vaccination series initiation by race/ethnicity., Results: The uptake of recent Pap testing among those who had not initiated the HPV vaccination series was significantly lower (81.0%) compared to those who had initiated vaccination (90.5%) (aPR=0.93, 95% CI: 0.90-0.96). This finding was consistent across most sociodemographic factors, though not statistically significant for Blacks, Hispanics, those with lower levels of education, or those with higher levels of income., Conclusion: Young women who had not initiated HPV vaccination were less likely to have had a recent Pap test compared to women who had initiated vaccination. Concerted efforts are needed to increase uptake of recommended cervical cancer screening and HPV vaccination among young women., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Importance: Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies., Objective: To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013., Evidence Review: The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs., Findings: In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries., Conclusions and Relevance: Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation.

Purpose: Although disparities in colorectal cancer (CRC) with regard to race, socioeconomic status, and geography are well documented, the extent to which these factors contribute to premature death resulting from CRC nationwide and by state is unknown., Patients and Methods: We calculated age-standardized CRC death rates for three broad educational categories as a marker of socioeconomic status by race/ethnicity and state among individuals age 25 to 64 years from 2008 through 2010. We also calculated the proportion of premature death resulting from CRC that could potentially be averted in each state by applying the average death rate for the five states with the lowest rates among the most educated whites (Connecticut, North Dakota, Utah, Vermont, and Wisconsin) to all populations., Results: Compared with those with the most education, those with the least education had significantly higher CRC death rates in virtually all states for each racial/ethnic group. For example, rate ratios ranged from 1.15 (95% CI, 0.66 to 2.01) in Delaware to 3.18 (95% CI, 2.01 to 5.05) in New Mexico among whites. Overall, half the premature deaths resulting from CRC that occurred nationwide from 2008 through 2010, or 7,690 deaths annually, would have been avoided if everyone had experienced the lowest death rates of the most educated whites. More premature deaths could be averted in southern states (60% to 70%) than in northern and western states (30% to 40%). Restricting the analyses to persons age 50 to 64 years, for whom CRC screening is recommended, resulted in similar findings., Conclusion: The majority of premature deaths from CRC in southern states and half these deaths nationwide are due to racial/ethnic, socioeconomic, and geographic inequalities., (© 2014 by American Society of Clinical Oncology.)

Background: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration., Methods: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets., Findings: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990., Interpretation: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action., Funding: Bill & Melinda Gates Foundation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To describe trends in country and sex-specific incidence rates of head and neck cancer (HNC), focusing on changes across calendar periods., Materials and Methods: Sex and country specific rates of HNC were calculated for 1998-2002 and 1983-1987 using population-based registry data assembled by the Cancer Incidence in Five Continents (CI5) data system for 83 registries representing 35 countries. HNCs were categorized into three groups: oral cavity (including tongue and mouth), oropharynx (including tonsil and oropharynx) and other HNC (including larynx and poorly-specified tumors of the lip/oral cavity/pharynx). Age-standardized rates per 100,000 persons were calculated using the 1960 world standard population. Changes in rates between 1998-2002 and 1993-1987 were assessed., Results: During these periods there was substantial global variation in HNC incidence trends by cancer site, country/registry and sex. Rates of oral cavity cancer increased among men and women in some European and Asian countries (Czech Republic, Slovak Republic, Denmark, Estonia, Finland, the United Kingdom and Japan). In France and Italy, rates declined among men but increased among women. Oral cavity incidence rates declined among men and women in many Asian registries as well as in Canada and the United States. Oropharyngeal cancer rates increased among both men and women in a number of European countries (Belarus, Czech Republic, Denmark, Finland, Iceland, Latvia, Norway and the United Kingdom) whereas they declined in some Asian countries. The largest increase in oropharyngeal rates was among Brazilian men. Rates of other HNCs varied substantially by country and sex., Conclusion: From 1983-1987 to 1998-2002, trends in HNC rates differed by subtype, country and sex. Oral cavity cancer incidence rates increased in many countries with tobacco epidemics that are currently peaking and declined in areas where tobacco use peaked some time ago. In contrast, rates of oropharyngeal cancer increased in a number of countries where tobacco use has declined, perhaps due to the emerging importance of human papillomavirus infection. Continued monitoring of trends in incidence rates is needed to inform global cancer prevention strategies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updates on cancer incidence and death rates and trends in these outcomes for the United States. This year's report includes the prevalence of comorbidity at the time of first cancer diagnosis among patients with lung, colorectal, breast, or prostate cancer and survival among cancer patients based on comorbidity level., Methods: Data on cancer incidence were obtained from the NCI, the CDC, and the NAACCR; and data on mortality were obtained from the CDC. Long-term (1975/1992-2010) and short-term (2001-2010) trends in age-adjusted incidence and death rates for all cancers combined and for the leading cancers among men and women were examined by joinpoint analysis. Through linkage with Medicare claims, the prevalence of comorbidity among cancer patients who were diagnosed between 1992 through 2005 residing in 11 Surveillance, Epidemiology, and End Results (SEER) areas were estimated and compared with the prevalence in a 5% random sample of cancer-free Medicare beneficiaries. Among cancer patients, survival and the probabilities of dying of their cancer and of other causes by comorbidity level, age, and stage were calculated., Results: Death rates continued to decline for all cancers combined for men and women of all major racial and ethnic groups and for most major cancer sites; rates for both sexes combined decreased by 1.5% per year from 2001 through 2010. Overall incidence rates decreased in men and stabilized in women. The prevalence of comorbidity was similar among cancer-free Medicare beneficiaries (31.8%), breast cancer patients (32.2%), and prostate cancer patients (30.5%); highest among lung cancer patients (52.9%); and intermediate among colorectal cancer patients (40.7%). Among all cancer patients and especially for patients diagnosed with local and regional disease, age and comorbidity level were important influences on the probability of dying of other causes and, consequently, on overall survival. For patients diagnosed with distant disease, the probability of dying of cancer was much higher than the probability of dying of other causes, and age and comorbidity had a smaller effect on overall survival., Conclusions: Cancer death rates in the United States continue to decline. Estimates of survival that include the probability of dying of cancer and other causes stratified by comorbidity level, age, and stage can provide important information to facilitate treatment decisions., (© 2013 American Cancer Society.)

Background: Although screening of human immunodeficiency virus (HIV)-positive individuals for anal intraepithelial neoplasia (AIN; a precursor of anal cancer) has been practiced in San Francisco among HIV health care providers since the early 1990s, to the authors' knowledge no study to date has focused on evaluating recent AIN trends., Methods: Cases of high-grade AIN 3 and invasive anal cancer from 2000 to 2009 were obtained from the San Francisco/Oakland Surveillance, Epidemiology, and End Results (SEER) population-based cancer registry. Age-standardized rates of AIN 3 and anal cancer were calculated overall and by demographic characteristics (sex, race, and age group). Log-linear regression calculated annual percent change in rates during 2000 to 2009, and rate ratios (RRs) and 95% confidence intervals (95% CIs), evaluated differences in rates during 2000 through 2004 and 2005 through 2009., Results: During 2000 through 2009, the majority of AIN 3 cases occurred among men (1152 of 1320 men; 87.3%). Rates of AIN 3 during the corresponding period increased by 11.48% per year (P < .05) among men and were stable among women. Comparing rates among men during 2000 to 2004 with those during 2005 to 2009, the largest increases were noted among those aged 50 years to 64 years (RR, 2.47; 95% CI, 1.93-3.17) and among black individuals (RR, 3.49; 95% CI, 2.14-5.85). During the same period, anal cancer rates were stable among men and women., Conclusions: Rates of AIN 3 increased in San Francisco during 2000 through 2009, in conjunction with an anal cytology screening program for high-risk groups, whereas rates of invasive anal cancer were unchanged. Continued surveillance is necessary to evaluate the impact of screening and human papillomavirus vaccination on the prevention of human papillomavirus-related AIN and anal cancer., (Copyright © 2013 American Cancer Society.)

Background: Mortality rates continue to increase for liver, esophagus, and pancreatic cancers in non-Hispanic whites and for liver cancer in non-Hispanic blacks. However, the extent to which trends vary by socioeconomic status (SES) is unknown., Methods: We calculated age-standardized death rates for liver, esophagus, and pancreas cancers for non-Hispanic whites and non-Hispanic blacks aged 25-64 years by sex and level of education (≤12, 13-15, and ≥16 years, as a SES proxy) during 1993-2007 using mortality data from 26 states with consistent education information on death certificates. Temporal trends were evaluated using log-linear regression, and rate ratios (RRs) with 95 % confidence intervals (CIs) compared death rates in persons with ≤12 versus ≥16 years of education., Results: Generally, death rates increased for cancers of the liver, esophagus, and pancreas in non-Hispanic whites and non-Hispanic blacks (liver cancer only) with ≤12 and 13-15 years of education, with steeper increases in the least educated group. In contrast, rates remained stable in persons with ≥16 years of education. During 1993-2007, the RR (rates in ≤12 versus ≥16 years of education) increased for all three cancers, particularly for liver cancer among men which increased from 1.76 (95 % CI, 1.38-2.25) to 3.23 (95 % CI, 2.78-3.75) in non-Hispanic whites and from 1.28 (95 % CI, 0.71-2.30) to 3.64 (95 % CI, 2.44-5.44) in non-Hispanic blacks., Conclusions: The recent increase in mortality rates for liver, esophagus, and pancreatic cancers in non-Hispanic whites and for liver cancer in non-Hispanic blacks reflects increases among those with lower education levels.

Background: Although overall cervical cancer incidence rates have decreased in both black and white women in the U.S. since the mid 1950s due to widespread screening, rates continue to be higher among blacks than among whites. However, whether this pattern differs by age is unknown., Methods: Cervical cancer cases (1975-2009, N=36,503) were obtained from nine Surveillance, Epidemiology, and End Results (SEER) Program registries. Age-standardized incidence rates for white and black women were calculated from 1975-1979 through 2005-2009 by age group (<50, 50-64, and ≥65 years). Rate ratios (RRs) and 95% confidence intervals (CIs) evaluated differences in rates for blacks vs. whites by age group and stage at diagnosis during 1975-1979 and 2005-2009., Results: Among women aged <50 years, the black-to-white disparity RR decreased from nearly two-fold (RR, 1.9; 95% CI, 1.7-2.1) during 1975-1979 to unity during 2005-2009 (RR, 0.9; 95% CI, 0.8-1.0). In contrast, rates remained significantly elevated for blacks vs. whites aged 50-64 years (RR, 2.4; 95% CI, 2.1-2.7 and 1.7; 95% CI, 1.5-2.0), and for those aged ≥65 years (RR, 3.3; 95% CI, 2.9-3.8 and 2.2; 95% CI, 1.9-2.7) during both time periods, although the disparities decreased over time. Similar disparities persisted for older black women with cervical cancer of all stages., Conclusion: Disparities in cervical cancer incidence rates were eliminated for younger blacks vs. whites but persisted for blacks aged 50 years and older. Additional strategies are needed to increase follow-up and treatment of precancerous lesions among middle-aged and older black women., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Overall declines in human immunodeficiency virus (HIV) mortality may mask patterns for subgroups, and prior studies of disparities in mortality have used area-level vs individual-level socioeconomic status measures. The aim of this study was to examine temporal trends in HIV mortality by sex, race/ethnicity, and individual level of education (as a proxy for socioeconomic status)., Methods: We examined HIV deaths among non-Hispanic white, non-Hispanic black, and Hispanic men and women aged 25 to 64 years in 26 states (1993-2007; N=91 307) reported to the National Vital Statistics System. The main outcome measures were age-standardized HIV death rates, rate differences, and rate ratios by educational attainment and between the least- and the most-educated (≤12 vs ≥16 years) individuals., Results: Between 1993-1995 and 2005-2007, mortality declined for most men and women by race/ethnicity and educational levels, with the greatest absolute decreases for nonwhites owing to their higher baseline rates. Among men with the most education, rates per 100 000 population decreased from 117.89 (95% CI, 101.08-134.70) to 15.35 (12.08-18.62) in blacks vs from 26.42 (24.93-27.92) to 1.79 (1.50-2.08) in whites. Rates were unchanged for the least-educated black women (26.76; 95% CI, 24.30-29.23; during 2005-2007) and remained high for similarly educated black men (52.71; 48.96-56.45). Relative declines were greater with increasing levels of education (P < .001), resulting in widening disparities. Among men, the disparity rate ratio (comparing the least and the most educated) increased from 1.04 (95% CI, 0.89-1.21) during 1993-1995 to 3.43 (2.74-4.30) during 2005-2007 for blacks and from 0.98 (0.91-1.05) to 2.82 (2.34-3.40) for whites., Conclusion: Although absolute declines in HIV mortality were greatest for nonwhites, rates remain high among blacks, especially in the lowest educated groups, underscoring the need for additional interventions.

Background: Despite substantial declines in cervical cancer mortality because of widespread screening, socioeconomic status (SES) disparities persist. The authors examined trends in cervical cancer mortality rates and the risk of late-stage diagnoses by SES., Methods: Using data from the National Vital Statistics System, trends in age-standardized mortality rates among women ages 25 to 64 years (1993-2007) by education level (≤12 years, 13-15 years, and ≥16 years) and race/ethnicity for non-Hispanic white (NHW) women and non-Hispanic black (NHB) women in 26 states were assessed using log-linear regression. Rate ratios (RRs) and 95% confidence intervals (CIs) were used to assess disparities between those with ≤12 years versus ≥16 years of education during 1993 to 1995 and 2005 to 2007. Avertable deaths were calculated by applying mortality rates from the most educated women to others in 48 states. Trends in the risk of late-stage diagnosis by race/ethnicity and insurance status were evaluated in the National Cancer Data Base., Results: Declines in mortality were steepest for those with the highest education levels (3.2% per year among NHW women and 6.8% per year among NHB women). Consequently, the education disparity widened between the periods 1993 to 1995 and 2005 to 2007 from 3.1 (95% CI, 2.4-3.9) to 4.4 (95% CI, 3.5-5.6) for NHW women and from 3.8 (95% CI, 2.0-7.0) to 5.6 (95% CI, 3.1-10.0) for NHB women. The risk of late-stage diagnosis increased for uninsured versus privately insured women over time. During 2007, 74% of cervical cancer deaths in the United States may have been averted by eliminating SES disparities., Conclusions: SES disparities in cervical cancer mortality and the risk of late-stage diagnosis increased over time. Most deaths in 2007 may have been averted by eliminating SES disparities., (Copyright © 2012 American Cancer Society.)

Objective: Deaths related to HIV/AIDS have declined due to improved HIV therapies. However, people with AIDS remain at elevated risk for cancer and cancer deaths. Prior studies evaluated cancer deaths using death certificates, which may be inaccurate. We utilized population attributable risk methods (which do not rely on death certificates) to assess cancer mortality., Design: Data from a US population-based record linkage study were used to identify incident cancers and deaths in 372 364 people with AIDS (1980-2006) followed for up to 5 years after AIDS onset. We utilized Cox regression to compare mortality in individuals with and without cancer and to calculate cancer-attributable mortality across calendar periods (AIDS onset in 1980-1989, 1990-1995, and 1996-2006)., Results: Mortality declined across calendar periods for all people with AIDS but remained higher among those with cancer relative to those without. During 1996-2006, among individuals with an AIDS-defining cancer (ADC) who died, 88.3% of deaths were attributable to their ADC; likewise, among individuals with a non-AIDS-defining cancer (NADC), 87.1% of deaths were attributable to their NADC. The fraction of all deaths in people with AIDS attributable to ADC (i.e. population-attributable risk) decreased significantly from 6.3% (1980-1990) to 3.9% (1996-2006), but NADC population attributable mortality increased significantly over time from 0.5% (1980-1989) to 2.3% (1996-2006)., Conclusion: Among individuals with AIDS and cancer who subsequently die, most deaths are attributable to cancer. With a decline in overall mortality, the proportion of all deaths attributable to NADCs has increased. These results highlight the need for improved cancer prevention and treatment.

Despite declines in incidence rates for the most common cancers, the incidence of several cancers has increased in the past decade, including cancers of the pancreas, liver, thyroid, and kidney and melanoma of the skin, as well as esophageal adenocarcinoma and certain subsites of oropharyngeal cancer associated with human papillomavirus (HPV) infection. Population-based incidence data compiled by the North American Association of Central Cancer Registries were used to examine trends in incidence rates from 1999 through 2008 for the 7 cancers listed by sex, age group, race/ethnicity, and stage at diagnosis. Joinpoint regression was used to calculate average annual percent changes in incidence rates (1999-2008). Rates for HPV-related oropharyngeal cancer, esophageal adenocarcinoma, cancer of the pancreas, and melanoma of the skin increased only in whites, except for esophageal adenocarcinoma, which also increased in Hispanic men. Liver cancer rates increased in white, black, and Hispanic men and in black women only. In contrast, incidence rates for thyroid and kidney cancers increased in all racial/ethnic groups, except American Indian/Alaska Native men. Increases in incidence rates by age were steepest for liver and HPV-related oropharyngeal cancers among those aged 55 [corrected] to 64 years and for melanoma of the skin in those aged 65 years and older. Notably, for HPV-related oropharyngeal cancer in men and thyroid cancer in women, incidence rates were higher in those aged 55 to 64 years than in those aged 65 years and older. Rates increased for both local and advanced stage diseases for most cancer sites. The reasons for these increasing trends are not entirely known. Part of the increase (for esophageal adenocarcinoma and cancers of the pancreas, liver, and kidney) may be linked to the increasing prevalence of obesity as well as increases in early detection practices for some cancers. These rising trends will exacerbate the growing cancer burden associated with population expansion and aging. Additional research is needed to determine the underlying reasons for these increasing trends., (Copyright © 2012 American Cancer Society, Inc.)

Background: Highly active antiretroviral therapy (HAART) results in partial immune restoration for people with AIDS, but its impact on cancer risk among children is unknown., Methods: Data from the U.S. HIV/AIDS Cancer Match Study were used to evaluate cancer risk for people diagnosed with AIDS as children (diagnosed with AIDS at ages 0-14 years, during 1980-2007, followed for up to 10 years; N = 5,850). We calculated standardized incidence ratios (SIR) to compare cancer risk to the general population. Poisson regression evaluated changes in cancer incidence between the pre-HAART (1980-1995) and HAART eras (1996-2007)., Results: There were 106 cancers observed with significantly elevated risks for the two major AIDS-defining cancers: Kaposi sarcoma [KS; N = 20, SIR = 1,694; 95% confidence interval (CI), 986-2,712 and SIR = 1,146; 95% CI, 236-3,349] during the pre-HAART and HAART eras, respectively, and non-Hodgkin lymphoma (NHL; N = 64, SIR = 338; 95% CI, 242-458 and SIR = 116; 95% CI, 74-175). Incidence of both cancers declined 87% and 60%, respectively, in the HAART era (P < 0.05). Of non-AIDS-defining cancers, leiomyosarcoma risk (N = 9) was elevated during both time periods (SIR = 863; 95% CI, 235-2,211 and SIR = 533; 95% CI, 173-1,243)., Conclusion: People diagnosed with AIDS during childhood remain at elevated risk for KS, NHL, and leiomyosarcoma in the HAART era. Incidence of KS and NHL declined relative to widespread HAART use, but there was no change in the incidence of other cancers., Impact: People diagnosed with AIDS during childhood remain at elevated risk for certain cancers. Continued monitoring is warranted as this immunosuppressed population ages into adulthood where cancer risks generally increase.

Background: The overall burden of cancer may increase as individuals with acquired immunodeficiency syndrome (AIDS) live longer because of highly active antiretroviral therapy (HAART), which has been widely available since 1996., Methods: A population-based, record-linkage study identified cancers in 472,378 individuals with AIDS from 1980 to 2006. By using nonparametric competing-risk methods, the cumulative incidence of cancer was estimated across 3 calendar periods (AIDS onset in 1980-1989, 1990-1995, and 1996-2006)., Results: Measured at 5 years after AIDS onset, the cumulative incidence of AIDS-defining cancer (ADC) declined sharply across the 3 AIDS calendar periods (from 18% in 1980-1989, to 11% in 1990-1995, to 4.2% in 1996-2006 [ie, the HAART era]). The cumulative incidence of Kaposi sarcoma declined from 14.3% during 1980 to 1989, to 6.7% during 1990 to 1995, and to 1.8% during 1996 to 2006. The cumulative incidence of non-Hodgkin lymphoma (NHL) declined from 3.8% during 1990 through 1995 to 2.2% during 1996 through 2006; during the HAART era, NHL was the most common ADC (53%). The cumulative incidence of non-AIDS-defining cancer (NADC) increased from 1.1% to 1.5% with no change thereafter (1%; 1996-2006), in part because of declines in competing mortality. However, cumulative incidence increased steadily over time for specific NADCs (anal cancer, Hodgkin lymphoma, and liver cancer). The cumulative incidence of lung cancer increased from 0.14% during 1980 to 1989 to 0.32% during 1990 to 1995, and no change was observed thereafter., Conclusions: Dramatically declining cumulative incidence was noted in 2 major ADCs (Kaposi sarcoma and NHL), and increases were observed in some NADCs (specifically, cancers of the anus, liver, and lung and Hodgkin lymphoma). As HIV/AIDS is increasingly managed as a chronic disease, greater attention should be focused on cancer screening and prevention., (Published 2010 American Cancer Society.)

Trimodal or bimodal age-specific incidence rates for Burkitt lymphoma (BL) were observed in the United States general population, but the role of immunosuppression could not be excluded. Incidence rates, rate ratios, and 95% confidence intervals for BL and other non-Hodgkin lymphoma (NHL), by age and CD4 lymphocyte count categories, were estimated using Poisson regression models using data from the United States HIV/AIDS Cancer Match study (1980-2005). BL incidence was 22 cases per 100 000 person-years and 586 for non-BL NHL. Adjusted BL incidence rate ratio among males was 1.6× that among females and among non-Hispanic blacks, 0.4× that among non-Hispanic whites, but unrelated to HIV-transmission category. Non-BL NHL incidence increased from childhood to adulthood; in contrast, 2 age-specific incidence peaks during the pediatric and adult/geriatric years were observed for BL. Non-BL NHL incidence rose steadily with decreasing CD4 lymphocyte counts; in contrast, BL incidence was lowest among people with ≤ 50 CD4 lymphocytes/μL versus those with ≥ 250 CD4 lymphocytes/μL (incidence rate ratio 0.3 [95% confidence interval = 0.2-0.6]). The bimodal peaks for BL, in contrast to non-BL NHL, suggest effects of noncumulative risk factors at different ages. Underascertainment or biological reasons may account for BL deficit at low CD4 lymphocyte counts.

Background: People with human immunodeficiency virus (HIV) infection and AIDS have an elevated risk for cancer. Highly active antiretroviral therapy (HAART), which has been widely available since 1996, has resulted in dramatic decreases in AIDS-related deaths., Methods: We evaluated cancer as a cause of death in a US registry-based cohort of 83,282 people with AIDS (1980-2006). Causes of death due to AIDS-defining cancers (ADCs) and non-ADCs (NADCs) were assessed. We evaluated mortality rates and the fraction of deaths due to cancer. Poisson regression assessed rates according to calendar year of AIDS onset., Results: Overall mortality decreased from 302 deaths per 1000 person-years in 1980-1989, to 140 deaths per 1000 person-years in 1990-1995, and to 29 deaths per 1000 person-years in 1996-2006. ADC-related mortality decreased from 2.95 deaths per 1000 person-years in 1980-1989 to 0.65 deaths per 1000 person-years in 1996-2006 (P < .01), but the fraction of ADC-related deaths increased from 1.05% to 2.47% in association with decreases in other AIDS-related deaths. Non-Hodgkin lymphoma was the most common cancer-related cause of death (36% of deaths during 1996-2006). Likewise, NADC-related mortality decreased from 2.21 to 0.84 deaths per 1000 person-years from the period 1980-1989 to the period 1996-2006 (P < .05), but the fraction of NADC-deaths increased to 3.16% during 1996-2006. Lung cancer was the most common NADC cause of death (21% of cancer-related deaths in 1996-2006)., Conclusions: Cancer-related mortality decreased in the HAART era, but because of decreasing mortality due to AIDS, cancers account for a growing fraction of deaths. Improved cancer prevention and treatment, particularly for non-Hodgkin lymphoma and lung cancer, would reduce mortality among people with AIDS.

Background: Persons living with AIDS today remain at elevated cancer risk. Highly active antiretroviral therapy (HAART), widely available since 1996, prolongs life, but immune function is not fully restored. We conducted this study to assess long-term cancer risk among persons with AIDS relative to the general population and the impact of HAART on cancer incidence., Methods: Records of 263 254 adults and adolescents with AIDS (1980-2004) from 15 US regions were matched to cancer registries to capture incident cancers during years 3 through 5 and 6 through 10 after AIDS onset. Standardized incidence ratios (SIRs) were used to assess risks relative to the general population. Rate ratios (RRs) were used to compare cancer incidence before and after 1996 to assess the impact of availability of HAART., Results: Risk was elevated for the 2 major AIDS-defining cancers: Kaposi sarcoma (SIRs, 5321 and 1347 in years 3-5 and 6-10, respectively) and non-Hodgkin lymphoma (SIRs, 32 and 15). Incidence of both malignancies declined in the HAART era (1996-2006). Risk was elevated for all non-AIDS-defining cancers combined (SIRs, 1.7 and 1.6 in years 3-5 and 6-10, respectively) and for the following specific non-AIDS-defining cancers: Hodgkin lymphoma and cancers of the oral cavity and/or pharynx, tongue, anus, liver, larynx, lung and/or bronchus, and penis. Anal cancer incidence increased between 1990-1995 and 1996-2006 (RR, 2.9; 95% confidence interval [CI], 2.1-4.0), as did that of Hodgkin lymphoma (RR, 2.0; 95% CI, 1.3-2.9)., Conclusion: Among people who survived for several years or more after an AIDS diagnosis, we observed high risks of AIDS-defining cancers and increasing incidence of anal cancer and Hodgkin lymphoma.

Background: Our objective was to assess trends in the prevalence of hepatitis B virus (HBV) infection in the United States after widespread hepatitis B vaccination., Methods: The prevalence of HBV infection and immunity was determined in a representative sample of the US population for the periods 1999-2006 and 1988-1994. National Health and Nutrition Examination Surveys participants 6 years of age were tested for antibody to hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg), and antibody to hepatitis B surface antigen (anti-HBs). Prevalence estimates were weighted and age-adjusted., Results: During the period 1999-2006, age-adjusted prevalences of anti-HBc (4.7%) and HBsAg (0.27%) were not statistically different from what they were during 1988-1994 (5.4% and 0.38%, respectively). The prevalence of anti-HBc decreased among persons 6-19 years of age (from 1.9% to 0.6%; P < .01) and 20-49 years of age (from 5.9% to 4.6%; P < .01) but not among persons 50 years of age (7.2% vs 7.7%). During 1999-2006, the prevalence of anti-HBc was higher among non-Hispanic blacks (12.2%) and persons of "Other" race (13.3%) than it was among non-Hispanic whites (2.8%) or Mexican Americans (2.9%), and it was higher among foreign-born participants (12.2%) than it was among US-born participants (3.5%). Prevalence among US-born children 6-19 years of age (0.5%) did not differ by race or ethnicity. Disparities between US-born and foreign-born children were smaller during 1999-1996 (0.5% vs 2.0%) than during 1988-1994 (1.0% vs 12.8%). Among children 6-19 years of age, 56.7% had markers of vaccine-induced immunity., Conclusions: HBV prevalence decreased among US children, which reflected the impact of global and domestic vaccination, but it changed little among adults, and approximately 730,000 US residents (95% confidence interval, 550,000-940,000) are chronically infected.

Background: Hepatitis B virus (HBV) infection is a well recognized risk for healthcare workers (HCWs), and routine vaccination of HCWs has been recommended since 1982. By 1995, the level of vaccination coverage among HCWs was only 67%., Objective: To obtain an accurate estimate of hepatitis B vaccination coverage levels among HCWs and to describe the hospital characteristics and hepatitis B vaccination policies associated with various coverage levels., Design: Cross-sectional survey., Methods: A representative sample of 425 of 6,116 American Hospital Association member hospitals was selected to participate, using probability-proportional-to-size methods during 2002-2003. The data collected included information regarding each hospital's hepatitis B vaccination policies. Vaccination coverage levels were estimated from a systematic sample of 25 HCWs from each hospital whose medical records were reviewed for demographic and vaccination data. The main outcome measure was hepatitis B vaccination coverage levels., Results: Among at-risk HCWs, 75% had received 3 or more doses of the hepatitis B vaccine, corresponding to an estimated 2.5 million vaccinated hospital-based HCWs. The coverage level was 81% among staff physicians and nurses. Compared with nurses, coverage was significantly lower among phlebotomists (71.1%) and nurses' aides and/or other patient care staff (70.9%; P<.05). Hepatitis B vaccination coverage was highest among white HCWs (79.5%) and lowest among black HCWs (67.6%; P<.05). Compared with HCWs who worked in hospitals that required vaccination only of HCWs with identified risk for exposure to blood or other potentially infectious material, hepatitis B vaccination coverage was significantly lower among HCWs who worked in hospitals that required vaccination of HCWs without identified risk for exposure to blood or other potentially infectious material (76.6% vs 62.4%; P<.05)., Conclusions: In the United States, an estimated 75% of HCWs have been vaccinated against hepatitis B. Important differences in coverage levels exist among various demographic groups. Hospitals need to identify methods to improve hepatitis B vaccination coverage levels and should consider developing targeted vaccination programs directed at unvaccinated, at-risk HCWs who have frequent or potential exposure to blood or other potentially infectious material.

Background: Defining the primary characteristics of persons infected with hepatitis C virus (HCV) enables physicians to more easily identify persons who are most likely to benefit from testing for the disease., Objective: To describe the HCV-infected population in the United States., Design: Nationally representative household survey., Setting: U.S. civilian, noninstitutionalized population., Participants: 15,079 participants in the National Health and Nutrition Examination Survey between 1999 and 2002., Measurements: All participants provided medical histories, and those who were 20 to 59 years of age provided histories of drug use and sexual practices. Participants were tested for antibodies to HCV (anti-HCV) and HCV RNA, and their serum alanine aminotransferase (ALT) levels were measured., Results: The prevalence of anti-HCV in the United States was 1.6% (95% CI, 1.3% to 1.9%), equating to an estimated 4.1 million (CI, 3.4 million to 4.9 million) anti-HCV-positive persons nationwide; 1.3% or 3.2 million (CI, 2.7 million to 3.9 million) persons had chronic HCV infection. Peak prevalence of anti-HCV (4.3%) was observed among persons 40 to 49 years of age. A total of 48.4% of anti-HCV-positive persons between 20 and 59 years of age reported a history of injection drug use, the strongest risk factor for HCV infection. Of all persons reporting such a history, 83.3% had not used injection drugs for at least 1 year before the survey. Other significant risk factors included 20 or more lifetime sex partners and blood transfusion before 1992. Abnormal serum ALT levels were found in 58.7% of HCV RNA-positive persons. Three characteristics (abnormal serum ALT level, any history of injection drug use, and history of blood transfusion before 1992) identified 85.1% of HCV RNA-positive participants between 20 and 59 years of age., Limitations: Incarcerated and homeless persons were not included in the survey., Conclusions: Many Americans are infected with HCV. Most were born between 1945 and 1964 and can be identified with current screening criteria. History of injection drug use is the strongest risk factor for infection.

Worldwide, two billion people have been infected with hepatitis B virus (HBV), 360 million have chronic infection, and 600,000 die each year from HBV-related liver disease or hepatocellular carcinoma. This comprehensive review of hepatitis B epidemiology and vaccines focuses on definitive and influential studies and highlights current trends, policies, and directions. HBV can be transmitted vertically, through sexual or household contact, or by unsafe injections, but chronic infections acquired during infancy or childhood account for a disproportionately large share of worldwide morbidity and mortality. Vaccination against HBV infection can be started at birth and provides long-term protection against infection in more than 90% of healthy people. In the 1990s, many industrialized countries and a few less-developed countries implemented universal hepatitis B immunization and experienced measurable reductions in HBV-related disease. For example, in Taiwan, the prevalence of chronic infection in children declined by more than 90%. Many resource-poor nations have recently initiated universal hepatitis B immunization programs with assistance from the Global Alliance for Vaccines and Immunization. Further progress towards the elimination of HBV transmission will require sustainable vaccination programs with improved vaccination coverage, practical methods of measuring the impact of vaccination programs, and targeted vaccination efforts for communities at high risk of infection.

Objectives: We sought to determine hepatitis B virus (HBV) infection prevalence, associated exposures, and incidence among male inmates at a state correctional facility., Methods: A cross-sectional serological survey was conducted in June 2000, and susceptible inmates were retested in June 2001., Results: At baseline, 230 inmates (20.5%; 95% confidence interval [CI]=18.2%, 22.9%) exhibited evidence of HBV infection, including 11 acute and 11 chronic infections. Inmates with HBV infection were more likely than susceptible inmates to have injected drugs (38.8% vs 18.0%; adjusted prevalence odds ratio [OR]=3.0; 95% CI=1.9, 4.9), to have had more than 25 female sex partners (27.7% vs 17.5%; adjusted prevalence OR=2.0; 95% CI=1.4, 3.0), and to have been incarcerated for more than 14 years (38.4% vs 17.6%; adjusted prevalence OR=1.7; 95% CI=1.1, 2.6). One year later, 18 (3.6%) showed evidence of new HBV infection. Among 19 individuals with infections, molecular analysis identified 2 clusters involving 10 inmates, each with a unique HBV sequence., Conclusions: We documented ongoing HBV transmission at a state correctional facility. Similar transmission may occur at other US correctional facilities and could be prevented by vaccination of inmates.

Objectives: We assessed the effect on trends in hepatitis A incidence of the 1996 recommendation for routine hepatitis A vaccination of American Indian/Alaska Native (AIAN) children., Methods: We examined trends in hepatitis A incidence among AIAN peoples during 1990-2001 and vaccination coverage levels among children on the largest American Indian reservation., Results: Hepatitis A rates among AIANs declined 20-fold during 1997-2001. Declines in hepatitis A incidence occurred among AIANs in reservation and metropolitan areas. Among 1956 children living on the Navajo Nation whose medical records were reviewed, 1508 (77.1%) had received at least one dose of hepatitis A vaccine, and 1020 (52.1%) had completed the vaccine series., Conclusions: Hepatitis A rates among AIAN peoples have declined dramatically coincident with implementation of routine hepatitis A vaccination of AIAN children.

Context: The impact of routine hepatitis A vaccination of children living in large communities with elevated disease rates has not been evaluated., Objective: To determine the effect of routine vaccination of children on disease incidence in a community with recurrent hepatitis A epidemics., Design, Setting, and Participants: Community-based demonstration project conducted from January 12, 1995, through December 31, 2000, in Butte County, California, among children aged 2 to 17 years., Intervention: In 1995, vaccination was offered to children aged 2 to 12 years during vaccination clinics conducted on 2 occasions 6 to 12 months apart at most schools in the county. In 1996-2000, vaccine was distributed to community health care clinicians, who vaccinated eligible children without charge. Vaccine was also available at health department clinics, selected child care centers, and other sites., Main Outcome Measures: Hepatitis A vaccination coverage, hepatitis A incidence, and vaccine effectiveness., Results: During the study period, 29 789 (66.2%) of an estimated 44 982 eligible children received at least 1 vaccine dose; 17 681 (39.3%) received a second dose. The number of hepatitis A cases among the entire county population declined 93.5% during the study period, from 57 cases in 1995 to 4 in 2000, the lowest number of cases reported in the county since hepatitis A surveillance began in 1966. The 2000 incidence rate of 1.9 per 100 000 population was the lowest of any county in the state. Of the 245 cases reported during the 6-year period, 40 (16.3%) occurred among children 17 years of age or younger, of which 16 (40%) occurred in 1995 and only 1 in 2000. One of the 27 case patients eligible for vaccination had been vaccinated, having received the first dose 3 days before symptom onset. The estimated protective vaccine efficacy was 98% (95% confidence interval, 86%-100%)., Conclusions: In this population, hepatitis A vaccine was highly effective in preventing disease among recipients. Childhood vaccination appears to have decreased hepatitis A incidence among children and adults and controlled the disease in a community with recurrent epidemics.