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Hepatitis C virus (HCV) infection is common among people living with HIV. HIV and HCV coinfected patients have higher overall mortality rates compared with HIV mono-infected patients. With its high cure rate of HCV infection, direct-acting antiviral (DAA) treatment provides an opportunity to improve the survival of the HIV/HCV coinfected population. The objective of this study is to investigate the association between DAA treatment and all-cause mortality among HIV/HCV coinfected people. The study included 7103 Medicare beneficiaries in the United States who were infected with both HIV and HCV between 2014 and 2017. Cox proportional hazards regression model was used to estimate adjusted hazard ratios (aHRs) of death for patients with and without DAA treatment while controlling for patient characteristics. During the study period, 1675 patients initiated DAA treatment (23.6%). The adjusted hazard ratio (aHR) of all-cause mortality between patients with and without DAA treatment was 0.37 (95% CI, 0.29–0.48), regardless of cirrhosis status. DAA treatment was associated with a smaller reduction in all-cause mortality for females (aHR, 0.50 [95% CI, 0.30–0.85]) compared with males (aHR, 0.34 [95% CI, 0.25–0.46]). DAA treatment was associated with improved survival among all HIV/HCV coinfected patients regardless of sex or HCV disease progression. [ABSTRACT FROM AUTHOR]

Introduction: The advent of direct-acting antiviral agents for treating hepatitis C virus infection has made hepatitis C virus elimination possible. Rural patients with hepatitis C virus infection may be less likely to access direct-acting antiviral agents, but the real-world evidence is scarce on urban-rural disparities in direct-acting antiviral agent utilization.Methods: This retrospective cohort study was conducted in 2019-2020 using Medicare data to examine urban-rural disparities in direct-acting antiviral agent utilization among newly diagnosed patients with hepatitis C virus infection in 2014-2016. Direct-acting antiviral agent use was defined as filling ≥1 prescription for direct-acting antiviral agents during 2014-2017, and patient's urban-rural status was classified on the basis of their ZIP code of residence. This study evaluated the associations between multilevel factors and direct-acting antiviral agent use with a focus on urban-rural disparities. It also assessed changes over time in urban-rural disparities in direct-acting antiviral agent utilization using multivariable cause-specific Cox regression analyses with time-varying hazard ratios.Results: Among 204,018 new patients with hepatitis C virus infection, about 30% received direct-acting antiviral agents during 2014-2017. Cumulative direct-acting antiviral agent use gradually increased over time in both urban and rural patients. However, the increase was greater in urban patients than in rural patients. In the first year of follow-up, rural patients had a similar rate of receiving direct-acting antiviral agents (adjusted hazard ratio=1.03, 95% CI=1.00, 1.07), but they were less likely to use direct-acting antiviral agents in later years than urban patients (adjusted hazard ratio=0.85, 95% CI=0.81, 0.90 in the second year, adjusted hazard ratio=0.82, 95% CI=0.76, 0.89 in the third year, and adjusted hazard ratio=0.76, 95% CI=0.64, 0.90 in the fourth year of follow-up).Conclusions: This study reveals important gaps in hepatitis C virus treatment and suggests increasing urban-rural disparities in direct-acting antiviral agent utilization. Enhancing direct-acting antiviral agent uptake in rural populations with hepatitis C virus infection will help reduce hepatitis C virus‒related health disparities and reach the national goal of eliminating hepatitis C virus infection. [ABSTRACT FROM AUTHOR]

Rationale: The use of electronic cigarettes (e-cigarettes) has rapidly increased in the United States, and thousands of e-cigarette flavors are available. However, there remains a dearth of evidence on e-cigarette flavor use patterns among older e-cigarette users.Objectives: This longitudinal study examined changes in flavor use patterns in long-term e-cigarette users, assessed self-reported adverse reactions, and evaluated users' anticipated reactions to possible U.S. Food and Drug Administration e-cigarette flavor regulatory scenarios.Methods: The study population was 383 adult participants who completed two online e-cigarette surveys in 2012-2014 (baseline survey) and in 2017-2019 (follow-up survey). In both surveys, participants were asked, "Thinking about your preferred liquid, what is the name of this liquid flavor?" and to list all flavors used in the past 30 days. Flavor preference was classified using the Penn State Three-Step Flavor Classification method. Participants reported adverse events (open-ended description) with the associated flavor. Regulatory scenarios were presented, and participants selected perceived actions from among a list of 15 options.Results: Participants' age averaged 44 ± 12 years; 86% were exclusive e-cigarette users, and 13% reported "poly-use" (i.e., e-cigarette and other tobacco product use). E-cigarette flavor preference migration occurred in all demographic groups: only 36-44% maintained a preference for their original flavor. Preference for tobacco and menthol or mint decreased over time (40% baseline vs. 22% follow-up); preference for fruit remained stable (23% baseline and follow-up), but chocolate/candy or other sweets preference significantly increased (16% baseline vs. 29% follow-up), and other flavors increased slightly. Migration to sweet flavors was more noticeable in younger adults (18-45 yr); exclusive e-cigarette users preferred sweet flavors more commonly than poly-users did (31% vs. 19%). Flavor-associated adverse reactions, mainly respiratory irritations, were reported by 26 (6.9%) participants. Nearly 50% of the participants reported that they would "find a way" to buy their preferred flavor or add flavoring agents themselves if nontobacco flavors were banned.Conclusions: Flavor migration toward sweet flavors occurred in long-term e-cigarette users, a trend most pronounced in younger and exclusive e-cigarette users. The anticipated maintenance of access to flavors despite regulation suggests an element of e-cigarette-related dependence that requires further evaluation. This information could help clinicians understand the health impacts of e-cigarette flavors, develop appropriate strategies for smoking cessation, and inform the U.S. Food and Drug Administration to plan future regulation of e-cigarette flavors. [ABSTRACT FROM AUTHOR]

This article describes the New York State Department of Health's GeoDatabase project, which developed new methods and techniques for designing and building a geocoding and mapping data repository for sexually transmitted disease (STD) control. The GeoDatabase development was supported through the Centers for Disease Control and Prevention's Outcome Assessment through Systems of Integrated Surveillance workgroup. The design and operation of the GeoDatabase relied upon commercial-off-the-shelf tools that other public health programs may also use for disease-control systems. This article provides a blueprint of the structure and software used to build the GeoDatabase and integrate location data from multiple data sources into the everyday activities of STD control programs. [ABSTRACT FROM AUTHOR]

Background: Persons with a congenital deficiency of FVIII or F IX (hemophilia A and hemophilia B, respectively) receive factor concentrate to treat or prevent bleeding.Study Design and Methods: A population-based study of all persons with hemophilia residing in New York State at any time during 1993 through 1998 was conducted. All available medical records for each patient were reviewed to determine type of therapy.Results: Case finding yielded 1160 cases, for a prevalence of 63.9 per 1 million population in 1998. Recombinant factor concentrates were used by 56 percent of patients. Patients with severe disease used more (158,234 IU/patient) factor concentrate than did patients with moderate disease (46,315 IU) or mild disease (5794 IU). Over half (57%) of all factor concentrate was prescribed for patients with severe disease on prophylactic therapy. Patients undergoing immune tolerance therapy used the most per person-455,116 IU each. Hemophilia treatment centers provided factor concentrate for 62 percent of all patients who used factor and 73 percent of patients with severe disease.Conclusion: Hemophilia patients, especially patients with severe disease, use large amounts of expensive factor concentrates to prevent and to treat bleeding episodes. Specialized hemophilia treatment centers play a key role in the care of these patients. [ABSTRACT FROM AUTHOR]

Purpose: Contact tracing has proven successful at controlling coronavirus 2019 (COVID-19) globally, and the Center for Health Security has recommended that the United States add 100,000 contact tracers to the current workforce.Methods: To address gaps in local contact tracing, health professional students partnered with their academic institution to conduct contact tracing for all COVID-19 cases diagnosed onsite, which included identifying and reaching their contacts, educating participants, and providing social resources to support effective quarantine and isolation.Results: From March 24 to May 28, 536 laboratory-confirmed COVID-19 cases were contacted and reported an average of 2.6 contacts. Contacts were informed of their exposure, asked to quarantine, and monitored for the onset of symptoms. Callers reached 94% of cases and 84% of contacts. Seventy-four percent of cases reported at least one contact. Household members had higher rates of reporting symptoms (odds ratio, 1.65; 95% confidence interval, 1.19-2.28). The average test turnaround time decreased from 21.8 days for the first patients of this program to 2.3 days on the eleventh week.Conclusions: This provides evidence for the untapped potential of community contact tracing to respond to regional needs, confront barriers to effective quarantine, and mitigate the spread of COVID-19. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is common in people living with HIV/AIDS (PLWHA). The advent of direct-acting antiviral agents (DAAs) has made HCV elimination a realistic goal. We conducted a retrospective cohort study using the US Medicare Fee-For-Service claims data and outpatient prescription drug data to assess the HCV DAA initiation and completion among newly diagnosed HIV-HCV-coinfected Medicare patients enrolled in 2014-2016. DAA initiation was defined as filling at least 1 prescription of DAAs during 2014-2016. DAA completion was defined as taking an 8-week or longer DAA treatment course for patients without cirrhosis and a 12-week or longer treatment duration for those with cirrhosis. Among 12 152 HIV-HCV-coinfected Medicare patients, 20.9% received the DAA treatment in 2014-2016. The average time from HCV diagnosis to DAA initiation was 277 days. The overall DAA completion rate was 92% among 2537 patients who used DAAs. Interventions are needed to improve DAA uptake in PLWHA., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Human papillomavirus (HPV) vaccination in young women is low. Women aged 21 to 65 years in the United States (U.S.) have not reached the Healthy People 2020 objective of 93% for cervical cancer screening. The main aim of this study was to investigate the association between HPV vaccination status and cervical cancer screening among privately insured women aged 21 to 26 years in the U.S.This was a retrospective cohort study using the IBM MarketScan database (2006-2016). The study population included 190,982 HPV-vaccinated women and 763,928 matched unvaccinated women. Adjusted incidence rate ratio (IRR) and the 95% confidence intervals (CIs) were obtained using the generalized estimating equations models with a Poisson distribution.Among a total of 954,910 women included in the analysis, age (mean [SD]) was 23.3 [1.6] years. During 967,317 person-years of follow-up, a total of 475,702 incidents of cervical cancer screening were identified. The incidence density rates of cervical cancer screening were 461 per 1000 person-years (PY) for unvaccinated women and 787 per 1000 PY for those who received 3 doses of the HPV vaccine. After adjusting for other covariates, the IRR of cervical cancer screening was 34% higher among HPV-vaccinated women with at least one vaccine dose than unvaccinated women (adjusted IRR = 1.34, 95% CI: 1.33-1.35; P < .0001). The IRR of cervical cancer screening varied by the dose of HPV vaccination. There was evidence of a linear dose-response relationship between the number of HPV vaccine doses and cervical cancer screening (P-trend < .0001). Compared with unvaccinated women, the IRR of cervical cancer screening were 14%, 39%, and 60% higher among those who received 1, 2, and 3 doses of the HPV vaccine, respectively.In this large retrospective cohort study of privately insured women, HPV-vaccinated women were more likely to be screened for cervical cancer compared with unvaccinated women., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Expanding access to direct-acting antiviral agents (DAAs) for treating hepatitis C virus (HCV) infection is the national goal for HCV elimination, but important urban-rural disparities exist in DAA use. Evidence is needed to evaluate intervention efforts to reduce urban-rural disparities in DAA utilization. Methods: We used Medicare data to compare DAA use between urban HCV patients and rural HCV patients in two states: State A with a telementoring approach to train rural providers to treat HCV patients and State B without such an intervention. We focused on DAA utilization among newly diagnosed HCV patients in 2014-2016 and defined DAA use as filling at least one prescription of DAAs during 2014-2017. We classified patient's urban-rural status based on their ZIP code of residence. We assessed overtime changes in urban-rural disparities in DAA utilization for each state using multivariable cause-specific Cox regression analyses with time-varying hazard ratios. Results: Among 1,872 new HCV patients in State A, 135 (17.00%) rural patients and 243 (22.54%) urban patients received DAAs in 2014-2017. Although there was noticeable urban-rural disparities in DAA use during the first 24 months of follow-up (hazard ratios [HRs] = 0.73 [0.51 to 1.03] for 0-12 months and 0.61 [0.39 to 0.95] for 13-24 months), the disparities became nonsignificant afterward (HR = 1.06 [0.58 to 1.93] after 24 months). Most DAA users in rural areas (94, 70%) in State A received DAAs prescribed by primary care providers (PCPs). In State B, among 8,928 new HCV patients, 227 (18.22%) rural patients and 1,600 (20.83%) urban patients received DAAs in 2014-2017. Rural patients were less likely to receive DAAs over time (HR = 1.12 [0.93 to 1.36] in the first 12 months and HR = 0.62 [0.40 to 0.96] after 24 months). Only 81 (36%) DAA users in rural areas in State B were treated by PCPs. Conclusions: Our study suggests that the telementoring approach may help reduce urban-rural disparities in DAA utilization.

Rationale: The use of electronic cigarettes (e-cigarettes) has rapidly increased in the United States, and thousands of e-cigarette flavors are available. However, there remains a dearth of evidence on e-cigarette flavor use patterns among older e-cigarette users. Objectives: This longitudinal study examined changes in flavor use patterns in long-term e-cigarette users, assessed self-reported adverse reactions, and evaluated users' anticipated reactions to possible U.S. Food and Drug Administration e-cigarette flavor regulatory scenarios. Methods: The study population was 383 adult participants who completed two online e-cigarette surveys in 2012-2014 (baseline survey) and in 2017-2019 (follow-up survey). In both surveys, participants were asked, "Thinking about your preferred liquid, what is the name of this liquid flavor?" and to list all flavors used in the past 30 days. Flavor preference was classified using the Penn State Three-Step Flavor Classification method. Participants reported adverse events (open-ended description) with the associated flavor. Regulatory scenarios were presented, and participants selected perceived actions from among a list of 15 options. Results: Participants' age averaged 44 ± 12 years; 86% were exclusive e-cigarette users, and 13% reported "poly-use" (i.e., e-cigarette and other tobacco product use). E-cigarette flavor preference migration occurred in all demographic groups: only 36-44% maintained a preference for their original flavor. Preference for tobacco and menthol or mint decreased over time (40% baseline vs. 22% follow-up); preference for fruit remained stable (23% baseline and follow-up), but chocolate/candy or other sweets preference significantly increased (16% baseline vs. 29% follow-up), and other flavors increased slightly. Migration to sweet flavors was more noticeable in younger adults (18-45 yr); exclusive e-cigarette users preferred sweet flavors more commonly than poly-users did (31% vs. 19%). Flavor-associated adverse reactions, mainly respiratory irritations, were reported by 26 (6.9%) participants. Nearly 50% of the participants reported that they would "find a way" to buy their preferred flavor or add flavoring agents themselves if nontobacco flavors were banned. Conclusions: Flavor migration toward sweet flavors occurred in long-term e-cigarette users, a trend most pronounced in younger and exclusive e-cigarette users. The anticipated maintenance of access to flavors despite regulation suggests an element of e-cigarette-related dependence that requires further evaluation. This information could help clinicians understand the health impacts of e-cigarette flavors, develop appropriate strategies for smoking cessation, and inform the U.S. Food and Drug Administration to plan future regulation of e-cigarette flavors.

Objectives: To examine factors associated with discontinuation of new hepatitis C drugs-second-generation direct-acting antivirals (DAAs)-among Medicare beneficiaries with chronic hepatitis C., Study Design: A retrospective analysis using 2014-2016 Medicare claims., Methods: The study population was patients with chronic hepatitis C in fee-for-service Medicare with Part D who initiated a DAA therapy between January 1, 2014, and September 1, 2016. We defined discontinuation of DAA therapy as filling prescriptions for fewer weeks than the expected duration of the DAA identified. We estimated adjusted odds ratios (aORs) of DAA discontinuation by patient characteristics using multivariable logistic regression. We estimated the model separately for patients with a Part D low-income subsidy (LIS) and those without an LIS., Results: Of 82,056 patients who initiated a DAA therapy during the study period, 5171 (6.3%) did not complete the therapy. Discontinuation rates varied across DAAs, ranging from 4.7% (elbasvir/grazoprevir) to 11.8% (ombitasvir/paritaprevir/ritonavir/dasabuvir). Women with an LIS were more likely to discontinue DAA therapy than men with an LIS (aOR, 1.16; 95% CI, 1.08-1.25; P <.01). Non-LIS black and Hispanic patients had higher odds of discontinuation than non-LIS white patients (black: aOR, 1.49; 95% CI, 1.28-1.73; P <.01; Hispanic: aOR, 1.56; 95% CI, 1.01-2.44; P <.05). High comorbidity index score increased the odds of DAA discontinuation among patients with an LIS., Conclusions: Real-world discontinuation of DAA therapy was low, but it was 3 times more likely than in clinical trials and varied by patient characteristics. Efforts to increase DAA adherence would help lower patients' risk of developing resistance to future treatments and reduce potential waste of resources.

Background: New hepatitis C virus (HCV) drugs-direct-acting antivirals (DAAs)-are highly effective but costly, which raises a concern about limited access to DAAs by vulnerable populations. Previous studies of disparities in DAA use across patient groups showed mixed results, but their generalizability was limited due to using data from commercial insurers or from 2014 only-the first year DAAs were available. Disparities in DAA use in a national cohort in the years when more DAAs were available is unknown., Objective: To examine whether disparities in DAA use by patient race/ethnicity and socioeconomic status in Medicare changed between 2014 and 2016., Methods: The study population was made up of chronic hepatitis C patients in fee-for-service Medicare with Part D between 2014 and 2016. We used multinomial logistic regression to estimate adjusted odds ratios (aOR) of using DAAs by patient race/ethnicity and socioeconomic status. We estimated the model separately for 2014 and 2014-2016., Results: Of 281,810 Medicare patients who were followed to the end of 2016, a total of 90,419 (32.1%) filled prescriptions for DAAs. In the 2014 analysis, blacks were less likely to use DAAs than whites (aOR = 0.95; 95% CI = 0.91-0.99). However, in the 2014-2016 analysis, blacks had higher odds of using DAAs than whites (aOR = 1.24; 95% CI = 1.22-1.27). No significant Hispanic-white gap existed during the study period. Income was positively associated with DAA use in both periods. Between 2014 and 2016, patients who received a Part D low-income subsidy had lower odds of using DAAs than patients who did not (aOR = 0.90; 95% CI = 0.88-0.92), and patients in areas with the higher income tertiles were more likely to initiate DAAs than those in areas with the lowest income tertile., Conclusions: DAA use among Medicare patients remained far below the level needed to eradicate HCV. The black-white gap in HCV treatment was closed by 2016, but disparities by patient socioeconomic status remained. DAA use also varied by patient age and health risk, as well as across geographic regions. Continued efforts to improve DAA uptake in all HCV patients are needed to eradicate HCV., Disclosures: This study was supported by the National Institute on Aging (1 R01 AG055636-01A1) and National Institute of Child Health & Human Development (R24 HD04025). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Feldman owns stock in Gilead Sciences and Abbvie. No other potential competing interest exists.

Objectives: The recent arrival of new hepatitis C virus (HCV) drugs has brought fiscal pressures onto Medicare Part D; spending on HCV drugs in Part D jumped from $283 million in 2013 to $4.5 billion in 2014. We examined the current benefit designs for HCV drugs in Part D plans and analyzed patients' financial burden for those drugs., Study Design: A cross-sectional analysis of CMS' July 2015 Part D Plan Formulary File and the Wolters Kluwer Health Medi-Span Electronic Drug File v.2., Methods: We analyzed the type and amount of cost sharing for HCV drugs and the extent to which plans apply utilization management tools. We then estimated total out-of-pocket spending for beneficiaries to complete a course of treatment., Results: All Part D plans covered at least 1 recently introduced HCV drug, as of July 2015. Nearly all plans charged relatively high coinsurance and required prior authorization for new HCV drugs. For enrollees with no subsidy, the mean out-of-pocket spending needed to complete a course of treatment is substantial, ranging from $6297 to $10,889. For enrollees with a low-income subsidy, out-of-pocket spending varies between $10.80 and $1191., Conclusions: Under the current Part D benefits, HCV drug users with no subsidy face sizable financial burdens, even with catastrophic coverage and the recent in-gap discount for brand name drugs. As baby boomers-the group most likely to have HCV-join Medicare, efforts should be made to ensure patient access to these needed drugs.

Objective: The aim of this study is to evaluate portal hypertension as an independent risk factor in general surgical procedures., Background: Data on the impact of portal hypertension in general surgical outcomes has been limited. Published literature has focused mainly on its effect in liver surgery. The Child Pugh score and Model for End Stage Liver Disease are utilized for surgical risk assessment in liver disease but they do not accurately reflect degree of portal hypertension., Methods: From 2005 to 2012, patients with esophageal varices (EV) in the National Surgical Quality Improvement Program (NSQIP) formed the portal hypertension cohort, and were case matched to patients without esophageal varices (NEV) based on sex, age, surgery type, and year of operation. Thirty day mortality and morbidity were analyzed using generalized estimating equations for binary outcomes. EV patients were also dichotomized by Model for End Stage Liver Disease (MELD) score (≤15 vs >15) and compared with NEV patients., Results: One thousand five hundred and seventy-four EV patients were matched to 3148 NEV patients. In multivariable analysis, EV patients had a 3.01 higher odds of 30 day mortality (P < 0.001) and 1.28 higher odds of complications (P < 0.001) compared with NEV patients. EV patients with MELD >15 had 4.64 higher odds of death within 30 days (P < 0.001) and had 1.75 higher odds of complications within 30 days (P < 0.001) compared with NEV patients; EV patients with MELD 15 or less had 1.95 higher odds of 30 day mortality (P < 0.001) compared with NEV patients., Conclusions: Portal hypertension is associated with a significant mortality and morbidity risk in general surgery, and should not be underestimated even in patients with MELD 15 or less where the early mortality risk remained significant.

Background: The Centers for Disease Control and Prevention recommended an "opt-out" human immunodeficiency virus (HIV) testing strategy in 2006 for all persons aged 13 to 64 years at healthcare settings. We conducted this study to identify individual, health, and policy factors that may be associated with HIV testing in US adults., Methods: The 2008 Behavioral Risk Factors Surveillance System data were utilized. Individuals' residency states were classified into 4 categories based on the legislation status to HIV testing laws in 2007 and HIV/acquired immune deficiency syndrome morbidity. A multivariate logistic regression adjusting for survey designs was performed to examine factors associated with HIV testing., Results: A total of 281,826 adults aged 18 to 64 years answered HIV testing questions in 2008. The proportions of US adults who had ever been tested for HIV increased from 35.9% in 2006 to 39.9% in 2008. HIV testing varied across the individual's characteristics including sociodemographics, access to regular health care, and risk for HIV infection. Compared with residents of "high morbidity-opt out" states, those living in "high morbidity-opt in" states with legislative restrictions for HIV testing had a slightly lower odds of being tested for HIV (adjusted odds ratio = 0.96; 95% confidence interval = 0.92, 1.01). Adults living in "low morbidity" states were significantly less likely to be tested for HIV, regardless of legislative status., Conclusions: To implement routine HIV testing in the general population, the role of public health resources should be emphasized and legislative barriers should be further reduced. Strategies need to be developed to reach people who do not have regular access to health care.

Background: While high-risk geographic clusters of cervical cancer mortality have previously been assessed, factors associated with this geographic patterning have not been well studied. Once these factors are identified, etiologic hypotheses and targeted population-based interventions may be developed and lead to a reduction in geographic disparities in cervical cancer mortality., Methods: The authors linked multiple data sets at the county level to assess the effects of social domains, behavioral risk factors, local physician and hospital availability, and Chlamydia trachomatis infection on overall spatial clustering and on individual clusters of cervical cancer mortality rates in 2000-2004 among 3,105 US counties in the 48 states and the District of Columbia., Results: During the study period, a total of 19,898 cervical cancer deaths occurred in women aged 20 and older. The distributions of county-level characteristics indicated wide ranges in social domains measured by demographics and socioeconomic status, local health care resources, and the rate of chlamydial infection. We found that overall geographic clustering of increased cervical cancer mortality was related to the high proportion of black population, low socioeconomic status, low Papanicolaou test rate, low health care coverage, and the high chlamydia rate; however, unique characteristics existed for each individual cluster, and the Appalachian cluster was not related to a high proportion of black population or to chlamydia rates., Discussion: This study indicates that local social domains, behavioral risk, and health care sources are associated with geographic disparities in cervical cancer mortality rates. The association between the chlamydia rate and the cervical cancer mortality rate may be confounded by other factors known to be a risk for cervical cancer mortality, such as the infection with human papillomavirus. The findings will help cancer researchers examine etiologic hypotheses and develop tailored, cluster-specific interventions to reduce cervical cancer disparities.

Human noroviruses (NoVs) of genogroup II, genotype 4 (GII.4) are the most common strains detected in outbreaks of acute gastroenteritis worldwide. To gain insight into the epidemiology and genetic variation of GII.4 strains, we analyzed 773 NoV outbreaks reported to the CDC from 1994 to 2006. Of these NoV outbreaks, 629 (81.4%) were caused by GII viruses and 342 (44.2%) were caused by GII.4 strains. The proportion of GII.4 outbreaks increased from 5% in 1994 to 85% in 2006, but distinct annual differences were noted, including sharp increases in 1996, 2003, and 2006 each associated with newly emerging GII.4 strains. Sequence analysis of the full-length VP1 gene of GII.4 strains identified in this study and from GenBank segregated these viruses into at least 9 distinct subclusters which had 1.3 to 3.2% amino acid variation between strains in different subclusters. We propose that GII.4 subclusters be defined as having >5% sequence variation between strains. Our data confirm other studies on the rapid emergence and displacement of highly virulent GII.4 strains.