Melanoma in adolescents and young adults (ages 15-39 years): United States, 1999-2006
Weir HK , Marrett LD , Cokkinides V , Barnholtz-Sloan J , Patel P , Tai E , Jemal A , Li J , Kim J , Ekwueme DU . J Am Acad Dermatol 2011 65 S38-49 BACKGROUND: Invasive melanoma of the skin is the third most common cancer diagnosed among adolescents and young adults (aged 15-39 years) in the United States. Understanding the burden of melanoma in this age group is important to identifying areas for etiologic research and in developing effective prevention approaches aimed at reducing melanoma risk. METHODS: Melanoma incidence data reported from 38 National Program of Cancer Registries and/or Surveillance Epidemiology and End Results statewide cancer registries covering nearly 67.2% of the US population were used to estimate age-adjusted incidence rates for persons 15-39 years of age. Incidence rate ratios were calculated to compare rates between demographic groups. RESULTS: Melanoma incidence was higher among females (age-adjusted incidence rates = 9.74; 95% confidence interval 9.62-9.86) compared with males (age-adjusted incidence rates = 5.77; 95% confidence interval 5.68-5.86), increased with age, and was higher in non-Hispanic white compared with Hispanic white and black, American Indians/Alaskan Natives, and Asian and Pacific Islanders populations. Melanoma incidence rates increased with year of diagnosis in females but not males. The majority of melanomas were diagnosed on the trunk in all racial and ethnic groups among males but only in non-Hispanic whites among females. Most melanomas were diagnosed at localized stage, and among those melanomas with known histology, the majority were superficial spreading. LIMITATIONS: Accuracy of melanoma cases reporting was limited because of some incompleteness (delayed reporting) or nonspecific reporting including large proportion of unspecified histology. CONCLUSIONS: Differences in incidence rates by anatomic site, histology, and stage among adolescents and young adults by race, ethnicity, and sex suggest that both host characteristics and behaviors influence risk. These data suggest areas for etiologic research around gene-environment interactions and the need for targeted cancer control activities specific to adolescents and young adult populations. |
Pulmonary function and left ventricular mass in African Americans: the Atherosclerosis Risk in Communities (ARIC) Study
Charles LE , Burchfiel CM , Andrew ME , Gu JK , Petrini MF , Butler Jr KR . Echocardiography 2011 29 (2) 131-9 PURPOSE: Impaired pulmonary function has been associated with increased cardiovascular disease incidence and mortality. The objective of this study was to investigate associations between pulmonary function and left ventricular (LV) mass. METHODS: Participants were African American women (n = 1,069) and men (n = 555) aged 49-73 years, from the Atherosclerosis Risk in Communities study. Mean pulmonary function values at the first (1987-1989) and second (1990-1992) examinations were used. Echocardiograms were performed at the third and early in the fourth examinations (1993-1996). Analysis of covariance and linear regression were used to assess associations. RESULTS: Mean levels of LV mass decreased with increasing quintiles of forced expiratory volume in one second (FEV(1) ) among female never smokers (P = 0.039). Forced vital capacity (FVC) showed stronger associations than FEV(1) with LV mass. Among men, LV mass was positively associated with FEV(1) among current and never smokers, and with FVC among never smokers. Additional analyses among never smokers revealed significant inverse associations between LV mass and FVC among women with waist-to-hip ratios of >0.85 and those with no history of diabetes. In contrast, significant positive associations between LV mass and FVC were seen among male never smokers with body mass index (BMI) of ≤24.9 kg/m(2) , waist-to-hip ratios of ≤0.95, no history of hypertension or diabetes, and ≤60 years old. BMI and waist-to-hip ratio significantly modified associations among men. CONCLUSIONS: Among never smokers, LV mass and pulmonary function were inversely associated among women and positively associated among men. Further studies are warranted. |
Effect of current depression on the association of work-related asthma with adverse asthma outcomes: a cross-sectional study using the Behavioral Risk Factor Surveillance System
Mazurek JM , Knoeller GE , Moorman JE . J Affect Disord 2011 136 (3) 1135-42 BACKGROUND: Depression has been associated with a decreased level of asthma control. The aim of our study was to examine associations between health-professional diagnosed work-related asthma (WRA) and current depression and the effect of current depression on the associations of WRA with adverse asthma outcomes. METHOD: We analyzed data from the 2006 and 2008 Behavioral Risk Factor Surveillance System Asthma Call-Back Survey and the Anxiety and Depression Module conducted in 25 states and District of Columbia for ever-employed adults with current asthma. We computed weighted proportions and prevalence ratios adjusted for age, sex, race/ethnicity, education, current employment status, and smoking status. Survey participants who were ever told by a doctor or other health professional that their asthma was related to any job they ever had were determined to have WRA. Participants with current depression were identified using self-report of depressive symptoms. RESULTS: Of ever-employed adults with current asthma, an estimated 9.1% had WRA and 17.0% had current depression. Persons with WRA were significantly more likely than those with non-WRA to have current depression. Persons with either WRA, current depression, or both WRA and current depression were significantly more likely to have adverse asthma outcomes than persons with asthma and neither condition. The associations with adverse asthma outcomes were stronger when both current depression and WRA were present. LIMITATIONS: This is a cross-sectional and hypothesis-generating study. CONCLUSIONS: Depression may play an important role in asthma management and should be considered when assessing patients with asthma and, in particular, those with WRA. |
The health burden and economic costs of cutaneous melanoma mortality by race/ethnicity-United States, 2000 to 2006
Ekwueme DU , Guy GP Jr , Li C , Rim SH , Parelkar P , Chen SC . J Am Acad Dermatol 2011 65 S133-43 BACKGROUND: Cutaneous melanoma is the most deadly form of skin cancer with more than 8000 deaths per year in the United States. The health burden and economic costs associated with melanoma mortality by race/ethnicity have not been appropriately addressed. OBJECTIVE: We sought to quantify the health burden and economic costs associated with melanoma mortality among racial/ethnic groups in the United States. METHODS: We used 2000 to 2006 national mortality data and US life tables to estimate the number of deaths, and years of potential life lost (YPLL). Further, we estimated the economic costs of melanoma mortality in terms of productivity losses. All the estimates were stratified by race/ethnicity and sex. RESULTS: From 2000 to 2006, we estimated an increase of 13,349 (8.7%) YPLL because of melanoma mortality compared with a 2.8% increase among all malignant cancers across all race/ethnicity. On average, an individual in the United States loses 20.4 years of potential life during their lifetime as a result of melanoma mortality compared with 16.6 years for all malignant cancers. The estimated annual productivity loss attributed to melanoma mortality was $3.5 billion. Our estimates suggest that an individual who died from melanoma in 2000 through 2006 would lose an average of $413,370 in forgone lifetime earnings. YPLL rates and total productivity losses are much higher among non-Hispanic whites as compared with non-Hispanic blacks and Hispanics. LIMITATIONS: The estimated economic costs did not include treatment, morbidity, and intangible costs. CONCLUSIONS: We estimated substantial YPLL and productivity losses as a result of melanoma mortality during an individual's lifetime. By examining the burden by race/ethnicity, this study provides useful information to assist policy-makers in making informed resource allocation decisions regarding cutaneous melanoma mortality. |
Association between cutaneous melanoma incidence rates among white US residents and county-level estimates of solar ultraviolet exposure
Richards TB , Johnson CJ , Tatalovich Z , Cockburn M , Eide MJ , Henry KA , Lai SM , Cherala SS , Huang Y , Ajani UA . J Am Acad Dermatol 2011 65 S50-7 BACKGROUND: Recent US studies have raised questions as to whether geographic differences in cutaneous melanoma incidence rates are associated with differences in solar ultraviolet (UV) exposure. OBJECTIVES: We sought to assess the association of solar UV exposure with melanoma incidence rates among US non-Hispanic whites. METHODS: We assessed the association between county-level estimates of average annual solar UV exposure for 1961 to 1990 and county-level melanoma incidence rates during 2004 to 2006. We used Poisson multilevel mixed models to calculate incidence density ratios by cancer stage at diagnosis while controlling for individuals' age and sex and for county-level estimates of solar UV exposure, socioeconomic status, and physician density. RESULTS: Age-adjusted rates of early- and late-stage melanoma were both significantly higher in high solar UV counties than in low solar UV counties. Rates of late-stage melanoma incidence were generally higher among men, but younger women had a higher rate of early-stage melanoma than their male counterparts. Adjusted rates of early-stage melanoma were significantly higher in high solar UV exposure counties among men aged 35 years or older and women aged 65 years or older. LIMITATIONS: The relationship between individual-level UV exposure and risk for melanoma was not evaluated. CONCLUSIONS: County-level solar UV exposure was associated with the incidence of early-stage melanoma among older US adults but not among younger US adults. Additional studies are needed to determine whether exposure to artificial sources of UV exposure or other factors might be mitigating the relationship between solar UV exposure and risk for melanoma. |
Association of cutaneous melanoma incidence with area-based socioeconomic indicators-United States, 2004-2006
Singh SD , Ajani UA , Johnson CJ , Roland KB , Eide M , Jemal A , Negoita S , Bayakly RA , Ekwueme DU . J Am Acad Dermatol 2011 65 S58-68 BACKGROUND: Socioeconomic status (SES) has been associated with melanoma incidence and outcomes. Examination of the relationship between melanoma and SES at the national level in the United States is limited. Expanding knowledge of this association is needed to improve early detection and eliminate disparities. OBJECTIVE: We sought to provide a detailed description of cutaneous melanoma incidence and stage of disease in relationship to area-based socioeconomic measures including poverty level, education, income, and unemployment in the United States. METHODS: Invasive cutaneous melanoma data reported by 44 population-based central cancer registries for 2004 to 2006 were merged with county-level SES estimates from the US Census Bureau. Age-adjusted incidence rates were calculated by gender, race/ethnicity, poverty, education, income, unemployment, and metro/urban/rural status using software. Poisson multilevel mixed models were fitted, and incidence density ratios were calculated by stage for area-based SES measures, controlling for age, gender, and state random effects. RESULTS: Counties with lower poverty, higher education, higher income, and lower unemployment had higher age-adjusted melanoma incidence rates for both early and late stage. In multivariate models, SES effects persisted for early-stage but not late-stage melanoma incidence. LIMITATIONS: Individual-level measures of SES were unavailable, and estimates were based on county-level SES measures. CONCLUSION: Our findings show that melanoma incidence in the United States is associated with aggregate county-level measures of high SES. Analyses using finer-level SES measures, such as individual or census tract level, are needed to provide more precise estimates of these associations. |
Transmission of Norovirus among NBA players and staff, Winter 2010-2011
Desai R , Yen C , Wikswo M , Gregoricus NA , Provo JE , Parashar UD , Hall AJ . Clin Infect Dis 2011 53 (11) 1115-7 In December 2010, 24 players and staff members from 13 National Basketball Association teams were affected with gastroenteritis symptoms. Four of 5 stool specimens from ill players and staff tested positive for norovirus genogroup II. We document evidence of transmission both within teams and, potentially, between teams in 2 instances. |
Universal voluntary HIV testing in antenatal care settings: a review of the contribution of provider-initiated testing & counselling
Hensen B , Baggaley R , Wong VJ , Grabbe KL , Shaffer N , Lo YR , Hargreaves J . Trop Med Int Health 2011 17 (1) 59-70 OBJECTIVE: To assess the contribution of provider-initiated testing and counselling (PITC) to achieving universal testing of pregnant women and, from available data on components of PITC, assess whether PITC adoption adheres to pre-test information, post-test counselling procedures and linkage to treatment. METHODS: Systematic review of published literature. Findings were collated and data extracted on HIV testing uptake before and after the adoption of a PITC model. Data on pre- and post-test counselling uptake and linkage to anti-retrovirals, where available, were also extracted. RESULTS: Ten eligible studies were identified. Pre-intervention testing uptake ranged from 5.5% to 78.7%. Following PITC introduction, testing uptake increased by a range of 9.9% to 65.6%, with testing uptake ≥85% in eight studies. Where reported, pre-test information was provided to between 91.5% and 100% and post-test counselling to between 82% and 99.8% of pregnant women. Linkage to ARVs for prevention of mother to child transmission (PMTCT) was reported in five studies and ranged from 53.7% to 77.2%. Where reported, PITC was considered acceptable by ANC attendees. CONCLUSION: Our review provides evidence that the adoption of PITC within ANC can facilitate progress towards universal voluntary testing of pregnant women. This is necessary to increase the coverage of PMTCT services and facilitate access to treatment and prevention interventions. We found some evidence that PITC adoption does not undermine processes inherent to good conduct of testing, with high levels of pre-test information and post-test counselling, and two studies suggesting that PITC is acceptable to ANC attendees. |
Unsafe sex among HIV-infected adults in Kenya: results of a nationally representative survey
Mwangi M , Bunnell R , Nyoka R , Gichangi A , Makokha E , Kim A , Kichamu G , Marum L , Ichwara J , Mermin J . J Acquir Immune Defic Syndr 2011 58 (1) 80-8 OBJECTIVE: Assess factors associated with knowledge of HIV status, sexual activity, and unprotected sex with a partner of unknown or negative HIV status (unsafe sex) among HIV-infected adults in Kenya. DESIGN: Nationally representative Kenya AIDS Indicator Survey among adults aged 15-64 years in 2007. METHODS: A standardized questionnaire was administered and blood samples tested for HIV. We assessed factors associated with knowledge of HIV infection, sexual activity, and unsafe sex. Analyses took into account stratification and clustering in the survey design and estimates were weighted to account for sampling probability. RESULTS: Of 15,853 participants with blood samples, 1104 (6.9%) were HIV infected. Of these, 83.8% did not know their HIV status (56% had never tested; 27.8% reported their last HIV test was negative), and 80.4% were sexually active. Of 861 sexually active adults, 76.9% reported unsafe sex in the past year. Adults who did not know their HIV status were more likely to be sexually active [never tested adjusted odds ratio (AOR): 5.5, 95% confidence interval (CI): 2.8 to 10.7; ever tested, incorrect knowledge AOR: 6.5, CI: 2.1 to 19.6) and to report unsafe sex (never tested AOR: 51.7, CI: 27.3 to 97.6; ever tested, incorrect knowledge of status AOR: 18.6, CI: 8.6 to 40.5) than those who knew their status. CONCLUSIONS: The majority of adults did not know they were infected and engaged in unsafe sex. Adults who knew their HIV status were less likely to be sexually active and report unsafe sex compared with those unaware of their infection. HIV prevention interventions that target HIV-infected adults are urgently needed. |
Identification of structural interventions for HIV/AIDS prevention: the concept mapping exercise
Abdul-Quader AS , Collins C . Public Health Rep 2011 126 (6) 777-88 Structural interventions have been defined as those prevention interventions that include physical, social, cultural, organizational, community, economic, legal, and policy factors. In an effort to examine the feasibility, evaluability, and sustainability of structural interventions for HIV prevention, the Centers for Disease Control and Prevention implemented a project that involved asking experts in HIV prevention and other areas of public health-including injury and violence prevention, tobacco control, drug abuse, and nutrition-to provide input on the identification of structural interventions based on the aforementioned definition. The process resulted in a list of 123 interventions that met the definition. The experts were asked to group these interventions into categories based on similarity of ideas. They were also asked to rate these interventions in terms of impact they would have, if implemented, on reducing HIV transmission. The findings highlight the need for conducting further research on structural interventions, including feasibility of implementation and effectiveness of reducing HIV transmission risks. |
Challenges of establishing the correct diagnosis of outbreaks of acute febrile illnesses in Africa: the case of a likely Brucella outbreak among nomadic pastoralists, Northeast Kenya, March-July 2005
Ari MD , Guracha A , Fadeel MA , Njuguna C , Njenga MK , Kalani R , Abdi H , Warfu O , Omballa V , Tetteh C , Breiman RF , Pimentel G , Feikin DR . Am J Trop Med Hyg 2011 85 (5) 909-912 An outbreak of acute febrile illness was reported among Somali pastoralists in remote, arid Northeast Kenya, where drinking raw milk is common. Blood specimens from 12 patients, collected mostly in the late convalescent phase, were tested for viral, bacterial, and parasitic pathogens. All were negative for viral and typhoid serology. Nine patients had Brucella antibodies present by at least one of the tests, four of whom had evidence suggestive of acute infection by the reference serologic microscopic agglutination test. Three patients were positive for leptospiral antibody by immunoglobulin M enzyme-linked immunosorbent assay, and two were positive for malaria. Although sensitive and specific point-of-care testing methods will improve diagnosis of acute febrile illness in developing countries, challenges of interpretation still remain when the outbreaks are remote, specimens collected too late, and positive results for multiple diseases are obtained. Better diagnostics and tools that can decipher overlapping signs and symptoms in such settings are needed. |
Characteristics of HIV-1 serodiscordant couples enrolled in a clinical trial of antiretroviral pre-exposure prophylaxis for HIV-1 prevention
Mujugira A , Baeten JM , Donnell D , Ndase P , Mugo NR , Barnes L , Campbell JD , Wangisi J , Tappero JW , Bukusi E , Cohen CR , Katabira E , Ronald A , Tumwesigye E , Were E , Fife KH , Kiarie J , Farquhar C , John-Stewart G , Kidoguchi L , Panteleeff D , Krows M , Shah H , Revall J , Morrison S , Ondrejcek L , Ingram C , Coombs RW , Lingappa JR , Celum C . PLoS One 2011 6 (10) e25828 INTRODUCTION: Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort. METHODS: HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months. RESULTS: From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758) of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28-40) and (26-39) respectively]. Most couples (98%) were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0) and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1-2.0)]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8); 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10) copies/mL (IQR 3.31-4.53) and median CD4 count was 496 cells/microL (IQR 375-662); the majority (64%) had WHO stage 1 HIV-1 disease. CONCLUSIONS: Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245). |
North American West Nile virus genotype isolates demonstrate differential replicative capacities in response to temperature.
Andrade CC , Maharaj PD , Reisen WK , Brault AC . J Gen Virol 2011 92 2523-33 The presence of West Nile virus (WNV) was first documented in California, USA, during the summer of 2003, and subsequently the virus has become endemic throughout the state. Sequence analysis has demonstrated that the circulating strains are representative of the North American (WN02) genotype that has displaced the East Coast genotype (NY99). A recent study has indicated that enhanced vector competence at elevated temperatures may have played a role in the displacement of the East Coast genotype by WN02. In the current study, four WN02 strains from California, including an initial 2003 isolate (COAV997), were compared to strain NY99 in growth curve assays in mosquito and duck embryonic fibroblast (DEF) cell lines at differing, biologically relevant temperatures to assess the relative temperature sensitivities of these natural isolates. COAV997 was significantly debilitated in viral replication in DEF cells at 44 degrees C. Full-length sequence comparison of COAV997 against the NY99 reference strain revealed non-synonymous mutations in the envelope glycoprotein (V159A), non-structural protein 1 (NS1) (K110N) and non-structural protein 4A (NS4A) (F92L), as well as two mutations in the 3' UTR: C-->T at nt 10 772 and A-->G at nt 10 851. These non-synonymous mutations were introduced into the NY99 viral backbone by site-directed mutagenesis. A mutant containing the NS1-K110N and NS4A-F92L mutations exhibited a debilitated growth phenotype in DEF cells at 44 degrees C, similar to that of COAV997. One explanation for the subsistence of this genotype is that COAV997 was obtained from an area of California where avian host species might not present elevated temperatures. These data indicate that the NS1 and NS4A mutations identified in some WN02 isolates could reduce thermal stability and impede replication of virus at temperatures observed in febrile avian hosts. |
Sporulation and survival of Toxoplasma gondii oocysts in different types of commercial cat litter
Dubey JP , Ferreira LR , Martins J , Jones JL . J Parasitol 2011 97 (5) 751-4 Toxoplasma gondii oocysts are environmentally resistant and can survive outdoors for many months in dry and cold climates. In the present study, sporulation and survival of T. gondii oocysts was studied in different types of cat litters commercially available in the United States. Oocysts sporulated within 2-3 days in all types of cat litters and occasionally remained viable for 14 days. Results indicate that cat litter should be changed daily to prevent sporulation and infectivity to people. |
Spotted fever group rickettsiae in ticks collected from wild animals in Israel
Keysary A , Eremeeva ME , Leitner M , Din AB , Wikswo ME , Mumcuoglu KY , Inbar M , Wallach AD , Shanas U , King R , Waner T . Am J Trop Med Hyg 2011 85 (5) 919-23 We report molecular evidence for the presence of spotted fever group rickettsiae (SFGR) in ticks collected from roe deer, addax, red foxes, and wild boars in Israel. Rickettsia aeschlimannii was detected in Hyalomma marginatum and Hyalomma detritum while Rickettsia massiliae was present in Rhipicephalus turanicus ticks. Furthermore, a novel uncultured SFGR was detected in Haemaphysalis adleri and Haemaphysalis parva ticks from golden jackals. The pathogenicity of the novel SFGR for humans is unknown; however, the presence of multiple SFGR agents should be considered when serological surveillance data from Israel are interpreted because of significant antigenic cross-reactivity among Rickettsia. The epidemiology and ecology of SFGR in Israel appear to be more complicated than was previously believed. |
Association of prenatal exposure to polybrominated diphenyl ethers and infant birth weight
Harley KG , Chevrier J , Schall RA , Sjodin A , Bradman A , Eskenazi B . Am J Epidemiol 2011 174 (8) 885-92 Polybrominated diphenyl ethers (PBDEs) are a class of persistent compounds that have been used as flame retardants in vehicles, household furnishings, and consumer electronics. This study examined whether concentrations of PBDEs in maternal serum during pregnancy were associated with infant birth weight, length, head circumference, and length of gestation. Participants were pregnant women (n = 286) enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal cohort study of low-income, predominantly Mexican families living in the Salinas Valley, California. Blood samples were collected near the 26th week of pregnancy in 1999-2000, and concentrations of 10 PBDE congeners (BDE-17, -28, -47, -66, -85, -99, -100, -153, -154, and -183) were measured. Multiple linear regression models were used to investigate the association of lipid-adjusted, log(10)-transformed PBDE concentrations and birth outcome. In adjusted analyses, negative associations with birth weight were seen with BDE-47 (beta = -115 g, 95% confidence interval (CI): -229, -2), BDE-99 (beta = -114 g, 95% CI: -225, -4), and BDE-100 (beta = -122 g, 95% CI: -235, -9). These findings were diminished slightly and were no longer statistically significant when maternal weight gain was included in the models. PBDE congeners were not associated with birth length, head circumference, or gestational duration. |
Tuberculosis genotyping information management system: enhancing tuberculosis surveillance in the United States.
Ghosh S , Moonan P , Cowan L , Grant J , Kammerer S , Navin T . Infect Genet Evol 2011 12 (4) 782-8 Molecular characterization of Mycobacterium tuberculosis complex isolates (genotyping) can be used by public health programs to more readily identify tuberculosis (TB) transmission. The Centers for Disease Control and Prevention's National Tuberculosis Genotyping Service has offered M. tuberculosis genotyping for every culture-confirmed case in the United States since 2004. The TB Genotyping Information Management System (TB GIMS), launched in March 2010, is a secure online database containing genotype results linked with case characteristics from the national TB registry for state and local TB programs to access, manage and analyze these data. As of September 2011, TB GIMS contains genotype results for 89% of all culture-positive TB cases for 2010. Over 400 users can generate local, national reports and maps using TB GIMS. Automated alerts on geospatially concentrated cases with matching genotypes that may represent outbreaks are also generated by TB GIMS. Thus, TB genotyping results are available to enhance national TB surveillance activities and apply genotyping results to conduct TB control activities in the United States. |
What questions should newborn screening long-term follow-up be able to answer? A statement of the US Secretary for Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children.
Hinton CF , Feuchtbaum L , Kus CA , Kemper AR , Berry SA , Levy-Fisch J , Luedtke J , Kaye C , Boyle CA . Genet Med 2011 13 (10) 861-865 The US Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children provides guidance on reducing the morbidity and mortality associated with heritable disorders detectable through newborn screening. Efforts to systematically evaluate health outcomes, beyond long-term survival, with a few exceptions, are just beginning. To facilitate these nascent efforts, the US Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children initiated a project to define the major overarching questions to be answered to assure that newborn screening is meeting its goal of achieving the best quality outcome for the affected children and their families. The questions identified follow the central components of long-term follow-up-care coordination, evidence-based treatment, continuous quality improvement, and new knowledge discovery-and are framed from the perspectives of the state and nation, primary and specialty healthcare providers, and the impacted families. These overarching questions should be used to guide the development of long-term follow-up data systems, quality health indicators, and specific data elements for evaluating the newborn screening system. |
Melanoma surveillance in the United States
Plescia M , Protzel Berman P , White MC . J Am Acad Dermatol 2011 65 S1-2 The Centers for Disease Control and Prevention (CDC), in collaboration with partners in the cancer research community and state health departments, is pleased to support this series of important articles on “Melanoma Surveillance in the United States.” This supplement represents advancements in our knowledge of melanoma incidence and trends and provides the most comprehensive, state-by-state examination of the status of melanoma cancer in the United States to date. A common and largely preventable disease, it is important to monitor and watch trends to identify opportunities for action. CDC’s National Program of Cancer Registries provides the foundation for melanoma surveillance and offers opportunities to ensure treatment quality and use cancer registry data to drive decision making on policy and systems change. These data can also be used to guide future prevention efforts and tailor early detection and primary prevention efforts to communities with the greatest needs. | CDC has been building the science base for chronic disease prevention and health promotion to improve the health of Americans. This series continues to enhance our knowledge of what works and what more needs to be done to lessen the burden of melanoma in the United States. The cost of cancer extends beyond the number of lives cut short and new diagnoses each year. Persons with melanoma, and their family members, friends, and caregivers, may face physical, emotional, social, and economic challenges as a result of their cancer diagnosis and treatment. New analyses conducted by CDC health economists in this supplement identify the costs associated with melanoma to understand the impact of the disease on society and allow us to make the business case for prevention and policy change. CDC’s Comprehensive Cancer Control Programs in states, territories, and tribal organizations provide opportunities to develop and implement policy, system, and environmental changes that can reduce exposure to ultraviolet radiation and thereby prevent skin cancer, increase access to quality treatment, and address the long-term needs of cancer survivors. |
Melanoma surveillance in the United States: overview of methods
Watson M , Johnson CJ , Chen VW , Thomas CC , Weir HK , Sherman R , Cockburn M , Jackson-Thompson J , Saraiya M . J Am Acad Dermatol 2011 65 S6-S16 BACKGROUND: Skin cancer is the most common form of cancer in the United States. Melanoma skin cancer is particularly deadly; more than 8000 US residents die from it each year. Although recent reports suggest that melanoma incidence rates have been increasing, these apparent increases could be caused by an increase in reporting and/or screening, and by an actual increase in the occurrence of melanoma. OBJECTIVE: In this report, we describe methods used in this supplement to assess the current burden of melanoma in the United States using data from two federal cancer surveillance programs: the Centers for Disease Control and Prevention (CDC) National Program of Cancer Registries and the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results program. We also provide basic descriptive epidemiologic data about melanoma in the United States. METHODS: Cancer incidence data from population-based cancer registries that participate in the CDC National Program of Cancer Registries and/or the NCI Surveillance, Epidemiology, and End Results Program covering 78% of the US population for 2004 to 2006 were used. RESULTS: Over 45 thousand melanomas were diagnosed annually, with a rate of 19 cases per 100,000 persons. LIMITATIONS: Melanoma rates may vary because of differences in reporting, diagnosis, and screening. CONCLUSION: To our knowledge, the articles in this supplement constitute the first comprehensive examination of the overall burden of melanoma in the United States based on data from a majority of the US population. |
Melanoma survival in the United States, 1992 to 2005
Pollack LA , Li J , Berkowitz Z , Weir HK , Wu XC , Ajani UA , Ekwueme DU , Li C , Pollack BP . J Am Acad Dermatol 2011 65 S78-86 BACKGROUND: Population-based data on melanoma survival are important for understanding the impact of demographic and clinical factors on prognosis. OBJECTIVE: We describe melanoma survival by age, sex, race/ethnicity, stage, depth, histology, and site. METHODS: Using Surveillance, Epidemiology, and End Results data, we calculated unadjusted cause-specific survival up to 10 years from diagnosis for 68,495 first primary cases of melanoma diagnosed from 1992 to 2005. Cox multivariate analysis was performed for 5-year survival. Data from 1992 to 2001 were divided into 3 time periods to compare stage distribution and differences in stage-specific 5-year survival over time. RESULTS: Melanomas that had metastasized (distant stage) or were thicker than 4.00 mm had a poor prognosis (5-year survival: 15.7% and 56.6%). The 5-year survival for men was 86.8% and for persons given the diagnosis at age 65 years or older was 83.2%, varying by stage at diagnosis. Scalp/neck melanoma had lower 5-year survival (82.6%) than other anatomic sites; unspecified/overlapping lesions had the least favorable prognosis (41.5%). Nodular and acral lentiginous melanomas had the poorest 5-year survival among histologic subtypes (69.4% and 81.2%, respectively). Survival differences by race/ethnicity were observed in the unadjusted survival, but nonsignificant in the multivariate analysis. Overall 5-year melanoma survival increased from 87.7% to 90.1% for melanomas diagnosed in 1992 through 1995 compared with 1999 through 2001, and this change was not clearly associated with a shift toward localized diagnosis. LIMITATIONS: Prognostic factors included in revised melanoma staging guidelines were not available for all study years and were not examined. CONCLUSIONS: Poorer survival from melanoma was observed among those given the diagnosis at late stage and older age. Improvements in survival over time have been minimal. Although newly available therapies may impact survival, prevention and early detection are relevant to melanoma-specific survival. |
Mixing in age-structured population models of infectious diseases
Glasser J , Feng Z , Moylan A , Del Valle S , Castillo-Chavez C . Math Biosci 2011 235 (1) 1-7 Infectious diseases are controlled by reducing pathogen replication within or transmission between hosts. Models can reliably evaluate alternative strategies for curtailing transmission, but only if interpersonal mixing is represented realistically. Compartmental modelers commonly use convex combinations of contacts within and among groups of similarly aged individuals, respectively termed preferential and proportionate mixing. Recently published face-to-face conversation and time-use studies suggest that parents and children and co-workers also mix preferentially. As indirect effects arise from the off-diagonal elements of mixing matrices, these observations are exceedingly important. Accordingly, we refined the formula published by Jacquez et al. [19] to account for these newly-observed patterns and estimated age-specific fractions of contacts with each preferred group. As the ages of contemporaries need not be identical nor those of parents and children to differ by exactly the generation time, we also estimated the variances of the Gaussian distributions with which we replaced the Kronecker delta commonly used in theoretical studies. Our formulae reproduce observed patterns and can be used, given contacts, to estimate probabilities of infection on contact, infection rates, and reproduction numbers. As examples, we illustrate these calculations for influenza based on "attack rates" from a prospective household study during the 1957 pandemic and for varicella based on cumulative incidence estimated from a cross-sectional serological survey conducted from 1988-94, together with contact rates from the several face-to-face conversation and time-use studies. Susceptibility to infection on contact generally declines with age, but may be elevated among adolescents and adults with young children. |
Estimated global incidence of Japanese encephalitis: a systematic review
Campbell GL , Hills SL , Fischer M , Jacobson JA , Hoke CH , Hombach JM , Marfin AA , Solomon T , Tsai TF , Tsu VD , Ginsburg AS . Bull World Health Organ 2011 89 (10) 766-774E OBJECTIVE: To update the estimated global incidence of Japanese encephalitis (JE) using recent data for the purpose of guiding prevention and control efforts. METHODS: Thirty-two areas endemic for JE in 24 Asian and Western Pacific countries were sorted into 10 incidence groups on the basis of published data and expert opinion. Population-based surveillance studies using laboratory-confirmed cases were sought for each incidence group by a computerized search of the scientific literature. When no eligible studies existed for a particular incidence group, incidence data were extrapolated from related groups. FINDINGS: A total of 12 eligible studies representing 7 of 10 incidence groups in 24 JE-endemic countries were identified. Approximately 67,900 JE cases typically occur annually (overall incidence: 1.8 per 100,000), of which only about 10% are reported to the World Health Organization. Approximately 33,900 (50%) of these cases occur in China (excluding Taiwan) and approximately 51,000 (75%) occur in children aged 0-14 years (incidence: 5.4 per 100,000). Approximately 55,000 (81%) cases occur in areas with well established or developing JE vaccination programmes, while approximately 12,900 (19%) occur in areas with minimal or no JE vaccination programmes. CONCLUSION: Recent data allowed us to refine the estimate of the global incidence of JE, which remains substantial despite improvements in vaccination coverage. More and better incidence studies in selected countries, particularly China and India, are needed to further refine these estimates. |
Targeting children through school-based education and policy strategies: comprehensive cancer control activities in melanoma prevention
Townsend JS , Pinkerton B , McKenna SA , Higgins SM , Tai E , Steele CB , Derrick SR , Brown C . J Am Acad Dermatol 2011 65 S104-13 BACKGROUND: Primary school-based educational strategies are proven interventions to raise children's awareness and knowledge about sun safety. OBJECTIVE: We highlight barriers and facilitators to implementing interventions across multiple populations in 3 state comprehensive cancer control programs/partnerships that implemented primary school-based sun-safety educational programs. METHODS: Using a case study approach, we collected semistructured program information and evaluation results from New Mexico's Raising Awareness in Youth about Sun Safety Project, the Sun Protection in Florida Project, and the Arizona SunWise Program. RESULTS: Each program used different strategies for implementing school-based educational programs in their respective state based on local needs, funding constraints, and unique characteristics of their populations. Barriers to implementation included difficulties reaching schools and school administrators and changes in staff workload. Facilitators to implementation included using innovative recruitment approaches (mini grants, school assemblies), having community partners, reaching out to educators in various settings, and having program advocates within schools. Each program placed emphasis on supplementing educational programs with sun-safety policies. LIMITATIONS: We only present a case study from 3 comprehensive cancer control programs/partnerships. Rigorous evaluation methods are needed to test the effectiveness of the various strategies that were used to implement these programs on a population-based level. CONCLUSION: Partnerships and program advocates are important for successfully implementing and sustaining sun-safety programs. Innovative strategies for reaching school administrators are likely needed to effectively implement sun-safety programs and policies. School policy and environmental change are important and valued components of sun-safety programs. |
From brain passage to cell adaptation: the road of human rabies vaccine development
Wu X , Smith TG , Rupprecht CE . Expert Rev Vaccines 2011 10 (11) 1597-608 A major challenge for global rabies prevention and control is the lack of sufficient and affordable high quality vaccines. Such candidates should be pure, potent, safe, effective and economical to produce, with broad cross-reactivity against viral variants of public health and veterinary importance. The history of licensed human vaccines reviewed herein demonstrates clearly how the field has evolved to the current state of more passive development and postexposure management. Modern cell culture techniques provide adequate viral substrates for production of representative verified virus seeds. In contrast to outdated nervous tissue-based rabies vaccines, once a suitable substrate is identified, production of high titer virus results in a major qualitative and quantitative difference. Given the current scenario of only inactivated vaccines for humans, highly cell-adapted and stable, attenuated rabies viruses are ideal candidates for consideration to meet the need for seed viruses in the future. |
Immunogenicity of hepatitis B vaccine among hemodialysis patients: effect of revaccination of non-responders and duration of protection
Chaves SS , Daniels D , Cooper BW , Malo-Schlegel S , Macarthur S , Robbins KC , Kobetitsch JF , McDaniel A , D'Avella JF , Alter MJ . Vaccine 2011 29 (52) 9618-23 BACKGROUND: Hepatitis B vaccination is recommended for patients on hemodialysis, however, seroprotection after a primary vaccine series is suboptimum. Limited data are available on the effect of revaccination of non-responders and on persistence of immunity in this population. METHODS: Hepatitis B vaccine (40mcg/dose) was given to 77 susceptible patients on hemodialysis (0, 1, and 6 month schedule). Levels of hepatitis B surface antibody (anti-HBs) were tested ≥28 days after the third dose was administered, and non-responders revaccinated with an additional 3-dose series. Vaccine responders (anti-HBs ≥10mIU/mL) were re-tested every 6 months and booster doses given as needed. Kaplan-Meier survival curve was used to estimate the probability of maintaining protective antibody level. Cox-proportional hazards models were used to assess the association between time to loss of protective antibody levels and certain explanatory variables. RESULTS: Overall primary vaccine-induced response was 79.2% (95% CI 68.2%, 87.3%), including 49/77 (63.6%; 95% CI 51.8%, 74.7%) patients who received the initial primary hepatitis B vaccine series and 12/21 (57.1%; 95% CI 34.4%, 77.4%) non-responders who were revaccinated with an additional series. Among weak responders (anti-HBs level 10.0-99.9mIU/mL), protective antibody levels persisted in 44% for 12 months post-vaccination; whereas among strong responders (anti-HBs level ≥100mIU/mL), protective antibody levels persisted in 92% for 12 months, and 68% for 24 months post-vaccination. A weak post-vaccination response increased the risk of losing protective antibody levels (adjusted hazard ratio, 9.7; 95% confidence interval, 3.5-28.5; p<0.0001). CONCLUSION: Revaccinating patients undergoing hemodialysis who do not respond to a primary vaccine series substantially increases the pool of protected patients. The threshold for defining hepatitis B vaccine-induced immunity should be revisited in this patient population to maximize the duration of protection. |
Improving immunogenicity and effectiveness of influenza vaccine in older adults
Cao W , Kim JH , Chirkova T , Reber AJ , Biber R , Shay DK , Sambhara S . Expert Rev Vaccines 2011 10 (11) 1529-37 Aging is associated with a decline in immune function (immunosenescence) that leads to progressive deterioration in both innate and adaptive immune functions. These changes contribute to the subsequent increased risk for infectious diseases and their sequelae. Vaccination is the most effective and inexpensive public health strategy for prevention of infection, despite the decreased efficacy of vaccines in older adults due to immunosenescence. The rapid rise in the older adult population globally represents a great challenge for vaccination programs. This article first addresses the status of innate and adaptive immune functions in aging and then focuses on influenza vaccine. The development history of influenza vaccines, current status, and potential strategies to improve the immunogenicity and vaccine effectiveness in older adults are discussed. |
Institutional requirements for influenza vaccination of healthcare personnel: results from a nationally representative survey of acute care hospitals--United States, 2011
Miller BL , Ahmed F , Lindley MC , Wortley PM . Clin Infect Dis 2011 53 (11) 1051-9 BACKGROUND: Many health professional organizations now endorse influenza vaccination as a condition of employment in healthcare settings. Our objective was to describe institutional requirements for influenza vaccination of healthcare personnel (HCP) among US hospitals during the 2010-2011 influenza season. METHODS: A survey was mailed in 2011 to a nationally representative sample of 998 acute care hospitals. An institutional requirement was defined as "a policy that requires HCP to receive or decline influenza vaccination, with or without consequences for vaccine refusal." A weighted analysis included univariate analyses and logistic regression. RESULTS: Of responding hospitals (n = 808; 81.0%), 440 (55.6%) reported institutional requirements for influenza vaccination. Although employees were uniformly subject to requirements, nonemployees often were not. The proportion of requirements with consequences for vaccine refusal was 44.4% (n = 194); where consequences were imposed, nonmedical exemptions were often granted (69.3%). Wearing a mask was the most common consequence (74.2% of 194 requirements); by contrast, 29 hospitals (14.4%) terminated unvaccinated HCP. After adjustment for demographic factors, the following characteristics remained significantly associated with requirements: location in a state requiring HCP to receive or decline influenza vaccine, caring for inpatients that are potentially vulnerable to influenza, use of ≥9 Advisory Committee on Immunization Practices-recommended, evidence-based influenza vaccination campaign strategies, and for-profit ownership. CONCLUSIONS: Influenza vaccination requirements were prevalent among hospitals of varying size and location. However, few policies were as stringent or as comprehensive as those endorsed by health professional organizations. Because influenza vaccination requirements are a viable alternative for hospitals unable to achieve high coverage through voluntary policies, there is still substantial room for improvement. |
Causality assessment of serious neurologic adverse events following 2009 H1N1 vaccination
Williams SE , Pahud BA , Vellozzi C , Donofrio PD , Dekker CL , Halsey N , Klein NP , Baxter RP , Marchant CD , Larussa PS , Barnett ED , Tokars JI , McGeeney BE , Sparks RC , Aukes LL , Jakob K , Coronel S , Sejvar JJ , Slade BA , Edwards KM . Vaccine 2011 29 (46) 8302-8 BACKGROUND: Adverse events occurring after vaccination are routinely reported to the Vaccine Adverse Event Reporting System (VAERS). We studied serious adverse events (SAEs) of a neurologic nature reported after receipt of influenza A (H1N1) 2009 monovalent vaccine during the 2009-2010 influenza season. Investigators in the Clinical Immunization Safety Assessment (CISA) network sought to characterize these SAEs and to assess their possible causal relationship to vaccination. METHODS: Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) physicians reviewed all SAE reports (as defined by the Code of Federal Regulations, 21CFR section 314.80) after receipt of H1N1 vaccine reported to VAERS between October 1, 2009 and March 31, 2010. Non-fatal SAE reports with neurologic presentation were referred to CISA investigators, who requested and reviewed additional medical records and clinical information as available. CISA investigators assessed the causal relationship between vaccination and the event using modified WHO criteria as defined. RESULTS: 212 VAERS reports of non-fatal serious neurological events were referred for CISA review. Case reports were equally distributed by gender (50.9% female) with an age range of 6 months to 83 years (median 38 years). The most frequent diagnoses reviewed were: Guillain-Barre Syndrome (37.3%), seizures (10.8%), cranial neuropathy (5.7%), and acute disseminated encephalomyelitis (3.8%). Causality assessment resulted in classification of 72 events as "possibly" related (33%), 108 as "unlikely" related (51%), and 20 as "unrelated" (9%) to H1N1 vaccination; none were classified as "probable" or "definite" and 12 were unclassifiable (6%). CONCLUSION: The absence of a specific test to indicate whether a vaccine component contributes to the pathogenesis of an event occurring within a biologically plausible time period makes assessing causality difficult. The development of standardized protocols for providers to use in evaluation of adverse events following immunization, and rapid identification and follow-up of VAERS reports could improve causality assessment. |
Chlamydia vaccines: recent developments and the role of adjuvants in future formulations
Igietseme JU , Eko FO , Black CM . Expert Rev Vaccines 2011 10 (11) 1585-96 Bacteria of the genus Chlamydia cause a plethora of ocular, genital and respiratory diseases that continue to pose a considerable public health challenge worldwide. The major diseases are conjunctivitis and blinding trachoma, non-gonococcal urethritis, cervicitis, pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility and interstitial pneumonia. The rampart asymptomatic infections prevent timely and effective antibiotic treatments, and quite often clinical presentation of sequelae is the first evidence of an infection. Besides, significant broad coverage in population screening and treatment is economically and logistically impractical, and mass education for public awareness has been ineffective. The current medical opinion is that an efficacious prophylactic vaccine is the best approach to protect humans from chlamydial infections. Unfortunately, a human vaccine has yet to be realized despite successful veterinary vaccines. Fortunately, recent advances in chlamydial immunobiology, cell biology, molecular pathogenesis, genomics, antigen discovery and animal models of infections are hastening progress toward an efficacious vaccine. Thus, it is established that Chlamydia immunity is mediated by T cells and a complementary antibody response, and several potential vaccine candidates have been identified. However, further advances are needed in effective vaccine delivery systems and safe potent adjuvants to boost and sustain immune responses for long-lasting protective immunity. This article focuses on the current status of human chlamydial vaccine research, specifically how application of new delivery systems and human compatible adjuvants could lead to a timely achievement of efficacious Chlamydia vaccines. The ranking of the candidate vaccine antigens for human vaccine development will await the availability of results from studies in which the antigens are tested by comparable experimental standards, such as antigen-adjuvant combination, route of delivery and possible toxicity. |
Psychopathy, reactive aggression, and precarious proclamations: a review of behavioral, cognitive, and biological research
Reidy DE , Shelley-Tremblay JF , Lilienfeld SO . Aggress Violent Behav 2011 16 (6) 512-524 Psychopathic personality (psychopathy) is associated with a heightened risk for physical aggression, although the nature of this link remains unclear. Despite widespread claims that psychopathy is associated with reactive aggression, the evidence for this assertion is mixed. We provide a comprehensive review of behavioral, cognitive, and biological research on the relation between psychopathy and aggression, and conclude that although psychopathy is clearly associated with instrumental aggression, its association with reactive aggression is not robust. In fact, at least some research points to a potential protective role of psychopathy against reactive aggression. We conclude that future research must clarify the differential implications of the separable components of the broad psychopathy construct before the relations between psychopathy and physical aggression can be adequately understood. 2011. |
Evaluation of pooling strategies for acute HIV-1 infection screening using nucleic acid amplification testing.
Sullivan TJ , Patel P , Hutchinson A , Ethridge SF , Parker MM . J Clin Microbiol 2011 49 (10) 3667-8 A 128-member specimen pooling scheme for acute HIV infection (AHI) detection was evaluated using 21 AHI specimens (range, 1,520 to 500,000 copies/ml) previously identified by RNA testing of 16-member plasma pools. HIV-1 RNA was detectable in 128-member pools for all 21 specimens; however, one pool created from a specimen with 1,827 copies/ml was nonreactive in one of three replicates. |
Translational research to develop a human PBPK models tool kit - volatile organic compounds (VOCs)
Mumtaz MM , Ray M , Crowell SR , Keys D , Fisher J , Ruiz P . J Toxicol Environ Health A 2012 75 (1) 6-24 Toxicity and exposure evaluations remain the two of the key components of human health assessment. While improvement in exposure assessment relies on a better understanding of human behavior patterns, toxicity assessment still relies to a great extent on animal toxicity testing and human epidemiological studies. Recent advances in computer modeling of the dose-response relationship and distribution of xenobiotics in humans to important target tissues have advanced our abilities to assess toxicity. In particular, physiologically based pharmacokinetic (PBPK) models are among the tools than can enhance toxicity assessment accuracy. Many PBPK models are available to the health assessor, but most are so difficult to use that health assessors rarely use them. To encourage their use these models need to have transparent and user-friendly formats. To this end the Agency for Toxic Substances and Disease Registry (ATSDR) is using translational research to increase PBPK model accessibility, understandability, and use in the site-specific health assessment arena. The agency has initiated development of a human PBPK tool-kit for certain high priority pollutants. The tool kit comprises a series of suitable models. The models are recoded in a single computer simulation language and evaluated for use by health assessors. While not necessarily being state-of-the-art code for each chemical, the models will be sufficiently accurate to use for screening purposes. This article presents a generic, seven-compartment PBPK model for six priority volatile organic compounds (VOCs): benzene (BEN), carbon tetrachloride (CCl(4)), dichloromethane (DCM), perchloroethylene (PCE), trichloroethylene (TCE), and vinyl chloride (VC). Limited comparisons of the generic and original model predictions to published kinetic data were conducted. A goodness of fit was determined by calculating the means of the sum of the squared differences (MSSDs) for simulation vs. experimental kinetic data using the generic and original models. Using simplified solvent exposure assumptions for oral ingestion and inhalation, steady-state blood concentrations of each solvent were simulated for exposures equivalent to the ATSDR Minimal Risk Levels (MRLs). The predicted blood levels were then compared to those reported in the National Health and Nutrition ExaminationSurvey (NHANES). With the notable exception of BEN, simulations of combined oral and inhalation MRLs using our generic VOC model yielded blood concentrations well above those reported for the 95th percentile blood concentrations for the U.S. populations, suggesting no health concerns. When the PBPK tool kit is fully developed, risk assessors will have a readily accessible tool for evaluating human exposure to a variety of environmental pollutants. |
Dermal penetration potential of perfluorooctanoic acid (PFOA) in human and mouse skin
Franko J , Meade BJ , Frasch HF , Barbero AM , Anderson SE . J Toxicol Environ Health A 2012 75 (1) 50-62 Recent data, using a murine model, have indicated that dermal exposure to perfluorooctanoic acid (PFOA) induces immune modulation, suggesting that this may be an important route of PFOA exposure. To investigate the dermal penetration potential of PFOA, serum concentrations were analyzed in mice following topical application. Statistically significant and dose-responsive increases in serum PFOA concentrations were identified. In vitro dermal penetration studies also demonstrated that PFOA permeates both mouse and human skin. Investigation into the mechanisms mediating PFOA penetration demonstrated that dermal absorption was strongly dependent upon the ionization status of PFOA. In addition, PFOA solid, but not 1% PFOA/acetone solution, was identified as corrosive using a cultured epidermis in vitro model. Despite its corrosive potential, expression of inflammatory cytokines in the skin of topically exposed mice was not altered. These data suggest that PFOA is dermally absorbed and that under certain conditions the skin may be a significant route of exposure. |
Tuberculosis biomarker and surrogate endpoint research roadmap
Nahid P , Saukkonen J , Mac Kenzie WR , Johnson JL , Phillips PPJ , Andersen J , Bliven-Sizemore E , Belisle JT , Boom WH , Luetkemeyer A , Campbell TB , Eisenach KD , Hafner R , Lennox JL , Makhene M , Swindells S , Villarino ME , Weiner M , Benson C , Burman W . Am J Respir Crit Care Med 2011 184 (8) 972-979 The Centers for Disease Control and Prevention and National Institutes of Health convened a multidisciplinary meeting to discuss surrogate markers of treatment response in tuberculosis. The goals were to assess recent surrogate marker research and to provide specific recommendations for (1) the qualification and validation of biomarkers of treatment outcome; (2) the standardization of specimen and data collection for future clinical trials, including a minimum set of samples and collection time points; and (3) the creation of a specimen repository to support biomarker testing. This article summarizes these recommendations and provides a roadmap for their implementation. |
A multicenter evaluation of a new antibody test kit for lymphatic filariasis employing recombinant Brugia malayi antigen Bm-14
Weil GJ , Curtis KC , Fischer PU , Won KY , Lammie PJ , Joseph H , Melrose WD , Brattig NW . Acta Trop 2011 120 Suppl 1 S19-22 Antibody tests are useful for mapping the distribution of lymphatic filariasis (LF) in countries and regions and for monitoring progress in elimination programs based on mass drug administration (MDA). Prior antibody tests have suffered from poor sensitivity and/or specificity or from a lack of standardization. We conducted a multicenter evaluation of a new commercial ELISA that detects IgG4 antibodies to the recombinant filarial antigen Bm14. Four laboratories tested a shared panel of coded serum or plasma samples that included 55 samples from people with microfilaremic Wuchereria bancrofti or Brugia infections and 26 control samples. Qualitative results were identical in all four test sites. In addition, each laboratory tested samples from their own serum banks. The test detected antibodies in 32 of 36 samples (91%) from people with Brugian filariasis and in 96 of 98 samples (98%) from people with Bancroftian filariasis. Specificity testing showed that many serum or plasma samples from patients with other filarial infections such as onchocerciasis had positive antibody tests. Specificity was otherwise excellent, although 3 of 30 samples from patients with ascariasis and 4 of 51 with strongyloidiasis had positive antibody tests; it is likely that some or all of these people had previously lived in filariasis-endemic areas. Antibody test results obtained with eluates from blood dried on filter paper were similar to those obtained with plasma tested at the same dilution. This test may be helpful for diagnosing LF in patients with clinical signs of filariasis. It may also be a useful tool for use in LF endemic countries to monitor the progress of filariasis elimination programs and for post-MDA surveillance. |
Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum
Torres-Altoro MI , Mathur BN , Drerup JM , Thomas R , Lovinger DM , O'Callaghan JP , Bibb JA . J Neurochem 2011 119 (2) 303-13 The neurological effects of organophosphate (OP) pesticides, commonly used on foods and in households, are an important public health concern. Furthermore, subclinical exposure to combinations of organophosphates is implicated in Gulf War illness. Here, we characterized the effects of the broadly used insecticide chlorpyrifos (CPF) on dopamine and glutamatergic neurotransmission effectors in corticostriatal motor/reward circuitry. CPF potentiated protein kinase A (PKA)-dependent phosphorylation of the striatal protein dopamine- and cAMP-regulated phosphoprotein of M(r) 32 kDa (DARPP-32) and the glutamate receptor 1 (GluR1) subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in mouse brain slices. It also increased GluR1 phosphorylation by PKA when administered systemically. This correlated with enhanced glutamate release from cortical projections in rat striatum. Similar effects were induced by the sarin congener, diisopropyl fluorophosphate, alone or in combination with the putative neuroprotectant, pyridostigmine bromide and the pesticide N,N-diethyl-meta-toluamide (DEET). This combination, meant to mimic the neurotoxicant exposure encountered by veterans of the 1991 Persian Gulf War, also induced hyperphosphorylation of the neurofibrillary tangle-associated protein tau. Diisopropyl fluorophosphate and pyrodostigmine bromide, alone or in combination, also increased the aberrant activity of the protein kinase, Cdk5, as indicated by conversion of its activating cofactor p35 to p25. Thus, consistent with recent findings in humans and animals, organophosphate exposure causes dysregulation in the motor/reward circuitry and invokes mechanisms associated with neurological disorders and neurodegeneration. (J. Neurochem. (2011) 119, 303-313.) |
Implementation of the INNO-LiPA Rif. TB(R) line-probe assay in rapid detection of multidrug-resistant tuberculosis in Latvia
Skenders GK , Holtz TH , Riekstina V , Leimane V . Int J Tuberc Lung Dis 2011 15 (11) 1546-53 SETTING: In Latvia, 11% of tuberculosis (TB) patients have multidrug-resistant TB (MDR-TB). The INNO-LiPA Rif.TB (R) line-probe assay (LPA) detects rifampin (RMP) resistance and may accelerate the time to effective MDRTB treatment. OBJECTIVE: To determine the impact of LPA on time to diagnosis, initiation of treatment, sputum culture conversion and treatment outcome. DESIGN: From October 2004 to September 2006, we performed LPA and drug susceptibility testing (DST) using BACTEC and Lowenstein-Jensen (LJ) media among all individuals at risk for MDR-TB compared to a 2003 cohort of 48 MDR-TB patients detected by BACTEC. RESULTS: In a total of 107 sputum smear-positive individuals at risk for MDR-TB, Mycobacterium tuberculosis was isolated from 85; 23 were RMP-resistant on LJ compared to 22 on LPA (96% sensitivity). There was a significant difference in the mean time between specimen collection and LPA result (10.0 days) and BACTEC DST result (17.0 days, P = 0.0005) in the LPA cohort. The LPA cohort achieved culture conversion a median of 105 days after treatment initiation vs. a median of 88.5 days (P = 0.54) in the BACTEC cohort. There was no difference in the proportion achieving culture conversion (P = 0.54) or in treatment outcome ( P = 0.65). CONCLUSION: LPA accelerated empiric treatment, but did not reduce the time to culture conversion or improve the rate of culture conversion or treatment outcome. |
Interlaboratory evaluation of trace element determination in workplace air filter samples by inductively coupled plasma mass spectrometry
Ashley K , Shulman SA , Brisson MJ , Howe AM . J Environ Monit 2011 14 (2) 360-7 Inductively coupled plasma mass spectrometry (ICP-MS) is becoming more widely used for trace elemental analysis in the occupational hygiene field, and consequently new ICP-MS international standard procedures have been promulgated by ASTM International and ISO. However, there is a dearth of interlaboratory performance data for this analytical methodology. In an effort to fill this data void, an interlaboratory evaluation of ICP-MS for determining trace elements in workplace air samples was conducted, towards fulfillment of method validation requirements for international voluntary consensus standard test methods. The study was performed in accordance with applicable statistical procedures for investigating interlaboratory precision. The evaluation was carried out using certified 37-mm diameter mixed-cellulose ester (MCE) filters that were fortified with 21 elements of concern in occupational hygiene. Elements were spiked at levels ranging from 0.025 to 10 mug filter(-1), with three different filter loadings denoted "Low", "Medium" and "High". Participating laboratories were recruited from a pool of over fifty invitees; ultimately twenty laboratories from Europe, North America and Asia submitted results. Triplicates of each certified filter with elemental contents at three different levels, plus media blanks spiked with reagent, were conveyed to each volunteer laboratory. Each participant was also provided a copy of the test method which each participant was asked to follow; spiking levels were unknown to the participants. The laboratories were requested to prepare the filters by one of three sample preparation procedures, i.e., hotplate digestion, microwave digestion or hot block extraction, which were described in the test method. Participants were then asked to analyze aliquots of the prepared samples by ICP-MS, and to report their data in units of mug filter(-1). Most interlaboratory precision estimates were acceptable for medium- and high-level spikes (RSD <25%), but generally yielded greater uncertainties than were anticipated at the outset of the study. |
Lack of maternal folic acid supplementation is associated with heart defects in Down syndrome: a report from the National Down Syndrome Project.
Bean LJH , Allen EG , Tinker SW , Hollis ND , Locke AE , Druschel C , Hobbs CA , O'Leary L , Romitti PA , Royle MH , Torfs CP , Dooley KJ , Freeman SB , Sherman SL . Birth Defects Res A Clin Mol Teratol 2011 91 (10) 885-93 BACKGROUND: Maternal folic acid supplementation has been associated with a reduced risk for neural tube defects and may be associated with a reduced risk for congenital heart defects and other birth defects. Individuals with Down syndrome are at high risk for congenital heart defects and have been shown to have abnormal folate metabolism. METHODS: As part of the population-based case-control National Down Syndrome Project, 1011 mothers of infants with Down syndrome reported their use of supplements containing folic acid. These data were used to determine whether a lack of periconceptional maternal folic acid supplementation is associated with congenital heart defects in Down syndrome. We used logistic regression to test the relationship between maternal folic acid supplementation and the frequency of specific heart defects correcting for maternal race or ethnicity, proband sex, maternal use of alcohol and cigarettes, and maternal age at conception. RESULTS: Lack of maternal folic acid supplementation was more frequent among infants with Down syndrome and atrioventricular septal defects (odds ratio [OR], 1.69; 95% confidence interval [CI], 1.08-2.63; p = 0.011) or atrial septal defects (OR, 1.69; 95% CI, 1.11-2.58; p = 0.007) than among infants with Down syndrome and no heart defect. Preliminary evidence suggests that the patterns of association differ by race or ethnicity and sex of the proband. There was no statistically significant association with ventricular septal defects (OR, 1.26; 95% CI, 0.85-1.87; p = 0.124). CONCLUSIONS: Our results suggest that lack of maternal folic acid supplementation is associated with septal defects in infants with Down syndrome. (Birth Defects Research (Part A), 2011. (c) 2011 Wiley-Liss, Inc.) |
Trends in health-related behavioral risk factors among pregnant women in the United States: 2001-2009
Zhao G , Ford ES , Tsai J , Li C , Ahluwalia IB , Pearson WS , Balluz LS , Croft JB . J Womens Health (Larchmt) 2011 21 (3) 255-63 BACKGROUND: Unhealthy lifestyle behaviors during pregnancy often predispose women to multiple risks including adverse pregnancy outcomes and impaired health status for mothers. This study assessed the trends in the prevalence of health-related behavioral risk factors over time among U.S. pregnant women. METHODS: Data from 22,604 pregnant women aged 18-44 years who participated in the 2001-2009 Behavioral Risk Factor Surveillance System were analyzed to assess the trends in the prevalence of behavioral risk factors. Correlates of having individual or clustering healthy behaviors were also assessed among 2295 pregnant women in the 2009 survey. RESULTS: From 2001 to 2009, among pregnant women, the age-adjusted prevalence of engaging in leisure-time exercise and receiving influenza vaccination increased significantly (p<0.05 for linear trends); the prevalence of any alcohol consumption decreased marginally (p=0.065 for linear trend); and the prevalence of binge drinking, smoking, and consuming fruits and vegetables ≥5 times/day varied little. Over the 9 years, the percentages of pregnant women who reported having all four healthy behaviors (i.e., not currently smoking, no alcohol consumption, engaging in leisure-time exercise, and receiving influenza vaccination) increased linearly from 7.3% in 2001 to 21.2% in 2009 (p<0.001). Sociodemographic characteristics, perceived health status, and health-care availability were differentially associated with certain individual or clustered healthy behaviors. CONCLUSION: Increased efforts emphasizing multiple health-related behavioral risk factors including reducing alcohol use, binge drinking, and smoking and improving fruit and vegetable consumption during pregnancy are needed. |
Use of folic acid and vitamin supplementation among adults with depression and anxiety: a cross-sectional, population-based survey
Zhao G , Ford ES , Li C , Greenlund KJ , Croft JB , Balluz LS . Nutr J 2011 10 102 BACKGROUND: Evidence suggests that folate deficiency may be causatively linked to depressive symptoms. However, little is known on the status of use of folic acid and vitamin supplements among people with mental disorders. This study examined the prevalence and the likelihood of use of folic acid or vitamin supplements among adults with depression and anxiety in comparison to those without these conditions. METHODS: Using data from 46,119 participants (aged ≥ 18 years) in the 2006 Behavioral Risk Factor Surveillance System survey, we estimated the adjusted prevalence and odds ratios with 95% confidence intervals for taking folic acid and vitamin supplements among those with ever diagnosed depression (n = 8, 019), ever diagnosed anxiety (n = 5, 546) or elevated depressive symptoms (n = 3, 978, defined as having a depression severity score of ≥ 10 on the Patient Health Questionnaire-8 diagnostic algorithm). RESULTS: Overall, women were more likely than men to take folic acid supplements 1-4 times/day (50.2% versus 38.7%, P < 0.001) and vitamin supplements (62.5% versus 49.8%, P < 0.001). After multivariate adjustment, men with ever diagnosed depression or anxiety were 42% and 83%, respectively, more likely to take folic acid supplements < 1 time/day; 44% and 39%, respectively, more likely to take folic acid supplements 1-4 times/day; and 40% and 46%, respectively, more likely to take vitamin supplements compared to men without these conditions (P < 0.05 for all comparisons). Women with ever diagnosed depression were 13% more likely to take folic acid supplements 1-4 times/day and 15% more likely to take vitamin supplements than women without this condition (P < 0.05 for both comparisons). Use of folic acid and vitamin supplements did not differ significantly by elevated depressive symptoms in either sex. CONCLUSION: The prevalence and the likelihood of taking folic acid and vitamin supplements varied substantially by a history of diagnosed depression among both men and women and by a history of diagnosed anxiety among men, but not by presence of elevated depressive symptoms in either sex. |
Effects of multimicronutrient home fortification on anemia and growth in Bhutanese refugee children
Bilukha O , Howard C , Wilkinson C , Bamrah S , Husain F . Food Nutr Bull 2011 32 (3) 264-276 BACKGROUND: Anemia remains a significant public health problem in refugee settings. Home fortification with micronutrient powders has been proposed as a feasible option to alleviate micronutrient deficiencies; its efficacy in reducing anemia in children aged 6 to 24 months has been demonstrated in several trials. OBJECTIVE: To evaluate the effectiveness of a large-scale micronutrient powder distribution program in reducing anemia prevalence and promoting growth in refugee children aged 6 to 59 months. METHODS: Four representative cross-sectional surveys were conducted 13 months before and 7, 14, and 26 months after initiation of the supplementation program. Data collected on children aged 6 to 59 months included hemoglobin concentration, anthropometric indicators, morbidity, feeding practices, and information on the micronutrient distribution program. The study had a pre-post design with no control group. RESULTS: The overall prevalence of anemia in children did not change significantly between baseline (43.3%) and endpoint (40.2%). The prevalence of moderate anemia decreased over the same period from 18.9% to 14.4% (p < .05). The levels of severe anemia were negligible (< 1%) in all surveys. The prevalence of stunting decreased significantly from 39.2% at baseline to 23.4% at endpoint (p < .001), a relative decrease of 40%. Reported coverage, use, and acceptance of micronutrient supplements remained consistently high throughout the study. CONCLUSIONS: In the absence of a control group, changes in key outcomes should be interpreted with caution. The minor effect on hemoglobin status requires further investigation of underlying causes of anemia in this population. The large positive effect on linear growth may be a significant benefit of supplementation if confirmed by future studies. |
Improved recognition of lifeline tactile signals by miners
Kingsley Westerman C , Peters R . Coal Age 2011 116 (9) 40-43 Conducting regular assessments of each miner’s knowledge and skills with respect to lifelines should be a key component of miner safety training. The better prepared miners are to escape from the mine quickly, the better their ultimate chances of survival. Recent NIOSH research reveals several ways miners can be helped to improve their recognition of lifeline tactile signals. | Lifelines with various tactile signals have been required by federal regulation 30 CFR Part 74.380 since 2009. There are now five types of tactile signals on lifelines: directional cones (which indicate the direction to go outby), a coil to indicate a refuge chamber, two sets of double cones to indicate a self-contained, self-rescuer (SCSR) cache, two directional cones in a row to indicate a branch line, and a ball to indicate a personnel door. These signals were instituted to provide an additional navigational tool to help miners escape in the event of an emergency. | Despite the implementation of this new safety feature, miners may not always remember what the signals mean, especially in an emergency situation. It is important miners are able to identify the signals reliably because it could save them a significant amount of time while trying to escape. In addition to telling them which direction is outby, the signals could save them time because, instead of following a branch line to find out where it leads, miners can feel the signal at the beginning of the branch line and immediately know what is available at the end. They can also immediately identify when a line is a branch line as opposed to the main lifeline which leads them directly out of the mine. |
First evidence of spatial clustering of lymphatic filariasis in an Aedes polynesiensis endemic area
Joseph H , Moloney J , Maiava F , McClintock S , Lammie P , Melrose W . Acta Trop 2011 120 Suppl 1 S39-47 Successful elimination of lymphatic filariasis (LF) requires accurate identification of residual foci of transmission and stringent surveillance strategies to combat potential resurgence. This is challenging in areas where the day-biting Aedes polynesiensis is endemic, such as Samoa, since in previous studies no geographical clustering of infection has been demonstrated. Another challenge for this low prevalence phase is the choice of diagnostic assay as testing for circulating filarial antigen (CFA) or microfilariae (Mf) alone may not have adequate sensitivity. This could be solved by using the commercially available filariasis Cellabs enzyme linked immunosorbent assay (CELISA) to measure antibody. In the current study five Samoan villages were chosen based on previous epidemiological assessments to represent a range of infection prevalences. CFA, Mf, and antibody levels in children ≤10 years had been recorded and results linked to household of residence and/or primary school of attendance. To ascertain the location of exposure, two scenarios based on potential foci of transmission around communities and schools were explored. Both scenarios revealed significant spatial clusters of households with infected individuals and a relationship to antibody positive children when they were included in the spatial analysis. Fasitoo-Tai had the highest LF prevalence and largest geographical spatial clusters for both scenarios. In Falefa, spatial clusters were detected only for the primary school scenario. In Tafua, which spanned an area of 19.5km(2), no spatial clusters were detected. Lastly, in Siufaga, the village with the lowest LF prevalence, significant clustering of infected individuals was observed and, for the primary school scenario, this was geographically related to exposure. These promising findings are the first published evidence of spatial clustering of LF in a day-biting Ae. polynesiensis endemic area. |
Economic costs of excessive alcohol consumption in the U.S., 2006
Bouchery EE , Harwood HJ , Sacks JJ , Simon CJ , Brewer RD . Am J Prev Med 2011 41 (5) 516-24 BACKGROUND: Excessive alcohol consumption causes premature death (average of 79,000 deaths annually); increased disease and injury; property damage from fire and motor vehicle crashes; alcohol-related crime; and lost productivity. However, its economic cost has not been assessed for the U.S. since 1998. PURPOSE: To update prior national estimates of the economic costs of excessive drinking. METHODS: This study (conducted 2009-2010) followed U.S. Public Health Service Guidelines to assess the economic cost of excessive alcohol consumption in 2006. Costs for health care, productivity losses, and other effects (e.g., property damage) in 2006 were obtained from national databases. Alcohol-attributable fractions were obtained from multiple sources and used to assess the proportion of costs that could be attributed to excessive alcohol consumption. RESULTS: The estimated economic cost of excessive drinking was $223.5 billion in 2006 (72.2% from lost productivity, 11.0% from healthcare costs, 9.4% from criminal justice costs, and 7.5% from other effects) or approximately $1.90 per alcoholic drink. Binge drinking resulted in costs of $170.7 billion (76.4% of the total); underage drinking $27.0 billion; and drinking during pregnancy $5.2 billion. The cost of alcohol-attributable crime was $73.3 billion. The cost to government was $94.2 billion (42.1% of the total cost), which corresponds to about $0.80 per alcoholic drink consumed in 2006 (categories are not mutually exclusive and may overlap). CONCLUSIONS: On a per capita basis, the economic impact of excessive alcohol consumption in the U.S. is approximately $746 per person, most of which is attributable to binge drinking. Evidence-based strategies for reducing excessive drinking should be widely implemented. |
Electronic nicotine delivery systems: adult use and awareness of the 'e-cigarette' in the USA
Regan AK , Promoff G , Dube SR , Arrazola R . Tob Control 2011 22 (1) 19-23 BACKGROUND: Electronic nicotine delivery systems (ENDS), also referred to as electronic cigarettes or e-cigarettes, were introduced into the US market in 2007. Despite concerns regarding the long-term health impact of this product, there is little known about awareness and use of ENDS among adults in the USA. METHODS: A consumer-based mail-in survey (ConsumerStyles) was completed by 10,587 adults (≥18 years) in 2009 and 10,328 adults in 2010. Data from these surveys were used to monitor awareness, ever use and past month use of ENDS from 2009 to 2010 and to assess demographic characteristics and tobacco use of ENDS users. RESULTS: In this US sample, awareness of ENDS doubled from 16.4% in 2009 to 32.2% in 2010 and ever use more than quadrupled from 2009 (0.6%) to 2010 (2.7%). Ever use of ENDS was most common among women and those with lower education, although these were not the groups who had heard of ENDS most often. Current smokers and tobacco users were most likely to try ENDS. However, current smokers who had tried ENDS did not say they planned to quit smoking more often than smokers who had never tried them. CONCLUSIONS: Given the large increase in awareness and ever use of ENDS during this 1-year period and the unknown impact of ENDS use on cigarette smoking behaviours and long-term health, continued monitoring of these products is needed. |
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