Characteristics associated with genetic counseling referral and BRCA1/2 testing among women in a large integrated health system.
Bellcross CA , Peipins LA , McCarty FA , Rodriguez JL , Hawkins NA , Hensley Alford S , Leadbetter S . Genet Med 2014 17 (1) 43-50 BACKGROUND: Evidence shows underutilization of cancer genetics services. To explore the reasons behind this underutilization, this study evaluated characteristics of women who were referred for genetic counseling and/or had undergone BRCA1/2 testing. METHODS: An ovarian cancer risk perception study stratified 16,720 eligible women from the Henry Ford Health System into average-, elevated-, and high-risk groups based on family history. We randomly selected 3,307 subjects and interviewed 2,524 of them (76.3% response rate). RESULTS: Among the average-, elevated-, and high-risk groups, 2.3, 10.1, and 20.2%, respectively, reported genetic counseling referrals, and 0.8, 3.3, and 9.5%, respectively, reported having undergone BRCA testing. Personal breast cancer history, high risk, and perceived ovarian cancer risk were associated with both referral and testing. Discussion of family history with a doctor predicted counseling referral, whereas belief that family history influenced risk was the strongest BRCA testing predictor. Women perceiving their cancer risk as much higher than other women their age were twice as likely (95% confidence interval: 2.0-9.6) to report genetic counseling referral. CONCLUSION: In a health system with ready access to cancer genetic counseling and BRCA testing, women who were at high risk underutilized these services. There were strong associations between perceived ovarian cancer risk and genetic counseling referral, and between a belief that family history influenced risk and BRCA testing. |
Team-based care and improved blood pressure control: a Community Guide systematic review
Proia KK , Thota AB , Njie GJ , Finnie RK , Hopkins DP , Mukhtar Q , Pronk NP , Zeigler D , Kottke TE , Rask KJ , Lackland DT , Brooks JF , Braun LT , Cooksey T . Am J Prev Med 2014 47 (1) 86-99 CONTEXT: Uncontrolled hypertension remains a widely prevalent cardiovascular risk factor in the U.S. team-based care, established by adding new staff or changing the roles of existing staff such as nurses and pharmacists to work with a primary care provider and the patient. Team-based care has the potential to improve the quality of hypertension management. The goal of this Community Guide systematic review was to examine the effectiveness of team-based care in improving blood pressure (BP) outcomes. EVIDENCE ACQUISITION: An existing systematic review (search period, January 1980-July 2003) assessing team-based care for BP control was supplemented with a Community Guide update (January 2003-May 2012). For the Community Guide update, two reviewers independently abstracted data and assessed quality of eligible studies. EVIDENCE SYNTHESIS: Twenty-eight studies in the prior review (1980-2003) and an additional 52 studies from the Community Guide update (2003-2012) qualified for inclusion. Results from both bodies of evidence suggest that team-based care is effective in improving BP outcomes. From the update, the proportion of patients with controlled BP improved (median increase=12 percentage points); systolic BP decreased (median reduction=5.4 mmHg); and diastolic BP also decreased (median reduction=1.8 mmHg). CONCLUSIONS: Team-based care increased the proportion of people with controlled BP and reduced both systolic and diastolic BP, especially when pharmacists and nurses were part of the team. Findings are applicable to a range of U.S. settings and population groups. Implementation of this multidisciplinary approach will require health system-level organizational changes and could be an important element of the medical home. |
A triple play: psychological distress, physical comorbidities, and access and use of health services among U.S. adults with disabilities
Okoro CA , Dhingra SS , Li C . J Health Care Poor Underserved 2014 25 (2) 814-36 PURPOSE: Among adults with disabilities, we examined whether increasing levels of psychological distress were associated with higher estimated prevalences of chronic conditions, obesity, health care access, and use of preventive services. METHODS: We analyzed data from the 2007 Behavioral Risk Factor Surveillance System. The Kessler-6 scale was used to assess psychological distress. RESULTS: Increasing levels of psychological distress were associated with an increased prevalence of chronic diseases and conditions, and decreased access to health care and utilization of preventive services in keeping with what has been established for non-disabled populations. Among adults with disabilities, aged 18-64 years and 65 years or older, increasing levels of distress were also associated with increased receipt of mental health treatment. However, compared to adults aged 18-64 years, larger proportions of older adults reported non-receipt of mental health treatment (mild to moderate psychological distress: 58.0% versus 70.6%; serious psychological distress: 40.5% versus 54.5%). CONCLUSIONS: While adults with disabilities who had increased levels of psychological distress were more likely to receive mental health services, they also had higher estimated prevalences of chronic conditions, barriers to health care, and non-receipt of preventive cancer screenings. |
Estimates of young breast cancer survivors at risk for infertility in the U.S
Trivers KF , Fink AK , Partridge AH , Oktay K , Ginsburg ES , Li C , Pollack LA . Oncologist 2014 19 (8) 814-22 BACKGROUND: Standard treatments for breast cancer can impair fertility. It is unknown how many U.S. survivors are at risk for infertility. We estimated the population at risk for infertility secondary to treatment among reproductive-aged breast cancer survivors. METHODS: We combined data from three sources: the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results cancer registry data on incident breast cancers diagnosed in women aged 15-44 years between 2004 and 2006; treatment data from NPCR's 2004 Breast and Prostate Cancer Data Quality and Patterns of Care (PoC) study; and data on women's intentions to have children from the 2006-2010 National Survey of Family Growth (NSFG). RESULTS: In the cancer registry data, an average of 20,308 women with breast cancer aged <45 years were diagnosed annually. Based on estimates from PoC data, almost all of these survivors (97%, 19,416 women) were hormone receptor positive or received chemotherapy and would be at risk for infertility. These women need information about the impact of treatments on fertility. Estimates based on NSFG data suggest approximately half of these survivors (9,569 women) might want children and could benefit from fertility counseling and fertility preservation. CONCLUSION: Nearly all young breast cancer survivors in the U.S. are at risk for infertility. Physicians should discuss the potential impact of treatment on fertility. A smaller but sizeable number of at-risk survivors may be interested in having children. Given the magnitude of potential infertility and its quality-of-life implications, these survivors should have access to and potential coverage for fertility services. |
Active asthma and the prevalence of physician-diagnosed COPD
Mirabelli MC , Beavers SF , Chatterjee AB . Lung 2014 192 (5) 693-700 INTRODUCTION: Despite the considerable overlap of asthma and chronic obstructive pulmonary disease (COPD), the extent to which the two diagnoses are the manifestations of the same disease remains unresolved. We conducted these analyses to evaluate the role of active asthma in the prevalence of physician-diagnosed COPD. METHODS: From 2006 through 2010, 74,209 adults aged 18-99 years and with a history of asthma participated in the Behavioral Risk Factor Surveillance System (BRFSS) Asthma Call-back Survey and responded to interview-administered questionnaires via telephone. We used publicly available data from 71,639 (97%) participants to identify respondents with and without active manifestations of asthma and self-reported, physician-diagnosed COPD. We generated population-weighted estimates of physician-diagnosed COPD prevalence and conducted linear regression to estimate associations between active asthma status and the prevalence of COPD among current smokers, former smokers, and lifetime nonsmokers separately. RESULTS: Physician-diagnosed COPD was reported in an estimated 29% of the population with any history of asthma, including both active and inactive asthma. Age-specific prevalences of physician-diagnosed COPD were consistently higher among adults with active asthma than adults without active asthma. Compared to inactive asthma, active asthma was associated with an 8.3% [95 % confidence interval (CI) 6.1, 10.5] higher prevalence of physician-diagnosed COPD among lifetime nonsmokers, a 20.6% (95 % CI 18.0, 23.3) higher prevalence among former smokers, and a 26.7% (95 % CI 22.5, 30.9) higher prevalence among current smokers. CONCLUSIONS: Among adults with a history of asthma, active manifestations of asthma may play an important role in the epidemiology of COPD. |
Chronic condition self-management surveillance: what is and what should be measured?
Ruiz S , Brady TJ , Glasgow RE , Birkel R , Spafford M . Prev Chronic Dis 2014 11 E103 INTRODUCTION: The rapid growth in chronic disease prevalence, in particular the prevalence of multiple chronic conditions, poses a significant and increasing burden on the health of Americans. Maximizing the use of proven self-management (SM) strategies is a core goal of the US Department of Health and Human Services. Yet, there is no systematic way to assess how much SM or self-management support (SMS) is occurring in the United States. The purpose of this project was to identify appropriate concepts or measures to incorporate into national SM and SMS surveillance. METHODS: A multistep process was used to identify candidate concepts, assess existing measures, and select high-priority concepts for further development. A stakeholder survey, an environmental scan, subject matter expert feedback, and a stakeholder priority-setting exercise were all used to select the high-priority concepts for development. RESULTS: The stakeholder survey gathered feedback on 32 candidate concepts; 9 concepts were endorsed by more than 66% of respondents. The environmental scan indicated few existing measures that adequately reflected the candidate concepts, and those that were identified were generally specific to a defined condition and not gathered on a population basis. On the basis of the priority setting exercises and environmental scan, we selected 1 concept from each of 5 levels of behavioral influence for immediate development as an SM or SMS indicator. CONCLUSION: The absence of any available measures to assess SM or SMS across the population highlights the need to develop chronic condition SM surveillance that uses national surveys and other data sources to measure national progress in SM and SMS. |
Viral etiologies of hospitalized acute lower respiratory infection patients in China, 2009-2013
Feng L , Li Z , Zhao S , Nair H , Lai S , Xu W , Li M , Wu J , Ren L , Liu W , Yuan Z , Chen Y , Wang X , Zhao Z , Zhang H , Li F , Ye X , Li S , Feikin D , Yu H , Yang W . PLoS One 2014 9 (6) e99419 BACKGROUND: Acute lower respiratory infections (ALRIs) are an important cause of acute illnesses and mortality worldwide and in China. However, a large-scale study on the prevalence of viral infections across multiple provinces and seasons has not been previously reported from China. Here, we aimed to identify the viral etiologies associated with ALRIs from 22 Chinese provinces. METHODS AND FINDINGS: Active surveillance for hospitalized ALRI patients in 108 sentinel hospitals in 24 provinces of China was conducted from January 2009-September 2013. We enrolled hospitalized all-age patients with ALRI, and collected respiratory specimens, blood or serum collected for diagnostic testing for respiratory syncytial virus (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV) and human bocavirus (hBoV). We included 28,369 ALRI patients from 81 (of the 108) sentinel hospitals in 22 (of the 24) provinces, and 10,387 (36.6%) were positive for at least one etiology. The most frequently detected virus was RSV (9.9%), followed by influenza (6.6%), PIV (4.8%), ADV (3.4%), hBoV (1.9), hMPV (1.5%) and hCoV (1.4%). Co-detections were found in 7.2% of patients. RSV was the most common etiology (17.0%) in young children aged <2 years. Influenza viruses were the main cause of the ALRIs in adults and elderly. PIV, hBoV, hMPV and ADV infections were more frequent in children, while hCoV infection was distributed evenly in all-age. There were clear seasonal peaks for RSV, influenza, PIV, hBoV and hMPV infections. CONCLUSIONS: Our findings could serve as robust evidence for public health authorities in drawing up further plans to prevent and control ALRIs associated with viral pathogens. RSV is common in young children and prevention measures could have large public health impact. Influenza was most common in adults and influenza vaccination should be implemented on a wider scale in China. |
Pharmacokinetics and preliminary safety study of pod-intravaginal rings delivering antiretroviral combinations for HIV prophylaxis in a macaque model
Moss JA , Srinivasan P , Smith TJ , Butkyavichene I , Lopez G , Brooks AA , Martin A , Dinh CT , Smith JM , Baum MM . Antimicrob Agents Chemother 2014 58 (9) 5125-35 Pre-exposure prophylaxis using oral regimens of the HIV nucleoside reverse transcriptase inhibitors tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) has demonstrated efficacy in three clinical trials. Adherence was determined to be a key parameter for success. Incorporation of the TDF-FTC combination into intravaginal rings (IVRs) for sustained mucosal delivery could increase product adherence and efficacy when compared with oral and vaginal gel formulations. A novel pod-IVR technology capable of delivering multiple drugs is described and constitutes the first report of an IVR delivering TDF and FTC, as well as a triple combination IVR delivering TDF, FTC and the entry inhibitor maraviroc (MVC). The pharmacokinetics and preliminary local safety of the two combination pod-IVRs were evaluated in the pig-tailed macaque model. The devices exhibited sustained release at controlled rates over the 28-day study. Median steady-state drug levels in vaginal tissues were: TDF-FTC group; tenofovir (TFV, in vivo hydrolysis product of TDF), 30 mug g-1; FTC, 500 mug g-1; and TDF-FTC-MVC group; TFV, 10 mug g-1; FTC, 150 mug g-1; MVC, 20 mug g-1. No adverse events were observed and there were no toxicological findings. Mild to moderate increases in inflammatory infiltrates were observed in the vaginal tissues of some animals in both the presence and absence of the IVRs. The IVRs did not disturb the vaginal microbiota and levels of proinflammatory cytokines remained stable throughout the study. Pod-IVR candidates based on the TDF-FTC combination have potential for the prevention of vaginal HIV acquisition and merit clinical investigation. |
Prevalence of chronic hepatitis B virus infection before and after implementation of a hepatitis B vaccination program among children in Nepal
Upreti SR , Gurung S , Patel M , Dixit SM , Krause LK , Shakya G , Wannemuehler K , Rajbhandari R , Bohara R , Schluter WW . Vaccine 2014 32 (34) 4304-9 BACKGROUND: In Nepal, an estimated 2-4% of the population has chronic hepatitis B virus (HBV) infection. To combat this problem, from 2002 to 2004, a national three dose hepatitis B vaccination program was implemented to decrease infection rates among children. The program does not currently include a birth dose to prevent perinatal HBV transmission. In 2012, to assess the impact of the program, we conducted a serosurvey among children born before and after vaccine introduction. METHODS: In 2012, a cross-sectional nationally representative stratified cluster survey was conducted to estimate hepatitis B surface antigen (HBsAg) prevalence among children born from 2006 to 2007 (post-vaccine cohort) and among children born from 2000 to 2002 (pre-vaccine cohort). Demographic data, as well as written and oral vaccination history were collected. All children were tested for HBsAg; mothers of HBsAg positive children were also tested. Furthermore, we evaluated the field sensitivity and specificity of the SD Bioline HBsAg rapid diagnostic test by comparing results with an enzyme immunoassay. RESULTS: Among 2181 post-vaccination cohort children with vaccination data by either card or recall, 86% (95% confidence interval [CI] 77-95%) received ≥3 hepatitis B vaccine doses. Of 1200 children born in the pre-vaccination cohort, 0.28% (95% CI 0.09-0.85%) were positive for HBsAg; of 2187 children born in the post-vaccination cohort, 0.13% (95% CI 0.04-0.39%) were positive for HBsAg (p=0.39). Of the six children who tested positive for HBsAg, two had mothers who were positive for HBsAg. Finally, we found the SD Bioline HBsAg rapid diagnostic test to have a sensitivity of 100% and a specificity of 100%. CONCLUSIONS: This is the first nationally representative hepatitis B serosurvey conducted in Nepal. Overall, a low burden of chronic HBV infection was found in children born in both the pre and post-vaccination cohorts. Current vaccination strategies should be continued. |
Factors associated with mortality among persistently viraemic triple-antiretroviral-class-experienced patients receiving antiretroviral therapy in the HIV Outpatient Study (HOPS)
Palella FJ Jr , Armon C , Buchacz K , Chmiel JS , Novak RM , D'Aquila RT , Brooks JT . J Antimicrob Chemother 2014 69 (10) 2826-34 BACKGROUND: Identifying factors associated with mortality for HIV-infected patients with persistent viraemia despite antiretroviral (ARV) therapy may inform diagnostic and treatment strategies. METHODS: We analysed data from viraemic triple-ARV-class-experienced HIV Outpatient Study patients seen during 1 January 1999 to 31 December 2012 who, despite treatment that included ARVs from three major drug classes [nucleoside analogue reverse transcriptase inhibitors, non-nucleoside analogue reverse transcriptase inhibitors and protease inhibitors (PIs)], had plasma HIV RNA levels [viral load (VL)] >1000 copies/mL ['triple ARV class failure' (TCF)]. The baseline was defined as the date of meeting the TCF criteria during 1999-2008. We identified factors associated with mortality using Cox regression. RESULTS: Of 597 patients who met the TCF criteria (median follow-up after baseline 4.9 years), 115 (19.3%) died. Baseline factors associated with mortality were age per 10 years [hazard ratio (HR) 1.61, 95% CI 1.28-2.02], risk of HIV from use of injection drugs (HR 1.81, 95% CI 1.10-2.98), CD4+ T cell count <200 cells/mm3 (HR 3.68, 95% CI 2.41-5.62), VL ≥5.0 log10 copies/mL (HR 2.91, 95% CI 1.88-4.49) and receiving a first combination ARV therapy regimen that was PI-based (HR 2.44, 95% CI 1.47-4.06); receiving a novel ARV agent during follow-up (HR 0.45, 95% CI 0.22-0.93) was protective. Genotypic resistance testing results were available for 274 (45.9%) of the TCF patients, of whom 47 (17.2%) died. In this group, factors associated with death were increasing age (HR 1.94, 95% CI 1.36-2.78, per 10 year increment), risk of HIV from use of injection drugs (HR 2.71, 95% CI 1.37-5.39), baseline VL ≥5.0 log10 copies/mL (HR 5.35, 95% CI 2.82-10.1) and receiving PI-based first combination ARV therapy regimen (HR 3.20, 95% CI 1.25-8.17). No HIV mutations or combinations of mutations were significantly associated with survival. CONCLUSIONS: Factors significantly associated with mortality risk among TCF patients who received ongoing ARV therapy included traditional clinical predictors but not the presence, type or number of HIV genetic mutations. The use of novel ARV drugs by these ARV therapy-experienced patients was associated with an improved survival. |
Behavioral and clinical characteristics of persons receiving medical care for HIV infection - Medical Monitoring Project, United States, 2009
Blair JM , Fagan JL , Frazier EL , Do A , Bradley H , Valverde EE , McNaghten A , Beer L , Zhang S , Huang P , Mattson CL , Freedman MS , Johnson CH , Sanders CC , Spruit-McGoff KE , Heffelfinger JD , Skarbinski J . MMWR Suppl 2014 63 Suppl 5 (5) 1-22 PROBLEM: As of December 31, 2009, an estimated 864,748 persons were living with human immunodeficiency virus (HIV) infection in the 50 U.S. states, the District of Columbia, and six U.S.-dependent areas. Whereas HIV surveillance programs in the United States collect information about persons with a diagnosis of HIV infection, supplemental surveillance systems collect in-depth information about the behavioral and clinical characteristics of persons receiving outpatient medical care for HIV infection. These data are needed to reduce HIV-related morbidity and mortality and HIV transmission. REPORTING PERIOD COVERED: Data were collected during June 2009-May 2010 for patients receiving medical care at least once during January-April 2009. DESCRIPTION OF THE SYSTEM: The Medical Monitoring Project (MMP) is an ongoing surveillance system that assesses behaviors and clinical characteristics of HIV-infected persons who have received outpatient medical care. For the 2009 data collection cycle, participants must have been aged ≥18 years and have received medical care during January-April 2009 at sampled facilities that provide HIV medical care within participating MMP project areas. Behavioral and selected clinical data were collected using an in-person interview, and most clinical data were collected using medical record abstraction. A total of 23 project areas in 16 states and Puerto Rico were funded to collect data during the 2009 data collection cycle. The data were weighted for probability of selection and nonresponse to be representative of adults receiving outpatient medical care for HIV infection in the United States and Puerto Rico. Prevalence estimates are presented as weighted percentages. The period of reference is the 12 months before the patient interview unless otherwise noted. RESULTS: The patients in MMP represent 421,186 adults who received outpatient medical care for HIV infection in the United States and Puerto Rico during January-April 2009. Of adults who received medical care for HIV infection, an estimated 71.2% were male, 27.2% were female, and 1.6% were transgender. An estimated 41.4% were black or African American, 34.6% were white, and 19.1% were Hispanic or Latino. The largest proportion (23.1%) were aged 45-49 years. Most patients (81.1%) had medical coverage; 40.3% had Medicaid, 30.6% had private health insurance, and 25.7% had Medicare. An estimated 69.6% of patients had three or more documented CD4+ T-lymphocyte cell (CD4+) or HIV viral load tests. Most patients (88.7%) were prescribed antiretroviral therapy (ART), and 71.6% had a documented viral load that was undetectable or ≤200 copies/mL at their most recent test. Among sexually active patients, 55.0% had documentation in the medical record of being tested for syphilis, 23.2% for gonorrhea, and 23.9% for chlamydia. Noninjection drugs were used for nonmedical purposes by an estimated 27.1% of patients, whereas injection drugs were used for nonmedical purposes by 2.1% of patients. Overall, 12.9% of patients engaged in unprotected sex with a partner of negative or unknown HIV status. Unmet supportive service needs were prevalent, with an estimated 22.8% in need of dental care and 12.0% in need of public benefits, including Social Security Income or Social Security Disability Insurance. Fewer than half of patients (44.8%) reported receiving HIV and sexually transmitted disease prevention counseling from a health-care provider. INTERPRETATION: The findings in this report indicate that most adults living with HIV who received medical care in 2009 were taking ART, had CD4+ and HIV viral load testing at regular intervals, and had health insurance or other coverage. However, some patients did not receive clinical services and treatment in accordance with guidelines. Some patients engaged in behaviors, such as unprotected sex, that increase the risk for transmitting HIV to sex partners, and some used noninjection or injection drugs or both. PUBLIC HEALTH ACTIONS: Local and state health departments and federal agencies can use MMP data for program planning to determine allocation of services and resources, guide prevention planning, assess unmet medical and supportive service needs, inform health-care providers, and help focus intervention programs and health policies at the local, state, and national levels. |
Comparison of trends in tuberculosis incidence among adults living with HIV and adults without HIV - Kenya, 1998-2012
Yuen CM , Weyenga HO , Kim AA , Malika T , Muttai H , Katana A , Nganga L , Cain KP , De Cock KM . PLoS One 2014 9 (6) e99880 BACKGROUND: In Kenya, the comparative incidences of tuberculosis among persons with and without HIV have not been described, and the differential impact of public health interventions on tuberculosis incidence in the two groups is unknown. METHODS: We estimated annual tuberculosis incidence stratified by HIV status during 2006-2012 based on the numbers of reported tuberculosis patients with and without HIV infection, the prevalence of HIV infection in the general population, and the total population. We also made crude estimates of annual tuberculosis incidence stratified by HIV status during 1998-2012 by assuming a constant ratio of HIV prevalence among tuberculosis patients compared to the general population. RESULTS: Tuberculosis incidence among both adults with HIV and adults without HIV increased during 1998-2004 then remained relatively stable until 2007. During 2007-2012, tuberculosis incidence declined by 28-44% among adults with HIV and by 11-26% among adults without HIV, concurrent with an increase in antiretroviral therapy uptake. In 2012, tuberculosis incidence among adults with HIV (1,839-1,936 cases/100,000 population) was still eight times as high as among adults without HIV (231-238 cases/100,000 population), and approximately one third of tuberculosis cases were attributable to HIV. CONCLUSIONS: Although tuberculosis incidence has declined among adults with and without HIV, the persistent high incidence of tuberculosis among those with HIV and the disparity between the two groups are concerning. Early diagnosis of HIV, early initiation of antiretroviral therapy, regular screening for tuberculosis, and isoniazid preventive therapy among persons with HIV, as well as tuberculosis control in the general population, are required to address these issues. |
Coxsackievirus A6 associated hand, foot and mouth disease in adults: clinical presentation and review of the literature
Downing C , Ramirez-Fort MK , Doan HQ , Benoist F , Oberste MS , Khan F , Tyring SK . J Clin Virol 2014 60 (4) 381-6 BACKGROUND: Hand, foot, and mouth disease (HFMD) is generally considered a rare illness in adults. Classically, HFMD has been strongly associated with coxsackievirus strain A16 and enterovirus 71. The coxsackievirus A6 (CVA6) strain has been linked to severe worldwide outbreaks since 2008. CVA6 is associated with a more severe and profound course of disease, affecting both children and adults. OBJECTIVES: To present a series of five adult patients diagnosed with HFMD due to CVA6. We investigate method of diagnosis and compare clinical presentation of adult cases to those in children. STUDY DESIGN: Each patient underwent a full-body skin exam as well as inspection of the oral cavity. Rapid plasma reagin (RPR) and serologic assays by complement fixation against coxsackievirus B (1-6) and A (2,4,7,9,10,16) were performed as indicated. As standard serological testing does not detect CVA6, real-time reverse transcription-polymerase chain reaction (qRT-PCR) of serum, buccal swabs, and skin scrapings were performed by the Centers for Disease Control and Prevention (CDC). RESULTS: Each patient had clinical findings consistent with various stages of HFMD. One patient presented with delayed onychomadesis and desquamation of the palms and soles. RPR and serologic assays by complement fixation against CVB (1-6) and CVA (2,4,7,9,10,16) were mostly negative, although elevated in two patients due to cross-reactivity. qRT-PCR identified CVA6 genetic material in samples from all patients. CONCLUSION: This series demonstrates that there is a wide array of disease presentation of CVA6 associated HFMD in adults. |
Drinking motives among HIV primary care patients
Elliott JC , Aharonovich E , O'Leary A , Wainberg M , Hasin DS . AIDS Behav 2014 18 (7) 1315-23 Heavy drinking among individuals with HIV is associated with poor medication adherence and other health problems. Understanding reasons for drinking (drinking motives) in this population is therefore important and could inform intervention. Using concepts of drinking motives from previous alcohol research, we assessed these motives and drinking in 254 HIV-positive primary care patients (78.0 % male; 94.5 % African American or Hispanic) prior to their participation in an alcohol intervention trial. Three motives had good factor structure and internal consistency: "drinking to cope with negative affect", "drinking for social facilitation" (both associated with heavier drinking), and "drinking due to social pressure" (associated with less drinking). Drinking motives may provide important content for alcohol intervention; clinical trials could indicate whether inclusion of such content improves intervention efficacy. Discussing motives in session could help providers assist clients in better managing psychological and social aspects of their lives without reliance on alcohol. |
Summertime acute heat illness in U.S. emergency departments from 2006 through 2010: analysis of a nationally representative sample
Hess JJ , Saha S , Luber G . Environ Health Perspect 2014 122 (11) 1209-15 BACKGROUND: Patients with acute heat illness present primarily to emergency departments (EDs), yet little is known regarding these visits. OBJECTIVE: To describe acute heat illness visits to US EDs from 2006-2010 and identify factors associated with hospital admission or death-in-the-ED. METHODS: We extracted ED case-level data from the Nationwide Emergency Department Sample (NEDS) for 2006-10, defining cases as ED visits from May-September with any heat illness diagnosis (ICD-9-CM 992.0-992.9). We correlated visit rates and temperature anomalies analyzed demographics and ED disposition, identified risk factors for adverse outcomes, and examined ED case fatality rates (CFR). RESULTS: There were 326,497 (95% CI: 308,372-344,658) cases, with 287,875 (88.2%) treated-and-released, 38,392 (11.8%) admitted, and 230 (0.07%) died-in-the-ED. Heat illness diagnoses were first-listed in 68%. 74.7% had heat exhaustion, 5.4% heat stroke. Visit rates were highly correlated with annual temperature anomalies (correlation coefficient 0.90, p=0.037). Treat-and-release rates were highest for younger adults (26.2/100,000/year), while hospitalization and death-in-the-ED rates were highest for older adults (6.7 and 0.03/100,000/year respectively); all rates were highest in rural areas. Heat stroke had an ED CFR of 99.4/10,000 (78.7-120.1) visits and was diagnosed in 77.0% of deaths. Adjusted odds of hospital admission or death-in-the-ED were higher among elders, males, urban and low income residents, and those with chronic conditions. CONCLUSIONS: Heat illness presented to the ED frequently, with highest rates in rural areas. Case definitions should include all diagnoses. Visit rates were correlated with temperature anomalies. Heat stroke had a high ED CFR. Males, elders, and the chronically ill were at greatest risk of admission or death-in-the-ED. Chronic disease burden exponentially increased this risk. |
Impact of neighborhood biomass cooking patterns on episodic high indoor particulate matter concentrations in clean fuel homes in Dhaka, Bangladesh
Salje H , Gurley ES , Homaira N , Ram PK , Haque R , Petri W , Moss WJ , Luby SP , Breysse P , Azziz-Baumgartner E . Indoor Air 2014 24 (2) 213-20 Exposure to particulate matter (PM2.5 ) from the burning of biomass is associated with increased risk of respiratory disease. In Dhaka, Bangladesh, households that do not burn biomass often still experience high concentrations of PM2.5 , but the sources remain unexplained. We characterized the diurnal variation in the concentrations of PM2.5 in 257 households and compared the risk of experiencing high PM2.5 concentrations in biomass and non-biomass users. Indoor PM2.5 concentrations were estimated every minute over 24 h once a month from April 2009 through April 2010. We found that households that used gas or electricity experienced PM2.5 concentrations exceeding 1000 mug/m(3) for a mean of 35 min within a 24-h period compared with 66 min in biomass-burning households. In both households that used biomass and those that had no obvious source of particulate matter, the probability of PM2.5 exceeding 1000 mug/m(3) were highest during distinct morning, afternoon, and evening periods. In such densely populated settings, indoor pollution in clean fuel households may be determined by biomass used by neighbors, with the highest risk of exposure occurring during cooking periods. Community interventions to reduce biomass use may reduce exposure to high concentrations of PM2.5 in both biomass and non-biomass using households. |
Outbreak of Francisella novicida bacteremia among inmates at a Louisiana correctional facility
Brett ME , Respicio-Kingry LB , Yendell S , Ratard R , Hand J , Balsamo G , Scott-Waldron C , O'Neal C , Kidwell D , Yockey B , Singh P , Carpenter J , Hill V , Petersen JM , Mead P . Clin Infect Dis 2014 59 (6) 826-33 BACKGROUND: Francisella novicida is a rare cause of human illness despite its close genetic relationship to F. tularensis, the agent of tularemia. During April-July 2011, three inmates at a Louisiana correctional facility developed F. novicida bacteremia; one died acutely. METHODS: We interviewed surviving inmates; reviewed laboratory, medical, and housing records; and conducted an environmental investigation. Clinical and environmental samples were tested by culture, real-time PCR and multi-gene sequencing. Isolates were typed by pulsed-field gel electrophoresis (PFGE). RESULTS: Clinical isolates were identified as F. novicida based on sequence analyses of the 16S rRNA, pgm and pdpD genes. PmeI PFGE patterns for the clinical isolates were indistinguishable. Source patients were aged 40-56 years, male, African American, and all were immunocompromised. Two patients presented with signs of bacterial peritonitis; the third had pyomyositis of the thigh. The three inmates had no contact with one another; their only shared exposures were consumption of municipal water and of ice mass produced at the prison in an unenclosed building. Swabs from one set of ice machines and associated ice scoops yielded evidence of F. novicida by PCR and sequencing. All other environmental specimens tested negative. CONCLUSIONS: To our knowledge, this is the first reported common-source outbreak of F. novicida infections in humans. Epidemiological and laboratory evidence implicate contaminated ice as the likely vehicle of transmission; liver disease may be a predisposing factor. Clinicians, laboratorians and public health officials should be aware of the potential for misidentification of F. novicida as F. tularenis. |
Deriving group A Streptococcus typing information from short-read whole-genome sequencing data.
Athey TB , Teatero S , Li A , Marchand-Austin A , Beall BW , Fittipaldi N . J Clin Microbiol 2014 52 (6) 1871-6 Typing of group A Streptococcus (GAS) is crucial for infection control and epidemiology. While whole-genome sequencing (WGS) is revolutionizing the way that bacterial organisms are typed, it is necessary to provide backward compatibility with currently used typing schemas to facilitate comparisons and understanding of epidemiological trends. Here, we sequenced the genomes of 191 GAS isolates representing 42 different emm types and used bioinformatics tools to derive commonly used GAS typing information directly from the short-read WGS data. We show that emm typing and multilocus sequence typing can be achieved rapidly and efficiently using this approach, which also permits the determination of the presence or absence of genes associated with GAS tissue tropism. We also report on how the WGS data analysis was instrumental in identifying ambiguities present in the commonly used emm type database hosted by the U.S. Centers for Disease Control and Prevention. |
Heterogeneity of the internal transcribed spacer region in Leishmania tropica isolates from southern Iran.
Ghatee MA , Sharifi I , Kuhls K , Kanannejad Z , Fasihi Harandi M , de Almeida ME , Hatam G , Mirhendi H . Exp Parasitol 2014 144 44-51 Most of cutaneous leishmaniasis cases occur in only 7 countries, including Iran. Leishmania tropica is the main cause of anthroponotic cutaneous leishmaniasis in Iran. In order to study the heterogeneity and phylogeny of L. tropica in southern Iran, a total of 61 isolates were obtained from Bam district and the cities Kerman and Shiraz. The internal transcribed spacer (ITS) from the ribosomal DNA locus was amplified and then analysed by sequencing. Analysis of the ITS sequences showed four haplotypes in the isolates, including 3 haplotypes among the 58 isolates from the south eastern region, including Bam district and Kerman city, and 2 haplotypes among the 3 isolates from Shiraz city. The results showed a monophyletic structure for the south eastern population. In comparison to GenBank sequences of L. tropica from different countries, most of the southeast Iranian and Indian isolates are comprised in one cluster, while isolates from other countries and few other Iranian isolates group in a different cluster. Analysis of ITS sequences of south eastern L. tropica showed a homogeneous population which could be the basis for other molecular epidemiology studies using more discriminative markers and tracing possible changes in the population structure of L. tropica. |
Genome Sequences of Nine Bordetella holmesii Strains Isolated in the United States.
Harvill ET , Goodfield LL , Ivanov Y , Smallridge WE , Meyer JA , Cassiday PK , Tondella ML , Brinkac L , Sanka R , Kim M , Losada L . Genome Announc 2014 2 (3) An increasing number of pertussis-like cases are attributed to the emergent pathogen Bordetella holmesii. The genomes of 9 clinical isolates show that they are clonal, lack the virulence factors encoded by B. pertussis, and are more similar to nonpertussis bordetellae. New markers for B. holmesii can be developed using these sequences. |
Whole-genome analysis of Exserohilum rostratum from an outbreak of fungal meningitis and other infections.
Litvintseva AP , Hurst S , Gade L , Frace MA , Hilsabeck R , Schupp JM , Gillece JD , Roe C , Smith D , Keim P , Lockhart SR , Changayil S , Weil MR , MacCannell DR , Brandt ME , Engelthaler DM . J Clin Microbiol 2014 52 (9) 3216-22 Exserohilum rostratum was the cause of most cases of fungal meningitis and other infections associated with the injection of contaminated methylprednisolone acetate produced by the New England Compounding Center (NECC). Until this outbreak, very few human cases of Exserohilum had been reported and very little was known about this dematiaceous fungus, which usually infects plants. Here we report using whole genome sequencing (WGS) for detection of single nucleotide polymorphisms (SNP) and phylogenetic analysis to investigate molecular origin of the outbreak using 22 isolates of E. rostratum isolated from 19 case-patients with meningitis or epidural/spinal abscesses, six isolates isolated from contaminated NECC vials, and seven isolates that are unrelated to the outbreak. Our analysis indicates that all 28 isolates associated with the outbreak had nearly identical genomes of 33.8 Mb. A total of eight SNPs were detected among the outbreak genomes, with no more than two SNPs separating any two of the 28 genomes. The outbreak genomes were separated from the next most closely related control strain by approximately 136,000 SNPs. We also observed significant genomic variability among strains unrelated to the outbreak, which may suggest a possibility of cryptic speciation in E. rostratum. |
Evidence synthesis and guideline development in genomic medicine: current status and future prospects.
Schully SD , Lam TK , Dotson WD , Chang CQ , Aronson N , Birkeland ML , Brewster SJ , Boccia S , Buchanan AH , Calonge N , Calzone K , Djulbegovic B , Goddard KA , Klein RD , Klein TE , Lau J , Long R , Lyman GH , Morgan RL , Palmer CG , Relling MV , Rubinstein WS , Swen JJ , Terry SF , Williams MS , Khoury MJ . Genet Med 2014 17 (1) 63-7 PURPOSE: With the accelerated implementation of genomic medicine, health-care providers will depend heavily on professional guidelines and recommendations. Because genomics affects many diseases across the life span, no single professional group covers the entirety of this rapidly developing field. METHODS: To pursue a discussion of the minimal elements needed to develop evidence-based guidelines in genomics, the Centers for Disease Control and Prevention and the National Cancer Institute jointly held a workshop to engage representatives from 35 organizations with interest in genomics (13 of which make recommendations). The workshop explored methods used in evidence synthesis and guideline development and initiated a dialogue to compare these methods and to assess whether they are consistent with the Institute of Medicine report "Clinical Practice Guidelines We Can Trust." RESULTS: The participating organizations that develop guidelines or recommendations all had policies to manage guideline development and group membership, and processes to address conflicts of interests. However, there was wide variation in the reliance on external reviews, regular updating of recommendations, and use of systematic reviews to assess the strength of scientific evidence. CONCLUSION: Ongoing efforts are required to establish criteria for guideline development in genomic medicine as proposed by the Institute of Medicine. |
A roadmap for adapting an evidence-based HIV prevention intervention: Personal Cognitive Counseling (PCC) for episodic substance-using men who have sex with men
Knight KR , Das M , DeMicco E , Raiford JL , Matheson T , Shook A , Antunez E , Santos GM , Dadasovich R , Dilley JW , Colfax GN , Herbst JH . Prev Sci 2014 15 (3) 364-75 Episodic (less than weekly) drug use and binge drinking increase HIV-related sexual risk behaviors among men who have sex with men (MSM), yet no evidence-based interventions exist for these men. We describe an adaptation process of the Personalized Cognitive Counseling (PCC) intervention for utilization with high-risk, HIV-negative episodic, substance-using MSM. Participants (N = 59) were racially diverse, and reported unprotected anal intercourse and concurrent binge drinking (85 %), use of poppers (36 %), methamphetamine (20 %) and cocaine (12 %). Semi-structured interviews with 20 episodic, substance-using MSM elicited sexual narratives for engaging in unprotected anal intercourse while using alcohol or drugs. Emergent qualitative themes were translated into self-justifications and included in a revised PCC self-justification elicitation instrument (SJEI). The adapted SJEI was pretested with 19 episodic, substance-using MSM, and the final adapted PCC was pilot-tested for acceptability and feasibility with 20 episodic, substance-using MSM. This process can be used as a roadmap for adapting PCC for other high-risk populations of MSM. |
Adapted personalized cognitive counseling for episodic substance-using men who have sex with men: a randomized controlled trial
Coffin PO , Santos GM , Colfax G , Das M , Matheson T , DeMicco E , Dilley J , Vittinghoff E , Raiford JL , Carry M , Herbst JH . AIDS Behav 2014 18 (7) 1390-400 Episodic drug use and binge drinking are associated with HIV risk among substance-using men who have sex with men (SUMSM), yet no evidence-based interventions exist for these men. We adapted personalized cognitive counseling (PCC) to address self-justifications for high-risk sex among HIV-negative, episodic SUMSM, then randomized men to PCC (n = 162) with HIV testing or control (n = 164) with HIV testing alone. No significant between-group differences were found in the three primary study outcomes: number of unprotected anal intercourse events (UAI), number of UAI partners, and UAI with three most recent non-primary partners. In a planned subgroup analysis of non-substance dependent men, there were significant reductions in UAI with most recent non-primary partners among PCC participants (RR = 0.56; 95 %CI 0.34-0.92; P = 0.02). We did not find evidence that PCC reduced sexual risk behaviors overall, but observed significant reductions in UAI events among non-dependent SUMSM. PCC may be beneficial among SUMSM screening negative for substance dependence. |
The CDC Clear Communication Index Is a new evidence-based tool to prepare and review health information
Baur C , Prue C . Health Promot Pract 2014 15 (5) 629-37 This article presents the Centers for Disease Control and Prevention Clear Communication Index (the Index), a tool that emphasizes the primary audience's needs and provides a set of evidence-based criteria to develop and assess public communication products for diverse audiences. The Index consists of four open-ended introductory questions and 20 scored items that affect information clarity and audience comprehension, according to the scientific literature. A research team fielded an online survey to test the Index's validity. Respondents answered 10 questions about either an original health material or one redesigned with the Index. For 9 out of 10 questions, the materials revised using the Index were rated higher than the original materials. Regardless of education level, respondents rated the revised materials more favorably than the original ones. The results indicate that the Index performed as intended and made it more likely that audiences could correctly identify the intended main message and understand the words and numbers in the materials. The results also support the widely held view that audiences are more positive about clearly designed materials. The Index shows that an evidence-based scoring rubric can assess and improve the clarity of health materials. |
Improving ventilator-associated event surveillance in the National Healthcare Safety Network and addressing knowledge gaps: update and review
Magill SS , Rhodes B , Klompas M . Curr Opin Infect Dis 2014 27 (4) 394-400 PURPOSE OF REVIEW: The Centers for Disease Control and Prevention (CDC) recently transitioned from ventilator-associated pneumonia (VAP) surveillance to ventilator-associated event (VAE) surveillance in adult inpatient settings. Since the transition, several modifications have been made to improve surveillance methods, and there is a growing body of data regarding the epidemiology, risk factors, and preventability of VAEs. RECENT FINDINGS: The VAE surveillance definition algorithm is based on objective criteria and includes three tiers: ventilator-associated conditions, infection-related ventilator-associated complications, and possible and probable VAP. VAE surveillance expands the purview of surveillance beyond pneumonia alone to include additional complications of mechanical ventilation. Most VAEs are caused by pneumonia, pulmonary edema, atelectasis, or acute respiratory distress syndrome. VAEs are associated with adverse outcomes including prolonged mechanical ventilation, longer intensive care and hospital length-of-stay, and higher mortality rates. Studies to date suggest that minimizing sedation and optimizing fluid management can reduce VAE rates. SUMMARY: We review the CDC's recent updates on VAE surveillance definitions, methods, and tools, and provide an overview of the growing evidence base for VAE as a patient safety measure. Further work is needed to affirm and extend the current knowledge about how best to prevent VAEs. |
Ischemic cardiac events and other adverse events following ACAM2000(®) smallpox vaccine in the Vaccine Adverse Event Reporting System.
McNeil MM , Cano M , Miller E , Petersen BW , Engler RJ , Bryant-Genevier MG . Vaccine 2014 32 (37) 4758-65 BACKGROUND: The Vaccine Adverse Event Reporting System (VAERS) is a passive reporting system, used for monitoring the safety of all US licensed vaccines. In March 2008, ACAM2000(R) replaced Dryvax(R) as the only licensed smallpox vaccine and is administered to all persons entering military service and certain civilian researchers. In 2011, routine data mining of VAERS identified a vaccine safety concern resulting in acute ischemic cardiac events (ICE) following ACAM2000(R). METHODS: During March 1, 2008 through June 30, 2013, we reviewed all serious reports received following ACAM2000(R)and classified them by diagnostic category. We identified possible ICE cases by searching the Medical Dictionary for Regulatory Affairs (MedDRA) terms for "myocardial ischaemia," "acute myocardial infarction," "myocardial infarction," and "ischaemia," and applied standardized surveillance case definitions. RESULTS: VAERS received 1149 reports following ACAM2000(R) administration; 169 (14.7%) were serious (resulting in permanent disability, hospitalization, life-threatening illnesses or death), including one death. The two most frequent diagnostic categories for serious reports were cardiovascular and other infectious conditions. The MedDRA search found 31 reports of possible ICE after receipt of ACAM2000(R) vaccine. Of a total 30 possible ICE cases with demographic information, all but one was male; the age range was 20-45 years (median 32) and median interval to onset of symptoms was 12 days. On clinical review there were 16 cases of myocarditis/pericarditis and 15 ICE cases. CONCLUSIONS: Our review of the data mining signal did not substantiate the concerns about ICE after ACAM2000(R). Our study also suggests that with current pre-vaccination screening, cardiac morbidity in generally healthy vaccinated populations remains uncommon. |
Receipt of pertussis vaccine during pregnancy across 7 Vaccine Safety Datalink Sites
Kharbanda EO , Vazquez-Benitez G , Lipkind H , Naleway AL , Klein NP , Craig Cheetham T , Hambidge SJ , Vellozzi C , Nordin JD . Prev Med 2014 67 316-9 OBJECTIVE: In response to widespread pertussis outbreaks and infant deaths, in 2010, the California Department of Health (CDPH) and in 2011 the Advisory Committee on Immunization Practices (ACIP) advised that the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine be administered during pregnancy. Goals of this study were to describe Tdap coverage among pregnant women following these recommendations. METHODS: In this observational cohort study, we utilized electronic medical record and claims data from seven Vaccine Safety Datalink sites to identify pregnancies and Tdap administrations. All Tdap doses were classified as pre-pregnancy, during pregnancy or post-pregnancy/postpartum. For pregnancies ending in a live birth, we evaluated factors associated with Tdap vaccination. RESULTS: Among 289,141 live births at the California VSD sites, receipt of Tdap during pregnancy increased substantially in the years 2010, 2011, and 2012, when coverage was 15.9, 30.0 and 19.5%, respectively. Among 82,398 women with live births at the Oregon, Washington, Colorado, Wisconsin and Minnesota VSD sites, receipt of Tdap during pregnancy first increased in 2012, at 16.0%. Women receiving early prenatal care and other vaccine(s) during pregnancy had higher Tdap coverage. CONCLUSION: We observed substantial increases in Tdap coverage during pregnancy following CDPH and ACIP recommendations. |
Use of MenACWY-CRM vaccine in children aged 2 through 23 months at increased risk for meningococcal disease: recommendations of the Advisory Committee on Immunization Practices, 2013
MacNeil JR , Rubin L , McNamara L , Briere EC , Clark TA , Cohn AC . MMWR Morb Mortal Wkly Rep 2014 63 (24) 527-30 During its October 2013 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended use of a third meningococcal conjugate vaccine, MenACWY-CRM (Menveo, Novartis), as an additional option for vaccinating infants aged 2 through 23 months at increased risk for meningococcal disease. MenACWY-CRM is the first quadrivalent meningococcal conjugate vaccine licensed for use in children aged 2 through 8 months. MenACWY-D (Menactra, Sanofi Pasteur) is recommended for use in children aged 9 through 23 months who are at increased risk for meningococcal disease, and Hib-MenCY-TT (MenHibrix, GlaxoSmithKline) is recommended for use in children aged 6 weeks through 18 months at increased risk. This report summarizes information on MenACWY-CRM administration in infants and provides recommendations for vaccine use in infants aged 2 through 23 months who are at increased risk for meningococcal disease. Because the burden of meningococcal disease in infants is low in the United States and the majority of cases that do occur are caused by serogroup B, which is not included in any vaccine licensed in the United States, only those infants who are at increased risk for meningococcal disease are recommended to receive a meningococcal vaccine. |
Effectiveness of seven-valent pneumococcal conjugate vaccine (PCV-7) against invasive pneumococcal disease in HIV-infected and -uninfected children in South Africa: a matched case-control study
Cohen C , von Mollendorf C , de Gouveia L , Naidoo N , Meiring S , Quan V , Nokeri V , Smidt MF , Malope-Kgokong B , Moore D , Reubenson G , Moshe M , Madhi SA , Eley B , Hallbauer U , Kularatne R , Conklin L , O'Brien KL , Zell ER , Klugman K , Whitney CG , von Gottberg A . Clin Infect Dis 2014 59 (6) 808-18 BACKGROUND: South Africa introduced seven-valent pneumococcal conjugate vaccine (PCV-7) in April 2009 using a 2+1 schedule (six and fourteen weeks and nine months). We estimated the effectiveness of ≥2 PCV-7 doses against invasive pneumococcal disease (IPD) in HIV-infected and -uninfected children. METHODS: IPD (pneumococcus identified from a normally sterile site) cases were identified through national laboratory-based surveillance. Specimens were serotyped by Quellung or polymerase chain reaction. Four controls, matched for age, HIV status and hospital were sought for each case. Using conditional logistic regression, we calculated vaccine effectiveness (VE) as one minus the adjusted odds ratio for vaccination. RESULTS: From March 2010 through November 2012, we enrolled 187 HIV-uninfected (48 [26%] vaccine-serotype) and 109 HIV-infected (43 [39%] vaccine-serotype) cases and 752 HIV-uninfected and 347 HIV-infected controls aged ≥16 weeks. Effectiveness of ≥2 PCV-7 doses against vaccine-serotype IPD was 74% (95% CI: 25, 91) among HIV-uninfected and -12% (95% CI: -449, 77) among HIV-infected children. Effectiveness of ≥3 doses against vaccine-serotype IPD was 90% (95% CI: 14, 99) among HIV-uninfected and 57% (95% CI: -371, 96) among HIV-infected children. Among HIV-exposed-uninfected children effectiveness of ≥2 doses was 92% (95% CI: 47, 99) against vaccine-serotype IPD. Effectiveness of ≥2 doses against all-serotype multidrug-resistant IPD was 96% (95% CI: 62, 100) among HIV-uninfected children. CONCLUSIONS: A 2+1 PCV-7 schedule was effective in preventing vaccine-serotype IPD in HIV-uninfected and HIV-exposed-uninfected children. This finding supports the World Health Organization recommendation for this schedule as an alternative to a three-dose primary series among HIV-uninfected individuals. |
Impact of different dosing schedules on the immunogenicity of the human rotavirus vaccine in infants in Pakistan - a randomized trial
Ali SA , Kazi AM , Cortese MM , Fleming JA , Parashar UD , Jiang B , McNeal MM , Steele D , Bhutta Z , Zaidi A . J Infect Dis 2014 210 (11) 1772-9 BACKGROUND: Current oral rotavirus vaccines perform sub optimally in the resource poor settings. We investigated the effect of an additional dose and later schedule on the immunogenicity of monovalent rotavirus vaccine (RV1) in a developing country. METHODS: Infants received RV1 at 6 and 10, 10 and 14, or 6, 10 and 14 weeks of age. The primary objective was to compare anti-rotavirus IgA seroconversion at 18 weeks in the 6/10/14 arm to the cumulative seroconversion (highest result at 14 or 18 weeks) in the 6/10 arm. RESULTS: Overall, 480 (76.2%) of 630 randomized infants completed the trial per protocol. Seroconversion in the 6/10/14 arm was 36.7% (95% CI: 29.8, 44.2) compared to 36.1% (CI: 29.0, 43.9) in the 6/10 arm, (p=1.0); the result from the 10/14 arm was 38.5% (CI: 31.2, 46.3). Seroconversion in the 6/10 arm at 14 weeks (post-hoc) was lower at 29.7% (CI: 23.1, 37.3). CONCLUSION: In Pakistani infants, the immunogenicity of RV1 did not increase significantly with three doses at 6, 10 and 14 weeks compared to two doses at 6 and 10 weeks. Additional strategies should be evaluated for improving rotavirus vaccine immunogenicity in high burden countries. |
Influenza vaccination among persons with work-related asthma
Mazurek JM , White GE , Moorman JE , Storey E . Am J Prev Med 2014 47 (2) 203-11 BACKGROUND: Seasonal influenza vaccination is recommended for all asthma patients. Persons with work-related asthma may have more severe disease than those with non-work-related asthma and may particularly benefit from receiving influenza vaccination. PURPOSE: To determine if influenza vaccination coverage differs among individuals aged 18-64 years with work-related and non-work-related asthma. METHODS: Data from the 2006-2009 Behavioral Risk Factor Surveillance System Asthma Call-Back Survey collected in 38 states and the District of Columbia were analyzed in 2013. Multivariable logistic regression and predictive marginal analyses were conducted to identify factors independently associated with influenza vaccination among respondents aged 18-64 years with work-related asthma. RESULTS: Among adults aged 18-64 years with current asthma, an estimated 42.7% received influenza vaccination in the past 12 months. Although influenza vaccination coverage was significantly higher among adults with work-related asthma than those with non-work-related asthma (48.5% vs 42.8%), this association became non-significant after adjustment for demographic and clinical characteristics (prevalence ratio=1.08, 95% CI=0.99, 1.20). Among individuals with work-related asthma, receiving the influenza vaccine was associated with being 50-64 years old, being unemployed in the prior year, and seeking urgent treatment for worsening asthma symptoms. CONCLUSIONS: Among persons with work-related and non-work-related asthma, less than half received influenza vaccination in the prior year, both below the Healthy People 2010 target of 60%. These results suggest the need for strengthening current vaccination interventions to meet the updated Healthy People 2020 objective of achieving at least 70% influenza vaccination coverage. |
Characterization of rotavirus genotypes before and after the introduction of a monovalent rotavirus vaccine in Colombia
Pelaez-Carvajal D , Cotes-Cantillo K , Paternina-Caicedo A , Gentsch J , de la Hoz-Restrepo F , Patel M . J Med Virol 2014 86 (6) 1083-6 Strain monitoring for emergence of novel strains after the introduction of rotavirus vaccine is an integral component of routine rotavirus immunization programs. Using a laboratory based strain surveillance system between 2008 and 2012, a wide variation in strain pattern in Colombia was founded both before and after the introduction of a monovalent rotavirus vaccine in 2009. G2P[4], a strain fully heterotypic to the vaccine was predominant before vaccine introduction in 2008 (47%) and after vaccine introduction in 2010 (54%), 2011 (86%), and 2012 (32%). The presence of this strain before the introduction of vaccine and decreasing prevalence during the most recent surveillance year suggests secular variation rather than vaccine pressure as a cause for this fluctuation. While strain monitoring can be valuable after vaccine introduction, these surveillance data alone without information on disease incidence or strain specific vaccine effectiveness can be prone to misinterpretation with regard to the role of vaccine pressure on emergence of new or persistent strains. |
Coxsackievirus B1 reveals strain specific differences in plasmacytoid dendritic cell mediated immunogenicity
Hamalainen S , Nurminen N , Ahlfors H , Oikarinen S , Sioofy-Khojine AB , Frisk G , Oberste MS , Lahesmaa R , Pesu M , Hyoty H . J Med Virol 2014 86 (8) 1412-20 Enterovirus infections are usually mild but can also cause severe illnesses and play a role in chronic diseases, such as cardiomyopathies and type 1 diabetes. Host response to the invading virus can markedly modulate the course of the infection, and this response varies between individuals due to the polymorphism of immune response genes. However, it is currently not known if virus strains also differ in their ability to stimulate the host immune system. Coxsackievirus B1 (CBV1) causes severe epidemics in young infants and it has recently been connected with type 1 diabetes in seroepidemiological studies. This study evaluated the ability of different field isolates of CBV1 to induce innate immune responses in PBMCs. CBV1 strains differed markedly in their capacity to induce innate immune responses. Out of the 18 tested CBV1 strains two induced exceptionally strong alpha interferon (IFN-alpha) response in PBMC cultures. The responding cell type was found to be the plasmacytoid dendritic cell. Such a strong innate immune response was accompanied by an up-regulation of several other immune response genes and secretion of cytokines, which modulate inflammation, and adaptive immune responses. These results suggest that enterovirus-induced immune activation depends on the virus strain. It is possible that the immunotype of the virus modulates the course of the infection and plays a role in the pathogenesis of chronic immune-mediated enterovirus diseases. |
Hemoglobin and hip fracture risk in older non-Hispanic white adults
Looker AC . Osteoporos Int 2014 25 (10) 2389-98 The relationship between hemoglobin and hip fracture was examined in older non-Hispanic white adults from the third National Health and Nutrition Examination Survey (NHANES III). Both low and high hemoglobin values were associated with increased hip fracture risk before and after adjusting for selected risk factors. INTRODUCTION: The few studies to date that have examined the relationship between hemoglobin and fracture risk have focused on low hemoglobin values. The present study examined hip fracture risk across the hemoglobin distribution in older non-Hispanic white adults from the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). METHODS: Hemoglobin was measured using a Coulter S-plus Jr.(R) (Coulter Electronics, Hialeah, FL) in 2,122 non-Hispanic whites age 65 years and older. Hip fracture cases were identified using linked Medicare and mortality records obtained through 2007. Cox proportional hazards models were used to assess the best-fitting model and to estimate the hazards ratio (HR) for hip fracture by hemoglobin decile before and after adjusting for selected confounders. RESULTS: There were 239 hip fracture cases in the analytic sample. The best fitting model was quadratic. When compared to values in the middle of the distribution, those with hemoglobin in the lowest and highest deciles had increased hip fracture risk (HRlowest decile = 2.96, 95 % confidence interval (CI) 1.44-6.08; HRhighest decile = 2.06, 95 % CI 1.09-3.92) after adjusting for age and sex. Both HRs remained significant after adjusting for additional confounders (HRlowest decile = 2.24, 95 % CI 1.09-3.92; HRhighest decile = 2.37, 95 % CI 1.35-4.16). CONCLUSIONS: Both low and high hemoglobin values were associated with increased hip fracture risk. The mechanism underlying the relationship is not clear, but there were some suggestions that it may differ for low versus high hemoglobin. |
Child passenger deaths involving alcohol-impaired drivers
Quinlan K , Shults RA , Rudd RA . Pediatrics 2014 133 (6) 966-72 BACKGROUND AND OBJECTIVE: Approximately 1 in 5 child passenger deaths in the United States involves an alcohol-impaired driver, most commonly the child's own driver. The objective of this study was to document recent trends and state-specific rates of these deaths. METHODS: A descriptive analysis of 2001-2010 Fatality Analysis Reporting System data for child passengers aged <15 years killed in alcohol-impaired driving crashes. Driver impairment was defined as a blood alcohol concentration of ≥0.08 g/dL. RESULTS: During 2001-2010, 2344 children <15 years were killed in crashes involving at least 1 alcohol-impaired driver. Of these children, 1515 (65%) were riding with an impaired driver. Annual deaths among children riding with an alcohol-impaired driver decreased by 41% over the decade. Among the 37 states included in the state-level analysis, Texas (272) and California (135) had the most children killed while riding with an impaired driver and South Dakota (0.98) and New Mexico (0.86) had the highest annualized child passenger death rates (per 100 000 children). Most (61%) child passengers of impaired drivers were unrestrained at the time of the crash. One-third of the impaired drivers did not have a valid driver's license. CONCLUSIONS: Alcohol-impaired driving remains a substantial threat to the safety of child passengers in the United States, and typically involves children being driven by impaired drivers. This risk varies meaningfully among states. To make further progress, states and communities could consider increased use of effective interventions and efforts aimed specifically at protecting child passengers from impaired drivers. |
Rapid urine antigen testing for Streptococcus pneumoniae in adults with community-acquired pneumonia: clinical use and barriers
Harris AM , Beekmann SE , Polgreen PM , Moore MR . Diagn Microbiol Infect Dis 2014 79 (4) 454-7 Streptococcus pneumoniae (pneumococcus) is the most common bacterial etiology of community-acquired pneumonia (CAP) in adults, a leading cause of death. The majority of pneumococcal CAP is diagnosed by blood culture, which likely underestimates the burden of disease. The 2007 CAP guidelines recommend routine use of the rapid pneumococcal urinary antigen (UAg) test. To assess the how pneumococcal UAg testing is being used among hospitalized adult CAP patients and what barriers restrict its use, a Web-based survey was distributed in 2013 to 1287 infectious disease physician members of the Emerging Infectious disease Network of the Infectious Disease Society of America. Of 493 eligible responses, 65% use the pneumococcal UAg test. The primary barrier to UAg use was availability (46%). UAg users reported ordering fewer other diagnostic tests and tailoring antibiotic therapy. Increased access to UAg tests could improve pneumonia management and pneumococcal CAP surveillance. |
Lung macrophages "digest" carbon nanotubes using a superoxide/peroxynitrite oxidative pathway
Kagan VE , Kapralov AA , St Croix CM , Watkins SC , Kisin ER , Kotchey GP , Balasubramanian K , Vlasova II , Yu J , Kim K , Seo W , Mallampalli RK , Star A , Shvedova AA . ACS Nano 2014 8 (6) 5610-21 In contrast to short-lived neutrophils, macrophages display persistent presence in the lung of animals after pulmonary exposure to carbon nanotubes. While effective in the clearance of bacterial pathogens and injured host cells, the ability of macrophages to "digest" carbonaceous nanoparticles has not been documented. Here, we used chemical, biochemical, and cell and animal models and demonstrated oxidative biodegradation of oxidatively functionalized single-walled carbon nanotubes via superoxide/NO* --> peroxynitrite-driven oxidative pathways of activated macrophages facilitating clearance of nanoparticles from the lung. |
Measurement of mercury species in human blood using triple spike isotope dilution with SPME-GC-ICP-DRC-MS
Sommer YL , Verdon CP , Fresquez MR , Ward CD , Wood EB , Pan Y , Caldwell KL , Jones RL . Anal Bioanal Chem 2014 406 (20) 5039-47 The measurement of different mercury compounds in human blood can provide valuable information about the type of mercury exposure. To this end, our laboratory developed a biomonitoring method for the quantification of inorganic (iHg), methyl (MeHg), and ethyl (EtHg) mercury in whole blood using a triple-spike isotope dilution (TSID) quantification method employing capillary gas chromatography (GC) and inductively coupled dynamic reaction cell mass spectrometry (ICP-DRC-MS). We used a robotic CombiPAL(R) sample handling station featuring twin fiber-based solid-phase microextraction (SPME) injector heads. The use of two SPME fibers significantly reduces sample analysis cycle times making this method very suitable for high sample throughput, which is a requirement for large public health biomonitoring studies. Our sample preparation procedure involved solubilization of blood samples with tetramethylammonium hydroxide (TMAH) followed by the derivatization with sodium tetra(n-propyl)borate (NaBPr4) to promote volatility of mercury species. We thoroughly investigated mercury species stability in the blood matrix during the course of sample treatment and analysis. The method accuracy for quantifying iHg, MeHg, and EtHg was validated using NIST standard reference materials (SRM 955c level 3) and the Centre de Toxicologie du Quebec (CTQ) proficiency testing (PT) samples. The limit of detection (LOD) for iHg, MeHg, and EtHg in human blood was determined to be 0.27, 0.12, and 0.16 mug/L, respectively. |
Identification of specific antigenic epitope at N-terminal segment of enterovirus 71 (EV-71) VP1 protein and characterization of its use in recombinant form for early diagnosis of EV-71 infection
Zhang J , Jiang B , Xu M , Dai X , Purdy MA , Meng J . Virus Res 2014 189 248-53 Human enterovirus 71 (EV-71) is the main etiologic agent of hand, foot and mouth disease (HFMD). We sought to identify EV-71 specific antigens and develop serologic assays for acute-phase EV-71 infection. A series of truncated proteins within the N-terminal 100 amino acids (aa) of EV-71 VP1 was expressed in Escherichia coli. Western blot (WB) analysis showed that positions around 11-21 aa contain EV-71-specific antigenic sites, whereas positions 1-5 and 51-100 contain epitopes shared with human coxsackievirus A16 (CV-A16) and human echovirus 6 (E-6). The N-terminal truncated protein of VP1, VP16-43, exhibited good stability and was recognized by anti-EV-71 specific rabbit sera. Alignment analysis showed that VP16-43 is highly conserved among EV-71 strains from different genotypes but was heterologous among other enteroviruses. When the GST-VP16-43 fusion protein was incorporated as antibody-capture agent in a WB assay and an ELISA for detecting anti-EV-71 IgM in human sera, sensitivities of 91.7% and 77.8% were achieved, respectively, with 100% specificity for both. The characterized EV-71 VP1 protein truncated to positions 6-43 aa has potential as an antigen for detection of anti-EV-71 IgM for early diagnosis of EV-71 infection in a WB format. |
Induction of stem-like cells with malignant properties by chronic exposure of human lung epithelial cells to single-walled carbon nanotubes
Luanpitpong S , Wang L , Castranova V , Rojanasakul Y . Part Fibre Toxicol 2014 11 (1) 22 BACKGROUND: Carbon nanotubes (CNT) hold great promise to create new and better products for commercial and biomedical applications, but their long-term adverse health effects are a major concern. The objective of this study was to address human lung cancer risks associated with chronic pulmonary exposure to single-walled (SW) CNT through the fundamental understanding of cellular and molecular processes leading to carcinogenesis. We hypothesized that the acquisition of cancer stem cells (CSC), a subpopulation that drive tumor initiation and progression, may contribute to CNT carcinogenesis. METHODS: Non-tumorigenic human lung epithelial cells were chronically exposed to well-dispersed SWCNT for a period of 6 months at the physiologically relevant concentration of 0.02 mug/cm2 surface area dose. Chronic SWCNT-exposed cells were evaluated for the presence of CSC-like cells under CSC-selective conditions of tumor spheres and side population (SP). CSC-like cells were isolated using fluorescence-activated cell sorting and were assessed for aggressive behaviors, including acquired apoptosis resistance and increased cell migration and invasion in vitro, and tumor-initiating capability in vivo. Non-small cell lung cancer cells served as a positive control. RESULTS: We demonstrated for the first time the existence of CSC-like cells in all clones of chronic SWCNT-exposed lung epithelial cells. These CSC-like cells, in contrary to their non-CSC counterpart, possessed all biological features of lung CSC that are central to irreversible malignant transformation, self-renewal, aggressive cancer behaviors, and in vivo tumorigenesis. These cells also displayed aberrant stem cell markers, notably Nanog, SOX-2, SOX-17 and E-cadherin. Restored expression of tumor suppressor p53 abrogated CSC properties of CSC-like cells. Furthermore, we identified specific stem cell surface markers CD24low and CD133high that are associated with SWCNT-induced CSC formation and tumorigenesis. CONCLUSIONS: Our findings provide new and compelling evidence for the acquisition of CSC-like cells induced by chronic SWCNT exposure, which are likely to be a major driving force for SWCNT tumorigenesis. Thus, our study supports prudent adoption of prevention strategies and implementation of exposure control for SWCNT. We also suggest that the detection of CSC and associated surface markers may provide an effective screening tool for prediction of the carcinogenic potential of SWCNT and related nanoparticles. |
Infection of human islets of langerhans with two strains of coxsackie B virus serotype 1: assessment of virus replication, degree of cell death and induction of genes involved in the innate immunity pathway
Anagandula M , Richardson SJ , Oberste MS , Sioofy-Khojine AB , Hyoty H , Morgan NG , Korsgren O , Frisk G . J Med Virol 2014 86 (8) 1402-11 Type 1 diabetes mellitus is believed to be triggered, in part, by one or more environmental factors and human enteroviruses (HEVs) are among the candidates. Therefore, this study has examined whether two strains of HEV may differentially affect the induction of genes involved in pathways leading to the synthesis of islet hormones, chemokines and cytokines in isolated, highly purified, human islets. Isolated, purified human pancreatic islets were infected with strains of Coxsackievirus B1.Viral replication and the degree of CPE/islet dissociation were monitored. The expression of insulin, glucagon, CXCL10, TLR3, IF1H1, CCL5, OAS-1, IFNbeta, and DDX58 was analyzed. Both strains replicated in islets but only one of strain caused rapid islet dissociation/CPE. Expression of the insulin gene was reduced during infection of islets with either viral strain but the gene encoding glucagon was unaffected. All genes analyzed which are involved in viral sensing and the development of innate immunity were induced by Coxsackie B viruses, with the notable exception of TLR3. There was no qualitative difference in the expression pattern between each strain but the magnitude of the response varied between donors. The lack of virus induced expression of TLR3, together with the differential regulation of IF1H1, OAS1 and IFNbeta, (each of which has polymorphic variants influence the predisposition to type 1 diabetes), that might result in defective clearance of virus from islet cells. The reduced expression of the insulin gene and the unaffected expression of the gene encoding glucagon by Coxsackie B1 infection is consistent with the preferential beta-cell tropism of the virus. |
Kyasanur Forest disease virus infection in mice is associated with higher morbidity and mortality than infection with the closely related Alkhurma hemorrhagic fever virus
Dodd KA , Bird BH , Jones ME , Nichol ST , Spiropoulou CF . PLoS One 2014 9 (6) e100301 BACKGROUND: Kyasanur Forest disease virus (KFDV) and Alkhurma hemorrhagic fever virus (AHFV) are closely related members of the Flavivirus genus and are important causes of human disease in India and the Arabian Peninsula, respectively. Despite high genetic similarity, the viruses have distinctly different host ranges and ecologies. Human cases of KFDV or AHFV develop a spectrum of disease syndromes ranging from liver pathology to neurologic disease. Case reports suggest KFDV is more commonly associated with hepatic and gastrointestinal manifestations whereas AHFV is more commonly associated with neurologic disease. METHODOLOGY/PRINCIPAL FINDINGS: Inoculation of three immunocompetent laboratory mouse strains revealed that KFDV was consistently more lethal than AHFV. In subsequent studies utilizing C57BL/6J mice, we demonstrated that KFDV infection was associated with higher viral loads and significantly higher mortality. KFDV-infected mice rapidly developed more severe disease than AHFV-infected mice, as evidenced by significant abnormalities on clinical chemistry panels and more severe pathology in the brain and gastrointestinal tract. CONCLUSIONS/SIGNIFICANCE: Infections of C57BL/6J mice with KFDV or AHFV resulted in clinical disease syndromes that closely approximate the diseases seen in human cases. Despite high genetic similarity, there were clear differences in survival, viral kinetics, clinical chemistry data and histology. These results suggest that distinct mouse models for AHFV and KFDV are necessary in order to gain a better understanding of the unique pathogenesis of each virus, as well as to provide platforms for testing promising vaccines and therapeutics. |
Biogenesis of influenza A virus hemagglutinin cross-protective stem epitopes
Magadan JG , Altman MO , Ince WL , Hickman HD , Stevens J , Chevalier A , Baker D , Wilson PC , Ahmed R , Bennink JR , Yewdell JW . PLoS Pathog 2014 10 (6) e1004204 Antigenic variation in the globular domain of influenza A virus (IAV) hemagglutinin (HA) precludes effective immunity to this major human pathogen. Although the HA stem is highly conserved between influenza virus strains, HA stem-reactive antibodies (StRAbs) were long considered biologically inert. It is now clear, however, that StRAbs reduce viral replication in animal models and protect against pathogenicity and death, supporting the potential of HA stem-based immunogens as drift-resistant vaccines. Optimally designing StRAb-inducing immunogens and understanding StRAb effector functions require thorough comprehension of HA stem structure and antigenicity. Here, we study the biogenesis of HA stem epitopes recognized in cells infected with various drifted IAV H1N1 strains using mouse and human StRAbs. Using a novel immunofluorescence (IF)-based assay, we find that human StRAbs bind monomeric HA in the endoplasmic reticulum (ER) and trimerized HA in the Golgi complex (GC) with similar high avidity, potentially good news for producing effective monomeric HA stem immunogens. Though HA stem epitopes are nestled among several N-linked oligosaccharides, glycosylation is not required for full antigenicity. Rather, as N-linked glycans increase in size during intracellular transport of HA through the GC, StRAb binding becomes temperature-sensitive, binding poorly to HA at 4 degrees C and well at 37 degrees C. A de novo designed, 65-residue protein binds the mature HA stem independently of temperature, consistent with a lack of N-linked oligosaccharide steric hindrance due to its small size. Likewise, StRAbs bind recombinant HA carrying simple N-linked glycans in a temperature-independent manner. Chemical cross-linking experiments show that N-linked oligosaccharides likely influence StRAb binding by direct local effects rather than by globally modifying the conformational flexibility of HA. Our findings indicate that StRAb binding to HA is precarious, raising the possibility that sufficient immune pressure on the HA stem region could select for viral escape mutants with increased steric hindrance from N-linked glycans. |
Cynomolgus and pigtail macaque IgG subclasses: characterization of IGHG genes and computational analysis of IgG/Fc receptor binding affinity
Nguyen DC , Sanghvi R , Scinicariello F , Pulit-Penaloza J , Hill N , Attanasio R . Immunogenetics 2014 66 (6) 361-77 Macaques are the most widely used experimental nonhuman primate (NHP) species. Rhesus (Macaca mulatta, Macmul), cynomolgus (Macaca fascicularis, Macfas), and pigtail (Macaca nemestrina, Macnem) macaques continue to be popular models for vaccine and infectious diseases research, especially HIV infection and AIDS, and for the development of antibody-based therapeutic strategies. Increased understanding of the immune system of these species is necessary for their optimal use as models of human infections and intervention. In the past few years, the antibody/Fc receptor system has been characterized in a stepwise manner in these species. We have continued this characterization by identifying the four IG heavy gamma (IGHG) genes of Macfas and Macnem in this study. Our results show that these genes share a high degree of similarity with those from other NHP species, while presenting consistent differences when compared to human IGHG genes. Furthermore, comparison of Macfas IGHG genes with those described in other studies suggests the existence of polymorphism. Using sequence- and structure-based computational tools, we performed in silico analysis on multiple polymorphic Macfas IgG and their interactions with human IgG Fc receptors (FcgammaR), thus predicting that Macfas IGHG polymorphisms influence IgG protein stability and/or binding affinity towards FcgammaR. The presence of macaque IGHG polymorphisms and macaque/human amino acid changes at locations potentially involved in antibody functional properties indicate the need for cautious design and data interpretation of studies in these models, possibly requiring the characterization of antibody/Fc receptor interactions at the individual level. |
Differential expression of anti-glycan antibodies in schistosome-infected humans, rhesus monkeys and mice
Luyai AE , Heimburg-Molinaro J , Prasanphanich NS , Mickum ML , Lasanajak Y , Song X , Nyame AK , Wilkins P , Rivera-Marrero CA , Smith DF , Van Die I , Secor WE , Cummings RD . Glycobiology 2014 24 (7) 602-18 Schistosomiasis is a debilitating parasitic disease of humans, endemic in tropical areas, for which no vaccine is available. Evidence points to glycan antigens as being important in immune responses to infection. Here we describe our studies on the comparative humoral immune responses to defined schistosome-type glycan epitopes in Schistosoma mansoni-infected humans, rhesus monkeys and mice. Rhesus anti-glycan responses over the course of infection were screened on a defined glycan microarray comprising semi-synthetic glycopeptides terminating with schistosome-associated or control mammalian-type glycan epitopes, as well as a defined glycan microarray of mammalian-type glycans representing over 400 glycan structures. Infected rhesus monkeys generated a high immunoglobulin G (IgG) antibody response to the core xylose/core alpha3 fucose epitope of N-glycans, which peaked at 8-11 weeks post infection, coinciding with maximal ability to kill schistosomula in vitro. By contrast, infected humans generated low antibody levels to this epitope. At 18 months following praziquantel therapy to eliminate the parasite, antibody levels were negligible. Mice chronically infected with S. mansoni generated high levels of anti-fucosylated LacdiNAc (GalNAcbeta1, 4(Fucalpha1, 3)GlcNAc) IgM antibodies, but lacked a robust response to the core xylose/core alpha3 fucose N-glycan antigens compared with other species studied, and their sera demonstrated an intermediate level of schistosomula killing in vitro. These differential responses to parasite glycan antigens may be related to the ability of rhesus monkeys to self-cure in contrast to the chronic infection seen in humans and mice. Our results validate defined glycan microarrays as a useful technology to evaluate diagnostic and vaccine antigens for schistosomiasis and perhaps other infections. |
Prevalence estimates of gestational diabetes mellitus in the United States, Pregnancy Risk Assessment Monitoring System (PRAMS), 2007-2010
DeSisto CL , Kim SY , Sharma AJ . Prev Chronic Dis 2014 11 E104 INTRODUCTION: The true prevalence of gestational diabetes mellitus (GDM) is unknown. The objective of this study was 1) to provide the most current GDM prevalence reported on the birth certificate and the Pregnancy Risk Assessment Monitoring System (PRAMS) questionnaire and 2) to compare GDM prevalence from PRAMS across 2007-2008 and 2009-2010. METHODS: We examined 2010 GDM prevalence reported on birth certificate or PRAMS questionnaire and concordance between the sources. We included 16 states that adopted the 2003 revised birth certificate. We also examined trends from 2007 through 2010 and included 21 states that participated in PRAMS for all 4 years. We combined GDM prevalence across 2-year intervals and conducted t tests to examine differences. Data were weighted to represent all women delivering live births in each state. RESULTS: GDM prevalence in 2010 was 4.6% as reported on the birth certificate, 8.7% as reported on the PRAMS questionnaire, and 9.2% as reported on either the birth certificate or questionnaire. The agreement between sources was 94.1% (percent positive agreement = 3.7%, percent negative agreement = 90.4%). There was no significant difference in GDM prevalence between 2007-2008 (8.1%) and 2009-2010 (8.5%, P = .15). CONCLUSION: Our results indicate that GDM prevalence is as high as 9.2% and is more likely to be reported on the PRAMS questionnaire than the birth certificate. We found no statistical difference in GDM prevalence between the 2 phases. Further studies are needed to understand discrepancies in reporting GDM by data source. |
Blood folate concentrations among women of childbearing age by race/ethnicity and acculturation, NHANES 2001-2010
Marchetta CM , Hamner HC . Matern Child Nutr 2014 12 (1) 39-50 Hispanic women have higher rates of neural tube defects and report lower total folic acid intakes than non-Hispanic white (NHW) women. Total folic acid intake, which is associated with neural tube defect risk reduction, has been found to vary by acculturation factors (i.e. language preference, country of origin, or time spent in the United States) among Hispanic women. It is unknown whether this same association is present for blood folate status. The objective of this research was to assess the differences in serum and red blood cell (RBC) folate concentrations between NHW women and Mexican American (MA) women and among MA women by acculturation factors. Cross-sectional data from the 2001-2010 National Health and Nutrition Examination Survey (NHANES) were used to investigate how blood folate concentrations differ among NHW or MA women of childbearing age. The impact of folic acid supplement use on blood folate concentrations was also examined. MA women with lower acculturation factors had lower serum and RBC folate concentrations compared with NHW women and to their more acculturated MA counterparts. Consuming a folic acid supplement can minimize these disparities, but MA women, especially lower acculturated MA women, were less likely to report using supplements. Public health efforts to increase blood folate concentrations among MA women should consider acculturation factors when identifying appropriate interventions. |
Understanding factors that influence protective glove use among automotive spray painters
Ceballos D , Reeb-Whitaker C , Glazer P , Murphy-Robinson H , Yost M . J Occup Environ Hyg 2014 11 (5) 306-13 Dermal contact with isocyanate-based coatings may lead to systemic respiratory sensitization. The most common isocyanates found in sprayed automotive coatings are monomeric and oligomeric 1,6-hexamethylene diisocyanate (HDI) and isophorone diisocyanate (IPDI). Most spray painters use thin (4-5 mil) latex gloves that are not effective at preventing dermal exposures when spraying isocyanate paints. Personal interviews with collision repair industry personnel and focus groups with spray painters were held to characterize risk awareness, to examine perceptions and challenges concerning protective glove use and selection, and to generate ideas for protective glove use interventions. The most popular gloves among spray painters were thin (4-5 mil) and thick (14 mil) latex. We found that medium to thick (6-8 mil) nitrile were not always perceived as comfortable and were expected to be more expensive than thin (4-5 mil) latex gloves. Of concern is the user's difficulty in distinguishing between nitrile and latex gloves; latex gloves are now sold in different colors including blue, which has traditionally been associated with nitrile gloves. Even though spray painters were familiar with the health hazards related to working with isocyanate paints, most were not always aware that dermal exposure to isocyanates could contribute to the development of occupational asthma. There is a need for more research to identify dermal materials that are protective against sprayed automotive coatings. Automotive spray painters and their employers need to be educated in the selection and use of protective gloves, specifically on attributes such as glove material, color, and thickness. |
Workplace violence prevention for nurses on-line course: program development
Hartley D , Ridenour M , Craine J , Morrill A . Work 2014 51 (1) 79-89 BACKGROUND: Many entry-level and experienced healthcare professionals have not received training in workplace violence prevention strategies. OBJECTIVE: This paper describes the development, content, and initial qualitative evaluation of an on-line course designed to give healthcare workers an opportunity to acquire free workplace violence prevention training while earning free continuing education units. METHODS: A group of healthcare violence prevention researchers worked via email and face-to-face meetings to decide appropriate content for the course. Educational strategies used in the course include: text; video re-enactments of real-life workplace violence incidents; and videos of nurses discussing incidents of violence. Initial evaluation involved a focus group of nurses to discuss the course content and navigation. RESULTS: The on-line course has thirteen units that take approximately 15 minutes each to complete. The focus group participants liked the "resume-where-you-left-off" technology that enables the user to complete any portion of the course, leave to do something, and return to the course where they left off. Participants viewed the "Nurses' Voices" videos as relevant illustrations of violence that nurses face in their workplaces. CONCLUSIONS: The focus group participants considered the course to be an effective learning tool for people new to the profession and for those with seniority. |
Occupational exposure to extremely low frequency magnetic fields and brain tumour risks in the INTEROCC study
Turner MC , Benke G , Bowman JD , Figuerola J , Fleming S , Hours M , Kincl L , Krewski D , McLean D , Parent ME , Richardson L , Sadetzki S , Schlaefer K , Schlehofer B , Schuz J , Siemiatycki J , Van Tongeren M , Cardis E . Cancer Epidemiol Biomarkers Prev 2014 23 (9) 1863-72 BACKGROUND: Occupational exposure to extremely low frequency magnetic fields (ELF) is a suspected risk factor for brain tumours, however the literature is inconsistent. Few studies have assessed whether ELF in different time windows of exposure may be associated with specific histologic types of brain tumours. This study examines the association between ELF and brain tumours in the large-scale INTEROCC study. METHODS: Cases of adult primary glioma and meningioma were recruited in seven countries (Australia, Canada, France, Germany, Israel, New Zealand, United Kingdom) between 2000 and 2004. Estimates of mean workday ELF exposure based on a job exposure matrix assigned. Estimates of cumulative exposure, average exposure, maximum exposure, and exposure duration were calculated for the lifetime, and 1-4, 5-9, and 10+ years prior to the diagnosis/reference date. RESULTS: There were 3,761 included brain tumour cases (1,939 glioma, 1,822 meningioma) and 5,404 population controls. There was no association between lifetime cumulative ELF exposure and glioma or meningioma risk. However, there were positive associations between cumulative ELF 1-4 years prior to the diagnosis/reference date and glioma (odds ratio (OR) ≥ 90th percentile vs < 25th percentile = 1.67, 95% confidence interval (CI) 1.36-2.07, p < 0.0001 linear trend), and, somewhat weaker associations with meningioma (OR ≥ 90th percentile vs < 25th percentile = 1.23, 95% CI 0.97-1.57, p = 0.02 linear trend). CONCLUSIONS: Results showed positive associations between ELF in the recent past and glioma. IMPACT: Occupational ELF exposure may play a role in the later stages (promotion and progression) of brain tumourigenesis. |
Association between psychosocial job characteristics and sickness absence due to low back symptoms using combined DCS and ERI models
Yu S , Lu ML , Gu G , Zhou W , He L , Wang S . Work 2014 51 (3) 411-21 OBJECTIVE: To evaluate the combined demand-control-support (DCS) and effort-reward-overcommitment (ERI-OC) stress models in association with sickness absence due to low back symptoms (SA-LBS). METHODS: A total of 2,737 blue-collar workers recruited from 13 companies in the most populous province (Henan) of China were included in the study. Personal and physical job characteristics, psychosocial scales of the stress models, and SA-LBS data in the preceding year were collected by a self-reported questionnaire and analyzed by a multivariable logistic regression model. Tertile exposure levels (low, medium and high) were constructed to discriminate a risk level. Odds ratios (OR) with 95% confidence intervals (CI) were used as the association with SA-LBS. RESULTS: A large percentage (84.5%) of the Chinese workers did not take sick leave after reporting low back symptoms during the preceding year. High job demand or medium-high reward was associated with SA-LBS. The association of the combined stress models and SA-LBS was not evident. CONCLUSIONS: The ERI-OC model appeared to be more predictive of SA-LBS than the DCS model in the study population. The advantage of using combined stress models for predicting SA-LBS is not evident. |
Development and characterization of an exposure platform suitable for physico-chemical, morphological and toxicological characterization of printer-emitted particles (PEPs)
Pirela SV , Pyrgiotakis G , Bello D , Thomas T , Castranova V , Demokritou P . Inhal Toxicol 2014 26 (7) 400-8 An association between laser printer use and emissions of particulate matter (PM), ozone and volatile organic compounds has been reported in recent studies. However, the detailed physico-chemical, morphological and toxicological characterization of these printer-emitted particles (PEPs) and possible incorporation of engineered nanomaterials into toner formulations remain largely unknown. In this study, a printer exposure generation system suitable for the physico-chemical, morphological, and toxicological characterization of PEPs was developed and used to assess the properties of PEPs from the use of commercially available laser printers. The system consists of a glovebox type environmental chamber for uninterrupted printer operation, real-time and time-integrated particle sampling instrumentation for the size fractionation and sampling of PEPs and an exposure chamber for inhalation toxicological studies. Eleven commonly used laser printers were evaluated and ranked based on their PM emission profiles. Results show PM peak emissions are brand independent and varied between 3000 to 1 300 000 particles/cm(3), with modal diameters ranging from 49 to 208 nm, with the majority of PEPs in the nanoscale (<100 nm) size. Furthermore, it was shown that PEPs can be affected by certain operational parameters and printing conditions. The release of nanoscale particles from a nano-enabled product (printer toner) raises questions about health implications to users. The presented PEGS platform will help in assessing the toxicological profile of PEPs and the link to the physico-chemical and morphological properties of emitted PM and toner formulations. |
The association of Toxoplasma gondii infection with neurocognitive deficits in a population-based analysis
Pearce BD , Kruszon-Moran D , Jones JL . Soc Psychiatry Psychiatr Epidemiol 2014 49 (6) 1001-10 PURPOSE: To examine the relationship between infection with Toxoplasma gondii (toxo) and cognition. METHODS: Multivariate logistic regression was used to test the association of toxo seropositivity with indices of cognitive function among over 4,200 adults in the third National Health and Nutrition Examination Survey. RESULTS: Toxo-seropositive participants were more likely than seronegative participants to score in the worst quartile of the simple reaction time test (OR 1.3, 95 % CI 1.0, 1.6), symbol-digit substitution test (SDST, OR 1.5, 95 % CI 1.2, 1.9) and the serial-digit learning test (trials to criterion) (SDLTNT, OR 1.4, 95 % CI 1.1, 1.8) in models adjusted for age, race/ethnicity, gender and foreign birth. After further adjustment for all cofactors, the association between toxo seropositivity and these outcomes was no longer significant. However, seropositivity was associated with worse scores on the SDST (OR 2.9, 95 % CI 1.8, 4.8) among those in the lowest income category and the SDLTNT (OR 1.5, 95 % CI 1.1, 2.5) among those foreign born. CONCLUSIONS: Toxo seropositivity may be associated with poor cognitive test scores in certain subgroups; however, causation cannot be established in this cross-sectional study. |
Physical activity and health-related quality of life: US adults with and without limitations
Brown DR , Carroll DD , Workman LM , Carlson SA , Brown DW . Qual Life Res 2014 23 (10) 2673-80 PURPOSE: The purpose of this study was to examine the dose-response relationship between physical activity (PA) and health-related quality of life (HRQOL) among adults with and without limitations. METHODS: We dichotomized HRQOL as ≥14 unhealthy (physical or mental) days (past 30 days), or <14 unhealthy days. By using a moderate-intensity minute equivalent, PA categories were as follows: inactive, 10-60, 61-149, 150-300, and >300 min/week. Persons with limitations reported having problems that limited their activities or required use of special equipment. Age-adjusted prevalence estimates and logistic regression analyses were performed with 2009 Behavioral Risk Factor Surveillance System data (n = 357,665), controlling for demographics, BMI, smoking, and heavy alcohol use. RESULTS: For adults without limitations, the odds of ≥14 unhealthy days were lower among adults obtaining any PA (10-60 min/week, AOR = 0.79, 95 % CI 0.70, 0.88), compared with those inactive. A quadratic trend (P < 0.001) indicated enhanced HRQOL with each PA level, but improvements were less marked between lower and upper sufficient PA categories (150-300 and >300 min/week). Because of a significant age interaction, persons with limitations were stratified by age (18-34, 35-64, and 65+ years). Findings for persons aged 35 years or older with limitations were similar to those without limitations. Lower odds of poor HRQOL for persons aged 18-34 years with limitations were associated with recommended levels of PA (150-300 min/week; AOR = 0.61, 95 % CI 0.43, 0.88 and >300 min/week; AOR = 0.58, 95 % CI 0.43, 0.80). CONCLUSIONS: PA is positively associated with HRQOL among persons with and without limitations. |
Go Green, Get Healthy: an agencywide effort to reduce energy use and move the Centers for Disease Control and Prevention toward sustainability
York L , Janet L , Lanasa S . J Energ Eng 2014 140 (2) 7 Americans look to the Centers for Disease Control and Prevention (CDC) to lead by providing an example of healthy people in healthy environments. Recognizing the synergy between environmental health and personal health and well-being, the CDC formed the Go Green, Get Healthy (GGGH) initiative. The GGGH rolls healthier worksite initiatives, quality-of-work-life programs, and internal environmental protection efforts into a coordinated campaign for widespread cultural change with energy conservation as one of the major goals. The CDC hopes that this success will be a model for other agencies and organizations. The Office of Sustainability at the CDC actively engages the entire agency in environmental stewardship and specifically, energy conservation (in the GGGH initiative) by providing a vision with leadership support, education for every individual, effective communication methods, and a robust tracking system for comprehensive data and feedback. The campaign works effectively by breaking down the task of greening the agency into sectors. Each sector needs support of CDC leadership and work of responsible offices, complimented by the grassroots dedication of individuals in the GGGH workgroups and collaborative external partnerships. Several low/no-cost examples are included to demonstrate progress toward a sustainable CDC and these can be used to help other organizations discover a greener and healthier model for their sustainability and conservation efforts with a minimal outlay of funds. Through physical changes, culture changes, and policy/operational changes, energy and water can be saved. This paper seeks to convey the following main learning points: (1)identify low/no-cost ways to reduce energy and water consumption; (2)describe ways to influence workers to adopt more sustainable behaviors; and (3)discuss ways to integrate energy-management decision-making processes and standard operating procedures. |
Do maladaptive behaviors exist at one or both ends of personality traits?
Pettersson E , Mendle J , Turkheimer E , Horn EE , Ford DC , Simms LJ , Clark LA . Psychol Assess 2014 26 (2) 433-46 In the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; American Psychiatric Association, 2013) personality disorder trait model, maladaptive behavior is located at one end of continuous scales. Widiger and colleagues, however, have argued that maladaptive behavior exists at both ends of trait continua. We propose that the role of evaluative variance differentiates these two perspectives and that once evaluation is isolated, maladaptive behaviors emerge at both ends of nonevaluative trait dimensions. In Study 1, we argue that evaluative variance is worthwhile to measure separately from descriptive content because it clusters items by valence regardless of content (e.g., lazy and workaholic; apathetic and anxious; gullible and paranoid; timid and hostile, etc.), which is unlikely to describe a consistent behavioral style. We isolate evaluation statistically (Study 2) and at the time of measurement (Study 3) to show that factors unrelated to valence evidence maladaptive behavior at both ends. We argue that nonevaluative factors, which display maladaptive behavior at both ends of continua, may better approximate ways in which individuals actually behave. |
A new stochastic kriging method for modeling multi-source exposure-response data in toxicology studies
Wang K , Chen X , Yang F , Porter DW , Wu N . ACS Sustain Chem Eng 2014 2 (7) 1581-1591 One of the most fundamental steps in risk assessment is to quantify the exposure-response relationship for the material/chemical of interest. This work develops a new statistical method, referred to as SKQ (stochastic kriging with qualitative factors), to synergistically model exposure-response data, which often arise from multiple sources (e.g. laboratories, animal providers, and shapes of nanomaterials) in toxicology studies. Compared to the existing methods, SKQ integrates data across multiple sources and allows for the derivation of more accurate information from limited data. Second, SKQ is highly flexible and able to model practically any continuous response surfaces (e.g. dose-time-response surface). Third, SKQ is able to accomodate variance heterogeneity across experimental conditions and to provide valid statistical inference (i.e. quantify uncertainties of the model estimates). Through empirical studies, we have demonstrated SKQ's ability to efficiently model exposure-response surfaces by pooling information across multiple data sources. SKQ fits into the mosaic of efficient decision-making methods for assessing the risk of a tremendously large variety of nanomaterials and helps to alleviate safety concerns regarding the enormous amount of new nanomaterials. |
Notes from the field: increase in fentanyl-related overdose deaths - Rhode Island, November 2013-March 2014
Mercado-Crespo MC , Sumner SA , Spelke MB , Sugerman DE , Stanley C . MMWR Morb Mortal Wkly Rep 2014 63 (24) 531 During November 2013-March 2014, twice as many all-intent drug overdose deaths were reported in Rhode Island as were reported during the same period in previous years. Most deaths were among injection-drug users, and a large percentage involved fentanyl, a synthetic opioid that is 50-100 times more potent than morphine. Clusters of fentanyl-related deaths have been reported recently in several states. From April 2005 to March 2007, time-limited active surveillance from CDC and the Drug Enforcement Administration identified 1,013 deaths caused by illicit fentanyl use in New Jersey; Maryland; Chicago, Illinois; Detroit, Michigan; and Philadelphia, Pennsylvania. Acetyl fentanyl, an illegally produced fentanyl analog, caused a cluster of overdose deaths in northern Rhode Island in 2013. |
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