Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.
Holmes MV , Dale CE , Zuccolo L , Silverwood RJ , Guo Y , Ye Z , Prieto-Merino D , Dehghan A , Trompet S , Wong A , Cavadino A , Drogan D , Padmanabhan S , Li S , Yesupriya A , Leusink M , Sundstrom J , Hubacek JA , Pikhart H , Swerdlow DI , Panayiotou AG , Borinskaya SA , Finan C , Shah S , Kuchenbaecker KB , Shah T , Engmann J , Folkersen L , Eriksson P , Ricceri F , Melander O , Sacerdote C , Gamble DM , Rayaprolu S , Ross OA , McLachlan S , Vikhireva O , Sluijs I , Scott RA , Adamkova V , Flicker L , Bockxmeer FM , Power C , Marques-Vidal P , Meade T , Marmot MG , Ferro JM , Paulos-Pinheiro S , Humphries SE , Talmud PJ , Mateo Leach I , Verweij N , Linneberg A , Skaaby T , Doevendans PA , Cramer MJ , Harst Pv , Klungel OH , Dowling NF , Dominiczak AF , Kumari M , Nicolaides AN , Weikert C , Boeing H , Ebrahim S , Gaunt TR , Price JF , Lannfelt L , Peasey A , Kubinova R , Pajak A , Malyutina S , Voevoda MI , Tamosiunas A , Maitland-van der Zee AH , Norman PE , Hankey GJ , Bergmann MM , Hofman A , Franco OH , Cooper J , Palmen J , Spiering W , Jong PA , Kuh D , Hardy R , Uitterlinden AG , Ikram MA , Ford I , Hypponen E , Almeida OP , Wareham NJ , Khaw KT , Hamsten A , Husemoen LL , Tjonneland A , Tolstrup JS , Rimm E , Beulens JW , Verschuren WM , Onland-Moret NC , Hofker MH , Wannamethee SG , Whincup PH , Morris R , Vicente AM , Watkins H , Farrall M , Jukema JW , Meschia J , Cupples LA , Sharp SJ , Fornage M , Kooperberg C , LaCroix AZ , Dai JY , Lanktree MB , Siscovick DS , Jorgenson E , Spring B , Coresh J , Li YR , Buxbaum SG , Schreiner PJ , Ellison RC , Tsai MY , Patel SR , Redline S , Johnson AD , Hoogeveen RC , Hakonarson H , Rotter JI , Boerwinkle E , Bakker PI , Kivimaki M , Asselbergs FW , Sattar N , Lawlor DA , Whittaker J , Davey Smith G , Mukamal K , Psaty BM , Wilson JG , Lange LA , Hamidovic A , Hingorani AD , Nordestgaard BG , Bobak M , Leon DA , Langenberg C , Palmer TM , Reiner AP , Keating BJ , Dudbridge F , Casas JP . BMJ 2014 349 g4164 OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health. |
Women's clinical preventive services in the United States: who is doing what?
Stormo AR , Saraiya M , Hing E , Henderson JT , Sawaya GF . JAMA Intern Med 2014 174 (9) 1512-4 A well-woman preventive care visit is a core service supported by the Human Resources and Services Administration,1 yet it is unclear which preventive services are provided by primary care physicians (PCPs) and which are provided by obstetrician/gynecologists (OB/GYNs).2,3 We examined patterns of selected age-appropriate preventive care visits across a woman’s lifespan, focusing on the wide range of preventive services provided to nonpregnant women. |
Impact of the National Breast and Cervical Cancer Early Detection Program on cervical cancer mortality among uninsured low-income women in the U.S., 1991-2007
Ekwueme DU , Uzunangelov VJ , Hoerger TJ , Miller JW , Saraiya M , Benard VB , Hall IJ , Royalty J , Li C , Myers ER . Am J Prev Med 2014 47 (3) 300-8 BACKGROUND: The benefits of the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) on cervical cancer screening for participating uninsured low-income women have never been measured. PURPOSE: To estimate the benefits in life-years (LYs) gained; quality-adjusted life-years (QALYs) gained; and deaths averted. METHODS: A cervical cancer simulation model was constructed based on an existing cohort model. The model was applied to NBCCEDP participants aged 18-64 years. Screening habits for uninsured low-income women were estimated using National Health Interview Survey data from 1990 to 2005 and NBCCEDP data from 1991 to 2007. The study was conducted during 2011-2012 and covered all 68 NBCCEDP grantees in 50 states, the District of Columbia, five U.S. territories, and 12 tribal organizations. Separate simulations were performed for the following three scenarios: (1) women who received NBCCEDP (Program) screening; (2) women who received screening without the program (No Program); and (3) women who received no screening (No Screening). RESULTS: Among 1.8 million women screened in 1991-2007, the Program added 10,369 LYs gained compared to No Program, and 101,509 LYs gained compared to No Screening. The Program prevented 325 women from dying of cervical cancer relative to No Program, and 3,829 relative to No Screening. During this time period, the Program accounted for 15,589 QALYs gained when compared with No Program, and 121,529 QALYs gained when compared with No Screening. CONCLUSIONS: These estimates suggest that NBCCEDP cervical cancer screening has reduced mortality among medically underserved low-income women who participated in the program. |
Describing the burden of non-communicable disease risk factors among adults with diabetes in Wallis and Futuna
Girin N , Brostrom R , Ram S , McKenzie J , Kumar AMV , Roseveare C . Public Health Action 2014 4 S39-S43 BACKGROUND: The South Pacific Territory of Wallis and Futuna has a high burden of non-communicable diseases (NCD): 18% of adults have diabetes mellitus (DM) and 87% are classified as overweight or obese. OBJECTIVE: To characterise the burden of additional World Health Organization (WHO) recognised NCD risk factors, such as smoking, obesity, high blood pressure, eating less than five fruit or vegetable servings per day and a sedentary lifestyle, among adults with DM. DESIGN: Re-analysis of cross-sectional data from a 2009 national survey. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Of 487 adults sampled, 87 (18%) had DM. Nearly 99% of individuals with DM had at least one additional NCD risk factor, and 62% had three or more concurrent NCD risk factors. Individuals with DM were more likely to be obese (OR 1.66, 95%CI 1.01-2.74) and had a much higher prevalence of high blood pressure (OR 3.02, 95%CI 1.87-4.86). CONCLUSION: DM is rarely identified in the absence of other NCD risk factors. We recommend an integrated approach to the management of DM and other NCD risk factors in routine care rather than a disease-specific approach. |
Characteristics of adults in the hepatitis B research network in North America reflect their country of origin and hepatitis B virus genotype.
Ghany M , Perrillo R , Li R , Belle SH , Janssen HL , Terrault NA , Shuhart MC , Lau DT , Kim WR , Fried MW , Sterling RK , Di Bisceglie AM , Han SH , Ganova-Raeva LM , Chang KM , Suk-Fong Lok A . Clin Gastroenterol Hepatol 2014 13 (1) 183-92 BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the US and Canada might be disproportionately affected. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network. METHODS: The HBRN collected data on clinical characteristics of 1625 adults with chronic HBV infection who are not receiving antiviral therapy from 21 clinical centers in North America. RESULTS: Half of the subjects in the HBRN are male, and the mean age is 42 years; 72% are Asian, 15% are Black, and 11% are White, with 82% born outside of North America. The most common HBV genotype was B (39%); 745 of subjects were negative for the hepatitis B e antigen. The median serum level of HBV DNA when the study began was 3.6 log10 IU/mL; 68% of male subjects and 67% of female subjects had levels of alanine aminotransferase above the normal range. CONCLUSIONS: The HBRN cohort will be used to address important clinical and therapeutic questions for North Americans infected with chronic HBV and to guide health policies on HBV prevention and management in North America. |
Severity of rhinovirus infection in hospitalized adults is unrelated to genotype.
McCulloch DJ , Sears MH , Jacob JT , Lyon GM , Burd EM , Caliendo AM , Hill CE , Nix WA , Oberste MS , Kraft CS . Am J Clin Pathol 2014 142 (2) 165-72 OBJECTIVES: To determine whether rhinovirus (RV) species is associated with more severe clinical illness in adults. METHODS: Seventy-two RV-positive viral respiratory samples from adult patients were sequenced and analyzed phylogenetically after reverse transcriptase polymerase chain reaction of the region spanning the VP4 gene and 5' terminus of the VP2 gene. The clinical features and severity of illness associated with the different RV species were compared. RESULTS: Phylogenetic analysis identified three distinct clusters as RV-A (54%), B (11%), or C (35%) species. In an unadjusted model, patients with RV-B infection were significantly more likely to have the composite outcome variable of death or intensive care unit admission (P = .03), but this effect diminished when controlling for patient sex. A logistic model of the relationship between RV species and adverse outcomes produced nonsignificant odds ratios when controlling for patient sex. CONCLUSIONS: Infection with RV-A or RV-B was associated with greater severity of illness in our adult population; however, the association disappeared after controlling for confounders. |
Screening for tuberculosis and LTBI in diabetes patients, Pohnpei, Federated States of Micronesia
Defang RR , Brostrom R , Ram S , Johnson E , Perman PS . Public Health Action 2014 4 S53-S55 A retrospective cohort study was performed in Pohnpei, a small Pacific Island, to evaluate the feasibility and results of screening adult diabetes (DM) patients for tuberculosis (TB) and latent tuberculous infection (LTBI) using a symptom screen, tuberculin skin testing and chest radiography. Of 79 patients, 65 (82%) completed screening. Two (3%) patients with active TB and 16 (25%) with LTBI were referred for anti-tuberculosis treatment and isoniazid preventive therapy, respectively. It is feasible and worthwhile to screen diabetes patients for TB, but a number of changes are needed to improve both the screening process and the diagnostic yield. |
Opportunities for tuberculosis diagnosis and prevention among persons living with HIV: a cross-sectional study of policies and practices at four large Ryan White Program-funded HIV clinics
Pascopella L , Franks J , Marks SM , Salcedo K , Schmitz K , Colson PW , Hirsch-Moverman Y , Flood J , Sayles J . PLoS One 2014 9 (7) e101313 OBJECTIVE: We describe the frequency and attributes of tuberculosis testing and treatment at four publicly-funded HIV clinics. METHODS: We abstracted medical records from a random sample of 600 HIV-infected patients having at least one clinic visit in 2009 at four clinics in New York and Los Angeles Metropolitan Statistical areas. We described testing and treatment for tuberculosis infection (TBI), 2008-2010, and estimated adjusted odds ratios (aORs). We interviewed key informants and described clinic policies and practices. RESULTS: Of 600 patients, 500 were eligible for testing, and 393 (79%) were tested 2008-2010; 107 (21%) did not receive at least one tuberculin skin test or interferon gamma release assay. Results were positive in 20 (5%) patients, negative in 357 (91%), and unknown in 16 (4%). Fourteen (70%) of 20 patients with TBI initiated treatment at the clinics; only three were documented to have completed treatment. Three hundred twenty three (54%) patients had chest radiography, 346 (58%) had tuberculosis symptom screening, and three had tuberculosis disease (117 per 100,000 person-years, 95% confidence interval (CI) = 101-165). Adjusting for site, non-Hispanic ethnicity (aOR = 4.9, 95% CI = 2.6-9.5), and employment (aOR = 1.9, 95% CI = 1.0-3.4) were associated with TBI testing; female gender (aOR = 2.0, 95% CI = 1.4-3.3), non-black race (aOR = 1.7, 95% CI = 1.3-2.5), and unemployment (aOR = 1.5, 95% CI = 1.1-2.1) were associated with chest radiography. Clinics evaluated TBI testing performance annually and identified challenges to TB prevention. CONCLUSIONS: Study clinics routinely tested patients for TBI, but did not always document treatment. In a population with a high TB rate, ensuring treatment of TBI may enhance TB prevention. |
Outcomes of influenza A(H1N1)pdm09 virus infection: results from two international cohort studies
Lynfield R , Davey R , Dwyer DE , Losso MH , Wentworth D , Cozzi-Lepri A , Herman-Lamin K , Cholewinska G , David D , Kuetter S , Ternesgen Z , Uyeki TM , Lane HC , Lundgren J , Neaton JD . PLoS One 2014 9 (7) e101785 BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. METHODS AND FINDINGS: Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17 countries at 2 days (IQR 1-3) and 6 days (IQR 4-10) following ILI onset, respectively. Disease progression was experienced by 29 (1 death) outpatients (5.1%; 95% CI: 3.4-7.2%) and 80 inpatients [death (32), hospitalization >28 days (43) or ICU transfer (20)] (21.6%; 95% CI: 17.5-26.2%). Disease progression (death) for hospitalized patients was 53.1% (26.6%) and 12.8% (3.8%), respectively, for those enrolled in the ICU and general ward. In pooled analyses for both studies, predictors of disease progression were age, longer duration of symptoms at enrollment and immunosuppression. Patients hospitalized during the pandemic period had a poorer prognosis than in subsequent seasons. CONCLUSIONS: Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection. These data reinforce the need for international trials of novel treatment strategies for influenza infection and serve as a reminder of the need to monitor the severity of seasonal and pandemic influenza epidemics globally. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: FLU 002- NCT01056354, FLU 003- NCT01056185. |
Prevalence and correlates of cryptococcal antigen positivity among AIDS patients - United States, 1986-2012
McKenney J , Smith RM , Chiller TM , Detels R , French A , Margolick J , Klausner JD . MMWR Morb Mortal Wkly Rep 2014 63 (27) 585-7 Cryptococcal meningitis (CM) is one of the leading opportunistic infections associated with human immunodeficiency virus (HIV) infection. The worldwide burden of CM among persons living with HIV/acquired immunodeficiency syndrome (AIDS) was estimated in 2009 to be 957,900 cases, with approximately 624,700 deaths annually. The high burden of CM globally comes despite the fact that cryptococcal antigen (CrAg) is detectable weeks before the onset of symptoms, allowing screening for cryptococcal infection and early treatment to prevent CM and CM-related mortality (2). However, few studies have been conducted in the United States to assess the prevalence of cryptococcal infection. To quantify the prevalence of undiagnosed cryptococcal infection in HIV-infected persons in the United States during 1986-2012, stored sera from 1,872 participants in the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study with CD4 T-cell counts <100 cells/microL were screened for CrAg, using the CrAg Lateral Flow Assay (LFA) (Immy, Inc.). This report describes the results of that analysis, which indicated the overall prevalence of CrAg positivity in this population to be 2.9% (95% confidence interval [CI] = 2.2%-3.7%). |
Epidemiology of influenza virus types and subtypes in South Africa, 2009-2012
Cohen AL , Hellferscee O , Pretorius M , Treurnicht F , Walaza S , Madhi S , Groome M , Dawood H , Variava E , Kahn K , Wolter N , von Gottberg A , Tempia S , Venter M , Cohen C . Emerg Infect Dis 2014 20 (7) 1149-56 To determine clinical and epidemiologic differences between influenza caused by different virus types and subtypes, we identified patients and tested specimens. Patients were children and adults hospitalized with confirmed influenza and severe acute respiratory illness (SARI) identified through active, prospective, hospital-based surveillance from 2009-2012 in South Africa. Respiratory specimens were tested, typed, and subtyped for influenza virus by PCR. Of 16,005 SARI patients tested, 1,239 (8%) were positive for influenza virus. Patient age and co-infections varied according to virus type and subtype, but disease severity did not. Case-patients with influenza B were more likely than patients with influenza A to be HIV infected. A higher proportion of case-patients infected during the first wave of the 2009 influenza pandemic were 5-24 years of age (19%) than were patients infected during the second wave (9%). Although clinical differences exist, treatment recommendations do not differ according to subtype; prevention through vaccination is recommended. |
Evaluation of a surveillance case definition for anogenital warts, Kaiser Permanente Northwest
Naleway AL , Weinmann S , Crane B , Gee J , Markowitz LE , Dunne EF . Sex Transm Dis 2014 41 (8) 496-500 BACKGROUND: Most studies of anogenital wart (AGW) epidemiology have used large clinical or administrative databases and unconfirmed case definitions based on combinations of diagnosis and procedure codes. METHODS: We developed and validated an AGW case definition using a combination of diagnosis codes and other information available in the electronic medical record (provider type, laboratory testing). We calculated the positive predictive value (PPV) of this case definition compared with manual medical record review in a random sample of 250 cases. Using this case definition, we calculated the annual age- and sex-stratified prevalence of AGW among individuals 11 through 30 years of age from 2000 through 2005. RESULTS: We identified 2730 individuals who met the case definition. The PPV of the case definition was 82%, and the average annual prevalence was 4.16 per 1000. Prevalence of AGW was higher in females compared with males in every age group, with the exception of the 27- to 30-year-olds. Among females, prevalence peaked in the 19- to 22-year-olds, and among males, the peak was observed in 23- to 26-year-olds. CONCLUSIONS: The case definition developed in this study is the first to be validated with medical record review and has a good PPV for the detection of AGW. The prevalence rates observed in this study were higher than other published rates, but the age- and sex-specific patterns observed were consistent with previous reports. |
Influenza and other respiratory virus infections in outpatients with medically attended acute respiratory infection during the 2011-12 influenza season
Zimmerman RK , Rinaldo CR , Nowalk MP , Gk B , Thompson MG , Moehling KK , Bullotta A , Wisniewski S . Influenza Other Respir Viruses 2014 8 (4) 397-405 BACKGROUND: Respiratory tract infections are a major cause of outpatient visits, yet only a portion is tested to determine the etiologic organism. Multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) assays for detection of multiple viruses are being used increasingly in clinical settings. METHODS: During January-April 2012, outpatients with acute respiratory illness (≤7 days) were tested for influenza using singleplex RT-PCR (SRT-PCR). A subset was assayed for 18 viruses using MRT-PCR to compare detection of influenza and examine the distribution of viruses and characteristics of patients using multinomial logistic regression. RESULTS: Among 662 participants (6 months-82 years), detection of influenza was similar between the MRT-PCR and SRT-PCR (kappa = 0.83). No virus was identified in 267 (40.3%) samples. Commonly detected viruses were human rhinovirus (HRV, 15.4%), coronavirus (CoV, 10.4%), respiratory syncytial virus (RSV, 8.4%), human metapneumovirus (hMPV, 8.3%), and influenza (6%). Co-detections were infrequent (6.9%) and most commonly occurred among those <18 years old. In regression analyses, compared with non-viral illnesses, RSV and hMPV were significantly more frequent in children and less frequent in 18- to 49-year-olds than in those ≥50 years (P = 0.01), fever was more common in hMPV and influenza infections (P = 0.008), nasal congestion was more frequent in CoV, HRV, hMPV, influenza and RSV infections (P = 0.001), and body mass index was higher among those with influenza (P = 0.036). CONCLUSIONS: Using MRT-PCR, a viral etiology was found in three-fifths of patients with medically attended outpatient visits for acute respiratory illness during the influenza season; co-detected viruses were infrequent. Symptoms varied by viral etiology. |
Acquired macrolide-resistant Treponema pallidum after a human bite
Fanfair RN , Wallingford M , Long LL , Chi KH , Pillay A , Chen CY , Workowski KA . Sex Transm Dis 2014 41 (8) 493-5 Syphilis is a systemic disease caused by the spirochete Treponema pallidum that is usually acquired through sexual exposure. |
Comparative epidemiology of human metapneumovirus- and respiratory syncytial virus-associated hospitalizations in Guatemala
McCracken JP , Arvelo W , Ortiz J , Reyes L , Gray J , Estevez A , Castaneda O , Langley G , Lindblade KA . Influenza Other Respir Viruses 2014 8 (4) 414-21 BACKGROUND: Human metapneumovirus (HMPV) is an important cause of acute respiratory infections (ARI), but little is known about how it compares with respiratory syncytial virus (RSV) in Central America. OBJECTIVES: In this study, we describe hospitalized cases of HMPV- and RSV-ARI in Guatemala. METHODS: We conducted surveillance at three hospitals (November 2007-December 2012) and tested nasopharyngeal and oropharyngeal swab specimens for HMPV and RSV using real-time reverse transcription-polymerase chain reaction. We calculated incidence rates, and compared the epidemiology and outcomes of HMPV-positive versus RSV-positive and RSV-HMPV-negative cases. RESULTS: We enrolled and tested specimens from 6288 ARI cases; 596 (9%) were HMPV-positive and 1485 (24%) were RSV-positive. We observed a seasonal pattern of RSV but not HMPV. The proportion HMPV-positive was low (3%) and RSV-positive high (41%) for age <1 month, whereas these proportions were similar (~20%) by age 2 years. The annual incidence of hospitalized HMPV-ARI was 102/100 000 children aged <5 years [95% confidence interval (CI): 75-178], 2.6/100 000 persons aged 5-17 years (95%CI: 1.2-5.0), and 2.6/100 000 persons aged ≥18 years (95%CI: 1.5-4.9). Among children aged <5 years, HMPV-positive cases were less severe than HMPV-RSV-negative cases after adjustment for confounders [odds ratio (OR) for intensive care = 0.63, 95% CI 0.47-0.84]; OR for death = 0.46, 95% CI 0.23-0.92). CONCLUSIONS: Human metapneumovirus is a substantial contributor to ARI hospitalization in Guatemala, but HMPV hospitalizations are less frequent than RSV and, in young children, less severe than other etiologies. Preventive interventions should take into account the wide variation in incidence by age and unpredictable timing of incidence peaks. |
Health-promoting environments in U.S. medical facilities: physician perceptions, DocStyles 2012
Goldstein IM , Foltz JL , Onufrak S , Belay B . Prev Med 2014 67 65-70 OBJECTIVE: Medical facilities are natural leaders for health promotion because of their mission, influence, and reach. We sought to determine the frequency of physicians reporting supportive, health-promoting environments in their facility and identify characteristics of physicians and medical practices associated with support. METHODS: We analyzed a sample of 1,485 U.S. primary care physicians in DocStyles 2012 survey. Physicians rated their facility's support for healthy nutrition, physical activity, and lactation environments. Frequencies and adjusted odds ratios for supportive environments (rated "Good" or "Very Good") were assessed by select characteristics. RESULTS: The frequency of physicians reporting supportive environments was 70.0% for nutrition, 60.0% for physical activity, 76.0% for lactation, and 40.4% for all 3 environments combined. Supportive nutrition [odds ratio: 2.91 (1.49-5.66)] and physical activity [2.13 (1.19-3.83)] environments were associated with physicians seeing upper middle class to affluent patients versus poor patients. Supportive lactation environments were associated with pediatricians [3.35 (2.14-5.25)] and obstetricians/gynecologists [3.39 (2.15-5.33)] versus internists. CONCLUSIONS: Less than half of physicians reported their facility supportive of all these environments, suggesting there are many missed opportunities for U.S. medical facilities to promote wellness. Facilities serving poor patients and those staffed by internists and family/general practitioners may represent one area of need. |
Cluster randomized trial of text message reminders to retail staff in Tanzanian drug shops dispensing artemether-lumefantrine: effect on dispenser knowledge and patient adherence
Bruxvoort K , Festo C , Kalolella A , Cairns M , Lyaruu P , Kenani M , Kachur SP , Goodman C , Schellenberg D . Am J Trop Med Hyg 2014 91 (4) 844-853 Artemisinin combination therapies are available in private outlets, but patient adherence might be compromised by poor advice from dispensers. In this cluster randomized trial in drug shops in Tanzania, 42 of 82 selected shops were randomized to receive text message reminders about what advice to provide when dispensing artemether-lumefantrine (AL). Eligible patients purchasing AL at shops in both arms were followed up at home and questioned about each dose taken. Dispensers were interviewed regarding knowledge of AL dispensing practices and receipt of the malaria-related text messages. We interviewed 904 patients and 110 dispensers from 77 shops. Although there was some improvement in dispenser knowledge, there was no difference between arms in adherence measured as completion of all doses (intervention 68.3%, control 69.8%, p [adjusted] = 0.6), or as completion of each dose at the correct time (intervention 33.1%, control 32.6%, p [adjusted] = 0.9). Further studies on the potential of text messages to improve adherence are needed. |
Collaboratively reframing mental health for integration of HIV care in Ethiopia
Wissow LS , Tegegn T , Asheber K , McNabb M , Weldegebreal T , Jerene D , Ruff A . Health Policy Plan 2014 30 (6) 791-803 BACKGROUND: Integrating mental health with general medical care can increase access to mental health services, but requires helping generalists acquire a range of unfamiliar knowledge and master potentially complex diagnostic and treatment processes. METHOD: We describe a model for integrating complex specialty care with generalist/primary care, using as an illustration the integration of mental health into hospital-based HIV treatment services in Ethiopia. Generalists and specialists collaboratively developed mental health treatments to fit the knowledge, skills and resources of the generalists. The model recognizes commonalities between mental health and general medical care, focusing on practical interventions acceptable to patients. It was developed through a process of literature review, interviews, observing clinical practice, pilot trainings and expert consultation. Preliminary evaluation results were obtained by debriefing generalist trainees after their return to their clinical sites. RESULTS: In planning interviews, generalists reported discomfort making mental health diagnoses but recognition of symptom groups including low mood, anxiety, thought problems, poor child behaviour, seizures and substance use. Diagnostic and treatment algorithms were developed for these groups and tailored to the setting by including possible medical causes and burdens of living with HIV. First-line treatment included modalities familiar to generalists: empathetic patient-provider interactions, psychoeducation, cognitive reframing, referral to community supports and elements of symptom-specific evidence-informed counselling. Training introduced basic skills, with evolving expertise supported by job aides and ongoing support from mental health nurses cross-trained in HIV testing. Feedback from trainees suggested the programme fit well with generalists' settings and clinical goals. CONCLUSIONS: An integration model based on collaboratively developing processes that fit the generalist setting shows promise as a method for incorporating complex, multi-faceted interventions into general medical settings. Formal evaluations will be needed to compare the quality of care provided with more traditional approaches and to determine the resources required to sustain quality over time. |
Emergency department visits by adults for psychiatric medication adverse events
Hampton LM , Daubresse M , Chang HY , Alexander GC , Budnitz DS . JAMA Psychiatry 2014 71 (9) 1006-14 IMPORTANCE: In 2011, an estimated 26.8 million US adults used prescription medications for mental illness. OBJECTIVE: To estimate the numbers and rates of adverse drug event (ADE) emergency department (ED) visits involving psychiatric medications among US adults between January 1, 2009, and December 31, 2011. DESIGN AND SETTING: Descriptive analyses of active, nationally representative surveillance of ADE ED visits using the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance system and of drug prescribing during outpatient visits using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. PARTICIPANTS: Medical records from national probability samples of ED and outpatient visits by adults 19 years or older were reviewed and analyzed. EXPOSURES: Antidepressants, antipsychotics, lithium salts, sedatives and anxiolytics, and stimulants. MAIN OUTCOMES AND MEASURES: National estimates of ADE ED visits resulting from therapeutic psychiatric medication use and of psychiatric medication ADE ED visits per 10 000 outpatient visits at which psychiatric medications were prescribed. RESULTS: From 2009 through 2011, there were an estimated 89 094 (95% CI, 68 641-109 548) psychiatric medication ADE ED visits annually, with 19.3% (95% CI, 16.3%-22.2%) resulting in hospitalization and 49.4% (95% CI, 46.5%-52.4%) involving patients aged 19 to 44 years. Sedatives and anxiolytics, antidepressants, antipsychotics, lithium salts, and stimulants were implicated in an estimated 30 707 (95% CI, 23 406-38 008), 25 377 (95% CI, 19 051-31 704), 21 578 (95% CI, 16 599-26 557), 3620 (95% CI, 2311-4928), and 2779 (95% CI, 1764-3794) respective ADE ED visits annually. Antipsychotics and lithium salts were implicated in 11.7 (95% CI, 10.1-13.2) and 16.4 (95% CI, 13.0-19.9) ADE ED visits per 10 000 outpatient prescription visits, respectively, compared with 3.6 (95% CI, 3.2-4.1) for sedatives and anxiolytics, 2.9 (95% CI, 2.3-3.5) for stimulants, and 2.4 (95% CI, 2.1-2.7) for antidepressants. The commonly used sedative zolpidem tartrate was implicated in 11.5% (95% CI, 9.5%-13.4%) of all adult psychiatric medication ADE ED visits and in 21.0% (95% CI, 16.3%-25.7%) of visits involving adults 65 years or older, in both cases significantly more than any other psychiatric medication. CONCLUSIONS AND RELEVANCE: Psychiatric medications are implicated in many ADEs treated in US EDs. Efforts to reduce ADEs should include adults of all ages but might prioritize medications causing high numbers and rates of ED visits. |
Phthalate exposure and pubertal development in a longitudinal study of US girls
Wolff MS , Teitelbaum SL , McGovern K , Windham GC , Pinney SM , Galvez M , Calafat AM , Kushi LH , Biro FM . Hum Reprod 2014 29 (7) 1558-66 STUDY QUESTION: Does phthalate exposure during early childhood alter the timing of pubertal development in girls? SUMMARY ANSWER: Urinary concentrations of high-molecular weight phthalate (high-MWP) metabolites are associated with later pubarche. WHAT IS KNOWN ALREADY: Phthalates are anti-androgenic environmental agents known to alter early development, with possible effects on pubertal onset. STUDY DESIGN, SIZE, AND DURATION: This multi-ethnic study included 1239 girls from New York City, greater Cincinnati, and the San Francisco Bay Area who were 6-8 years old at enrollment (2004-2007) and who were followed until 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Phthalate metabolites were measured in urine collected at enrollment from 1170 girls; concentrations ranged from <1 to >10 000 microg/l. Breast and pubic hair stages and body size were assessed one to two times annually to determine the age at transition from stage 1 to 2 for breast and pubic hair development. Associations between exposures and pubertal ages were estimated using Cox proportional hazard ratios (HR) with 95% confidence intervals (CI) and survival analyses. Associations were examined with respect to age-specific body mass-index percentile, one of the strongest predictors of pubertal onset. MAIN RESULTS AND THE ROLE OF CHANCE: Urinary concentrations of high-MWP including di(2-ethylhexyl) phthalate (SigmaDEHP) metabolites were associated with later pubic hair development during 7 years of observation. The relationship was linear and was stronger among normal-weight girls. Among normal-weight girls, age at pubic hair stage 2 (PH2) was 9.5 months older for girls in the fifth compared with the first quintile of urinary SigmaDEHP (medians: 510 and 59 microg/g creatinine, respectively; adjusted HR 0.70, CI 0.53-0.93, P-trend 0.005. Age at first breast development was older for fifth quintile of mono-benzyl phthalate versus first (HR 0.83, CI 0.68-1.02; P-trend 0.018). No associations were observed between low-molecular weight phthalate urinary metabolite concentrations and age at pubertal transition in adjusted analyses. LIMITATIONS, REASONS FOR CAUTION: While there is evidence that phthalate exposures are fairly consistent over time, the exposure measure in this study may not reflect an earlier, more susceptible window of exposure. We investigated alternative explanations that might arise from exposure misclassification or confounding. WIDER IMPLICATIONS OF THE FINDINGS: Phthalates are widespread, hormonally active pollutants that may alter pubertal timing. Whether exposures delay or accelerate pubertal development may depend on age at exposure as well as other factors such as obesity and exposures earlier in life. Whether exposures act independently or as part of real life mixtures may also change their effects on maturation from birth through childhood. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by the US National Institutes of Health, Environmental Protection Agency, New York State Empire Clinical Research Investigator Program and the Avon Foundation. L.H.K. is employed by Kaiser Permanente. The remaining authors declare they have no actual or potential competing financial interests. |
An evidence-based public health approach to climate change adaptation
Hess JJ , Eidson M , Tlumak JE , Raab KK , Luber G . Environ Health Perspect 2014 122 (11) 1177-86 BACKGROUND: Public health is committed to evidence-based practice, yet there has been minimal discussion of how to apply an evidence-based practice framework to climate change adaptation. OBJECTIVES: To review the literature on evidence-based public health (EBPH), determine whether it can be applied to climate change adaptation, and consider how emphasizing evidence-based practice may influence research and practice decisions related to public health adaptation to climate change. METHODS: We conducted a substantive review of EBPH, identified a consensus EBPH framework, and modified it to support an EBPH approach to climate change adaptation. We applied the framework to an example and considered implications for stakeholders. DISCUSSION: A modified EBPH framework can accommodate the wide range of exposures, outcomes, and modes of inquiry associated with climate change adaptation and the variety of settings in which adaptation activities will be pursued. Several factors limit application currently, including lack of higher level evidence of intervention efficacy and lack of guidelines for reporting climate change health impact projections. To enhance the evidence base there must be increased attention to designing, evaluating, and reporting adaptation interventions; standardized health impact projection reporting; and increased attention to knowledge translation. This has implications for funders, researchers, journal editors, practitioners, and policymakers. CONCLUSIONS: The current approach to EBPH can, with modifications, support climate change adaptation activities, but there is little evidence regarding interventions and knowledge translation, and guidelines for projecting health impacts are lacking. Realizing the goal of an evidence-based approach will require systematic, coordinated efforts among various stakeholders. |
Global incidence of human Shiga toxin-producing Escherichia coli infections and deaths: a systematic review and knowledge synthesis
Majowicz SE , Scallan E , Jones-Bitton A , Sargeant JM , Stapleton J , Angulo FJ , Yeung DH , Kirk MD . Foodborne Pathog Dis 2014 11 (6) 447-55 OBJECTIVES: Shiga toxin-producing Escherichia coli (STEC) are an important cause of foodborne disease, yet global estimates of disease burden do not exist. Our objective was to estimate the global annual number of illnesses due to pathogenic STEC, and resultant hemolytic uremic syndrome (HUS), end-stage renal disease (ESRD), and death. MATERIALS: We searched Medline, Scopus, SIGLE/OpenGrey, and CABI and World Health Organization (WHO) databases for studies of STEC incidence in the general population, published between January 1, 1990 and April 30, 2012, in all languages. We searched health institution websites for notifiable disease data and reports, cross-referenced citations, and consulted international knowledge experts. We employed an a priori hierarchical study selection process and synthesized results using a stochastic simulation model to account for uncertainty inherent in the data. RESULTS: We identified 16 articles and databases from 21 countries, from 10 of the 14 WHO Sub-Regions. We estimated that STEC causes 2,801,000 acute illnesses annually (95% Credible Interval [Cr.I.]: 1,710,000; 5,227,000), and leads to 3890 cases of HUS (95% Cr.I.: 2400; 6700), 270 cases of ESRD (95% Cr.I.: 20; 800), and 230 deaths (95% Cr.I.: 130; 420). Sensitivity analyses indicated these estimates are likely conservative. CONCLUSIONS: These are the first estimates of the global incidence of STEC-related illnesses, which have not been explicitly included in previous global burden of disease estimations. Compared to other pathogens with a foodborne transmission component, STEC appears to cause more cases than alveolar echinococcosis each year, but less than typhoid fever, foodborne trematodes, and nontyphoidal salmonellosis. APPLICATIONS: Given the persistence of STEC globally, efforts aimed at reducing the burden of foodborne disease should consider the relative contribution of STEC in the target population. |
Draft Genome Sequence of Environmental Vibrio cholerae 2012EL-1759 with Similarities to the V. cholerae O1 Classical Biotype.
Katz LS , Turnsek M , Kahler A , Hill VR , Boyd EF , Tarr CL . Genome Announc 2014 2 (4) Vibrio cholerae 2012EL-1759 is an environmental isolate from Haiti that was recovered in 2012 during a cholera outbreak. The genomic backbone is similar to that of the prototypical V. cholerae O1 classical biotype strain O395, and it carries the Vibrio pathogenicity islands (VPI-1 and VPI-2) and a cholera toxin (CTX) prephage. |
Draft Whole-Genome Sequences of Nine Non-O157 Shiga Toxin-Producing Escherichia coli Strains.
Lindsey RL , Trees E , Sammons S , Loparev V , Frace M , Strockbine N , Sabol AL , Sowers E , Stripling D , Martin H , Knipe K , Rowe L , Gerner-Smidt P . Genome Announc 2014 2 (4) Shiga toxin-producing Escherichia coli (STEC) is an important food-borne pathogen. Here, we report the draft whole-genome sequences of nine STEC strains isolated from clinical cases in the United States. This is the first report of such information for STEC of serotypes O69, H11, O145:H25, O118:H16, O91:H21, O146:H21, O45:H2, O128:H2, and O121:H19. |
Utility before business.
Teutsch SM , Fielding JE , Khoury MJ , Evans JP . Genet Med 2014 Today, enthusiasm for genomics far outstrips the relatively modest, albeit increasing, number of clinical scenarios for which it provides established health benefits.1 Nonetheless, laboratories have incentives to introduce and offer genetic tests at an astounding rate, reflecting not only the increased ability to perform them accurately in many clinical laboratories but the precipitous drop in the cost of testing. However, the actual cost of the tests themselves should be the least of our concerns; the clinical usefulness should be foremost. This set of circumstances has many similarities to that of newborn screening, for which the costs of the tests themselves have plummeted and the marginal cost of additional tests is so low as to be insignificant, supporting the argument that we should do every possible test. However, the overriding question for both genetic testing and new tests that could be added to newborn screening is the same: What are the health benefits achieved and harms incurred as a result of the information gained from these tests? | The Secretary’s Advisory Committee on Genetics, Health, and Society2 and the Evaluation of Genomic Tests in Prevention and Practice Working Group3 wrestled with the question of the clinical utility of genomic testing, including its definition and its relationship to oversight of laboratory testing. The Secretary’s Advisory Committee on Genetics, Health, and Society clearly came down on the side of stricter oversight of genomic testing, emphasizing that, in general, clinical use of tests should be deferred until clear evidence of clinical utility is demonstrated, as it has been in guiding some cancer chemotherapies, for example. |
Strategies to prevent methicillin-resistant Staphylococcus aureus transmission and infection in acute care hospitals: 2014 update
Calfee DP , Salgado CD , Milstone AM , Harris AD , Kuhar DT , Moody J , Aureden K , Huang SS , Maragakis LL , Yokoe DS . Infect Control Hosp Epidemiol 2014 35 (7) 772-96 Previously published guidelines are available that provide | comprehensive recommendations for detecting and preventing healthcare-associated infections (HAIs). The intent of this | document is to highlight practical recommendations in a concise format designed to assist acute care hospitals in implementing and prioritizing their methicillin-resistant Staphylococcus aureus (MRSA) prevention efforts. This document | updates “Strategies to Prevent Transmission of MethicillinResistant Staphylococcus aureus in Acute Care Hospitals,”1 | published in 2008. This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America | (SHEA) and is the product of a collaborative effort led by | SHEA, the Infectious Diseases Society of America (IDSA), the | American Hospital Association (AHA), the Association for | Professionals in Infection Control and Epidemiology (APIC), | and The Joint Commission, with major contributions from | representatives of a number of organizations and societies | with content expertise. The list of endorsing and supporting | organizations is presented in the introduction to the 2014 | updates.2 |
Understanding antibiotic use in Minya district, Egypt: physician and pharmacist prescribing and the factors influencing their practices
Dooling KL , Kandeel A , Hicks LA , El-Shoubary W , Fawzi K , Kandeel Y , Etman A , Lohiniva AL , Talaat M . Antibiotics (Basel) 2014 3 (2) 233-243 Overuse of antibiotics has contributed to the emergence of antibiotic-resistant bacteria globally. In Egypt, patients can purchase antibiotics without a prescription, and we hypothesized frequent inappropriate antibiotic prescribing and dispensing. We interviewed physicians (n = 236) and pharmacists (n = 483) and conducted focus groups in Minya, Egypt, to assess attitudes and practices regarding antibiotic prescribing for outpatient acute respiratory infections (ARI). Antibiotics were reportedly prescribed most of the time or sometimes for colds by 150 (64%) physicians and 326 (81%) pharmacists. The most commonly prescribed antibiotics were beta-lactams. Macrolides were the second most commonly prescribed for colds and sinusitis. The prescription of more than one antibiotic to treat pneumonia was reported by 85% of physicians. Most respondents thought antibiotic overuse contributes to resistance and reported -patient self-medication{norm of matrix} as the biggest driver of overuse. Fifty physicians (21%) reported that they had prescribed antibiotics unnecessarily, citing patient over-the-counter access as the reason. Physicians <40 years of age and those who treat adults were more likely to prescribe antibiotics for colds. Overall, we found a high rate of unwarranted outpatient antibiotic prescribing and dispensing for ARIs. Patient access to OTC antibiotics contributes to over-prescribing. National guidelines for ARI treatment, provider education and national policy requiring a physician's prescription for antibiotics may improve appropriate antibiotic use in Egypt. |
The incidence and prevalence of systemic lupus erythematosus, 2002-2004: the Georgia Lupus Registry
Lim SS , Bayakly AR , Helmick CG , Gordon C , Easley KA , Drenkard C . Arthritis Rheumatol 2014 66 (2) 357-68 OBJECTIVE: The Georgia Lupus Registry is a population-based registry designed to improve our ability to estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in a large population. METHODS: Potential cases of SLE were identified from multiple sources during the years 2002 through 2004. Cases were defined according to the American College of Rheumatology (ACR) criteria for SLE or a combined definition. Age-standardized rates were determined and stratified by race and sex. With capture-recapture analyses, we estimated the under-ascertainment of cases. RESULTS: Using the ACR case definition, the overall crude and age-adjusted incidence rate was 5.6 per 100,000, with capture-recapture and combined definition rates being slightly higher. The age-adjusted incidence rate in women was >5 times higher than that for men (9.2 versus 1.8). Black women had an incidence rate nearly 3 times higher than that in white women, with a significantly higher rate in the group ages 30-59 years. The overall crude and age-adjusted prevalence rates were 74.4 and 73 per 100,000, respectively. The age-adjusted prevalence rate in women was nearly 9 times higher than that for men (127.6 versus 14.7). Black women had very high rates (196.2). A striking difference was seen in the proportion of prevalent cases with end-stage renal disease, with 7-fold greater involvement among black patients. CONCLUSION: With the more complete case-finding methods we used, the incidence and prevalence rates of SLE are among the highest reported in the US. The results continue to underscore striking sex, age, and racial disparities between black patients and white patients with SLE. |
Virus-like particle secretion and genotype-dependent immunogenicity of dengue virus serotype 2 DNA vaccine.
Galula JU , Shen WF , Chuang ST , Chang GJ , Chao DY . J Virol 2014 88 (18) 10813-30 Dengue virus (DENV), composed of four distinct serotypes, is the most important and fast emerging arthropod-borne pathogen imposing a great deal of economic and public health burden. We constructed five genotypes of dengue virus serotype 2 (DENV-2) DNA vaccine candidates and evaluated immunogenicity, neutralizing (Nt) activity of elicited antibodies and the protective efficacy elicited in mice immunized with the vaccine candidates. We observed a significant correlation between the level of in vitro VLP secretion, the elicited antibody response and protective efficacy by different genotypic DNA vaccines in immunized mice. However, higher total IgG antibodies did not always translate into higher Nt antibodies against homologous and heterologous viruses. We also found that in contrast to previous reports, more than fifty percent of the total IgG are targeting EDIII of E protein and a substantial fraction of this population are interdomain antibodies that are highly neutralizing flavivirus sub-group cross-reactive, such as monoclonal antibody 1B7-5. In addition, the lack of critical epitope(s) in sylvatic virus recognized by interdomain antibodies, could be the major cause of poor protection of pVD2-Asian 1 genotype vaccinated mice from the lethal challenge of sylvatic virus. In conclusion, although pVD2-Asian 1 is immunogenic, elicits sufficient Nt antibody titers against all DENV-2 genotypes, and provides 100% protection against homologous Asian 1 and heterologous Cosmopolitan genotype virus challenge, it is critical to monitor the potential emergence of sylvatic genotype viruses since current vaccine candidates under development may not protect vaccinated humans from these viruses. IMPORTANCE: Five genotype-specific dengue virus serotype 2 (DENV-2) DNA vaccine candidates were evaluated for their immunogenicity, homologous and heterologous neutralizing (Nt) antibody titers and cross-genotype protection in murine model. Protective immunity elicited by our prototype vaccine candidate (Asian 1, strain 16681) in mice was protective against other genotype viruses but not against the sylvatic genotype virus, whose emergence and potential risk after introduction into human population have previously been demonstrated. The underlying mechanism of lack of protection elicited by the prototype vaccine may at least be contributed by the absence of a flavivirus sub-group cross-reactive, highly neutralizing 1B7-5-like epitope in the sylvatic DENV-2. DENV DNA vaccine directs the synthesis and assembly of virus-like particles (VLP), induces immune responses similar to live-attenuated vaccines; and its flexibility permits the fast deployment of vaccine to combat emerging viruses such as sylvatic genotype viruses. Enhanced VLP secretion by the replacement of EDI-II of pVD2-Cosmopolitan with Asian 1 EDI-II has elicited significantly higher total IgG and Nt antibodies and suggests a novel approach to enhance immunogenicity of DNA vaccine. A DENV vaccine capable of eliciting protective immunity against existing and emerging genotype viruses should be the focus of future DENV vaccine development. |
The role of older children and adults in wild poliovirus transmission
Blake IM , Martin R , Goel A , Khetsuriani N , Everts J , Wolff C , Wassilak S , Aylward RB , Grassly NC . Proc Natl Acad Sci U S A 2014 111 (29) 10604-9 As polio eradication inches closer, the absence of poliovirus circulation in most of the world and imperfect vaccination coverage are resulting in immunity gaps and polio outbreaks affecting adults. Furthermore, imperfect, waning intestinal immunity among older children and adults permits reinfection and poliovirus shedding, prompting calls to extend the age range of vaccination campaigns even in the absence of cases in these age groups. The success of such a strategy depends on the contribution to poliovirus transmission by older ages, which has not previously been estimated. We fit a mathematical model of poliovirus transmission to time series data from two large outbreaks that affected adults (Tajikistan 2010, Republic of Congo 2010) using maximum-likelihood estimation based on iterated particle-filtering methods. In Tajikistan, the contribution of unvaccinated older children and adults to transmission was minimal despite a significant number of cases in these age groups [reproduction number, R = 0.46 (95% confidence interval, 0.42-0.52) for >5-y-olds compared to 2.18 (2.06-2.45) for 0- to 5-y-olds]. In contrast, in the Republic of Congo, the contribution of older children and adults was significant [R = 1.85 (1.83-4.00)], perhaps reflecting sanitary and socioeconomic variables favoring efficient virus transmission. In neither setting was there evidence for a significant role of imperfect intestinal immunity in the transmission of poliovirus. Bringing the immunization response to the Tajikistan outbreak forward by 2 wk would have prevented an additional 130 cases (21%), highlighting the importance of early outbreak detection and response. |
Formative investigation of acceptability of typhoid vaccine during a typhoid fever outbreak in Neno District, Malawi
Blum LS , Dentz H , Chingoli F , Chilima B , Warne T , Lee C , Hyde T , Gindler J , Sejvar J , Mintz ED . Am J Trop Med Hyg 2014 91 (4) 729-37 Typhoid fever affects an estimated 22 million people annually and causes 216,000 deaths worldwide. We conducted an investigation in August and September 2010 to examine the acceptability of typhoid vaccine in Neno District, Malawi where a typhoid outbreak was ongoing. We used qualitative methods, including freelisting exercises, key informant and in-depth interviews, and group discussions. Respondents associated illness with exposure to "bad wind," and transmission was believed to be airborne. Typhoid was considered extremely dangerous because of its rapid spread, the debilitating conditions it produced, the number of related fatalities, and the perception that it was highly contagious. Respondents were skeptical about the effectiveness of water, sanitation, and hygiene (WaSH) interventions. The perceived severity of typhoid and fear of exposure, uncertainty about the effectiveness of WaSH measures, and widespread belief in the efficacy of vaccines in preventing disease resulted in an overwhelming interest in receiving typhoid vaccine during an outbreak. |
Interim CDC guidance for polio vaccination for travel to and from countries affected by wild poliovirus
Wallace GS , Seward JF , Pallansch MA . MMWR Morb Mortal Wkly Rep 2014 63 (27) 591-4 In the prevaccine era, infection with wild poliovirus (WPV) was common worldwide, with seasonal peaks and epidemics in the summer and fall in temperate areas. The incidence of poliomyelitis in the United States declined rapidly after the licensure of inactivated polio vaccine (IPV) in 1955 and live oral polio vaccine (OPV) in the 1960s. The last cases of indigenously acquired WPV in the United States occurred in 1979, the last WPV case in a U.S. resident traveling abroad occurred in 1986, and the last WPV imported case was in 1993. Since 2000, the United States has exclusively used IPV, resulting in prevention of 8-10 vaccine-associated paralytic poliomyelitis cases annually. In 2005, an unvaccinated U.S. adult traveling abroad acquired vaccine-associated paralytic poliomyelitis after contact with an infant recently vaccinated with OPV. |
Nocardia vulneris sp. nov., isolated from wounds of human patients in North America.
Lasker BA , Bell M , Klenk HP , Sproer C , Schumann P , Brown JM . Antonie Van Leeuwenhoek 2014 106 (3) 543-53 Nocardia species are ubiquitous in the environment with an increasing number of species isolated from clinical sources. From 2005 to 2009, eight isolates (W9042, W9247, W9290, W9319, W9846, W9851T, W9865, and W9908) were obtained from eight patients from three states in the United States and Canada; all were from males ranging in age from 47 to 81 years old; and all were obtained from finger (n = 5) or leg (n = 3) wounds. Isolates were characterized by polyphasic analysis using molecular, phenotypic, morphologic and chemotaxonomic methods. Sequence analysis of 16S rRNA gene sequences showed the eight isolates are 100 % identical to each other and belong in the genus Nocardia. The nearest phylogenetically related neighbours were found to be the type strains for Nocardia altamirensis (99.33 % sequence similarity), Nocardia brasiliensis (99.37 %), Nocardia iowensis (98.95 %) and Nocardia tenerifensis (98.44 %). The G+C content of isolate W9851T was determined to be 68.4 mol %. The DNA-DNA relatedness between strain W9851T and the N. brasiliensis type strain was 72.8 % and 65.8 % when measured in the laboratory and in silico from genome sequences, respectively, and 95.6 % ANI. Whole-cell peptidoglycan was found to contain meso-diaminopimelic acid; MK-8-(H4)omega-cyc was identified as the major menaquinone; the major fatty acids were identified as C16:0, 10 Me C18:0, and C18:1 w9c, the predominant phospholipids were found to include diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannosides; whole-cell sugars detected were arabinose and galactose; and mycolic acids ranging from 38 to 60 carbon atoms were found to be present. These chemotaxonomic analyses are consistent with assignment of the isolates to the genus Nocardia. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectra of the clinical isolates showed genus and species level profiles that were different from other Nocardia species. All isolates were resistant to ciprofloxacin, clarithromycin and imipenem but were susceptible to amikacin, amoxicillin/clavulanate, linezolid and trimethoprim/sulfamethoxazole. The results of our polyphasic analysis suggest the new isolates obtained from wound infections represent a novel species within the genus Nocardia, for which the name Nocardia vulneris sp. nov. is proposed, with strain W9851T (= DSM 45737T = CCUG 62683T = NBRC 108936T) as the type strain. |
Validation of a histoplasma ELISA antigenuria test in Colombian patients with AIDS for diagnosis and follow-up during therapy
Caceres DH , Scheel CM , Tobon AM , Ahlquist Cleveland A , Restrepo A , Brandt ME , Chiller T , Gomez BL . Clin Vaccine Immunol 2014 We validated an antigen capture ELISA test in Colombian persons with AIDS and proven histoplasmosis, and evaluated the correlation between antigenuria and clinical improvement during follow up. The sensitivity of the H. capsulatum ELISA was 86% and the overall specificity was 94%. The antigen test successfully monitored response to therapy. |
Validation of a LC-MS/MS method for quantifying urinary nicotine, six nicotine metabolites and the minor tobacco alkaloids-anatabine and anabasine-in smokers' urine
McGuffey JE , Wei B , Bernert JT , Morrow JC , Xia B , Wang L , Blount BC . PLoS One 2014 9 (7) e101816 Tobacco use is a major contributor to premature morbidity and mortality. The measurement of nicotine and its metabolites in urine is a valuable tool for evaluating nicotine exposure and for nicotine metabolic profiling-i.e., metabolite ratios. In addition, the minor tobacco alkaloids-anabasine and anatabine-can be useful for monitoring compliance in smoking cessation programs that use nicotine replacement therapy. Because of an increasing demand for the measurement of urinary nicotine metabolites, we developed a rapid, low-cost method that uses isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneously quantifying nicotine, six nicotine metabolites, and two minor tobacco alkaloids in smokers' urine. This method enzymatically hydrolyzes conjugated nicotine (primarily glucuronides) and its metabolites. We then use acetone pretreatment to precipitate matrix components (endogenous proteins, salts, phospholipids, and exogenous enzyme) that may interfere with LC-MS/MS analysis. Subsequently, analytes (nicotine, cotinine, hydroxycotinine, norcotinine, nornicotine, cotinine N-oxide, nicotine 1'-N-oxide, anatabine, and anabasine) are chromatographically resolved within a cycle time of 13.5 minutes. The optimized assay produces linear responses across the analyte concentrations typically found in urine collected from daily smokers. Because matrix ion suppression may influence accuracy, we include a discussion of conventions employed in this procedure to minimize matrix interferences. Simplicity, low cost, low maintenance combined with high mean metabolite recovery (76-99%), specificity, accuracy (0-10% bias) and reproducibility (2-9% C.V.) make this method ideal for large high through-put studies. |
Hepatitis C virus hypervariable region 1 variants presented on hepatitis B virus capsid-like particles induce cross-neutralizing antibodies
Lange M , Fiedler M , Bankwitz D , Osburn W , Viazov S , Brovko O , Zekri AR , Khudyakov Y , Nassal M , Pumpens P , Pietschmann T , Timm J , Roggendorf M , Walker A . PLoS One 2014 9 (7) e102235 Hepatitis C virus (HCV) infection is still a serious global health burden. Despite improved therapeutic options, a preventative vaccine would be desirable especially in undeveloped countries. Traditionally, highly conserved epitopes are targets for antibody-based prophylactic vaccines. In HCV-infected patients, however, neutralizing antibodies are primarily directed against hypervariable region I (HVRI) in the envelope protein E2. HVRI is the most variable region of HCV, and this heterogeneity contributes to viral persistence and has thus far prevented the development of an effective HVRI-based vaccine. The primary goal of an antibody-based HCV vaccine should therefore be the induction of cross-reactive HVRI antibodies. In this study we approached this problem by presenting selected cross-reactive HVRI variants in a highly symmetric repeated array on capsid-like particles (CLPs). SplitCore CLPs, a novel particulate antigen presentation system derived from the HBV core protein, were used to deliberately manipulate the orientation of HVRI and therefore enable the presentation of conserved parts of HVRI. These HVRI-CLPs induced high titers of cross-reactive antibodies, including neutralizing antibodies. The combination of only four HVRI CLPs was sufficient to induce antibodies cross-reactive with 81 of 326 (24.8%) naturally occurring HVRI peptides. Most importantly, HVRI CLPs with AS03 as an adjuvant induced antibodies with a 10-fold increase in neutralizing capability. These antibodies were able to neutralize infectious HCVcc isolates and 4 of 19 (21%) patient-derived HCVpp isolates. Taken together, these results demonstrate that the induction of at least partially cross-neutralizing antibodies is possible. This approach might be useful for the development of a prophylactic HCV vaccine and should also be adaptable to other highly variable viruses. |
Impact of GeneXpert MTB/RIF on patients and tuberculosis programs in a low-burden setting: a hypothetical trial
Davis JL , Kawamura LM , Chaisson LH , Grinsdale J , Benhammou J , Ho C , Babst A , Banouvong H , Metcalfe JZ , Pandori M , Hopewell PC , Cattamanchi A . Am J Respir Crit Care Med 2014 189 (12) 1551-9 RATIONALE: Guidelines recommend routine nucleic-acid amplification testing in patients with presumed tuberculosis (TB), but these tests have not been widely adopted. GeneXpert MTB/RIF (Xpert), a novel, semiautomated TB nucleic-acid amplification test, has renewed interest in this technology, but data from low-burden countries are limited. OBJECTIVES: We sought to estimate Xpert's potential clinical and public health impact on empiric treatment, contact investigation, and housing in patients undergoing TB evaluation. METHODS: We performed a prospective, cross-sectional study with 2-month follow-up comparing Xpert with standard strategies for evaluating outpatients for active pulmonary TB at the San Francisco Department of Public Health TB Clinic between May 2010 and June 2011. We calculated the diagnostic accuracy of standard algorithms for initial empiric TB treatment, contact investigation, and housing in reference to three Mycobacterium tuberculosis sputum cultures, as compared with that of a single sputum Xpert test. We estimated the incremental diagnostic value of Xpert, and the hypothetical reductions in unnecessary treatment, contact investigation, and housing if Xpert were adopted to guide management decisions. MEASUREMENTS AND MAIN RESULTS: A total of 156 patients underwent Xpert testing. Fifty-nine (38%) received empiric TB treatment. Thirteen (8%) had culture-positive TB. Xpert-guided management would have hypothetically decreased overtreatment by 94%, eliminating a median of 44 overtreatment days (interquartile range, 43-47) per patient and 2,169 total overtreatment days (95% confidence interval, 1,938-2,400) annually, without reducing early detection of TB patients. We projected similar benefits for contact investigation and housing. CONCLUSIONS: Xpert could greatly reduce the frequency and impact of unnecessary empiric treatment, contact investigation, and housing, providing substantial patient and programmatic benefits if used in management decisions. |
Analytical reactivity of 13 commercially available rapid influenza diagnostic tests with H3N2v and recently circulating influenza viruses
Bose ME , Sasman A , Mei H , McCaul KC , Kramp WJ , Chen LM , Shively R , Williams TL , Beck ET , Henrickson KJ . Influenza Other Respir Viruses 2014 8 (4) 474-81 OBJECTIVES: Rapid influenza diagnostic tests (RIDTs) used widely in clinical practice are simple to use and provide results within 15 minutes; however, reported performance is variable, which causes concern when novel or variant viruses emerge. This study's goal was to assess the analytical reactivity of 13 RIDTs with recently circulating seasonal and H3N2v influenza viruses, using three different viral measures. DESIGN: Virus stocks were characterized by infectious dose (ID50 ) and nucleoprotein (NP) concentration, diluted at half-log dilutions, and tested with each RIDT and real-time RT-PCR. RESULTS: Strong correlation was observed between NP concentration and RIDT reactivity; however, only weak correlation was seen with ID50 or Ct values. Only four RIDTs detected viral NP at the lowest dilution for all influenza A viruses (IAV). Influenza A viruses not detected by more than one RIDT had lower NP levels. Of the 13 RIDTs, 9 had no significant differences in reactivity across IAV when compared to NP levels. CONCLUSIONS: Previous reports of RIDT performance typically compare reactivity based on ID50 titers, which in this study correlated only weakly with proportional amounts of viral NP in prepared virus samples. In the context of the strong correlation of RIDT reactivity with NP concentration, H3N2v was found to be as reactive as seasonal circulating IAV. While these findings may not reflect clinical performance of these RIDTs, measuring NP concentration can be useful in the future to assess comparable reactivity of available RIDTs, or to assess reactivity with newly evolving or emerging viruses. |
Caveolin-1 regulates lung cancer stem-like cell induction and p53 inactivation in carbon nanotube-driven tumorigenesis
Luanpitpong S , Wang L , Stueckle TA , Tse W , Chen YC , Rojanasakul Y . Oncotarget 2014 5 (11) 3541-54 Cancer stem cells (CSCs) may represent targets for carcinogenic initiation by chemical and environmental agents. Recent studies have raised a concern over the potential carcinogenicity of carbon nanotubes (CNTs), one of the most commonly used engineered nanomaterials with asbestos-like properties. Here, we show that chronic (6-month) exposure of human lung epithelial cells to single-walled (SW) CNTs at the workplace-relevant concentration induced an emergence of lung CSCs, as indicated by the induction of CSC tumor spheres and side population (SP). These CSCs, which were found to overexpress tumor promoter caveolin-1 (Cav-1), displayed aggressive cancer phenotypes of apoptosis resistance and enhanced cell invasion and migration compared with their non-CSC counterpart. Using gene manipulation strategies, we reveal for the first time that Cav-1 plays an essential role in CSC regulation and aggressiveness of SWCNT-transformed cells partly through p53 dysregulation, consistent with their suggested role by microarray and gene ontology analysis. Cav-1 not only promoted tumorigenesis in a xenograft mouse model but also metastasis of the transformed cells to neighboring tissues. Since CSCs are crucial to the initiation and early development of carcinogenesis, our findings on CSC induction by SWCNTs and Cav-1 could aid in the early detection and risk assessment of the disease. |
Comprehensive comparison of cultivable norovirus surrogates in response to different inactivation and disinfection treatments
Cromeans T , Park GW , Costantini V , Lee D , Wang Q , Farkas T , Lee A , Vinje J . Appl Environ Microbiol 2014 80 (18) 5743-51 Human norovirus is the leading cause of epidemic and sporadic acute gastroenteritis. Since no cell culture method for human norovirus exists, cultivable surrogate viruses (CSV) including feline calicivirus (FCV), murine norovirus (MNV), porcine enteric calicivirus (PEC) and Tulane virus (TuV) have been used to study the response to inactivation and disinfection methods. We compared the infectivity reduction of CSV and Aichi virus (AiV) by extreme pH, 56 degrees C heating, alcohols, chlorine on surfaces, and high hydrostatic pressure (HHP) using the same matrix and identical test parameters for all viruses, and compared with reduction of human norovirus RNA. At pH 2 FCV was inactivated by 6 log10 whereas MNV, TuV and AiV were resistant. All CSV were completely inactivated at 56 degrees C within 20 min. MNV was inactivated 5 log10 by alcohols compared to 2 and 3 log10 for FCV and PEC, respectively. TuV and AiV were relatively insensitive to alcohols. FCV was reduced 5 log10 by 1,000 ppm chlorine compared to 1 log10 for the other CSV. All CSV except FCV dried on stainless steel surfaces were insensitive to 200 ppm chlorine. HHP completely inactivated FCV, MNV, and PEC at ≥300 megapascal (MPa), TuV at 600 MPa while AiV was completely resistant up to 800 MPa. By RT-qPCR, genogroup (G)I norovirus was more sensitive than GII norovirus to alcohols, chlorine, and HHP. Although inactivation profiles were variable for each treatment, overall TuV and MNV were the most resistant CSV and therefore are best candidates to study public health outcomes of norovirus infections. |
Determination of 241Am in Urine Using Sector Field Inductively Coupled Plasma Mass Spectrometry (SF-ICP-MS)
Xiao G , Saunders D , Jones RL , Caldwell KL . J Radioanal Nucl Chem 2014 301 (1) 285-291 Quantification of Am-241 in urine at low levels is important for assessment of individuals' or populations' accidental, environmental, or terrorism-related internal contamination, but no convenient, precise method has been established to rapidly determine these low levels. Here we report a new analytical method to measure Am-241 as developed and validated at the Centers for Disease Control and Prevention (CDC) by means of the selective retention of Am from urine directly on DGA resin, followed by SF-ICP-MS detection. The method provides rapid results with a limit of detection (LOD) of 0.22 pg/L (0.028 Bq/L), which is lower than 1/3 of the C/P CDG for Am-241 at 5 days post-exposure. The results obtained by this method closely agree with CDC values as measured by liquid scintillation counting, and with National Institute of Standards Technology (NIST) Certified Reference Materials (CRM) target values. |
Standardized severe maternal morbidity review: rationale and process
Kilpatrick SJ , Berg C , Bernstein P , Bingham D , Delgado A , Callaghan WM , Harris K , Lanni S , Mahoney J , Main E , Nacht A , Schellpfeffer M , Westover T , Harper M . Obstet Gynecol 2014 124 361-366 Severe maternal morbidity and mortality have been rising in the United States. To begin a national effort to reduce morbidity, a specific call to identify all pregnant and postpartum women experiencing admission to an intensive care unit or receipt of 4 or more units of blood for routine review has been made. While advocating for review of these cases, no specific guidance for the review process was provided. Therefore, the aim of this expert opinion is to present guidelines for a standardized severe maternal morbidity interdisciplinary review process to identify systems, professional, and facility factors that can be ameliorated, with the overall goal of improving institutional obstetric safety and reducing severe morbidity and mortality among pregnant and recently pregnant women. This opinion was developed by a multidisciplinary working group that included general obstetrician-gynecologists, maternal-fetal medicine subspecialists, certified nurse-midwives, and registered nurses all with experience in maternal mortality reviews. A process for standardized review of severe maternal morbidity addressing committee organization, review process, medical record abstraction and assessment, review culture, data management, review timing, and review confidentiality is presented. Reference is made to a sample severe maternal morbidity abstraction and assessment form. |
Maternal stressors and social support as risks for delivering babies with structural birth defects
Carmichael SL , Ma C , Tinker S , Rasmussen SA , Shaw GM . Paediatr Perinat Epidemiol 2014 28 (4) 338-44 BACKGROUND: We examined the association of maternal stressful life events and social support with risks of birth defects using National Birth Defects Prevention Study data, a population-based case-control study. METHODS: We examined seven stressful life events and three social support questions applicable to the periconceptional period, among mothers of 552 cases with neural tube defects (NTDs), 413 cleft palate (CP), 797 cleft lip +/- cleft palate (CLP), 189 d-transposition of the great arteries (dTGA), 311 tetralogy of Fallot (TOF), and 2974 non-malformed controls. A stressful life events index equalled the sum of 'yes' responses to the seven questions. Social support questions were also summed to form an index. Data were analyzed using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusted for maternal race-ethnicity, age, education, body mass index, smoking, drinking, and intake of vitamin supplements. RESULTS: Associations with the stress index tended to be higher with higher scores, but few 95% CIs excluded one. A four-point increase in the index was moderately associated with NTDs (OR 1.5, [95% CI 1.1, 2.0]) and CLP (OR 1.3, [95% CI 1.0, 1.7]). The social support index tended to be associated with reduced risk but most 95% CIs included one, with the exception of dTGA (OR for a score of 3 vs 0 was 0.5 [95% CI 0.3, 0.8]). CONCLUSIONS: Maternal periconceptional stressful life events, social support, and the two factors in combination were at most modestly, if at all, associated with risks of the studied birth defects. |
Emergency department visits for mental health conditions among US children, 2001-2011
Simon AE , Schoendorf KC . Clin Pediatr (Phila) 2014 53 (14) 1359-66 We examined mental health-related visits to emergency departments (EDs) among children from 2001 to 2011. We used the National Hospital Ambulatory Medical Care Survey-Emergency Department, 2001-2011 to identify visits of children 6 to 20 years old with a reason-for-visit code or ICD-9-CM diagnosis code reflecting mental health issues. National percentages of total visits, visit counts, and population rates were calculated, overall and by race, age, and sex. Emergency department visits for mental health issues increased from 4.4% of all visits in 2001 to 7.2% in 2011. Counts increased 55 000 visits per year and rates increased from 13.6 visits/1000 population in 2001 to 25.3 visits/1000 in 2011 (P < .01 for all trends). Black children (all ages) had higher visit rates than white children and 13- to 20-year-olds had higher visit rates than children 6 to 12 years old (P < .01 for all comparisons). Differences between groups did not decline over time. |
Corticosteroid use and risk of orofacial clefts
Skuladottir H , Wilcox AJ , Ma C , Lammer EJ , Rasmussen SA , Werler MM , Shaw GM , Carmichael SL . Birth Defects Res A Clin Mol Teratol 2014 100 (6) 499-506 BACKGROUND: Maternal use of corticosteroids during early pregnancy has been inconsistently associated with orofacial clefts in the offspring. A previous report from the National Birth Defect Prevention Study (NBDPS), using data from 1997 to 2002, found an association with cleft lip and palate (odds ratio, 1.7; 95% confidence interval [CI], 1.1-2.6), but not cleft palate only (odds ratio, 0.5, 95%CI, 0.2-1.3). From 2003 to 2009, the study population more than doubled in size, and our objective was to assess this association in the more recent data. METHODS: The NBDPS is an ongoing multi-state population-based case-control study of birth defects, with ascertainment of cases and controls born since 1997. We assessed the association of corticosteroids and orofacial clefts using data from 2372 cleft cases and 5922 controls born from 2003 to 2009. Maternal corticosteroid exposure was based on telephone interviews. RESULTS: The overall association of corticosteroids and cleft lip and palate in the new data was 1.0 (95% CI, 0.7-1.4). There was little evidence of associations between specific corticosteroid components or timing and clefts. CONCLUSION: In contrast to the 1997 to 2002 data from the NBDPS, the 2003 to 2009 data show no association between maternal corticosteroid use and cleft lip and palate in the offspring. |
Restaurant menu labeling use among adults - 17 States, 2012
Lee-Kwan SH , Pan L , Maynard L , Kumar G , Park S . MMWR Morb Mortal Wkly Rep 2014 63 (27) 581-4 Many persons underestimate the calories in restaurant foods. Increased attention has been given to menu labeling (ML) as a way to provide consumers with point-of-purchase information that can help them reduce calorie intake and make healthier dietary choices. In 2010, a federal law was passed requiring restaurants with 20 or more establishments to display calorie information on menus and menu boards.* The regulations to implement this federal law have not been finalized, but some states and local jurisdictions have implemented their own ML policies, and many restaurants have already begun providing ML. To assess fast food and chain restaurant ML use by state and by demographic subgroup, CDC examined self-reported ML use by adults in 17 states that used the Sugar-Sweetened Beverages and Menu Labeling optional module in the 2012 Behavioral Risk Factor Surveillance System (BRFSS) survey. Based on approximately 97% of adult BRFSS respondents who noticed ML information at restaurants, the estimated overall proportion of ML users in the 17 states was 57.3% (range = 48.7% in Montana to 61.3% in New York). The prevalence of ML use was higher among women than men for all states; the patterns varied by age group and race/ethnicity across states. States and public health professionals can use these findings to track the use of ML and to develop targeted interventions to increase awareness and use of ML among nonusers. |
The role of nodose ganglia in the regulation of cardiovascular function following pulmonary exposure to ultrafine titanium dioxide
Kan H , Wu Z , Lin YC , Chen TH , Cumpston JL , Kashon ML , Leonard S , Munson AE , Castranova V . Nanotoxicology 2014 8 (4) 447-54 The inhalation of nanosized air pollutant particles is a recognised risk factor for cardiovascular disease; however, the link between occupational exposure to engineered nanoparticles and adverse cardiovascular events remains unclear. In the present study, the authors demonstrated that pulmonary exposure of rats to ultrafine titanium dioxide (UFTiO2) significantly increased heart rate and depressed diastolic function of the heart in response to isoproterenol. Moreover, pulmonary inhalation of UFTiO2 elevated mean and diastolic blood pressure in response to norepinephrine. Pretreatment of the rats ip with the transient receptor potential (TRP) channel blocker ruthenium red inhibited substance P synthesis in nodose ganglia and associated functional and biological changes in the cardiovascular system. In conclusion, the effects of pulmonary inhalation of UFTiO2 on cardiovascular function are most likely triggered by a lung-nodose ganglia-regulated pathway via the activation of TRP channels in the lung. |
Exposure to volatile organic compounds in healthcare settings
LeBouf RF , Virji MA , Saito R , Henneberger PK , Simcox N , Stefaniak AB . Occup Environ Med 2014 71 (9) 642-50 OBJECTIVES: To identify and summarise volatile organic compound (VOC) exposure profiles of healthcare occupations. METHODS: Personal (n=143) and mobile area (n=207) evacuated canisters were collected and analysed by a gas chromatograph/mass spectrometer to assess exposures to 14 VOCs among 14 healthcare occupations in five hospitals. Participants were volunteers identified by their supervisors. Summary statistics were calculated by occupation. Principal component analysis (PCA) was used to reduce the 14 analyte inputs to five orthogonal factors and identify occupations that were associated with these factors. Linear regressions were used to assess the association between personal and mobile area samples. RESULTS: Exposure profiles differed among occupations; ethanol had the highest geometric mean (GM) among nursing assistants ( approximately 4900 and approximately 1900 microg/m3, personal and area), and 2-propanol had the highest GM among medical equipment preparers ( approximately 4600 and approximately 2000 microg/m3, personal and area). The highest total personal VOC exposures were among nursing assistants ( approximately 9200 microg/m3), licensed practical nurses ( approximately 8700 microg/m3) and medical equipment preparers ( approximately 7900 microg/m3). The influence of the PCA factors developed from personal exposure estimates varied by occupation, which enabled a comparative assessment of occupations. For example, factor 1, indicative of solvent use, was positively correlated with clinical laboratory and floor stripping/waxing occupations and tasks. Overall, a significant correlation was observed (r=0.88) between matched personal and mobile area samples, but varied considerably by analyte (r=0.23-0.64). CONCLUSIONS: Healthcare workers are exposed to a variety of chemicals that vary with the activities and products used during activities. These VOC profiles are useful for estimating exposures for occupational hazard ranking for industrial hygienists as well as epidemiological studies. |
Immune stimulation following dermal exposure to unsintered indium tin oxide
Brock K , Anderson SE , Lukomska E , Long C , Anderson K , Marshall N , Jean Meade B . J Immunotoxicol 2014 11 (3) 268-72 In recent years, several types of pulmonary pathology, including alveolar proteinosis, fibrosis, and emphysema, have been reported in workers in the indium industry. To date, there remains no clear understanding of the underlying mechanism(s). Pulmonary toxicity studies in rats and mice have demonstrated the development of mediastinal lymph node hyperplasia and granulomas of mediastinal lymph nodes and bronchus-associated lymphoid tissues following exposure to indium tin oxide. Given the association between exposure to other metals and the development of immune-mediated diseases, these studies were undertaken to begin to investigate the immuno-modulatory potential of unsintered indium tin oxide (uITO) in a mouse model. Using modifications of the local lymph node assay, BALB/c mice (five animals/group) were exposed topically via intact or breached skin or injected intradermally at the base of the ear pinnae with either vehicle or increasing concentrations 2.5-10% uITO (90:10 indium oxide/tin oxide, particle size <50 nm). Dose-responsive increases in lymphocyte proliferation were observed with a calculated EC3 of 4.7% for the intact skin study. Phenotypic analysis of draining lymph node cells following intradermal injection with 5% uITO yielded a profile consistent with a T-cell-mediated response. These studies demonstrate the potential for uITO to induce sensitization and using lymphocyte proliferation as a biomarker of exposure, and demonstrate the potential for uITO to penetrate both intact and breached skin. |
Placental infections with histologically confirmed Plasmodium falciparum are associated with adverse birth outcomes in India: a cross-sectional study
Ahmed R , Singh N , Ter Kuile FO , Bharti PK , Singh PP , Desai M , Udhayakumar V , Terlouw DJ . Malar J 2014 13 (1) 232 BACKGROUND: Few studies have assessed placental malaria infections from low transmission areas by histopathology to define their impact and underlying mechanisms. METHODS: Peripheral smears and rapid diagnostic tests (RDTs), placental smears and histological samples, birth weight and gestational age were collected from 2,282 deliveries in three hospitals during a one-year (2006-2007) continuous cross-sectional survey in Madhya Pradesh. Placental histopathology included all 50 cases positive by microscopy or RDT plus 456 randomly selected samples of women negative for malaria by microscopy or RDT. Histological examination included parasites, inflammatory cells, pigment in fibrin, and morphological changes. RESULTS: There were 52 histology-positive cases; 38 (73.1%) active (acute and chronic) and 14 past infections. Intervillous parasitaemia was low (60% had < 1% parasitaemia) and monocytosis mostly mild (63%). Compared with uninfected placentas, acute Plasmodium falciparum infections were associated with stillbirth (RR 3.8, 95% CI 1.2-12.1), lower maternal haemoglobin (mean difference: 1.5 g/dL, 95% CI 0.5-2.5), lower birth weight (mean difference 451 g, 95% CI 169-609) and shorter gestation (mean difference 0.8 weeks, 95% CI 0.2-1.4). Chronic or past infections were not associated with these outcomes. Among the 11 peripheral Plasmodium vivax cases, placental parasites were absent, but they were associated with increased placental polymorphonuclear cells. CONCLUSIONS: Malaria associated stillbirth and low birth weight in women with low protective immunity may result, at least in part, from a shortened gestation triggered by acute infection, stressing the importance of early malaria detection. |
Filarial excretory-secretory products induce human monocytes to produce lymphangiogenic mediators
Weinkopff T , Mackenzie C , Eversole R , Lammie PJ . PLoS Negl Trop Dis 2014 8 (7) e2893 The nematodes Wuchereria bancrofti and Brugia spp. infect over 120 million people worldwide, causing lymphedema, elephantiasis and hydrocele, collectively known as lymphatic filariasis. Most infected individuals appear to be asymptomatic, but many exhibit sub-clinical manifestations including the lymphangiectasia that likely contributes to the development of lymphedema and elephantiasis. As adult worm excretory-secretory products (ES) do not directly activate lymphatic endothelial cells (LEC), we investigated the role of monocyte/macrophage-derived soluble factors in the development of filarial lymphatic pathology. We analyzed the production of IL-8, IL-6 and VEGF-A by peripheral blood mononuclear cells (PBMC) from naive donors following stimulation with filarial ES products. ES-stimulated PBMCs produced significantly more IL-8, IL-6 and VEGF-A compared to cells cultured in medium alone; CD14+ monocytes appear to be the primary producers of IL-8 and VEGF-A, but not IL-6. Furthermore, IL-8, IL-6 and VEGF-A induced in vitro tubule formation in LEC Matrigel cultures. Matrigel plugs supplemented with IL-8, IL-6, VEGF-A, or with supernatants from ES-stimulated PBMCs and implanted in vivo stimulated lymphangiogenesis. Collectively, these data support the hypothesis that monocytes/macrophages exposed to filarial ES products may modulate lymphatic function through the secretion of soluble factors that stimulate the vessel growth associated with the pathogenesis of filarial disease. |
Investigating the important correlates of maternal education and childhood malaria infections
Njau JD , Stephenson R , Menon M , Kachur SP , McFarland DA . Am J Trop Med Hyg 2014 91 (3) 509-19 The relationship between maternal education and child health has intrigued researchers for decades. This study explored the interaction between maternal education and childhood malaria infection. Cross-sectional survey data from three African countries were used. Descriptive analysis and multivariate logistic regression models were completed in line with identified correlates. Marginal effects and Oaxaca decomposition analysis on maternal education and childhood malaria infection were also estimated. Children with mothers whose education level was beyond primary school were 4.7% less likely to be malaria-positive (P < 0.001). The Oaxaca decomposition analysis exhibited an 8% gap in childhood malaria infection for educated and uneducated mothers. Over 60% of the gap was explained by differences in household wealth (26%), household place of domicile (21%), malaria transmission intensities (14%), and media exposure (12%). All other correlates accounted for only 27%. The full adjusted model showed a robust and significant relationship between maternal education and childhood malaria infection. |
Case definition: postartemisinin delayed hemolysis
Arguin PM . Blood 2014 124 (2) 157-8 In this issue of Blood, Jaureguiberry et al appear to have proven that the hypothesis of early destruction of pitted erythrocytes is correct and propose a method for screening patients for this syndrome. Early destruction of pitted erythrocytes has been the leading hypothesis for postartesunate delayed hemolysis since it was first recognized a few years ago. |
Tobacco use among youths - Argentina, 2007 and 2012
Konfino J , Ferrante D , Goldberg L , Caixeta R , Palipudi KM . MMWR Morb Mortal Wkly Rep 2014 63 (27) 588-90 Tobacco use is the leading preventable cause of deaths worldwide. The MPOWER package, the six recommended policies of the World Health Organization (WHO) to reverse the tobacco epidemic, strongly recommends monitoring tobacco use trends. Because evidence indicates that smoking addiction often starts before the age of 18 years, there is a need to monitor tobacco use among youths. During 2011, a National Tobacco Control Law was enacted in Argentina that included implementation of 100% smoke-free environments, a comprehensive advertising ban (prohibiting advertising, promotion, and sponsorship of cigarettes or tobacco products through any media or communications outlets), pictorial health warnings, and a prohibition against the sale of tobacco products through any means to persons aged <18 years. To ascertain trends in tobacco use among youths in Argentina, the Argentina Ministry of Health and CDC analyzed data from the Global Youth Tobacco Survey (GYTS) for 2007 and 2012 (the next year that it was administered in Argentina). The findings indicated that the overall proportion of youths aged approximately 13-15 years who reported ever smoking a cigarette declined from 52.0% in 2007 to 41.9% in 2012 with significant decreases among both males and females. In 2012, 52.5% of youths in Argentina reported secondhand smoke (SHS) exposure in their homes and 47.5% in enclosed public places in the 7 days preceding the survey. Increased public education and tobacco control efforts will be important to discouraging tobacco use and decreasing SHS exposure among youths in Argentina. |
Intermediate cessation outcomes among quitline callers during a national tobacco education campaign
Zhang L , Vickerman K , Malarcher A , Mowery P . Nicotine Tob Res 2014 16 (11) 1478-86 INTRODUCTION: From March 19 through June 10, 2012, the Centers for Disease Control and Prevention launched the first federally funded National Tobacco Education Campaign: Tips From Former Smokers (Tips). This study examined the campaign's impact on quitline callers' intermediate cessation outcomes. METHODS: We used quitline data from 23 states to examine changes in enrollment, service utilization, quit attempts and self-reported quitting for 7 days or longer during Tips versus a similar time period in 2011. We used multivariate models to examine the relationship between Tips exposure (measured as gross rating points or GRPs) and cessation outcomes during the campaign in 2012. We also assessed whether the Tips campaign's impact differed by state tobacco control funding. RESULTS: Compared with similar weeks in 2011, the number of quitline callers and callers who received counseling and/or nicotine replacement therapies increased by 88.6% (48,738 in 2011 vs. 91,911 during Tips) and 70.8% (40,546 in 2011 vs. 69,254 during Tips), respectively. Greater numbers of callers reported having made 24-hr quit attempts or quitting for 7 days or longer during the campaign. Higher Tips campaign GRPs were positively associated with quit attempts and quitting for 7 days or longer among persons from states with higher tobacco control funding. In states with lower funding, the highest GRP group (2,000+ GRPs) had lower levels of cessation than the middle GRP group (1,200-1,999 GRPs). CONCLUSIONS: An evidence-based national tobacco education campaign with adequate reach and frequency can lead to substantial increases in quitline use and, to a lesser degree, intermediate cessation outcomes. |
Genomic analysis of the causative agents of coccidiosis in domestic chickens.
Reid AJ , Blake DP , Ansari HR , Billington K , Browne HP , Bryant JM , Dunn M , Hung SS , Kawahara F , Miranda-Saavedra D , Malas T , Mourier T , Naghra H , Nair M , Otto TD , Rawlings ND , Rivailler P , Sanchez-Flores A , Sanders M , Subramaniam C , Tay YL , Woo Y , Wu X , Barrell B , Dear PH , Doerig C , Gruber A , Ivens AC , Parkinson J , Rajandream MA , Shirley MW , Wan KL , Berriman M , Tomley FM , Pain A . Genome Res 2014 24 (10) 1676-85 Global production of chickens has trebled in the past two decades and they are now the most important source of dietary animal protein worldwide. Chickens are subject to many infectious diseases that reduce their performance and productivity. Coccidiosis, caused by apicomplexan protozoa of the genus Eimeria, is one of the most important poultry diseases. Understanding the biology of Eimeria parasites underpins development of new drugs and vaccines needed to improve global food security. We have produced annotated genome sequences of all seven species of Eimeria that infect domestic chickens, which reveal the full extent of previously described repeat-rich and repeat-poor regions and show that these parasites possess the most repeat-rich proteomes ever described. Furthermore, while no other apicomplexan has been found to possess retrotransposons, Eimeria is home to a family of chromoviruses. Analysis of Eimeria genes involved in basic biology and host-parasite interaction highlights adaptations to a relatively simple developmental life cycle and a complex array of co-expressed surface proteins involved in host cell binding. |
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