Matrix metalloproteinases, tissue inhibitors of metalloproteinases, and heart failure outcomes
Bhalla V , Georgiopoulou VV , Azeem AA , Marti CN , Cole RT , Laskar SR , De Staercke C , Hooper WC , Smith AL , Kalogeropoulos AP , Butler J . Int J Cardiol 2011 151 (2) 237-9 Heart failure (HF) prevalence continues to increase and is associated with a high mortality, morbidity, and cost burden for the society. [1, 2] The most common cause of HF in the United States is coronary artery disease. [3] Left ventricular (LV) dysfunction, irrespective of the cause of heart failure (HF), leads to perturbed wall stress resulting in remodeling and HF progression. Matrix metalloproteinases (MMP) are a family of proteolytic enzymes that are involved in the protein degradation in the extracellular matrix and play an important role in remodeling. [4, 5] Multiple classes of MMPs have been identified in human myocardium.[5, 6] Certain MMPs, specifically MMP-2, MMP-3, and MMP-9 have been shown to have high expression in the left ventricle. [7, 8] Tissue inhibitors of metalloproteinases (TIMPS) are low-molecular-weight molecules that bind to MMPs forming MMP-TIMP complexes that exhibit an inhibitory control on MMPs. Several studies have delineated the relationship between MMPs and TIMPs, and that the changes in the MMP/TIMP ratio correlate with left ventricular hypertrophy and dilation. [9, 10] Loss of inhibitory control of TIMP on MMP correlates with progression of left ventricular remodeling via increased MMP activity, extra-cellular matrix proteolysis, and myocardial remodeling changes. [11] There have been conflicting reports on MMPs and TIMPs levels association with HF outcomes. [12-17] These studies have generally not assessed the multiple members of the MMP and TIMP family simultaneously and have assessed varying HF outcomes. In this study, we sought to assess the association between multiple MMPs and TIMPs with clinical outcomes, health status, and exercise capacity among HF patients. |
Factors associated with emergency medical services scope of practice for acute cardiovascular events
Williams I , Valderrama AL , Bolton P , Greek A , Greer S , Patterson DG , Zhang Z . Prehosp Emerg Care 2011 16 (2) 189-97 OBJECTIVES: To examine prehospital emergency medical services (EMS) scope of practice for acute cardiovascular events and characteristics that may affect scope of practice; and to describe variations in EMS scope of practice for these events and the characteristics associated with that variability. METHODS: In 2008, we conducted a telephone survey of 1,939 eligible EMS providers in nine states to measure EMS agency characteristics, medical director involvement, and 18 interventions authorized for prehospital care of acute cardiovascular events by three levels of emergency medical technician (EMT) personnel. RESULTS: A total of 1,292 providers responded to the survey, for a response rate of 67%. EMS scope of practice interventions varied by EMT personnel level, with the proportion of authorized interventions increasing as expected from EMT-Basic to EMT-Paramedic. Seven of eight statistically significant associations indicated that EMS agencies in urban settings were less likely to authorize interventions (odds ratios <0.7) for any level of EMS personnel. Based on the subset of six statistically significant associations, fire department-based EMS agencies were two to three times more likely to authorize interventions for EMT-Intermediate personnel. Volunteer EMS agencies were more than twice as likely as nonvolunteer agencies to authorize interventions for EMT-Basic and EMT-Intermediate personnel but were less likely to authorize any one of the 11 interventions for EMT-Paramedics. Greater medical director involvement was associated with greater likelihood of authorization of seven of the 18 interventions for EMT-Basic and EMT-Paramedic personnel but had no association with EMT-Intermediate personnel. CONCLUSIONS: We noted statistically significant variations in scope of practice by rural vs. urban setting, medical director involvement, and type of EMS service (fire department-based/non-fire department-based; volunteer/paid). These variations highlight local differences in the composition and capacity of EMS providers and offer important information for the transition towards the implementation of a national scope of practice model. |
Adherence to guidelines for youths with diabetes mellitus
Waitzfelder B , Pihoker C , Klingensmith G , Case D , Anderson A , Bell RA , Lawrence JM , Mayer-Davis EJ , Imperatore G , Standiford D , Rodriguez BL , Dabelea D , Seid M . Pediatrics 2011 128 (3) 531-8 OBJECTIVE: To describe demographic and clinical characteristics associated with self-reported receipt of tests and measurements recommended by the American Diabetes Association (ADA) for children and youths with diabetes. METHODS: The study included 1514 SEARCH for Diabetes in Youth study participants who completed a survey about diabetes care received. Quality-of-care measures were based on ADA guidelines for eye examinations and glycohemoglobin (hemoglobin A1c [HbA1c]), lipid level, microalbuminuria, and blood pressure measurements, and a composite variable of these 5 indicators was created. Multivariate logistic regression models were used to assess the association of selected demographic and clinical characteristics with the reported receipt of all recommended tests and measurements according to age and diabetes type subgroups. RESULTS: Overall, 95% of the participants reported having their blood pressure checked at all or most visits, 88% had lipid levels measured, 83% had kidney function tested, 68% underwent HbA1c testing, and 66% underwent an eye examination, in accordance with ADA recommendations. Participants aged 18 years or older, particularly those with type 2 diabetes, tended to have fewer tests of all kinds performed. Age and family income emerged as important correlates of overall quality of care in multivariate models; older age and lower income were associated with not meeting guidelines. CONCLUSIONS: Although there was relatively good adherence to ADA-recommended guidelines for most indicators, efforts are needed to improve rates of HbA1c testing and eye examinations, particularly among older youths. |
CD4 cell counts at HIV diagnosis among HIV outpatient study participants, 2000-2009
Buchacz K , Armon C , Palella FJ , Baker RK , Tedaldi E , Durham MD , Brooks JT . AIDS Res Treat 2012 2012 869841 BACKGROUND: It is unclear if CD4 cell counts at HIV diagnosis have improved over a 10-year period of expanded HIV testing in the USA. METHODS: We studied HOPS participants diagnosed with HIV infection ≤6 months prior to entry into care during 2000-2009. We assessed the correlates of CD4 count <200 cells/mm(3) at HIV diagnosis (late HIV diagnosis) by logistic regression. RESULTS: Of 1,203 eligible patients, 936 (78%) had a CD4 count within 3 months after HIV diagnosis. Median CD4 count at HIV diagnosis was 299 cells/mm(3) and did not significantly improve over time (P = 0.13). Comparing periods 2000-2001 versus 2008-2009, respectively, 39% and 35% of patients had a late HIV diagnosis (P = 0.34). Independent correlates of late HIV diagnosis were having an HIV risk other than being MSM, age ≥35 years at diagnosis, and being of nonwhite race/ethnicity. CONCLUSIONS: There is need for routine universal HIV testing to reduce the frequency of late HIV diagnosis and increase opportunity for patient- and potentially population-level benefits associated with early antiretroviral treatment. |
Life-threatening pneumonia caused by macrolide-resistant Mycoplasma pneumoniae
Hsieh YC , Tsao KC , Huang CG , Tong S , Winchell JM , Huang YC , Shia SH , Lai SH , Lin TY . Pediatr Infect Dis J 2011 31 (2) 208-9 Two siblings had pneumonia caused by macrolide-resistant Mycoplasma pneumoniae as determined by polymerase chain reaction and serology. One of them developed adult respiratory distress syndrome and required extracorporeal membrane oxygenation therapy. This report highlights the need for studies to evaluate the optimal treatment in severe cases of macrolide-resistant M. pneumoniae pneumonia. |
Adolescents with perinatally acquired HIV: emerging behavioral and health needs for long-term survivors
Koenig LJ , Nesheim S , Abramowitz S . Curr Opin Obstet Gynecol 2011 23 (5) 321-7 PURPOSE OF REVIEW: Because of widespread availability of highly active antiretroviral therapy in the developed world, a large proportion of children with perinatally acquired HIV have survived to adolescence and young adulthood. Although their survival is remarkable, many now experience the long-term effects of HIV infection and its treatment. Further, as these youths have entered adolescence, more is known about the impact of normative developmental transitions on health maintenance behaviors. RECENT FINDINGS: Although perinatally infected adolescents are healthier than they were a decade or more ago, they are significantly experienced with antiretroviral therapy, with increased virological resistance and other consequences of extended antiretroviral use. Three behavioral health challenges have been documented in the first cohort of long-term survivors: decreased medication adherence, sexual debut and accompanying pregnancy and transmission risk, and mental health problems. These issues are consistent with a developmental press for autonomy, mature sexual relationships and future planning, but must be carefully managed to preserve health. SUMMARY: Adolescents with perinatally acquired HIV require coordinated multidisciplinary support services - including adherence support, reproductive health counseling addressing both pregnancy planning and disease transmission, and mental health and educational/vocational planning - so that they can fully benefit from treatment advances. |
Caveat emptor? Control of latent tuberculosis infection in the United States
Schwartzman K , Cain KP . Am J Respir Crit Care Med 2011 184 (5) 501-2 The United States and other countries are grappling with the need to treat large numbers of persons with latent tuberculosis infection (LTBI) to further reduce tuberculosis (TB) incidence (1, 2). However, the success of LTBI treatment as a TB control strategy has been limited by competing priorities and by suboptimal uptake and completion. New regimens offer the promise of s horter treatment and enhanced completion (3, 4), so it is relevant to revisit screening (also referred to as targeted LTBI testing) and treatment priorities—especially given the severe fiscal constraints now confronting TB control authorities. In this context, the article by Linas and colleagues in this issue of the Journal (pp. 590) provides welcome information (5). The authors have developed a comprehensive decision analysis model, to predict costs and effectiveness of LTBI screening and treatment in various patient groups. | Two findings have very specific implications for policy and practice. The first is that in foreign-born persons, the interferon-γ release assay (IGRA) may be preferable to the tuberculin skin test (TST). This is because the IGRA has similar or slightly lower overall cost, but is more effective than the TST, primarily because it obviates the need for a return visit to obtain results. In some other groups, IGRAs are more expensive, but potentially cost-effective because of additional TB cases prevented. Much of the value of IGRAs is ascribed to reduced attrition. However, it is not entirely clear that patients who miss TST reading would initiate and complete LTBI treatment if an IGRA were used instead. Hence the apparent advantages of IGRAs may be overstated. | The second major finding, in our view, is that the relative cost-effectiveness estimates can guide programs in targeting groups for whom screening and treatment will offer the highest yield at lowest cost. Specifically, as with close contacts and HIV-infected persons, screening and treatment of foreign-born persons is likely to be relatively cost-effective—both for recent arrivals (in the United States < 5 yr), and for foreign-born persons under 45 years of age who have resided in the United States for longer. On the other hand, screening and treatment of persons with other medical or social risk factors (e.g., other immune-suppressive treatment, homelessness, injection drug use) appears less cost-effective, and is predicted to have limited impact in reducing the burden of TB in the United States. |
South American Plasmodium falciparum after the malaria eradication era: clonal population expansion and survival of the fittest hybrids.
Griffing SM , Mixson-Hayden T , Sridaran S , Alam MT , McCollum AM , Cabezas C , Marquino Quezada W , Barnwell JW , Macedo De Oliveira A , Lucas C , Arrospide N , Escalante AA , Bacon DJ , Udhayakumar V . PLoS One 2011 6 (9) e23486 Malaria has reemerged in many regions where once it was nearly eliminated. Yet the source of these parasites, the process of repopulation, their population structure, and dynamics are ill defined. Peru was one of malaria eradication's successes, where Plasmodium falciparum was nearly eliminated for two decades. It reemerged in the 1990s. In the new era of malaria elimination, Peruvian P. falciparum is a model of malaria reinvasion. We investigated its population structure and drug resistance profiles. We hypothesized that only populations adapted to local ecological niches could expand and repopulate and originated as vestigial populations or recent introductions. We investigated the genetic structure (using microsatellites) and drug resistant genotypes of 220 parasites collected from patients immediately after peak epidemic expansion (1999-2000) from seven sites across the country. The majority of parasites could be grouped into five clonal lineages by networks and AMOVA. The distribution of clonal lineages and their drug sensitivity profiles suggested geographic structure. In 2001, artesunate combination therapy was introduced in Peru. We tested 62 parasites collected in 2006-2007 for changes in genetic structure. Clonal lineages had recombined under selection for the fittest parasites. Our findings illustrate that local adaptations in the post-eradication era have contributed to clonal lineage expansion. Within the shifting confluence of drug policy and malaria incidence, populations continue to evolve through genetic outcrossing influenced by antimalarial selection pressure. Understanding the population substructure of P. falciparum has implications for vaccine, drug, and epidemiologic studies, including monitoring malaria during and after the elimination phase. |
Cryptococcus gattii: where do we go from here?
Harris J , Lockhart S , Chiller T . Med Mycol 2011 50 (2) 113-29 Infections caused by the emerging pathogen Cryptococcus gattii are increasing in frequency in North America. During the past decade, interest in the pathogen has continued to grow, not only in North America but also in other areas of the world where infections have recently been documented. This review synthesizes existing data and raises issues that remain to be addressed. |
Exposure to PBDEs in the office environment: evaluating the relationships between dust, handwipes, and serum
Watkins DJ , McClean MD , Fraser AJ , Weinberg J , Stapleton HM , Sjodin A , Webster TF . Environ Health Perspect 2011 119 (9) 1247-52 BACKGROUND: Polybrominated diphenyl ethers (PBDEs) have been widely used as flame retardants in consumer products and are ubiquitous in residential indoor air and dust. However, little is known about exposure in the office environment. OBJECTIVES: We examined relationships between PBDE concentrations in the office environment and internal exposure using concurrent measurements of PBDEs in serum, handwipes, and office dust. METHODS: We collected serum, dust, and handwipe samples from 31 participants who spent at least 20 hr/week in an office. We used a questionnaire to collect information about work and personal habits. RESULTS: We found positive associations between PBDEs in room dust, handwipes (a measure of personal exposure), and serum. PBDE office dust concentrations were weakly correlated with measurements in handwipes: r = 0.35 (p = 0.06) for pentaBDE (sum of BDE congeners 28/33, 47, 99, 100, and 153) and 0.33 (p = 0.07) for BDE-209. Hand washing also predicted pentaBDE levels in handwipes: low hand-washers had 3.3 times the pentaBDE levels in their handwipes than did high hand-washers (p = 0.02). PentaBDE in handwipes predicted pentaBDE levels in serum (p = 0.03): Serum concentrations in the highest handwipe tertile were on average 3.5 times the lowest handwipe tertile. The geometric mean concentration of pentaBDEs in serum was 27 ng/g lipid. We detected BDE-209 in 20% of serum samples, at levels ranging from < 4.8 to 9.7 ng/g lipid. CONCLUSION: Our research suggests that exposure to pentaBDE in the office environment contributes to pentaBDE body burden, with exposure likely linked to PBDE residues on hands. In addition, hand washing may decrease exposure to PBDEs. |
Impact of the improved Patsari biomass stove on urinary polycyclic aromatic hydrocarbon biomarkers and carbon monoxide exposures in rural Mexican women
Riojas-Rodriguez H , Schilmann A , Marron-Mares AT , Masera O , Li Z , Romanoff L , Sjodin A , Rojas-Bracho L , Needham LL , Romieu I . Environ Health Perspect 2011 119 (9) 1301-7 BACKGROUND: Cooking with biomass fuels on open fires results in exposure to health-damaging pollutants such as carbon monoxide (CO), polycyclic aromatic hydrocarbons (PAHs), and particulate matter. OBJECTIVE: We compared CO exposures and urinary PAH biomarkers pre- and postintervention with an improved biomass stove, the Patsari stove. METHODS: In a subsample of 63 women participating in a randomized controlled trial in central Mexico, we measured personal CO exposure for 8 hr during the day using continuous monitors and passive samplers. In addition, first-morning urine samples obtained the next day were analyzed for monohydroxylated PAH metabolites by gas chromatography/isotope dilution/high-resolution mass spectrometry. Exposure data were collected during the use of an open fire (preintervention) and after installation of the improved stove (postintervention) for 47 women, enabling paired comparisons. RESULTS: Median pre- and postintervention values were 4 and 1 ppm for continuous personal CO and 3 and 1 ppm for passive sampler CO, respectively. Postintervention measurements indicated an average reduction of 42% for hydroxylated metabolites of naphthalene, fluorene, phenanthrene, and pyrene on a whole-weight concentration basis (micrograms per liter of urine), and a 34% reduction on a creatinine-adjusted basis (micrograms per gram of creatinine). Pre- and postintervention geometric mean values for 1-hydroxypyrene were 3.2 and 2.0 mcg/g creatinine, respectively. CONCLUSION: Use of the Patsari stove significantly reduced CO and PAH exposures in women. However, levels of many PAH biomarkers remained higher than those reported among smokers. |
Dioxin exposure and age of pubertal onset among Russian boys
Korrick SA , Lee MM , Williams PL , Sergeyev O , Burns JS , Patterson DG , Turner WE , Needham LL , Altshul L , Revich B , Hauser R . Environ Health Perspect 2011 119 (9) 1339-44 BACKGROUND: Animal data demonstrate associations of dioxin, furan, and polychlorinated biphenyl (PCB) exposures with altered male gonadal maturation. It is unclear whether these associations apply to human populations. OBJECTIVES: We investigated the association of dioxins, furans, PCBs, and corresponding toxic equivalent (TEQ) concentrations with pubertal onset among boys in a dioxin-contaminated region. METHODS: Between 2003 and 2005, 499 boys 8-9 years of age were enrolled in a longitudinal study in Chapaevsk, Russia. Pubertal onset [stage 2 or higher for genitalia (G2+) or testicular volume (TV) > 3 mL] was assessed annually between ages 8 and 12 years. Serum levels at enrollment were analyzed by the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. We used Cox proportional hazards models to assess age at pubertal onset as a function of exposure adjusted for potential confounders. We conducted sensitivity analyses excluding boys with pubertal onset at enrollment. RESULTS: The median (range) total serum TEQ concentration was 21 (4-175) pg/g lipid, approximately three times higher than values in European children. At enrollment, boys were generally healthy and normal weight (mean body mass index, 15.9 kg/m2), with 30% having entered puberty by G2+ and 14% by TV criteria. Higher dioxin TEQs were associated with later pubertal onset by TV (hazard ratio = 0.68, 95% confidence interval, 0.49-0.95 for the highest compared with the lowest quartile). Similar associations were observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin concentrations for TV but not G2+. Results were robust to sensitivity analyses. CONCLUSIONS: Findings support an association of higher peripubertal serum dioxin TEQs and concentrations with later male pubertal onset reflected in delayed testicular maturation. |
Down syndrome: national conference on patient registries, research databases, and biobanks.
Oster-Granite ML , Parisi MA , Abbeduto L , Berlin DS , Bodine C , Bynum D , Capone G , Collier E , Hall D , Kaeser L , Kaufmann P , Krischer J , Livingston M , McCabe LL , Pace J , Pfenninger K , Rasmussen SA , Reeves RH , Rubinstein Y , Sherman S , Terry SF , Siewhitten M , Williams S , McCabe ER , Maddox YT . Mol Genet Metab 2011 104 13-22 A December 2010 meeting, "Down Syndrome: National Conference on Patient Registries, Research Databases, and Biobanks," was jointly sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health (NIH) in Bethesda, MD, and the Global Down Syndrome Foundation (GDSF)/Linda Crnic Institute for Down Syndrome based in Denver, CO. Approximately 70 attendees and organizers from various advocacy groups, federal agencies (Centers for Disease Control and Prevention, and various NIH Institutes, Centers, and Offices), members of industry, clinicians, and researchers from various academic institutions were greeted by Drs. Yvonne Maddox, Deputy Director of NICHD, and Edward McCabe, Executive Director of the Linda Crnic Institute for Down Syndrome. They charged the participants to focus on the separate issues of contact registries, research databases, and biobanks through both podium presentations and breakout session discussions. Among the breakout groups for each of the major sessions, participants were asked to generate responses to questions posed by the organizers concerning these three research resources as they related to Down syndrome and then to report back to the group at large with a summary of their discussions. This report represents a synthesis of the discussions and suggested approaches formulated by the group as a whole. |
Joint associations between genetic variants and reproductive factors in glioma risk among women.
Wang SS , Hartge P , Yeager M , Carreon T , Ruder AM , Linet M , Inskip PD , Black A , Hsing AW , Alavanja M , Beane-Freeman L , Safaiean M , Chanock SJ , Rajaraman P . Am J Epidemiol 2011 174 (8) 901-8 In a pooled analysis of 4 US epidemiologic studies (1993-2001), the authors evaluated the role of 5 female reproductive factors in 357 women with glioma and 822 controls. The authors further evaluated the independent association between 5 implicated gene variants and glioma risk among the study population, as well as the joint associations of female reproductive factors (ages at menarche and menopause, menopausal status, use of oral contraceptives, and menopausal hormone therapy) and these gene variants on glioma risk. Risk estimates were calculated as odds ratios and 95% confidence intervals that were adjusted for age, race, and study. Three of the gene variants (rs4295627, a variant of CCDC26; rs4977756, a variant of CDKN2A and CDKN2B; and rs6010620, a variant of RTEL1) were statistically significantly associated with glioma risk in the present population. Compared with women who had an early age at menarche (<12 years of age), those who reported menarche at 12-13 years of age or at 14 years of age or older had a 1.7-fold higher risk and a 1.9-fold higher risk of glioma, respectively (P for trend = 0.009). Postmenopausal women and women who reported ever having used oral contraceptives had a decreased risk of glioma. The authors did not observe joint associations between these reproductive characteristics and the implicated glioma gene variants. These results require replication, but if confirmed, they would suggest that the gene variants that have previously been implicated in the development of glioma are unlikely to act through the same hormonal mechanisms in women. |
Standards for epidemiologic studies and surveillance of epilepsy
Thurman DJ , Beghi E , Begley CE , Berg AT , Buchhalter JR , Ding D , Hesdorffer DC , Hauser WA , Kazis L , Kobau R , Kroner B , Labiner D , Liow K , Logroscino G , Medina MT , Newton CR , Parko K , Paschal A , Preux PM , Sander JW , Selassie A , Theodore W , Tomson T , Wiebe S . Epilepsia 2011 52 2-26 Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population-based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies. 2011 International League Against Epilepsy. |
New food safety training opportunity using cutting edge technology!
Selman C . J Environ Health 2011 74 (2) 30-1 Because of constant advances in laboratory methods, more foodborne illness outbreaks are recognized and investigated each year. Environmental health | specialists are trained to conduct the environmental assessment of foodborne illness | outbreak investigations. As such, they play | a critical role in understanding the environmental causes of a specific outbreak. They | also assist in preventing future outbreaks. | Yet environmental health specialists don’t | investigate foodborne illness outbreaks every | day. These outbreaks generally occur irregularly. And long periods of disuse can erode | the knowledge and skills needed for outbreak investigations. Training environmental | health specialists and regulators requires an | efficient mechanism. They need to be ready | to conduct and participate effectively in environmental assessments of foodborne illness | outbreaks. That means they need access to an | efficient method of refresher training. |
Genome sequences for five strains of the emerging pathogen Haemophilus haemolyticus.
Jordan IK , Conley AB , Antonov IV , Arthur RA , Cook ED , Cooper GP , Jones BL , Knipe KM , Lee KJ , Liu X , Mitchell GJ , Pande PR , Petit RA , Qin S , Rajan VN , Sarda S , Sebastian A , Tang S , Thapliyal R , Varghese NJ , Ye T , Katz LS , Wang X , Rowe L , Frace M , Mayer LW . J Bacteriol 2011 193 (20) 5879-80 We report the first whole-genome sequences for five strains, two carried and three pathogenic, of the emerging pathogen Haemophilus haemolyticus. Preliminary analyses indicate that these genome sequences encode markers that distinguish H. haemolyticus from its closest Haemophilus relatives and provide clues to the identity of its virulence factors. |
Evaluation of intra-host variants of the entire hepatitis B virus genome.
Ramachandran S , Zhai X , Thai H , Campo DS , Xia G , Ganova-Raeva LM , Drobeniuc J , Khudyakov YE . PLoS One 2011 6 (9) e25232 Genetic analysis of hepatitis B virus (HBV) frequently involves study of intra-host variants, identification of which is commonly achieved using short regions of the HBV genome. However, the use of short sequences significantly limits evaluation of genetic relatedness among HBV strains. Although analysis of HBV complete genomes using genetic cloning has been developed, its application is highly labor intensive and practiced only infrequently. We describe here a novel approach to whole genome (WG) HBV quasispecies analysis based on end-point, limiting-dilution real-time PCR (EPLD-PCR) for amplification of single HBV genome variants, and their subsequent sequencing. EPLD-PCR was used to analyze WG quasispecies from serum samples of patients (n = 38) infected with HBV genotypes A, B, C, D, E and G. Phylogenetic analysis of the EPLD-isolated HBV-WG quasispecies showed the presence of mixed genotypes, recombinant variants and sub-populations of the virus. A critical observation was that HBV-WG consensus sequences obtained by direct sequencing of PCR fragments without EPLD are genetically close, but not always identical to the major HBV variants in the intra-host population, thus indicating that consensus sequences should be judiciously used in genetic analysis. Sequence-based studies of HBV WG quasispecies should afford a more accurate assessment of HBV evolution in various clinical and epidemiological settings. |
High-risk behaviour in steady and in casual relationships among men who have sex with men in Israel
Mor Z , Davidovich U , Bessudu-Manor N , McFarlane M , Feldshtein G , Chemtob D . Sex Transm Infect 2011 87 (6) 532-7 OBJECTIVE: To explore the differences in sexual risk behaviour between men who have sex with men (MSM) with steady partners versus casual partner(s) in the gay community. METHODS: This online cross-sectional convenience-sampling study assessed MSM practices, their knowledge and their motivation regarding safe sex. Participants not knowing their HIV status or who performed insertive or receptive unprotected anal intercourse (UAI) or with a sex partner whose HIV status was unknown or discordant were considered 'at-risk'. RESULTS: Of all 2569 participants who completed the questionnaire, 907/2569 (35.3%) had a steady partner, and 896/2569 (34.9%) had a casual partner(s) in the past 6 months. 262/907 (28.9%) with steady partners and 248/896 (27.7%) with casual partners demonstrated at-risk sexual behaviour. Of all participants with steady partners, 108/907 (11.9%) performed UAI with their partner without undergoing mutual HIV testing. Of all participants with steady partners, 476/907 (52.5%) had a concurrent casual partner, and 144/476 (30.3%) performed UAI with both the steady and the casual partner. Of all participants with steady partners, 775/907 (85.4%) negotiated the possibility of sex outside their relationship with their main partner. The length of the steady relationship correlated with the number of concurrent casual partners. CONCLUSIONS: At-risk sexual behaviour was associated with insufficient negotiation skills, difficulties in condom use and a general risk-taking profile. Health educators should encourage MSM with steady partners to perform HIV testing before practising UAI, to improve their negotiation skills during the contact and to support open discussions with regard to sexual contact besides the steady relationship, as it may not be monogamous. |
Characteristics of parents receiving counseling from child's doctor to limit child's sugar drink consumption
Park S , Sherry B , Blanck HM . J Public Health (Oxf) 2011 34 (2) 228-35 BACKGROUND: Due to limited information on sugar drink counseling, characteristics of parents who reported ever receiving counseling from a child's doctor to limit a child's sugar drink intake were examined. METHODS: This cross-sectional analysis was conducted on a convenient sample of 1570 US parents (aged ≥18 years) using the 2009 HealthStyles Survey. The outcome measure was parents with children aged ≤18 years who reported being told by a child's doctor to limit a child's sugar drink intake. Data were weighted to provide national estimates. Multivariable logistic regression was used to examine factors associated with ever receiving sugar-drink counseling from a child's doctor. RESULTS: Only 23% of parents reported receiving counseling from a child's doctor to limit a child's sugar drink intake. Parental factors significantly associated with receiving this counseling were: being male (adjusted odds ratio (OR) = 1.38; 95% confidence interval (CI) = 1.02, 1.86), having an annual household income of <$25 000 (versus ≥$60 000, OR = 2.12; 95% CI = 1.33, 3.38) and parents who agreed with 'enjoying learning about health issues' (versus disagree, OR = 2.43; 95% CI = 1.36, 4.36). Age, race/ethnicity, education and marital status were not significantly associated with receiving counseling. CONCLUSIONS: Few parents reported ever receiving counseling from a child's doctor, and we found a few differences among those reporting sugar drink counseling. |
Development of DENVax: a chimeric dengue-2 PDK-53-based tetravalent vaccine for protection against dengue fever.
Osorio JE , Huang CY , Kinney RM , Stinchcomb DT . Vaccine 2011 29 (42) 7251-60 Dengue virus infection is the leading arboviral cause of disease worldwide. A vaccine is being developed based on the attenuated DEN-2 virus, DEN-2 PDK-53. In this review, we summarize the characteristics of the parent DEN-2 PDK-53 strain as well as the chimeric viruses containing the prM and E genes of DEN-1, DEN-3 or DEN-4 virus in the genetic backbone of the DEN-2 PDK-53 virus (termed DENVax). Tetravalent DENVax formulations containing cloned, fully sequenced isolates of the DEN-2 PDK-53 virus and the three chimeras have been evaluated for safety and efficacy in preclinical animal models. Based on the safety, immunogenicity and efficacy in preclinical studies, Phase 1 clinical testing of DENVax has been initiated. |
Next generation dengue vaccines: a review of candidates in preclinical development.
Schmitz J , Roehrig J , Barrett A , Hombach J . Vaccine 2011 29 (42) 7276-84 Dengue represents a major public health problem of growing global importance. In the absence of specific dengue therapeutics, strategies for disease control have increasingly focused on the development of dengue vaccines. While a licensed dengue vaccine is not yet available, several vaccine candidates are currently being evaluated in clinical trials and are described in detail in accompanying articles. In addition, there are a large variety of candidates in preclinical development, which are based on diverse technologies, ensuring a continued influx of innovation into the development pipeline. Potentially, some of the current preclinical candidates may become next generation dengue vaccines with superior product profiles. This review provides an overview of the various technological approaches to dengue vaccine development and specifically focuses on candidates in preclinical development. |
Overview of the Clinical Consult Case Review of adverse events following immunization: Clinical Immunization Safety Assessment (CISA) network 2004-2009
Williams SE , Klein NP , Halsey N , Dekker CL , Baxter RP , Marchant CD , Larussa PS , Sparks RC , Tokars JI , Pahud BA , Aukes L , Jakob K , Coronel S , Choi H , Slade BA , Edwards KM . Vaccine 2011 29 (40) 6920-7 BACKGROUND: In 2004 the Clinical Consult Case Review (CCCR) working group was formed within the CDC-funded Clinical Immunization Safety Assessment (CISA) Network to review individual cases of adverse events following immunizations (AEFI). METHODS: Cases were referred by practitioners, health departments, or CDC employees. Vaccine Adverse Event Reporting System (VAERS) searches and literature reviews for similar cases were performed prior to review. After CCCR discussion, AEFI were assessed for a causal relationship with vaccination and recommendations regarding future immunizations were relayed back to the referring physicians. In 2010, surveys were sent to referring physicians to determine the utility and effectiveness of the CCCR service. RESULTS: CISA investigators reviewed 76 cases during 68 conference calls between April 2004 and December 2009. Almost half of the cases (35/76) were neurological in nature. Similar AEFI for the specific vaccines received were discovered for 63 cases through VAERS searches and for 38 cases through PubMed searches. Causality assessment using the modified WHO criteria resulted in classifying 3 cases as definitely related to vaccine administration, 12 as probably related, 16 as possibly related, 18 as unlikely related, 10 as unrelated, and 17 had insufficient information to assign causality. The physician satisfaction survey was returned by 30 (57.7%) of those surveyed and a majority of respondents (93.3%) felt that the CCCR service was useful. CONCLUSIONS: The CCCR provides advice about AEFI to practitioners, assigns potential causality, and contributes to an improved understanding of adverse health events following immunizations. |
Increases in vaccination coverage of healthcare personnel following institutional requirements for influenza vaccination: a national survey of US hospitals
Miller BL , Ahmed F , Lindley MC , Wortley PM . Vaccine 2011 29 (50) 9398-403 BACKGROUND: Institutional requirements for influenza vaccination, ranging from policies that mandate declinations to those terminating unvaccinated healthcare personnel (HCP), are increasingly common in the US. Our objective was to determine HCP vaccine uptake following requirements for influenza vaccination at US hospitals. METHODS: Survey mailed in 2011 to a nationally representative sample of 998 acute care hospitals. An institutional requirement was defined as an institutional policy that requires receipt or declination of influenza vaccination, with or without consequences for vaccine refusal. Respondents reported institutional-level, seasonal influenza vaccination coverage, if known, during two consecutive influenza seasons: the season prior to (i.e., pre-requirement), and the first season of requirement (i.e., post-requirement). Weighted univariate and multivariate analyses accounted for sampling design and non-response. RESULTS: 808 (81.0%) hospitals responded. Of hospitals with institutional requirements for influenza vaccination (n=440), 228 hospitals met analytic inclusion criteria. Overall, mean reported institutional-level influenza vaccination coverage among HCP rose from 62.0% in the pre-requirement season to 76.6% in the post-requirement season, representing a single-season increase of 14.7 (95% CI: 12.6-16.7) percentage points. After adjusting for potential confounders, single-season increases in influenza vaccination uptake remained greater among hospitals that imposed consequences for vaccine refusal, and among hospitals with lower pre-requirement vaccination coverage. Institutional characteristics were not associated with vaccination increases of differential magnitude. CONCLUSION: Hospitals that are unable to improve suboptimal influenza vaccination coverage through multi-faceted, voluntary vaccination campaigns may consider institutional requirements for influenza vaccination. Rapid and measurable increases in vaccination coverage followed institutional requirements at hospitals of varying demographic characteristics. |
Structural gene (prME) chimeras of St Louis encephalitis virus and West Nile virus exhibit altered in vitro cytopathic and growth phenotypes.
Maharaj PD , Anishchenko M , Langevin SA , Fang Y , Reisen WK , Brault AC . J Gen Virol 2011 93 39-49 Despite utilizing the same avian hosts and mosquito vectors, St. Louis encephalitis virus (SLEV) and West Nile virus (WNV) display dissimilar vector infectivity and vertebrate pathogenic phenotypes. SLEV exhibits a low oral infection threshold for Culex mosquito vectors and is avirulent in avian hosts, producing low-magnitude viremias. In contrast, WNV is less orally infective to mosquitoes and elicits high-magnitude viremias in a wide range of avian species. In order to identify the genetic determinants of these different phenotypes and to assess the utility of mosquito and vertebrate cell lines for recapitulating in vivo differences observed between these viruses, reciprocal WNV and SLEV premembrane and envelope protein (prME) chimeric viruses were generated and growth of these mutant viruses characterized in mammalian (Vero), avian (duck) and mosquito cells [Aedes (C6/36) and Culex (CT)]. In both vertebrate lines, WNV grew to 100-fold higher titer than SLEV and growth and cytopathogenicity phenotypes, determined by chimeric phenotypes, were modulated by genetic elements outside of the prME gene region. Both chimeras exhibited distinctive growth patterns from SLEV in C6/36 cells, indicating the role of both structural and nonstructural gene regions for growth in this cell line. In contrast, growth of chimeric viruses was indistinguishable from the virus containing homologous prME genes in CT cells, indicating that structural genetic elements could specifically dictate growth differences of these viruses in relevant vectors. These data provide genetic insight into divergent enzootic maintenance strategies that could also be useful for the assessment of emergence mechanisms of closely related flaviviruses. |
Novel multitarget real-time PCR assay for rapid detection of Bordetella species in clinical specimens.
Tatti KM , Sparks KN , Boney KO , Tondella ML . J Clin Microbiol 2011 49 (12) 4059-66 A novel multi-target real-time PCR (R-PCR) assay for the rapid identification and speciation of Bordetella pertussis, B. parapertussis, and B. holmesii was developed using multi-copy insertion sequences (IS) in combination with the pertussis toxin subunit S1 (ptxS1) singleplex assay. The R-PCR targets for the multiplex assay include IS481 commonly found in B. pertussis and B. holmesii, IS1001 of B. parapertussis, and the IS1001-like sequence of B. holmesii. Overall, 402 Bordetella spp. and 66 non-Bordetella spp. isolates were tested in the multi-target assay. Cross-reactivity was found only with 5 B. bronchiseptica isolates which were positive with IS1001 of B. parapertussis. The lower limit of detection (LLOD) of the multiplex assay was similar to the LLOD of each target in an individual assay format which was approximately 1 genomic equivalent per reaction for all targets. A total of 197 human clinical specimens obtained during cough-illness outbreak investigations were used to evaluate the multi-target R-PCR assay. The multiplex assay results from 87 clinical specimens were compared to the individual R-PCR assays and culture. The multi-target assay is useful as a diagnostic tool to confirm B. pertussis infections and to rapidly identify other Bordetella species. In conclusion, the use of this multi-target R-PCR approach increases specificity, while decreasing the amount of time, reagents, and specimen necessary for R-PCR reactions used for accurate diagnosis of pertussis-like illness. |
Twenty-four hour human urine and serum profiles of bisphenol A during high-dietary exposure
Teeguarden JG , Calafat AM , Ye X , Doerge DR , Churchwell MI , Gunawan R , Graham MK . Toxicol Sci 2011 123 (1) 48-57 By virtue of its binding to steroid hormone receptors, bisphenol A (BPA, the unconjugated bioactive monomer) is hypothesized to be estrogenic when present in sufficient quantities in the body, raising concerns that widespread exposure to BPA may impact human health. To better understand the internal exposure of adult humans to BPA and the relationship between the serum and urinary pharmacokinetics of BPA, a clinical exposure study was conducted. Blood and urine samples were collected approximately hourly over a 24-h period from 20 adult volunteers who ingested 100% of one of three specified meals comprising standard grocery store food items for breakfast, lunch, and dinner. The volunteers' average consumption of BPA, estimated from the urinary excretion of total BPA ((TOT)BPA = conjugated BPA + BPA), was 0.27 mcg/kg body weight (range, 0.03-0.86), 21% greater than the 95th percentile of aggregate exposure in the adult U.S. population. A serum time course of (TOT)BPA was observable only in individuals with exposures 1.3-3.9 times higher than the 95th percentile of aggregate U.S. exposure. The (TOT)BPA urine concentration T(max) was 2.75 h (range, 0.75-5.75 h) post-meal, lagging the serum concentration T(max) by approximately 1 h. Serum (TOT)BPA area under the curve per unit BPA exposure was between 21.5 and 79.0 nM*h*kg/mcg BPA. Serum (TOT)BPA concentrations ranged from less than or equal to limit of detection (LOD, 1.3 nM) to 5.7 nM and were, on average, 42 times lower than urine concentrations. During these high dietary exposures, (TOT)BPA concentrations in serum were undetectable in 83% of the 320 samples collected and BPA concentrations were determined to be less than or equal to LOD in all samples. |
Bipolar diffusion charging of high-aspect ratio aerosols
Ku BK , Deye GJ , Kulkarni P , Baron PA . J Electrostat 2011 69 (6) 641-647 Recent studies have raised concerns over applicability of the conventional charging theories to non-spherical particles such as soot aggregates and single-walled carbon nanotube aerosols of complex shape and morphology. It is expected that the role of particle structure and shape on particle diffusion charging characteristics may be significant in the submicron size range for carbon nanotubes (CNTs) and nanofibers (CNFs). In this study, we report experimental data on equilibrium charging characteristics of high-aspect ratio aerosol particles such as CNFs and multi-walled CNTs (MWCNTs) when exposed to a bipolar ion atmosphere. A neutral fraction was measured, i.e., the fraction of particles carrying no electrical charge. A differential mobility analyzer (DMA) was used to classify aerosols, leaving a bipolar radioactive charger to infer the bipolar charging characteristics at different mobility diameters in the submicron size range. The measured neutral fractions for CNF aerosol particles were lower than the corresponding Boltzmann values by 24.4%, 42.0%, and 45.8% for mobility diameters of 400nm, 600nm, and 700nm, respectively, while the neutral fractions for measured aerodynamic diameters of 221nm, 242nm, and 254nm were much lower than those expected by Boltzmann charge distribution, by 43.8%, 63.1%, and 67.3%, respectively. Neutral fractions of spherical particles of polystyrene latex (PSL) and diethylhexyl sebacate (DEHS) particles, measured under identical experimental conditions and procedure, agreed well with the Boltzmann charge distribution. The measured neutral fractions for MWCNT aerosol particles were lower than the corresponding Boltzmann values by 22.3%-25.0% for mobility diameters in the size range from 279nm to 594nm. Charging-equivalent diameters of CNF particles correlated well with either mobility diameter or equal-area diameter, which were found to be larger than their mobility or equal-area diameters by up to a factor of 5 in the size range of 400nm-700nm, while those of MWCNT particles were larger than the corresponding diameters by a factor of 2 in the size range of 279nm-594nm. |
Comparative safety, immunogenicity, and efficacy of several anti-H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine)
Gambaryan AS , Lomakina NF , Boravleva EY , Kropotkina EA , Mashin VV , Krasilnikov IV , Klimov AI , Rudenko LG . Influenza Other Respir Viruses 2011 6 (3) 188-95 OBJECTIVE: Parallel testing of inactivated (split and whole virion) and live vaccine was conducted to compare the immunogenicity and protective efficacy against homologous and heterosubtypic challenge by H5N1 highly pathogenic avian influenza virus. METHOD: Four experimental live vaccines based on two H5N1 influenza virus strains were tested; two of them had hemagglutinin (HA) of A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site, and two others had hemagglutinins from attenuated H5N1 virus A/Chicken/Kurgan/3/05, with amino acid substitutions of Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and Lys131/Thr in HA2 while maintaining the polybasic HA cleavage site. The neuraminidase and non-glycoprotein genes of the experimental live vaccines were from H2N2 cold-adapted master strain A/Leningrad/134/17/57 (VN-Len and Ku-Len) or from the apathogenic H6N2 virus A/Gull/Moscow/3100/2006 (VN-Gull and Ku-Gull). Inactivated H5N1 and H1N1 and live H1N1 vaccine were used for comparison. All vaccines were applied in a single dose. Safety, immunogenicity, and protectivity against the challenge with HPAI H5N1 virus A/Chicken/Kurgan/3/05 were estimated. RESULTS: All experimental live H5 vaccines tested were apathogenic as determined by weight loss and conferred more than 90% protection against lethal challenge with A/Chicken/Kurgan/3/05 infection. Inactivated H1N1 vaccine in mice offered no protection against challenge with H5N1 virus, while live cold-adapted H1N1 vaccine reduced the mortality near to zero level. CONCLUSIONS: The high yield, safety, and protectivity of VN-Len and Ku-Len made them promising strains for the production of inactivated and live vaccines against H5N1 viruses. (Please cite this paper as: Gambaryan et al. (2011) Comparative safety, immunogenicity, and efficacy of several anti-H5N1 influenza experimental vaccines in a mouse and chicken models. Parallel testing of killed and live H5 vaccine. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00291.x.) |
A national profile of health care and family impacts of children with muscular dystrophy and special health care needs in the United States
Ouyang L , Grosse SD , Fox MH , Bolen J . J Child Neurol 2011 27 (5) 569-76 We used the 2005-2006 National Survey of Children with Special Health Care Needs to compare 3 types of outcomes between children with and those without parental reported muscular dystrophy: (1) functional limitations; (2) health care experiences in terms of the 5 components of a medical home; and (3) family impacts, including financial or out-of-pocket costs and parental employment and time use. We used weighted logistic regression to examine their associations with muscular dystrophy after adjustment for socio-demographic characteristics. Among children with special health care needs, children with reported muscular dystrophy were much more likely to have difficulties with ambulation and self-care. They were more likely to have family members who reported financial problems, reduced or stopped employment, and spent more than 10 hours weekly providing or coordinating care. Muscular dystrophy was not associated with the likelihood of having a medical home after adjustment for socioeconomic status and other socio-demographic characteristics. |
Do foreign- and U.S.-born mothers across racial/ethnic groups have a similar risk profile for selected sociodemographic and periconceptional factors?
Ramadhani TA , Canfield MA , Farag NH , Royle M , Correa A , Waller DK , Scheuerle A . Birth Defects Res A Clin Mol Teratol 2011 91 (9) 823-830 BACKGROUND: We examined differences in selected pregnancy-related risk factors, including maternal sociodemographic characteristics, health-related conditions, and periconceptional behavioral factors, among foreign-born versus U.S.-born control mothers across race/ethnic groups. METHODS: We used data from the National Birth Defects Prevention Study, and calculated odds ratios (ORs) and 95% confidence intervals (CIs) of the risk factors, for foreign-born Hispanic, non-Hispanic white, non-Hispanic black, and Asian/Pacific Islander (API) mothers, compared to their U.S.-born counterparts. RESULTS: Across all race/ethnic groups, foreign-born mothers were older and had lower odds of obesity compared to their U.S.-born counterparts. With the exception of foreign-born black mothers, foreign-born mothers from other race/ethnic groups had significantly lower odds of binge drinking during the periconceptional period. Compared to U.S.-born, foreign-born Hispanic mothers had twice the odds of gestational diabetes (OR = 2.23; 95% CI = 1.36-3.66). Certain health behaviors were less prevalent in foreign-born black mothers (e.g., folic acid use; OR = 0.54; 95% CI = 0.31-0.96) and foreign-born API mothers (e.g., cigarette smoking; OR = 0.10; 95% CI = 0.02-0.48). CONCLUSIONS: Significant differences in pregnancy related risk factors during the periconceptional period and throughout pregnancy were observed between maternal nativity groups and across race/ethnicity. Prevention efforts for both prepregnancy and after conception should be designed and delivered according to maternal nativity for each racial/ethnic group. Birth Defects Research (Part A), 2011. (c) 2011 Wiley-Liss, Inc. |
Maternal occupational pesticide exposure and risk of hypospadias in the National Birth Defects Prevention Study
Rocheleau CM , Romitti PA , Sanderson WT , Sun L , Lawson CC , Waters MA , Stewart PA , Olney RS , Reefhuis J . Birth Defects Res A Clin Mol Teratol 2011 91 (11) 927-36 BACKGROUND: Hypospadias is a common congenital malformation among men in which the urethral opening is ventrally displaced. Pesticide exposure has been suggested as a possible etiologic factor, but previous epidemiologic studies have produced inconsistent results. METHODS: We used data from the National Birth Defects Prevention Study (NBDPS), a population-based case-control study, to examine maternal occupational exposure to fungicides, insecticides, and herbicides among 647 hypospadias case infants and 1496 unaffected male control infants with estimated delivery dates from October 1997 to December 2002. Periconceptional (1 month before conception through the first trimester of pregnancy) pesticide exposures were assigned by an expert rater, assisted by a job-exposure matrix (JEM), from a job history completed by mothers during a telephone interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with multivariable logistic regression, and adjusted for relevant covariates. RESULTS: Maternal periconceptional occupational exposure to any pesticides (yes/no) was not associated with an increased risk of hypospadias (OR = 0.78; 95% CI = 0.61-1.01). Maternal occupational periconceptional pesticide exposure type (insecticides, fungicides, and herbicides) and estimated quantity also showed no significantly increased risk of hypospadias and no evidence of a dose-response relationship; however, the estimated pesticide exposure levels in this population were low. CONCLUSION: Using broad classes of insecticides, herbicides, and fungicides, we found no evidence that low intensity maternal periconceptional occupational pesticide exposure was a risk factor for hypospadias. Birth Defects Research (Part A) 2011. (c) 2011 Wiley-Liss, Inc. |
Exposure characterization of metal oxide nanoparticles in the workplace
Curwin B , Bertke S . J Occup Environ Hyg 2011 8 (10) 580-7 This study presents exposure data for various metal oxides in facilities that produce or use nanoscale metal oxides. Exposure assessment surveys were conducted at seven facilities encompassing small, medium, and large manufacturers and end users of nanoscale (particles <0.1 mum diameter) metal oxides, including the oxides of titanium, magnesium, yttrium, aluminum, calcium, and iron. Half- and full-shift sampling consisting of various direct-reading and mass-based area and personal aerosol sampling was employed to measure exposure for various tasks. Workers in large facilities performing handling tasks had the highest mass concentrations for all analytes. However, higher mass concentrations occurred in medium facilities and during production for all analytes in area samples. Medium-sized facilities had higher particle number concentrations in the air, followed by small facilities for all particle sizes measured. Production processes generally had the highest particle number concentrations, particularly for the smaller particles. Similar to particle number, the medium-sized facilities and production process had the highest particle surface area concentration. TEM analysis confirmed the presence of the specific metal oxides particles of interest, and the majority of the particles were agglomerated, with the predominant particle size being between 0.1 and 1 mum. The greatest potential for exposure to workers occurred during the handling process. However, the exposure is occurring at levels that are well below established and proposed limits. |
Feasibility of using a World Health Organization-standard methodology for Sample Vital Registration with Verbal Autopsy (SAVVY) to report leading causes of death in Zambia: results of a pilot in four provinces, 2010
Mudenda SS , Kamocha S , Mswia R , Conkling M , Sikanyiti P , Potter D , Mayaka WC , Marx MA . Popul Health Metr 2011 9 40 BACKGROUND: Verbal autopsy (VA) can be used to describe leading causes of death in countries like Zambia where vital events registration does not produce usable data. The objectives of this study were to assess the feasibility of using verbal autopsy to determine age-, sex-, and cause-specific mortality in a community-based setting in Zambia and to estimate overall age-, sex-, and cause-specific mortality in the four provinces sampled. METHODS: A dedicated census was conducted in regions of four provinces chosen by cluster-sampling methods in January 2010. Deaths in the 12-month period prior to the census were identified during the census. Subsequently, trained field staff conducted verbal autopsy interviews with caregivers or close relatives of the deceased using structured and unstructured questionnaires. Additional deaths were identified and respondents were interviewed during 12 months of fieldwork. After the interviews, two physicians independently reviewed each VA questionnaire to determine a probable cause of death. RESULTS: Among the four provinces (1,056 total deaths) assessed, all-cause mortality rate was 17.2 per 1,000 person-years (95% confidence interval [CI]: 12.4, 22). The seven leading causes of death were HIV/AIDS (287, 27%), malaria (111, 10%), injuries and accidents (81, 8%), diseases of the circulatory system (75, 7%), malnutrition (58, 6%), pneumonia (56, 5%), and tuberculosis (50, 5%). Those who died were more likely to be male, have less than or equal to a primary education, and be unmarried, widowed, or divorced compared to the baseline population. Nearly half (49%) of all reported deaths occurred at home. CONCLUSIONS: The 17.2 per 1,000 all-cause mortality rate is somewhat similar to modeled country estimates. The leading causes of death -- HIV/AIDS, malaria, injuries, circulatory diseases, and malnutrition -- reflected causes similar to those reported for the African region and by other countries in the region. Results can enable the targeting of interventions by region, disease, and population to reduce preventable death. Collecting vital statistics using standardized Sample Vital Registration with Verbal Autopsy (SAVVY) methods appears feasible in Zambia. If conducted regularly, these data can be used to evaluate trends in estimated causes of death over time. |
Deaths: leading causes for 2007
Heron M . Natl Vital Stat Rep 2011 59 (8) 1-95 OBJECTIVES: This report presents final 2007 data on the 10 leading causes of death in the United States by age, race, sex, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the Division of Vital Statistics' annual report of final mortality statistics. METHODS: Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2007. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. RESULTS: In 2007, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Cerebrovascular diseases; Chronic lower respiratory diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Septicemia. They accounted for approximately 76 percent of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2007 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. |
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