Update of HPV-associated female genital cancers in the United States, 1999-2004
Watson M , Saraiya M , Wu X . J Womens Health (Larchmt) 2009 18 (11) 1731-8 In 2008, CDC published a supplement to the journal Cancer describing incidence patterns of human papillomavirus (HPV)-associated cancers prior to availability of an HPV vaccine. This report updates the information on HPV-associated female genital cancer incidence with more recent data, adds information on trends, and includes American Indian/Alaska Native (AI/AN) populations. We used combined data from two federal cancer surveillance programs, CDC's National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology, and End Results (SEER) Program, covering 92% of the U.S. population from 1999 to 2004, to examine recent trends and incidence of invasive cervical carcinoma and vaginal and vulvar squamous cell carcinoma (SCC). Incidence of in situ vaginal and vulvar SCC are also presented. The average annual age-adjusted rate of cervical cancer among women of all races/ethnicities was 8.5/100,000. Annual cervical cancer incidence rates were highest but declined more rapidly among Hispanic and black women compared with non-Hispanic and white women. The rate of vulvar cancer among all women was 1.7/100,000 and was higher among white women than other racial groups. Vulvar cancer rates rose among black women (+2.9% per year) and were relatively stable among all other racial and ethnic groups over the 6-year period. Vaginal cancer was rare (rate 0.5/100,000); the rate was higher among black women than other racial groups and higher among Hispanic women than among non-Hispanic women. A significant decline of vaginal cancer was observed only among black women (-6.2% per year). This article confirms previous findings on racial disparities in HPV-associated female genital cancers. Any post-HPV vaccine declines in these cancers should be interpreted in light of current declines. Enhancing current cancer surveillance systems, combined with special studies to collect data on in situ or precancerous lesions of these cancers, will provide important information in determining the potential impact of the HPV vaccine. |
Diabetes trends in hospitalized HIV-infected persons in the United States, 1994-2004
Kourtis AP , Bansil P , Kahn HS , Posner SF , Jamieson DJ . Curr HIV Res 2009 7 (5) 481-6 The prevalence of diabetes in the United States is rising. As HIV-infected people live longer, they become more susceptible to chronic diseases such as diabetes. Additionally, some antiretroviral agents have been linked to impaired glucose tolerance and increased diabetes risk. To estimate the burden and trends of diabetes among hospitalized HIV-infected persons in the United States, we used data from the 1994-2004 Nationwide Inpatient Sample, a nationally representative survey of inpatient hospitalizations. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for demographic and hospital characteristics using logistic regression. Between 1994 and 2004, the rate of hospitalizations with a diabetes code per 100 hospitalizations increased from 3.9 to 8.4 (2.2 fold) among HIV-infected persons. Among HIV-uninfected people, the corresponding rate increased from 12.8 to 17.7 (1.4 fold). Since 1998, the mean age of HIV-infected hospitalized people with a diabetes diagnosis rose from 45 to 66 years and became similar to that of HIV-uninfected people. Compared to 1994-1996, in 2002-2004 the probability of hospitalizations with diabetes increased among both HIV-infected and HIV-uninfected persons (OR, 1.92, 95% CI, 1.79-2.05 and OR, 1.38, 95% CI, 1.36-1.40, respectively). Given the increasing prevalence of diabetes in hospitalized HIV-infected persons, it will be important to monitor the trends closely in addition to the effects of different types of antiretroviral regimens, in order to optimize comprehensive long-term care of HIV-infected persons. |
Linezolid in the treatment of multidrug-resistant tuberculosis
Schecter GF , Scott C , True L , Raftery A , Flood J , Mase S . Clin Infect Dis 2009 50 (1) 49-55 BACKGROUND: Linezolid is a new antibiotic with activity against Mycobacterium tuberculosis in vitro and in animal studies. Several small case series suggest that linezolid is poorly tolerated because of the side effects of anemia/thrombocytopenia and peripheral neuropathy. To characterize our clinical experience with linezolid, the California Department of Public Health Tuberculosis Control Branch's Multidrug-Resistant Tuberculosis (MDR-TB) Service reviewed cases in which the MDR-TB treatment regimens included linezolid therapy. METHODS: Record review was performed for 30 patients treated with linezolid as part of an MDR-TB regimen. Data were collected on clinical and microbiological characteristics, linezolid tolerability, and treatment outcomes. The dosage of linezolid was 600 mg daily. Vitamin B6 at a dosage of 50-100 mg daily was used to mitigate hematologic toxicity. RESULTS: During 2003-2007, 30 patients received linezolid for the treatment of MDR-TB. Patients had isolates resistant to a median of 5 drugs (range, 2-13 drugs). Of the 30 cases, 29 (97%) were pulmonary; of these 29, 21 (72%) had positive results of acid-fast bacilli smear, and 16 (55%) were cavitary. Culture conversion occurred in all pulmonary cases at a median of 7 weeks. At data censure (31 December 2008), 22 (73%) of 30 patients had successfully completed treatment. Five continued to receive treatment. There were no deaths. Three patients had a poor outcome, including 2 defaults and 1 treatment failure. Side effects occurred in 9 patients, including peripheral and optic neuropathy, anemia/thrombocytopenia, rash, and diarrhea. However, only 3 patients stopped linezolid treatment because of side effects. CONCLUSIONS: Linezolid was well tolerated, had low rates of discontinuation, and may have efficacy in the treatment of MDR-TB. |
Pandemic H1N1 and the 2009 Hajj
Ebrahim SH , Memish ZA , Uyeki TM , Khoja TA , Marano N , McNabb SJ . Science 2009 326 (5955) 938-40 It will take vigilance, commitment, and action by all global stakeholders to reduce the potential impact of pandemic influenza during the upcoming Hajj pilgrimage. |
Pandemic influenza preparedness and response among immigrants and refugees
Truman BI , Tinker T , Vaughan E , Kapella BK , Brenden M , Woznica CV , Rios E , Lichtveld M . Am J Public Health 2009 99 S278-86 Some immigrants and refugees might be more vulnerable than other groups to pandemic influenza because of preexisting health and social disparities, migration history, and living conditions in the United States. Vulnerable populations and their service providers need information to overcome limited resources, inaccessible health services, limited English proficiency and foreign language barriers, cross-cultural misunderstanding, and inexperience applying recommended guidelines. To increase the utility of guidelines, we searched the literature, synthesized relevant findings, and examined their implications for vulnerable populations and stakeholders. Here we summarize advice from an expert panel of public health scientists and service program managers who attended a meeting convened by the Centers for Disease Control and Prevention, May 1 and 2, 2008, in Atlanta, Georgia. |
Role of the primary care safety net in pandemic influenza
Rust G , Melbourne M , Truman BI , Daniels E , Fry-Johnson Y , Curtin T . Am J Public Health 2009 99 S316-23 An influenza pandemic would have a disproportionately adverse impact on minority populations, the poor, the uninsured, and those living in underserved communities. Primary care practices serving the underserved would face special challenges in an influenza pandemic. Although not a formalized system, components of the primary care safety net include federally qualified health centers, public hospital clinics, volunteer or free clinics, and some local public health units. In the event of an influenza pandemic, the primary care safety net is needed to treat vulnerable populations and to provide health care surge capacity to prevent the overwhelming of hospital emergency departments. We examined the strength, capacity, and preparedness of key components of the primary care safety net in responding to pandemic influenza. |
Clinical performance of a rapid influenza test and comparison of nasal versus throat swabs to detect 2009 pandemic influenza A (H1N1) infection in Thai children
Suntarattiwong P , Jarman RG , Levy J , Baggett HC , Gibbons RV , Chotpitayasunondh T , Simmerman JM . Pediatr Infect Dis J 2009 29 (4) 366-7 We identified febrile pediatric outpatients seeking care for influenza like illness in Bangkok. Two nasal and 1 throat swab were tested using the QuickVue A+B rapid influenza kit and reverse transcription-polymerase chain reaction. Among 142 pandemic influenza A (H1N1)-positive patients, the QuickVue test identified 89 positive tests for a sensitivity of 62.7% (95% confidence interval [CI]: 54.7-70.6). Specificity was 99.2% (95% CI: 98-100). In the 0 to 2 years age group, sensitivity was 76.7% (95% CI: 61.5-91.8). Throat and nasal swabs are equally useful diagnostic specimens for reverse transcription-polymerase chain reaction diagnosis. |
A cluster-randomized trial of enhanced labor ward-based PMTCT services to increase nevirapine coverage in Lusaka, Zambia
Megazzini KM , Sinkala M , Vermund SH , Redden DT , Krebs DW , Acosta EP , Mwanza J , Goldenberg RL , Chintu N , Bulterys M , Stringer JS . AIDS 2009 24 (3) 447-55 OBJECTIVE: Determine whether enhanced labor ward-based services for prevention of mother-to-child transmission of HIV (PMTCT) would improve nevirapine (NVP) coverage. DESIGN: Cluster-randomized trial at 12 public-sector delivery centers in Lusaka, Zambia. METHODS: Following a baseline surveillance period, 12 labor wards were randomized, six to offer opt-in HIV testing to women of unknown serostatus (with NVP administration as indicated) and to assess NVP adherence among known HIV-infected women. The six control labor wards provided the standard of care. The NVP coverage endpoint was defined as the proportion of HIV-infected/exposed women/infant pairs with confirmed NVP ingestion. We used generalized estimating equations (GEE) to determine the odds of coverage associated with the intervention and ultimately used the parameters for the estimated GEE model to estimate relative risk. RESULTS: Between October 2005 and January 2006, 7664 women gave birth at participating clinics. We collected anonymous-linked blood from 7592 (99%) umbilical cords; tested 7438 (97%) for HIV, 1618 (22%) were seropositive, and of these, 1279 (79%) were tested for NVP. At baseline (preintervention), the probability of HIV-infected/exposed women/infant pairs receiving NVP in treatment clinics (42%) was 0.89 times the probability of being covered in control clinics (53%) whereas during the intervention period the probability of treatment clinic coverage (52%) was 1.22 the probability control clinic coverage (43%), representing a multiplicative effect of 1.37 upon the RR at baseline (ratio of relative risks 1.37, bootstrapped 95% CI, 1.04-1.77). CONCLUSION: Labor ward-based PMTCT programs are feasible and can have a significant, positive impact on NVP coverage. |
Evaluation of seasonal patterns of Kawasaki syndrome- and rotavirus-associated hospitalizations in California and New York, 2000-2005
MacNeil A , Holman RC , Yorita KL , Steiner CA , Parashar UD , Belay ED . BMC Pediatr 2009 9 65 BACKGROUND: Kawasaki Syndrome (KS) is an uncommon childhood disease with unknown etiology. It has been suggested that rotavirus infection may play a causative role in the development of KS. METHODS: To examine potential temporal associations between KS and rotavirus infection, seasonal patterns of KS- and rotavirus-associated hospitalizations among children in California and New York during 2000-2005 were compared. RESULTS: Rotavirus hospital admissions were markedly winter seasonal, with very few summer hospitalizations. KS hospitalizations occurred year-round but also peaked slightly during winter and spring. CONCLUSION: The strong winter seasonal pattern of rotavirus clearly differed from the year-round pattern of KS hospitalizations. While the present study cannot completely rule out rotavirus as having a role in the development of KS, other agents must be involved in the etiology of KS. |
Incidence, seasonality and mortality associated with influenza pneumonia in Thailand: 2005-2008
Simmerman JM , Chittaganpitch M , Levy J , Chantra S , Maloney S , Uyeki T , Areerat P , Thamthitiwat S , Olsen SJ , Fry A , Ungchusak K , Baggett HC , Chunsuttiwat S . PLoS One 2009 4 (11) e7776 BACKGROUND: Data on the incidence, seasonality and mortality associated with influenza in subtropical low and middle income countries are limited. Prospective data from multiple years are needed to develop vaccine policy and treatment guidelines, and improve pandemic preparedness. METHODS: During January 2005 through December 2008, we used an active, population-based surveillance system to prospectively identify hospitalized pneumonia cases with influenza confirmed by reverse transcriptase-polymerase chain reaction or cell culture in 20 hospitals in two provinces in Thailand. Age-specific incidence was calculated and extrapolated to estimate national annual influenza pneumonia hospital admissions and in-hospital deaths. RESULTS: Influenza was identified in 1,346 (10.4%) of pneumonia patients of all ages, and 10 influenza pneumonia patients died while in the hospital. 702 (52%) influenza pneumonia patients were less than 15 years of age. The average annual incidence of influenza pneumonia was greatest in children less than 5 years of age (236 per 100,000) and in those age 75 or older (375 per 100,000). During 2005, 2006 and 2008 influenza A virus detection among pneumonia cases peaked during June through October. In 2007 a sharp increase was observed during the months of January through April. Influenza B virus infections did not demonstrate a consistent seasonal pattern. Influenza pneumonia incidence was high in 2005, a year when influenza A(H3N2) subtype virus strains predominated, low in 2006 when A(H1N1) viruses were more common, moderate in 2007 when H3N2 and influenza B co-predominated, and high again in 2008 when influenza B viruses were most common. During 2005-2008, influenza pneumonia resulted in an estimated annual average 36,413 hospital admissions and 322 in-hospital pneumonia deaths in Thailand. CONCLUSION: Influenza virus infection is an important cause of hospitalized pneumonia in Thailand. Young children and the elderly are most affected and in-hospital deaths are more common than previously appreciated. Influenza occurs year-round and tends to follow a bimodal seasonal pattern with substantial variability. The disease burden varies significantly from year to year. Our findings support a recent Thailand Ministry of Public Health (MOPH) decision to extend annual influenza vaccination to older adults and suggest that children should also be targeted for routine vaccination. |
Invasive pneumococcal disease in Alaskan children: impact of the seven-valent pneumococcal conjugate vaccine and the role of water supply
Wenger JD , Zulz T , Bruden D , Singleton R , Bruce MG , Bulkow L , Parks D , Rudolph K , Hurlburt D , Ritter T , Klejka J , Hennessy T . Pediatr Infect Dis J 2009 29 (3) 251-6 BACKGROUND: Alaska Native (AN) children, especially those in the Yukon-Kuskokwim region (YK-AN children), suffer some of the highest rates of invasive pneumococcal disease (IPD) in the world. Rates of IPD declined after statewide introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2001, but increased in subsequent years. METHODS: Population-based laboratory surveillance data (1986-2007) for invasive Streptococcus pneumoniae infection in Alaskan children <5 years old were used to evaluate the association of IPD rates and serotype distribution with immunization, socioeconomic status, and in-home water service. RESULTS: Introduction of PCV7 vaccine resulted in elimination of IPD caused by vaccine serotypes, but was followed by increasing rates of IPD caused by nonvaccine serotypes. Among YK-AN children IPD rates dropped by 60%, but then rose due to non-PCV7 serotypes to levels 5- to 10-fold higher than rates in non-YK-AN children and non-AN children. IPD rates in YK-AN children were twice as high in villages where <10% of houses had in-home piped water compared with villages where more than 80% of houses had in-home piped water (390 cases/100,000 vs. 146 cases/100,000, P = 0.008). CONCLUSIONS: High IPD rates in Alaska are associated with lack of in-home piped water (controlling for household crowding and per capita income). The effect of in-home piped water is most likely mediated through reduced water supply leading to limitations on handwashing. |
Isoniazid tuberculosis preventive therapy in HIV-infected adults accessing antiretroviral therapy: a Botswana experience, 2004-2006
Mosimaneotsile B , Mathoma A , Chengeta B , Nyirenda S , Agizew TB , Tedla Z , Motsamai OI , Kilmarx PH , Wells CD , Samandari T . J Acquir Immune Defic Syndr 2009 54 (1) 71-7 OBJECTIVES: To describe reasons for exclusion from isoniazid tuberculosis preventive therapy (IPT) and outcomes of persons living with HIV (PLWH) during 6 months of IPT. METHODS: In a clinical trial conducted in government clinics, first screening (screen 1) used National IPT Program guidelines and a second screening (screen 2) was trial specific. Adherence was defined as attending 6 monthly visits. RESULTS: Between 2004 and 2006, at 4018 screening visits, 2934 (73%) PLWH met screen 1 criteria; 1995 (68%) met screen 2 criteria and were enrolled. Major reasons for exclusion were illness (66%) at screen 1 and abnormal chest radiographs (36%) at screen 2. Tuberculin skin tests were ≥5 mm in 24% of those enrolled and 31% had CD4 lymphocyte counts <200 cells/mm. During the 6 months, 8 (0.40%) developed tuberculosis disease, 28 (1.4%) had severe adverse events (19/28 were hepatitis including one death probably isoniazid-associated), 20 others died, and 22% initiated antiretroviral therapy (ART). Although adherence was 86%, being on ART improved adherence: relative risk 1.41 (95% confidence limits 1.04-1.91). In multivariate analysis, ART was associated with a 4.38 greater odds of adherence to IPT. CONCLUSIONS: Six months of IPT was relatively safe and well-tolerated by PLWH. Adherence to IPT was significantly better among those receiving ART with IPT. |
Chemical risk assessment and uncertainty associated with extrapolation across exposure duration
Pohl H , Sj Chou CH , Ruiz P , Holler J . Regul Toxicol Pharmacol 2009 57 (1) 18-23 The Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on priority substances in which available epidemiologic and toxicologic data are reviewed, summarized, and interpreted. When adequate data are available, ATSDR derives health guidance values called minimal risk levels (MRLs) for acute, intermediate, and chronic durations of exposure for oral and inhalation routes of exposure. The MRLs are generally derived by use of the no-observed-adverse-effect level (NOAEL) or the lowest-observed-adverse-effect level / uncertainty factor (LOAEL/UF) approach. The UF usually employed are for LOAEL- to- NOAEL extrapolation, animal to -human extrapolation, and inter-human variability. These health guidance values are intended to serve as screening tools for health assessors and other responders to identify contaminants of concern and potential health effects in the community at hazardous waste sites and during unplanned releases. When guidance values are not available for a specific exposure scenario because of a lack of chronic data, extrapolation across exposure durations may be made. For example, chronic guidance values may be derived from subchronic data by applying an additional uncertainty factor of 10 for extrapolation to chronic exposure duration. In this paper, we analyzed the ratio of chemical-specific LOAELs from acute to intermediate and from intermediate to chronic durations for oral and inhalation exposure routes. In addition, we investigated the impact of chemical structure and chemical structure activity relationship on validation of predictions across exposure durations. |
Survey of nonsusceptible nasopharyngeal streptococcus pneumoniae isolates in children attending day-care centers in Brazil
Franco CM , Andrade AL , Andrade JG , Silva SA , Oliveira CR , Pimenta FC , Lamaro-Cardoso J , Brandao AP , Almeida SC , Calix JJ , Nahm MH , de Cunto Brandileone MC . Pediatr Infect Dis J 2009 29 (1) 77-9 A survey of nasopharyngeal carriage of penicillin nonsusceptible pneumococcal (PNSp) isolates was conducted among 1192 children attending 62 day care centers in Brazil, where pneumococcal vaccination has not been routinely introduced. Nasopharyngeal pneumococcal carriage was detected in 686 (57.6%) infants, and 178 (25.9%) of them carried PNSp isolates. Being less than 24 months of age, hospitalization in the previous 3 months, and recurrent acute otitis media were independently associated with PNSp. Serotypes 14, 23F, 19A, 6A, 6B and 19F were the most common serotype isolated accounting for 80% of the PNSp. A high proportion (35/332) of non-(sero)typeable isolates was detected, 62.9% of them PNSp. Serotypes coverage projected for the pneumococcal conjugate vaccine (PCV) 13-valent vaccine (72%) was significantly higher compared with PCV7 (58.4%) and PCV 10-valent vaccine (59.3%). |
Epidemiology of rabies post-exposure prophylaxis--United States of America, 2006-2008
Christian KA , Blanton JD , Auslander M , Rupprecht CE . Vaccine 2009 27 (51) 7156-61 BACKGROUND: The United States of America (USA) does not have a national reporting system for rabies post-exposure prophylaxis (PEP). We describe the epidemiology of PEP in the USA so recommendations can be made during a PEP shortage. METHODS: A two-part questionnaire designed to evaluate PEP distribution practices and estimate PEP use was administered to state health department representatives. RESULTS: Seventy-five percent of participants responded that no public health guidance was needed to make a recommendation for PEP. The annual national average PEP use is 23,415 courses of PEP (range: 10,645-35,845). CONCLUSION: PEP is loosely monitored and a precise estimate of PEP use is unknown. Improved national surveillance for PEP is needed. |
Evolving public health approaches to the global challenge of foodborne infections
Tauxe RV , Doyle MP , Kuchenmuller T , Schlundt J , Stein CE . Int J Food Microbiol 2009 139 S16-28 The landscape of foodborne infections is in flux. New pathogens emerge, established pathogens may acquire new characteristics and appear in unexpected food vehicles, while many existing problems remain unsolved. Consumers want more fresh foods year round, populations age and migrate, and the technologies and trade practices that produce foods change. Protecting the public health and minimizing the burden of foodborne illness mean expecting the unexpected, and being prepared to understand it when it occurs, so that prevention can be improved. Public health surveillance is also constantly evolving, as new diseases emerge and are judged worthy of notification, as new diagnostic tests change the ease and specificity of routine diagnosis and as social interest in particular issues waxes and wanes. Accurate health information, including reliable estimates of the burden of foodborne disease, can improve foodborne disease prevention, foster global health security, promote economic growth and development and strengthen evidence-based policy making. |
Evaluation of the discriminative accuracy of genomic profiling in the prediction of common complex diseases.
Moonesinghe R , Liu T , Khoury MJ . Eur J Hum Genet 2009 18 (4) 485-9 Genetic testing for susceptibility to common diseases based on a combination of genetic markers may be needed because the effect size associated with each genetic marker is small. Whether or not a genome profile based on a combination of markers could yield a useful test can be evaluated by assessing the discriminative accuracy. The authors present a simple method to calculate the clinical discriminative accuracy of a genomic profile when the relative risk and genotype frequency of each genotype are known. In addition, the clinical discriminative accuracy of a genetic test is presented for given values of the heritability and prevalence of the disease and for the population-attributable fraction of the combined genetic markers. For given values of relative risk and genotype frequency, the discriminative accuracy increases with increasing heritability but declines with increasing prevalence of the disease. For a given value of population-attributable fraction, the discriminative accuracy increases with increasing relative risks, but declines with increasing genotype frequency. On the basis of population-attributable fraction and estimates of heritability of disease, the number of risk genotypes required to have a reasonable clinical discriminative accuracy is much higher than the genome profiles available at present.European Journal of Human Genetics advance online publication, 25 November 2009; doi:10.1038/ejhg.2009.209. |
Using lifetime risk estimates in personal genomic profiles: estimation of uncertainty.
Yang Q , Flanders WD , Moonesinghe R , Ioannidis JP , Guessous I , Khoury MJ . Am J Hum Genet 2009 85 (6) 786-800 Personal genome tests are now offered direct-to-consumer (DTC) via genetic variants identified by genome-wide association studies (GWAS) for common diseases. Tests report risk estimates (age-specific and lifetime) for various diseases based on genotypes at multiple loci. However, uncertainty surrounding such risk estimates has not been systematically investigated. With breast cancer as an example, we examined the combined effect of uncertainties in population incidence rates, genotype frequency, effect sizes, and models of joint effects among genetic variants on lifetime risk estimates. We performed simulations to estimate lifetime breast cancer risk for carriers and noncarriers of genetic variants. We derived population-based cancer incidence rates from Surveillance, Epidemiology, and End Results (SEER) Program and comparative international data. We used data for non-Hispanic white women from 2003 to 2005. We derived genotype frequencies and effect sizes from published GWAS and meta-analyses. For a single genetic variant in FGFR2 gene (rs2981582), combination of uncertainty in these parameters produced risk estimates where upper and lower 95% simulation intervals differed by more than 3-fold. Difference in population incidence rates was the largest contributor to variation in risk estimates. For a panel of five genetic variants, estimated lifetime risk of developing breast cancer before age 80 for a woman that carried all risk variants ranged from 6.1% to 21%, depending on assumptions of additive or multiplicative joint effects and breast cancer incidence rates. Epidemiologic parameters involved in computation of disease risk have substantial uncertainty, and cumulative uncertainty should be properly recognized. Reliance on point estimates alone could be seriously misleading. |
A genetic test registry: bringing credible and actionable data together.
Khoury MJ , Reyes M , Gwinn M , Feero WG . Public Health Genomics 2009 13 (6) 360-1 Javitt et al. [1]propose a blueprint for a mandated genetic test registry to support informed health care decision making. According to the authors, the core aim of the registry is ‘to promote transparency, which includes disclosure of both what is known and what is not known.’ They propose that for each test, the registry should include not only a description of the test and its intended use, but also information about its analytic and clinical validity, clinical utility, and proficiency testing. | We agree that reporting data on validity and utility is an essential element of quality assurance in genetic testing. Nevertheless, whether reporting to a genetic test registry is mandated or not, there is a fundamental challenge in implementation of such a registry, particularly with regard to the sources, standards and quality of submitted data and their systematic evaluation. As acknowledged by the authors, laboratories performing genetic tests may have only some of the data needed to evaluate validity and utility of tests. In particular, information on clinical validity and utility will have to be brought together from multiple sources, including basic research, clinical trials, and epidemiological and clinical studies. The available information is frequently fragmented, sometimes contradictory, or simply not available. Thus, a comprehensive assessment of clinical validity and utility requires knowledge synthesis in the form of systematic evidence reviews from multiple sources. Most laboratories are currently not equipped to conduct such analyses. |
Male circumcision to reduce the risk of HIV and sexually transmitted infections among men who have sex with men
Templeton DJ , Millett GA , Grulich AE . Curr Opin Infect Dis 2009 23 (1) 45-52 PURPOSE OF REVIEW: The success of male circumcision in reducing HIV acquisition among African heterosexuals has led to renewed interest in this biological intervention for HIV/sexually transmissible infection (STI) prevention in men who have sex with men (MSM). This review summarizes the available data on the association of circumcision and HIV/STI among MSM populations. RECENT FINDINGS: Results of observational studies indicate that circumcision has limited impact on HIV/STI acquisition among MSM populations overall. Longitudinal data suggest that circumcision may reduce the risk of incident syphilis, but there is little evidence of a protective effect for other STIs. The subgroup of MSM who predominantly practise the insertive role in anal intercourse may be at lower risk of HIV, although the relative inefficiency of HIV acquisition for insertive compared with receptive partners has resulted in imprecise estimates of effect. SUMMARY: The evidence that circumcision reduces HIV and other STIs among MSM is weak and inconsistent. However, recent studies have found that circumcised MSM who predominantly take the insertive role in anal intercourse may be at a lower risk of HIV infection. Although MSM may be willing to undergo adult circumcision, should it be proven to reduce HIV acquisition risk, there is substantial potential that behavioural disinhibition could offset any benefits achieved by a circumcision intervention. |
Pap testing and sexual activity among young women in the United States
Saraiya M , Martinez G , Glaser K , Kulasingam S . Obstet Gynecol 2009 114 (6) 1213-1219 OBJECTIVE: To understand whether and how recency of sexual activity is associated with Pap testing rates among young women. METHODS: We analyzed data on self-reported receipt of Pap testing and initiation of sexual activity among young women and girls aged 15 to 24 years using the 2002 National Survey of Family Growth, an in-person, population-based survey of reproductive-aged men and women in the United States. The primary outcome was receiving a Pap test and its relationship to initiation of sexual activity. A multivariable model was used to predict the probability of having had a Pap test in the previous 12 months. RESULTS: Thirty-three percent of the 2,513 women had never had sex. Of these, 13.9% had had a Pap test in the previous year. Sixty-seven percent of sexually-active women aged 15-24 reported receiving a Pap test (corresponding to 13.1 million tests). Approximately 59% women aged 15-20 years old who reported having initiated sexual activity in the previous 3 years also reported a Pap test in the previous year. CONCLUSION: The current guidelines recommend screening 3 years after initiation of vaginal intercourse or at age 21, whichever is earlier. Contrary to the current guidelines, many young women who have not had sex or who initiated sex within the previous 3 years reported having had a Pap test. Assuming that the patterns observed in this study persist, there is an urgent need for education regarding the need to adhere to guidelines to reduce the burden of potentially unnecessary Pap tests in young women. LEVEL OF EVIDENCE: III. |
Preferred modes of travel among older adults: what factors affect the choice to walk instead of drive?
Naumann RB , Dellinger AM , Anderson ML , Bonomi AE , Rivara FP , Thompson RS . J Safety Res 2009 40 (5) 395-8 INTRODUCTION: There are many factors that influence older adults' travel choices. This paper explores the associations between mode of travel choice for a short trip and older adults' personal characteristics. METHODS: This study included 406 drivers over the age of 64 who were enrolled in a large integrated health plan in the United States between 1991 and 2001. Bivariate analyses and generalized linear modeling were used to examine associations between choosing to walk or drive and respondents' self-reported general health, physical and functional abilities, and confidence in walking and driving. RESULTS: Having more confidence in their ability to walk versus drive increased an older adult's likelihood of walking to make a short trip by about 20% (PR=1.22; 95% CI: 1.06-1.40), and walking for exercise increased the likelihood by about 50% (PR=1.53; 95% CI=1.22-1.91). Reporting fair or poor health decreased the likelihood of walking, as did cutting down on the amount of driving due to a physical problem. DISCUSSION: Factors affecting a person's decision to walk for exercise may not be the same as those that influence their decision to walk as a mode of travel. It is important to understand the barriers to walking for exercise and walking for travel to develop strategies to help older adults meet both their exercise and mobility needs. IMPACT ON INDUSTRY: Increasing walking over driving among older adults may require programs that increase confidence in walking and encourage walking for exercise. |
Risk assessment and screening for sexually transmitted infections, HIV, and hepatitis virus among long-distance truck drivers in New Mexico, 2004-2006
Valway S , Jenison S , Keller N , Vega-Hernandez J , Hubbard McCree D . Am J Public Health 2009 99 (11) 2063-8 OBJECTIVES: We examined sexually transmitted infection (STI), HIV, and hepatitis virus prevalence and risk behaviors among truck drivers. METHODS: We asked participants about their risk behaviors, and we screened them for STIs, HIV, and hepatitis infections. We used logistic regression to identify factors associated with outcomes. RESULTS: Of the 652 enrolled participants, 21% reported sex with sex workers or casual partners in the prior year. Driving solo (odds ratio [OR] = 15.04; 95% confidence interval [CI] = 1.92, 117.53; P = .01), history of injection drug use (IDU; OR = 2.69; 95% CI = 1.19, 6.12; P = .02), and history of an STI (OR = 2.47; 95% CI = 1.19, 5.09; P = .01) were independently associated with high-risk sexual behaviors. Fourteen percent of participants reported drug use in the previous year, and 11% reported having ever injected drugs. Participants tested positive as follows: 54 for HCV antibodies (8.5%), 66 for hepatitis B anticore (anti-HBc) antibodies (10.4%), 8 for chlamydia (1.3%), 1 for gonorrhea (0.2%), 1 for syphilis (0.2%), and 1 for HIV (0.2%). History of injecting drugs (OR = 26.91; 95% CI = 11.61, 62.39; P < .01) and history of anti-HBc antibodies (OR = 7.89; 95% CI = 3.16, 19.68; P < .01) were associated with HCV infection. CONCLUSIONS: Our results suggest a need for hepatitis C screening and STI risk-reduction interventions in this population. |
Self-reported and clinical measurement of three chronic disease risks among low-income women in West Virginia
Ahluwalia IB , Tessaro I , Rye S , Parker L . J Womens Health (Larchmt) 2009 18 (11) 1857-62 BACKGROUND: This study assessed the validity of several self-reported cardiovascular risk factors among low-income women aged 40-64 years in West Virginia. METHODS: A cross-sectional survey was conducted of 733 women participating in the Well Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) project in West Virginia to examine agreement between self-report and clinical screenings in the prevalence of risk factors related to coronary heart disease (CHD). Women participating in the study were interviewed face-to-face before administration of clinical screenings that assessed height, weight, Quetelet's index, high blood pressure (systolic ≥140 mm Hg or diastolic ≥90 mm Hg), and elevated total cholesterol concentrations (≥200 mg/dL and ≥240 mg/dL). RESULTS: The overall results showed high sensitivity and specificity for each of the risk factors examined; for overweight/obesity, the sensitivity was 96% and specificity was 93%; for cholesterol ≥240 mg/dL, sensitivity was 85% and specificity was 67%; for hypertension, sensitivity was 77% and specificity was 86%. Using a threshold value of ≥240 mg/dL for hypercholesterolemia led to higher sensitivity but a lower specificity than for a value of ≥200 mg/dL. CONCLUSIONS: This study found that among low-income women at higher risk for cardiovascular disease (CVD), self-reported values for high body mass index (BMI), hypercholesterolemia, and hypertension were well correlated with clinical measures, as indicated by high sensitivity values. Thus, self-reported values can be used for surveillance, targeted screenings, and health promotion activities, including lifestyle changes. |
The Carolina HPV Immunization Attitudes and Beliefs Scale (CHIAS): scale development and associations with intentions to vaccinate
McRee AL , Brewer NT , Reiter PL , Gottlieb SL , Smith JS . Sex Transm Dis 2009 37 (4) 234-9 BACKGROUND: No standardized instruments, to our knowledge, exist to assess attitudes and beliefs about human papillomavirus (HPV) vaccination. METHODS: We developed the Carolina HPV Immunization Attitudes and Beliefs Scale (CHIAS), using data collected on 783 parents who had not yet vaccinated their daughters against HPV. We conducted a principal components analysis of 16 HPV vaccine attitude and belief items, assessed the scale's psychometric properties, and used linear regression to examine the relationship of CHIAS factors and parents' vaccination intentions. RESULTS: Analyses identified 4 CHIAS factors, all of which had acceptable scale alphas and 1-year test-retest reliability. In multivariate models, higher vaccination intentions were associated with: believing HPV vaccine is effective (beta = 0.06) or has less harmful effects (beta = -0.47), perceiving more barriers to access (beta = 0.18), and having less uncertainty about the vaccine (beta = -0.23) (all P < 0.05). CONCLUSIONS: Findings suggest that parent attitudes about HPV vaccine are important to their intentions to vaccinate their adolescent daughters against HPV. The CHIAS offers researchers a compact, standardized measure of important HPV vaccine attitudes and beliefs. |
Concurrent alcohol use or heavier use of alcohol and cigarette smoking among women of childbearing age with accessible health care
Tsai J , Floyd RL , Green PP , Denny CH , Coles CD , Sokol RJ . Prev Sci 2009 11 (2) 197-206 This study was conducted to provide nationally representative findings on the prevalence and distribution of concurrent alcohol use or heavier use of alcohol and cigarette smoking among women of childbearing age with accessible health care. For the years 2003-2005, a total of 20,912 women 18-44 years of age who participated in the National Health Interview Survey (NHIS) reported that during the study period, there was a place where they would usually go for health care when sick or in need of advice about their health. The prevalence and distribution of concurrent alcohol use or heavier use of alcohol and cigarette smoking reported by such women was calculated. Logistic regression analysis was used to evaluate the "most often visited health care place" among concurrent users who reported having seen or talked to a health care provider during the previous 12 months. Among surveyed women with accessible health care, 12.3% reported concurrent alcohol use and cigarette smoking, and 1.9% reported concurrent heavier use of alcohol and cigarette smoking during the study period. Of women who reported either type of concurrent use, at least 84.4% also indicated having seen or talked to one or more health care providers during the previous 12 months. Such women were more likely than non-concurrent users to indicate that the "most often visited health care place" was a "hospital emergency room or outpatient department or some other place" or a "clinic or health center," as opposed to an "HMO or doctor's office." Concurrent alcohol use or heavier use of alcohol and cigarette smoking among women of childbearing age is an important public health concern in the United States. The findings of this study highlight the importance of screening and behavioral counseling interventions for excessive drinking and cigarette smoking by health care providers in both primary care and emergency department settings. |
Disentangling adolescent pathways of sexual risk taking
Brookmeyer KA , Henrich CC . J Prim Prev 2009 30 (6) 677-96 Using data from the National Longitudinal Survey of Youth, the authors aimed to describe the pathways of risk within sexual risk taking, alcohol use, and delinquency, and then identify how the trajectory of sexual risk is linked to alcohol use and delinquency. Risk trajectories were measured with adolescents aged 15-24 years (N = 1,778). Using Latent Class Growth Analyses (LCGA), models indicated that the majority of adolescents engaged in sexual risk and alcohol use. In joint trajectory analyses, LCGA revealed six risk taking classes: sex and alcohol, moderate risk taking, joint risk taking, moderate alcohol, alcohol risk, and alcohol and delinquency experimentation. EDITORS' STRATEGIC IMPLICATIONS: School administrators and curriculum designers should pay attention to the study's findings with respect to the need for prevention programs to target early adolescents and integrate prevention messages about alcohol use and sexual risk taking. |
Emotional intimacy predicts condom use: findings in a group at high sexually transmitted disease risk
Damani R , Ross MW , Aral SO , Berman S , St Lawrence J , Williams ML . Int J STD AIDS 2009 20 (11) 761-4 Previous studies have reported an inverse relationship between condom use and emotional intimacy. The aim of this study was to determine the relationship between condom use and emotional intimacy. The study was a gonorrhoea case-comparison study with the samples being drawn from public health clinics (cases) and select bars/nightclubs (places) of Houston, TX (n = 215). Data were collected by questionnaires administered on a laptop computer. The majority of respondents were African-American (97.7%), women (69.3%) and had either high school or GED education (72.6%). Condom use with the last sexual partner was analysed along with intimacy with that partner assessed on a 3-point scale. Analysis showed that higher intimacy was related to greater condom use which was significant in men but not in women. In conclusion, these data were opposite to those of previous studies, which showed an inverse relationship between condom use and emotional intimacy. We hypothesize that in a high-risk environment, people exert more effort in protecting those they feel closer to. These data suggest a need to further explore the complex relationship between emotional intimacy and condom use. |
Transfusion-transmitted arboviruses
Petersen LR , Busch MP . Vox Sang 2009 98 (4) 495-503 There exists considerable risk for transfusion transmission of arboviruses due to short periods of asymptomatic viraemia in populations with variable and sometimes extremely high incidence of arboviral infections. Aside from West Nile virus, few arbovirus transfusion transmissions have been proven, mostly due to difficulties in ruling out vector-borne transmission in recipients with arbovirus disease. Nevertheless, arbovirus transfusion risk models and assessments of viraemia prevalence in blood donations indicate substantial transfusion transmission of dengue and Chikungunya viruses in epidemic areas. Many other arboviruses, several of which are importation risks in the Americas, Europe and Asia, also cause large outbreaks and threaten transfusion safety. Prevention largely depends on excluding donors from outbreak areas or implementation of highly sensitive nucleic acid amplification tests. Because of the increasing emergence of arboviral disease globally, it is prudent to prepare for both endemic and exotic arboviruses capable of producing large epidemics and subsequent transfusion transmission risk. |
Infectious granulomatous dermatitis associated with rothia mucilaginosa bacteremia: a case report
Morgan EA , Henrich TJ , Jarell AD , Shieh WJ , Zaki SR , Marty FM , Thorner AR , Milner DA , Velazquez EF . Am J Dermatopathol 2009 32 (2) 175-9 Infections with rare pathogens are being recognized with increasing frequency in severely immunocompromised patients. As a result of these patients' underlying compromised defenses and susceptibility to atypical organisms, tissue biopsies from patients within this population may demonstrate nonclassical histopathological findings. Here, we describe an unusual granulomatous reaction to gram-positive cocci in the skin of a 52-year-old man undergoing salvage chemotherapy for acute myeloid leukemia. The patient presented with a papular eruption on the arms, trunk, and face and fever; concomitant blood cultures were positive for Rothia mucilaginosa and Streptococcus salivarius. Histologic evaluation revealed a granulomatous dermatitis associated with numerous small, round, predominantly intracellular bacteria. Classically, cutaneous infiltrates associated with coccoid bacterial infections are suppurative and not granulomatous. The intracellular organisms stained positive for Gram, periodic acid-Schiff, and Grocott methenamine silver stains, suggestive of R. mucilaginosa. Rothia mucilaginosa, a component of the oral flora, was first reported as a human pathogen in 1978. Although the majority of cases in the literature have described R. mucilaginosa bacteremia, other reported manifestations include meningitis, endocarditis, pneumonia, osteomyelitis, and peritonitis. To our knowledge, however, only 1 prior report has described a cutaneous manifestation of R. mucilaginosa septicemia, which occurred in a patient with neutropenia. This is the second reported case of an infectious granulomatous dermatitis associated with R. mucilaginosa bacteremia and raises awareness of this unusual histopathological presentation in the setting of a bacterial infection affecting the skin. |
Vaccine safety: current systems and recent findings
Wharton M . Curr Opin Pediatr 2009 22 (1) 88-93 PURPOSE OF REVIEW: An understanding of vaccine safety is important for all immunization providers, who have responsibilities to identify, report, and prevent adverse events. RECENT FINDINGS: New analytic methods can provide more rapid information on adverse events compared with traditional observational studies. Some adverse events following vaccination are preventable. Syncope is increasingly recognized postvaccination and may be associated with severe injury or death. Both human and system factors should be addressed to prevent vaccine administration errors. Ongoing basic science and clinical research is critical to improved understanding of vaccine safety. A recent study suggests that many cases of encephalopathy following whole-cell pertussis vaccine were due to severe myoclonic epilepsy of infancy, a severe seizure disorder associated with mutations of the sodium channel gene SCN1A. SUMMARY: Vaccine safety requires prelicensure evaluation, postlicensure surveillance and investigation, addressing preventable adverse events, reconsideration of vaccine policy as understanding of risks and benefits changes, and ongoing research to better understand the response to vaccination and the pathogenesis of adverse events. |
The expanding vaccine development pipeline, 1995-2008
Davis MM , Butchart AT , Coleman MS , Singer DC , Wheeler JR , Pok A , Freed GL . Vaccine 2009 28 (5) 1353-6 Successful launches of recently licensed vaccines contrast with pharmaceutical industry concerns about unfavorable market conditions, making the status and future of vaccine development uncertain. We assessed trends in private-sector vaccine research and development for the period 1995-2008, using a global pharmaceutical database to identify prophylactic vaccines in preclinical, Phase I, Phase II, or Phase III stages of development. We counted companies that research and/or manufacture vaccines ("vaccine originators") and their vaccine products in each year. The global number of vaccine originators doubled (to 136), as did the number of prophylactic vaccine products in development (to 354); the majority of this growth was in preclinical and early phase clinical research. Because rapid growth in earlier research phases has not yet led to growth in Phase III, it is not yet clear whether recent industry expansion will translate to an increase in the number of available vaccines in the near future. |
The interferon alpha/beta receptor provides protection against influenza virus replication but is dispensable for inflammatory response signaling
Goodman AG , Zeng H , Proll SC , Peng X , Cilloniz C , Carter VS , Korth MJ , Tumpey TM , Katze MG . J Virol 2009 84 (4) 2027-37 The innate immune response provides the first line of defense against foreign pathogens by responding to molecules which are a signature of a pathogenic infection. Certain RNA viruses, such as influenza virus, produce double-stranded RNA as an intermediate during the replication life cycle which activates pathogen-recognition receptors capable of inducing interferon production. By engaging interferon receptors, interferon activates the JAK-STAT pathway and results in positive feedback of interferon production, amplifying the response to viral infection. To examine how deficiencies in interferon signaling affect the cellular response to infection, we performed influenza virus infections in mouse embryonic fibroblasts lacking the interferon-alpha/beta receptor, the interferon-gamma receptor, or both. In the absence of the interferon-alpha/beta receptor, we observed increased viral replication but decreased activation of PKR, Stat1, and NF-kappaB; the presence or absence of the interferon-gamma receptor did not exhibit discernable differences of these readouts. Analysis of gene expression profiles showed that while cells lacking the interferon-alpha/beta receptor exhibited decreased transcription of antiviral genes, genes related to inflammatory and apoptotic responses were transcribed to similar levels as cells containing the receptor. These results indicate that while the interferon-alpha/beta receptor is needed to curb viral replication, it is dispensable for the induction of certain inflammatory and apoptotic genes. We have identified potential pathways, via IRF3 activation, or Hoxa13, Polr2a, Nr4a1, or Ing1 induction, that contribute to this redundancy. This study illustrates another way in which the host has evolved to establish several overlapping mechanisms to respond to viral infections. |
The use of electronic pharmacy data to investigate prescribed medications and fatal motor vehicle crashes in a military population, 2002-2006
Hooper TI , DeBakey SF , Pearse L , Pratt S , Hoffman KJ . Accid Anal Prev 2010 42 (1) 261-8 The authors examined the association between prescribed medications and fatal motor vehicle crashes (MVCs) in an active duty military population between 2002 and 2006. Using a case-control design, MVC deaths were ascertained using a military mortality registry, and an integrated health system database provided information on health system eligibility, pharmacy transactions, and medical encounters. Cases and controls were matched on comparable observation time outside periods of deployment. Among selected categories, only one, antidepressant medications, was an independent predictor of fatal MVC (odds ratio, 3.19; 95% confidence interval, 1.01-10.07). Male gender, Black race, enlisted rank, service branch (Navy and Marine Corps), and selected co-morbidities were also independent predictors. Unexpectedly, the odds of younger age quartiles (< 27 years) and history of deployment were reduced for MVC cases. Although results need to be considered in the context of data limitations, the association between prescribed antidepressants and fatal MVC may reflect unmeasured co-morbidities, such as combined effects of prescribed and over-the-counter medications and/or alcohol or other substance abuse. Younger individuals, representing new military accessions in training or returning from deployment with serious injuries, may have fewer opportunities to operate vehicles, or targeted efforts to reduce MVC following deployment may be showing a positive effect. |
Experimental study of pleated fabric cartridges in a pulse-jet cleaned dust collector
Lo LM , Chen DR , Pui DYH . Powder Technol 2010 197 (3) 141-149 Six pleated filter cartridges with different base media and geometrical dimensions were tested in a full-size dust collector periodically cleaned by a short burst of pulse-jet. The evaluation was performed under two different cleaning modes called clean-on-demand (to clean the filter once the pressure drop reaches a preset value) and clean-on-time (to clean the filter at a fixed time interval). The filter performance was evaluated by the effective residual pressure drop and downstream particle concentration. The results showed that the pleat ratio, defined as the ratio of pleat height to pleat pitch, had a great influence on the preferred operating mode for cleaning the filter. Clean-on-time mode demonstrated better performance for filters with a high pleat ratio (N4.0), while clean-on-demand mode performed better for filters with a low pleat ratio (b4.0). The test results also showed the tank pressure was critical for cleaning the pleated filter cartridges, whereas the pulse duration only had a small effect on the cleaning efficiency. With the same base media, cartridges with surface treatment such as fine fiber were superior to those without surface treatment. Pulse-jet cleaning could also promote particle penetration through filter media. The downstream particle concentration during cleaning was at least twice of that during filtration process for all pleated filter cartridges tested. Further, the downstream particle concentration was independent of the applied cleaning mode and the cleaning intensity in this study. |
Inhibition of AP-1 and MAPK signaling and activation of Nrf2/ARE pathway by quercitrin
Ding M , Zhao J , Bowman L , Lu Y , Shi X . Int J Oncol 2010 36 (1) 59-67 Quercitrin, glycosylated form of flavonoid compounds, is widely distributed in nature. Extensive studies have demonstrated that quercitrin exhibits strong antioxidant and anti-carcinogenic activities. However, the molecular mechanism is poorly understood. The present study examines the effects of quercitrin on tumor promotion in mouse JB6 cells, a validated model for screening cancer chemopreventive agents and elucidating the molecular mechanisms. Quercitrin blocked TPA-induced neoplastic transformation in JB6 P+ cells. Pretreatment of JB6 cells with quercitrin down-regulated transactivation of AP-1 and NF-kappaB induced by UVB or TPA. In the skin of AP-1-luciferase transgenic mice, topical treatment of the mouse with quercitrin markedly blocked the TPA-induced AP-1 transactivation. Further studies indicated that these inhibitory actions appear to be mediated through the inhibition of MAPKs phosphorylation, including ERKs, p38 kinase, and JNKs. In addition, quercitrin stimulated the activation of NF-E2-related factor (Nrf2) and GST ARE-luciferase activity. Comet assays showed that quercitrin could block DNA damage induced by UVB. To our knowledge, these results provide the first evidence that quercitrin contributes to the inhibition of neoplastic transformation by blocking activation of the MAPK pathway and stimulation of cellular protection signaling. Moreover, to our knowledge, these findings provide the first molecular basis for the anti-carcinogenic action of quercitrin. |
Molecular characterization of antibody epitopes of ehrlichia chaffeensis ankyrin protein 200 and tandem repeat protein 47 and evaluation of synthetic immunodeterminants for serodiagnosis of human monocytotropic ehrlichiosis
Luo T , Zhang X , Nicholson WL , Zhu B , McBride JW . Clin Vaccine Immunol 2009 17 (1) 87-97 Recently major species-specific antibody epitopes in three immunoreactive tandem repeat proteins (TRP) of E. chaffeensis, TRP32, TRP47 and TRP120, have been identified and molecularly characterized within tandem repeat (TR) regions. In this study, we mapped the major immunodeterminants of the E. chaffeensis 200 kDa ankyrin protein (Ank200) and the minor immunodeterminants in N- and C-terminal regions of E. chaffeensis TRP47. Major antibody epitopes of Ank200 were localized to four polypeptide regions (18-mer, 20-mer, 20-mer, and 21-mer, respectively) in terminal acidic domains, which reacted with antibodies in sera from HME patients and an E. chaffeensis-infected dog. Two minor epitope-containing regions were identified in the N-terminus and the C-terminus of TRP47. The sensitivity and specificity of synthetic peptides representing these and other well-defined major immunodeterminants of E. chaffeensis were determined by enzyme-linked immunosorbent assay (ELISA). Thirty-one HME patient sera that had detectable E. chaffeensis antibodies (titers from 64 to 8192) by indirect fluorescent-antibody assay (IFA) were tested. All 31 sera reacted with at least one E. chaffeensis peptide and 30 sera (96.8%) with TRP120 peptide, 27 (87.1%) with TRP32 peptides, 24 (77.4%) with TRP47 peptides, 19 (61.3%) with Ank200 peptides, and 28 (90.3%) with recombinant TRP120-TR protein. A mixture of the two most sensitive peptides from TRP120 and TRP32 did not provide enhanced analytical sensitivity over the TRP120 alone. Our results demonstrate that the TRP120 peptide could be utilized for development of standardized sensitive point-of-care and reference laboratory immunodiagnostics for HME. This is the first study to compare molecularly-defined major antibody epitopes with IFA for diagnosis of HME. |
NRF2 cysteine residues are critical for oxidant/electrophile-sensing, kelch-like ECH-associated protein-1-dependent ubiquitination-proteasomal degradation, and transcription activation
He X , Ma Q . Mol Pharmacol 2009 76 (6) 1265-78 Cells respond to oxidants and electrophiles by activating receptor/transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) to coordinate the induction of cytoprotective genes critical for defense against oxidative and other stresses. Activation involves blocking the ubiquitination-proteasomal degradation of Nrf2. Modification of cysteine thiol groups by inducers in the linker region of Kelch-like ECH-associated protein-1 (Keap1), which congregates Nrf2 into the Keap1/Cul3 E3 complex for ubiquitination, is important but not sufficient for activation of Nrf2. Here we show that evolutionarily conserved cysteine residues of Nrf2 are critical for Nrf2 regulation. FlAsH (an arsenic-based fluorophore) and phenylarsine oxide (PAO) potently induce Nrf2 target genes and bind to Nrf2 in vitro and in vivo. Binding is inhibited by prototypical inducers arsenic and tert-butylhydroquinone. PAO affinity pull-down and mutation of individual cysteine to alanine reveal that Cys235, Cys311, Cys316, Cys414, and Cys506 are critical for binding, and binding is modulated by intramolecular interactions. To corroborate the functions of cysteine residues, Nrf2 wild-type or mutants are expressed in Nrf2 knockout cells to reconstitute Nrf2 regulation. Nrf2 mutants have reduced t(1/2) that inversely correlates with increased binding to Keap1 and polyubiquitination of mutant proteins. It is remarkable that the mutants fail to respond to arsenic for Nrf2 activation and gene induction. Furthermore, mutations at Cys119, Cys235, and Cys506 impede binding of Nrf2 to endogenous antioxidant response element and to coactivator cAMP response element-binding protein-binding protein/p300. The findings demonstrate that Nrf2 cysteine residues critically regulate oxidant/electrophile sensing, repress Keap1-dependent ubiquitination-proteasomal degradation, and promote recruitment of coactivators, such that chemical sensing, receptor activation, and transcription activation are integrated at the receptor molecule. |
Rapid and chemically selective nicotine quantification in smokeless tobacco products using GC-MS
Stanfill SB , Jia LT , Ashley DJ , Watson CH . J Chromatogr Sci 2009 47 (10) 902-9 In recent years, there has been a rapid proliferation of smokeless products with a wide range of nicotine content and flavoring formulations that may appeal to new users and existing cigarette smokers. The CDC nicotine method, which employs gas chromatography-flame ionization detection (GC-FID), provides a robust means for measuring nicotine in smokeless tobacco. However, several compounds, identified in a few flavored smokeless products, interfere with nicotine quantification using GC-FID. In response, the standard nicotine method (26.7 min run time) was modified to use faster GC ramping (3.7 min run time) and detection with mass spectrometry (GC-MS) in selected ion-monitoring mode to reduce signal interferences that can bias nicotine values. Seven conventional smokeless samples (n = 12) and blank tobacco samples spiked at three nicotine concentration levels (n = 5) were analyzed using the GC-FID and GC-MS methods and found to be in excellent agreement. However, only the GC-MS method provided confirmation of chromatographic peak purity in certain highly flavored products. The GC-MS method is not intended to replace the GC-FID method but to provide a method versatile enough to analyze a wide range of nicotine values in domestic and international samples of varying complexity. Accurate nicotine quantification is important for determining total nicotine content in tobacco and in subsequent calculations of un-protonated nicotine content. |
A rapid real-time PCR assay for the detection of HIV-1 proviral DNA using double-stranded primer
Pau CP , Wells SK , Rudolph DL , Owen SM , Granade TC . J Virol Methods 2009 164 55-62 In this study, a rapid real-time PCR assay to detect HIV-1 proviral DNA in whole blood was developed using a novel double-stranded primer that does not require a target-specific fluorescent probe or intercalating dye systems. Co-amplification of a human gene RNase P served as the internal control to monitor the efficiency of the DNA extraction and PCR amplification. The HIV-1 amplification efficiency was 100% and could amplify 1 copy of HIV-1 DNA 64% of the time and all attempts to amplify 4 copies were successful in less than 51min. All 22 HIV-1 sero-positive and 20 sero-negative whole blood specimens tested were classified correctly by this assay. In addition, 22 cultured PBMC specimens infected with various HIV-1 subtypes or CRF (A=2, AC=1, B=4, C=3, D=3, AE=2, F=1, BF=2, G=4) were amplified equally well with a similar threshold cycle (C(t)) number (22.9+/-1.2). The high amplification efficiency and short PCR cycles were in part due to the short target sequence amplified by eliminating the probe-binding sequence between the primers. This assay may be useful as an alternative confirmation test in a variety of HIV testing venues. |
Transcriptional responses to oxidative stress: pathological and toxicological implications
Ma Q . Pharmacol Ther 2009 125 (3) 376-93 The utilization of molecular oxygen as the terminal electron acceptor for energy production has in many ways shaped the evolution of complex life, physiology, and certain disease processes. The generation of reactive oxygen species (ROS), either as by-products of O(2) metabolism or by specialized enzymes, has the potential to damage cellular components and functions. Exposure to a variety of exogenous toxicants also promotes ROS production directly or through indirect means to cause toxicity. Oxidative stress activates the expression of a wide range of genes that mediate the pathogenic effect of ROS or are required for the detection and detoxification of the oxidants. In many cases, these are mediated by specific transcription factors whose expression, structure, stability, nuclear targeting, or DNA-binding affinity is regulated by the level of oxidative stress. This review examines major transcription factors that mediate transcriptional responses to oxidative stress, focusing on recent progress in the signaling pathways and mechanisms of activation of transcription factors by oxidative stress and the implications of this regulation in the development of disease and chemical toxicity. |
Validation and clinical application of a molecular method for the identification of Histoplasma capsulatum in human specimens in Colombia, South America
Munoz C , Gomez BL , Tobon A , Arango K , Restrepo A , Correa MM , Muskus C , Cano LE , Gonzalez A . Clin Vaccine Immunol 2009 17 (1) 62-7 Conventional diagnosis of histoplasmosis presents difficulties delaying diagnosis, indicating the need for implementation of molecular assays. We evaluated 146 clinical samples from 135 patients suspected to have histoplasmosis using a previously reported nested PCR assay (Hc100). In order to determine the specificity of this molecular test, we also used samples from healthy individuals (n=20), from patients suspected to have respiratory disease with negative fungal cultures (n=29), and patients with other proven infections (n=60). Additionally, a sizable collection of DNA from cultures of H.capsulatum and other medically relevant pathogens were studied. A panfungal PCR assay amplifying the ITS2 region was also used to identify all fungal DNAs. All PCR amplified products were sequenced. From the 146 clinical samples, 67 (45.9%) were positive by culture and PCR, while 9 samples negative by culture were positive by PCR. All the sequences corresponding to the 76 amplified products presented ≥98% identity with H.capsulatum. The Hc100 PCR exhibited a sensitivity of 100% and a specificity of 92.4% and 95.2% when compared to negative controls nd to samples from other proven clinical entities, respectively; PPV was 83% and NPV was 100%; the positive and negative likelihood rates were 25 and 0, respectively. These results suggest that the Hc100-based nested PCR assay for detection of H.capsulatum DNA is a useful test in areas where this mycosis is endemic. |
Validation of analytical methods and instrumentation for beryllium measurement: review and summary of available guides, procedures, and protocols
Ekechukwu A , Hendricks W , White KT , Liabastre A , Archuleta M , Hoover MD . J Occup Environ Hyg 2009 6 (12) 766-74 This document provides a listing of available sources that can be used to validate analytical methods and/or instrumentation for beryllium determination. A literature review was conducted of available standard methods and publications used for method validation and/or quality control. An annotated listing of the articles, papers, and books reviewed is given in the Appendix. Available validation documents and guides are listed therein; each has a brief description of application and use. In the referenced sources, there are varying approaches to validation and varying descriptions of the validation process at different stages in method development. This discussion focuses on validation and verification of fully developed methods and instrumentation that have been offered for use or approval by other laboratories or official consensus bodies such as ASTM International, the International Standards Organization, the International Electrotechnical Commission, and the Association of Official Analytical Chemists. This review was conducted as part of a collaborative effort to investigate and improve the state of validation for measuring beryllium in the workplace and the environment. Documents and publications from the United States and Europe are included. |
2-Tiered antibody testing for early and late lyme disease using only an immunoglobulin G blot with the addition of a VlsE Band as the second-Tier test
Branda JA , Aguero-Rosenfeld ME , Ferraro MJ , Johnson BJ , Wormser GP , Steere AC . Clin Infect Dis 2009 50 (1) 20-6 BACKGROUND: Standard 2-tiered immunoglobulin G (IgG) testing has performed well in late Lyme disease (LD), but IgM testing early in the illness has been problematic. IgG VlsE antibody testing, by itself, improves early sensitivity, but may lower specificity. We studied whether elements of the 2 approaches could be combined to produce a second-tier IgG blot that performs well throughout the infection. METHODS: Separate serum sets from LD patients and control subjects were tested independently at 2 medical centers using whole-cell enzyme immunoassays and IgM and IgG immunoblots, with recombinant VlsE added to the IgG blots. The results from both centers were combined, and a new second-tier IgG algorithm was developed. RESULTS: With standard 2-tiered IgM and IgG testing, 31% of patients with active erythema migrans (stage 1), 63% of those with acute neuroborreliosis or carditis (stage 2), and 100% of those with arthritis or late neurologic involvement (stage 3) had positive results. Using new IgG criteria, in which only the VlsE band was scored as a second-tier test among patients with early LD (stage 1 or 2) and 5 of 11 IgG bands were required in those with stage 3 LD, 34% of patients with stage 1, 96% of those with stage 2, and 100% of those with stage 3 infection had positive responses. Both new and standard testing achieved 100% specificity. CONCLUSIONS: Compared with standard IgM and IgG testing, the new IgG algorithm (with VlsE band) eliminates the need for IgM testing; it provides comparable or better sensitivity, and it maintains high specificity. |
Analysis of blood spots for polyfluoroalkyl chemicals
Kato K , Wanigatunga AA , Needham LL , Calafat AM . Anal Chim Acta 2009 656 51-5 Polyfluoroalkyl chemicals (PFCs) have been detected in humans, in the environment, and in ecosystems around the world. The potential for developmental and reproductive toxicities of some PFCs is of concern especially to children's health. In the United States, a sample of a baby's blood, called a "dried blood spot" (DBS), is obtained from a heel stick within 48 h of a child's birth. DBS could be useful for assessing prenatal exposure to PFCs. We developed a method based on online solid phase extraction coupled with high performance liquid chromatography-isotope dilution tandem mass spectrometry for measuring four PFCs in DBS, perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate, perfluorooctanoate (PFOA), and perfluorononanoate. The analytical limits of detection using one whole DBS (approximately 75 microL of blood) were <0.5 ng mL(-1). To validate the method, we analyzed 98 DBS collected in May 2007 in the United States. PFOS and PFOA were detected in all DBS at concentrations in the low ng mL(-1) range. These data suggest that DBS may be a suitable matrix for assessing perinatal exposure to PFCs, but additional information related to sampling and specimen storage is needed to demonstrate the utility of these measures for assessing exposure. |
Comparison of storage phosphor computed radiography with conventional film-screen radiography in the recognition of pneumoconiosis
Laney AS , Petsonk EL , Wolfe AL , Attfield MD . Eur Respir J 2009 36 (1) 122-7 Traditional film-screen radiography (FSR) has been useful in the recognition and evaluation of interstitial lung diseases, but is becoming increasingly obsolete. To evaluate the applicability of storage phosphor digital computed radiography (CR) images in the recognition of small lung opacities, we compared image quality and the profusion of small opacities between FSR and CR radiographs.We screened 1388 working coal miners during the course of the study with FSR and CR images obtained on the same day from all participants. Each traditional chest film was independently interpreted by two of eight experienced readers using the International Labour Office (ILO) classification of radiographs of pneumoconiosis, as were CR images displayed on medical-grade computer monitors.The prevalence of small opacities (ILO category 1/0 or greater) did not differ between the two imaging modalities (5.2%, for FSR and 4.8% for soft copy CR, p>0.50). Inter-reader agreement was also similar between FSR and CR. Significant differences between image modalities were observed in the shape of small opacities, and in the proportion of miners demonstrating high opacity profusion (category ≥2/1).Our results indicate that, with appropriate attention to image acquisition and soft copy display, CR digital radiography can be equivalent to FSR in the identification of small interstitial lung opacities. |
Comparison of three weighting schemes in weighted regression analysis for use in a chemistry laboratory
Jain RB . Clin Chim Acta 2009 411 270-9 BACKGROUND: To minimize the effect of heteroscedasticity in chemical and other data, weighted regression analysis is the preferred regression technique. In this work a regression weight that maximizes accuracy and precision was sought. METHOD: Using real and simulated data from a serum cotinine assay, performance of 3 weighting schemes, namely, 1/X, 1/X(2), and 1/s(2)(Y) to calibrate chemical data was evaluated. Two performance measures were used to evaluate the accuracy and precision of each scheme to estimate concentrations in unknown specimens. RESULTS: The weight, 1/X-particularly for low concentrations-was not acceptable. The performance of both, 1/X(2) and 1/s(2)(Y) was close, 1/X(2) being slightly better in many cases. Overall, however, when the variance of instrument signal increased beyond certain limits, none of the weighting schemes performed acceptably. CONCLUSION: Because of its simplicity and ease of use, 1/X(2) is recommended for general application. If, however, instrument signal variance is too high to be managed by statistical techniques, the only solution is to control such variance through laboratory-based solutions. |
Determination of 43 polycyclic aromatic hydrocarbons in air particulate matter by use of direct elution and isotope dilution gas chromatography/mass spectrometry
Li Z , Pittman EN , Trinidad DA , Romanoff LC , Mulholland J , Sjodin A . Anal Bioanal Chem 2009 396 (3) 1321-30 We are reporting a method for measuring 43 polycyclic aromatic hydrocarbons (PAH) and their methylated derivatives (Me-PAHs) in air particulate matter (PM) samples using isotope dilution gas chromatography/high-resolution mass spectrometry (GC/HRMS). In this method, PM samples were spiked with internal standards, loaded into solid phase extraction cartridges, and eluted by dichloromethane. The extracts were concentrated, spiked with a recovery standard, and analyzed by GC/HRMS at 10,000 resolution. Sixteen (13)C-labeled PAHs and two deuterated Me-PAHs were used as internal standards to account for instrument variability and losses during sample preparation. Recovery of labeled internal standards was in the range of 86-115%. The proposed method is less time-consuming than commonly used extraction methods, such as sonication and accelerated solvent extraction (ASE), and it eliminates the need for a filtration step required after the sonication extraction method. Limits of detection ranged from 41 to 332 pg/sample for the 43 analytes. This method was used to analyze reference materials from the National Institute of Standards and Technology. The results were consistent with those from ASE and sonication extraction, and these results were also in good agreement with the certified or reference concentrations. The proposed method was then used to measure PAHs on PM(2.5) samples collected at three sites (urban, suburban, and rural) in Atlanta, GA. The results showed distinct seasonal and spatial variation and were consistent with an earlier study measuring PM(2.5) samples using an ASE method, further demonstrating the compatibility of this method and the commonly used ASE method. |
Differential patterns of liver proteins in experimental murine hepatosplenic schistosomiasis
Manivannan B , Rawson P , Jordan TW , Secor WE , La Flamme AC . Infect Immun 2009 78 (2) 618-28 Schistosoma mansoni eggs produced by adult worms in the mesenteric vasculature become trapped in the liver where they induce granulomatous lesions and strong immune responses. Infected individuals suffer from intestinal schistosomiasis (INT) in 90% of cases whereas the remaining 10% present with severe hepatosplenic schistosomiasis (HS). The CBA/J mouse model mimics human disease with 20% of infected mice developing hypersplenomegaly syndrome (HSS) that resembles HS and 80% developing moderate splenomegaly syndrome (MSS) similar to INT. We studied differential patterns of protein expression in livers of 20-week infected CBA/J mice with MSS or HSS to understand the molecular changes that underlie these two disease forms. Using Differential In Gel Electrophoresis to identify differentially expressed protein spots, we found 80 protein spots significantly changed with infection and 35 changes specific to severe disease. In particular, the abundance of prohibitin 2, transferrin isoforms and major urinary protein isoforms were significantly altered in HSS mice. Furthermore, annexin5, glutathione S-transferase Pi class, and S. mansoni phosphoenolpyruvate carboxykinase expression changed significantly with schistosome infection. Additionally, major urinary protein decreased and transferrin increased significantly in the serum of HSS compared to MSS or control mice, and these differences correlated to the degree of splenomegaly. These findings indicate that the liver protein abundance differs between MSS and HSS mice and may be used in the development of diagnostic markers for early detection of hepatosplenic schistosomiasis. |
Evaluation of a molecular beacon real-time PCR assay for detection of Baylisascaris procyonis in different soil types and water samples
Gatcombe RR , Jothikumar N , Dangoudoubiyam S , Kazacos KR , Hill VR . Parasitol Res 2009 106 (2) 499-504 Baylisascaris procyonis is a helminth parasite commonly found in North American raccoons (Procyon lotor) that is a cause of clinical neural, ocular, and visceral larva migrans in humans when infective eggs are ingested. Rapid detection of B. procyonis eggs in contaminated soil and water would assist public health analysts in evaluating risks associated with public exposure to areas of known raccoon activity. In this study, a molecular beacon probe-based real-time polymerase chain reaction (PCR) assay was developed to enable rapid and specific detection of eggs of Baylisascaris spp. The molecular beacon assay targeted the cytochrome oxidase subunit 2 (cox-2) gene of B. procyonis. To determine method sensitivity, experiments testing various egg levels (250, 25, and five eggs) were performed by seeding into 0.5-g soil samples or 0.5-mL water samples. Different soil sample types were extracted using a commercial nucleic acid extraction kit. Specificity testing using previously characterized helminth tissue specimens indicated that the assay was specific to Baylisascaris spp. Little real-time PCR inhibition was observed for most of the soil and water samples. A seed level of 250 eggs was detected for all soil types, and two seed levels (25 and five eggs) were detected for surface water samples. These results demonstrate that the reported real-time PCR assay was effective for the sensitive detection of B. procyonis in a wide range of soil types, and should be a useful tool for investigations of soil or water potentially contaminated with eggs of this parasite. |
Extraction of beryllium from refractory beryllium oxide with dilute ammonium bifluoride and determination by fluorescence: a multiparameter performance evaluation
Goldcamp MJ , Goldcamp DM , Ashley K , Fernback JE , Agrawal A , Millson M , Marlow D , Harrison K . J Occup Environ Hyg 2009 6 (12) 735-44 Beryllium exposure can cause a number of deleterious health effects, including beryllium sensitization and the potentially fatal chronic beryllium disease. Efficient methods for monitoring beryllium contamination in workplaces are valuable to help prevent dangerous exposures to this element. In this work, performance data on the extraction of beryllium from various size fractions of high-fired beryllium oxide (BeO) particles (from < 32 microm up to 212 microm) using dilute aqueous ammonium bifluoride (ABF) solution were obtained under various conditions. Beryllium concentrations were determined by fluorescence using a hydroxybenzoquinoline fluorophore. The effects of ABF concentration and volume, extraction temperature, sample tube types, and presence of filter or wipe media were examined. Three percent ABF extracts beryllium nearly twice as quickly as 1% ABF; extraction solution volume has minimal influence. Elevated temperatures increase the rate of extraction dramatically compared with room temperature extraction. Sample tubes with constricted tips yield poor extraction rates owing to the inability of the extraction medium to access the undissolved particles. The relative rates of extraction of Be from BeO of varying particle sizes were examined. Beryllium from BeO particles in fractions ranging from less than 32 microm up to 212 microm were subjected to various extraction schemes. The smallest BeO particles are extracted more quickly than the largest particles, although at 90 degrees C even the largest BeO particles reach nearly quantitative extraction within 4 hr in 3% ABF. Extraction from mixed cellulosic-ester filters, cellulosic surface-sampling filters, wetted cellulosic dust wipes, and cotton gloves yielded 90% or greater recoveries. Scanning electron microscopy of BeO particles, including partially dissolved particles, shows that dissolution in dilute ABF occurs not just on the exterior surface but also via accessing particles' interiors due to porosity of the BeO material. Comparison of dissolution kinetics data shows that as particle diameter approximately doubles, extraction time is increased by a factor of about 1.5, which is consistent with the influence of porosity on dissolution. |
Interferon-gamma release assays: new diagnostic tests for Mycobacterium tuberculosis infection, and their use in children
Lewinsohn DA , Lobato MN , Jereb JA . Curr Opin Pediatr 2009 22 (1) 71-6 PURPOSE OF REVIEW: The testing and treatment of children at risk for Mycobacterium tuberculosis infection represents an important public health priority in the United States. Until recently, diagnosis has relied upon the tuberculin skin test (TST). New interferon-gamma release assays (IGRAs) offer improvements over TST, but these tests have not been studied in children until recently. RECENT FINDINGS: Evidence regarding IGRA performance in children is accumulating rapidly. Overall, the findings demonstrate performance of IGRAs equivalent or superior to that of the TST. However, IGRAs have biological limitations similar to TST and some technical problems of their own, and critical gaps in our knowledge remain. SUMMARY: Current evidence supports usage of IGRAs in children aged 5 years or older. IGRAs are preferred over TST when specificity is paramount or wherein patients might fail to return for TST reading. Evidence for use in children aged less than 5 years is insufficient at this time: the sensitivity is poorly defined, and TST is preferred for testing these children. Future IGRA research should focus on children aged less than 5 years for informing expanded usage in this vulnerable population. |
Interlaboratory comparability of serum cotinine measurements at smoker and nonsmoker concentration levels: a round-robin study
Bernert JT , Jacob P 3rd , Holiday DB , Benowitz NL , Sosnoff CS , Doig MV , Feyerabend C , Aldous KM , Sharifi M , Kellogg MD , Langman LJ . Nicotine Tob Res 2009 11 (12) 1458-1466 INTRODUCTION: Cotinine, the primary proximate metabolite of nicotine, is commonly measured as an index of exposure to tobacco in both active users of tobacco and nonsmokers with possible exposure to secondhand smoke (SHS). A number of laboratories have implemented analyses for measuring serum cotinine in recent years, but there have been few interlaboratory comparisons of the results. Among nonsmokers exposed to SHS, the concentration of cotinine in blood can be quite low, and extensive variability in these measurements has been reported in the past. METHODS: In this study, a group of seven laboratories, all experienced in serum cotinine analysis, measured eight coded serum pools with concentrations ranging from background levels of about 0.05 ng/ml to relatively high concentrations in the active smokers range. All laboratories used either gas-liquid chromatography with nitrogen-phosphorus detection or liquid chromatography with mass spectrometric detection. RESULTS: All seven laboratories reliably measured the cotinine concentrations in samples that were within the range of their methods. In each case, the results for the pools were correctly ranked in order, and no significant interlaboratory bias was observed at the 5% level of significance for results from any of the pools. DISCUSSION: We conclude that present methods of chromatographic analysis of serum cotinine, as used by these experienced laboratories, are capable of providing accurate and precise results in both the smoker and the nonsmoker concentration range. |
Low-level prenatal exposure to nicotine and infant neurobehavior
Yolton K , Khoury J , Xu Y , Succop P , Lanphear B , Bernert JT , Lester B . Neurotoxicol Teratol 2009 31 (6) 356-63 OBJECTIVE: To examine the association between prenatal exposure to nicotine from tobacco smoke and infant neurobehavior using tobacco biomarkers and a sensitive and comprehensive measure of infant neurobehavior. STUDY DESIGN: Participants were 318 infants (206 White, 95 Black, 17 Other) and their mothers. Prenatal tobacco smoke exposure was measured twice during pregnancy and once at delivery using maternal serum cotinine. Infant neurobehavior was assessed with the NICU Network Neurobehavioral Scale at approximately 5 weeks after birth. RESULTS: Prenatal tobacco smoke exposure was significantly associated with infant neurobehavior after controlling for important covariates, but the specific behaviors associated with exposure varied by race. In White infants, higher cotinine was associated with increased arousal (p=.030) and excitability (p=.034), and decreased self-regulation (p=.010). In contrast, among Black infants, higher cotinine was associated with decreased arousal (p=.001), excitability (p=.021), and special handling required to complete the assessment (p=.003), and increased self-regulation (p=.021) and hypotonicity (p=.016). In secondary analyses, we found racial differences in the effects of postnatal exposure to second hand smoke and low-level prenatal exposure. CONCLUSIONS: Low-level prenatal tobacco smoke exposure is associated with infant neurobehavior at 5 weeks of age, but the specific effects differ by race. These effects may reflect racial differences in nicotine metabolism that are similar to differences reported in adult and child studies of tobacco. |
Prevalence of Down syndrome among children and adolescents in 10 regions of the United States
Shin M , Besser LM , Kucik JE , Lu C , Siffel C , Correa A , Congenital Anomaly Multistate Prevalence Survival (CAMPS) Collaborative . Pediatrics 2009 124 (6) 1565-1571 OBJECTIVE: We aimed to estimate the prevalence of Down syndrome (DS) among children and adolescents aged 0 to 19 years in 10 regions of the United States. METHODS: This study was a cross-sectional analysis of live-born infants with DS during 1979-2003 from 10 population-based birth defects registries in the United States. We estimated the prevalence of DS at birth and among children aged 0 to 19 years in each region and in all regions pooled. The prevalence of DS among children and adolescents was calculated overall and according to age group, race/ethnicity, infant gender, and presence of a major heart defect. RESULTS: From 1979 through 2003, the prevalence of DS at birth increased by 31.1%, from 9.0 to 11.8 per 10000 live births in 10 US regions. In 2002, the prevalence among children and adolescents (0-19 years old) was 10.3 per 10000. The prevalence of DS among children in a given age group consistently increased over time but decreased with age within a given birth cohort. The pooled prevalence of DS among children and adolescents was lower among non-Hispanic black individuals and other racial/ethnic groups compared with non-Hispanic white individuals; it was also lower among females than males. CONCLUSIONS: This study provides prevalence estimates of DS among children and adolescents from 10 US regions. These estimates varied according to region, race/ethnicity, and gender, suggesting possible variation in prevalence at birth or in survival rates on the basis of these characteristics. |
Reliability and validity of birth certificate prepregnancy weight and height among women enrolled in prenatal WIC program: Florida, 2005
Park S , Sappenfield WM , Bish C , Bensyl DM , Goodman D , Menges J . Matern Child Health J 2009 15 (7) 851-9 To investigate the reliability and validity of weight, height, and body mass index (BMI) from birth certificates with directly measured values from the Women, Infants, and Children (WIC) Program. Florida birth certificate data were linked and compared with first trimester WIC data for women with a live birth during the last quarter of calendar year 2005 (n = 23,314 women). Mean differences for weight, height, and BMI were calculated by subtracting birth certificate values from WIC values. Reliability was estimated by Pearson's correlation. Validity was measured by sensitivity and specificity using WIC data as the reference. Overall mean differences plus or minus standard error (SE) were 1.93 +/- 0.04 kg for weight, -1.03 +/- 0.03 cm for height, and 1.07 +/- 0.02 kg/m(2) for BMI. Pearson's correlation ranged from 0.83 to 0.95, which indicates a strong positive association. Compared with other categories, women in the second weight group (56.7-65.8 kg), the highest height group (≥167.6 cm), or BMI < 18.5 had the greatest mean differences for weight (2.2 +/- 0.08 kg), height (-2.4 +/- 0.05 cm), and BMI (1.5 +/- 0.06), respectively. Mean differences by maternal characteristics were similar, but statistically significant, likely in part from the large sample size. The sensitivity for birth certificate data was 77.3% (+/-1.42) for underweight (BMI < 18.5) and 76.4% (+/-0.51) for obesity (BMI ≥ 30). Specificity was 96.8% (+/-0.12) for underweight and 97.5% (+/-0.12) for obesity. Birth certificate data had higher underweight prevalence (6 vs. 4%) and lower obesity prevalence (24 vs. 29%), compared with WIC data. Although birth certificate data overestimated underweight and underestimated obesity prevalence, the difference was minimal and has limited impact on the reliability and validity for population-based surveillance and research purposes related to recall or reporting bias. |
Hospitalizations for coccidioidomycosis at forty-one children's hospitals in the United States
Fisher BT , Chiller TM , Prasad PA , Beveridge M , Walsh TJ , Zaoutis TE . Pediatr Infect Dis J 2009 29 (3) 243-7 BACKGROUND: Coccidioidomycosis is often a self-limiting pulmonary infection, but it can cause more clinically apparent disease leading to hospitalization. We describe the characteristics of initial and subsequent hospitalizations in children with coccidioidomycosis. METHODS: Using the Pediatric Health Information System (PHIS), an inpatient database, we identified retrospectively a cohort of patients hospitalized between April 1, 2002 and June 30, 2007 at children's hospitals across the United States. Demographic, clinical, and therapeutic data for the initial and subsequent hospitalizations were collected and analyzed. RESULTS: We identified 199 children who had 295 hospitalizations for coccidioidomycosis. The median hospital length of stay was 7 days (interquartile range: 3-14 days). Hospital incidence rates were stable from 2003 to 2005 but increased significantly from 2005 to 2006 (8.31/100,000 discharges vs. 12.95/100,000 discharges; chi = 4.65, P = 0.031). Fluconazole was the most commonly used antifungal agent, but 17.1% of patients were initially managed without antifungal therapy. The presence of an underlying comorbid condition was common (34.2%) as was the need for surgical intervention (41%). In-hospital mortality was low (1.5%). CONCLUSIONS: The increase in hospitalization rates associated with coccidioidomycosis from 2005 to 2006 mirrors the increase in cases reported to the Centers for Disease Control and Prevention during the same time period. Hospital admission for coccidioidomycosis seems to be more common in patients with underlying comorbid conditions and frequently necessitates surgical intervention. |
Reconciling longwall gob gas reservoirs and venthole production performances using multiple rate drawdown well test analysis
Karacan C . Int J Coal Geol 2009 80 181-195 Longwall mining is an underground mining method during which a mechanical shearer progressively mines a large block of coal, called a panel, in an extensive area. During this operation the roof of the coal seam is supported only temporarily with hydraulic supports that protect the workers and the equipment on the coal face. As the coal is extracted, the supports automatically advance and the roof strata cave behind the supports. Caving results in fracturing and relaxation of the overlying strata, which is called "gob." Due its highly fractured nature, gob contains many flow paths for gas migration. Thus, if the overlying strata contain gassy sandstones or sandstone channels, gas shales or thinner coal seams which are not suitable for mining, then the mining-induced changes can cause unexpected or uncontrolled gas migration into the underground workplace. Vertical gob gas ventholes (GGV) are drilled into each longwall panel to capture the methane within the overlying fractured strata before it enters the work environment. Thus, it is important, first to understand the properties of the gas reservoir created by mining disturbances and, second, to optimize the well parameters and placement accordingly. In this paper, the production rate-pressure behaviors of six GGVs drilled over three adjacent panels were analyzed by using conventional multi-rate drawdown analysis techniques. The analyses were performed for infinite acting and pseudo-steady state flow models, which may be applicable during panel mining (DM) and after mining (AM) production periods of GGVs. These phases were analyzed separately since the reservoir properties, due to dynamic subsidence, boundary conditions and gas capacity of the gob reservoir may change between these two stages. The results suggest that conventional well test analysis techniques can be applicable to highly complex gob reservoirs and GGVs to determine parameters such as skin, permeability, radius of investigation, flow efficiency and damage ratio. The insights obtained from well test analyses can be used for a better understanding of the gob and for designing more effective gob gas venthole systems. |
Elastic and shear moduli of coal measure rocks derived from basic well logs using fractal statistics and radial basis functions
Karacan C . Int J Rock Mech Min Sci 2009 46 (8) 1281-1295 Gamma ray, density, sonic and core logs obtained from two boreholes drilled over a longwall panel in Southwestern (SW) Pennsylvania were analyzed for formation boundaries, log-derived porosities and densities and for rock elastic properties from sonic transit times. Gamma ray (GR) and density logs (DL) were analyzed using univariate statistical techniques and fractal statistics for similarity and ordering of the log data in depth. A Fourier transformation with low-pass filter was used as a noise elimination (filtering) technique from the original logs. Filtered data was tested using basic univariate and fractal statistics, rescaled range (R/S) and power spectrum (PS) analysis to compare the information characteristics of the filtered logs with the original data. The randomness of log data in depth was analyzed for fractional Gaussian noise (fGn) or fractional Brownian motion (fBm) character. A new prediction technique using radial basis function (RBF) networks was developed to calculate shear and Young’s moduli of the formations when sonic logs are not available. For this approach, the filtered logs were used as input to an RBF based upon a combination of supervised and unsupervised learning. The network was trained and tested using rock elastic properties calculated from the sonic log of one of the boreholes. The network was used to predict the elastic and shear moduli of the coalmeasure rocks over a longwall coal mine in SW Pennsylvania. This approach demonstrated that it could be used for prediction of elastic and shear moduli of coal-measure rocks with reasonable accuracy. |
Analytical performance criteria. Beryllium research needs
Ashley K , McCawley M . J Occup Environ Hyg 2009 6 (12) D92-6 The Beryllium Research Needs Subcommittee of the Beryllium Health and Safety Committee (BHSC) comprises primarily U.S. Department of Energy (DOE) workers and contractors, workers and contractors from the United Kingdom's Atomic Weapons Establishment, as well as other parties interested in beryllium health research. This subcommittee has attempted to identify and prioritize those research topics that have utility for sampling, analysis, control, and prevention of chronic beryllium disease. As part of this effort, in 2002, the subcommittee reviewed the current literature and attempted to identify a list of topics most pertinent to help prevent chronic beryllium disease for which research was lacking. After some debate, a list of 27 topics was proposed. | The advent of a new website for the BHSC offers the potential for continual comment and updating in a more interactive format. Postings can be shared and polls conducted for both members and nonmembers. The list offers a potential scorecard on beryllium health and safety research by allowing researchers and users to post steps being taken to meet the needs in the list, as well as identifying potentially new topics that will further the goal of controlling exposure and preventing beryllium sensitization and disease. |
Evaluation of peripheral visual performance when using incandescent and LED miner cap lamps
Sammarco JJ , Reyes MA , Bartels JR , Gallagher S . IEEE Trans Ind Appl 2009 45 (6) 1923-1929 Illumination plays a critical role in an underground miner’s safety because miners depend most heavily on visual cues to recognize hazards. Mobile mining machinery, located in the miners peripheral field-of-view (±10° to about ±60° off-axis), may pose potential pinning and striking hazards. The main objective of this research was to determine if there were peripheral visual performance improvements for the detection of moving objects when using cool-white light-emitting diode (LED) cap lamps as compared to incandescent (INC) light bulbs commonly used in miner cap lamps. The cap lamp variable of interest is the spectral power distribution (SPD); the illuminances were normalized by a diffusion filter. The second objective was to determine if age is a factor for peripheral visual performance. This is important because the workforce is aging - the average miner age is about 43 years old. Thirty subjects participated in the study; ten subjects each in the age groups of younger (18 to 25 years), middle (40 to 50 years), and older (50+ years). Visual performance was quantified by the subjects’ speed and accuracy of response to detect the rotation of high-contrast (white) circular targets located 3.83 meters (m) away at -20°, 40°, and 50° off-axis. The speed of detection and the number of missed target rotations (accuracy) were measured. The prototype LED cap lamp results were best with a 11% to 15% improvement compared to the INC and LED cap lamps respectively. Age does appear to be a significant factor. For the middle and older age groups’, target movement detection time increased 75% and 60% and the number of missed targets increased 500% and 450% respectively in comparison to the youngest age group. The results also suggest that target location is a significant factor. The subjects’ target movement detection time for the 40° and 50° target movements increased 16% and 69% respectively as compared to the -20° target. |
Fall from equipment injuries in U.S. mining: identification of specific research areas for future investigation
Moore SM , Porter WL , Dempsey PG . J Safety Res 2009 40 (6) 455-60 INTRODUCTION: The objective of this study was to evaluate the circumstances leading to fall from equipment injuries in the mining industry. METHOD: The 2006 and 2007 Mine Safety and Health Administration annual injury databases were utilized for this study whereby the injury narrative, nature of injury, body part injured, mine type, age at injury, and days lost were evaluated for each injury. RESULTS: The majority of injuries occurred at surface mining facilities (approximately 60%) with fractures and sprains/strains being the most common injuries occurring to the major joints of the body. Nearly 50% of injuries occurred during ingress/egress, predominantely during egress, and approximately 25% of injuries occurred during maintenance tasks. The majority of injuries occurred in relation to large trucks, wheel loaders, dozers, and conveyors/belts. The severity of injury was independent of age and the median days lost was seven days; however, there was a large range in severity. IMPACT ON INDUSTRY: From the data obtained in this study, several different research areas have been identified for future work, which include balance and stability control when descending ladders and equipment design for maintenance tasks. |
The bottom-up approach to integrative validity: a new perspective for program evaluation
Chen HT . Eval Program Plann 2009 33 (3) 205-14 The Campbellian validity model and the traditional top-down approach to validity have had a profound influence on research and evaluation. That model includes the concepts of internal and external validity and within that model, the preeminence of internal validity as demonstrated in the top-down approach. Evaluators and researchers have, however, increasingly recognized that in an evaluation, the over-emphasis on internal validity reduces that evaluation's usefulness and contributes to the gulf between academic and practical communities regarding interventions. This article examines the limitations of the Campbellian validity model and the top-down approach and provides a comprehensive, alternative model, known as the integrative validity model for program evaluation. The integrative validity model includes the concept of viable validity, which is predicated on a bottom-up approach to validity. This approach better reflects stakeholders' evaluation views and concerns, makes external validity workable, and becomes therefore a preferable alternative for evaluation of health promotion/social betterment programs. The integrative validity model and the bottom-up approach enable evaluators to meet scientific and practical requirements, facilitate in advancing external validity, and gain a new perspective on methods. The new perspective also furnishes a balanced view of credible evidence, and offers an alternative perspective for funding. |
Seat belt use in States and territories with primary and secondary laws--United States, 2006
Beck LF , Shults RA . J Safety Res 2009 40 (6) 469-72 PROBLEM: Motor-vehicle crashes are a leading cause of death in the United States. In the event of a crash, seat belts are highly effective in preventing serious injury and death. METHODS: Data from the 2006 Behavioral Risk Factor Surveillance System were used to calculate prevalence of seat belt use by state and territory and by type of state seat belt law (primary vs. secondary enforcement). RESULTS: In 2006, seat belt use among adults ranged from 58.3% to 91.9% in the states and territories. Seat belt use was 86.0% in states and territories with primary enforcement laws and 75.9% in states with secondary enforcement laws. DISCUSSION: Seat belt use continues to increase in the United States. Primary enforcement laws remain a more effective strategy than secondary enforcement laws in getting motor-vehicle occupants to wear their seat belts. |
The effectiveness of limiting alcohol outlet density as a means of reducing excessive alcohol consumption and alcohol-related harms
Campbell CA , Hahn RA , Elder R , Brewer R , Chattopadhyay S , Fielding J , Naimi TS , Toomey T , Lawrence B , Middleton JC , Task Force on Community Preventive Services . Am J Prev Med 2009 37 (6) 556-69 The density of alcohol outlets in communities may be regulated to reduce excessive alcohol consumption and related harms. Studies directly assessing the control of outlet density as a means of controlling excessive alcohol consumption and related harms do not exist, but assessments of related phenomena are indicative. To assess the effects of outlet density on alcohol-related harms, primary evidence was used from interrupted time-series studies of outlet density; studies of the privatization of alcohol sales, alcohol bans, and changes in license arrangements-all of which affected outlet density. Most of the studies included in this review found that greater outlet density is associated with increased alcohol consumption and related harms, including medical harms, injury, crime, and violence. Primary evidence was supported by secondary evidence from correlational studies. The regulation of alcohol outlet density may be a useful public health tool for the reduction of excessive alcohol consumption and related harms. |
Reframing the dissemination challenge: a marketing and distribution perspective
Kreuter MW , Bernhardt JM . Am J Public Health 2009 99 (12) 2123-7 A fundamental obstacle to successful dissemination and implementation of evidence-based public health programs is the near-total absence of systems and infrastructure for marketing and distribution. We describe the functions of a marketing and distribution system, and we explain how it would help move effective public health programs from research to practice. Then we critically evaluate the 4 dominant strategies now used to promote dissemination and implementation, and we explain how each would be enhanced by marketing and distribution systems. Finally, we make 6 recommendations for building the needed system infrastructure and discuss the responsibility within the public health community for implementation of these recommendations. Without serious investment in such infrastructure, application of proven solutions in public health practice will continue to occur slowly and rarely. |
Follow-up for cervical abnormalities in a managed care plan, 1999-2004
Benard VB , Berkman ND , Kuo T , Martin CK , Richardson LC . Prev Med 2009 50 81-5 OBJECTIVE: To determine the follow-up for women after receiving an abnormal Pap test before and after the updated American Society of Colposcopic and Cervical Pathology (ASCCP) guidelines for management of abnormal cytology. METHODS: In 1999 and 2004, women who had been enrolled in a US health care plan for at least 21 months and were between 18 and 70 years of age were included. We calculated differences in type of follow-up between the time periods before and after ASCCP guideline changes in 2002. RESULTS: Overall, 1.7 million women met study criteria and received at least one Pap test. Overall, 227,802 (14%) women received additional follow-up. Of these women, 73% had a repeat Pap test within 9 months as their first follow-up, 13% received colposcopy, and 7% had other events. The proportion of women receiving a repeat Pap test decreased significantly during the post-guideline time period. The odds of a woman receiving a colposcopy versus a repeat Pap test were 41 percent higher in the post-guideline period, after controlling for other variables. CONCLUSIONS: Our findings indicate that for the time period after the ASCCP guidelines changed, more colposcopies and fewer repeat Pap tests were performed as a follow-up of abnormal Pap test. |
Randomized trial of the effects of housing assistance on the health and risk behaviors of homeless and unstably housed people living with HIV
Wolitski RJ , Kidder DP , Pals SL , Royal S , Aidala A , Stall R , Holtgrave DR , Harre D , Courtenay-Quirk C , Housing Health Study Team . AIDS Behav 2009 14 (3) 493-503 Homelessness affects HIV risk and health, but little is known about the longitudinal effects of rental assistance on the housing status and health of homeless and unstably housed people living with HIV/AIDS. Homeless/unstably housed people living with HIV/AIDS (N = 630) were randomly assigned to immediate Housing Opportunities for People with AIDS (HOPWA) rental assistance or customary care. Self-reported data, CD4, and HIV viral load were collected at baseline, 6, 12, and 18 months. Results showed that housing status improved in both groups, with greater improvement occurring in the treatment group. At 18 months, 51% of the comparison group had their own housing, limiting statistical power. Intent-to-treat analyses demonstrated significant reductions in medical care utilization and improvements in self-reported physical and mental health; significant differential change benefiting the treatment group was observed for depression and perceived stress. Significant differences between homeless and stably housed participants were found in as-treated analyses for health care utilization, mental health, and physical health. HOPWA rental assistance improves housing status and, in some cases, health outcomes of homeless and unstably housed people living with HIV/AIDS. |
Role of self-concept in answering survey questions on complementary and alternative medicine: challenges to and strategies for improving data quality
Willson S , Stussman B , Maitland A , Nahin RL . J Altern Complement Med 2009 15 (12) 1319-25 OBJECTIVES: The aim of this study was to assess the construct validity of survey questions about the use of herbal and other nonvitamin/nonmineral dietary supplements. DESIGN: We conducted one-on-one, in-depth cognitive interviews with 32 respondents to test questions from the complementary and alternative medicine (CAM) supplement for the 2007 National Health Interview Survey. Respondents were sampled purposively according to their use of CAM. Interviewers probed respondents for their understanding of the questions, and analysis was guided by grounded theory, an approach that generates explanations of response error that are closely tied to the empirical data. RESULTS: We found two sources of misinterpretation of CAM questions. First, some respondents did not have any pre-established definition of what constitutes an herbal supplement while others had interpretations that did not match the intended definitions. These problems are common to many survey questions. However, a second finding is that misinterpretation also arose when respondents incorporated notions of self-concept into the act of taking "natural herbs," and answered based on their understanding of this image rather than on actual behavior. CONCLUSIONS: There are several sources of misinterpretation of CAM questions. One of the most important sources is whether or not the respondent has created a concept of self-image that includes the use of herbal supplements. Common questionnaire design techniques such as providing definitions to respondents will not help to eliminate misinterpretation due to self-image. We found that careful question wording that does not evoke definitions of self, combined with visual aids that narrow the focus of the questions, can lead to more accurate answers. |
Molecular detection of novel adenoviruses in fecal specimens of captive monkeys with diarrhea in China
Banyai K , Esona MD , Liu A , Wang Y , Tu X , Jiang B . Vet Microbiol 2009 142 416-9 Adenovirus (AdV) has been recently detected among monkeys with diarrhea in a major research primate colony in China. To better assess disease burden and epidemiology of adenoviruses in the colony, we examined the prevalence of this virus in fecal specimens by PCR using broadly reactive hexon gene-specific primers. Of the 29 strains that were characterized by sequence and phylogenetic analysis, we identified a broad spectrum of simian AdV (SAdV) types, including species SAdV-A (n=14) and HAdV-G (n=9). Six additional strains represented two genetic clusters distantly related to other known SAdVs. A better understanding of the epidemiology of SAdVs and their potential role in gastroenteritis is critical to the implementation of advanced prevention strategies against AdV infection in captive primates. |
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