Lower risk of Creutzfeldt-Jakob disease in pituitary growth hormone recipients initiating treatment after 1977
Abrams JY , Schonberger LB , Belay ED , Maddox RA , Leschek EW , Mills JL , Wysowski DK , Fradkin JE . J Clin Endocrinol Metab 2011 96 (10) E1666-9 CONTEXT: Creutzfeldt-Jakob disease (CJD) caused by contaminated cadaveric pituitary-derived human GH (hGH) has been responsible for hundreds of deaths worldwide. Studies of U.S. National Hormone and Pituitary Program (NHPP) hGH recipients have found CJD only in patients treated before 1977, when a new purification procedure with column chromatography was implemented for hGH extraction. OBJECTIVE: Our objective was to provide updated information on transmission of CJD to NHPP hGH recipients and determine whether recipients of hGH produced after 1977 had a significantly lower CJD risk than pre-1977 recipients. PATIENTS: A total of 5570 NHPP hGH recipients were included in the study: 2099 in the pre-1977 cohort and 3471 in the post-1977 cohort. MAIN OUTCOME MEASURE: We used probability distribution functions to determine whether the observed number of CJD cases in the post-1977 cohort was significantly fewer than expected if the CJD risk was equal to that of the pre-1977 cohort, controlling for treatment duration and follow-up time. RESULTS: All 22 CJD cases (diagnosed from 1984-2009) occurred in the pre-1977 hGH recipients. Almost half (47.9%) of pre-1977 recipients had a treatment duration of at least 5 yr compared with only 13.8% for post-1977 recipients. Based on the rates present in the pre-1977 cohort, the probability of observing no cases in the post-1977 cohort by chance alone was low (P = 0.0019). CONCLUSIONS: Risk of acquiring CJD was significantly lower for post-1977 NHPP hGH recipients than for pre-1977 recipients, suggesting that the new purification procedure in 1977 may have greatly reduced or eliminated CJD agent in hGH. |
Gynecologic oncologists and ovarian cancer treatment: avenues for improved survival
Stewart SL , Rim SH , Richards TB . J Womens Health (Larchmt) 2011 20 (9) 1257-60 Ovarian cancer is the deadliest gynecologic malignancy in the United States. Evidence-based interventions for the prevention and early detection of ovarian cancer do not currently exist. However, several treatment guidelines, including the receipt of treatment from a gynecologic oncologist, have been shown to result in improved survival from ovarian cancer. |
Association of sleep-related problems with CKD in the United States, 2005-2008
Plantinga L , Lee K , Inker LA , Saran R , Yee J , Gillespie B , Rolka D , Saydah S , Powe NR . Am J Kidney Dis 2011 58 (4) 554-64 BACKGROUND: Sleep-related problems, which have been associated with poor health outcomes, have not been investigated thoroughly in people with chronic kidney disease (CKD). We examined the prevalence of a variety of sleep-related problems in persons with and without CKD. STUDY DESIGN: National cross-sectional survey (National Health and Nutrition Examination Survey 2005-2008). SETTING & PARTICIPANTS: Community-based survey of 9,110 noninstitutionalized US civilian residents 20 years or older. PREDICTOR: CKD, defined as estimated glomerular filtration rate (eGFR) of 15-59 mL/min/1.73 m(2) (stages 3 and 4) or eGFR ≥60 mL/min/1.73 m(2) and albumin-creatinine ratio ≥30 mg/g (stages 1 and 2). OUTCOME: Sleep quality, defined using self-report in a multi-item sleep questionnaire including items from previously validated instruments. MEASUREMENTS: Albuminuria and eGFR assessed from urine and blood samples; sleep, demographics, and comorbid conditions assessed using a standardized questionnaire. RESULTS: Inadequate sleep (≤6 hours per night) differed by CKD severity (37.4%, 43.0%, and 30.9% for no CKD, CKD stages 1 and 2, and CKD stages 3 and 4, respectively; P = 0.003). Frequent sleeping pill use (8.4%, 9.9%, and 16.6%), leg symptoms (39.2%, 48.0%, and 50.9%), and nocturia (20.9%, 35.2%, and 43.6%; P < 0.001 for all) also differed by CKD severity. After adjustment for age, sex, race/ethnicity, obesity, diabetes, and cardiovascular disease, the prevalence of these sleep-related problems remained higher in people with CKD stages 1 and 2 relative to no CKD. Most other measures of sleep quality, disorder, and functional outcomes did not differ by CKD. LIMITATIONS: Inability to establish causality and possible unmeasured confounding. CONCLUSION: Providers should be aware of early sleep-related CKD manifestations, including inadequate sleep, leg symptoms, and nocturia, and of the high rate of reported sleep medication use in this population. |
Colorectal cancer screening use among insured primary care patients
Shires DA , Divine G , Schum M , Gunter MJ , Baumer DL , Kasprzyk D , Montano DE , Smith JL , Elston-Lafata J . Am J Manag Care 2011 17 (7) 480-8 OBJECTIVE: To compare colorectal cancer (CRC) screening use, including changes over time and demographic characteristics associated with screening receipt, between 2 insured primary care populations. STUDY DESIGN: Clinical and administrative records from 2 large health systems, one in New Mexico and the other in Michigan, were used to determine use of CRC screening tests between 2004 and 2008 among patients aged 51 to 74 years. METHODS: Generalized estimating equations were used to evaluate trends in CRC screening use over time and the association of demographic and other factors with screening receipt. RESULTS: Rates of CRC screening use ranged from 48.1% at the New Mexico site to 68.7% at the Michigan site, with colonoscopy being the most frequently used modality. Fecal occult blood test was used inconsistently by substantial proportions of patients who did not meet the definition of screening users. Screening use was positively and significantly associated with older age, male sex, and more periodic health examinations and other types of primary care visits; at the Michigan site, it was also associated with African American race, married status, and higher annual estimated household income. CONCLUSIONS: Among insured primary care patients, CRC screening use falls short. Further research is needed to determine what factors are barriers to routine fecal occult blood test or colonoscopy use among insured patients who have access to and regularly use primary care and how those barriers can be eliminated. |
Respiratory syncytial virus-associated hospitalizations among infants and young children in the United States, 1997-2006
Stockman LJ , Curns AT , Anderson LJ , Fischer-Langley G . Pediatr Infect Dis J 2011 31 (1) 5-9 BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease among young children in the United States. RSV-associated hospitalization increased among children in the United States during 1980 through 1996. In this study, we updated national estimates of RSV hospitalization rates among US children through 2006. METHODS: We conducted a retrospective analysis of hospital discharges for lower respiratory tract illness (LRTI) in children <5 years old from the National Hospital Discharge Survey. LRTI hospitalizations were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification codes. RSV-coded hospitalizations were International Classification of Diseases, Ninth Revision, Clinical Modification codes 466.11, 480.1, and 079.6. RSV-associated hospitalizations were the sum of RSV-coded hospitalizations and a proportion of hospitalizations coded as bronchiolitis and pneumonia during the RSV season. RESULTS: RSV-coded hospitalizations accounted for 24% of an estimated 5.5 million LRTI hospitalizations among children <5 years of age during the 10 study years, 1997-2006. The RSV-coded hospitalization rate in infants <1 year old was 26.0 per 1000, with no significant difference between study years. The hospitalization rate was highest among infants <3 months old (48.9 per 1000), followed by infants 3 to 5 months old (28.4 per 1000), and lower among those >1 year old (1.8 per 1000). An estimated 132,000 to 172,000 RSV-associated hospitalizations occurred annually in children <5 years of age. CONCLUSION: RSV hospitalization rates remained steady during 1997 to 2006 and were a substantial burden in the United States, especially among infants and young children. A safe and effective RSV vaccine is needed. |
Retention in an antiretroviral therapy programme during an era of decreasing drug cost in Limbe, Cameroon
Mosoko JJ , Akam W , Weidle PJ , Brooks JT , Aweh AJ , Kinge TN , Pals S , Raghunathan PL . J Int AIDS Soc 2011 14 32 BACKGROUND: In 2002, Cameroon initiated scale up of antiretroviral therapy (ART); on 1 October 2004, a substantial reduction in ART cost occurred. We assessed the impact of this event and other factors on enrolment and retention in care among HIV-infected patients initiating ART from February 2002 to December 2005 at the single ART clinic serving the Southwest Region in Limbe, Cameroon. METHODS: We retrospectively analyzed clinical and pharmacy payment records of HIV-infected patients initiating ART according to national guidelines. We compared two cohorts of patients, enrolled before and after 1 October 2004, to determine if price reduction was associated with enhanced enrolment. We assessed factors associated with retention and survival by Cox proportional hazards models. Retention in care implied patients who had contact with the healthcare system as of 31 December 2005 (including those who were transferred to continue care in other ART centres), although these patients may have interrupted therapy at some time. A patient who was not retained in care may have dropped out (lost to follow up) or died. RESULTS: Mean enrolment rates for 2920 patients who initiated ART before and after the price reduction were 46.5 and 95.5 persons/month, respectively (p < 0.001). The probabilities of remaining alive and in care were 0.66 (95% CI 0.64-0.68) at six months, 0.58 (95% CI 0.56-0.60) at one year, 0.47 (95% CI 0.45-0.49) at two years and 0.35 (95% CI 0.32-0.38) at three years; they were not significantly different between the two cohorts of patients enrolled before and after the price reduction over the first 15 months of comparable follow up (hazard ratio 1.1; 95% CI 0.9-1.2, p = 0.27). In multivariable analysis using multiple imputations to compensate for missing values, factors associated with dropping out of care or dying were male gender (HR 1.33 [1.18-1.50], p = 0.003), treatment paid by self, family or partly by other (HR 3.05 [1.99-4.67], p < 0.001), and, compared with residents of Limbe, living more than 150 km from Limbe (HR 1.41 [1.18-1.69], p < 0.001), or being residents of Douala (HR 1.51 [1.16-1.98], p < 0.001). CONCLUSIONS: Reducing the cost of ART increased enrolment of clients in the programme, but did not change retention in care. In a system where most clients pay for ART, an accessible clinic location may be more important than the cost of medication for retention in care. Decentralizing ART clinics might improve retention and survival among patients on ART. |
Emergence of 2009A/H1N1 cases in a tertiary care hospital in New Delhi, India
Broor S , Gupta S , Mohapatra S , Kaushik S , Mir MA , Jain P , Dar L , Lal RB . Influenza Other Respir Viruses 2011 5 (6) e552-7 OBJECTIVE: To determine virologic and epidemiologic characteristics of pandemic (H1N1) 2009 at All India Institute of Medical Sciences (AIIMS) a tertiary care hospital in New Delhi, India. METHODS: Nasal and throat swabs from patients with febrile acute respiratory illness (FARI) from August to December 2009 (n = 1401) were tested for 2009A/H1N1 and seasonal influenza A viruses by real-time RT-PCR. RESULTS: Of 1401 samples tested, 475 (33.9%) were positive for influenza A, of these majority (412; 87%) were 2009A/H1N1, whereas the remaining 63 (13%) were seasonal influenza A (49 were A/H3 and 14 were A/H1). While co-circulation of 2009A/H1N1 and A/H3 was observed in August-September, subsequent months had exclusive pandemic influenza activity (October-December 2009). Pandemic 2009A/H1N1 emergence did not follow typical seasonal influenza seasonality in New Delhi, which normally peaks in July-August, but instead showed bimodal peaks in weeks 39 and 48 in 2009. The percent of specimens testing positive for 2009A/H1N1 influenza virus was found to be highest in >5- to 18-year age group (41.2%; OR = 2.3; CI = 1.6-3.2; P = 0.00). CONCLUSIONS: Taken together, our data provide high prevalence of pandemic 2009A/H1N1 in urban New Delhi with bimodal peaks in weeks 39 and 48 and highest risk group being the children of school-going age (aged >5-18). |
Estimated HIV incidence in the United States, 2006-2009
Prejean J , Song R , Hernandez A , Ziebell R , Green T , Walker F , Lin LS , An Q , Mermin J , Lansky A , Hall HI . PLoS One 2011 6 (8) e17502 BACKGROUND: The estimated number of new HIV infections in the United States reflects the leading edge of the epidemic. Previously, CDC estimated HIV incidence in the United States in 2006 as 56,300 (95% CI: 48,200-64,500). We updated the 2006 estimate and calculated incidence for 2007-2009 using improved methodology. METHODOLOGY: We estimated incidence using incidence surveillance data from 16 states and 2 cities and a modification of our previously described stratified extrapolation method based on a sample survey approach with multiple imputation, stratification, and extrapolation to account for missing data and heterogeneity of HIV testing behavior among population groups. PRINCIPAL FINDINGS: Estimated HIV incidence among persons aged 13 years and older was 48,600 (95% CI: 42,400-54,700) in 2006, 56,000 (95% CI: 49,100-62,900) in 2007, 47,800 (95% CI: 41,800-53,800) in 2008 and 48,100 (95% CI: 42,200-54,000) in 2009. From 2006 to 2009 incidence did not change significantly overall or among specific race/ethnicity or risk groups. However, there was a 21% (95% CI:1.9%-39.8%; p = 0.017) increase in incidence for people aged 13-29 years, driven by a 34% (95% CI: 8.4%-60.4%) increase in young men who have sex with men (MSM). There was a 48% increase among young black/African American MSM (12.3%-83.0%; p<0.001). Among people aged 13-29, only MSM experienced significant increases in incidence, and among 13-29 year-old MSM, incidence increased significantly among young, black/African American MSM. In 2009, MSM accounted for 61% of new infections, heterosexual contact 27%, injection drug use (IDU) 9%, and MSM/IDU 3%. CONCLUSIONS/SIGNIFICANCE: Overall, HIV incidence in the United States was relatively stable 2006-2009; however, among young MSM, particularly black/African American MSM, incidence increased. HIV continues to be a major public health burden, disproportionately affecting several populations in the United States, especially MSM and racial and ethnic minorities. Expanded, improved, and targeted prevention is necessary to reduce HIV incidence. |
Increased HIV and primary and secondary syphilis diagnoses among young men - United States, 2004-2008
Torrone EA , Bertolli JM , Li J , Sweeney PA , Jeffries WL , Ham DC , Peterman TA . J Acquir Immune Defic Syndr 2011 58 (3) 328-35 OBJECTIVES: National data document increases in HIV and syphilis diagnoses in young black men who have sex with men (MSM), but trends could be driven by increases in a few large areas. We describe the extent to which metropolitan areas of varying population sizes have reported increases in HIV and syphilis diagnoses in young MSM. METHODS: We examined trends in HIV and primary and secondary syphilis case reports from 2004 to 2008 in metropolitan areas having more than 500,000 persons and at least 500 black men aged 13-24 years (n=73). We examined differences by age at diagnosis, race/ethnicity, and area size. RESULTS: Comparing 2004/2005 to 2007/2008, HIV diagnoses increased in 85% (n=62) of areas among black MSM aged 13-24 years; primary and secondary syphilis diagnoses in young black men increased in 70% of areas (n=51). Areas had an average percentage increase of 68.7% (Interquartile range (IQR): 25.0, 103.1) in HIV diagnoses among young black MSM and an average increase of 203.5% (IQR: 0.0, 192.7) in primary and secondary syphilis. Across area size strata, the youngest group of black men had the highest average percentage increase in diagnoses of HIV and syphilis as well as the highest percentage of areas with increases in diagnoses. CONCLUSIONS: HIV and syphilis diagnoses increased among young black men in almost all areas, suggesting widespread increases across metropolitan areas of different sizes. Findings highlight the need for continued prevention efforts for young MSM, particularly young black MSM. |
Characterization of acetaminophen overdose-related emergency department visits and hospitalizations in the United States
Manthripragada AD , Zhou EH , Budnitz DS , Lovegrove MC , Willy ME . Pharmacoepidemiol Drug Saf 2011 20 (8) 819-26 PURPOSE: To estimate the number of acetaminophen overdose-related emergency department (ED) visits and hospitalizations in the United States, characterize these by intentionality, age, and gender, and compare the strengths and limitations of the utilized databases. METHODS: We used data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) and the National Electronic Injury Surveillance System (NEISS) to estimate the number of relevant ED visits in the United States between 2000 and 2007, and the National Hospital Discharge Survey (NHDS) to estimate the number of relevant hospitalizations in the United States between 1991 and 2006. National estimates and their standard errors were calculated using information provided in each database. We used the standard United States population in 2000 to calculate age-adjusted rates. RESULTS: We estimate an annual average of 44,348 (NHAMCS, 2000-2007) or 78,414 (NEISS, 2006-2007) acetaminophen overdose-related ED visits and 33,520 (NHDS, 2000-2006) hospitalizations. For 2000-2006 we calculated an age-adjusted rate of 13.9 acetaminophen overdose-related hospitalizations per 100,000 US population, with the highest rate (15.7) occurring from 2005 to 2006. Between 1991 and 2006, there was no decrease noted in hospitalizations for intentional or unintentional overdoses. The majority of overdoses reported in NEISS (69.8%) and NHDS (74.2%) were classified as intentional (suicides or suicidal gestures), whereas in NHAMCS, intentionality was evenly distributed. CONCLUSIONS: Our results suggest that acetaminophen overdose, both intentional and unintentional, remains a significant public health concern. With an understanding of their methodological characteristics and limitations, these national databases can be useful tools to characterize acetaminophen overdose-related ED visits and hospitalizations. Published in 2011 by John Wiley & Sons, Ltd. |
Toxicology, environmental health, and the "One Health" concept
Buttke DE . J Med Toxicol 2011 7 (4) 329-32 The One Health concept promotes collaboration among veterinarians, physicians, scientists, and other professions to promote human, animal, and ecosystem health. One Health illustrates the interconnectedness and interdependence of human, animal, and ecosystem health. This concept has traditionally focused on zoonoses that are infectious diseases, not on chemical- or poison-related illnesses in animals and their relationship to the detection and prevention of human illness. The purpose of this article is to describe key experiences of scientists in the Health Studies Branch within the National Center for Environmental of Health of the Centers for Disease Control and Prevention in which the study of animal illness facilitated a public health investigation into an outbreak of chemical-associated human disease. The experiences highlight how utilizing the One Health approach may improve chemical-associated outbreak investigations and facilitate appropriate intervention strategies. An appropriate One Health approach in toxicology and environmental health in outbreak settings should include consideration of the common environments and food sources shared by humans and animals and consideration of the potential for contaminated animal products as food sources in human exposures. |
Phthalate exposure associated with self-reported diabetes among Mexican women
Svensson K , Hernandez-Ramirez RU , Burguete-Garcia A , Cebrian ME , Calafat AM , Needham LL , Claudio L , Lopez-Carrillo L . Environ Res 2011 111 (6) 792-6 BACKGROUND: Phthalates are ubiquitous industrial chemicals used as plasticizers in plastics made of polyvinyl chloride (PVC) to confer flexibility and durability. They are also present in products used for personal-care, industry and in medical devices. Phthalates have been associated with several adverse health effects, and recently it has been proposed that exposure to phthalates, could have an effect on metabolic homeostasis. This exploratory cross-sectional study evaluated the possible association between phthalate exposure and self-reported diabetes among adult Mexican women. METHODS: As part of an on-going case-control study for breast cancer, only controls were selected, which constituted 221 healthy women matched by age (+/-5 years) and place of residence with the cases. Women with diabetes were identified by self-report. Urinary concentrations of nine phthalate metabolites were measured by online solid phase extraction coupled to high performance liquid chromatography-isotope-dilution tandem mass spectrometry. RESULTS: Participants with diabetes had significantly higher concentrations of di(2-ethylhexyl) pththalate (DEHP) metabolites: mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) but lower levels of monobenzyl phthalate (MBzP) a metabolite of benzylbutyl phthalate, compared to participants without diabetes. A marginally significant positive associations with diabetes status were observed over tertiles with MEHHP (OR(T3 vs. T1)=2.66; 95% CI: 0.97-7.33; p for trend=0.063) and MEOHP (OR(T3 vs. T1)=2.27; 95% CI; 0.90-5.75; P for trend=0.079) even after adjusting for important confounders. CONCLUSIONS: The results suggest that levels of some phthalates may play a role in the genesis of diabetes. |
Point-of-use membrane filtration and hyperchlorination to prevent patient exposure to rapidly growing mycobacteria in the potable water supply of a skilled nursing facility
Williams MM , Chen TH , Keane T , Toney N , Toney S , Armbruster CR , Butler WR , Arduino MJ . Infect Control Hosp Epidemiol 2011 32 (9) 837-44 BACKGROUND: Healthcare-associated outbreaks and pseudo-outbreaks of rapidly growing mycobacteria (RGM) are frequently associated with contaminated tap water. A pseudo-outbreak of Mycobacterium chelonae-M. abscessus in patients undergoing bronchoscopy was identified by 2 acute care hospitals. RGM was identified in bronchoscopy specimens of 28 patients, 25 of whom resided in the same skilled nursing facility (SNF). An investigation ruled out bronchoscopy procedures, specimen collection, and scope reprocessing at the hospitals as sources of transmission. OBJECTIVE: To identify the reservoir for RGM within the SNF and evaluate 2 water system treatments, hyperchlorination and point-of-use (POU) membrane filters, to reduce RGM. DESIGN: A comparative in situ study of 2 water system treatments to prevent RGM transmission. SETTING: An SNF specializing in care of patients requiring ventilator support. METHODS: RGM and heterotrophic plate count (HPC) bacteria were examined in facility water before and after hyperchlorination and in a subsequent 24-week assessment of filtered water by colony enumeration on Middlebrook and R2A media. RESULTS: Mycobacterium chelonae was consistently isolated from the SNF water supply. Hyperchlorination reduced RGM by 1.5 log(10) initially, but the population returned to original levels within 90 days. Concentration of HPC bacteria also decreased temporarily. RGM were reduced below detection level in filtered water, a 3-log(10) reduction. HPC bacteria were not recovered from newly installed filters, although low quantities were found in water from 2-week-old filters. CONCLUSION: POU membrane filters may be a feasible prevention measure for healthcare facilities to limit exposure of sensitive individuals to RGM in potable water systems. |
Hundreds of partial pipe replacements conducted in Washington D.C. before July 2004: Brown and Sinks respond
Brown MJ , Sinks TH . Environ Res 2011 111 (6) 889 This response to a letter to the Editor by Edwards details the lack of sufficient data for further analyses. |
Results of a cross-national structured cognitive interviewing protocol to test measures of disability
Miller K , Mont D , Maitland A , Altman B , Madans J . Qual Quant 2011 45 (4) 801-815 This paper describes the Washington Group project to test a short battery of disability questions developed for national censuses. The study used an unusually structured cognitive test protocol and was administered to a total of 1,290 respondents selected from convenience samples in fifteen countries in Central and South America, Asia and Africa. The test protocol consisted of the six core disability questions followed by questions designed to illustrate: (1) whether core questions were administered with relative ease; (2) how core questions were interpreted by respondents; (3) the factors considered by respondents when forming answers to core questions; and (4) the degree of consistency between responses to core questions and a set of more detailed functioning questions. Additionally, demographic and general health sections allowed for an examination of comparability, specifically, whether test questions performed consistently across all respondents, or if nationality, education, gender or socio-economic status impacted the ways in which respondents interpreted or considered each core question. (PsycINFO Database Record (c) 2011 APA, all rights reserved) (journal abstract). |
Strengthening systems for communicable disease surveillance: creating a laboratory network in Rwanda
Kebede S , Gatabazi JB , Rugimbanya P , Mukankwiro T , Perry HN , Alemu W , Ndihokubwayo JB , Kramer MH , Mukabayire O . Health Res Policy Syst 2011 9 27 BACKGROUND: The recent emergence of a novel strain of influenza virus with pandemic potential underscores the need for quality surveillance and laboratory services to contribute to the timely detection and confirmation of public health threats. To provide a framework for strengthening disease surveillance and response capacities in African countries, the World Health Organization Regional Headquarters for Africa (AFRO) developed Integrated Disease Surveillance and Response (IDSR) aimed at improving national surveillance and laboratory systems. IDSR emphasizes the linkage of information provided by public health laboratories to the selection of relevant, appropriate and effective public health responses to disease outbreaks. METHODS: We reviewed the development of Rwanda's National Reference Laboratory (NRL) to understand essential structures involved in creating a national public health laboratory network. We reviewed documents describing the NRL's organization and record of test results, conducted site visits, and interviewed health staff in the Ministry of Health and in partner agencies. Findings were developed by organizing thematic categories and grouping examples within them. We purposefully sought to identify success factors as well as challenges inherent in developing a national public health laboratory system. RESULTS: Among the identified success factors were: a structured governing framework for public health surveillance; political commitment to promote leadership for stronger laboratory capacities in Rwanda; defined roles and responsibilities for each level; coordinated approaches between technical and funding partners; collaboration with external laboratories; and use of performance results in advocacy with national stakeholders. Major challenges involved general infrastructure, human resources, and budgetary constraints. CONCLUSIONS: Rwanda's experience with collaborative partnerships contributed to creation of a functional public health laboratory network. |
Pneumococcal antigen testing of blood culture broth to enhance the detection of Streptococcus pneumoniae bacteremia
Baggett HC , Rhodes J , Dejsirilert S , Salika P , Wansom T , Jorakate P , Kaewpan A , Olsen SJ , Maloney SA , Peruski LF . Eur J Clin Microbiol Infect Dis 2011 31 (5) 753-6 The purpose of this investigation was to enhance the detection of pneumococcal bacteremia cases using the Binax NOW(R) immunochromatographic test (ICT) on blood culture broth as part of surveillance in two rural Thailand provinces. Blood cultures were collected as clinically indicated from hospitalized patients. ICT was performed on broth from culture bottles flagged as positive by BactT/ALERT(R) (alarm-positive) but which failed to grow organisms on subculture. During the period May 2005-June 2007, ICT was positive on 43 (24%) of 182 alarm-positive blood cultures with no growth on subculture. Compared to pneumococcal bacteremia cases confirmed by culture, cases detected only by ICT had a longer median time from culture collection to incubation and a longer median time from alarm positivity to subculture, and were more likely to be from patients pretreated with antibiotics. In a subsequent surveillance period (July 2007-December 2009), ICT continued to detect additional pneumococcal cases, but in a lower proportion of samples (7 of 221, 3.2%). Recently, as part of a separate study, ICT applied to uninoculated blood culture broth produced weak-positive results, mandating caution if testing broth from patient blood cultures. The antigen testing of blood culture broth appears to enhance the detection of pneumococcal bacteremia, but a controlled evaluation is needed. |
Designing prospective cohort studies for assessing reproductive and developmental toxicity during sensitive windows of human reproduction and development - the LIFE Study
Buck Louis GM , Schisterman EF , Sweeney AM , Wilcosky TC , Gore-Langton RE , Lynch CD , Boyd Barr D , Schrader SM , Kim S , Chen Z , Sundaram R . Paediatr Perinat Epidemiol 2011 25 (5) 413-424 The relationship between the environment and human fecundity and fertility remains virtually unstudied from a couple-based perspective in which longitudinal exposure data and biospecimens are captured across sensitive windows. In response, we completed the LIFE Study with methodology that intended to empirically evaluate a priori purported methodological challenges: * implementation of population-based sampling frameworks suitable for recruiting couples planning pregnancy; * obtaining environmental data across sensitive windows of reproduction and development; * home-based biospecimen collection; and * development of a data management system for hierarchical exposome data. We used two sampling frameworks (i.e. fish/wildlife licence registry and a direct marketing database) for 16 targeted counties with presumed environmental exposures to persistent organochlorine chemicals to recruit 501 couples planning pregnancies for prospective longitudinal follow-up while trying to conceive and throughout pregnancy. Enrolment rates varied from <1% of the targeted population (n = 424 423) to 42% of eligible couples who were successfully screened; 84% of the targeted population could not be reached, while 36% refused screening. Among enrolled couples, approximately 85% completed daily journals while trying; 82% of pregnant women completed daily early pregnancy journals, and 80% completed monthly pregnancy journals. All couples provided baseline blood/urine samples; 94% of men provided one or more semen samples and 98% of women provided one or more saliva samples. Women successfully used urinary fertility monitors for identifying ovulation and home pregnancy test kits. Couples can be recruited for preconception cohorts and will comply with intensive data collection across sensitive windows. However, appropriately sized sampling frameworks are critical, given the small percentage of couples contacted found eligible and reportedly planning pregnancy at any point in time. |
Foodborne outbreak of Salmonella subspecies IV infections associated with contamination from bearded dragons
Lowther SA , Medus C , Scheftel J , Leano F , Jawahir S , Smith K . Zoonoses Public Health 2011 58 (8) 560-6 Approximately 1.4 million Salmonella infections and 400 deaths occur annually in the United States. Approximately 6% of human Salmonella cases are thought to be associated with reptiles; Salmonella enterica subspecies IV is primarily reptile-associated. During 1-4 December, 2009, three isolates of Salmonella IV 6,7:z4,z24:- with indistinguishable pulsed-field gel electrophoresis (PFGE) patterns were identified through Minnesota Department of Health laboratory-based surveillance. None of the three patients associated with the isolates reported reptile contact; however, all had attended the same potluck dinner. Dinner attendees were asked questions regarding illness history, foods they prepared for and consumed at the event, and pet ownership. Cases were defined as illness in a person who had eaten potluck food and subsequently experienced fever and diarrhoea (three or more loose stools in 24 h) or laboratory-confirmed infection with Salmonella IV matching the outbreak PFGE subtype. Nineteen days after the event, environmental samples were collected from a food preparer's house where two pet bearded dragons were kept. Sixty-six of 73 potluck food consumers were interviewed; 19 cases were identified; 18 persons reported illness but did not meet the case definition. Median incubation period was 19 h (range: 3-26 h). Median duration of illness was 5 days (range: 1-11 days). Consumption of gravy, prepared by the bearded dragons' asymptomatic owner, was associated with illness (16/32 exposed versus 1/12 unexposed; risk ratio: 6.0; exact P = 0.02). Salmonella Labadi was recovered from 10 samples, including from one bearded dragon, the bathroom door knob and sink drain, and the kitchen sink drain. The outbreak PFGE subtype of Salmonella subspecies IV was isolated from vacuum-cleaner bag contents. This foodborne outbreak probably resulted from environmental contamination from bearded dragons. Reptiles pose a community threat when food for public consumption is prepared in households with reptiles. |
Assessing causal relationships in genomics: From Bradford-Hill criteria to complex gene-environment interactions and directed acyclic graphs.
Geneletti S , Gallo V , Porta M , Khoury MJ , Vineis P . Emerg Themes Epidemiol 2011 8 (1) 5 Observational studies of human health and disease (basic, clinical and epidemiological) are vulnerable to methodological problems -such as selection bias and confounding- that make causal inferences problematic. Gene-disease associations are no exception, as they are commonly investigated using observational designs. A rich body of knowledge exists in medicine and epidemiology on the assessment of causal relationships involving personal and environmental causes of disease; it includes seminal causal criteria developed by Austin Bradford Hill and more recently applied directed acyclic graphs (DAGs). However, such knowledge has seldom been applied to assess causal relationships in clinical genetics and genomics, even in studies aimed at making inferences relevant for human health. Conversely, incorporating genetic causal knowledge into clinical and epidemiological causal reasoning is still a largely unexplored area.As the contribution of genetics to the understanding of disease aetiology becomes more important, causal assessment of genetic and genomic evidence becomes fundamental. The method we develop in this paper provides a simple and rigorous first step towards this goal. The present paper is an example of integrative research, i.e., research that integrates knowledge, data, methods, techniques, and reasoning from multiple disciplines, approaches and levels of analysis to generate knowledge that no discipline alone may achieve. |
Cancer GAMAdb: database of cancer genetic associations from meta-analyses and genome-wide association studies.
Schully SD , Yu W , McCallum V , Benedicto CB , Dong LM , Wulf A , Clyne M , Khoury MJ . Eur J Hum Genet 2011 19 (8) 928-30 In the field of cancer, genetic association studies are among the most active and well-funded research areas, and have produced hundreds of genetic associations, especially in the genome-wide association studies (GWAS) era. Knowledge synthesis of these discoveries is the first critical step in translating the rapidly emerging data from cancer genetic association research into potential applications for clinical practice. To facilitate the effort of translational research on cancer genetics, we have developed a continually updated database named Cancer Genome-wide Association and Meta Analyses database that contains key descriptive characteristics of each genetic association extracted from published GWAS and meta-analyses relevant to cancer risk. Here we describe the design and development of this tool with the aim of aiding the cancer research community to quickly obtain the current updated status in cancer genetic association studies. |
Use of complementary and alternative medicine among USA adults with functional limitations: For treatment or general use?
Okoro CA , Zhao G , Li C , Balluz LS . Complement Ther Med 2011 19 (4) 208-15 OBJECTIVES: This study compared the use of complementary and alternative medicine (CAM) to treat health conditions with CAM use for general wellness or disease prevention among USA adults with and without functional limitations. DESIGN: This was a cross-sectional survey. METHODS: Data were obtained from the 2007 U.S. National Health Interview Survey (n=20,710). RESULTS: Overall use of CAM treatment was higher among adults with functional limitations than among those without (61.4% versus 41.8%; p<0.001). Adults with functional limitations were more likely to use 3 of 4 CAM groupings: biologically based therapies (BBT) (47.9% versus 29.5%, p<0.001), manipulative and body-based therapies (73.7% versus 54.1%, p<0.001), and mind-body therapies (MBT) (39.3% versus 17.4%, p<0.001). Use of alternative medical systems for treatment was highly prevalent among adults (86.9% versus 80.0%, p=0.06), regardless of functional status. Adults with functional limitations were as likely to use CAM to treat the condition underlying their functioning difficulty (48.7%) as they were to treat other conditions (51.3%). Massage therapy was used most often to treat conditions that limited functional ability (53.4%). Older age was a predictor of the use of BBT for treatment, whereas younger age was a predictor of the use of MBT. CONCLUSIONS: The prevalence of CAM use for treatment of conditions is high. Public health strategies are needed to promote disclosure of CAM use to health care providers, promote increased screening for CAM use by health care providers, and promote health care interactions that facilitate communication about CAM safety and efficacy. |
Incidence of catheter-associated and non-catheter-associated urinary tract infections in a healthcare system
Weber DJ , Sickbert-Bennett EE , Gould CV , Brown VM , Huslage K , Rutala WA . Infect Control Hosp Epidemiol 2011 32 (8) 822-3 The Centers for Disease Control and Prevention (CDC) has | estimated that each year in the United States, 1.7 million | infections that occur in hospitals result in 99,000 deaths.1 | Of | these infections, urinary tract infection (UTI) is the most | common, accounting for 32% of all healthcare-associated infections1 | and resulting in a total cost in the United States of | $390-450 million (in 2007 dollars).2 | The major risk factor | for UTI is an indwelling urinary catheter. For this reason, | surveillance efforts by the National Nosocomial Infections | Surveillance System (NNIS)3 | and, more recently, the National | Healthcare Safety Network (NHSN) have focused on urinary | catheter-associated urinary tract infection (CAUTI) in the | intensive care unit (ICU).4 | In addition, recent authoritative | guidelines for the prevention of UTI have also focused on | CAUTI.56 | The mean incidence rate of CAUTI (per 1,000 catheterdays) in patients in the ICU has been reported to range from | 3.1 to 7.4." Only limited data are available regarding the incidence of CAUTI outside of the ICU. Because NHSN does | not publish data regarding the incidence of non-catheterassociated UTI, the current incidence rate of this infection is | not available. For these reasons, we undertook this study to | evaluate the incidence of both catheter-associated and noncatheter-associated UTI stratified by medical service and type | of unit in a university hospital. |
Student immunity requirements of health professional schools: vaccination and other means of fulfillment-United States, 2008
Miller BL , Lindley MC , Ahmed F , Wortley PM . Infect Control Hosp Epidemiol 2011 32 (9) 908-11 US health professional schools with student immunity requirements for recommended vaccines frequently accept evidence of immunity other than vaccination but vary widely on the types of evidence that are accepted. Exemptions for nonmedical reasons and, to a lesser extent, medical reasons are often obtainable by a student-written document. |
Paralytic poliomyelitis associated with Sabin monovalent and bivalent oral polio vaccines in Hungary
Estivariz CF , Molnar Z , Venczel L , Kapusinszky B , Zingeser JA , Lipskaya GY , Kew OM , Berencsi G , Csohan A . Am J Epidemiol 2011 174 (3) 316-25 Historical records of patients with vaccine-associated paralytic poliomyelitis (VAPP) in Hungary during 1961-1981 were reviewed to assess the risk of VAPP after oral polio vaccine (OPV) administration. A confirmed VAPP case was defined as a diagnosis of paralytic poliomyelitis and residual paralysis at 60 days in a patient with an epidemiologic link to the vaccine. Archived poliovirus isolates were retested using polymerase chain reaction and sequencing of the viral protein 1 capsid region. This review confirmed 46 of 47 cases previously reported as VAPP. Three cases originally linked to monovalent OPV (mOPV) 3 and one case linked to mOPV1 presented after administration of bivalent OPV 1 + 3 (bOPV). The adjusted VAPP risk per million doses administered was 0.18 for mOPV1 (2 cases/11.13 million doses), 2.96 for mOPV3 (32 cases/10.81 million doses), and 12.82 for bOPV (5 cases/390,000 doses). Absence of protection from immunization with inactivated poliovirus vaccine or exposure to OPV virus from routine immunization and recent injections could explain the higher relative risk of VAPP in Hungarian children. In polio-endemic areas in which mOPV3 and bOPV are needed to achieve eradication, the higher risk of VAPP would be offset by the high risk of paralysis due to wild poliovirus and higher per-dose efficacy of mOPV3 and bOPV compared with trivalent OPV. |
Parents' acceptance of adolescent immunizations outside of the traditional medical home
Clevenger LM , Pyrzanowski J , Curtis CR , Bull S , Crane LA , Barrow JC , Kempe A , Daley MF . J Adolesc Health 2011 49 (2) 133-40 PURPOSE: Numerous barriers to vaccination exist for adolescents. Using the medical home as the sole source of adolescent vaccination has potential limitations. The objectives of the present study were to examine parents' acceptance of adolescent vaccination outside of the medical home and parents' preferred setting for adolescent vaccination. METHODS: A standardized, pilot-tested telephone survey was administered to a stratified random sample (n = 1,998) of Colorado households between August 2007 and February 2008. Households with English-speaking parents and adolescent(s) aged 11-17 years were eligible. RESULTS: Survey response rate was 43%; there were no significant differences between respondents and nonrespondents for three known demographic variables. Although most parents (78%) preferred a doctor's office for adolescent vaccination, a majority were also definitively or probably accepting of vaccination in public health clinics (74%), school health clinics (70%), obstetrics and gynecology clinics (69%; asked for females only), and emergency departments (67%). Parents were less accepting of vaccination in family planning clinics (41%) and retail-based clinics (36%). Perceived convenience and adolescents' comfort in the setting were positively associated with vaccination acceptance in most settings; concern with keeping track of vaccines given outside of the medical home was negatively associated with acceptance. Parents in rural areas were more likely than parents in urban areas to identify a setting outside of the medical home as the preferred "best" setting for vaccination. CONCLUSIONS: Most parents assessed a doctors' office as the best setting for adolescent vaccination. However, vaccination in certain settings outside of the medical home seems to be acceptable to many parents. |
Improving influenza vaccine virus selection: Report of a WHO informal consultation held at WHO headquarters, Geneva, Switzerland, 14-16 June 2010
Ampofo WK , Baylor N , Cobey S , Cox NJ , Daves S , Edwards S , Ferguson N , Grohmann G , Hay A , Katz J , Kullabutr K , Lambert L , Levandowski R , Mishra AC , Monto A , Siqueira M , Tashiro M , Waddell AL , Wairagkar N , Wood J , Zambon M , Zhang W . Influenza Other Respir Viruses 2011 6 (2) 142-52, e1-5 For almost 60 years, the WHO Global Influenza Surveillance and Response System (GISRS) has been the key player in monitoring the evolution and spread of influenza viruses and recommending the strains to be used in human influenza vaccines. The GISRS has also worked to continually monitor and assess the risk posed by potential pandemic viruses and to guide appropriate public health responses. The expanded and enhanced role of the GISRS following the adoption of the International Health Regulations (2005), recognition of the continuing threat posed by avian H5N1 and the aftermath of the 2009 H1N1 pandemic provide an opportune time to critically review the process by which influenza vaccine viruses are selected. In addition to identifying potential areas for improvement, such a review will also help to promote greater appreciation by the wider influenza and policy-making community of the complexity of influenza vaccine virus selection. The selection process is highly coordinated and involves continual year-round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs). |
The cost-effectiveness of male HPV vaccination in the United States
Chesson HW , Ekwueme DU , Saraiya M , Dunne EF , Markowitz LE . Vaccine 2011 29 (46) 8443-50 INTRODUCTION: The objective of this study was to estimate the cost-effectiveness of adding human papillomavirus (HPV) vaccination of 12-year-old males to a female-only vaccination program for ages 12-26 years in the United States. METHODS: We used a simplified model of HPV transmission to estimate the reduction in the health and economic burden of HPV-associated diseases in males and females as a result of HPV vaccination. Estimates of the incidence, cost-per-case, and quality-of-life impact of HPV-associated health outcomes were based on the literature. The HPV-associated outcomes included were: cervical intraepithelial neoplasia (CIN); genital warts; juvenile-onset recurrent respiratory papillomatosis (RRP); and cervical, vaginal, vulvar, anal, oropharyngeal, and penile cancers. RESULTS: The cost-effectiveness of male vaccination depended on vaccine coverage of females. When including all HPV-associated outcomes in the analysis, the incremental cost per quality-adjusted life year (QALY) gained by adding male vaccination to a female-only vaccination program was $23,600 in the lower female coverage scenario (20% coverage at age 12 years) and $184,300 in the higher female coverage scenario (75% coverage at age 12 years). The cost-effectiveness of male vaccination appeared less favorable when compared to a strategy of increased female vaccination coverage. For example, we found that increasing coverage of 12-year-old girls would be more cost-effective than adding male vaccination even if the increased female vaccination strategy incurred program costs of $350 per additional girl vaccinated. CONCLUSIONS: HPV vaccination of 12-year-old males might potentially be cost-effective, particularly if female HPV vaccination coverage is low and if all potential health benefits of HPV vaccination are included in the analysis. However, increasing female coverage could be a more efficient strategy than male vaccination for reducing the overall health burden of HPV in the population. |
Hexamethylene diisocyanate asthma is associated with genetic polymorphisms of CD14, IL-13, and IL-4 receptor a.
Bernstein DI , Kissling GE , Khurana Hershey G , Yucesoy B , Johnson VJ , Cartier A , Gautrin D , Sastre J , Boulet LP , Malo JL , Quirce S , Tarlo SM , Langmeyer S , Luster MI , Lummus ZL . J Allergy Clin Immunol 2011 128 (2) 418-20 Diisocyanates are among the most common causes of occupational asthma. However, susceptibility factors and immune biomarkers of diisocyanate asthma (DA) have not been clearly defined. For example, serum diisocyanate antigen specific IgE and IgG have been extensively investigated but these immunoassays lack diagnostic accuracy in identifying workers with confirmed DA1, 2, 3. Various genetic variants have been identified as risk factors for DA in association studies. Certain HLA class II alleles and SNPs of antioxidant enzymes (e.g., glutathione-s-transferases, N- acetyl transferases) have been associated with confirmed DA, although these findings have not yet been replicated in multiple populations4. | In 2006, we first reported that DA confirmed by specific inhalation challenge (SIC) testing was significantly associated with cytokine genotype combinations of interleukin 4 receptor alpha (IL4RA), interleukin 13 (IL13) and CD14 single nucleotide polymorphisms (SNPs), but exclusively in hexamethylene diisocyanate (HDI) exposed workers5. In this report, we confirm the aforementioned genotype associations in an expanded group of workers with confirmed DA when compared to diisocyanate exposed workers without DA. |
Multi-walled carbon nanotube-induced gene expression in the mouse lung: association with lung pathology.
Pacurari M , Qian Y , Porter DW , Wolfarth M , Wan Y , Luo D , Ding M , Castranova V , Guo NL . Toxicol Appl Pharmacol 2011 255 (1) 18-31 Due to the fibrous shape and durability of multi-walled carbon nanotubes (MWCNT), concerns regarding their potential for producing environmental and human health risks, including carcinogenesis, have been raised. This study sought to investigate how previously identified lung cancer prognostic biomarkers and the related cancer signaling pathways are affected in the mouse lung following pharyngeal aspiration of well-dispersed MWCNT. A total of 63 identified lung cancer prognostic biomarker genes and major signaling biomarker genes were analyzed in mouse lungs (n=80) exposed to 0, 10, 20, 40, or 80mug of MWCNT by pharyngeal aspiration at 7 and 56days post-exposure using quantitative PCR assays. At 7 and 56days post-exposure, a set of 7 genes and a set of 11 genes, respectively, showed differential expression in the lungs of mice exposed to MWCNT vs. the control group. Additionally, these significant genes could separate the control group from the treated group over the time series in a hierarchical gene clustering analysis. Furthermore, 4 genes from these two sets of significant genes, coiled-coil domain containing-99 (Ccdc99), muscle segment homeobox gene-2 (Msx2), nitric oxide synthase-2 (Nos2), and wingless-type inhibitory factor-1 (Wif1), showed significant mRNA expression perturbations at both time points. It was also found that the expression changes of these 4 overlapping genes at 7days post-exposure were attenuated at 56days post-exposure. Ingenuity Pathway Analysis (IPA) found that several carcinogenic-related signaling pathways and carcinogenesis itself were associated with both the 7 and 11 gene signatures. Taken together, this study identifies that MWCNT exposure affects a subset of lung cancer biomarkers in mouse lungs. |
Secondary organic aerosol formation from ozone reactions with single terpenoids and terpenoid mixtures
Waring MS , Wells JR , Siegel JA . Atmos Environ (1994) 2011 45 (25) 4235-4242 Ozone reacts with indoor-emitted terpenoids to form secondary organic aerosol (SOA). Most SOA research has focused on ozone reactions with single terpenoids or with consumer products, and this paper reports the results from an investigation of SOA formation from ozone reactions with both single terpenoids and mixtures of D-limonene, alpha-pinene, and alpha-terpineol. Transient experiments were conducted at low (25 ppb) and high (100 ppb) initial concentrations of ozone. The three terpenoids were tested singly and in combinations in a manner that controlled for their different reaction rates with ozone. The SOA formation was assessed by examining the evolution in time of the resulting number size-distributions and estimates of the mass concentrations. The results suggest that at higher ozone and terpenoid concentrations. SOA number formation follows a linear trend as a function of the initial rate of reaction. This finding was valid for both single terpenoids and mixtures. Generally speaking, higher ozone and terpenoid concentrations also led to larger geometric mean diameters and smaller geometric standard deviations of fitted lognormal distributions of the formed SOA. By assuming a density, mass concentrations were also assessed and did not follow as consistent of a trend. At low ozone concentration conditions, reactions with only D-limonene yielded the largest number concentrations of any experiment, even more than experiments with mixtures containing D-limonene and much higher overall terpenoid concentrations. This finding was not seen for high ozone concentrations. These experiments demonstrate quantifiable trends for SOA forming reactions of ozone and mixtures, and this work provides a framework for expanding these results to more complex mixtures and consumer products. (C) 2011 Elsevier Ltd. All rights reserved. |
The methoxychlor metabolite, HPTE, inhibits rat luteal cell progesterone production
Akgul Y , Derk RC , Meighan T , Rao KM , Murono EP . Reprod Toxicol 2011 32 (1) 77-84 The methoxychlor metabolite, HPTE, was shown to inhibit P450-cholesterol side-chain cleavage (P450scc) activity resulting in decreased progesterone production by cultured ovarian follicular cells in previous studies. It is not known whether HPTE has any effect on progesterone formation by the corpus luteum. RESULTS: Exposure to 100nM HPTE reduced progesterone production by luteal cells with progressive declines to <22% of control at 500nM HPTE. Similarly, HPTE progressively inhibited progesterone formation and P450scc catalytic activity of hCG- or 8 Br-cAMP-stimulated luteal cells. However, HPTE did not alter mRNA and protein levels of P450scc. Compounds acting as estrogen (17beta-estradiol, bisphenol-A or octylphenol), antiestrogen (ICI) or antiandrogen (monobutyl phthalate, flutamide or M-2) added alone to luteal cells did not mimic the action of HPTE on progesterone and P450scc activity. These results suggest that HPTE directly inhibits P450scc catalytic activity resulting in reduced progesterone formation, and this action was not mediated through estrogen or androgen receptors. |
The pesticide deltamethrin increases free radical production and promotes nuclear translocation of the stress response transcription factor Nrf2 in rat brain
Li H , Wu S , Ma Q , Shi N . Toxicol Ind Health 2011 27 (7) 579-90 The transcription factor NF-E2-related factor 2 (Nrf2) plays a critical role in the mammalian response to chemical and oxidative stress through induction of phase II detoxification enzymes and oxidative stress response proteins. We reported that Nrf2 expression was activated by deltamethrin (DM), a prototype of the widely used pyrithroid pesticides, in PC12 cells. However, no study has examined Nrf2 nuclear translocation and free radical production, two hallmarks of oxidative stress, in the mammalian brain in vivo. To this end, we examined translocation of Nrf2 and production of free radicals in rat brain exposed to DM. Indeed, DM initiated nuclear translocation of Nrf2 in a dose-dependent manner. Furthermore, Nrf2 translocation was accompanied by the expression of heme oxygenase-1 gene, an Nrf2-regulated gene linked to free radical production. Deltamethrin exposure promoted free radical formation in rat brain and reactive oxygen species generation in PC12 cells. Translocation of Nrf2 may be a response to DM-dependent induction of free radicals and DM may act as a mammalian neurotoxin by initiating oxidative stress. |
An alternative in vivo method to refine the mouse bioassay for botulinum toxin detection
Wilder-Kofie TD , Luquez C , Adler M , Dykes JK , Coleman JD , Maslanka SE . Comp Med 2011 61 (3) 235-42 Botulism is a rare, life-threatening paralytic disease of both humans and animals that is caused by botulinum neurotoxins (BoNT). Botulism is confirmed in the laboratory by the detection of BoNT in clinical specimens, contaminated foods, and cultures. Despite efforts to develop an in vitro method for botulinum toxin detection, the mouse bioassay remains the standard test for laboratory confirmation of this disease. In this study, we evaluated the use of a nonlethal mouse toe-spread reflex model to detect BoNT spiked into buffer, serum, and milk samples. Samples spiked with toxin serotype A and nontoxin control samples were injected into the left and right extensor digitorum longus muscles, respectively. Digital photographs at 0,8, and 24 h were used to obtain objective measurements through effective paralysis scores, which were determined by comparing the width-to-length ratio between right and left feet. Both objective measurements and clinical observation could accurately identify over 80% of animals injected with 1 LD(50) (4.3 pg) BoNT type A within 24 h. Half of animals injected with 0.5 LD(50) BoNT type A and none injected with 0.25 LD(50) demonstrated localized paralysis. Preincubating the toxin with antitoxin prevented the development of positive effective paralysis scores, demonstrating that (1) the effect was specific for BoNT and (2) identification of toxin serotype could be achieved by using this method. These results suggest that the mouse toe-spread reflex model may be a more humane alternative to the current mouse bioassay for laboratory investigations of botulism. |
Maternal injuries during the periconceptional period and the risk of birth defects, National Birth Defects Prevention Study, 1997-2005
Tinker SC , Reefhuis J , Dellinger AM , Jamieson DJ . Paediatr Perinat Epidemiol 2011 25 (5) 487-496 Maternal injuries during pregnancy are common ( approximately 7% prevalence). However, few studies have examined the association between maternal injuries and birth defects. The National Birth Defects Prevention Study is a population-based case-control study of birth defects in 10 US states. Cases were ascertained through surveillance; controls were randomly selected from infants delivered without major birth defects in the study regions. Mothers completed a telephone interview on exposures before and during pregnancy, including injuries. We assessed associations between periconceptional (month before until the end of the third month of pregnancy) maternal injuries and birth defects. We used logistic regression to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CI). Periconceptional injuries were associated with interrupted aortic arch type B [AOR = 5.2, 95% CI 1.2, 23.2]; atrioventricular septal defect [AOR = 2.2, 95% CI 1.1, 4.4]; pulmonary atresia [AOR = 3.2, 95% CI 1.6, 6.4]; tricuspid atresia [AOR = 2.8, 95% CI 1.2, 6.7]; hypoplastic left heart syndrome [AOR = 2.0, 95% CI 1.1, 3.4]; anorectal atresia/stenosis [AOR = 1.7, 95% CI 1.0, 2.7]; longitudinal limb deficiency [AOR = 2.1, 95% CI 1.1, 3.9]; and gastroschisis [AOR = 1.8, 95% CI 1.2, 2.8]. Associations with longitudinal limb deficiency, gastroschisis and hypoplastic left heart syndrome were stronger for intentional injuries. Our results suggest maternal injury during the periconceptional period, particularly those inflicted intentionally, may be associated with select birth defects. This analysis was hypothesis-generating, with many associations tested. Further research is warranted. |
Acute and congenital Chagas disease
Bern C , Martin DL , Gilman RH . Adv Parasitol 2011 75 19-47 The acute phase of Chagas disease lasts 4-8 weeks and is characterized by microscopically detectable parasitaemia. Symptoms are usually mild with severe acute disease occurring in less than 1% of patients. Orally transmitted Trypanosoma cruzi outbreaks can have more severe acute morbidity and higher mortality than vector-borne infection. Congenital T. cruzi infection occurs in 1-10% of infants of infected mothers. Most congenital infections are asymptomatic or cause non-specific signs, requiring laboratory screening for detection. A small proportion of congenital infections cause severe morbidity with hepatosplenomegaly, anaemia, meningoencephalitis and/or respiratory insufficiency, with an associated high mortality. Infected infants are presumed to carry the same 20-30% lifetime risk of cardiac or gastrointestinal disease as other infected individuals. Most control programs in Latin America employ prenatal serological screening followed by microscopic examination of cord blood from infants of seropositive mothers. Recent data confirm that polymerase chain reaction (PCR) is more sensitive and detects congenital infections earlier than conventional techniques. For infants not diagnosed at birth, conventional serology is recommended at at 6 to 9 months of age. In programs that have been evaluated, less than 20% of at risk infants completed all steps of the screening algorithm. A sensitive, specific and practical screening test for newborns is needed to enable Chagas disease to be added to newborn screening programs. |
The association of current hormonal contraceptive use with type-specific HPV detection
Ghanem KG , Datta SD , Unger ER , Hagensee M , Shlay JC , Kerndt P , Hsu K , Koutsky LA . Sex Transm Infect 2011 87 (5) 385-8 BACKGROUND: Increased duration of hormonal contraceptive (HC) use may be positively associated with the risk of invasive cervical cancer. METHODS: This is a secondary analysis from the HPV Sentinel Surveillance Study. The authors examined the association between type-specific human papillomavirus (HPV) detection and current HC use among 7718 women attending 26 sexually transmitted disease, family planning and primary care clinics in the USA. RESULTS: There was an association between HC use and HPV-16 detection (adjusted prevalence rate ratio 1.34 (95% CI 1.05 to 1.71) for oral contraceptive users and 1.41 (1.01 to 2.04) for depot-medroxyprogesterone acetate users); there was no association between HC use and detection of other HPV types or any HPV overall. CONCLUSIONS: Longitudinal studies are needed to better define this type-specific association and its clinical significance. |
Transitions between childlessness and first birth: three generations of U.S. women
Kirmeyer SE , Hamilton BE . Vital Health Stat 2 2011 (153) 1-18 OBJECTIVE: This report analyzes the patterns of childlessness, and conversely, the first-birth patterns of three birth cohorts of American women. For this report, a cohort refers to women born in the same year. The cohorts compared were women born in 1910, 1935, and 1960 -- who, consequently, turned 25 during the Great Depression, the Baby Boom, and lastly, the post-Baby Boom period. The purpose of the report is to explore the differences in fertility characteristics of these three generations of women and to consider those differences in light of the social and economic conditions at the time. METHODS: Life table methodology, including the probability of having a first birth, the number of women remaining childless, and the expected number of years to remain childless, was applied to each of the three birth cohorts for comparison. Techniques extended from life table functions were also used and included measures of first-birth concentration as well as comparisons between childlessness and the total fertility rate (TFR). Data were based on the Centers for Disease Control and Prevention’s National Center for Health Statistics tables on cohort fertility. RESULTS: Of the three birth cohorts studied, the women born in 1910 had the highest proportion childless and a low TFR. In contrast, the women born in 1935 had both the lowest proportion childless and the highest TFR. The fertility of women who were born in 1960 is characterized as intermediate to the other cohorts in terms of childlessness, but is distinct with both lowest levels of childbearing and oldest ages of first births. First-time childbearing is more concentrated (that is, least spread out) by age of mother for the 1910 and 1935 cohorts than the 1960 cohort. Finally, data for all U.S. birth cohorts 1910-1960 suggest that the greater the proportion childless in a cohort, the lower the TFR. |
Childbearing differences among three generations of U.S. women
Kirmeyer SE , Hamilton BE . NCHS Data Brief 2011 (68) 1-8 Each year a generation of women is born who will share similar sociohistorical experiences before and throughout their reproductive lives. These unique experiences can produce similar childbearing patterns in terms of the average number of children ever born -- whether mothers are younger or older when their first birth occurs and the proportion of women who do not have children -- that can differ from the patterns found for other cohorts. Childbearing patterns have profound consequences for society. These consequences include the demand for schools and housing, as well as women’s participation in the labor force. Moreover, the lives of women who become mothers are significantly different from those who do not. Having children affects the acquisition of material goods and may impose costs for the mother in terms of personal and professional options. This report presents data on three selected birth cohorts of women representing generations born at 25-year intervals in 1910, 1935, and 1960, close to the average length of a generation in the United States. Data are from the cohort fertility tables, based on the National Vital Statistics System. |
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