Impact of the 2002 American Society for Colposcopy and Cervical Pathology guidelines on cervical cancer diagnosis in a geographically diverse population of commercially insured women, 1999-2004
Martin CK , Richardson LC , Berkman ND , Kuo TM , Yuen AN , Benard VB . J Low Genit Tract Dis 2011 15 (1) 25-32 OBJECTIVE: To report the impact of the release of the 2002 American Society for Colposcopy and Cervical Pathology guidelines on the management of abnormal cytological findings on time to diagnosis of cervical cancer in an insured population. METHODS: This retrospective study identified women with cervical cancer (invasive and carcinoma in situ) through commercially insured administrative claims data. The cervical cancer case definition required a claim for cervical cancer and a claim with a diagnostic procedure (colposcopy, conization, biopsy, or hysterectomy). Time to diagnosis was defined as days between the initial Pap screening and the diagnostic procedure. RESULTS: Between 1999 and 2004, there were 3,325 women aged 18 to 64 years who met the case definition for cervical cancer. Median time to diagnosis decreased from 42 days (interquartile range = 23-93 d) to 36.5 days (interquartile range = 20.5-80 d) for women with invasive cancer after the guideline change. The number of follow-up Pap screenings before biopsy also decreased (p = .0067). Among women with carcinoma in situ whose initial Pap screening was completed by a family practice clinician, time to diagnosis was projected to be more than 9 days longer compared with those whose screening was performed by a gynecologist. CONCLUSIONS: The 2002 American Society for Colposcopy and Cervical Pathology guidelines for the management of abnormal cytological findings seem to have had a positive impact on the time to diagnosis and Pap screening use before biopsy for women diagnosed with cervical cancer. |
Visual impairment and health-related quality of life among elderly adults with age-related eye diseases
Li Y , Crews JE , Elam-Evans LD , Fan AZ , Zhang X , Elliott AF , Balluz L . Qual Life Res 2010 20 (6) 845-52 PURPOSE: To examine the association between age-related eye disease (ARED), visual impairment, and health-related quality of life (HRQOL). METHODS: We used data from the 2006 and 2008 Behavioral Risk Factor Surveillance System to examine self-reported visual impairment and two HRQOL domains-physical impairment (including poor general health, physical unhealthy days, activity-limitation days, and disability) and mental distress (including mental unhealthy days, life dissatisfaction, major depression, lifetime depression, and anxiety) for people aged 65 years or older, by ARED status. RESULTS: People with any ARED were more likely than those without to report visual impairment as well as physical impairment and mental distress. The prevalence of visual impairment (P trend <0.001) and physical impairment (P trend <0.001) increased with increasing number of eye diseases after controlling for all covariates. There was no significant linear trend, however, in mental distress among people with one or more eye diseases. CONCLUSION: ARED was found to be associated with visual impairment and poorer HRQOL. Increasing numbers of AREDs were associated with increased levels of visual impairment and physical impairment, but were not associated with levels of mental distress. |
Correlates of depression among people with diabetes: the Translating Research Into Action for Diabetes (TRIAD) study
Waitzfelder B , Gerzoff RB , Karter AJ , Crystal S , Bair MJ , Ettner SL , Brown AF , Subramanian U , Lu SE , Marrero D , Herman WH , Selby JV , Dudley RA . Prim Care Diabetes 2010 4 (4) 215-22 AIM: The broad objective of this study was to examine multiple dimensions of depression in a large, diverse population of adults with diabetes. Specific aims were to measure the association of depression with: (1) patient characteristics; (2) outcomes; and (3) diabetes-related quality of care. METHODS: Cross-sectional analyses were performed using survey and chart data from the Translating Research Into Action for Diabetes (TRIAD) study, including 8790 adults with diabetes, enrolled in 10 managed care health plans in 7 states. Depression was measured using the Patient Health Questionnaire (PHQ-8). Patient characteristics, outcomes and quality of care were measured using validated survey items and chart data. RESULTS: Nearly 18% of patients had major depression, with prevalence 2-3 times higher among patients with low socioeconomic status. Pain and limited mobility were strongly associated with depression, controlling for other patient characteristics. Depression was associated with slightly worse glycemic control, but not other intermediate clinical outcomes. Depressed patients received slightly fewer recommended diabetes-related processes of care. CONCLUSIONS: In a large, diverse cohort of patients with diabetes, depression was most prevalent among patients with low socioeconomic status and those with pain, and was associated with slightly worse glycemic control and quality of care. |
Neurological infections: influenza in the spotlight
Sejvar JJ . Lancet Neurol 2011 10 (1) 16-8 Influenza, both 2009 H1N1 and seasonal influenza virus, continued to dominate the attention of doctors and the public during 2010. The medical community breathed a collective sigh of relief when the pandemic of influenza 2009 H1N1 virus, which, although undoubtedly associated with striking morbidity and mortality, was of a smaller magnitude than was initially feared. However, articles about pandemic and seasonal influenza were frequent in the published work on neuroinfectious disease in 2010, with at least 12 published case reports or small case series describing various neurological features of influenza infection. One article1 summarised collective features of 32 cases of neurological illness associated with 2009 H1N1 influenza that were published in case reports up to August, 2010. This summary suggested that the spectrum and severity of neurological complications of 2009 H1N1 influenza are consistent with those described with seasonal influenza, and include seizures, encephalopathy, acute necrotising encephalitis, extrapyramidal features, and myositis. Consistent with previous reports of seasonal influenza, neurological illness was most frequently reported in children, was generally unassociated with cerebrospinal-fluid pleocytosis or protein elevation, and resulted in largely favourable outcomes. |
Prevalence and correlates of GB virus C infection in HIV-infected and HIV-uninfected pregnant women in Bangkok, Thailand
Bhanich Supapol W , Remis RS , Raboud J , Millson M , Tappero J , Kaul R , Kulkarni P , McConnell MS , Mock PA , McNicholl JM , Roongpisuthipong A , Chotpitayasunondh T , Shaffer N , Butera S . J Med Virol 2011 83 (1) 33-44 GB virus C (GBV-C) is an apathogenic virus that has been shown to inhibit HIV replication. This study examined the prevalence and correlates of GBV-C infection and clearance in three cohorts of pregnant women in Thailand. The study population consisted of 1,719 (1,387 HIV-infected and 332 HIV-uninfected) women from three Bangkok perinatal HIV transmission studies. Stored blood was tested for GBV-C RNA, GBV-C antibody, and if RNA-positive, genotype. Risk factors associated with the prevalence of GBV-C infection (defined as presence of GBV-C RNA and/or antibody) and viral clearance (defined as presence of GBV-C antibody in the absence of RNA) among women with GBV-C infection were examined using multiple logistic regression. The prevalence of GBV-C infection was 33% among HIV-infected women and 15% among HIV-uninfected women. GBV-C infection was independently associated (AOR, 95% CI) with an increasing number of lifetime sexual partners (referent-1 partner, 2 partners [1.60, 1.22-2.08], 3-10 partners [1.92, 1.39-2.67], >10 partners [2.19, 1.33-3.62]); injection drug use (5.50, 2.12-14.2); and HIV infection (3.79, 2.58-5.59). Clearance of GBV-C RNA among women with evidence of GBV-C infection was independently associated with increasing age in years (referent <20, 20-29 [2.01, 1.06-3.79] and ≥30 [3.18, 1.53-6.60]), more than 10 lifetime sexual partners (3.05, 1.38-6.75), and HIV infection (0.29, 0.14-0.59). This study found that GBV-C infection is a common infection among Thai women and is associated with HIV infection and both sexual and parenteral risk behaviors. |
TB transmission on public transportation: a review of published studies and recommendations for contact tracing
Edelson PJ , Phypers M . Travel Med Infect Dis 2010 9 (1) 27-31 SETTING: The risk of transmission when persons with active tuberculosis travel on buses or trains is uncertain and no recommendations have been published for contact investigations on these conveyances. DESIGN: We conducted a systematic review of the published studies of tuberculosis transmission among bus or train travelers. RESULTS: Twelve published reports were identified, including one retrospective cohort study and eleven contact investigations. One contact investigation involved train travelers and one involved students on a 6 h bus excursion. The remaining nine involved exposures on school buses or in commuter vans. In eight reports, evidence of tuberculosis infection was found in 8.7%-55% of those tested; six of these studies reported identifying 1-24 cases of active tuberculosis. CONCLUSIONS: These reports support the need to be alert to the possibility of tuberculosis transmission on buses or trains. However, they do not offer the quantitative estimate of risk needed for defining policy regarding contact tracing for persons exposed on buses or trains. Decisions to carry out contact investigations should take into account the proximity to the index case, duration of exposure, and other risk factors that may affect the infectiousness of the case or the susceptibility of the contact. Additional reports taking these factors into consideration would help clarify the risk of tuberculosis transmission on public transport. |
A paradox: overscreening of older women for chlamydia while too few younger women are being tested
Berman SM , Satterwhite CL . Sex Transm Dis 2010 38 (2) 130-2 In this issue, Bernstein et al. report on a structural intervention aimed at reducing chlamydia screening among women aged ≥26 years.1 This article, though brief, provides an opportunity to highlight several issues related to chlamydia screening and sexually transmitted disease (STD)/human immunodeficiency virus (HIV) prevention in general. | The importance of screening young women for chlamydia should be reemphasized. The United States Preventive Services Task Force (USPSTF) recommends annual chlamydia screening for all sexually active young women aged <25 years.2 This is an “A” recommendation, meaning there is good evidence that the benefits of screening outweigh the harms.3 Conversely, USPSTF recommends against routinely screening women aged ≥25 years, unless the individuals are at increased risk of infection (e.g., history of sexually transmitted infections, new or multiple sex partners, inconsistent condom use, exchanging sex for money or drugs). |
H1N1pdm influenza infection in hospitalized cancer patients: clinical evolution and viral analysis
Souza TM , Salluh JI , Bozza FA , Mesquita M , Soares M , Motta FC , Pitrowsky MT , de Lourdes Oliveira M , Mishin VP , Gubareva LV , Whitney A , Rocco SA , Goncalves VM , Marques VP , Velasco E , Siqueira MM . PLoS One 2010 5 (11) e14158 BACKGROUND: The novel influenza A pandemic virus (H1N1pdm) caused considerable morbidity and mortality worldwide in 2009. The aim of the present study was to evaluate the clinical course, duration of viral shedding, H1N1pdm evolution and emergence of antiviral resistance in hospitalized cancer patients with severe H1N1pdm infections during the winter of 2009 in Brazil. METHODS: We performed a prospective single-center cohort study in a cancer center in Rio de Janeiro, Brazil. Hospitalized patients with cancer and a confirmed diagnosis of influenza A H1N1pdm were evaluated. The main outcome measures in this study were in-hospital mortality, duration of viral shedding, viral persistence and both functional and molecular analyses of H1N1pdm susceptibility to oseltamivir. RESULTS: A total of 44 hospitalized patients with suspected influenza-like illness were screened. A total of 24 had diagnosed H1N1pdm infections. The overall hospital mortality in our cohort was 21%. Thirteen (54%) patients required intensive care. The median age of the studied cohort was 14.5 years (3-69 years). Eighteen (75%) patients had received chemotherapy in the previous month, and 14 were neutropenic at the onset of influenza. A total of 10 patients were evaluated for their duration of viral shedding, and 5 (50%) displayed prolonged viral shedding (median 23, range=11-63 days); however, this was not associated with the emergence of a resistant H1N1pdm virus. Viral evolution was observed in sequentially collected samples. CONCLUSIONS: Prolonged influenza A H1N1pdm shedding was observed in cancer patients. However, oseltamivir resistance was not detected. Taken together, our data suggest that severely ill cancer patients may constitute a pandemic virus reservoir with major implications for viral propagation. |
From spectators to implementers: civil society organizations involved in AIDS programmes in China
Li H , Kuo NT , Liu H , Korhonen C , Pond E , Guo H , Smith L , Xue H , Sun J . Int J Epidemiol 2010 39 Suppl 2 ii65-71 BACKGROUND: Over the past 20 years, civil society organizations (CSOs) in China have significantly increased their involvement in the AIDS response. This article aims to review the extent of civil society participation in China AIDS programmes over the past two decades. METHODS: A desk review was conducted to collect Chinese government policies, project documents and published articles on civil society participation of HIV/AIDS programmes in China over the past two decades. Assessment focused on five aspects: (i) the political environment; (ii) access to financial resources; (iii) the number of CSOs working on HIV/AIDS; (iv) the scope of work; and (v) the impact of CSO involvement on programmes. RESULTS: The number of CSOs specificly working on HIV/AIDS increased from 0 before 1988 to over 400 in 2009. Among a sample of 368 CSOs, 135 (36.7%) were registered. CSOs were primarily supported by international programmes. Government financial support to CSOs has increased from USD248 000 in 2002 to USD1.46 million in 2008. Initially, civil society played a minimal role. It is now widely involved in nearly all aspects of HIV/AIDS-related prevention, treatment and care efforts, and has had a positive impact; for example, increased adherence of anti-retroviral treatment and HIV testing among hard-to-reach groups. The main challenges faced by CSOs include registration, capacity and long-term financial support. CONCLUSION: CSOs have significantly increased their participation and contribution to HIV/AIDS programmes in China. Policies for registration and financial support to CSOs need to be developed to enable them to play an even greater role in AIDS programmes. |
Where have all the vector control programs gone? Part two
Herring ME . J Environ Health 2010 73 (5) 24-25 Last month in this column (Herring, | 2010), we discussed the challenges | confronting state and local health departments in their efforts to reduce disease | threats and other health problems associated | with rodents and insect pests. This month, | we will focus on programs developed at the | Centers for Disease Control and Prevention | (CDC) in collaboration with other federal | agencies and national partner organizations | to address these challenges. | How Is CDC Responding? | CDC has been an advocate of integrated pest | management (IPM) for many years. CDC has | partnered with the U.S. Environmental Protection Agency (U.S. EPA), U.S. Department | of Housing and Urban Development, and | other agencies and organizations on several | projects and publications that promote the | use of IPM in homes, schools, businesses, | and communities. |
Effects of transmission reduction by insecticide-treated bed nets (ITNs) on parasite genetics population structure: I. The genetic diversity of Plasmodium falciparum parasites by microsatellite markers in western Kenya
Gatei W , Kariuki S , Hawley W , Ter Kuile F , Terlouw D , Phillips-Howard P , Nahlen B , Gimnig J , Lindblade K , Walker E , Hamel M , Crawford S , Williamson J , Slutsker L , Shi YP . Malar J 2010 9 353 BACKGROUND: Insecticide-treated bed nets (ITNs) reduce malaria transmission and are an important prevention tool. However, there are still information gaps on how the reduction in malaria transmission by ITNs affects parasite genetics population structure. This study examined the relationship between transmission reduction from ITN use and the population genetic diversity of Plasmodium falciparum in an area of high ITN coverage in western Kenya. METHODS: Parasite genetic diversity was assessed by scoring eight single copy neutral multilocus microsatellite (MS) markers in samples collected from P. falciparum-infected children (< five years) before introduction of ITNs (1996, baseline, n = 69) and five years after intervention (2001, follow-up, n = 74). RESULTS: There were no significant changes in overall high mixed infections and unbiased expected heterozygosity between baseline (%MA = 94% and He = 0.75) and follow up (%MA = 95% and He = 0.79) years. However, locus specific analysis detected significant differences for some individual loci between the two time points. Pfg377 loci, a gametocyte-specific MS marker showed significant increase in mixed infections and He in the follow up survey (%MA = 53% and He = 0.57) compared to the baseline (%MA = 30% and He = 0.29). An opposite trend was observed in the erythrocyte binding protein (EBP) MS marker. There was moderate genetic differentiation at the Pfg377 and TAA60 loci (FST = 0.117 and 0.137 respectively) between the baseline and post-ITN parasite populations. Further analysis revealed linkage disequilibrium (LD) of the microsatellites in the baseline (14 significant pair-wise tests and ISA = 0.016) that was broken in the follow up parasite population (6 significant pairs and ISA = 0.0003). The locus specific change in He, the moderate population differentiation and break in LD between the baseline and follow up years suggest an underlying change in population sub-structure despite the stability in the overall genetic diversity and multiple infection levels. CONCLUSIONS: The results from this study suggest that although P. falciparum population maintained an overall stability in genetic diversity after five years of high ITN coverage, there was significant locus specific change associated with gametocytes, marking these for further investigation. |
Characteristics of Cryptosporidium transmission in pre-weaned dairy cattle in Henan, China
Wang R , Wang H , Sun Y , Zhang L , Jian F , Qi M , Ning C , Xiao L . J Clin Microbiol 2010 49 (3) 1077-82 To estimate the prevalence and public health significance of cryptosporidiosis in pre-weaned calves in China, 801 fecal samples from eight farms in seven areas in Henan Province were examined for Cryptosporidium oocysts. The overall infection rate of Cryptosporidium was 21.5%, with the farm in Xinxiang having the highest prevalence (40%). No significant difference in infection rates was observed between seasons. Cryptosporidium spp. were characterized by PCR-restriction fragment length polymorphism (RFLP) analysis of the small subunit (SSU) rRNA gene and DNA sequencing of the 60 kDa glycoprotein (gp60) gene. The SSU rRNA-based PCR identified four Cryptosporidium species, including C. parvum (54/172), C. bovis (65/172), C. ryanae (19/172), C. andersoni (12/172), and the occurrence of infections with mixed species (22/172). The earliest detection of C. bovis was in calves of one week of age, showing that the prepatent period was shorter than the previously stated 10-12 days. Infections with C. parvum peaked in summer, whereas C. bovis dominated in autumn and winter. There was no apparent difference in the age of cattle infected with either C. parvum or C. bovis. Sequencing analysis of the gp60 gene showed all 67 C. parvum samples belonged to subtype IIdA19G1. These findings suggested that the transmission of Cryptosporidium spp. in pre-weaned calves in Henan, China appeared to be different from other areas both at genotype and subtype levels. Further molecular epidemiologic studies (including samples from both calves and humans) are needed to elucidate the transmission dynamics and public significance of C. parvum in cattle in China. |
Characterization of insecticide resistance in Trinidadian strains of Aedes aegypti mosquitoes
Polson KA , Brogdon WG , Rawlins SC , Chadee DD . Acta Trop 2011 117 (1) 31-8 Bioassays and biochemical assays were conducted on eight Trinidadian strains of Aedes aegypti larvae to determine the involvement of biochemical mechanisms in resistance to insecticides. Larval strains were assayed to dichlorodiphenyltrichloroethane (DDT), bendiocarb, temephos and permethrin, using the Centers for Disease Control and Prevention (CDC) time-mortality bioassay method. A Resistance Threshold (RT) was calculated for each insecticide in relation to the CAREC reference susceptible Ae. aegypti strain and larval strains with <80% mortality were considered to be resistant. Biochemical assays were performed to determine the activities of nonspecific esterases (alpha- and beta-), PNPA-esterases, mixed function oxidases (MFO), glutathione-S-transferases (GST) and acetylcholinesterase (AChE) enzymes which are involved in insecticide resistance in mosquitoes. Enzyme profiles of each strain were compared with those of the CAREC reference susceptible strain by Kruskal-Wallis and Dunn's multiple comparison tests (p<0.05). The CAREC 99th percentile was calculated for each enzyme and the percentage of individuals with enzyme activities above that of the CAREC 99th percentile was calculated. Activities were classified as unaltered (<50%), incipiently altered (15-50%) or altered (>50%) for each strain. The established RTs for permethrin and bendiocarb were 30 and 75 min, respectively; and 120 min for DDT and temephos. All strains were resistant to DDT (1.00-40.25% mortality) and temephos (11.50-74.50% mortality) while six strains were resistant to bendiocarb (51.50-78.50% mortality) and five to permethrin (6.50-42.50% mortality). Biochemical assays revealed that the median activity levels for all enzymes varied significantly (p<0.05). The Curepe strain had incipiently altered levels of alpha-esterase while the other seven strains had altered activity with five of them registering 100%. The St Clair strain showed altered activity levels of beta-esterase while three strains had incipiently altered levels. The majority of strains had altered activity of MFO enzymes but only the St Clair strain showed altered activity of GST. PNPA-esterases activity was unaltered in all strains and only the Haleland Park strain showed altered remaining AChE activity in the presence of propoxur. Elevated levels of enzymes (incipiently altered or altered), except in the case of PNPA-esterases, show that biochemical resistance may play an important role in the manifestation of insecticide resistance in Trinidadian populations of Ae. aegypti. It is therefore important for insecticide resistance surveillance to be ongoing as the detection of resistance before it spreads throughout an entire population makes it possible for early intervention. |
Perchlorate exposure in lactating women in an urban community in New Jersey
Borjan M , Marcella S , Blount B , Greenberg M , Zhang JJ , Murphy E , Valentin-Blasini L , Robson M . Sci Total Environ 2011 409 (3) 460-4 Perchlorate is most widely known as a solid oxidant for missile and rocket propulsion systems although it is also present as a trace contaminant in some fertilizers. It has been detected in drinking water, fruits, and vegetables throughout New Jersey and most of the United States. At sufficiently high doses, perchlorate interferes with the uptake of iodine into the thyroid and may interfere with the development of the skeletal system and the central nervous system of infants. Therefore, it is important to quantify perchlorate in breast milk to understand potential perchlorate exposure in infants. In this study we measured perchlorate in breast milk, urine, and drinking water collected from 106 lactating mothers from Central New Jersey. Each subject was asked to provide three sets of samples over a 3-month period. The average+/-SD perchlorate level in drinking water, breast milk, and urine was 0.168+/-0.132 ng/mL (n=253), 6.80+/-8.76 ng/mL (n=276), and 3.19+/-3.64 ng/mL (3.51+/-6.79 mug/g creatinine) (n=273), respectively. Urinary perchlorate levels were lower than reference range values for women of reproductive age (5.16+/-11.33 mug/g creatinine, p=0.03), likely because of perchlorate secretion in breast milk. Drinking water perchlorate levels were ≤1.05 ng/mL and were not positively correlated with either breast milk or urine perchlorate levels. These findings together suggest that drinking water was not the most important perchlorate exposure source for these women. Creatinine-adjusted urine perchlorate levels were strongly correlated with breast milk perchlorate levels (r=0.626, p=<0.0005). Breast milk perchlorate levels in this study are consistent with widespread perchlorate exposure in lactating women and thus infants. This suggests that breast milk may be a source of exposure to perchlorate in infants. |
Chlorine disinfection of Francisella tularensis
O'Connell HA , Rose LJ , Shams AM , Arduino MJ , Rice EW . Lett Appl Microbiol 2011 52 (1) 84-6 AIMS: To determine the range of free available chlorine (FAC) required for disinfection of the live vaccine strain (LVS) and wild-type strains of Francisella tularensis. METHODS AND RESULTS: Seven strains of planktonic F. tularensis were exposed to 0.5 mg.l(-1) FAC for two pH values, 7 and 8, at 5 and 25 degrees C. LVS was inactivated 2 to 4 times more quickly than any of the wild-type F. tularensis strains at pH 8 and 5 degrees C. CONCLUSIONS: Free available chlorine residual concentrations routinely maintained in drinking water distribution systems would require up to two hours to reduce all F. tularensis strains by 4 log10. LVS was inactivated most quickly of the tested strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides contact time (CT) values that are useful for drinking water risk assessment and also suggests that LVS may not be a good surrogate in disinfection studies. |
Partition of environmental chemicals between maternal and fetal blood and tissues
Needham LL , Grandjean P , Heinzow B , Jorgensen PJ , Nielsen F , Patterson DG , Sjodin A , Turner WE , Weihe P . Environ Sci Technol 2010 45 (3) 1121-6 Passage of environmental chemicals across the placenta has important toxicological consequences, as well as for choosing samples for analysis and for interpreting the results. To obtain systematic data, we collected in 2000 maternal and cord blood, cord tissue, placenta, and milk in connection with births in the Faroe Islands, where exposures to marine contaminants is increased. In 15 sample sets, we measured a total of 87 environmental chemicals, almost all of which were detected both in maternal and fetal tissues. The maternal serum lipid-based concentrations of organohalogen compounds averaged 1.7 times those of cord serum, 2.8 times those of cord tissue and placenta, and 0.7 those of milk. For organohalogen compounds detectable in all matrices, a high degree of correlation between concentrations in maternal serum and the other tissues investigated was generally observed (r(2) > 0.5). Greater degree of chlorination resulted in lower transfer from maternal serum into milk. Concentrations of pentachlorbenzene, gamma-hexachlorocyclohexane, and several polychlorinated biphenyl congeners with low chlorination were higher in fetal samples and showed poor correlation with maternal levels. Perfluorinated compounds occurred in lower concentrations in cord serum than in maternal serum. Cadmium, lead, mercury, and selenium were all detected in fetal samples, but only mercury showed close correlations among concentrations in different matrices. Although the environmental chemicals examined pass through the placenta and are excreted into milk, partitions between maternal and fetal samples are not uniform. |
Evaluation of three sampling methods to monitor outcomes of antiretroviral treatment programmes in low- and middle-income countries
Tassie JM , Malateste K , Pujades-Rodriguez M , Poulet E , Bennett D , Harries A , Mahy M , Schechter M , Souteyrand Y , Dabis F . PLoS One 2010 5 (11) e13899 BACKGROUND: Retention of patients on antiretroviral therapy (ART) over time is a proxy for quality of care and an outcome indicator to monitor ART programs. Using existing databases (Antiretroviral in Lower Income Countries of the International Databases to Evaluate AIDS and Medecins Sans Frontieres), we evaluated three sampling approaches to simplify the generation of outcome indicators. METHODS AND FINDINGS: We used individual patient data from 27 ART sites and included 27,201 ART-naive adults (≥15 years) who initiated ART in 2005. For each site, we generated two outcome indicators at 12 months, retention on ART and proportion of patients lost to follow-up (LFU), first using all patient data and then within a smaller group of patients selected using three sampling methods (random, systematic and consecutive sampling). For each method and each site, 500 samples were generated, and the average result was compared with the unsampled value. The 95% sampling distribution (SD) was expressed as the 2.5(th) and 97.5(th) percentile values from the 500 samples. Overall, retention on ART was 76.5% (range 58.9-88.6) and the proportion of patients LFU, 13.5% (range 0.8-31.9). Estimates of retention from sampling (n = 5696) were 76.5% (SD 75.4-77.7) for random, 76.5% (75.3-77.5) for systematic and 76.0% (74.1-78.2) for the consecutive method. Estimates for the proportion of patients LFU were 13.5% (12.6-14.5), 13.5% (12.6-14.3) and 14.0% (12.5-15.5), respectively. With consecutive sampling, 50% of sites had SD within +/-5% of the unsampled site value. CONCLUSIONS: Our results suggest that random, systematic or consecutive sampling methods are feasible for monitoring ART indicators at national level. However, sampling may not produce precise estimates in some sites. |
Detection of Coxiella burnetii in commercially available raw milk from the United States
Loftis AD , Priestley RA , Massung RF . Foodborne Pathog Dis 2010 7 (12) 1453-6 Unpasteurized (raw) milk can be purchased in 39 U.S. states, with direct consumer purchase for human consumption permitted in 29 of those 39 states. Raw milk (n=21; cow, 14; goat, 7) was purchased in 12 states, and Coxiella burnetii, the agent of Q fever, was detected in 9 of 21 (42.9%) samples tested by polymerase chain reaction. Viability of the pathogen was demonstrated by isolation of the agent in tissue culture. The demonstration of viable C. burnetii in commercially available raw milk poses a potential public health risk. |
Reasons for not HIV testing, testing intentions, and potential use of an over-the-counter rapid HIV test in an internet sample of men who have sex with men who have never tested for HIV
Mackellar DA , Hou SI , Whalen CC , Samuelsen K , Sanchez T , Smith A , Denson D , Lansky A , Sullivan P . Sex Transm Dis 2010 38 (5) 419-28 BACKGROUND: Correlates of main reasons for not HIV testing, HIV testing intentions, and potential use of an over-the-counter rapid HIV test (OTCRT) among men who have sex with men who have never tested for HIV (NTMSM) are unknown. METHODS: We evaluated these correlates among 946 NTMSM from 6 US cities who participated in an internet-based survey in 2007. FINDINGS: Main reasons for not testing were low perceived risk (32.2%), structural barriers (25.1%), and fear of testing positive (18.1%). Low perceived risk was associated with having fewer unprotected anal intercourse (UAI) partners and less frequent use of the internet for HIV information; structural barriers were associated with younger age and more UAI partners; fear of testing positive was associated with black and Hispanic race/ethnicity, more UAI partners, and more frequent use of the internet for HIV information. Strong testing intentions were held by 25.9% of all NTMSM and 14.8% of those who did not test because of low perceived risk. Among NTMSM who were somewhat unlikely, somewhat likely, and very likely to test for HIV, 47.4%, 76.5%, and 85.6% would likely use an OTCRT if it was available, respectively. CONCLUSIONS: Among NTMSM who use the internet, main reasons for not testing for HIV vary considerably by age, race/ethnicity, UAI, and use of the internet for HIV information. To facilitate HIV testing of NTMSM, programs should expand interventions and services tailored to address this variation. If approved, OTCRT might be used by many NTMSM who might not otherwise test for HIV. |
Reaching patients and their partners through mobile: text messaging for case management and partner notification
Kachur R , Adelson S , Firenze K , Herrera M . Sex Transm Dis 2010 38 (2) 149-50 Approximately 83% of all US adults own a cell phone,1 and 23% of households have no landline phone service.2 Text messaging is increasingly popular with more than 61% of Americans sending text messages.3 By extension, mobile phones have become a means for finding sex partners.4 In response, sexually transmitted disease (STD) and human immunodeficiency virus (HIV) prevention programs have used mobile phones and text messaging specifically, for clinical management, sexual health services, and health promotion efforts with positive results.5,6 There have also been case studies of individual patients using text messages to inform partners of an STD exposure,7,8 but the authors are unaware of any studies that specifically address the use of text messaging by disease intervention specialists (DIS) to perform partner notification. Recent field experiences, however, compel us to highlight the need for DIS to use mobile phones as an additional tool when conducting partner notification (txtPN). Increasingly, mobile phones may be the preferred or only means for reaching sex partners. Furthermore, health care providers and patients alike are finding these new technologies acceptable.5–11 | The New York State Department of Health has successfully used texting to notify patients of an STD diagnosis and to notify partners of exposure. This method is used if “traditional” efforts such as phone calls, mailed letters, the internet, and field visits do not yield contact. In June 2009, a DIS was made aware of an untreated chlamydia patient who could not be reached by the healthcare provider via mail, telephone, or voicemail. Internet contact information for this patient was not known. The DIS conducted a reverse search on the telephone number provided and discovered it was for a mobile phone. The DIS then sent a text message stating he was with the department of health and needed to speak with the patient regarding an urgent health matter. Within minutes the patient responded via text, saying she had recently moved out of state and would contact the DIS the next morning. She did, and, after verifying her date of birth, the DIS notified her that she had tested positive for chlamydia. The patient received treatment the following day. |
Long-term immunogenicity of inactivated hepatitis A vaccine: follow-up at 15 years
Byrd KK , Bruden DL , Bruce MG , Bulkow LR , Zanis CL , Snowball MM , Homan CE , Hennessy TW , Williams JL , Dunaway E , Chaves SS , McMahon BJ . J Pediatr Infect Dis 2010 5 (4) 321-326 We conducted a 10-15 years follow-up to a long-term prospective cohort study on the immunogenicity of inactivated hepatitis A vaccine in Alaska Native children, who were initially vaccinated between 3-6 years of age. Children received three vaccine doses (320 E.U.) and were randomized into the following vaccination schedules: A (0, 1, 2 months); B (0, 1, 6 months); and C (0, 1, 12 months). Sera were collected every 2 years and tested for hepatitis A virus (anti-HAV). Levels 20 mIU/mL were considered protective. Anti-HAV geometric mean concentrations were compared by vaccination schedule at 10, 12 and 14 years of follow-up, using ANOVA. Antibody decline over the entire 15-year follow-up period was also analyzed. While none of the inter-schedule comparisons differed significantly from each other at the 10, 12 and 14-year periods, schedules B and C had significantly higher anti-HAV levels than schedule A over the entire 15 years of the study (P0.01). All schedule B and C children maintained seroprotective levels in all follow-up periods. Fourteen percent of schedule A children fell below seroprotective levels at 14 years. Our model estimated that anti-HAV geometric mean concentrations would fall below seroprotective levels at 26, 30 and 32 years for schedules A, B and C, respectively. The data indicate that hepatitis A immunity lasts at least 15 years after vaccination in children and that a booster dose is not needed during that time. However, continued monitoring is necessary to assess the need for a booster dose later in the second and third decade after receipt of the primary series. |
Nasopharyngeal carriage of Streptococcus pneumoniae in very low-birth-weight infants after administration of heptavalent pneumococcal conjugate vaccine
Ang JY , Lua JL , Asmar BI , Shankaran S , Heyne RJ , Schelonka RL , Das A , Li L , Jackson DM , Higgins RD , D'Angio CT . Arch Pediatr Adolesc Med 2010 164 (12) 1173-5 The effect of pneumococcal conjugate vaccine-7 (PCV-7) in reducing pneumococcal nasopharyngeal (NP) carriage in very low birth weight (VLBW) infants has not been studied. Our primary objective was to characterize NP carriage of S. pneumoniae in a group of VLBW infants (401-1500 grams) before administration of first PCV-7 (PRE) and at 4-6 weeks after a 3-dose PCV-7 primary series (POST). We also investigated the correlation between vaccine induced pneumococcal IgG antibody level and pneumococcal NP carriage POST PCV-7. |
Perpetration of physical assault against dating partners, peers, and siblings among a locally representative sample of high school students in Boston, Massachusetts
Rothman EF , Johnson RM , Azrael D , Hall DM , Weinberg J . Arch Pediatr Adolesc Med 2010 164 (12) 1118-24 OBJECTIVES: To assess the co-occurrence of past-month physical assault of a dating partner and violence against peers and siblings among a locally representative sample of high school students and to explore correlates of dating violence (DV) perpetration. DESIGN: Cross-sectional survey design. SETTING: Twenty-two public high schools in Boston, Massachusetts. PARTICIPANTS: A sample of urban high school students (n = 1398) who participated in the Boston Youth Survey, implemented January through April of 2008. MAIN OUTCOMES MEASURES: Self-reported physical DV in the month before the survey, defined as pushing, shoving, slapping, hitting, punching, kicking, or choking a dating partner 1 or more times. RESULTS: Among the respondents, 18.7%, 41.2%, and 31.2% of students reported past-month perpetration of physical DV, peer violence, and sibling violence, respectively. Among violence perpetrators, the perpetration of DV only was rare (7.9%). Controlling for age and school, the association between sibling violence and DV was strong for boys (adjusted prevalence ratio, 3.81; 95% confidence interval, 2.07-6.99) and for girls (1.83; 1.44-2.31), and the association between peer violence and DV perpetration was strong for boys (5.13; 3.15-8.35) and for girls (2.57; 1.87-3.52). Dating violence perpetration was also associated with substance use, knife carrying, delinquency, and exposure to community violence. CONCLUSIONS: Adolescents who perpetrated physical DV were also likely to have perpetrated peer and/or sibling violence. Dating violence is likely one of many co-occurring adolescent problem behaviors, including sibling and peer violence perpetration, substance use, weapon carrying, and academic problems. |
Achieving public health impact in youth violence prevention through community-research partnerships
Massetti GM , Vivolo AM . Prog Community Health Partnersh 2010 4 (3) 243-51 PROBLEM: Violence is a leading cause of death and disability for U.S. youth. The U.S. Centers for Disease Control and Prevention (CDC)'s Division of Violence Prevention (DVP) is committed to developing communities' capacity to engage in evidence-based youth violence (YV) prevention. PURPOSE: We discuss the characteristics of communities that exert influence on the development and epidemiology of YV, and discuss opportunities for how community-research partnerships can enhance efforts to prevent violence in communities. KEY POINTS: The needs for YV prevention are unique; the nature and phenomenology of violence are community specific. Communities also vary widely in infrastructure and systems to support coordinated, evidence-based YV prevention strategies. These conditions highlight the need for community-research partnerships to enhance community capacity, employ local resources, and engage community members in the research process. CONCLUSION: DVP is committed to working towards creating communities in which youth are safe from violence. Approaches to YV prevention that emphasize community-research partnerships to build capacity and implement evidence-based prevention strategies can provide a supportive context for achieving that goal. |
RT-PCR/electrospray ionization mass spectrometry approach in detection and characterization of influenza viruses.
Deyde VM , Sampath R , Gubareva LV . Expert Rev Mol Diagn 2011 11 (1) 41-52 Reverse-transcription PCR (RT-PCR) coupled with electrospray ionization mass spectrometry (ESI-MS) is a high-throughput nucleic acid-based technology that relies on the accurate measurement of the molecular weight of PCR amplicons that can be used to deduce the base counts (number of As, Gs, Cs and Ts) of DNA. These amplicons represent highly variable regions with information-rich sequences, which are flanked by broad-range primers designed based on highly conserved loci. This technology was first introduced in 2005 for microbial identification and subtyping, and was later applied to influenza virus detection and identification. The influenza RT-PCR/ESI-MS assay allows analysis of approximately 300 samples per 24 h, and aids in the characterization of influenza viruses based on their 'core' gene signatures. Notably, this assay was used to identify one of the first cases of the 2009 H1N1 pandemic viruses. One of the main advantages of the RT-PCR/ESI-MS technology is its universality and adaptability for pathogen characterization. Efforts are being made to customize the currently used influenza surveillance assay for use in the diagnosis of the H1N1 pandemic virus. In this article, we provide a summary of known applications of the RT-PCR/ESI-MS assay in the field of influenza. |
Regulation of lung cancer cell migration and invasion by reactive oxygen species and caveolin-1
Luanpitpong S , Talbott SJ , Rojanasakul Y , Nimmannit U , Pongrakhananon V , Wang L , Chanvorachote P . J Biol Chem 2010 285 (50) 38832-40 The acquired capability of tumor cells to migrate and invade neighboring tissues is associated with high metastatic potential and advanced stage of cancers. Recently, signaling molecules such as reactive oxygen species (ROS) and caveolin-1 (Cav-1) have been implicated in the aggressive behavior of cancer cells. However, the roles of specific ROS in cancer cell migration and Cav-1 regulation are unclear. We demonstrate here that Cav-1 plays an important role in the migration and invasion of human lung carcinoma H460 cells and that these effects are differentially regulated by cellular ROS. Using various known inhibitors and donors of ROS, we found that different ROS have different effects on Cav-1 expression and cell migration and invasion. Superoxide anion and hydrogen peroxide down-regulated Cav-1 expression and inhibited cell migration and invasion, whereas hydroxyl radical up-regulated the Cav-1 expression and promoted cell migration and invasion. The down-regulating effect of superoxide anion and hydrogen peroxide on Cav-1 is mediated through a transcription-independent mechanism that involves protein degradation via the ubiquitin-proteasome pathway. These results indicate the essential role of different ROS in cancer cell motility and through Cav-1 expression, which may provide a key mechanism controlling tumor progression and metastasis. The up-regulation of Cav-1 and cell motility by hydroxyl free radical suggests an important role of this ROS as a positive regulator of tumor progression. |
Salmonella isolates with decreased susceptibility to extended-spectrum cephalosporins in the United States
Sjolund-Karlsson M , Rickert R , Matar C , Pecic G , Howie RL , Joyce K , Medalla F , Barzilay EJ , Whichard JM . Foodborne Pathog Dis 2010 7 (12) 1503-9 OBJECTIVE: We describe the antimicrobial susceptibility to extended-spectrum cephalosporins in non-Typhi Salmonella (NTS) isolated from humans in the United States and explore resistance mechanisms for isolates displaying decreased susceptibility to ceftriaxone or ceftiofur. We further explore the concordance between the newly revised Clinical and Laboratory Standards Institute (CLSI) breakpoints for ceftriaxone and the presence of a beta-lactamase. METHODS: In 2005 and 2006, public health laboratories in all U.S. state health departments forwarded every 20th NTS isolate from humans to Centers for Disease Control and Prevention as part of the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria. Minimum inhibitory concentrations (MICs) were determined by broth microdilution. Isolates displaying decreased susceptibility (MIC ≥ 2 mg/L) to ceftriaxone or ceftiofur were included in the study. The presence of beta-lactamase genes was investigated by polymerase chain reaction amplification and sequencing, targeting six different genes (bla(TEM), bla(OXA), bla(SHV), bla(CTX-M), bla(PSE), and bla(CMY)). Plasmid location of bla(CMY) was confirmed by transforming plasmids into Escherichia coli. RESULTS: Among the 4236 isolates of NTS submitted to NARMS in 2005 and 2006, 175 (4.1%) displayed decreased susceptibility to either ceftriaxone or ceftiofur. By polymerase chain reaction screening, one or more beta-lactamase genes could be detected in 139 (80.8%) isolates. The most prevalent resistance mechanism detected was the AmpC beta-lactamase gene bla(CMY.) Other beta-lactamase genes detected included 11 bla(TEM-1), 3 bla(PSE-1), 2 bla(OXA-1), and 1 bla(CTX-M-15). The ceftriaxone MIC values for the bla(CMY)-containing isolates ranged from 4 to 64 mg/L; all bla(CMY)-bearing isolates were classified as ceftriaxone resistant according to current CLSI guidelines. CONCLUSIONS: Among NTS isolates submitted to NARMS in 2005 and 2006, cephamycinase beta-lactamases are the predominant cause of decreased susceptibility to ceftriaxone. The fact that all bla(CMY)-containing isolates were classified as resistant to ceftriaxone (MIC ≥ 4 mg/L) supports the newly revised CLSI breakpoints for cephalosporins and Enterobacteriaceae. |
Sampling and mass spectrometric analytical methods for five antineoplastic drugs in the healthcare environment
Pretty JR , Connor TH , Spasojevic I , Kurtz KS , McLaurin JL , B' Hymer C , Debord DG . J Oncol Pharm Pract 2010 18 (1) 23-36 CONTEXT: Healthcare worker exposure to antineoplastic drugs continues to be reported despite safe handling guidelines published by several groups. Sensitive sampling and analytical methods are needed so that occupational safety and health professionals may accurately assess environmental and biological exposure to these drugs in the workplace. OBJECTIVE: To develop liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analytical methods for measuring five antineoplastic drugs in samples from the work environment, and to apply these methods in validating sampling methodology. A single method for quantifying several widely used agents would decrease the number of samples required for method development, lower cost, and time of analysis. Methods for measuring these drugs in workers' urine would also be useful in monitoring personal exposure levels. RESULTS: LC-MS/MS methods were developed for individual analysis of five antineoplastic drugs in wipe and air sample media projected for use in field sampling: cyclophosphamide, ifosfamide, paclitaxel, doxorubicin, and 5-fluorouracil. Cyclophosphamide, ifosfamide, and paclitaxel were also measured simultaneously in some stages of the work. Extraction methods for air and wipe samples were developed and tested using the aforementioned analytical methods. Good recoveries from the candidate air and wipe sample media for most of the compounds, and variable recoveries for test wipe samples depending on the surface under study, were observed. Alternate LC-MS/MS methods were also developed to detect cyclophosphamide and paclitaxel in urine samples. CONCLUSIONS: The sampling and analytical methods were suitable for determining worker exposure to antineoplastics via surface and breathing zone contamination in projected surveys of healthcare settings. |
A synthetic 7,8-dihydroxyflavone derivative promotes neurogenesis and exhibits potent antidepressant effect
Liu X , Chan CB , Jang SW , Pradoldej S , Huang J , He K , Phun LH , France S , Xiao G , Jia Y , Luo HR , Ye K . J Med Chem 2010 53 (23) 8274-86 7,8-Dihydroxyflavone is a recently identified small molecular tropomyosin-receptor-kinase B (TrkB) agonist. Our preliminary structural-activity relationship (SAR) study showed that the 7,8-dihydroxy groups are essential for the agonistic effect. To improve the lead compound's agonistic activity, we have conducted an extensive SAR study and synthesized numerous derivatives. We have successfully identified 4'-dimethylamino-7,8-dihydroxyflavone that displays higher TrkB agonistic activity than that of the lead. This novel compound also exhibits a more robust and longer TrkB activation effect in animals. Consequently, this new compound reveals more potent antiapoptotic activity. Interestingly, chronic oral administration of 4'-dimethylamino-7,8-dihydroxyflavone and its lead strongly promotes neurogenesis in dentate gyrus and demonstrates marked antidepressant effects. Hence, our data support that the synthetic 4'-dimethylamino-7,8-dihydroxyflavone and its lead both are orally bioavailable TrkB agonists and possess potent antidepressant effects. |
Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity
McMahan RH , Golden-Mason L , Nishimura MI , McMahon BJ , Kemper M , Allen TM , Gretch DR , Rosen HR . J Clin Invest 2010 120 (12) 4546-57 Having successfully developed mechanisms to evade immune clearance, hepatitis C virus (HCV) establishes persistent infection in approximately 75%-80% of patients. In these individuals, the function of HCV-specific CD8+ T cells is impaired by ligation of inhibitory receptors, the repertoire of which has expanded considerably in the past few years. We hypothesized that the coexpression of the negative regulatory receptors T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) and programmed death 1 (PD-1) in HCV infection would identify patients at risk of developing viral persistence during and after acute HCV infection. The frequency of PD-1-Tim-3- HCV-specific CTLs greatly outnumbered PD-1+Tim-3+ CTLs in patients with acute resolving infection. Moreover, the population of PD-1+Tim-3+ T cells was enriched for within the central memory T cell subset and within the liver. Blockade of either PD-1 or Tim-3 enhanced in vitro proliferation of HCV-specific CTLs to a similar extent, whereas cytotoxicity against a hepatocyte cell line that expressed cognate HCV epitopes was increased exclusively by Tim-3 blockade. These results indicate that the coexpression of these inhibitory molecules tracks with defective T cell responses and that anatomical differences might account for lack of immune control of persistent pathogens, which suggests their manipulation may represent a rational target for novel immunotherapeutic approaches. |
Use of the human monocytic leukemia THP-1 cell line and co-incubation with microsomes to identify and differentiate hapten and prohapten sensitizers
Chipinda I , Ruwona TB , Templeton SP , Siegel PD . Toxicology 2010 280 (3) 135-43 Consumer and medical products can contain leachable chemical allergens which can cause skin sensitization. Recent efforts have been directed at the development of non-animal based tests such as in vitro cell activation assays for the identification of skin sensitizers. Prohapten identification by in vitro assays is still problematic due to the lack of prohapten bioactivation. The present study evaluated the effect of hapten and prohapten exposure on cell surface markers expression (CD86, CD54 and CD40) in the human monocytic leukemia, THP-1, cell line. Upregulation of activation and costimulatory markers are key events in the allergic sensitization process and have been reported to serve as indicators of skin sensitization. Cells were exposed to the prohaptens benzo(a)pyrene (BaP), 7,12-dimethylbenz(a)anthracene (DMBA),carvone oxime (COx), cinnamic alcohol (CA) and isoeugenol (IEG) at concentrations ranging from 1 to 10muM for 24 and 48h. The direct-binding haptens dinitrochlorobenzene (DNCB) benzoquinone (BQ), hydroxylethyl acrylate (HEA) and benzylbromide (BB) were used as positive controls. Cells were also exposed to the irritants sodium dodecyl sulfate (SDS) and sulfanilamide (SFA). Bioactivation of prohaptens was achieved by adding aroclor-induced rat liver microsomes (S9) to the cell cultures. Consistent upregulation of surface expressions of CD86, CD54 (ICAM-1) and CD40 was observed in THP-1 cells treated with direct-acting haptens (+/-S9) or prohapten (+S9). Upregulation of these markers was not observed after exposure to skin irritants or prohaptens in the absence of exogenously added S9. In conclusion, modification of in vitro cell culture assays to include co-incubation with microsomes enhances identification of prohaptens and allows them to be clearly distinguished from direct-binding haptens. |
Znu is the predominant zinc importer in Yersinia pestis during in vitro growth but is not essential for virulence
Desrosiers DC , Bearden SW , Mier I Jr , Abney J , Paulley JT , Fetherston JD , Salazar JC , Radolf JD , Perry RD . Infect Immun 2010 78 (12) 5163-77 Little is known about Zn homeostasis in Yersinia pestis, the plague bacillus. The Znu ABC transporter is essential for zinc (Zn) uptake and virulence in a number of bacterial pathogens. Bioinformatics analysis identified ZnuABC as the only apparent high-affinity Zn uptake system in Y. pestis. Mutation of znuACB caused a growth defect in Chelex-100-treated PMH2 growth medium, which was alleviated by supplementation with submicromolar concentrations of Zn. Use of transcriptional reporters confirmed that Zur mediated Zn-dependent repression and that it can repress gene expression in response to Zn even in the absence of Znu. Virulence testing in mouse models of bubonic and pneumonic plague found only a modest increase in survival in low-dose infections by the znuACB mutant. Previous studies of cluster 9 (C9) transporters suggested that Yfe, a well-characterized C9 importer for manganese (Mn) and iron in Y. pestis, might function as a second, high-affinity Zn uptake system. Isothermal titration calorimetry revealed that YfeA, the solute-binding protein component of Yfe, binds Mn and Zn with comparably high affinities (dissociation constants of 17.8 +/- 4.4 nM and 6.6 +/- 1.2 nM, respectively), although the complete Yfe transporter could not compensate for the loss of Znu in in vitro growth studies. Unexpectedly, overexpression of Yfe interfered with the znu mutant's ability to grow in low concentrations of Zn, while excess Zn interfered with the ability of Yfe to import iron at low concentrations; these results suggest that YfeA can bind Zn in the bacterial cell but that Yfe is incompetent for transport of the metal. In addition to Yfe, we have now eliminated MntH, FetMP, Efe, Feo, a substrate-binding protein, and a putative nickel transporter as the unidentified, secondary Zn transporter in Y. pestis. Unlike other bacterial pathogens, Y. pestis does not require Znu for high-level infectivity and virulence; instead, it appears to possess a novel class of transporter, which can satisfy the bacterium's Zn requirements under in vivo metal-limiting conditions. Our studies also underscore the need for bacterial cells to balance binding and transporter specificities within the periplasm in order to maintain transition metal homeostasis. |
Performance of a rapid antigen test (Binax NOW((R)) RSV) for diagnosis of respiratory syncytial virus compared with real-time polymerase chain reaction in a pediatric population
Miernyk K , Bulkow L , Debyle C , Chikoyak L , Hummel KB , Hennessy T , Singleton R . J Clin Virol 2010 50 (3) 240-3 BACKGROUND: Infants from Alaska's Yukon-Kuskokwim Delta (YKD) have a high respiratory syncytial virus (RSV) hospitalization rate (104/1000/yr). Appropriate patient management requires rapid and accurate RSV diagnosis. Antigen-based methods are often used in clinical settings, but these tests can lack sensitivity. OBJECTIVE: We compared Binax NOW((R)) RSV (BN) used for RSV diagnosis in the YKD hospital with a real-time polymerase chain reaction assay (RT-qPCR) used for viral surveillance. STUDY DESIGN: Between October 2005 and September 2007 we obtained nasopharyngeal washes (NPW) from children <3 years hospitalized with a lower respiratory tract infection. The NPW were tested using BN and RT-qPCR. RESULTS: 79/311 (25%) children had RSV infection as determined by RT-qPCR. As compared with RT-qPCR, sensitivity and specificity of BN were 72% and 97%, respectively. The sensitivity of BN was higher in children <1 year compared with children ≥1 year (79% vs. 52%; p=0.025), children with bronchiolitis compared with children without bronchiolitis (89% vs. 38%; p<0.001), and children with a shorter duration of symptoms before testing (0-1 (92%) vs. 2-4 (78%) vs. 5+ (65%) days; p=0.04). The median RSV viral load in NPW positive by BN and RT-qPCR was 1.01x10(9)copies/mL vs. a median of 5.25x10(7)copies/mL for NPW positive by RT-qPCR only (p<0.001). CONCLUSION: RT-qPCR is more sensitive than BN in detecting RSV infection. BN sensitivity is high in children with bronchiolitis, but the sensitivity is low when children present with a non-bronchiolitis illness, especially after a longer duration of symptoms before testing. |
Proficiency testing outcomes of 3-hydroxyisovalerylcarnitine measurements by tandem mass spectrometry in newborn screening
Lim TH , De Jesus VR , Meredith NK , Sternberg MR , Chace DH , Mei JV , Hannon WH . Clin Chim Acta 2010 412 631-5 BACKGROUND: The use of tandem mass spectrometry (MS/MS) for the analysis of amino acids and acylcarnitines from dried-blood spots (DBS) has become routine practice in newborn screening laboratories. The Newborn Screening Quality Assurance Program (NSQAP) added 3-hydroxyisovalerylcarnitine (C5OH) into its routine quality control and proficiency testing (PT) DBS materials for MS/MS to assure the quality of C5OH screening. We report the results from NSQAP evaluations for C5OH-enriched DBS, and summarize participant screening practices based on their analytical methods. METHODS: NSQAP prepared C5OH-enriched DBS materials for its participants. Laboratories reported quantitative and qualitative results. Bias plots of quantitative results were constructed using reported data and the results were sorted by analytical method. RESULTS: NSQAP participants reported PT specimen 3964 as outside of normal limits for C5OH. The mean C5OH value for derivatized and non-derivatized methods was 2.80 and 2.67mumol/l, respectively. Reported data from other specimens showed a similar trend in derivatized vs. non-derivatized assay results. Differences in C5OH quantitative values were observed among laboratories using different internal standards. CONCLUSIONS: C5OH MS/MS measurements in DBS assays varied by method and the choice of internal standards. The use of NSQAP's DBS materials allows harmonization of C5OH measurements by newborn screening laboratories worldwide. |
Quality assurance in the HIV/AIDS laboratory network of China
Jiang Y , Qiu M , Zhang G , Xing W , Xiao Y , Pan P , Yao J , Ou CY , Su X . Int J Epidemiol 2010 39 Suppl 2 ii72-8 BACKGROUND: In 2009, there were 8273 local screening laboratories, 254 confirmatory laboratories, 35 provincial confirmatory central laboratories and 1 National AIDS Reference Laboratory (NARL) in China. These laboratories were located in Center for Disease Control and Prevention (CDC) facilities, hospitals, blood donation clinics, maternal and child health (MCH) hospitals and border health quarantine health-care facilities. METHODS: The NARL and provincial laboratories provide quality assurance through technical, bio-safety and managerial training; periodic proficiency testing; on-site supervisory inspections; and commercial serologic kit evaluations. RESULTS: From 2002 to 2009, more than 220 million HIV antibody tests were performed at screening laboratories, and all reactive and indeterminate samples were confirmed at confirmatory laboratories. The use of highly technically complex tests, including CD4 cell enumeration, viral load, dried blood spot (DBS)-based early infant diagnosis (EID), drug resistance (DR) genotyping, HIV-1 subtyping and incidence assays, have increased in recent years and their performance quality is closely monitored. CONCLUSION: China has made significant progress in establishing a well-coordinated HIV laboratory network and QA systems. However, the coverage and intensity of HIV testing and quality assurance programmes need to be strengthened so as to ensure that more infected persons are diagnosed and that they receive timely prevention and treatment services. |
Quantitative analysis of six heterocyclic aromatic amines in mainstream cigarette smoke condensate using isotope dilution liquid chromatography-electrospray ionization tandem mass spectrometry
Zhang L , Ashley DL , Watson CH . Nicotine Tob Res 2010 13 (2) 120-6 INTRODUCTION: Heterocyclic aromatic amines (HAAs) represent an important class of carcinogens in mainstream cigarette smoke. Accurate HAA quantification is challenging because of their relative low abundances and numerous chemical interferences that arise naturally from thousands of the constituents present in cigarette smoke. We have developed and validated a straightforward high-throughput method to quantify HAA levels in mainstream cigarette smoke and demonstrated the applicability by analyzing select research and domestic cigarette brands. METHODS: Machine-smoked cigarette condensate collected under both standard and intensive smoking regimens was examined. Mainstream smoke particulate from individual cigarettes trapped on a glass fiber filter pad was spiked with an appropriate internal standard solution and subsequently solvent extracted. The extract was quantitatively analyzed by high-performance liquid chromatography and tandem mass spectrometry. RESULTS: Method validation data showed excellent accuracy, reproducibility and high throughput; it is suitable for the routine analysis of HAAs in cigarette smoke condensate delivered under a wide of differing smoking conditions. The smoking machine deliveries of HAAs are strongly influenced by cigarettes' physical design, filler blend, and smoking regimen. CONCLUSIONS: A quick and accurate method has been developed for the analysis of 6 HAAs in mainstream cigarette smoke condensate. Results provided a good mean to access the ranges of HAAs in commercial products and evaluate the relative contribution of cigarette design, filler blend, and smoking regimen on delivery. Such data are vital in helping provide exposure ranges for potential human exposure estimates. |
Evaluation of diagnostic tests: dengue
Peeling RW , Artsob H , Pelegrino JL , Buchy P , Cardoso MJ , Devi S , Enria DA , Jeremy F , Gubler DJ , Guzman MC , Halstead SB , Hunsperger E , Kliks S , Margolis HS , Nathanson CM , Vinh CN , Rizzo N , Vazquez S , Yoksan S . Nat Rev Microbiol 2010 8 S30-8 Dengue is an arthropod-borne flavivirus that comprises four distinct serotypes (DEN-1, DEN-2, DEN-3 and DEN-4) that constitute an antigenic complex of the genus flavivirus, family Flaviviridae. Infection by one serotype induces life-long immunity against reinfection by the same serotype, but only transient and partial protection against infection with the other serotypes1,2. | Dengue virus infections can result in a range of clinical manifestations from asymptomatic infection to dengue fever (DF) and the severe disease dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Most dengue infections are asymptomatic or cause mild symptoms, which are characterized by undifferentiated fever with or without rash. Typical DF is characterized by high fever, severe headache, myalgia, arthralgia, retro-orbital pain and maculopapular rash. Some patients show petechiae, bruising or thrombocytopenia. The clinical presentation of acute dengue infection is non-specific but 5–10% of patients progress to severe DHF/DSS, which can result in death if it is not managed appropriately. Plasma extravasation is the main pathophysiological finding of DHF/DSS, which differentiates it from DF. DHF/DSS is characterized by high fever, bleeding, thrombocytopenia and haemoconcentration (an increase in the concentration of blood cells as a result of fluid loss). Approximately 3–4 days after the onset of fever, patients can present with petechiae, rash, epistaxis, and gingival and gastrointestinal bleeding. Pleural effusion and ascites are common. Some patients develop circulatory failure (DSS), presenting with a weak and fast pulse, narrowing of pulse pressure or hypotension, cold and moist skin and altered mental state. Although there are no specific antiviral treatments for dengue infection, patients usually recover when the need for fluid management is identified early and electrolytes are administered3. It has been proposed that the classification of dengue disease should be simplified as severe and non-severe dengue. This simplified classification would make patient management and surveillance easier4. |
Evaluation of serum bactericidal antibody assays for Haemophilus influenzae serotype a
Rouphael NG , Satola S , Farley MM , Rudolph K , Schmidt DS , Gomez-de-Leon P , Robbins JB , Schneerson R , Carlone GM , Romero-Steiner S . Clin Vaccine Immunol 2010 18 (2) 243-7 Haemophilus influenzae type a (Hia) is an important pathogen for some American Indian, Alaskan natives and Northern Canada aboriginal populations. Assays to measure serum bactericidal activity (SBA) to Hia have not been developed or validated. Here we describe two methods for the measurement of SBA: SBA with a viability end-point (CFU counts) and SBA with a fluorometric end-point using alamarBlue as metabolic indicator. Both SBA assays measure Hia-specific functional antibody and correlate with anti-Hia IgG ELISA concentration of naturally-acquired antibodies. |
Kdo2-lipid A, a TLR4-specific agonist, induces de novo sphingolipid biosynthesis in RAW264.7 macrophages, which is essential for induction of autophagy
Sims K , Haynes CA , Kelly S , Allegood JC , Wang E , Momin A , Leipelt M , Reichart D , Glass CK , Sullards MC , Merrill AH Jr . J Biol Chem 2010 285 (49) 38568-79 Activation of RAW264.7 cells with a lipopolysaccharide specific for the TLR4 receptor, Kdo(2)-lipid A (KLA), causes a large increase in cellular sphingolipids, from 1.5 to 2.6 x 10(9) molecules per cell in 24 h, based on the sum of subspecies analyzed by "lipidomic" mass spectrometry. Thus, this study asked the following question. What is the cause of this increase and is there a cell function connected with it? The sphingolipids arise primarily from de novo biosynthesis based on [U-(13)C]palmitate labeling, inhibition by ISP1 (myriocin), and an apparent induction of many steps of the pathway (according to the distribution of metabolites and microarray analysis), with the exception of ceramide, which is also produced from pre-existing sources. Nonetheless, the activated RAW264.7 cells have a higher number of sphingolipids per cell because KLA inhibits cell division; thus, the cells are larger and contain increased numbers of membrane vacuoles termed autophagosomes, which were detected by the protein marker GFP-LC3. Indeed, de novo biosynthesis of sphingolipids performs an essential structural and/or signaling function in autophagy because autophagosome formation was eliminated by ISP1 in KLA-stimulated RAW264.7 cells (and mutation of serine palmitoyltransferase in CHO-LYB cells); furthermore, an anti-ceramide antibody co-localizes with autophagosomes in activated RAW264.7 cells versus the Golgi in unstimulated or ISP1-inhibited cells. These findings establish that KLA induces profound changes in sphingolipid metabolism and content in this macrophage-like cell line, apparently to produce sphingolipids that are necessary for formation of autophagosomes, which are thought to play important roles in the mechanisms of innate immunity. |
Analysis of antibody responses to Mycobacterium leprae phenolic glycolipid-I, lipoarabinomannan and recombinant proteins to define disease-subtype specific antigenic profiles in leprosy
Spencer JS , Kim HJ , Wheat WH , Chatterjee D , Balagon MV , Cellona RV , Tan EV , Gelber R , Saunderson P , Duthie MS , Reece ST , Burman W , Belknap R , Mac Kenzie WR , Geluk A , Oskam L , Dockrell HM , Brennan PJ . Clin Vaccine Immunol 2010 18 (2) 260-7 A simple serodiagnostic test based on the Mycobacterium leprae-specific phenolic glycolipid, PGL-I, for individuals with leprosy is nearly universally positive in leprosy patients with high bacillary loads, but cannot be used as a stand-alone diagnostic test for the entire spectrum of the disease process. For patients with early infection with no detectable acid fast bacilli in lesions or with low or no antibody titer to PGL-I as in those at the tuberculoid end of the disease spectrum, this diagnostic approach has limited usefulness. To identify additional M. leprae antigens that might enhance the serological detection of these individuals, we have examined the reactivity patterns of patient sera to PGL-I, lipoarabinomannan (LAM) and six recombinant M. leprae proteins (ML1877, ML0841, ML2028, ML2038, ML0380 and ML0050) by Western blot and ELISA. Overall, the responses to ML2028 (Ag85B) and ML2038 (bacterioferritin) were consistently high in both multibacillary and paucibacillary groups and weak or absent in endemic controls, while responses to other antigens showed considerable variability, from strongly positive to completely negative. This analysis has given a clearer understanding of some of the differences in the antibody responses, between individuals at opposite ends of the disease spectrum, as well as illustrating the heterogeneity of antibody responses towards protein, carbohydrate, and glycolipid antigens within a clinical group. Correlating these response patterns with a particular disease state would allow for a more critical assessment of the form of disease within the leprosy spectrum and could lead to better patient management. |
Antimicrobial-resistant nocardia isolates, United States, 1995-2004
Uhde KB , Pathak S , McCullum I Jr , Jannat-Khah DP , Shadomy SV , Dykewicz CA , Clark TA , Smith TL , Brown JM . Clin Infect Dis 2010 51 (12) 1445-8 We conducted a 10-year retrospective evaluation of the epidemiology and identification of Nocardia isolates submitted to the Centers for Disease Control and Prevention for antimicrobial susceptibility testing. The species most commonly identified were N. nova (28%), N. brasiliensis (14%), and N. farcinica (14%). Of 765 isolates submitted, 61% were resistant to sulfamethoxazole and 42% were resistant to trimethoprim-sulfamethoxazole. |
Assessing blood pressure accuracy of an aneroid sphygmomanometer in a national survey environment
Ostchega Y , Prineas RJ , Nwankwo T , Zipf G . Am J Hypertens 2010 24 (3) 322-7 BACKGROUND: The "gold standard" employed for obtaining blood pressure (BP) for all the National Health and Nutrition Examination Surveys (NHANES) has been the mercury sphygmomanometer (HgS). Because of environmental concerns, there is a need to explore an alternative to HgS. METHODS: We compared the accuracy of the Welch Allyn 767 wall aneroid sphygmomanometer (AnS) to the HgS in children and adults and by BP cuff sizes. Each participant had three BP measurements per device recorded sequentially. The order of the devices and observer were random. A total of 727 individuals participating in the NHANES participated in the study. RESULTS: The mean AnS readings were not statistically significantly different from those of the HgS with the exception of systolic BP (SBP) in aged 8-17 years (mean difference 1.10, s.d. 4.87). There were no statistically significantly different by BP cuff sizes. Agreement for the prevalence of hypertension (BP ≥140 systolic or diastolic ≥90 mm Hg) was above chance (kappa = 0. 81; sensitivity = 81%; specificity = 98%) with AnS readings underestimating by 1.66% (18.33 vs. 20%, P > 0.05) compared to the HgS reading. CONCLUSIONS: With the exception of SBP in ages 8-17 years, the AnS device readings were not significantly different from HgS readings by age or BP cuff sizes selection. Agreement for hypertension classification is good. An accurate and well-calibrated AnS could therefore provide an acceptable alternative to the use of a HgS in surveys, although with appropriate caution given the 81% sensitivity with regard to hypertension thresholds that was observed.American Journal of Hypertension (2010). doi:10.1038/ajh.2010.232. |
Different substrate recognition requirements for cleavage of synaptobrevin-2 by Clostridium baratii and Clostridium botulinum type F neurotoxins
Kalb SR , Baudys J , Egan C , Smith TJ , Smith LA , Pirkle JL , Barr JR . Appl Environ Microbiol 2010 77 (4) 1301-8 Botulinum neurotoxins (BoNTs) cause botulism, which can be fatal if untreated. BoNTs cleave proteins necessary for nerve transmission, resulting in paralysis. The in vivo protein target has been reported for all seven serotypes of BoNT, A-G. Knowledge of the cleavage sites has led to the development of several assays to detect BoNT based on its ability to cleave a peptide substrate derived from its in vivo protein target. Most serotypes of BoNT can be further subdivided into subtypes, and previously, we demonstrated that three of the currently known subtypes of BoNT/F cleave a peptide substrate, a shortened version of synaptobrevin-2, between Q58 and K59. However, our research indicated that Clostridium baratii type F toxin did not cleave this peptide. In this study, we detail experiments demonstrating that Clostridium baratii type F toxin cleaves recombinant synaptobrevin-2 in the same location as proteolytic F toxin. In addition, we demonstrate that Clostridium baratii type F toxin can cleave a peptide substrate based on the sequence of synaptobrevin-2. This peptide substrate is an N-terminal extension of the original peptide substrate used for detection of other BoNT/F toxins and can be used to detect four of the currently known BoNT/F subtypes by mass spectrometry. |
Anesthesia-related maternal mortality in the United States: 1979-2002
Hawkins JL , Chang J , Palmer SK , Gibbs CP , Callaghan WM . Obstet Gynecol 2011 117 (1) 69-74 OBJECTIVE: To examine 12 years of anesthesia-related maternal deaths from 1991 to 2002 and compare them with data from 1979 to 1990, to estimate trends in anesthesia-related maternal mortality over time, and to compare the risks of general and regional anesthesia during cesarean delivery. METHODS: The authors reviewed anesthesia-related maternal deaths that occurred from 1991 to 2002. Type of anesthesia involved, mode of delivery, and cause of death were determined. Pregnancy-related mortality ratios, defined as pregnancy-related deaths due to anesthesia per million live births were calculated. Case fatality rates were estimated by applying a national estimate of the proportion of regional and general anesthetics to the national cesarean delivery rate. RESULTS: Eighty-six pregnancy-related deaths were associated with complications of anesthesia, or 1.6% of total pregnancy-related deaths. Pregnancy-related mortality ratios for deaths related to anesthesia is 1.2 per million live births for 1991-2002, a decrease of 59% from 1979-1990. Deaths mostly occurred among younger women, but the percentage of deaths among women aged 35-39 years increased substantially. Delivery method could not be determined in 14%, but the remaining 86% were undergoing cesarean delivery. Case-fatality rates for general anesthesia were 16.8 per million in 1991-1996 and 6.5 per million in 1997-2002, and for regional anesthesia were 2.5 and 3.8 per million, respectively. The resulting risk ratio between the two techniques for 1997-2002 was 1.7 (confidence interval 0.6-4.6, P=.2). CONCLUSION: Anesthetic-related maternal mortality decreased nearly 60% when data from 1979-1990 were compared with data from 1991-2002. Although case-fatality rates for general anesthesia are falling, rates for regional anesthesia are rising. LEVEL OF EVIDENCE: II. |
Trends in hospitalization for empyema in Alaska native children yournger than 10 years of age
Singleton RJ , Holman RC , Wenger J , Christensen KY , Bulkow LR , Zulz T , Steiner CA , Cheek JE . Pediatr Infect Dis J 2010 30 (6) 528-30 We analyzed hospitalizations for empyema among Alaska Native (AN) children and the general population of US children <10 years during the years 1998 to 2007. We also analyzed invasive pneumococcal disease in AN children. Between 1998 and 2000, the average annual hospitalization rate for empyema was higher for AN children (51.8 per 100,000/yr) than that for US children (24.2 [95% confidence interval: 20.4, 27.9] per 100,000/yr), and had increased in 2004-2007 in both populations (59.6 and 36.0 [95% confidence interval: 30.1, 41.8], respectively). Pneumococcal empyema increased in AN children despite a decrease in invasive pneumococcal disease pneumonia. |
Gestational hypertension: a neglected cardiovascular disease risk marker
Robbins CL , Dietz PM , Bombard J , Valderrama AL . Am J Obstet Gynecol 2010 204 (4) 336 e1-9 OBJECTIVE: The purpose of this study is to examine hypertension and cholesterol screening, knowledge of heart attack symptoms, and cardiovascular disease (CVD) risk factors among women with a history of gestational hypertension. STUDY DESIGN: We used weighted 2008 National Health Interview Survey data to examine health indicators and modifiable CVD risk factors and to estimate prevalence and adjusted odds ratios for recommended CVD screening and knowledge of heart attack symptoms by hypertension history among 11,970 adult women. RESULTS: Among women with gestational hypertension only (n = 301), 93% received the recommended screening for hypertension; 75% received screening for dyslipidemia, and 40% correctly identified 5 of 5 heart attack symptoms. The odds of CVD screenings and knowledge did not differ between women with a history of gestational hypertension and those with no hypertension. However, women with gestational hypertension had higher rates of obesity (43%), CVD (18%), and diabetes mellitus (13%), compared with women without a history of hypertension (21%, 8%, and 3%, respectively). CONCLUSION: A history of gestational hypertension is a neglected CVD risk marker. |
Mortality and end-stage renal disease incidence among dry cleaning workers
Calvert GM , Ruder AM , Petersen MR . Occup Environ Med 2010 68 (10) 709-16 OBJECTIVE: Perchloroethylene (PCE) is a known animal carcinogen and probable human carcinogen. Dry cleaning exposures, particularly PCE, are also associated with renal toxicity. The objective was to follow-up a cohort of dry cleaners to evaluate mortality and assess end-stage renal disease (ESRD) morbidity. METHODS: This study adds 8 years of mortality follow-up for 1704 dry cleaning workers in four cities. Employees eligible for inclusion worked for ≥1 year before 1960 in a shop using PCE as the primary solvent. Life table analyses for mortality and ESRD morbidity were conducted. Only employees alive on 1 January 1977 were included in ESRD analyses. RESULTS: Overall cancer deaths were in significant excess in this cohort (standardised mortality ratio (SMR) 1.22, 95% CI 1.09 to 1.36). Oesophageal, lung and tongue cancers had significant excesses of deaths. Oesophageal cancer risk was highest among those employed in a PCE-using shop for ≥5 years with ≥20 years' latency since first such employment. Deaths from non-malignant underlying diseases of the stomach and duodenum were in significant excess. Hypertensive ESRD morbidity was significantly elevated in the entire cohort (standardised incidence ratio (SIR) 1.98, 95% CI 1.11 to 3.27), and among workers employed only in PCE-using dry cleaning shops for ≥5 years. CONCLUSION: Employment in the dry cleaning industry and occupational exposure to PCE are associated with an increased risk for ESRD and for cancer at several sites. The employment duration findings for oesophageal cancer and hypertensive ESRD further support an association with PCE exposure instead of lifestyle or socioeconomic factors. |
Electromyography of the thigh muscles during lifting tasks in kneeling and squatting postures
Gallagher S , Pollard J , Porter WL . Ergonomics 2011 54 (1) 91-102 Underground coal miners who work in low-seam mines frequently handle materials in kneeling or squatting postures. To assess quadriceps and hamstring muscle demands in these postures, nine participants performed lateral load transfers in kneeling and squatting postures, during which electromyographic (EMG) data were collected. EMG activity was obtained at five points throughout the transfer for three quadriceps muscles and two hamstring muscles from each thigh. ANOVA results indicated that EMG data for nine of 10 thigh muscles were affected by an interaction between posture and angular position of the load lifted (p < 0.001). Muscles of the right thigh were most active during the lifting portion of the task (lifting a block from the participant's right) and activity decreased as the block was transferred to the left. Left thigh muscles showed the opposite pattern. EMG activity for the majority of thigh muscles was affected by the size of the base of support provided by different postures, with lower EMG activity observed with a larger base of support and increased activity in postures where base of support was reduced (p < 0.05). Thigh EMG activity was lowest in postures with fully flexed knees, which may explain worker preference for this posture. However, such postures are also associated with increased risk of meniscal damage. STATEMENT OF RELEVANCE: Kneeling and squatting postures are sometimes used for manual lifting activities, but are associated with increased knee injury risk. This paper examines the EMG responses of knee extensors/flexors to lifting in these postures, discusses the impact of posture and kneepads on muscle recruitment and explores the implications for work in such postures. |
The challenge of defining standards of prevention in HIV prevention trials
Philpott S , Heise L , McGrory E , Paxton L , Hankins C . J Med Ethics 2010 37 (4) 244-8 As new HIV prevention tools are developed, researchers face a number of ethical and logistic questions about how and when to include novel HIV prevention strategies and tools in the standard prevention package of ongoing and future HIV prevention trials. Current Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) guidance recommends that participants in prevention trials receive 'access to all state of the art HIV risk reduction methods', and that decisions about adding new tools to the prevention package be made in consultation with 'all relevant stakeholders'. The guidance, however, leaves open questions of both process and implementation. In March 2009, the Global Campaign for Microbicides, UNAIDS and the Centers for Disease Control and Prevention convened a consultation to develop practical answers to these questions. Fifty-nine diverse participants, including researchers, ethicists, advocates and policymakers, worked to develop consensus criteria on when to include new HIV prevention tools in future trials. Participants developed a set of questions to guide decision-making, including: whether the method has been recommended by international bodies or adopted at a national level; the size of the effect and weight of the evidence; relevance to the trial population; whether the tool has been approved or introduced in the trial country; whether adding the tool might lead to trial futility; outstanding safety issues and status of the trial. Further work is needed to develop, implement and evaluate approaches to facilitate meaningful stakeholder participation in this deliberative process. |
A model for allocating CDC's HIV prevention resources in the United States
Lasry A , Sansom SL , Hicks KA , Uzunangelov V . Health Care Manag Sci 2010 14 (1) 115-24 The Division of HIV/AIDS Prevention (DHAP) at the Centers for Disease Control and Prevention has an annual budget of approximately $325 million for funding HIV prevention programs in the U.S. The purpose of this paper is to thoroughly describe the methods used to develop a national HIV resource allocation model intended to inform DHAP on allocation strategies that might improve the overall effectiveness of HIV prevention efforts. The HIV prevention resource allocation problem consists of choosing how to apportion prevention resources among interventions and populations so that HIV incidence is minimized, given a budget constraint. We developed an epidemic model that projects HIV infections over time given a specific allocation scenario. The epidemic model is then embedded in a nonlinear mathematical optimization program to determine the allocation scenario that minimizes HIV incidence over a 5-year horizon. In our model, we consider the general U.S. population and specific at-risk populations. The at-risk populations include 15 subgroups structured by gender, race/ethnicity and HIV transmission risk group. HIV transmission risk groups include high-risk heterosexuals, men who have sex with men and injection drug users. We consider HIV screening interventions and interventions to reduce HIV-related risk behaviors. The output of the model is the optimal funding scenario indicating the amounts to be allocated to all combinations of populations and interventions. For illustrative purposes only, we provide a sample application of the model. In this example, the optimal allocation scenario is compared to the current baseline funding scenario to highlight how the current allocation of funds could be improved. In the baseline allocation, 29% of the annual budget is aimed at the general population, while the model recommends targeting 100% of the budget to the at-risk populations with no allocation targeted to the general population. Within the allocation to behavioral interventions the model recommends an increase in targeting diagnosed positives. Also, the model allocation suggests a greater focus on MSM and IDUs with a 72% of the annual budget allocated to them, while the baseline allocation for MSM and IDUs totals 37%. Incorporating future epidemic trends in the decision-making process informs the selection of populations and interventions that should be targeted. Improving the use of funds by targeting the interventions and population subgroups at greatest risk may lead to improved HIV outcomes. These models can also direct research by pointing to areas where the development of cost-effective interventions can have the most impact on the epidemic. |
Practice-based research network partnership with CDC to acquire clinical specimens to study the etiology of southern tick-associated rash illness (STARI)
Vaughn MF , Sloane PD , Knierim K , Varkey D , Pilgard MA , Johnson BJ . J Am Board Fam Med 2010 23 (6) 720-7 INTRODUCTION: Erythema migrans (EM) is an annular, erythematous, expanding rash that is characteristic of early Lyme disease. In the southern United States, however, many cases of EM seem to have an etiology different from that of Lyme disease. This little-understood condition is called Southern tick-associated rash illness. METHODS: With the goal of obtaining biological specimens and clinical histories from 12 to 20 STARI patients for use in etiologic research, microbiologists from the Centers for Disease Control and Prevention contacted the North Carolina Network Consortium, a statewide consortium of practice-based research networks. This article describes the methods by which the North Carolina Network Consortium successfully identified and enrolled Southern tick-associated rash illness patients into a primary care-based research protocol. RESULTS: A total of 23 patients were enrolled, with 100% attainment of the desired specimens. After an initial lack of success, the revised protocol identified and trained physicians practicing in endemic areas for the illness, used a coordinator with 24-hour availability, recruited participants using newspaper notices and medical providers, and provided regular reminders and progress updates. CONCLUSIONS: A practice-based research network can help basic scientists identify patients and collect specimens for clinically relevant research. |
Contributions of international cooperation projects to the HIV/AIDS response in China
Sun J , Liu H , Li H , Wang L , Guo H , Shan D , Bulterys M , Korhonen C , Hao Y , Ren M . Int J Epidemiol 2010 39 Suppl 2 ii14-20 BACKGROUND: For 20 years, China has participated in 267 international cooperation projects against the HIV/AIDS epidemic and received approximately 526 million USD from over 40 international organizations. These projects have played an important role by complementing national efforts in the fight against HIV/AIDS in China. METHODS: The diverse characteristics of these projects followed three phases over 20 years. Initially, stand-alone projects provided technical support in surveillance, training or advocacy for public awareness. As the epidemic spread across China, projects became a part of the comprehensive and integrated national response. Currently, international best practices encourage the inclusion of civil society and non-governmental organizations in an expanded response to the epidemic. RESULTS: Funding from international projects has accounted for one-third of the resources provided for the HIV/AIDS response in China. Beyond this strong financial support, these programmes have introduced best practices, accelerated the introduction of AIDS policies, strengthened capacity, improved the development of grassroots social organizations and established a platform for communication and experience sharing with the international community. However, there are still challenges ahead, including integrating existing resources and exploring new programme models. The National Centre for AIDS/STD Control and Prevention (NCAIDS) in China is consolidating all international projects into national HIV prevention, treatment and care activities. CONCLUSION: International cooperation projects have been an invaluable component of China's response to HIV/AIDS, and China has now been able to take this information and share its experiences with other countries with the help of these same international programmes. |
Evolving views of disability and public health: the roles of advocacy and public health
Krahn G , Campbell VA . Disabil Health J 2011 4 (1) 12-8 Promoting health, quality of life, and participation of persons with disabilities is a relatively recent development in public health. Its brief history reflects three distinct public health perspectives toward disability-a traditional approach that focuses on preventing disability, a contemporary approach that regards disability as a minority group experiencing disparities relative to people without disabilities, and an emerging perspective where disability status is considered one of multiple determinants of health. The field of disability and health has been influenced by the interaction of disability advocacy with the public health process of surveillance, epidemiology research, and intervention. Advocacy draws on political and legal arguments to press for action on issues such as health care access, control of services, and choice of residence. Public health uses surveillance to document magnitude of problems; epidemiology to identify specific groups, develop measures, and apply rigorous research methods; and intervention to improve health behaviors and health outcomes. The field of disability and public health, however, has lagged in addressing the role of environmental factors in the disabling process, in moving to societal participation as an outcome, and in implementing population scale interventions. |
Analysis of lognormally distributed exposure data with repeated measures and values below the limit of detection using SAS
Jin Y , Hein MJ , Deddens JA , Hines CJ . Ann Occup Hyg 2010 55 (1) 97-112 Studies of determinants of occupational exposure frequently involve left-censored lognormally distributed data, often with repeated measures. Left censoring occurs when observations are below the analytical limit of detection (LOD); repeated measures data results from taking multiple measurements on the same worker. A common method of dealing with this type of data has been to substitute a value (such as LOD/2) for the censored data followed by statistical analysis using the 'usual' methods. Recently, maximum likelihood estimation (MLE) methods have been employed to reduce bias associated with the substitution method. We compared substitution and MLE methods using simulated lognormally distributed exposure data subjected to varying amounts of censoring using two procedures available in SAS: LIFEREG and NLMIXED. In these simulations, the MLE method resulted in less bias and performed well even for censoring up to 80%, whereas the substitution method resulted in considerable bias. We illustrate the NLMIXED procedure using a dataset of chlorpyrifos air measurements collected from termiticide applicators on consecutive days over a 5-day workweek. We provide sample SAS code for several situations including one and two groups, with and without repeated measures, random slopes, and nested random effects. |
Smokers who are also using smokeless tobacco products in the US: a national assessment of characteristics, behaviours and beliefs of 'dual users'
McClave-Regan AK , Berkowitz J . Tob Control 2010 20 (3) 239-42 BACKGROUND: Marketing and advertising of smokeless tobacco products towards cigarette smokers has increased recently. Because the use of multiple tobacco products is a growing public health concern, the present work assesses the use of smokeless tobacco among cigarette smokers, a behaviour termed as 'dual use', as well as attitudes and beliefs on their 'dual use' of tobacco. METHODS: Data were used from the 2008 ConsumerStyles survey, a nationally representative, mail-in survey of consumers in the USA (n=10 108). RESULTS: 'Dual use' was more common among cigarette smokers who were young, white men living in the Midwest or South. The majority of 'dual users' reported using smokeless tobacco in places where they could not smoke (67.7%) and did not believe smokeless tobacco would help in quitting smoking (75.1%). 'Dual users' reported planning to quit within the next 6 months less often than adults who smoke cigarettes exclusively and close to half (42.3%) never plan to quit smoking. CONCLUSIONS: Tobacco use is attributed to a number of diseases and deaths worldwide, and cessation of tobacco use can reduce these health risks. The prevalent use of smokeless tobacco in places with smoking restrictions and lack of planning to quit by 'dual users' suggest the need to promote cessation among these users. |
The United States' engagement in global tobacco control: proposals for comprehensive funding and strategies
Bollyky TJ , Gostin LO . JAMA 2010 304 (23) 2637-8 Tobacco use accounts for more deaths globally than human immunodeficiency virus/AIDS, tuberculosis, and malaria combined—more than 5 million deaths annually—and this is expected to increase to more than 8 million by 2030, with nearly 80% of those deaths occurring in developing countries.1(pp13-14) Beyond health effects, tobacco has dramatic social and economic consequences, consuming health care budgets, depriving families of wage earners, and hindering economic development. Tobacco consumption is shifting from industrialized to developing countries, spurred by increasing incomes, trade liberalization, and intensive marketing. This shift is well established among men and in Asia, Eastern Europe, and Latin America, with smoking in Africa projected to increase over the next decade.2 Women are a major target of opportunity for the industry, which uses advertising tactics such as purse packs containing super-slim cigarettes.3 | Although Congress empowered the US Food and Drug Administration to regulate tobacco domestically, the United States has failed to lead globally. The United States is among a small minority of countries that has signed, but not ratified, the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) that 171 countries have ratified, covering 87% of the world's population.4 In 2009, the United States dedicated only $7 million of the more than $8 billion it spent on global health to international tobacco control, principally for surveillance and capacity building.5 Moreover, US trade policy supports and enables the industry to expand tobacco use overseas. Nearly every investment and trade agreement negotiated by the United States eliminates or reduces trading partners' tobacco tariffs and protects US tobacco companies' overseas manufacturing and investments.5 In this Commentary, we argue for robust US engagement in global tobacco control, first explaining why it is in the national interest of the United States and then suggesting a comprehensive strategy. |
Annual summary of vital statistics: 2008
Mathews TJ , Minino AM , Osterman MJ , Strobino DM , Guyer B . Pediatrics 2010 127 (1) 146-57 The number of births in the United States decreased between 2007 and 2008 (preliminary estimate: 4,251,095). Birth rates declined among all women aged 15 to 39 years; the decrease among teenagers reverses the increases seen in the previous 2 years. The total fertility rate decreased 2% in 2008 to 2085.5 births per 1000 women. The proportion of all births to unmarried women increased to 40.6% in 2008, up from 39.7% in 2007. The 2008 preterm birth rate was 12.3%, a decline of 3% from 2007. In 2008, 32.3% of all births occurred by cesarean delivery, up nearly 2% from 2007. Twin and triplet birth rates were unchanged. The infant mortality rate was 6.59 infant deaths per 1000 live births in 2008 (significantly lower than the rate of 6.75 in 2007). Life expectancy at birth was 77.8 years in 2008. Crude death rates for children aged 1 to 19 years decreased by 5.5% between 2007 and 2008. Unintentional injuries and homicide were, respectively, the first and second leading causes of death in this age group. These 2 causes of death jointly accounted for 51.2% of all deaths of children and adolescents in 2008. This annual article is a long-standing feature in Pediatrics and provides a summary of the most current vital statistics data for the United States. We also include a special feature this year on the differences in cesarean-delivery rates according to race and Hispanic origin. |
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