Transition from pediatric to adult care for youth diagnosed with type 1 diabetes in adolescence
Lotstein DS , Seid M , Klingensmith G , Case D , Lawrence JM , Pihoker C , Dabelea D , Mayer-Davis EJ , Gilliam LK , Corathers S , Imperatore G , Dolan L , Anderson A , Bell RA , Waitzfelder B . Pediatrics 2013 131 (4) e1062-70 OBJECTIVE: Youth with type 1 diabetes mellitus are at risk for poor glycemic control as they age into adulthood. The aim of this study was to describe sociodemographic and clinical correlates of poor glycemic control associated with the transfer of care from pediatric to adult diabetes providers among a cohort of youth with type 1 diabetes diagnosed in adolescence. METHODS: Analyses included 185 adolescent participants with recently diagnosed type 1 diabetes in the SEARCH for Diabetes in Youth Study with pediatric care at baseline who were age ≥18 years at follow-up. Demographic and clinical factors were measured by survey and laboratory results. Survival analysis was used to estimate the age of transition. Logistic regression analysis assessed the association of demographic and clinical factors with the transition of care and poor glycemic control at follow-up. RESULTS: Fifty-seven percent of participants had transitioned to adult diabetes care providers by the follow-up visit. The estimated median age of transition of care was 20.1 years (95% confidence interval 19.8-20.4). Older age, lower baseline glycosylated hemoglobin, and less parental education were independently associated with increased odds of transition. The odds of poor glycemic control at follow-up were 2.5 times higher for participants who transitioned to adult care compared with those who remained in pediatric care. CONCLUSIONS: Transferring from pediatric to adult care, experienced by more than half the sample, was associated with an increased risk of poor glycemic control at follow-up. These findings suggest that young adults need additional support when moving to adult care. |
Gender differences in colon cancer treatment
Oliver JS , Martin MY , Richardson L , Kim Y , Pisu M . J Womens Health (Larchmt) 2013 22 (4) 344-51 BACKGROUND: Despite women suffering a disproportionate burden of colon cancer mortality, few studies have examined gender differences in evidence-based treatment, especially in poorer states like Alabama. OBJECTIVE: To describe colon cancer treatment in older patients diagnosed in Alabama by gender. METHODS: Colon cancer patients 65 years and older diagnosed in 2000-2002 were identified from the Alabama Statewide Cancer Registry (N=1785). Treatment was identified from Medicare claims for 1999-2003. Outcomes were (1) receipt of surgery and adjuvant 5-fluorouracil chemotherapy (5FU) and (2) 5FU treatment duration (0-4, 5-7, and >7 months). Generalized Estimating Equation (GEE) models were used to determine significant gender differences, adjusting for clustering at the reporting hospital level, and controlling for race, age, stage, comorbid conditions, census tract-level socioeconomic variables, and adverse chemotherapy effects (when analyzing 5FU duration). RESULTS: Overall, 93.9% of the patients received surgery. Of stage II-III patients undergoing surgery, 60.4% stage III and 25.6% stage II patients received 5FU. Compared with men, women were more likely to have surgery (95.5% vs. 92.2%, p=0.003), less likely to have 5FU (38.6% vs. 45.2%, p=0.02), and more likely to have 0-4 months of 5FU (32.9% vs. 24.9%, p=0.05). Gender differences were significant for having chemotherapy (adjusted odds ratio [aOR] 0.78, confidence interval [CI] 0.61-1.00, p=0.049), but not for having 0-4 months of 5FU when adjusting for adverse effects (aOR 1.36, CI 0.95-1.94, p=0.09). CONCLUSIONS: In Alabama, some gender differences in stage-specific colon cancer treatment are worth further scrutiny. |
Maximizing the impact of HIV prevention efforts: interventions for couples
Medley A , Baggaley R , Bachanas P , Cohen M , Shaffer N , Lo YR . AIDS Care 2013 25 (12) 1569-80 Despite efforts to increase access to HIV testing and counseling services, population coverage remains low. As a result, many people in sub-Saharan Africa do not know their own HIV status or the status of their sex partner(s). Recent evidence, however, indicates that as many as half of HIV-positive individuals in ongoing sexual relationships have an HIV-negative partner and that a significant proportion of new HIV infections in generalized epidemics occur within serodiscordant couples. Integrating couples HIV testing and counseling (CHTC) into routine clinic- and community-based services can significantly increase the number of couples where the status of both partners is known. Offering couples a set of evidence-based interventions once their HIV status has been determined can significantly reduce HIV incidence within couples and if implemented with sufficient scale and coverage, potentially reduce population-level HIV incidence as well. This article describes these interventions and their potential benefits. |
Neisseria gonorrhoeae antimicrobial resistance among men who have sex with men and men who have sex exclusively with women: the Gonococcal Isolate Surveillance Project, 2005-2010
Kirkcaldy RD , Zaidi A , Hook EW 3rd , Holmes KH , Soge O , del Rio C , Hall G , Papp J , Bolan G , Weinstock HS . Ann Intern Med 2013 158 321-8 BACKGROUND: Gonorrhea treatment has been complicated by antimicrobial resistance in Neisseria gonorrhoeae. Gonococcal fluoroquinolone resistance emerged more rapidly among men who have sex with men (MSM) than men who have sex exclusively with women (MSW). OBJECTIVE: To determine whether N. gonorrhoeae urethral isolates from MSM were more likely than isolates from MSW to exhibit resistance to or elevated minimum inhibitory concentrations (MICs) of antimicrobials used to treat gonorrhea. DESIGN: 6 years of surveillance data from the Gonococcal Isolate Surveillance Project. SETTING: Publicly funded sexually transmitted disease clinics in 30 U.S. cities. PATIENTS: Men with a total of 34,600 episodes of symptomatic urethral gonorrhea. MEASUREMENTS: Percentage of isolates exhibiting resistance or elevated MICs and adjusted odds ratios for resistance or elevated MICs among isolates from MSM compared with isolates from MSW. RESULTS: In all U.S. regions except the West, isolates from MSM were significantly more likely to exhibit elevated MICs of ceftriaxone and azithromycin than isolates from MSW (P < 0.050). Isolates from MSM had a high prevalence of resistance to ciprofloxacin, penicillin, and tetracycline and were significantly more likely to exhibit antimicrobial resistance than isolates from MSW (P < 0.001). LIMITATIONS: Sentinel surveillance may not be representative of all patients with gonorrhea. HIV status, travel history, and antimicrobial use data were missing for some patients. CONCLUSION: Men who have sex with men are vulnerable to the emerging threat of antimicrobial-resistant N. gonorrhoeae. Because antimicrobial susceptibility testing is not routinely done in clinical practice, clinicians should monitor for treatment failures among MSM diagnosed with gonorrhea. Strengthened prevention strategies for MSM and new antimicrobial treatment options are needed. |
A prospective study of the causes of febrile illness requiring hospitalization in children in Cambodia
Chheng K , Carter MJ , Emary K , Chanpheaktra N , Moore CE , Stoesser N , Putchhat H , Sona S , Reaksmey S , Kitsutani P , Sar B , van Doorn HR , Uyen NH , Van Tan L , Paris D , Blacksell SD , Amornchai P , Wuthiekanun V , Parry CM , Day NP , Kumar V . PLoS One 2013 8 (4) e60634 BACKGROUND: Febrile illnesses are pre-eminent contributors to morbidity and mortality among children in South-East Asia but the causes are poorly understood. We determined the causes of fever in children hospitalised in Siem Reap province, Cambodia. METHODS AND FINDINGS: A one-year prospective study of febrile children admitted to Angkor Hospital for Children, Siem Reap. Demographic, clinical, laboratory and outcome data were comprehensively analysed. Between October 12(th) 2009 and October 12(th) 2010 there were 1225 episodes of febrile illness in 1180 children. Median (IQR) age was 2.0 (0.8-6.4) years, with 850 (69%) episodes in children <5 years. Common microbiological diagnoses were dengue virus (16.2%), scrub typhus (7.8%), and Japanese encephalitis virus (5.8%). 76 (6.3%) episodes had culture-proven bloodstream infection, including Salmonella enterica serovar Typhi (22 isolates, 1.8%), Streptococcus pneumoniae (13, 1.1%), Escherichia coli (8, 0.7%), Haemophilus influenzae (7, 0.6%), Staphylococcus aureus (6, 0.5%) and Burkholderia pseudomallei (6, 0.5%). There were 69 deaths (5.6%), including those due to clinically diagnosed pneumonia (19), dengue virus (5), and melioidosis (4). 10 of 69 (14.5%) deaths were associated with culture-proven bloodstream infection in logistic regression analyses (odds ratio for mortality 3.4, 95% CI 1.6-6.9). Antimicrobial resistance was prevalent, particularly in S. enterica Typhi, (where 90% of isolates were resistant to ciprofloxacin, and 86% were multi-drug resistant). Comorbid undernutrition was present in 44% of episodes and a major risk factor for acute mortality (OR 2.1, 95% CI 1.1-4.2), as were HIV infection and cardiac disease. CONCLUSION: We identified a microbiological cause of fever in almost 50% of episodes in this large study of community-acquired febrile illness in hospitalized children in Cambodia. The range of pathogens, antimicrobial susceptibility, and co-morbidities associated with mortality described will be of use in the development of rational guidelines for infectious disease treatment and control in Cambodia and South-East Asia. |
Public health strategies for prevention and control of HSV-2 in persons who use drugs in the United States
Semaan S , Leinhos M , Neumann MS . Drug Alcohol Depend 2013 131 (3) 182-97 BACKGROUND: Herpes simplex virus type 2 (HSV-2) affects HIV acquisition, transmission, and disease progression. Effective medications for genital herpes and for HIV/AIDS exist. Parenteral transmission of HIV among persons who inject drugs is decreasing. Reducing sexual transmission of HIV and HSV-2 among persons who use drugs (PWUD; i.e., heroin, cocaine, "speedball", crack, methamphetamine through injection or non-injection) necessitates relevant services. METHODS: We reviewed HSV-2 sero-epidemiology and HSV-2/HIV associations in U.S.-based studies with PWUD and the general literature on HSV-2 prevention and treatment published between 1995 and 2012. We used the 6-factor Kass framework to assess relevant HSV-2 public health strategies and services in terms of their goals and effectiveness; identification of, and minimization of burdens and concerns; fair implementation; and fair balancing of benefits, burdens, and concerns. RESULTS: Eleven studies provided HSV-2 serologic test results. High HSV-2 sero-prevalence (range across studies 38-75%) and higher sero-prevalence in HIV-infected PWUD (97-100% in females; 61-74% in males) were reported. Public health strategies for HSV-2 prevention and control in PWUD can include screening or testing; knowledge of HSV-2 status and partner disclosure; education, counseling, and psychosocial risk-reduction interventions; treatment for genital herpes; and HIV antiretroviral medications for HSV-2/HIV co-infected PWUD. CONCLUSIONS: HSV-2 sero-prevalence is high among PWUD, necessitating research on development and implementation of science-based public health interventions for HSV-2 infection and HSV-2/HIV co-infections, including research on effectiveness and cost-effectiveness of such interventions, to inform development and implementation of services for PWUD. |
Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies
Morgan RL , Baack B , Smith BD , Yartel A , Pitasi M , Falck-Ytter Y . Ann Intern Med 2013 158 329-37 BACKGROUND: Hepatitis C virus (HCV) is a leading cause of hepatocellular carcinoma (HCC). In the United States, this form of cancer occurs in approximately 15,000 persons annually. A systematic review of the evidence is needed to assess the benefits of treatment of HCV-infected persons on development of HCC. PURPOSE: To systematically review observational studies to determine the association between response to HCV therapy and development of HCC among persons at any stage of fibrosis and those with advanced liver disease. DATA SOURCES: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science, and the Database of Abstracts of Reviews and Effectiveness from inception through February 2012. STUDY SELECTION: English-language observational studies that compared therapy-derived sustained virologic response (SVR) with no response to therapy among HCV-infected persons, targeted an adult population, and had an average follow-up of at least 2 years. DATA EXTRACTION: Two investigators independently extracted data into uniform relative risk measures. The Grading of Recommendations Assessment, Development and Evaluation framework was used to determine the quality of the evidence. DATA SYNTHESIS: Thirty studies fulfilled the inclusion criteria, and 18 provided adjusted effect estimates that were used to calculate pooled relative risks. Among HCV-infected persons, SVR was associated with reduced risk for HCC (relative risk for all persons, 0.24 [95% CI, 0.18 to 0.31], moderate-quality evidence; advanced liver disease hazard ratio, 0.23 [CI, 0.16 to 0.35], moderate-quality evidence). LIMITATION: In the meta-analyses, some variables could not be controlled for because of the observational design of the included studies. CONCLUSION: Sustained virologic response after treatment among HCV-infected persons at any stage of fibrosis is associated with reduced HCC. The evidence was determined to be of moderate quality. |
Evaluation of using routine infant immunization visits to identify and follow-up HIV-exposed infants and their mothers in Tanzania
Goodson JL , Finkbeiner T , Davis NL , Lyimo D , Rwebembera A , Swartzendruber AL , Wallace AS , Kimambo S , Kimario CJ , Wiktor SZ , Luman ET . J Acquir Immune Defic Syndr 2013 63 (1) e9-e15 BACKGROUND: Without treatment, approximately half of HIV-infected infants die by age 2 years, and 80% die before age 5 years. Early identification of HIV-infected and HIV-exposed infants provides opportunities for life-saving interventions. We evaluated integration of HIV-related services with routine infant immunization in Tanzania. METHODS: During April 2009 to March 2010, at 4 urban and 4 rural sites, mothers' HIV status was determined at first-month immunization using antenatal cards. HIV-exposed infants were offered HIV testing and follow-up care. Impact of integrated service delivery was assessed by comparing average monthly vaccine doses administered during the study period and a 2-year baseline period; acceptance was assessed by interviewing mothers and service providers. FINDINGS: During 7569 visits, 308 HIV-exposed infants were identified and registered; of these, 290 (94%) were tested, 15 (5%) were HIV infected. At urban sites, first-month vaccine doses remained stable (+2% for pentavalent vaccine and -4% for polio vaccine), and vaccine doses given later in life (pentavalent, polio, and measles) increased 12%, 8%, and 11%, respectively. At rural sites, first-month vaccine doses decreased 33% and 35% and vaccine doses given later in life decreased 23%, 28%, and 28%. Mothers and service providers generally favored integrated services; however, HIV-related stigma and inadequate confidentiality controls of HIV testing were identified, particularly at rural sites. INTERPRETATION: Integration of HIV-related services at immunization visits identified HIV-exposed infants, HIV-infected infants, and HIV-infected mothers; however, decreases in vaccine doses administered at rural sites were concerning. HIV-related service integration with immunization visits needs careful monitoring to ensure optimum vaccine delivery. |
Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis
Nair H , Simoes EA , Rudan I , Gessner BD , Azziz-Baumgartner E , Zhang JS , Feikin DR , Mackenzie GA , Moisi JC , Roca A , Baggett HC , Zaman SM , Singleton RJ , Lucero MG , Chandran A , Gentile A , Cohen C , Krishnan A , Bhutta ZA , Arguedas A , Clara AW , Andrade AL , Ope M , Ruvinsky RO , Hortal M , McCracken JP , Madhi SA , Bruce N , Qazi SA , Morris SS , El Arifeen S , Weber MW , Scott JA , Brooks WA , Breiman RF , Campbell H . Lancet 2013 381 (9875) 1380-90 BACKGROUND: The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010. METHODS: We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies. FINDINGS: We identified 89 eligible studies and estimated that in 2010, 11.9 million (95% CI 10.3-13.9 million) episodes of severe and 3.0 million (2.1-4.2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265,000 (95% CI 160,000-450,000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals. INTERPRETATION: Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities. FUNDING: WHO. |
Global policy review of antiretroviral therapy eligibility criteria for treatment and prevention of HIV and tuberculosis in adults, pregnant women, and serodiscordant couples
Gupta S , Granich R , Suthar AB , Smyth C , Baggaley R , Sculier D , Date A , Desai MA , Lule F , Raizes E , Blanc L , Hirnschall G . J Acquir Immune Defic Syndr 2013 62 (3) e87-e97 OBJECTIVE: This article reviews the antiretroviral therapy (ART) initiation criteria from national treatment guidelines for 70 countries and determines the extent of consistency with the current World Health Organization (WHO) recommendations. METHODS: Published ART guidelines were collected from the Internet, databases, and WHO staff. ART eligibility criteria for asymptomatic people, pregnant women, people with HIV-associated tuberculosis, serodiscordant couples, injecting drug users, men who have sex with men, and sex workers were abstracted from them. Multiple regression analysis was used to determine the relation between ART eligibility criteria, ART coverage, and various population characteristics and policy interventions. RESULTS: Of the 70 countries, 42 (60%) follow WHO's ART guidelines for asymptomatic people and 31 (44%) for pregnant women, recommending ART at CD4 count of #350 cells/mm(3). Twenty-three (33%) countries recommend ART for people with HIV-associated tuberculosis irrespective of CD4 count. Nineteen countries are also recommending or considering earlier ART above CD4 count ≤ 350 cell/mm(3) for asymptomatic people, pregnant women, and/or serodiscordant couples. Multiple linear regression analysis shows that HIV prevalence, year of publication of guidelines, and HIV expenditure are significantly associated with published ART eligibility criteria. On average, the ART coverage is similar irrespective of published guidelines being consistent with the WHO recommendation (P < 0.53). CONCLUSIONS: Published guidelines from a significant number of countries are not following WHO recommendations. Although published guidelines may not reflect practice, it is important to adapt recommendations and services quickly to reflect the emerging science on the health and prevention benefits of earlier access to ART. (Copyright 2012 by Lippincott Williams and Wilkins.) |
HIV testing and intimate partner violence among non-pregnant women in 15 US states/territories: findings from Behavioral Risk Factor Surveillance System Survey data
Nasrullah M , Oraka E , Breiding MJ , Chavez PR . AIDS Behav 2013 17 (7) 2521-7 Intimate partner violence (IPV) has been shown to be associated with higher rates of HIV infection among women, underscoring the importance of encouraging IPV victims to receive HIV testing. However, we do not know how much HIV testing behavior is influenced by IPV victimization. The current study characterized the association between individual types of IPV and HIV testing in a large sample of non-pregnant women in 15 US states/territories. The 2005 Behavioral Risk Factor Surveillance System data were analyzed after restricting the sample to non-pregnant women. The dependent variable, whether a woman ever had an HIV test, was examined in relation to individual types of IPV victimization (threatened physical violence; attempted physical violence; completed physical violence; and unwanted sex). Associations between HIV testing and types of IPV were assessed using adjusted risk ratios (aRR) that controlled for demographics and HIV-related risk factors (intravenous drug use, sexually transmitted diseases, exchange sex, unprotected anal sex). Approximately 28.6 % of women reported ever having experienced IPV, and 52.8 % of these women reported being tested for HIV. Among women who had not experienced IPV, 32.9 % reported ever having been tested for HIV. HIV testing was associated with lifetime experience of threatened violence (aRR = 1.43; 95 % CI = 1.24-1.65), attempted violence (aRR = 1.43; 95 % CI = 1.20-1.69), completed physical violence (aRR = 1.30; 95 % CI = 1.13-1.48), and unwanted sex (aRR = 1.66; 95 % CI = 1.48-1.86). Women who experienced each type of IPV were more likely to have been ever tested for HIV compared to women with no IPV history. However, nearly half of those reporting IPV, even though at greater risk for HIV infection, had never been tested. Additional efforts are needed to address barriers to testing in this group. |
Characteristics of young infants in whom human parechovirus, enterovirus or neither were detected in cerebrospinal fluid during sepsis evaluations
Sharp J , Harrison CJ , Puckett K , Selvaraju SB , Penaranda S , Nix WA , Oberste MS , Selvarangan R . Pediatr Infect Dis J 2013 32 (3) 213-6 BACKGROUND: Human parechovirus (HPeV) causes central nervous system (CNS) infection in infants. To further understand HPeV CNS infection, we describe its clinical, laboratory and epidemiologic characteristics from a Midwestern US tertiary care center. Because HPeV CNS infections have appeared clinically and seasonally similar to enterovirus (EV) infections, we retrospectively compared characteristics of young infants undergoing sepsis evaluations in whom HPeV, EV or neither were detected in cerebrospinal fluid (CSF). METHODS: HPeV real-time reverse-transcription polymerase chain reaction (RT-PCR) assay was performed on frozen nucleic acid extracts of CSF specimens submitted for EV RT-PCR assay from children seen at our hospital in 2009. HPeV genotyping was performed by sequencing of the viral protein 1 region. Clinical data were abstracted from medical records retrospectively for EV-positive, HPeV-positive and age-matched controls in whom neither virus was detected from CSF testing. RESULTS: HPeV was detected in 66 of the 388 (17%) CSF specimens whereas EV was detected in 54 of the 388 (14%) from June through October 2009. Genotyping identified HPeV3 in 51 of the 66 (77%) positive CSF specimens. Males predominated (61%) with the most common presenting symptoms (91%) being fever and irritability. All HPeV-positive patients were <5 months of age. Eight required admission to the pediatric intensive care unit. In multivariate analysis, lower peripheral white blood cell counts with lower absolute lymphocyte count values, higher maximum temperatures, longer fever duration, absence of pleocytosis and longer hospitalization were independently associated with HPeV patients compared with patients with EV or patients negative for both HPeV and EV. CONCLUSIONS: Our data indicate that HPeV3, an emerging CNS pathogen of infants in the United States, should be considered in sepsis-like presentation even without CSF pleocytosis. Addition of HPeV RT-PCR to EV RT-PCR assay for CSF specimens of patients <6 months of age could reduce hospital stay and costs while improving clinical management. |
Concentrations of select persistent organic pollutants across pregnancy trimesters in maternal and in cord serum in Trujillo, Peru
Adetona O , Horton K , Sjodin A , Jones R , Hall DB , Aguillar-Villalobos M , Cassidy BE , Vena JE , Needham LL , Naeher LP . Chemosphere 2013 91 (10) 1426-33 Although the production and use of some persistent organic pollutants (POPs) have been banned or highly restricted, human exposure remains a subject of investigation due to their environmental persistence. Physiological changes during pregnancy may affect the disposition of POPs in the mother's body, and thus fetal exposure. Changes in serum concentrations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) across pregnancy trimesters, and trans-placental transfer to the fetus were investigated. Seventy-nine pregnant women in Trujillo, Peru were recruited in the first trimester of pregnancy, and provided blood samples for the analysis of 35 PCB congeners, 9 OCPs, and 11 polybrominated biphenyl diethers (PBDEs). Subsequently, maternal blood samples were collected in the second (n=64) and third trimesters (n=59), and cord blood samples (n=50) were collected at delivery. There were statistically significant changes across trimesters (p<0.05) for both fresh weight (increase) and lipid adjusted concentrations (decrease) of hexachlorobenzene (HCB), 2,2-Bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE), PCB-74, 118, 138-158, 153, 170, 180 and 194. Fresh weight concentrations of these POPs increased from first to third trimester by 10-28%. On the other hand lipid adjusted concentrations decreased from first to third trimester by 16-28%. Serum lipids increased from first to third trimester by 53% indicating the dilution of the POPs in the lipids. Concentrations of 2,2-Bis(4-chlorophenyl)-1,1,1-trichloroethane (p,p'-DDT), its metabolite p,p'-DDE, PCB-118, 138-158, 153, 170 and 180 above their limits of detection were measured in >60% of cord serum samples. Intra-individual correlations in maternal serum concentrations were high for most of the POPs (rho=0.62-0.99; p<0.05) while correlations between maternal and cord serum concentrations were also high (rho=0.68-0.99; p<0.05). Results indicate that the disposition in the body and blood concentrations of POPs may change during pregnancy, and show trans-placental transfer of DDT, DDE and PCBs. |
A multilevel approach to estimating small area childhood obesity prevalence at the census block-group level
Zhang X , Onufrak S , Holt JB , Croft JB . Prev Chronic Dis 2013 10 E68 INTRODUCTION: Traditional survey methods for obtaining nationwide small-area estimates (SAEs) of childhood obesity are costly. This study applied a geocoded national health survey in a multilevel modeling framework to estimate prevalence of childhood obesity at the census block-group level. METHODS: We constructed a multilevel logistic regression model to evaluate the influence of individual demographic characteristics, zip code, county, and state on the childhood obesity measures from the 2007 National Survey of Children's Health. The obesity risk for a child in each census block group was then estimated on the basis of this multilevel model. We compared direct survey and model-based SAEs to evaluate the model specification. RESULTS: Multilevel models in this study explained about 60% of state-level variances associated with childhood obesity, 82.8% to 86.5% of county-level, and 93.1% of zip code-level. The 95% confidence intervals of block- group level SAEs have a wide range (0.795-20.0), a low median of 2.02, and a mean of 2.12. The model-based SAEs of childhood obesity prevalence ranged from 2.3% to 54.7% with a median of 16.0% at the block-group level. CONCLUSION: The geographic variances among census block groups, counties, and states demonstrate that locale may be as significant as individual characteristics such as race/ethnicity in the development of the childhood obesity epidemic. Our estimates provide data to identify priority areas for local health programs and to establish feasible local intervention goals. Model-based SAEs of population health outcomes could be a tool of public health assessment and surveillance. |
A novel use of structural equation models to examine factors associated with prediabetes among adults aged 50 years and older: National Health and Nutrition Examination Survey 2001-2006
Bardenheier BH , Bullard KM , Caspersen CJ , Cheng YJ , Gregg EW , Geiss LS . Diabetes Care 2013 36 (9) 2655-62 OBJECTIVE: To use structural modeling to test a hypothesized model of causal pathways related with prediabetes among older adults in the U.S. RESEARCH DESIGN AND METHODS: Cross-sectional study of 2,230 older adults (≥50 years) without diabetes included in the morning fasting sample of the 2001-2006 National Health and Nutrition Examination Surveys. Demographic data included age, income, marital status, race/ethnicity, and education. Behavioral data included physical activity (metabolic equivalent hours per week for vigorous, moderate, muscle-strengthening, walking/biking, and house/yard work), and poor diet (refined grains, red meat, added sugars, solid fats, and high-fat dairy). Structural-equation modeling was performed to examine the interrelationships among these variables with family history of diabetes, high blood pressure, BMI, large waist (waist circumference: women, ≥35 inches; men, ≥40 inches), triglycerides ≥200 mg/dL, and total- and HDL (≥60 mg/dL) cholesterol. RESULTS: After dropping BMI and total cholesterol, our best-fit model included three single factors: socioeconomic position (SEP), physical activity, and poor diet. Large waist had the strongest direct effect on prediabetes (0.279), followed by male sex (0.270), SEP (-0.157), high blood pressure (0.122), family history of diabetes (0.070), and age (0.033). Physical activity had direct effects on HDL (0.137), triglycerides (-0.136), high blood pressure (-0.132), and large waist (-0.067); poor diet had direct effects on large waist (0.146) and triglycerides (0.148). CONCLUSIONS: Our results confirmed that, while including factors known to be associated with high risk of developing prediabetes, large waist circumference had the strongest direct effect. The direct effect of SEP on prediabetes suggests mediation by some unmeasured factor(s). |
Frequency and pattern of documented diagnostic features and the age of autism identification
Maenner MJ , Schieve LA , Rice CE , Cunniff C , Giarelli E , Kirby RS , Lee LC , Nicholas JS , Wingate MS , Durkin MS . J Am Acad Child Adolesc Psychiatry 2013 52 (4) 401-413 e8 OBJECTIVE: The DSM-IV-TR specifies 12 behavioral features that can occur in hundreds of possible combinations to meet diagnostic criteria for autism spectrum disorder (ASD). This paper describes the frequency and variability with which the 12 behavioral features are documented in a population-based cohort of 8-year-old children under surveillance for ASD, and examines whether documentation of certain features, alone or in combination with other features, is associated with earlier age of community identification of ASD. METHOD: Statistical analysis of behavioral features documented for a population-based sample of 2,757 children, 8 years old, with ASD in 11 geographically-defined areas in the US participating in the Autism and Developmental Disabilities Monitoring Network in 2006. RESULTS: The median age at ASD identification was inversely associated with the number of documented behavioral features, decreasing from 8.2 years for children with only seven behavioral features to 3.8 years for children with all 12. Documented impairments in nonverbal communication, pretend play, inflexible routines, and repetitive motor behaviors were associated with earlier identification, whereas impairments in peer relations, conversational ability, and idiosyncratic speech were associated with later identification. CONCLUSIONS: The age dependence of some of the behavioral features leading to an autism diagnosis, as well as the inverse association between age at identification and number of behavioral features documented, have implications for efforts to improve early identification. Progress in achieving early identification and provision of services for children with autism may be limited for those with fewer ASD behavioral features, as well as features likely to be detected at later ages. |
Are randomized trials obsolete or more important than ever in the genomic era?
Ioannidis JPA , Khoury MJ . Genome Med 2013 5 (4) 32 The genomic era has raised the possibility of major changes in the design, conduct, and even the existence of randomized trials as we know them [1-3]. Randomized trials are often seen as a slow, laborious, expensive, and difficult step in the translational process and are associated with a high attrition rate for drugs. Indeed, most tests that are in use for the screening, diagnosis, prognosis, monitoring or management of patients have never been scrutinized by a randomized trial. This has largely been due to a failure to realize that tests can do as much harm and as much good as drugs or devices; thus, a rigorous appraisal of their clinical utility, including both the possible benefits and the possible harms, is necessary. Moreover, numerous new omics-based tests are continually being proposed, especially in the context of targeted preventive or therapeutic interventions. Given rapid development of these new biomarkers, can we make randomized trials more adaptable to a changing landscape? Furthermore, do we still need randomized trials at all? Our answers to these two questions are: yes, to some extent; and yes, definitely. We will explain our reasoning in this article. |
Association of the Period3 clock gene length polymorphism with salivary cortisol secretion among police officers.
Wirth M , Burch J , Violanti J , Burchfiel C , Fekedulegn D , Andrew M , Zhang H , Miller DB , Youngstedt SD , Hebert JR , Vena JE . Neuro Endocrinol Lett 2013 34 (1) 27-37 OBJECTIVE: This study evaluated whether measures of waking or diurnal cortisol secretion, or self-reported psychological disturbances differed among police officers with a Period3 (PER3) clock gene length polymorphism. METHODS: The cortisol awakening response was characterized via the area under the salivary cortisol curve with respect to the increase (AUCI) or total waking cortisol (AUCG). Diurnal cortisol measures included the slope of diurnal cortisol and the diurnal AUCG. Psychological disturbances were characterized using the Center for Epidemiologic Studies Depression Scale, Impact of Events Scale, and Life Events Scale. RESULTS: Officers with a 4/5 or 5/5 genotype had higher awakening AUCG and greater diurnal cortisol AUCG levels compared to officers with the 4/4 genotype. Among those working more afternoon or night shifts, waking AUCI and AUCG were greater among officers with a 4/5 or 5/5 genotype compared to the 4/4 referents. CONCLUSION: Cortisol secretion was modified among police officers with different PER3 VNTR clock gene variants. |
National estimates of central line-associated bloodstream infections in critical care patients.
Wise ME , Scott RD 2nd , Baggs JM , Edwards JR , Ellingson KD , Fridkin SK , McDonald LC , Jernigan JA . Infect Control Hosp Epidemiol 2013 34 (6) 547-54 OBJECTIVE: Recent studies have demonstrated that central line-associated bloodstream infections (CLABSIs) are preventable through implementation of evidence-based prevention practices. Hospitals have reported CLABSI data to the Centers for Disease Control and Prevention (CDC) since the 1970s, providing an opportunity to characterize the national impact of CLABSIs over time. Our objective was to describe changes in the annual number of CLABSIs in critical care patients in the United States. DESIGN: Monte Carlo simulation. Setting. US acute care hospitals. PATIENTS: Nonneonatal critical care patients. METHODS: We obtained administrative data on patient-days for nearly all US hospitals and applied CLABSI rates from the National Nosocomial Infections Surveillance and the National Healthcare Safety Network systems to estimate the annual number of CLABSIs in critical care patients nationally during the period 1990-2010 and the number of CLABSIs prevented since 1990. RESULTS: We estimated that there were between 462,000 and 636,000 CLABSIs in nonneonatal critical care patients in the United States during 1990-2010. CLABSI rate reductions led to between 104,000 and 198,000 fewer CLABSIs than would have occurred if rates had remained unchanged since 1990. There were 15,000 hospital-onset CLABSIs in nonneonatal critical care patients in 2010; 70% occurred in medium and large teaching hospitals. CONCLUSIONS: Substantial progress has been made in reducing the occurrence of CLABSIs in US critical care patients over the past 2 decades. The concentration of critical care CLABSIs in medium and large teaching hospitals suggests that a targeted approach may be warranted to continue achieving reductions in critical care CLABSIs nationally. (See the commentary by Dixon-Woods and Perencevich, on pages 555-557.) |
Trichosporon asahii among intensive care unit patients at a medical center in Jamaica
Fanfair RN , Heslop O , Etienne K , Rainford L , Roy M , Gade L , Peterson J , O'Connell H , Noble-Wang J , Balajee SA , Brandt ME , Lindo JF , Park BJ . Infect Control Hosp Epidemiol 2013 34 (6) 638-41 We investigated an increase in Trichosporon asahii isolates among inpatients. We identified 63 cases; 4 involved disseminated disease. Trichosporon species was recovered from equipment cleaning rooms, washbasins, and fomites, which suggests transmission through washbasins. Patient washbasins should be single-patient use only; adherence to appropriate hospital disinfection guidelines was recommended. |
Factors associated with human papillomavirus vaccination among young adult women in the United States
Williams WW , Lu PJ , Saraiya M , Yankey D , Dorell C , Rodriguez JL , Kepka D , Markowitz LE . Vaccine 2013 31 (28) 2937-46 BACKGROUND: Human papillomavirus (HPV) vaccination is recommended to protect against HPV-related diseases. OBJECTIVE: To estimate HPV vaccine coverage and assess factors associated with vaccine awareness, initiation and receipt of 3 doses among women age 18-30 years. METHODS: Data from the 2010 National Health Interview Survey were analyzed to assess associations of HPV vaccination among women age 18-26 (n=1866) and 27-30 years (n=1028) with previous HPV exposure, cervical cancer screening and selected demographic, health care and behavioral characteristics using bivariate analysis and multivariable logistic regression. RESULTS: Overall, 23.2% of women age 18-26 and 6.7% of women age 27-30 years reported receiving at least 1 dose of HPV vaccine. In multivariable analyses among women age 18-26 years, not being married, having a regular physician, seeing a physician or obstetrician/gynecologist in the past year, influenza vaccination in the past year, and receipt of other recommended vaccines were associated with HPV vaccination. One-third of unvaccinated women age 18-26 years (n=490) were interested in receiving HPV vaccine. Among women who were not interested in receiving HPV vaccine (n=920), the main reasons reported included: not needing the vaccine (41.3%); concerns about safety of the vaccine (12.5%); not knowing enough about the vaccine (11.9%); not being sexually active (8.2%); a doctor not recommending the vaccine (7.6%); and already having HPV (2.7%). Among women with health insurance, 10 or more physician contacts within the past year and no contraindications, 74.5% reported not receiving HPV vaccine. CONCLUSIONS: HPV vaccination coverage among women age 18-26 years remains low. Opportunities to vaccinate are missed. Healthcare providers can play an important role in educating young women about HPV and encouraging vaccination. Successful public health and educational interventions will need to address physician attitudes and practice patterns and other factors that influence vaccination behaviors. |
Semi-automated solid phase extraction method for the mass spectrometric quantification of 12 specific metabolites of organophosphorus pesticides, synthetic pyrethroids, and select herbicides in human urine
Davis MD , Wade EL , Restrepo PR , Roman-Esteva W , Bravo R , Kuklenyik P , Calafat AM . J Chromatogr B Analyt Technol Biomed Life Sci 2013 929C 18-26 Organophosphate and pyrethroid insecticides and phenoxyacetic acid herbicides represent important classes of pesticides applied in commercial and residential settings. Interest in assessing the extent of human exposure to these pesticides exists because of their widespread use and their potential adverse health effects. An analytical method for measuring 12 biomarkers of several of these pesticides in urine has been developed. The target analytes were extracted from one milliliter of urine by a semi-automated solid phase extraction technique, separated from each other and from other urinary biomolecules by reversed-phase high performance liquid chromatography, and detected using tandem mass spectrometry with isotope dilution quantitation. This method can be used to measure all the target analytes in one injection with similar repeatability and detection limits of previous methods which required more than one injection. Each step of the procedure was optimized to produce a robust, reproducible, accurate, precise and efficient method. The required selectivity and sensitivity for trace-level analysis (e.g., limits of detection below 0.5ng/mL) was achieved using a narrow diameter analytical column, higher than unit mass resolution for certain analytes, and stable isotope labeled internal standards. The method was applied to the analysis of 55 samples collected from adult anonymous donors with no known exposure to the target pesticides. This efficient and cost-effective method is adequate to handle the large number of samples required for national biomonitoring surveys. |
T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro
Baranovich T , Wong SS , Armstrong J , Marjuki H , Webby RJ , Webster RG , Govorkova EA . J Virol 2013 87 (7) 3741-51 Several novel anti-influenza compounds are in various phases of clinical development. One of these, T-705 (favipiravir), has a mechanism of action that is not fully understood but is suggested to target influenza virus RNA-dependent RNA polymerase. We investigated the mechanism of T-705 activity against influenza A (H1N1) viruses by applying selective drug pressure over multiple sequential passages in MDCK cells. We found that T-705 treatment did not select specific mutations in potential target proteins, including PB1, PB2, PA, and NP. Phenotypic assays based on cell viability confirmed that no T-705-resistant variants were selected. In the presence of T-705, titers of infectious virus decreased significantly (P < 0.0001) during serial passage in MDCK cells inoculated with seasonal influenza A (H1N1) viruses at a low multiplicity of infection (MOI; 0.0001 PFU/cell) or with 2009 pandemic H1N1 viruses at a high MOI (10 PFU/cell). There was no corresponding decrease in the number of viral RNA copies; therefore, specific virus infectivity (the ratio of infectious virus yield to viral RNA copy number) was reduced. Sequence analysis showed enrichment of G-->A and C-->T transversion mutations, increased mutation frequency, and a shift of the nucleotide profiles of individual NP gene clones under drug selection pressure. Our results demonstrate that T-705 induces a high rate of mutation that generates a nonviable viral phenotype and that lethal mutagenesis is a key antiviral mechanism of T-705. Our findings also explain the broad spectrum of activity of T-705 against viruses of multiple families. |
Molecular characterization of Giardia duodenalis in Yemen
Alyousefi NA , Mahdy MA , Xiao L , Mahmud R , Lim YA . Exp Parasitol 2013 134 (2) 141-147 Giardia duodenalis is an important intestinal protozoan in Yemen with infection rates ranging from 18% to 27%. To date, there has been no genotyping study to provide a better understanding of the transmission dynamic. This study was conducted to genotype and subtype G. duodenalis in Yemen. Stool samples were collected from 503 Yemeni outpatients between 1 and 80 years old, including 219 males and 284 females. Giardia cysts were detected via microscopy after the formal-ether concentration. Genotyping of Giardia was carried out using PCR and sequence analysis of the 16s rRNA and b-giardin genes. Of the 89 microscopy-positive Giardia samples, 65 were successfully sequenced, of which 66% (43 of 65) were identified as G. duodenalis assemblage A and 34% (22 of 65) as assemblage B. Further subtyping analysis based on b-giardin gene identified the presence of subtypes A2 and A3, which belong to the anthroponotic sub-assemblage AII. Data of the study suggest that anthroponotic transmission played a potential role in the transmission of giardiasis in the community. However, further genotyping and subtyping studies of specimens from humans and animals living in the same households are needed for a more definitive understanding of giardiasis transmission in Yemen. |
Novel dual-mode immunomagnetic method for studying reactivation of nerve agent-inhibited butyrylcholinesterase
Abney CW , Knaack JL , Ali AA , Johnson RC . Chem Res Toxicol 2013 26 (5) 775-82 A novel immunomagnetic method has been developed for the simultaneous measurement of organophosphorus nerve agent (OPNA) adducts to butyrylcholinesterase (BuChE) and free OPNAs in serum. This new approach, deemed dual-mode immunomagnetic analysis (Dual-Mode IMA), combines immunomagnetic separation (IMS) and immunomagnetic scavenging (IMSc) and has been used to measure the effectiveness of cholinesterase reactivators on OPNA-inhibited BuChE in serum. BuChE inhibited by the nerve agent VX, uninhibited BuChE, and unbound VX were measured up to 1 h after the addition of oxime reactivators pralidoxime (2-PAM) and obidoxime. IMS experiments consisted of extracting BuChE and VX-BuChE serum adducts using antibutyrylcholinesterase monoclonal antibodies conjugated to protein-G ferromagnetic particles. In a parallel set of experiments using IMSc, BuChE-coated magnetic beads were used to extract free VX from protein-depleted serum. Adducts from both IMS and IMSc were analyzed using a published IMS liquid chromatography tandem mass spectrometry (IMS-LC-MS/MS) protocol, which has also been demonstrated with other OPNAs. By applying this Dual-Mode IMA approach, 2-PAM was observed to be more potent than obidoxime in reactivating VX-adducted BuChE. VX-BuChE peptide concentrations initially measured at 19.7 +/- 0.7 ng/mL decreased over 1 h to 10.6 +/- 0.6 ng/mL when reactivated with 2-PAM and 14.4 +/- 1.2 ng/mL when reactivated with obidoxime. These experiments also show that previously published IMS-LC-MS/MS analyses are compatible with serum treated with oximes. Dual-Mode IMA is the first immunoaffinity method developed for the simultaneous measurement of OPNA adducted BuChE, unadducted BuChE, and free nerve agent in serum and is a promising new tool for studying reactivator effectiveness on cholinesterases inhibited by nerve agents. |
Evaluation of quantification of HIV-1 RNA viral load in plasma and dried blood spots by use of the semiautomated Cobas Amplicor assay and the fully automated Cobas Ampliprep/TaqMan assay, version 2.0, in Kisumu, Kenya
Ouma KN , Basavaraju SV , Okonji JA , Williamson J , Thomas TK , Mills LA , Nkengasong JN , Zeh C . J Clin Microbiol 2013 51 (4) 1208-18 In Kenya, HIV-1 viral load monitoring is commonly performed with the Cobas Amplicor using plasma specimens. Interest is growing in transitioning to real-time PCR (RT-PCR), such as the Cobas Ampliprep/Cobas TaqMan (CAP/CTM), using dried blood spots (DBS). Before implementation, direct evaluation of the two assays using DBS field specimens is required. This study compares the sensitivity, specificity, negative and positive predictive values (NPV and PPV, respectively), concordance, and agreement between HIV-1 viral load measurements using plasma and DBS specimens obtained from 512 HIV-1-infected pregnant females enrolled in the Kisumu Breastfeeding Study and tested with the Cobas Amplicor and CAP/CTM assays. The sensitivity and NPV of viral load detection in DBS specimens were higher with CAP/CTM (sensitivity, 100%; 95% confidence interval [CI], 99.1 to 100.0%; NPV, 100%; 95% CI, 59.0 to 100.0%) than the Cobas Amplicor (sensitivity, 96.6%; 95% CI, 94.3 to 98.1%; NPV, 58.8%; 95% CI, 40.7 to 75.4%). The PPVs were comparable between both assays when using DBS. The specificity of viral load detection in DBS specimens was lower with CAP/CTM (77.8%; 95% CI, 40.0 to 97.2%) than that of the Cobas Amplicor (95.2%; 95% CI, 76.2 to 99.9%). Good concordance and agreement were observed when paired plasma and DBS specimens were tested with both assays. Lower specificity with the CAP/CTM is likely due to proviral HIV-1 DNA amplification and lower detection limits with RT-PCR. However, the CAP/CTM has better sensitivity and higher throughput than the Cobas Amplicor. These findings suggest that DBS may be a suitable alternative to plasma when using RT-PCR, which could increase access to viral load monitoring in resource-limited settings. |
An animal model of marginal iodine deficiency during development: the thyroid axis and neurodevelopmental outcome
Gilbert ME , Hedge JM , Valentin-Blasini L , Blount BC , Kannan K , Tietge J , Zoeller RT , Crofton KM , Jarrett JM , Fisher JW . Toxicol Sci 2013 132 (1) 177-95 Thyroid hormones (THs) are essential for brain development, and iodine is required for TH synthesis. Environmental chemicals that perturb the thyroid axis result in modest reductions in TH, yet there is a paucity of data on the extent of neurological impairments associated with low-level TH disruption. This study examined the dose-response characteristics of marginal iodine deficiency (ID) on parameters of thyroid function and neurodevelopment. Diets deficient in iodine were prepared by adding 975, 200, 125, 25, or 0 microg/kg potassium iodate to the base casein diet to produce five nominal iodine levels ranging from ample (Diet 1: 1000 microg iodine/kg chow, D1) to deficient (Diet 5: 25 microg iodine/kg chow, D5). Female Long Evans rats were maintained on these diets beginning 7 weeks prior to breeding until the end of lactation. Dams were sacrificed on gestational days 16 and 20, or when pups were weaned on postnatal day (PN) 21. Fetal tissue was harvested from the dams, and pups were sacrificed on PN14 and PN21. Blood, thyroid gland, and brain were collected for analysis of iodine, TH, and TH precursors and metabolites. Serum and thyroid gland iodine and TH were reduced in animals receiving two diets that were most deficient in iodine. T4 was reduced in the fetal brain but was not altered in the neonatal brain. Neurobehavior, assessed by acoustic startle, water maze learning, and fear conditioning, was unchanged in adult offspring, but excitatory synaptic transmission was impaired in the dentate gyrus in animals receiving two diets that were most deficient in iodine. A 15% reduction in cortical T4 in the fetal brain was sufficient to induce permanent reductions in synaptic function in adults. These findings have implications for regulation of TH-disrupting chemicals and suggest that standard behavioral assays do not readily detect neurotoxicity induced by modest developmental TH disruption. |
Application of mass spectrometry to molecular diagnostics of viral infections
Ganova-Raeva LM , Khudyakov YE . Expert Rev Mol Diagn 2013 13 (4) 377-88 Mass spectrometry (MS) has found numerous applications in life sciences. It has high accuracy, sensitivity and wide dynamic range in addition to medium- to high-throughput capabilities. These features make MS a superior platform for analysis of various biomolecules including proteins, lipids, nucleic acids and carbohydrates. Until recently, MS was applied for protein detection and characterization. During the last decade, however, MS has successfully been used for molecular diagnostics of microbial and viral infections with the most notable applications being identification of pathogens, genomic sequencing, mutation detection, DNA methylation analysis, tracking of transmissions, and characterization of genetic heterogeneity. These new developments vastly expand the MS application from experimental research to public health and clinical fields. Matching of molecular techniques with specific requirements of the major MS platforms has produced powerful technologies for molecular diagnostics, which will further benefit from coupling with computational tools for extracting clinical information from MS-derived data. |
Comparison of infectious virus in respirable aerosols exhaled by ferrets infected with influenza viruses exhibiting diverse transmissibility phenotypes
Gustin KM , Katz JM , Tumpey TM , Maines TR . J Virol 2013 87 (14) 7864-73 Influenza viruses pose a major public health burden to communities around the world by causing respiratory infections that can be highly contagious and spread rapidly through the population. Despite extensive research on influenza viruses, the modes of transmission occurring most often among humans are not entirely clear. Contributing to this knowledge gap is the lack of an understanding of the levels of infectious virus present in respirable aerosols exhaled from infected hosts. Here, we use the ferret model to evaluate aerosol shedding patterns and measure the amount of infectious virus present in exhaled respirable aerosols. By comparing these parameters among a panel of human and avian influenza viruses exhibiting diverse respiratory droplet transmission efficiencies, we are able to report that ferrets infected by highly transmissible influenza viruses exhale a greater number of aerosol particles and more infectious virus within respirable aerosols compared to ferrets infected by influenza viruses that do not readily transmit. Our findings improve our understanding of the ferret transmission model and provide support for the potential for influenza virus aerosol transmission. |
The lipid accumulation product for the early prediction of gestational insulin resistance and glucose dysregulation
Brisson D , Perron P , Kahn HS , Gaudet D , Bouchard L . J Womens Health (Larchmt) 2013 22 (4) 362-367 BACKGROUND: Recent insights linking insulin resistance and lipid overaccumulation suggest a novel approach for the early identification of women who may soon experience glucose dysregulation. Among women without a history of gestational diabetes, we tested the association between the lipid accumulation product (LAP) obtained in early pregnancy and glucose dysregulation or insulin resistance in the second trimester. METHODS: A total of 180 white pregnant women of French-Canadian origin were included in this study. At 11-14 weeks' gestation, fasting insulin, glucose, C-peptide concentrations, and estimated insulin resistance (HOMA-IR) were obtained. The waist circumference (WC) and fasting triglycerides (TG) were measured to calculate LAP as (WC[cm]- 58) x TG[mmol/L]. At 24-28 weeks' gestation, glucose was measured 2 hours after a 75-g oral glucose challenge and other fasting variables were repeated. RESULTS: Among the nulliparous women tested at the end of the second trimester, fasting insulin, C-peptide, insulin resistance (HOMA-IR index), fasting glucose, and 2-hour glucose progressively increased (p<=0.002) according to their first-trimester LAP tertiles. Similar results were observed in parous women except for the glucose variables. The first-trimester LAP tended to show a stronger correlation to the second-trimester HOMA-IR index (r=0.56) than fasting triglyceride levels alone (r=0.40) or waist circumference alone (r=0.44) among nulliparous women. Similar associations were observed for parous women. Adjustment for body mass index weakened these associations, especially among parous women. CONCLUSIONS: An increased value of LAP at the beginning of a pregnancy could be associated with an increased risk of insulin resistance or hyperglycemia later in gestation. (Copyright 2013, Mary Ann Liebert, Inc. 2013.) |
Epidemiology of obstetric-related ICU admissions in Maryland: 1999-2008
Wanderer JP , Leffert LR , Mhyre JM , Kuklina EV , Callaghan WM , Bateman BT . Crit Care Med 2013 41 (8) 1844-52 OBJECTIVE: To define the prevalence, indications, and temporal trends in obstetric-related ICU admissions. DESIGN: Descriptive analysis of utilization patterns. SETTING: All hospitals within the state of Maryland. PATIENTS: All antepartum, delivery, and postpartum patients who were hospitalized between 1999 and 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 2,927 ICU admissions from 765,598 admissions for antepartum, delivery, or postpartum conditions using appropriate International Classification of Diseases, 9th Revision, Clinical Modification codes. The overall rate of ICU utilization was 419.1 per 100,000 deliveries, with rates of 162.5, 202.6, and 54.0 per 100,000 deliveries for the antepartum, delivery, and postpartum periods, respectively. The leading diagnoses associated with ICU admission were pregnancy-related hypertensive disease (present in 29.9% of admissions), hemorrhage (18.8%), cardiomyopathy or other cardiac disease (18.3%), genitourinary infection (11.5%), complications from ectopic pregnancies and abortions (10.3%), nongenitourinary infection (10.1%), sepsis (7.1%), cerebrovascular disease (5.8%), and pulmonary embolism (3.7%). We assessed for changes in the most common diagnoses in the ICU population over time and found rising rates of sepsis (10.1 per 100,000 deliveries to 16.6 per 100,000 deliveries, p=0.003) and trauma (9.2 per 100,000 deliveries to 13.6 per 100,000 deliveries, p=0.026) with decreasing rates of anesthetic complications (11.3 per 100,000 to 4.7 per 100,000, p=0.006). The overall frequency of obstetric-related ICU admission and the rates for other indications remained relatively stable. CONCLUSIONS: Between 1999 and 2008, 419.1 per 100,000 deliveries in Maryland were complicated by ICU admission. Hospitals providing obstetric services should plan for appropriate critical care management and/or transfer of women with severe morbidities during pregnancy. |
Health outcomes of HIV-exposed uninfected African infants
Kourtis AP , Wiener J , Kayira D , Chasela C , Ellington SR , Hyde L , Hosseinipour M , Van Der Horst C , Jamieson DJ . AIDS 2013 27 (5) 749-759 OBJECTIVES: To evaluate severe (grade 3/4) morbidity and mortality in HIV-exposed, uninfected infants. DESIGN: Secondary data analysis of The Breastfeeding, Antiretrovirals, and Nutrition (BAN) clinical trial. METHODS: BAN randomized 2369 mother-infant pairs to maternal, infant, or no extended antiretroviral prophylaxis during breastfeeding. Morbidity outcomes examined were pneumonia/serious febrile illness, diarrhea/growth faltering, and malaria. Infant death was defined as neonatal (≤30 days of life), and postneonatal (31 days to 48 weeks of life). Cox proportional hazards models were used to evaluate the effect of covariates on infant morbidity and mortality. RESULTS: The rate of pneumonia/serious febrile illness was highest in the first 12 weeks (0.83/100 person-weeks) before rapidly decreasing; rates of all morbidity outcomes increased after 24 weeks. Rates of pneumonia/serious febrile illness and diarrhea/growth faltering were higher during the rainy season. Prophylactic infant cotrimoxazole significantly decreased the rates of all morbidity outcomes. White blood cell (WBC) count less than 9000/microliters at birth was associated with increased diarrhea/growth faltering [adjusted hazard ratio (aHR) 1.73, P1/40.04] and malaria (aHR 2.18, P1/40.02). Low birth weight (2000-2499 g) was associated with neonatal death (aHR 12.3, P<0.001). Factors associated with postneonatal death included rainy season (aHR 4.24, P1/40.002), infant cotrimoxazole (aHR 0.48, P1/40.03), and low infant WBC count at birth (aHR 2.53, P1/40.02). CONCLUSION: Infant morbidity rates increased after 24 weeks, when BAN infants weaned. Introduction of prophylactic cotrimoxazole was associated with reduced rates of morbidity and mortality in HIV-exposed uninfected infants. Unexpectedly, a low WBC count at birth was significantly associated with later infant morbidity and mortality in this cohort. (2013 Wolters Kluwer Health.) |
High viral load and elevated angiogenic markers associated with increased risk of preeclampsia among women initiating highly active antiretroviral therapy (HAART) in pregnancy in the Mma Bana study, Botswana
Powis KM , McElrath TF , Hughes MD , Ogwu A , Souda S , Datwyler SA , von Widenfelt E , Moyo S , Nadas M , Makhema J , Machakaire E , Lockman S , Essex M , Shapiro RL . J Acquir Immune Defic Syndr 2013 62 (5) 517-24 BACKGROUND: Risk factors associated with preeclampsia in HIV-infected women remain largely unknown. Systemic angiogenic imbalance contributes to preeclampsia in HIV-uninfected women, but changes in angiogenic markers after HAART initiation have not been studied. METHODS: The Mma Bana study randomized 560 HIV-infected, HAART-naive pregnant women with CD4 counts ≥ 200 cells/mm between 26-34 weeks gestation to lopinavir/ritonavir/zidovudine/lamivudine or abacavir/zidovudine/lamivudine. Another 170 participants with CD4 counts < 200 cells/mm initiated nevirapine/zidovudine/lamivudine between 18-34 weeks gestation. Characteristics of 11 women who developed preeclampsia were compared with the remaining 722 Mma Bana participants who delivered, using logistic regression. Plasma samples drawn at HAART initiation and one month later from 60 women without preeclampsia and at HAART initiation for all11 preeclamptic women were assayed for placental growth factor (PlGF) and soluble FMS toll-like tyrosine kinase-1 (sFlt-1) RESULTS: Pre-HAART viral load > 100,000 copies/ml was associated with preeclampsia (OR 5.8; 95% CI 1.8, 19.4; p = 0.004). Median pre-HAART PlGF level was lower and sFLT-1 was higher in women who developed preeclampsia versus those who did not (130 vs 992 pg/ml, p=0.001; 17.5 vs 9.4 pg/ml, p=0.03, respectively). In multivariate analysis, PlGF and viral load remained significantly associated with preeclampsia. No significant changes in angiogenic factors were noted after 1 month of HAART treatment among non-preeclamptic women. CONCLUSIONS: Pre-HAART viral load > 100,000 copies/ml and PlGF predicted preeclampsia among women starting HAART in pregnancy. Among non-preeclamptic women, HAART treatment did not significantly alter levels of PlGF or sFlt-1 on month into treatment. |
Current vision and future directions
Schoendorf KC . Paediatr Perinat Epidemiol 2013 27 (3) 228 I am excited and honoured to join Paediatric and Perinatal Epidemiology's Editorial Board. I will serve as an associate editor focusing on paediatric and child-related research, a counterpoint to Dr. Jennifer Zeitlin's concentration on reproductive and perinatal topics. As introduction to the Paediatric and Perinatal Epidemiology (PPE) readership, our editor-in-chief, Dr. Cande Ananth, requested that I provide a ‘vision statement’ elucidating my thoughts about the journal and its direction. | Unfortunately, I do not see things as clearly and precisely as I once did. At this stage of life, my vision depends upon various combinations of corrective eyewear, with significant interaction by object size, distance and lighting. Depending on the combination of those variables, I can identify small details but miss the full picture, or can recognise the outlines of large objects without perceiving the particulars. (I'm also exceptionally bad at identifying items in the refrigerator, but that seems a common Y-chromosome trait). However, this inconsistent perception is not a liability. Differing perspectives enhance appreciation of Monet's water lilies and Picasso's Ladies of Avignon; they also generally enrich insight and understanding of the full picture regardless of medium. |
Suspected outbreak of riboflavin deficiency among populations reliant on food assistance: a case study of drought-stricken Karamoja, Uganda, 2009-2010
Nichols EK , Talley LE , Birungi N , McClelland A , Madraa E , Chandia AB , Nivet J , Flores-Ayala R , Serdula MK . PLoS One 2013 8 (5) e62976 BACKGROUND: In 2009, a humanitarian response was launched to address a food security and livelihoods crisis in Karamoja, Uganda. During a polio immunization campaign in mid-August 2009, health workers in Nakapiripit District reported a concern about an increase in mouth sores, or angular stomatitis (AS) and gum ulcerations, among children in one village, and an investigation was launched. OBJECTIVE: This article describes the investigation, lessons learned, and provides guidance for monitoring micronutrient deficiencies among populations receiving food assistance. DESIGN: An investigation into a suspected outbreak of riboflavin (vitamin B2) deficiency was initiated, including a rapid assessment, mass screening, a convenience sample collection of blood specimens (n = 58 symptomatic cases and n = 18 asymptomatic individuals), and analysis of the general food ration (70% ration). RESULTS: Findings showed signs of AS in only 399 (0.2%) of 179,172 screened individuals, including adults and children. Biochemical analysis confirmed riboflavin deficiency in 84.5% of specimens from symptomatic individuals and 94.4% of specimens from asymptomatic individuals. Ration distribution data showed that 55% of distributions provided less than half the riboflavin RDA. CONCLUSION: Evidence was insufficient to confirm an actual outbreak of riboflavin deficiency, though the present investigation adds further documentation that micronutrient deficiencies continue to persist among populations in emergency settings. This article describes challenges, lessons learned, and guidance for monitoring micronutrient deficiencies among food assistance recipients, including: ongoing nutrition monitoring and surveillance; training and sensitization about micronutrient deficiencies, sensitization of the population about locally-available food, and identifying ways to improve micronutrient interventions. |
Simulation and evaluation of respirator faceseal leaks using computational fluid dynamics and infrared imaging
Lei Z , Yang J , Zhuang Z , Roberge R . Ann Occup Hyg 2013 57 (4) 493-506 This paper presents a computational fluid dynamics (CFD) simulation approach for the prediction of leakage between an N95 filtering facepiece respirator (FFR) and a headform and an infrared camera (IRC) method for validating the CFD approach. The CFD method was used to calculate leak location(s) and 'filter-to-faceseal leakage' (FTFL) ratio for 10 headforms and 6 FFRs. The computational geometry and leak gaps were determined from analysis of the contact simulation results between each headform-N95 FFR combination. The volumetric mesh was formed using a mesh generation method developed by the authors. The breathing cycle was described as a time-dependent profile of the air velocity through the nostril. Breathing air passes through both the FFR filter medium and the leak gaps. These leak gaps are the areas failing to achieve a seal around the circumference of the FFR. The CFD approach was validated by comparing facial temperatures and leak sites from IRC measurements with eight human subjects. Most leaks appear at the regions of the nose (40%) and right (26%) and left cheek (26%) sites. The results also showed that, with N95 FFR (no exhalation valves) use, there was an increase in the skin temperature at the region near the lip, which may be related to thermal discomfort. The breathing velocity and the viscous resistance coefficient of the FFR filter medium directly impacted the FTFL ratio, while the freestream flow did not show any impact on the FTFL ratio. The proposed CFD approach is a promising alternative method to study FFR leakage if limitations can be overcome. |
Discourse on malaria elimination: where do forcibly displaced persons fit in these discussions?
Williams HA , Hering H , Spiegel P . Malar J 2013 12 121 BACKGROUND: Individuals forcibly displaced are some of the poorest people in the world, living in areas where infrastructure and services are at a bare minimum. Out of a total of 10,549,686 refugees protected and assisted by the United Nations High Commissioner for Refugees globally, 6,917,496 (65.6%) live in areas where malaria is transmitted. Historically, national malaria control programmes have excluded displaced populations. RESULTS: The current discourse on malaria elimination rarely includes discussion of forcibly displaced persons who reside within malaria-eliminating countries. Of the 100 malaria-endemic countries, 64 are controlling malaria and 36 are in some stage of elimination. Of these, 30 malaria-controlling countries and 13 countries in some phase of elimination host displaced populations of ≥50,000, even though 13 of the 36 (36.1%) malaria-elimination countries host displaced populations of ≥50,000 people. DISCUSSION: Now is the time for the malaria community to incorporate forcibly displaced populations residing within malarious areas into malaria control activities. Beneficiaries, whether they are internally displaced persons or refugees, should be viewed as partners in the delivery of malaria interventions and not simply as recipients. CONCLUSION: Until equitable and sustainable malaria control includes everyone residing in an endemic area, the goal of malaria elimination will not be met. |
Evaluation of a well-established task-shifting initiative: the lay counselor cadre in Botswana
Ledikwe JH , Kejelepula M , Maupo K , Sebetso S , Thekiso M , Smith M , Mbayi B , Houghton N , Thankane K , O'Malley G , Semo BW . PLoS One 2013 8 (4) e61601 BACKGROUND: Evidence supports the implementation of task shifting to address health worker shortages that are common in resource-limited settings. However, there is need to learn from established programs to identify ways to achieve the strongest, most sustainable impact. This study examined the Botswana lay counselor cadre, a task shifting initiative, to explore effectiveness and contribution to the health workforce. METHODS: This evaluation used multiple methods, including a desk review, a national lay counselor survey (n=385; response=94%), in-depth interviews (n=79), lay counselors focus group discussions (n=7), lay counselors observations (n=25), and client exit interviews (n=47). RESULTS: Interview and focus group data indicate that lay counselors contribute to essentially all HIV-related programs in Botswana and they conduct the majority of HIV tests and related counseling at public health facilities throughout the country. Interviews showed that the lay counselor cadre is making the workload of more skilled health workers more manageable and increasing HIV acceptance in communities. The average score on a work-related knowledge test was 74.5%. However for 3 questions, less than half answered correctly. During observations, lay counselors demonstrated average competence for most skills assessed and clients (97.9%) were satisfied with services received. From the survey, lay counselors generally reported being comfortable with their duties; however, some reported clinical duties that extended beyond their training and mandate. Multiple factors affecting the performance of the lay counselors were identified, including insufficient resources, such as private counseling space and HIV test kits; and technical, administrative, and supervisory support. CONCLUSION: Lay counselors are fulfilling an important role in Botswana's healthcare system, serving as the entry point into HIV care, support, and treatment services. RECOMMENDATION: For this and other similar task shifting initiatives, it is important that lay counselors' responsibilities are clear and that training and support are adequate to optimize their effectiveness. |
U.S. outpatient antibiotic prescribing, 2010
Hicks LA , Taylor TH Jr , Hunkler RJ . N Engl J Med 2013 368 (15) 1461-2 Antibiotic use is an important factor in the spread of antibiotic resistance. It is estimated that 50% of antibiotic prescriptions may be unnecessary.1,2 We analyzed data on the prescription of antibiotics to outpatients in the United States to identify the areas in which interventions addressing appropriate use could have the greatest effect. | Data on oral antibiotic prescriptions dispensed during 2010 in the United States were extracted from the IMS Health Xponent database, which represents a 100% projection of prescription activity on the basis of a sample of more than 70% of U.S. prescriptions. Antibiotics were categorized according to the IMS Health Uniform System of Classification. The numbers of prescriptions and census denominators were used to calculate prescribing rates. Prescriptions were totaled for 17 provider specialty groups on the basis of the self-designated specialty of the prescriber (as defined by the American Medical Association) associated with each prescription. The Xponent database provided the number of prescribers in each specialty for the calculation of the number of prescriptions per provider. |
Combination injectable contraceptives for contraception
Gallo MF , Grimes DA , Lopez LM , Schulz KF , d'Arcangues C . Cochrane Database Syst Rev 2013 3 CD004568 BACKGROUND: Combination injectable contraceptives (CICs) provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes. OBJECTIVES: To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of CICs. SEARCH METHODS: In January and February 2013, we searched for randomized controlled trials (RCTs) of combination injectable contraceptives. Databases include MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS. We searched for current trials in ClinicalTrials.gov and ICTRP.Earlier searches also included AIM and IMEMR. For the initial review, we also assessed the references listed in review articles and in the eligible trial reports. SELECTION CRITERIA: RCTs were eligible if they compared a combination injectable contraceptive with any other contraceptive method (e.g., a second CIC,a progestin-only injectable contraceptive, another hormonal contraceptive or a barrier method) or a placebo. We limited the review to marketed CICs. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data on contraceptive efficacy, bleeding patterns, continuation, and side effects. We calculated the Peto odds ratio or mean difference with 95% confidence interval for dichotomous or continuous outcome, respectively. Survival analysis estimates for method discontinuation were presented where available. MAIN RESULTS: Twelve trials met the inclusion criteria. Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA)25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5mg. These contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems than progestin-only contraceptives. However, rates were higher for overall discontinuation and discontinuation due to other medical reasons.Acceptability results favored the CIC in one study and the progestin-only in another. Studies comparing two CICs found that NET-EN 50 mg plus E(2)V (5)mg resulted in less overall discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials.The NET-EN plus E (2) V group also had more regular bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates. AUTHORS' CONCLUSIONS: While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation depends on many factors. Future research should be directed toward improving the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinics, methods for women to administer their own injections, and counseling about possible bleeding pattern changes. |
The Senior Connection: design and rationale of a randomized trial of peer companionship to reduce suicide risk in later life
Van Orden KA , Stone DM , Rowe J , McIntosh WL , Podgorski C , Conwell Y . Contemp Clin Trials 2013 35 (1) 117-26 There is a pressing public health need to find interventions that reduce suicide risk in later life. Psychiatric and physical illness, functional decline, and social factors place seniors at risk for suicide. Reflecting this body of evidence, the Centers for Disease Control and Prevention (CDC) has identified the promotion and strengthening of social connectedness, between and within the individual, family, community, and broader societal levels, as a key strategy for suicide prevention. The Senior Connection, a randomized trial of peer companionship for older adults, is described here, with an emphasis on the most novel features of the study design-grounding in a psychological theory of suicide and intervening at an early stage in the suicide risk trajectory by linking primary care patients with the Aging Services Provider Network. |
An investigation into the seroprevalence of Toxoplasma gondii, Bartonella spp., feline immunodeficiency virus (FIV), and feline leukaemia virus (FeLV) in cats in Addis Ababa, Ethiopia
Tiao N , Darrington C , Molla B , Saville WJ , Tilahun G , Kwok OC , Gebreyes WA , Lappin MR , Jones JL , Dubey JP . Epidemiol Infect 2013 141 (5) 1029-33 Toxoplasma gondii and Bartonella spp. are zoonotic pathogens of cats. Feline immunodeficiency virus (FIV), and feline leukaemia virus (FeLV) are immunosuppressive viruses of cats that can affect T. gondii oocyst shedding. In this study, the prevalence of antibodies to T. gondii, Bartonella spp., FIV, as well as FeLV antigens were determined in sera from feral cats (Felis catus) from Addis Ababa, Ethiopia. Using the modified agglutination test, IgG antibodies to T. gondii were found in 41 (85.4%) of the 48 cats with titres of 1:25 in one, 1:50 in one, 1:200 in six, 1:400 in six, 1:800 in six, 1:1600 in eight, and 1:3200 in 13 cats. Toxoplasma gondii IgM antibodies were found in 11/46 cats tested by ELISA, suggesting recent infection. Antibodies to Bartonella spp. were found in five (11%) of 46 cats tested. Antibodies to FIV or FeLV antigen were not detected in any of the 41 cats tested. The results indicate a high prevalence of T. gondii and a low prevalence of Bartonella spp. infection in cats in Ethiopia. |
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