The effect of secondary prophylaxis versus episodic treatment on the range of motion of target joints in patients with haemophilia
Gupta S , Siddiqi AE , Soucie JM , Manco-Johnson M , Kulkarni R , Lane H , Ingram-Rich R , Gill JC . Br J Haematol 2013 161 (3) 424-33 This study prospectively compared the effect of secondary prophylaxis to episodic treatment on target joint (TJ) range of motion (ROM), number of joint haemorrhages and new TJ development in patients with moderate or severe haemophilia. Two-hundred and eighty-six males, 17% in prophylaxis, 83% in episodic treatment group, participating in the Centers for Disease Control and Prevention's Universal Data Collection project, fulfilled inclusion criteria: age >2 years at enrolment, free of TJs at enrolment, developed at least one TJ after enrolment, and received either prophylaxis or episodic treatment continuously for two follow-up visits after TJ development. The outcomes of interest - percentage change in TJ ROM, number of joint haemorrhages and new TJ development, were modelled using multivariate linear, Poisson and logistic regression techniques respectively. Individuals who received secondary prophylaxis in comparison to episodic treatment were younger at TJ development (P < 0.01); there was no difference in the decrease in TJ ROM between the two groups (P = 0.9). Factors significantly associated with a higher rate of haemarthroses included episodic treatment, severe haemophilia, age >5 years at TJ development, obesity and inhibitor negative status. Secondary prophylaxis significantly decreased haemarthroses but was not associated with a significant improvement in TJ ROM or with new TJ development. |
Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone
Irwin DJ , Abrams JY , Schonberger LB , Leschek EW , Mills JL , Lee VM , Trojanowski JQ . JAMA Neurol 2013 70 (4) 462-8 IMPORTANCE: Growing evidence of cell-to-cell transmission of neurodegenerative disease (ND)-associated proteins (NDAPs) (ie, tau, Abeta, and alpha-synuclein) suggests possible similarities to the infectious prion protein (PrPsc) in spongiform encephalopathies. There are limited data on the potential human-to-human transmission of NDAPs associated with Alzheimer disease (AD) and other non-PrPsc ND. OBJECTIVE: To examine evidence for human-to-human transmission of AD, Parkinson disease (PD), and related NDAPs in cadaveric human growth hormone (c-hGH) recipients. DESIGN: We conducted a detailed immunohistochemical analysis of pathological NDAPs other than PrPsc in human pituitary glands. We also searched for ND in recipients of pituitary-derived c-hGH by reviewing the National Hormone and Pituitary Program (NHPP) cohort database and medical literature. SETTING: University-based academic center and agencies of the US Department of Health and Human Services. PARTICIPANTS: Thirty-four routine autopsy subjects (10 non-ND controls and 24 patients with ND) and a US cohort of c-hGH recipients in the NHPP. MAIN OUTCOME MEASURES: Detectable NDAPs in human pituitary sections and death certificate reports of non-PrPsc ND in the NHPP database. RESULTS: We found mild amounts of pathological tau, Abeta, and alpha-synuclein deposits in the adeno/neurohypophysis of patients with ND and control patients. No cases of AD or PD were identified, and 3 deaths attributed to amyotrophic lateral sclerosis (ALS) were found among US NHPP c-hGH recipients, including 2 of the 796 decedents in the originally confirmed NHPP c-hGH cohort database. CONCLUSIONS AND RELEVANCE: Despite the likely frequent exposure of c-hGH recipients to NDAPs, and their markedly elevated risk of PrPsc-related disease, this population of NHPP c-hGH recipients does not appear to be at increased risk of AD or PD. We discovered 3 ALS cases of unclear significance among US c-hGH recipients despite the absence of pathological deposits of ALS-associated proteins (TDP-43, FUS, and ubiquilin) in human pituitary glands. In this unique in vivo model of human-to-human transmission, we found no evidence to support concerns that NDAPs underlying AD and PD transmit disease in humans despite evidence of their cell-to-cell transmission in model systems of these disorders. Further monitoring is required to confirm these conclusions. |
Acrylamide hemoglobin adduct levels and ovarian cancer risk: a nested case-control study
Xie J , Terry KL , Poole EM , Wilson KM , Rosner BA , Willett WC , Vesper HW , Tworoger SS . Cancer Epidemiol Biomarkers Prev 2013 22 (4) 653-60 BACKGROUND: Acrylamide is a probable human carcinogen formed during cooking of starchy foods. Two large prospective cohort studies of dietary acrylamide intake and ovarian cancer risk observed a positive association, although two other studies reported no association. METHODS: We measured acrylamide exposure using red blood cell acrylamide and glycidamide hemoglobin adducts among women in two large prospective cohorts: the Nurses' Health Study and Nurses' Health Study II. Between blood collection and 2010, we identified 263 incident cases of epithelial ovarian cancer, matching two controls per case. We used logistic regression models to examine the association between acrylamide exposure and ovarian cancer risk, adjusting for matching factors, family history of ovarian cancer, tubal ligation, oral contraceptive use, body mass index, parity, alcohol intake, smoking, physical activity, and caffeine intake. RESULTS: The multivariate-adjusted relative risk (RR) of ovarian cancer comparing the highest versus lowest tertile of total acrylamide adducts was 0.79 (95% CI, 0.50-1.24, P trend = 0.08). The comparable RR of ovarian cancer among non-smokers at blood draw was 0.85 (95% CI, 0.57-1.27, P trend = 0.14). The association did not differ by tumor histology (serous invasive versus not), P for heterogeneity = 0.86. Individual adduct types (acrylamide or glycidamide) were not associated with risk. CONCLUSIONS: We observed no evidence that acrylamide exposure as measured by adducts to hemoglobin is associated with an increased risk of ovarian cancer. IMPACT: Our finding indicates that acrylamide intake may not increase risk of ovarian cancer. |
Hepatitis C in the United States
Holmberg SD , Spradling PR , Moorman AC , Denniston MM . N Engl J Med 2013 368 (20) 1859-61 Care for hepatitis C is evolving rapidly, with increasingly effective and better-tolerated antiviral therapies being evaluated and approved for use. It’s clear, however, that not everyone who would qualify for therapy has been tested and identified, referred for appropriate care, and offered or given the best therapy available. Furthermore, currently used antiviral drugs — pegylated interferon and ribavirin “base” plus either telaprevir or boceprevir — can cost more than $70,000 for a full course of therapy. It is expected that the new oral antiviral agents will be just as expensive, at least in the short term. All these factors affect personal, medical, public health, and national policy decisions. One fundamental problem in making such decisions is that it’s difficult to estimate the number of people with chronic hepatitis C virus (HCV) infection in the United States who have been identified and have received appropriate care. | Over the past 4 years, members of the Division of Viral Hepatitis at the Centers for Disease Control and Prevention (CDC) have executed and analyzed two large studies of hepatitis C in the United States. Researchers conducting the Chronic Hepatitis Cohort Study (CHeCS) are currently examining records from more than 13,000 patients with hepatitis C (and more than 3500 with hepatitis B) who have been seen at four health care organizations in the United States (in Detroit, Michigan; Danville, Pennsylvania; Portland, Oregon; and Honolulu, Hawaii) since 2006. These patients are drawn from a population of about 1.6 million adults who have received care at these four sites during the approximately 6 years for which retrospective and prospective analysis has been under way.1,2 The National Health and Nutrition Examination Survey (NHANES) takes a different approach: random sampling of approximately 5000 non-institutionalized U.S. civilians per year, using standardized household interviews, physical examinations, and testing of serum samples.3 Details and results of these two studies give a consistent picture of the status of HCV infection in the United States (see flow chart). |
Provocative questions in cancer epidemiology in a time of scientific innovation and budgetary constraints.
Lam TK , Schully SD , Rogers SD , Benkeser R , Reid B , Khoury MJ . Cancer Epidemiol Biomarkers Prev 2013 22 (4) 496-500 In a time of scientific and technological developments and budgetary constraints, the National Cancer Institute's (NCI) Provocative Questions Project offers a novel funding mechanism for cancer epidemiologists. We reviewed the purposes underlying the Provocative Questions Project, present information on the contributions of epidemiologic research to the current Provocative Questions portfolio, and outline opportunities that the cancer epidemiology community might capitalize on to advance a research agenda that spans a translational continuum from scientific discoveries to population health impact. |
Recruiting women for a study on perceived risk of cancer: influence of survey topic salience and early versus late response
Leadbetter S , Hawkins NA , Scholl LE , McCarty FA , Rodriguez JL , Freedner-Maguire N , Alford SH , Bellcross CA , Peipins LA . Prev Chronic Dis 2013 10 E75 INTRODUCTION: Understanding the characteristics of early and late survey responders has implications for recruitment efforts and for informing potential response bias. The main objective of this analysis was to examine survey responder status (ie, early vs late response) by sociodemographic characteristics and by salience of study variables among respondents. METHODS: We analyzed data from a survey on family cancer history and perceived cancer risk among women at a large managed health-care organization. For baseline and 12-month follow-up surveys, we defined early versus late responder status according to the 95th percentile of the number of days it took to obtain completed interviews. RESULTS: We found no significant associations between responder status and sociodemographic characteristics at baseline or follow-up. At baseline, early responders were significantly more likely than late responders to have a personal history of breast cancer (5.2% vs 3.4%, P = .04) and to have been referred for genetic counseling (4.6% vs 2.0%, P = .004). The association between personal history of breast cancer and responder status persisted at follow-up; only 3.5% of late responders at baseline were also late responders at follow-up. Follow-up survey nonresponse rates did not vary by baseline responder status. CONCLUSION: Survey topic salience is associated with early response and is important for recruitment. However, once recruited, late responders do not remain late responders at follow-up, suggesting that extra efforts made to recruit late responders are worthwhile. Health-related agencies that conduct surveys should consider survey salience in survey administration and recruitment strategies. |
Biological markers of sexual activity: tools for improving measurement in HIV/sexually transmitted infection prevention research
Gallo MF , Steiner MJ , Hobbs MM , Warner L , Jamieson DJ , Macaluso M . Sex Transm Dis 2013 40 (6) 447-52 Research on interventions to prevent HIV and other sexually transmitted infections (STIs) is heavily influenced by participant reporting of sexual behavior, despite uncertainty about its validity. Exclusive reliance on participant self-report often is based, overtly or by implication, on 4 assumptions: (1) no feasible alternatives exist; (2) misreporting can be minimized to levels that can be disregarded; (3) misreporting tends to underreport sensitive behaviors; and (4) misreporting tends to be nondifferential with respect to the groups being compared. The objective of this review are to evaluate these assumptions, including a review of studies using semen biomarkers to evaluate the validity of self-reported data, and to make recommendations for applying biological markers of semen exposure detectable in women to further strengthen research on HIV/STI prevention. Increasing evidence shows that semen biomarkers provide an important means of assessing and augmenting the validity of studies on HIV/STI prevention. Additional biomarkers are needed to assess male exposure to vaginal sex and both male and female exposure to anal sex. Methods and study designs that incorporate biomarkers into studies collecting self-reported behavioral data should be considered where possible. |
Prevalence and healthcare actions of women in a large health system with a family history meeting the 2005 USPSTF recommendation for BRCA genetic counseling referral.
Bellcross CA , Leadbetter S , Alford SH , Peipins LA . Cancer Epidemiol Biomarkers Prev 2013 22 (4) 728-35 BACKGROUND: In 2005, the United States Preventive Services Task Force (USPSTF) released guidelines which outlined specific family history patterns associated with an increased risk for BRCA1/2 mutations, and recommended at-risk individuals be referred for genetic counseling and evaluation for BRCA testing. The purpose of this study was to assess the prevalence of individuals with a USPSTF increased-risk family history pattern, the frequency with which specific patterns were met, and resulting healthcare actions among women from the Henry Ford Health System. METHODS: As part of a study evaluating ovarian cancer risk perception and screening, 2,524 randomly selected participants completed a detailed interview (response rate 76%) from an initial eligible cohort of 16,720 women. RESULTS: Approximately 6% of participants had a family history fulfilling one or more of the USPSTF patterns. Although 90% of these women had shared their family history with their provider, less than 20% had been referred for genetic counseling and only 8% had undergone genetic testing. Caucasian women with higher income and education levels were more likely to receive referrals. Among the 95 participants in the total study cohort who reported BRCA testing, 78% did not have a family history that met one of the USPSTF patterns. CONCLUSIONS: These results suggest a higher prevalence of women with an increased-risk family history than originally predicted by the USPSTF, and lack of provider recognition and referral for genetic services. IMPACT: Improvements in healthcare infrastructure and clinician education will be required to realize population level benefits from BRCA genetic counseling and testing. |
Comparative effectiveness research in cancer genomics and precision medicine: current landscape and future prospects.
Simonds NI , Khoury MJ , Schully SD , Armstrong K , Cohn WF , Fenstermacher DA , Ginsburg GS , Goddard KA , Knaus WA , Lyman GH , Ramsey SD , Xu J , Freedman AN . J Natl Cancer Inst 2013 105 (13) 929-36 A major promise of genomic research is information that can transform health care and public health through earlier diagnosis, more effective prevention and treatment of disease, and avoidance of drug side effects. Although there is interest in the early adoption of emerging genomic applications in cancer prevention and treatment, there are substantial evidence gaps that are further compounded by the difficulties of designing adequately powered studies to generate this evidence, thus limiting the uptake of these tools into clinical practice. Comparative effectiveness research (CER) is intended to generate evidence on the "real-world" effectiveness compared with existing standards of care so informed decisions can be made to improve health care. Capitalizing on funding opportunities from the American Recovery and Reinvestment Act of 2009, the National Cancer Institute funded seven research teams to conduct CER in genomic and precision medicine and sponsored a workshop on CER on May 30, 2012, in Bethesda, Maryland. This report highlights research findings from those research teams, challenges to conducting CER, the barriers to implementation in clinical practice, and research priorities and opportunities in CER in genomic and precision medicine. Workshop participants strongly emphasized the need for conducting CER for promising molecularly targeted therapies, developing and supporting an integrated clinical network for open-access resources, supporting bioinformatics and computer science research, providing training and education programs in CER, and conducting research in economic and decision modeling. |
Unintentional prescription opioid-related overdose deaths: description of decedents by next of kin or best contact, Utah, 2008-2009
Johnson EM , Lanier WA , Merrill RM , Crook J , Porucznik CA , Rolfs RT , Sauer B . J Gen Intern Med 2013 28 (4) 522-9 BACKGROUND: Little is known about the characteristics that may predispose an individual to being at risk for fatal overdose from prescription opioids. OBJECTIVE: To identify characteristics related to unintentional prescription opioid overdose deaths in Utah. DESIGN: Interviews were conducted (October 2008-October 2009) with a relative or friend most knowledgeable about the decedent's life. SUBJECTS: Analyses involved 254 decedents aged 18 or older, where cause of death included overdose on at least one prescription opioid. KEY RESULTS: Decedents were more likely to be middle-aged, Caucasian, non-Hispanic/Latino, less educated, not married, or reside in rural areas than the general adult population in Utah. In the year prior to death, 87.4 % were prescribed prescription pain medication. Reported potential misuse prescription pain medication in the year prior to their death was high (e.g., taken more often than prescribed [52.9 %], obtained from more than one doctor during the previous year [31.6 %], and used for reasons other than treating pain [29.8 %, almost half of which "to get high"]). Compared with the general population, decedents were more likely to experience financial problems, unemployment, physical disability, mental illness (primarily depression), and to smoke cigarettes, drink alcohol, and use illicit drugs. The primary source of prescription pain medication was from a healthcare provider (91.8 %), but other sources (not mutually exclusive) included: for free from a friend or relative (24 %); from someone without their knowledge (18.2 %); purchase from a friend, relative, or acquaintance (16.4 %); and purchase from a dealer (not a pharmacy) (11.6 %). CONCLUSIONS: The large majority of decedents were prescribed opioids for management of chronic pain and many exhibited behaviors indicative of prescribed medication misuse. Financial problems, unemployment, physical disability, depression, and substance use (including illegal drugs) were also common. |
Bloodstream infection rates in outpatient hemodialysis facilities participating in a collaborative prevention effort: a quality improvement report
Patel PR , Yi SH , Booth S , Bren V , Downham G , Hess S , Kelley K , Lincoln M , Morrissette K , Lindberg C , Jernigan JA , Kallen AJ . Am J Kidney Dis 2013 62 (2) 322-30 BACKGROUND: Bloodstream infections (BSIs) cause substantial morbidity in hemodialysis patients. In 2009, the US Centers for Disease Control and Prevention (CDC) sponsored a collaborative project to prevent BSIs in outpatient hemodialysis facilities. We sought to assess the impact of a set of interventions on BSI and access-related BSI rates in participating facilities using data reported to the CDC's National Healthcare Safety Network (NHSN). STUDY DESIGN: Quality improvement project. SETTING & PARTICIPANTS: Patients in 17 outpatient hemodialysis facilities that volunteered to participate. QUALITY IMPROVEMENT PLAN: Facilities reported monthly event and denominator data to NHSN, received guidance from the CDC, and implemented an evidence-based intervention package that included chlorhexidine use for catheter exit-site care, staff training and competency assessments focused on catheter care and aseptic technique, hand hygiene and vascular access care audits, and feedback of infection and adherence rates to staff. OUTCOMES: Crude and modeled BSI and access-related BSI rates. MEASUREMENTS: Up to 12 months of preintervention (January 2009 through December 2009) and 15 months of intervention period (January 2010 through March 2011) data from participating centers were analyzed. Segmented regression analysis was used to assess changes in BSI and access-related BSI rates during the preintervention and intervention periods. RESULTS: Most (65%) participating facilities were hospital based. Pooled mean BSI and access-related BSI rates were 1.09 and 0.73 events per 100 patient-months during the preintervention period and 0.89 and 0.42 events per 100 patient-months during the intervention period, respectively. Modeled rates decreased 32% (P = 0.01) for BSIs and 54% (P < 0.001) for access-related BSIs at the start of the intervention period. LIMITATIONS: Participating facilities were not representative of all outpatient hemodialysis centers nationally. There was no control arm to this quality improvement project. CONCLUSIONS: Facilities participating in a collaborative successfully decreased their BSI and access-related BSI rates. The decreased rates appeared to be maintained in the intervention period. These findings suggest that improved implementation of recommended practices can reduce BSIs in hemodialysis centers. |
Modeling the impact of quadrivalent HPV vaccination on the incidence of Pap test abnormalities in the United States
Chesson HW , Flagg EW , Koutsky L , Hsu K , Unger ER , Shlay JC , Kerndt P , Ghanem KG , Zenilman JM , Hagensee M , Weinstock H , Datta SD . Vaccine 2013 31 (29) 3019-24 BACKGROUND: We present data on Pap test results and HPV prevalence from the HPV Sentinel Surveillance project, a multiyear surveillance project enrolling women from a diverse set of 26 clinics throughout the US from 2003 to 2005. We use mathematical modeling to illustrate the potential timing and magnitude of decreases in Pap test abnormalities in sexually transmitted disease (STD), family planning, and primary care clinics in the US as a result of HPV vaccination. METHODS: The probability of an abnormal Pap result was based on three factors: (1) infection with HPV 16/18, or both; (2) infection with high-risk HPV types other than HPV 16/18; and (3) infection with HPV 6/11, or both. We estimated the relative reduction in the probability of an abnormal Pap result over the first 25 years of a female-only, quadrivalent HPV vaccination program, compared to a scenario of no HPV vaccination in which the probability of abnormal Pap results was assumed constant. RESULTS: The probability of an abnormal Pap result ranged from 7.0% for the lowest risk group (those without any high-risk HPV types and without HPV 6/11) to 45.2% for the highest risk group (those with HPV 16/18 and at least one other high-risk HPV type). Estimated reductions in abnormal Pap results among women in the 21- to 29-year age group were 0.8%, 10.2%, and 11.3% in years 5, 15, and 25 of the vaccine program respectively, in the lower vaccine coverage scenario, and 7.4%, 21.4%, and 22.2%, respectively, in the higher coverage scenario. CONCLUSIONS: Our results suggest that HPV vaccination will have a discernable impact on the probability of Pap abnormalities, but the timing and magnitude of the reduction will depend substantially on vaccine coverage and the degree of cross-protection against high risk HPV types other than HPV 16/18. |
New vaccine introductions: assessing the impact and the opportunities for immunization and health systems strengthening
Wang SA , Hyde TB , Mounier-Jack S , Brenzel L , Favin M , Gordon WS , Shearer JC , Mantel CF , Arora N , Durrheim D . Vaccine 2013 31 Suppl 2 B122-8 In 2010, global immunization partners posed the question, "Do new vaccine introductions (NVIs) have positive or negative impacts on immunization and health systems of countries?" An Ad-hoc Working Group was formed for WHO's Strategic Advisory Group of Experts on immunization (SAGE) to examine this question through five approaches: a published literature review, a grey literature review, in-depth interviews with regional and country immunization staff, in-depth studies of recent NVIs in 3 countries, and a statistical analysis of the impact of NVI on DTP3 coverage in 176 countries. The WHO Health System Framework of building blocks was used to organize the analysis of these data to assess potential areas of impact of NVI on health systems. In April 2012, the Ad-hoc Working Group presented its findings to SAGE. While reductions in disease burden and improvements in disease and adverse events surveillance, training, cold chain and logistics capacity and injection safety were commonly documented as beneficial impacts, opportunities for strengthening the broader health system were consistently missed during NVI. Weaknesses in planning for human and financial resource needs were highlighted as a concern. Where positive impacts on health systems following NVI occurred, these were often in areas where detailed technical guidance or tools and adequate financing were available. SAGE supported the Ad-hoc Working Group's conclusion that future NVI should explicitly plan to optimize and document the impact of NVI on broader health systems. Furthermore, opportunities for improving integration of delivery of immunization services, commodities, and messages with other parts of the health system should be actively sought with the recognition that integration is a bidirectional process. To avoid the gaps in planning for NVI that can compromise existing immunization and health systems, donors and partners should provide sufficient and timely support to facilitate country planning. Areas for future research were also identified. Finally, to support countries in using NVI as an opportunity to strengthen immunization and health systems, the WHO guidance for countries on new vaccine introduction is being updated to reflect ways this might be accomplished. |
Enabling implementation of the Global Vaccine Action Plan: developing investment cases to achieve targets for measles and rubella prevention
Thompson KM , Strebel PM , Dabbagh A , Cherian T , Cochi SL . Vaccine 2013 31 Suppl 2 B149-56 Global prevention and control of infectious diseases requires significant investment of financial and human resources and well-functioning leadership and management structures. The reality of competing demands for limited resources leads to trade-offs and questions about the relative value of specific investments. Developing investment cases can help to provide stakeholders with information about the benefits, costs, and risks associated with available options, including examination of social, political, governance, and ethical issues. We describe the process of developing investment cases for globally coordinated management of action plans for measles and rubella as tools for enabling the implementation of the Global Vaccine Action Plan (GVAP). We focus on considerations related to the timing of efforts to achieve measles and rubella goals independently and within the context of ongoing polio eradication efforts, other immunization priorities, and other efforts to control communicable diseases or child survival initiatives. Our analysis suggests that the interactions between the availability and sustainability of financial support, sufficient supplies of vaccines, capacity of vaccine delivery systems, and commitments at all levels will impact the feasibility and timing of achieving national, regional, and global goals. The timing of investments and achievements will determine the net financial and health benefits obtained. The methodology, framing, and assumptions used to characterize net benefits and uncertainties in the investment cases will impact estimates and perceptions about the value of prevention achieved overall by the GVAP. We suggest that appropriately valuing the benefits of investments of measles and rubella prevention will require the use of integrated dynamic disease, economic, risk, and decision analytic models in combination with consideration of qualitative factors, and that synthesizing information in the form of investment cases may help stakeholders manage expectations as they chart the course ahead and navigate the decade of vaccines. |
The estimated mortality impact of vaccinations forecast to be administered during 2011-2020 in 73 countries supported by the GAVI Alliance
Lee LA , Franzel L , Atwell J , Datta SD , Friberg IK , Goldie SJ , Reef SE , Schwalbe N , Simons E , Strebel PM , Sweet S , Suraratdecha C , Tam Y , Vynnycky E , Walker N , Walker DG , Hansen PM . Vaccine 2013 31 Suppl 2 B61-72 INTRODUCTION: From August to December 2011, a multidisciplinary group with expertise in mathematical modeling was constituted by the GAVI Alliance and the Bill & Melinda Gates Foundation to estimate the impact of vaccination in 73 countries supported by the GAVI Alliance. METHODS: The number of deaths averted in persons projected to be vaccinated during 2011-2020 was estimated for ten antigens: hepatitis B, yellow fever, Haemophilus influenzae type B (Hib), Streptococcus pneumoniae, rotavirus, Neisseria meningitidis serogroup A, Japanese encephalitis, human papillomavirus, measles, and rubella. Impact was calculated as the difference in the number of deaths expected over the lifetime of vaccinated cohorts compared to the number of deaths expected in those cohorts with no vaccination. Numbers of persons vaccinated were based on 2011 GAVI Strategic Demand Forecasts with projected dates of vaccine introductions, vaccination coverage, and target population size in each country. RESULTS: By 2020, nearly all GAVI-supported countries with endemic disease are projected to have introduced hepatitis B, Hib, pneumococcal, rotavirus, rubella, yellow fever, N. meningitidis serogroup A, and Japanese encephalitis-containing vaccines; 55 (75 percent) countries are projected to have introduced human papillomavirus vaccine. Projected use of these vaccines during 2011-2020 is expected to avert an estimated 9.9 million deaths. Routine and supplementary immunization activities with measles vaccine are expected to avert an additional 13.4 million deaths. Estimated numbers of deaths averted per 1000 persons vaccinated were highest for first-dose measles (16.5), human papillomavirus (15.1), and hepatitis B (8.3) vaccination. Approximately 52 percent of the expected deaths averted will be in Africa, 27 percent in Southeast Asia, and 13 percent in the Eastern Mediterranean. CONCLUSION: Vaccination of persons during 2011-2020 in 73 GAVI-eligible countries is expected to have substantial public health impact, particularly in Africa and Southeast Asia, two regions with high mortality. The actual impact of vaccination in these countries may be higher than our estimates because several widely used antigens were not included in the analysis. The quality of our estimates is limited by lack of data on underlying disease burden and vaccine effectiveness against fatal disease outcomes in developing countries. We plan to update the estimates annually to reflect updated demand forecasts, to refine model assumptions based on results of new information, and to extend the analysis to include morbidity and economic benefits. |
Identifying optimal vaccination strategies for serogroup A Neisseria meningitidis conjugate vaccine in the African meningitis belt
Tartof S , Cohn A , Tarbangdo F , Djingarey MH , Messonnier N , Clark TA , Kambou JL , Novak R , Diomande FV , Medah I , Jackson ML . PLoS One 2013 8 (5) e63605 OBJECTIVE: The optimal long-term vaccination strategies to provide population-level protection against serogroup A Neisseria meningitidis (MenA) are unknown. We developed an age-structured mathematical model of MenA transmission, colonization, and disease in the African meningitis belt, and used this model to explore the impact of various vaccination strategies. METHODS: The model stratifies the simulated population into groups based on age, infection status, and MenA antibody levels. We defined the model parameters (such as birth and death rates, age-specific incidence rates, and age-specific duration of protection) using published data and maximum likelihood estimation. We assessed the validity of the model by comparing simulated incidence of invasive MenA and prevalence of MenA carriage to observed incidence and carriage data. RESULTS: The model fit well to observed age- and season-specific prevalence of carriage (mean pseudo-R2 0.84) and incidence of invasive disease (mean R2 0.89). The model is able to reproduce the observed dynamics of MenA epidemics in the African meningitis belt, including seasonal increases in incidence, with large epidemics occurring every eight to twelve years. Following a mass vaccination campaign of all persons 1-29 years of age, the most effective modeled vaccination strategy is to conduct mass vaccination campaigns every 5 years for children 1-5 years of age. Less frequent campaigns covering broader age groups would also be effective, although somewhat less so. Introducing conjugate MenA vaccine into the EPI vaccination schedule at 9 months of age results in higher predicted incidence than periodic mass campaigns. DISCUSSION: We have developed the first mathematical model of MenA in Africa to incorporate age structures and progressively waning protection over time. Our model accurately reproduces key features of MenA epidemiology in the African meningitis belt. This model can help policy makers consider vaccine program effectiveness when determining the feasibility and benefits of MenA vaccination strategies. |
Desirability and feasibility of a vaccine against cytomegalovirus
Griffiths P , Plotkin S , Mocarski E , Pass R , Schleiss M , Krause P , Bialek S . Vaccine 2013 31 Suppl 2 B197-203 Publication of a report from the Institute of Medicine in 2000 showing that a vaccine against cytomegalovirus (CMV) would likely be cost saving was very influential and encouraged the clinical evaluation of candidate vaccines. The major objective of a CMV vaccination program would be to reduce disease caused by congenital CMV infection, which is the leading viral cause of sensorineural hearing loss and neurodevelopmental delay. CMV has challenges as a vaccine target because it is a herpesvirus, it persists lifelong despite host immunity, infected individuals can be reinfected with new strains, overt disease occurs in those with immature or impaired immune systems and persons with this infection do not usually report symptoms. Nevertheless, natural immunity against CMV provides some protection against infection and disease, natural history studies have defined the serological and molecular biological techniques needed for endpoints in future clinical trials of vaccines and CMV is not highly communicable, suggesting that it may not be necessary to achieve very high levels of population immunity through vaccination in order to affect transmission. Three phase 2 CMV vaccine studies have been completed in the last 3 years and all report encouraging outcomes. A key international meeting was organized by the Food and Drug Administration in January 2012 at which interested parties from regulatory bodies, industry and academia discussed and prioritised designs for phase 2 and phase 3 clinical trials. Vaccines able to prevent primary infection with CMV and to boost the immune response of those already infected are desirable. The major target populations for a CMV vaccine include women of childbearing age and adolescents. Toddlers represent another potential population, since an effect of vaccine in this age group could potentially decrease transmission to adults. In addition, prospective recipients of transplants and patients with AIDS would be expected to benefit. |
The predictive influence of family and neighborhood assets on fighting and weapon carrying from mid- to late adolescence
Haegerich TM , Oman RF , Vesely SK , Aspy CB , Tolma EL . Prev Sci 2013 15 (4) 473-84 Using a developmental, social-ecological approach to understand the etiology of health-risk behavior and inform primary prevention efforts, we assess the predictive effects of family and neighborhood social processes on youth physical fighting and weapon carrying. Specifically, we focus on relationships among youth and their parents, family communication, parental monitoring, as well as sense of community and neighborhood informal social control, support, concerns, and disorder. This study advances knowledge through its investigation of family and neighborhood structural factors and social processes together, employment of longitudinal models that estimate effects over adolescent development, and use of self-report and observational measures. Data from 1,093 youth/parent pairs were analyzed from the Youth Assets Study using a Generalized Estimating Equation approach; family and neighborhood assets and risks were analyzed as time varying and lagged. Similar family assets affected physical fighting and weapon carrying, whereas different neighborhood social processes influenced the two forms of youth violence. Study findings have implications for the primary prevention of youth violence, including the use of family-based approaches that build relationships and parental monitoring skills and community-level change approaches that promote informal social control and reduce neighborhood concerns about safety. |
Similar uptake but different trafficking and escape routes of reovirus virions and infectious subvirion particles imaged in polarized Madin-Darby canine kidney cells
Boulant S , Stanifer M , Kural C , Cureton DK , Massol R , Nibert ML , Kirchhausen T . Mol Biol Cell 2013 24 (8) 1196-207 Polarized epithelial cells that line the digestive, respiratory, and genitourinary tracts form a barrier that many viruses must breach to infect their hosts. Current understanding of cell entry by mammalian reovirus (MRV) virions and infectious subvirion particles (ISVPs), generated from MRV virions by extracellular proteolysis in the digestive tract, are mostly derived from in vitro studies with nonpolarized cells. Recent live-cell imaging advances allow us for the first time to visualize events at the apical surface of polarized cells. In this study, we used spinning-disk confocal fluorescence microscopy with high temporal and spatial resolution to follow the uptake and trafficking dynamics of single MRV virions and ISVPs at the apical surface of live polarized Madin-Darby canine kidney cells. Both types of particles were internalized by clathrin-mediated endocytosis, but virions and ISVPs exhibited strikingly different trafficking after uptake. While virions reached early and late endosomes, ISVPs did not and instead escaped the endocytic pathway from an earlier location. This study highlights the broad advantages of using live-cell imaging combined with single-particle tracking for identifying key steps in cell entry by viruses. |
Programmed death 1 lives up to its reputation in active tuberculosis
Sable SB . J Infect Dis 2013 208 (4) 541-3 Programmed death 1 (PD-1; CD279), also known as programmed cell death protein 1 (PDCD-1), is a cell surface receptor of the immunoglobulin superfamily found on immune effector cells. It belongs to the extended CD28/CTLA-4 family of T-cell regulators and is expressed by a range of immune cells, including B cells, natural killer cells, and monocytes. Binding of PD-1 to one of its ligands, PD ligand 1 (PD-L1) or PD-L2, on antigen-presenting cells (APCs) is known to negatively regulate T-cell receptor signaling and inhibit T-cell activation [1]. In this issue of the Journal, Singh et al [2] demonstrate that the coinhibitory receptor PD-1 and the PD ligands are expressed on higher percentages of peripheral blood mononuclear cells (PBMCs) of patients with active tuberculosis than those of healthy controls in an area of tuberculosis endemicity. The expression of PD-1 on T cells is upregulated following in vitro stimulation with Mycobacterium tuberculosis antigens, and the PD-1 blockade in vitro enhances interferon γ (IFN-γ) and interleukin 2 production by specific T cells and rescues them from undergoing apoptosis. Of particular significance, the authors demonstrate during a 1-year follow-up period a significant decrease in the frequency of PD-1–expressing T cells after successful antituberculosis treatment that led to restoration of the M. tuberculosis–specific T-cell cytokine response in vitro. These data substantiate the role of PD-1–PD-L pathways in the inhibition of T-cell responses in patients with active tuberculosis. |
Effects of microparticle size and Fc density on macrophage phagocytosis
Pacheco P , White D , Sulchek T . PLoS One 2013 8 (4) e60989 Controlled induction of phagocytosis in macrophages offers the ability to therapeutically regulate the immune system as well as improve delivery of chemicals or biologicals for immune processing. Maximizing particle uptake by macrophages through Fc receptor-mediated phagocytosis could lead to new delivery mechanisms in drug or vaccine development. Fc ligand density and particle size were examined independently and in combination in order to optimize and tune the phagocytosis of opsonized microparticles. We show the internalization efficiency of small polystyrene particles (0.5 microm to 2 microm) is significantly affected by changes in Fc ligand density, while particles greater than 2 microm show little correlation between internalization and Fc density. We found that while macrophages can efficiently phagocytose a large number of smaller particles, the total volume of phagocytosed particles is maximized through the non-specific uptake of larger microparticles. Therefore, larger microparticles may be more efficient at delivering a greater therapeutic payload to macrophages, but smaller opsonized microparticles can deliver bio-active substances to a greater percentage of the macrophage population. This study is the first to treat as independent variables the physical and biological properties of Fc density and microparticle size that initiate macrophage phagocytosis. Defining the physical and biological parameters that affect phagocytosis efficiency will lead to improved methods of microparticle delivery to macrophages. |
Interlaboratory evaluation of rodent pulmonary responses to engineered nanomaterials: the NIEHS Nano Go Consortium
Bonner JC , Silva RM , Taylor AJ , Brown JM , Hilderbrand SC , Castranova V , Porter D , Elder A , Oberdorster G , Harkema JR , Bramble LA , Kavanagh TJ , Botta D , Nel A , Pinkerton KE . Environ Health Perspect 2013 121 (6) 676-82 BACKGROUND: Engineered nanomaterials (ENMs) have potential benefits, but also present safety concerns for human health. Inter-laboratory studies in rodents using standardized protocols are needed for ENM toxicity assessment. METHODS: Four labs evaluated lung responses in C57BL/6 mice to ENMs delivered by oropharyngeal aspiration (OPA). Three labs evaluated Sprague-Dawley (SD) or Fisher (F)344 rats following intratracheal instillation (IT). ENMs tested were three forms of titanium dioxide (TiO2); anatase/rutile spheres (TiO2-P25), anatase spheres (TiO2-A), anatase nanobelts (TiO2-NB), and three forms of multiwalled carbon nanotubes (MWCNT); original (O), purified (P), and carboxylic acid "functionalized" (F). Bronchoalveolar lavage fluid was collected after 1 day for differential cell counts, lactate dehydrogenase (LDH), and protein. Lungs were fixed for histopathology. Responses were also examined at 7 days (TiO2) and 21 days (MWCNTs). RESULTS: TiO2-A, TiO2-P25, and TiO2-NB caused significant neutrophilia in mice at 1 day in 3 out of 4 labs, respectively. TiO2-NB caused neutrophilia in rats at 1 day in 2 out of 3 labs, while TiO2-P25 or TiO2-A had no significant effect in any of the labs. Inflammation induced by TiO2 in mice and rats resolved by day 7. All MWCNT types caused neutrophilia at 1 day in 3 out of 4 mouse labs and all rat labs. Three out of 4 labs observed similar histopathology to O-MWCNT or TiO2-NB in mice. CONCLUSIONS: ENMs produced similar patterns of neutrophilia and pathology in rats and mice. Although inter-laboratory variability was found in the degree of neutrophilia caused by the three types of TiO2 nanoparticles, similar findings of relative potency for the three types of MWCNTs were found across all laboratories, thus providing greater confidence in these inter-laboratory comparisons. |
Accumulation of retained nonfunctional arteriovenous grafts correlates with severity of inflammation in asymptomatic ESRD patients
Wasse H , Cardarelli F , De Staercke C , Hooper WC , Long Q . Nephrol Dial Transplant 2013 28 (4) 991-7 BACKGROUND: The contribution of multiple retained nonfunctional arteriovenous grafts (AVGs) to the burden of chronic inflammation in chronic hemodialysis patients has not been well studied. Here, we sought to evaluate the association between plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and albumin and the number of retained nonfunctional AVGs. METHODS: This cross-sectional study enrolled 91 prevalent patients undergoing in-center hemodialysis without evidence of infection or inflammation. A baseline blood sample was obtained at study enrollment. A general linear model (GLM) was used to compare levels of biomarkers of systemic inflammation across groups defined by the number of retained, nonfunctional AVGs. RESULTS: A total of 43 patients had one or more retained thrombosed AVG and had significantly greater plasma log-CRP levels compared with patients without a previous AVG (P= 0.036), regardless of the current AV access type. Using a GLM, we found that for every additional retained thrombosed AVG, plasma log-CRP, log-IL-6 and TNF-alpha concentrations increased significantly by 0.30 mg/L (P= 0.011), 0.18 pg/mL (P= 0.046) and 0.72 pg/mL (P= 0.046), respectively, following adjustment. CONCLUSIONS: Hence, the severity of inflammation increases with the number of retained nonfunctional AVG's, suggesting that AVG accumulation may contribute to the cardiovascular morbidity and mortality associated with chronic inflammation in asymptomatic end-stage renal disease (ESRD) patients. Further study is indicated to determine whether patients with one or more thrombosed, retained AVG may benefit from periodic screening with CRP monitoring to identify those patients who may benefit from AVG resection. |
Development of a new test system to determine penetration of multi-walled carbon nanotubes through filtering facepiece respirators
Vo E , Zhuang Z . J Aerosol Sci 2013 61 50-59 Carbon nanotubes (CNTs) are currently used in numerous industrial and biomedical applications. Recent studies suggest that workers may be at risk of adverse health effects if they are exposed to CNTs. A National Institute for Occupational Safety and Health (NIOSH) survey of the carbonaceous nanomaterial industry found that 77% of the companies used respiratory protection. Elastomeric half-mask respirators and filtering facepiece respirators (FFRs) are commonly used. Although numerous respirator filtration studies have been done with surrogate engineered nanoparticles, such as sodium chloride, penetration data from engineered nanoparticles such as CNTs are lacking. The aims of this study were to develop a new CNT aerosol respirator testing system and to determine multi-walled CNT (MWCNT) penetration through FFRs.A custom-designed CNT aerosol respirator testing system (CNT-ARTS) was developed which was capable of producing a sufficient amount of airborne MWCNTs for testing of high efficiency FFRs. The size distribution of airborne MWCNTs was 20-10,000. nm, with 99% of the particles between 25 and 2840. nm. The count median diameter (CMD) was 209. nm with a geometric standard deviation (GSD) of 1.98. This particle size range is similar to those found in some work environments (particles <=6000. nm). The penetration of MWCNTs through six tested FFR models at two constant flow rates of 30 and 85 LPM was determined. Penetration at 85 LPM (0.58-2.04% for N95, 0.15-0.32% for N99, and 0.007-0.009% for P100 FFRs) was greater compared with the values at 30 LPM (0.28-1.79% for N95, 0.10-0.24% for N99, and 0.005-0.006% for P100 FFRs). The most penetrating particle size through all six tested FFR models was found to be in the range of 25-130. nm and 35-200. nm for the 30-LPM and 85-LPM flow rates, respectively. 2013. |
Distinct memory CD4(+) T cells with commitment to T follicular helper- and T helper 1-cell lineages are generated after acute viral infection
Hale JS , Youngblood B , Latner DR , Mohammed AU , Ye L , Akondy RS , Wu T , Iyer SS , Ahmed R . Immunity 2013 38 (4) 805-17 CD4(+) T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for long-lived antibody responses. However, it remains unclear whether there are CD4(+) memory T cells committed to the Tfh cell lineage after antigen clearance. By using adoptive transfer of antigen-specific memory CD4(+) T cell subpopulations in the lymphocytic choriomeningitis virus infection model, we found that there are distinct memory CD4(+) T cell populations with commitment to either Tfh- or Th1-cell lineages. Our conclusions are based on gene expression profiles, epigenetic studies, and phenotypic and functional analyses. Our findings indicate that CD4(+) memory T cells "remember" their previous effector lineage after antigen clearance, being poised to reacquire their lineage-specific effector functions upon antigen reencounter. These findings have important implications for rational vaccine design, where improving the generation and engagement of memory Tfh cells could be used to enhance vaccine-induced protective immunity. |
Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism
Christensen J , Gronborg TK , Sorensen MJ , Schendel D , Parner ET , Pedersen LH , Vestergaard M . JAMA 2013 309 (16) 1696-703 IMPORTANCE: Valproate is used for the treatment of epilepsy and other neuropsychological disorders and may be the only treatment option for women of childbearing potential. However, prenatal exposure to valproate may increase the risk of autism. OBJECTIVE: To determine whether prenatal exposure to valproate is associated with an increased risk of autism in offspring. DESIGN, SETTING, AND PARTICIPANTS: Population-based study of all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). We analyzed the risks associated with all autism spectrum disorders as well as childhood autism. Data were analyzed by Cox regression adjusting for potential confounders (maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity). Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first. MAIN OUTCOMES AND MEASURES: Absolute risk (cumulative incidence) and the hazard ratio (HR) of autism spectrum disorder and childhood autism in children after exposure to valproate in pregnancy. RESULTS: Of 655,615 children born from 1996 through 2006, 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14; median, 8.85). The estimated absolute risk after 14 years of follow-up was 1.53% (95% CI, 1.47%-1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46%-0.51%) for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% (95% CI, 2.59%-7.46%) for autism spectrum disorder (adjusted HR, 2.9 [95% CI, 1.7-4.9]) and an absolute risk of 2.50% (95% CI, 1.30%-4.81%) for childhood autism (adjusted HR, 5.2 [95% CI, 2.7-10.0]). When restricting the cohort to the 6584 children born to women with epilepsy, the absolute risk of autism spectrum disorder among 432 children exposed to valproate was 4.15% (95% CI, 2.20%-7.81%) (adjusted HR, 1.7 [95% CI, 0.9-3.2]), and the absolute risk of childhood autism was 2.95% (95% CI, 1.42%-6.11%) (adjusted HR, 2.9 [95% CI, 1.4-6.0]) vs 2.44% (95% CI, 1.88%-3.16%) for autism spectrum disorder and 1.02% (95% CI, 0.70%-1.49%) for childhood autism among 6152 children not exposed to valproate. CONCLUSIONS AND RELEVANCE: Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy. For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control. |
Prevalence of use of human milk in US advanced care neonatal units
Perrine CG , Scanlon KS . Pediatrics 2013 131 (6) 1066-71 BACKGROUND AND OBJECTIVE: The American Academy of Pediatrics recommends all preterm infants receive human milk. The objective of this study was to describe the use of human milk in advanced care neonatal units of US maternity hospitals. METHODS: We used Centers for Disease Control and Prevention's national Maternity Practices in Infant Nutrition and Care survey from 2007, 2009, and 2011 to analyze 2 questions to describe the prevalence of US advanced care (special/level 2 or intensive/level 3) neonatal units routinely providing human milk to infants, and the use of any donor milk in these units. RESULTS: In 2011, 30.8% of maternity hospitals reported that most infants (≥90%) were routinely provided human milk in advanced care units, compared with 26.7% in 2009 and 21.2% in 2007 (trend P < .001). States in the Northwest and Northeast had a higher prevalence of hospitals routinely providing human milk to ≥90% of infants in advanced care units. In 2011, 22.0% of maternity hospitals providing advanced care used banked donor milk, compared with 14.4% in 2009 and 11.5% in 2007 (trend P < .001). Most of this increase occurred in intensive care units (25.1% 2007 vs 45.2% 2011; trend P < .001). There was substantial geographic variation in the prevalence of advanced care units using donor milk; generally the prevalence was higher in the West and in states with a milk bank in the state or a neighboring state. CONCLUSIONS: The use of human milk in US advanced care neonatal units is increasing; however, only one-third of these units are routinely providing human milk to most infants. |
Trends in sugar-sweetened beverage consumption among youth and adults in the United States: 1999-2010
Kit BK , Fakhouri TH , Park S , Nielsen SJ , Ogden CL . Am J Clin Nutr 2013 98 (1) 180-8 BACKGROUND: Reducing sugar-sweetened beverage (SSB) consumption is a recommended strategy to promote optimal health. OBJECTIVE: The objective was to describe trends in SSB consumption among youth and adults in the United States. DESIGN: We analyzed energy intake from SSBs among 22,367 youth aged 2-19 y and 29,133 adults aged ≥20 y who participated in a 24-h dietary recall as part of NHANES, a nationally representative sample of the US population with a cross-sectional design, between 1999 and 2010. SSBs included soda, fruit drinks, sports and energy drinks, sweetened coffee and tea, and other sweetened beverages. Patterns of SSB consumption, including location of consumption and meal occasion associated with consumption, were also examined. RESULTS: In 2009-2010, youth consumed a mean (+/-SE) of 155 +/- 7 kcal/d from SSBs and adults consumed an age-adjusted mean (+/-SE) of 151 +/- 5 kcal/d from SSBs-a decrease from 1999 to 2000 of 68 kcal/d and 45 kcal/d, respectively (P-trend < 0.001 for each). In 2009-2010, SSBs contributed 8.0% +/- 0.4% and 6.9% +/- 0.2% of daily energy intake among youth and adults, respectively, which reflected a decrease compared with 1999-2000 (P-trend < 0.001 for both). Decreases in SSB consumption, both in the home and away from home and also with both meals and snacks, occurred over the 12-y study duration (P-trend < 0.01 for each). CONCLUSION: A decrease in SSB consumption among youth and adults in the United States was observed between 1999 and 2010. |
Occupational safety and health, green chemistry, and sustainability: a review of areas of convergence
Schulte PA , McKernan LT , Heidel DS , Okun AH , Dotson GS , Lentz TJ , Geraci CL , Heckel PE , Branche CM . Environ Health 2013 12 31 With increasing numbers and quantities of chemicals in commerce and use, scientific attention continues to focus on the environmental and public health consequences of chemical production processes and exposures. Concerns about environmental stewardship have been gaining broader traction through emphases on sustainability and "green chemistry" principles. Occupational safety and health has not been fully promoted as a component of environmental sustainability. However, there is a natural convergence of green chemistry/sustainability and occupational safety and health efforts. Addressing both together can have a synergistic effect. Failure to promote this convergence could lead to increasing worker hazards and lack of support for sustainability efforts. The National Institute for Occupational Safety and Health has made a concerted effort involving multiple stakeholders to anticipate and identify potential hazards associated with sustainable practices and green jobs for workers. Examples of potential hazards are presented in case studies with suggested solutions such as implementing the hierarchy of controls and prevention through design principles in green chemistry and green building practices. Practical considerations and strategies for green chemistry, and environmental stewardship could benefit from the incorporation of occupational safety and health concepts which in turn protect affected workers. |
The proportion of work-related emergency department visits not expected to be paid by workers' compensation: implications for occupational health surveillance, research, policy, and health equity
Groenewold MR , Baron SL . Health Serv Res 2013 48 1939-59 OBJECTIVE: To examine trends in the proportion of work-related emergency department visits not expected to be paid by workers' compensation during 2003-2006, and to identify demographic and clinical correlates of such visits. DATA SOURCE: A total of 3,881 work-related emergency department visit records drawn from the 2003-2006 National Hospital Ambulatory Medical Care Surveys. STUDY DESIGN: Secondary, cross-sectional analyses of work-related emergency department visit data were performed. Odds ratios and 95 percent confidence intervals were modeled using logistic regression. PRINCIPAL FINDINGS: A substantial and increasing proportion of work-related emergency department visits in the United States were not expected to be paid by workers' compensation. Private insurance, Medicaid, Medicare, and workers themselves were expected to pay for 40 percent of the work-related emergency department visits with this percentage increasing annually. Work-related visits by blacks, in the South, to for-profit hospitals and for work-related illnesses were all more likely not to be paid by workers' compensation. CONCLUSIONS: Emergency department-based surveillance and research that determine work-relatedness on the basis of expected payment by workers' compensation systematically underestimate the occurrence of occupational illness and injury. This has important methodological and policy implications. |
Exacerbation of symptoms in agricultural pesticide applicators with asthma
Henneberger PK , Liang X , London SJ , Umbach DM , Sandler DP , Hoppin JA . Int Arch Occup Environ Health 2013 87 (4) 423-32 PURPOSE: Exacerbation is a critical event in asthma management. We investigated whether exacerbation of symptoms is associated with farming exposures among agricultural pesticide applicators with asthma. METHODS: Participants were pesticide applicators with active asthma (wheezing and breathing problems in past 12 months) who completed enrollment questionnaires for the Agricultural Health Study (AHS). Exacerbation of asthma was defined as having visited a hospital emergency room or doctor for an episode of wheezing or whistling in the past 12 months. Exposures of interest were using 36 specific pesticides in the past 12 months and conducting various agricultural activities. Adjusted odds ratios (ORs) were estimated by logistic regression while controlling for potential confounders. RESULTS: The 926 AHS adult pesticide applicators with active asthma included 202 (22 %) with exacerbation. Inverse associations with exacerbation were observed for two herbicides [glyphosate, odds ratio (OR) = 0.5, 95 % confidence interval (CI) 0.3, 0.8, and paraquat, OR = 0.3, 95 % CI 0.1, 0.9] and several agricultural activities (repairing engines, grinding metal, driving diesel tractors, and performing veterinary procedures). Only asthma cases with allergies (i.e., doctor-diagnosed hay fever or eczema, 46 %) had positive exacerbation-pesticide associations, with OR = 2.1 (95 % CI 1.1, 4.1) for the herbicide pendimethalin and OR = 10.2 (95 % CI 1.9, 55) for the insecticide aldicarb. CONCLUSIONS: The inverse associations with two pesticides and specific farm activities are consistent with the possibility that asthma cases prone to exacerbation may avoid exposures that trigger symptoms. Although limited by small sample size and a cross-sectional design, our study suggests that use of specific pesticides may contribute to exacerbation of asthma among individuals with allergies. |
Safe conception for HIV-discordant couples: insemination with processed semen from the HIV-infected partner
Semprini AE , Macaluso M , Hollander L , Vucetich A , Duerr A , Mor G , Ravizza M , Jamieson DJ . Am J Obstet Gynecol 2013 208 (5) 402 e1-9 OBJECTIVE: The objective of the study was to evaluate the safety of semen washing with intrauterine insemination (SW-IUI) for achieving pregnancy when the man is human immunodeficiency virus (HIV) infected and the woman is HIV negative. STUDY DESIGN: We conducted a retrospective analysis of 635 HIV-discordant couples enrolled in a SW-IUI program and followed up 367 Italian women. We computed pregnancy, live birth, and multiple delivery rates and assessed the women's postinsemination HIV status. RESULTS: The retrospective analysis included 635 couples (2113 SW-IUI cycles): 41% of the women (95% confidence interval [CI], 37-45%) had a live birth (per-cycle live birth rate 13%; 95% CI, 11-14%). HIV status after SW-IUI was negative when available but unknown for 26% of the women: missing HIV status was not associated with correlates of HIV risk. The follow-up study included 367 couples (1365 cycles): 47% of the women (95% CI, 42-52%) had a live birth (per-cycle rate 14%; 95% CI, 12-16%). Ascertainment of postinsemination HIV status was complete and confirmed no HIV transmission attributable to SW-IUI. The upper 95% confidence limit of the HIV transmission rate was 1.8 per 1000 cycles in the retrospective analysis and 2.7 per 1000 cycles in the follow-up study. CONCLUSION: SW-IUI appears to be a safe and effective method for achieving pregnancy in HIV-discordant couples in which the man is HIV infected. |
When can a woman resume or initiate contraception after taking emergency contraceptive pills? A systematic review
Salcedo J , Rodriguez MI , Curtis KM , Kapp N . Contraception 2013 87 (5) 602-4 BACKGROUND: Hormonal emergency contraception can postpone ovulation, making a woman vulnerable to pregnancy later in the same cycle. However, concern exists as to whether concurrently administered emergency contraception pills (ECP) and other hormonal methods of contraception may affect the effectiveness of both medications. STUDY DESIGN: A systematic review of the literature using PubMed and the Cochrane databases was performed to identify articles concerning the resumption or initiation of regular contraception within the same cycle as ECP use. We searched for articles in any language, published between 1980 and April 2012 and included all methods of emergency contraception pills available in the USA. RESULTS: The search strategy identified 184 articles in the PubMed and Cochrane databases, of which none met inclusion criteria. CONCLUSION: The drug manufacturer advises continuation or initiation of routine contraception as soon as possible after use of ulipristal acetate, with concomitant use of a reliable barrier method until next menses. However, a theoretical concern exists that given ulipristal acetate's function as a selective progesterone receptor modulator, coadministration of a progestin could decrease its effectiveness as an emergency contraceptive. Initiation of hormonal contraception following levonorgestrel or the Yuzpe regimen for emergency contraception carries no similar concern for decreased method effectiveness. |
When can a woman start combined hormonal contraceptives (CHCs)?: a systematic review
Brahmi D , Curtis KM . Contraception 2013 87 (5) 524-38 BACKGROUND: Conventional methods of initiating combined hormonal contraceptives (CHCs), specifically combined oral contraceptives (COCs), the contraceptive patch and the contraceptive ring, require that women delay starting CHCs until menses begin, during which time a woman may be at risk of unintended pregnancy. The objective of this systematic review is to examine the evidence on the risk of becoming pregnant after starting the method (contraceptive effectiveness including surrogate measures such as ovarian follicular development and hormone levels), risk of already being pregnant, side effects and continuation when starting CHCs on different days of the menstrual cycle. STUDY DESIGN: We searched the MEDLINE database for all articles (in all languages) published in peer-reviewed journals from inception through March 2012 for evidence relevant to starting CHCs on different days of the menstrual cycle and the outcomes of contraceptive effectiveness (including ovarian follicular development and hormonal levels), side effects and continuation rates. RESULTS: From 1635 reviewed articles, 18 studies met our inclusion criteria. Evidence from four studies suggests that neither the risk of inadvertently starting COCs in a woman who is pregnant nor the risk of pregnancy after COC initiation are affected by the cycle day on which COCs are started. While follicular activity increased as the cycle day on which COCs were initiated increased, no women ovulated when starting on Day 5. When starting on Day 7, there was no increase in ovulation for a 30-mcg pill but a significant increase in ovulation with a 20-mcg pill compared with starting on Day 1. Evidence from two small studies suggests that 7 days of pills leads to inhibition of ovulation. One small study suggests that only 3 days of ring use is needed to inhibit ovulation, but this was following one complete treatment cycle of ring use. Evidence also suggests that starting CHCs on any day of the cycle does not affect bleeding problems or other side effects for both COCs and the patch. While starting CHCs via Quick Start (starting on the day of the health care visit) may initially increase continuation compared with more conventional starting strategies, evidence suggests that this difference disappears over time. CONCLUSION: The body of evidence suggested that (a) pregnancy rates did not differ by the timing of CHC initiation; (b) the more follicular activity that occurred prior to starting COCs, the more likely ovulation was to occur; however, no ovulations were seen when COCs were started at a follicle diameter of 10 mm (mean cycle day=7.6) or when the ring was started at follicle diameter of 13 mm (median cycle day=11); (c) bleeding patterns and other side effects did not vary with the timing of CHC initiation and (d) continuation rates of CHCs were initially improved by Quick Start, but differences between groups disappeared over time. |
Pregnancies after hysteroscopic sterilization: a systematic review
Cleary TP , Tepper NK , Cwiak C , Whiteman MK , Jamieson DJ , Marchbanks PA , Curtis KM . Contraception 2013 87 (5) 539-48 BACKGROUND: Female sterilization is the second most commonly used form of contraception in the United States. Newer approaches to female sterilization, including hysteroscopic methods, have been approved for use in the United States since 2002. Little is known about the occurrence and timing of pregnancies after these procedures. STUDY DESIGN: The objective of this systematic review was to identify evidence that assesses when and how often pregnancies occur following hysteroscopic sterilization. The PubMed database was searched for all studies published from database inception through March 2012 that reported whether or not pregnancies occurred following hysteroscopic sterilization. RESULTS: Twenty-four original research articles of fair quality met the inclusion criteria: 22 studies of women who underwent Essure(R) placement and 2 studies of women who underwent Adiana(R) placement. Eleven articles that documented bilateral tubal occlusion with hysterosalpingogram (HSG) or placement with X-ray or ultrasound following Essure(R) placement did not report any pregnancies with follow-up ranging from 7 months to 7 years. The remaining 11 articles identified 102 reported pregnancies. Eighteen of these pregnancies occurred prior to the 3-month period required before imaging for contraceptive reliability. Two articles did not report what follow-up imaging was performed among women after Essure(R) placement; one of these articles reported three pregnancies. Two reports from the same study of women who underwent Adiana(R) placement reported six pregnancies during the first year of follow-up, three pregnancies during the second year of follow-up and no pregnancies during the third year of follow-up. CONCLUSIONS: Fair-quality evidence suggests that among women who were followed beyond 3 months after hysteroscopic sterilization, pregnancies were rare and generally occurred among women who had no imaging follow-up or had inadequate confirmation of placement or occlusion. Few pregnancies occurred in women with documented bilateral tubal occlusion by HSG or correct placement at 3 months by ultrasound or X-ray. Only one study reported follow-up past 5 years. Further studies are needed to address the long-term effectiveness of hysteroscopic sterilization. |
Prevention and management of nausea and vomiting with emergency contraception: a systematic review
Rodriguez MI , Godfrey EM , Warden M , Curtis KM . Contraception 2013 87 (5) 583-9 BACKGROUND: Nausea and vomiting are side effects of emergency contraception pill (ECP) use. Different ECP regimens and the use of antinausea drugs may prevent these side effects. METHODS: We conducted two searches to identify data pertaining to the prevention of nausea and vomiting with ECP use and management of emesis with ECP use. Both searches queried the PubMed and Cochrane databases for peer-reviewed articles, in any language, published on January 1966-February 2012. Types of ECP included in our searches were levonorgestrel (LNG), Yuzpe regimens or ulipristal acetate (UA). Our search strategy for data on management of emesis with ECP use also included the gray literature. The gray literature includes materials such as reports, patent claims, prescribing information and package labels that are not published commercially. RESULTS: Eleven articles met the inclusion criteria. Split dose or two doses of LNG caused less nausea than UA and standard two-dose Yuzpe regimen in one study. Four studies demonstrated no difference between split-dose versus single-dose LNG. In two trials, meclizine and metoclopramide, given before Yuzpe ECPs, reduced nausea, but only meclizine reduced vomiting. CONCLUSION: The evidence does not support routine use of antiemetics with ECP use. Data to guide management of emesis with ECP are limited to expert opinion and package labeling. |
Advance supply of emergency contraception: a systematic review
Rodriguez MI , Curtis KM , Gaffield ML , Jackson E , Kapp N . Contraception 2013 87 (5) 590-601 BACKGROUND: Emergency contraceptive pills (ECPs) are an underutilized means to reduce unintended pregnancy. Advance provision of ECPs may increase timely use, thereby decreasing risk of unintended pregnancy. STUDY DESIGN: We searched MEDLINE and EMBASE through February 2012 for randomized, controlled trials (RCTs) pertaining to safety and efficacy of advance provision of ECP. The quality of each individual study was evaluated using the United States Preventive Services Task Force evidence grading system. RESULTS: The search strategy identified 714 articles. Seventeen papers reported on safety or efficacy of advance ECPs in adult or adolescent women. Any use of ECPs was two to seven times greater among women who received an advanced supply of ECP. However, a summary estimate (RR 0.90, 95% CI 0.69-1.18) of four RCTs did not demonstrate a significant reduction in unintended pregnancy over 12 months when advance provision was compared with standard provision of ECPs. Patterns of contraceptive use, pregnancy rates and incidence of sexually transmitted infections did not vary between treatment and control groups in the majority of studies among either adults or adolescents. CONCLUSION: Available evidence supports the safety of advance provision of ECPs. Efficacy of advance provision compared with standard provision of ECPs in reducing unintended pregnancy rates at the population level has not been demonstrated. |
Time-dependent fields of a current-carrying wire
Redzic DV , Hnizdo V . Eur J Phys 2013 34 (3) 495-501 The electric and magnetic fields of an infinite straight wire carrying a steady current which is turned on abruptly are determined using Jefimenko's equations, starting from the standard assumption that the wire is electrically neutral in its rest frame. Some nontrivial aspects of the solution are discussed in detail. |
Smoke-free rules and secondhand smoke exposure in homes and vehicles among US adults, 2009-2010
King BA , Dube SR , Homa DM . Prev Chronic Dis 2013 10 1-12 INTRODUCTION: An increasing number of US states and localities have implemented comprehensive policies prohibiting tobacco smoking in all indoor areas of public places and worksites. However, private settings such as homes and vehicles remain a major source of exposure to secondhand smoke (SHS) for many people. This study assessed the prevalence and correlates of voluntary smoke-free rules and SHS exposure in homes and vehicles among US adults. METHODS: We obtained data from the 2009-2010 National Adult Tobacco Survey, a landline and cellular-telephone survey of adults aged 18 years or older residing in the 50 US states or the District of Columbia. We calculated national and state estimates of smoke-free rules and past-7-day SHS exposure in homes and vehicles and examined national estimates by sex, age, race/ethnicity, and education. RESULTS: The national prevalence of voluntary smoke-free home rules was 81.1% (state range, 67.9%-92.9%), and the prevalence of household smoke-free vehicle rules was 73.6% (state range, 58.6%-85.8%). Among nonsmokers, the prevalence of SHS exposure was 6.0% in homes (state range, 2.4%-13.0%) and 9.2% in vehicles (state range, 4.8%-13.7%). SHS exposure among nonsmokers was greatest among men, younger adults, non-Hispanic blacks, and those with a lower level of education. CONCLUSION: Most US adults report having voluntary smoke-free home and vehicle rules; however, millions of people remain exposed to SHS in these environments. Disparities in exposure also exist among certain states and subpopulations. Efforts are needed to warn about the dangers of SHS and to promote voluntary smoke-free home and vehicle rules. |
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