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1.  Rural African American Parents’ Knowledge and Decisions About Human Papillomavirus Vaccination 
To identify predictors of human papillomavirus (HPV) vaccination among rural African American families.
Cross-sectional descriptive study in schools in three rural counties in southeastern United States. The sample consisted of African American parents or caregivers with children 9 to 13 years of age who attended elementary or middle school in 2010–2011.
Using an anonymous, 26-item survey, we collected descriptive data during parent-teacher events from African American parents with children in elementary or middle school. The main outcome was measured as a response of “yes” to the statement “I have or will vaccinate my child with the HPV vaccine.” In addition, composite scores of knowledge and positive attitudes and beliefs were compared. No interventions were conducted.
We identified predictors of HPV vaccination and found that religious affiliation had a correlation with vaccinating or planning to vaccinate a child.
Results indicate a need for further research on the role of local culture, including religion and faith, in rural African Americans’ decisions about giving their children the HPV vaccination.
Clinical Relevance
This study emphasizes the importance of understanding rural African American parents’ knowledge, attitudes, and spiritual beliefs when designing health education programs and public health interventions to increase HPV vaccination uptake among African American boys and girls living in rural areas.
PMCID: PMC3952034  PMID: 23126428
Human papillomavirus vaccination; African American; parents; consent; health disparities; rural health
2.  Frequency and determinants of disagreement and error in Gleason scores: a population-based study of prostate cancer 
The Prostate  2012;72(13):1389-1398.
To examine factors that affect accuracy and reliability of prostate cancer grade we compared Gleason scores documented in pathology reports and those assigned by urologic pathologists in a population-based study.
A stratified random sample of 318 prostate cancer cases diagnosed was selected to ensure representation of whites and African-Americans and to include facilities of various types. The slides borrowed from reporting facilities were scanned and the resulting digital images were re-reviewed by two urologic pathologists. If the two urologic pathologists disagreed, a third urologic pathologist was asked to help arrive at a final “gold standard” result. The agreements between reviewers and between the pathology reports and the “gold standard” were examined by calculating kappa statistics. The determinants of discordance in Gleason scores were evaluated using multivariate models with results expressed as odds ratios (OR) and 95% confidence intervals (CI).
The kappa values (95% CI) reflecting agreement between the pathology reports and the “gold standard,” were 0.61 (95% CI: 0.54, 0.68) for biopsies, and 0.37 (0.23, 0.51) for prostatectomies. Sixty three percent of discordant biopsies and 72% of discordant prostatectomies showed only minimal differences. Using free standing laboratories as reference, the likelihood of discordance between pathology reports and expert-assigned biopsy Gleason scores was particularly elevated for small community hospitals (OR=2.98; 95% CI: 1.73, 5.14).
The level of agreement between pathology reports and expert review depends on the type of diagnosing facility, but may also depend on the level of expertise and specialization of individual pathologists.
PMCID: PMC3339279  PMID: 22228120
prostate cancer; Gleason score; agreement; accuracy
3.  Invasive Pneumococcal Pneumonia and Respiratory Virus Co-infections 
Emerging Infectious Diseases  2012;18(2):294-297.
Each year, especially in the winter, many get sick and some die of invasive pneumococcal pneumonia. Does this type of pneumonia increase in the winter because people are in closer contact indoors?  Or are people more susceptible to this bacterial disease after having had a seasonal respiratory virus infection?  A season-by-season analysis found an association between pneumococcal pneumonia and two viruses (influenza and respiratory syncytial virus). The association varied by season and was strongest when the predominant influenza virus subtype was H3N2. Vaccination against influenza and RSV should also help protect against pneumococcal pneumonia.
To confirm whether respiratory virus infections increase susceptibility to invasive pneumococcal pneumonia, we examined data from 11 influenza seasons (1994–2005) in the United States. Invasive pneumococcal pneumonia was significantly associated with influenza and respiratory syncytial virus activities in 5 seasons. Association strength was higher when strain H3N2 was the predominant influenza A virus strain.
PMCID: PMC3310442  PMID: 22305270
Pneumococcal diseases; pneumonia; influenza; H3N2; respiratory syncytial virus; temporal association; viruses
4.  Differential expression and potential role of SOCS1 and SOCS3 in Wallerian degeneration in injured peripheral nerve 
Experimental neurology  2009;223(1):173-182.
Pro-inflammatory chemokines and cytokines play an important role in Wallerian degeneration (WD) after peripheral nerve injury. These pro-inflammatory signals are “turned-off” in a timely manner to ensure that the inflammatory response in the injured nerve is limited. The factors that regulate the turning-off of the pro-inflammatory state are not fully understood. The suppressors of cytokine signaling (SOCS) proteins are potential candidates that could limit the inflammatory response by acting to regulate cytokine signaling at the intracellular level. In this work we show that the expression SOCS1 and SOCS3 proteins differ from each other during WD in the mouse sciatic nerve after cut/ligation and crush injuries. SOCS1 is mainly expressed by macrophages and its expression is inversely correlated with phosphorylation of JAK2 and STAT3 signaling proteins and the expression of pro-inflammatory cytokines IL-1β and TNFα. In addition, treatment of cut/ligated nerves, which express lower levels of SOCS1 as compared to crush injury, with a SOCS1 mimetic peptide leads to a decrease in macrophage numbers at 14 days post-injury and reduces IL-1β mRNA expression 1 day post-injury. In contrast, SOCS3 expression is restricted mainly to Schwann cells and is negatively correlated with the expression of IL-6 and LIF. These data suggest that SOCS1 and SOCS3 may play different roles in WD and provide a better understanding of some of the potential regulatory mechanisms that may control inflammation and regeneration in the injured peripheral nerve.
PMCID: PMC2849922  PMID: 19576891
SOCS; Macrophage; Cytokine; Inflammation; Wallerian degeneration; Peripheral nerve
5.  Estimation of Coefficients of Individual Agreement (CIA’s) for Quantitative and Binary Data using SAS and R 
The coefficients of individual agreement (CIA’s), which are based on the ratio of the intra-and inter-observer disagreement, provide a general approach for evaluating agreement between two fixed methods of measurements or human observers. In this paper, programs in both SAS and R are presented for estimation of the CIA’s between two observers with quantitative or binary measurements. A detailed illustration of the computations, macro variable definitions, input and output for the SAS and R programs are also included in the text. The programs provide estimations of CIA’s, their standard errors as well as confidence intervals, for the cases with or without a reference method. Data from a carotid stenosis screening study is used as an example of quantitative measurements. Data from a study involving the evaluation of mammograms by ten radiologists is used to illustrate a binary data example.
PMCID: PMC2856751  PMID: 20079947
Agreement; Coefficient of individual agreement; Macro; Mean Squared Deviation
6.  Impact of Non-Pharmaceutical Interventions on URIs and Influenza in Crowded, Urban Households 
Public Health Reports  2010;125(2):178-191.
We compared the impact of three household interventions—education, education with alcohol-based hand sanitizer, and education with hand sanitizer and face masks—on incidence and secondary transmission of upper respiratory infections (URIs) and influenza, knowledge of transmission of URIs, and vaccination rates.
A total of 509 primarily Hispanic households participated. Participants reported symptoms twice weekly, and nasal swabs were collected from those with an influenza-like illness (ILI). Households were followed for up to 19 months and home visits were made at least every two months.
We recorded 5,034 URIs, of which 669 cases reported ILIs and 78 were laboratory-confirmed cases of influenza. Demographic factors significantly associated with infection rates included age, gender, birth location, education, and employment. The Hand Sanitizer group was significantly more likely to report that no household member had symptoms (p<0.01), but there were no significant differences in rates of infection by intervention group in multivariate analyses. Knowledge improved significantly more in the Hand Sanitizer group (p<0.0001). The proportion of households that reported ≥50% of members receiving influenza vaccine increased during the study (p<0.001). Despite the fact that compliance with mask wearing was poor, mask wearing as well as increased crowding, lower education levels of caretakers, and index cases 0–5 years of age (compared with adults) were associated with significantly lower secondary transmission rates (all p<0.02).
In this population, there was no detectable additional benefit of hand sanitizer or face masks over targeted education on overall rates of URIs, but mask wearing was associated with reduced secondary transmission and should be encouraged during outbreak situations. During the study period, community concern about methicillin-resistant Staphylococcus aureus was occurring, perhaps contributing to the use of hand sanitizer in the Education control group, and diluting the intervention's measurable impact.
PMCID: PMC2821845  PMID: 20297744
7.  Impact of Pneumococcal Conjugate Vaccination of Infants on Pneumonia and Influenza Hospitalization and Mortality in All Age Groups in the United States 
mBio  2011;2(1):e00309-10.
A seven-valent pneumococcal conjugate vaccine (PCV7) introduced in the United States in 2000 has been shown to reduce invasive pneumococcal disease (IPD) in both vaccinated children and adults through induction of herd immunity. We assessed the impact of infant immunization on pneumococcal pneumonia hospitalizations and mortality in all age groups using Health Care Utilization Project State Inpatient Databases (SID) for 1996 to 2006 from 10 states; SID contain 100% samples of ICD9-coded hospitalization data for the selected states. Compared to a 1996–1997 through 1998–1999 baseline, by the 2005–2006 season, both IPD and pneumococcal pneumonia hospitalizations and deaths had decreased substantially in all age groups, including a 47% (95% confidence interval [CI], 38 to 54%) reduction in nonbacteremic pneumococcal pneumonia (ICD9 code 481 with no codes indicating IPD) in infants <2 years old and a 54% reduction (CI, 53 to 56%) in adults ≥65 years of age. A model developed to calculate the total burden of pneumococcal pneumonia prevented by infant PCV7 vaccination in the United States from 2000 to 2006 estimated a reduction of 788,838 (CI, 695,406 to 875,476) hospitalizations for pneumococcal pneumonia. Ninety percent of the reduction in model-attributed pneumococcal pneumonia hospitalizations occurred through herd immunity among adults 18 years old and older; similar proportions were found in pneumococcal disease mortality prevented by the vaccine. In the first seasons after PCV introduction, when there were substantial state differences in coverage among <5-year-olds, states with greater coverage had significantly fewer influenza-associated pneumonia hospitalizations among children, suggesting that PCV7 use also reduces influenza-attributable pneumonia hospitalizations.
Pneumonia is the world’s leading cause of death in children and the leading infectious cause of death among U.S. adults 65 years old and older. Pneumococcal conjugate vaccination of infants has previously been shown to reduce invasive pneumococcal disease (IPD) among seniors through prevention of pneumococcal transmission from infants to adults (herd immunity). Our analysis documents a significant vaccine-associated reduction not only in IPD but also in pneumococcal pneumonia hospitalizations and inpatient mortality rates among both vaccinated children and unvaccinated adults. We estimate that fully 90% of the reduction in the pneumonia hospitalization burden occurred among adults. Moreover, states that more rapidly introduced their infant pneumococcal immunization programs had greater reductions in influenza-associated pneumonia hospitalization of children, presumably because the vaccine acts to prevent the pneumococcal pneumonia that frequently follows influenza virus infection. Our results indicate that seven-valent pneumococcal conjugate vaccine use has yielded far greater benefits through herd immunity than have previously been recognized.
PMCID: PMC3025524  PMID: 21264063
8.  Beneficial effects of secretory leukocyte protease inhibitor after spinal cord injury 
Brain  2009;133(1):126-138.
Secretory leukocyte protease inhibitor is a serine protease inhibitor produced by various cell types, including neutrophils and activated macrophages, and has anti-inflammatory properties. It has been shown to promote wound healing in the skin and other non-neural tissues, however, its role in central nervous system injury was not known. We now report a beneficial role for secretory leukocyte protease inhibitor after spinal cord injury. After spinal cord contusion injury in mice, secretory leukocyte protease inhibitor is expressed primarily by astrocytes and neutrophils but not macrophages. We show, using transgenic mice over-expressing secretory leukocyte protease inhibitor, that this molecule has an early protective effect after spinal cord contusion injury. Furthermore, wild-type mice treated for the first week after spinal cord contusion injury with recombinant secretory leukocyte protease inhibitor exhibit sustained improvement in locomotor control and reduced secondary tissue damage. Recombinant secretory leukocyte protease inhibitor injected intraperitoneally localizes to the nucleus of circulating leukocytes, is detected in the injured spinal cord, reduces activation of nuclear factor-κB and expression of tumour necrosis factor-α. Administration of recombinant secretory leukocyte protease inhibitor might therefore be useful for the treatment of acute spinal cord injury.
PMCID: PMC2801328  PMID: 20047904
spinal cord injury; neuroinflammation; wound healing; neutrophil; astrocytes; macrophage
9.  Antibiotic control of antibiotic resistance in hospitals: a simulation study 
BMC Infectious Diseases  2010;10:254.
Using mathematical deterministic models of the epidemiology of hospital-acquired infections and antibiotic resistance, it has been shown that the rates of hospital-acquired bacterial infection and frequency of antibiotic infections can be reduced by (i) restricting the admission of patients colonized with resistant bacteria, (ii) increasing the rate of turnover of patients, (iii) reducing transmission by infection control measures, and (iv) the use of second-line drugs for which there is no resistance. In an effort to explore the generality and robustness of the predictions of these deterministic models to the real world of hospitals, where there is variation in all of the factors contributing to the incidence of infection, we developed and used a stochastic model of the epidemiology of hospital-acquired infections and resistance. In our analysis of the properties of this model we give particular consideration different regimes of using second-line drugs in this process.
We developed a simple model that describes the transmission of drug-sensitive and drug-resistant bacteria in a small hospital. Colonized patients may be treated with a standard drug, for which there is some resistance, and with a second-line drug, for which there is no resistance. We then ran deterministic and stochastic simulation programs, based on this model, to predict the effectiveness of various treatment strategies.
The results of the analysis using our stochastic model support the predictions of the deterministic models; not only will the implementation of any of the above listed measures substantially reduce the incidences of hospital-acquired infections and the frequency of resistance, the effects of their implementation should be seen in months rather than the years or decades anticipated to control resistance in open communities. How effectively and how rapidly the application of second-line drugs will contribute to the decline in the frequency of resistance to the first-line drugs depends on how these drugs are administered. The earlier the switch to second-line drugs, the more effective this protocol will be. Switching to second-line drugs at random is more effective than switching after a defined period or only after there is direct evidence that the patient is colonized with bacteria resistant to the first antibiotic.
The incidence of hospital-acquired bacterial infections and frequencies of antibiotic resistant bacteria can be markedly and rapidly reduced by different readily implemented procedures. The efficacy using second line drugs to achieve these ends depends on the protocol used for their administration.
PMCID: PMC2940903  PMID: 20738872
10.  Evaluation of Agreement between Measurement Methods from Data with Matched Repeated Measurements via the Coefficient of Individual Agreement 
Journal of data science : JDS  2010;8(3):457-469.
We propose a simple method for evaluating agreement between methods of measurement when the measured variable is continuous and the data consists of matched repeated observations made with the same method under different conditions. The conditions may represent different time points, raters, laboratories, treatments, etc. Our approach allows the values of the measured variable and the magnitude of disagreement to vary across the conditions. The coefficient of individual agreement (CIA), which is based on the comparison of the between and within-methods mean squared deviation (MSD) is used to quantify the magnitude of agreement between measurement methods. The new approach is illustrated via two examples from studies designed to compare (a) methods of evaluating carotid stenosis and (b) methods of measuring percent body fat.
PMCID: PMC2907262  PMID: 20664753
coefficient of individual agreement; method comparisons; repeated measurements
11.  Assessing Intra, Inter and Total Agreement With Replicated Readings 
Statistics in medicine  2005;24(9):1371-1384.
In clinical studies, assessing agreement of multiple readings on the same subject plays an important role in the evaluation of continuous measurement scale. The multiple readings within a subject may be replicated readings by using the same method or/and readings by using several methods (e.g., different technologies or several raters). The traditional agreement data for a given subject often consist of either replicated readings from only one method or multiple readings from several methods where only one reading is taken from each of these methods. In the first case, only intra-method agreement can be evaluated. In the second case, traditional agreement indices such as intra-class correlation (ICC) or concordance correlation coefficient (CCC) is often reported as inter-method agreement. We argue that these indices are in fact measures of total agreement that contains both inter and intra agreement. Only if there are replicated readings from several methods for a given subject, then one can assess intra, inter and total agreement simultaneously. In this paper, we present new inter-method agreement index, inter-CCC, and total agreement index, total-CCC, for agreement data with replicated readings from several methods where the ICCs within methods are used to assess intra-method agreement for each of the several methods. The relationship of the total-CCC with the inter-CCC and the ICCs is investigated. We propose a generalized estimating equations (GEE) approach for estimation and inference. Simulation studies are conducted to assess the performance of the proposed approach and data from a carotid stenosis screening study is used for illustration.
PMCID: PMC1653479  PMID: 15570569
Agreement; Reliability; Concordance Correlation Coefficient; Intraclass Correlation; Generalized Estimating Equations
12.  Effectiveness of Interventions to Reduce Contact Rates during a Simulated Influenza Pandemic 
Emerging Infectious Diseases  2007;13(4):581-589.
Measures to decrease contact between persons during an influenza pandemic have been included in pandemic response plans. We used stochastic simulation models to explore the effects of school closings, voluntary confinements of ill persons and their household contacts, and reductions in contacts among long-term care facility (LTCF) residents on pandemic-related illness and deaths. Our findings suggest that school closings would not have a substantial effect on pandemic-related outcomes in the absence of measures to reduce out-of-school contacts. However, if persons with influenzalike symptoms and their household contacts were encouraged to stay home, then rates of illness and death might be reduced by ≈50%. By preventing ill LTCF residents from making contact with other residents, illness and deaths in this vulnerable population might be reduced by ≈60%. Restricting the activities of infected persons early in a pandemic could decrease negative health impact.
PMCID: PMC2725959  PMID: 17553273
influenza; models; statistical; patient isolation; quarantine; stochastic processes; research
13.  CD137 costimulatory T cell receptor engagement reverses acute disease in lupus-prone NZB × NZW F1 mice 
Journal of Clinical Investigation  2003;111(10):1505-1518.
Systemic lupus erythematosus (SLE) is a CD4+ T cell–dependent, immune complex–mediated, autoimmune disease that primarily affects women of childbearing age. Generation of high-titer affinity-matured IgG autoantibodies, specific for double-stranded DNA and other nuclear antigens, coincides with disease progression. Current forms of treatment of SLE including glucocorticosteroids are often inadequate and induce severe side effects. Immunological approaches for treating SLE in mice using anti-CD4 mAb’s or CTLA4-Ig and anti-CD154 mAb’s have proven to be effective. However, like steroid treatment, these regimens induce global immunosuppression, and their withdrawal allows for disease progression. In this report we show that lupus-prone NZB × NZW F1 mice given three injections of anti-CD137 (4-1BB) mAb’s between 26 and 35 weeks of age reversed acute disease, blocked chronic disease, and extended the mice’s lifespan from 10 months to more than 2 years. Autoantibody production in recipients was rapidly suppressed without inducing immunosuppression. Successful treatment could be traced to the fact that NZB × NZW F1 mice, regardless of their age or disease status, could not maintain pathogenic IgG autoantibody production in the absence of continuous CD4+ T cell help. Our data support the hypothesis that CD137-mediated signaling anergized CD4+ T cells during priming at the DC interface.
PMCID: PMC155050  PMID: 12750400

Results 1-13 (13)