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1.  Low testosterone is associated with disability in men with multiple sclerosis 
Gonadal steroids may modulate disease course in multiple sclerosis (MS).
To assess the prevalence and clinical associations of hypogonadism in MS men.
Males, aged 18-65 years, with relapsing remitting MS or CIS and first symptom <10 years prior, were selected from a longitudinal clinical study, Hormones were measured in stored morning blood samples. Expanded Disability Status Scale (EDSS) scores were collected every 6 months, and Symbol Digit Modalities test (SDMT) annually.
The analysis included 96 men with a mean age of 40 years, EDSS of 1.1, and disease duration of 4.6 years. Of these men, 39% were hypogonadal (total testosterone <288 ng/dL); none showed compensatory elevations in luteinizing hormone. Low testosterone levels and testosterone:estradiol ratios were negatively correlated with body mass index and leptin, and showed no correlation with 25-hydroxyvitamin D levels. In the primary cross-sectional analyses, there was a negative age-adjusted correlation between total testosterone and EDSS (p=0.044). In the age-adjusted longitudinal analyses, higher baseline testosterone levels were associated with less decline in SDMT (p=0.012).
Men with MS may experience hypogonadotropic hypogonadism. Low testosterone levels may be associated with worse clinical outcomes. A potential neuroprotective role for testosterone warrants further investigation.
PMCID: PMC4188801  PMID: 24710799
testosterone; multiple sclerosis; leptin; BMI; cognition
2.  Individual- and neighborhood-level education influences the effect of obesity on prostate cancer treatment failure after prostatectomy 
Cancer Causes & Control  2015;26(9):1329-1337.
The relationship between obesity and prostate cancer (CaP) treatment failure is complex and may vary by patient- and neighborhood-level educational attainment. We evaluated whether patient- and neighborhood-level education is associated with the effect of obesity on biochemical recurrence.
Seven hundred and forty-six CaP cases were classified into four groups: Concordant Low–Low: less educated cases (<4 years college) living in a less educated neighborhood (below-median proportion of college-educated residents; n = 164); Concordant High–High: highly educated cases (≥4 years college) living in a highly educated neighborhood (above-median proportion of college-educated residents; n = 326); Discordant Low–High: less educated cases living in a highly educated neighborhood (n = 69); and Discordant High–Low: highly educated cases living in a less educated neighborhood (n = 187). Cox regression models were used to examine associations between obesity and biochemical (PSA) failure after prostatectomy stratified by the concordant/discordant groups.
The association of obesity with biochemical failure varied significantly by educational concordance/discordance (p = 0.007). Obesity was associated with risk of biochemical failure for less educated cases residing in less educated neighborhoods (HR 3.72, 95 % CI 1.30–10.65). The relationship was not significant for other concordant/discordant groups.
Obesity effects on CaP outcomes vary by multilevel educational discordance/concordance. Strategies to decrease prostate cancer risk of progression may focus on reduction in obesity, particularly for less educated cases residing in less educated neighborhoods.
PMCID: PMC4540780  PMID: 26169299
Prostate cancer; Obesity; Education; Cross-level interaction; Neighborhood SES
3.  Barriers and facilitators to patient retention in HIV care 
BMC Infectious Diseases  2015;15:246.
Retention in HIV care improves survival and reduces the risk of HIV transmission to others. Multiple quantitative studies have described demographic and clinical characteristics associated with retention in HIV care. However, qualitative studies are needed to better understand barriers and facilitators.
Semi-structured interviews were conducted with 51 HIV-infected individuals, 25 who were retained in care and 26 not retained in care, from 3 urban clinics. Interview data were analyzed for themes using a modified grounded theory approach. Identified themes were compared between the two groups of interest: patients retained in care and those not retained in care.
Overall, participants identified 12 barriers and 5 facilitators to retention in HIV care. On average, retained individuals provided 3 barriers, while persons not retained in care provided 5 barriers. Both groups commonly discussed depression/mental illness, feeling sick, and competing life activities as barriers. In addition, individuals not retained in care commonly reported expensive and unreliable transportation, stigma, and insufficient insurance as barriers. On average, participants in both groups referenced 2 facilitators, including the presence of social support, patient-friendly clinic services (transportation, co-location of services, scheduling/reminders), and positive relationships with providers and clinic staff.
In our study, patients not retained in care faced more barriers, particularly social and structural barriers, than those retained in care. Developing care models where social and financial barriers are addressed, mental health and substance abuse treatment is integrated, and patient-friendly services are offered is important to keeping HIV-infected individuals engaged in care.
PMCID: PMC4485864  PMID: 26123158
Retention; Engagement; HIV; Care; Barriers; Facilitators
4.  Quantification of Global Cerebral Atrophy in Multiple Sclerosis from 3T MRI Using SPM: The Role of Misclassification Errors 
Journal of Neuroimaging  2014;25(2):191-199.
We tested the validity of a freely available segmentation pipeline to measure compartmental brain volumes from 3T MRI in patients with multiple sclerosis (MS). Our primary focus was methodological to explore the effect of segmentation corrections on the clinical relevance of the output metrics.
Three-dimensional T1-weighted images were acquired to compare 61 MS patients to 30 age- and gender-matched normal controls (NC). We also tested the within patient MRI relationship to disability (eg, expanded disability status scale [EDSS] score) and cognition. Statistical parametric mapping v. 8 (SPM8)-derived gray matter (GMF), white matter (WMF), and total brain parenchyma fractions (BPF) were derived before and after correcting errors from T1 hypointense MS lesions and/or ineffective deep GM contouring.
MS patients had lower GMF and BPF as compared to NC (P<.05). Cognitively impaired patients had lower BPF than cognitively preserved patients (P<.05). BPF was related to EDSS; BPF and GMF were related to disease duration (all P<.05). Errors caused bias in GMFs and WMFs but had no discernable influence on BPFs or any MRI-clinical associations.
We report the validity of a segmentation pipeline for the detection of MS-related brain atrophy with 3T MRI. Longitudinal studies are warranted to extend these results.
PMCID: PMC4409073  PMID: 25523616
Brain atrophy; multiple sclerosis; MRI; segmentation; lesions; gray matter
5.  Is Your Neighborhood Designed to Support Physical Activity? A Brief Streetscape Audit Tool 
Macro level built environment factors (eg, street connectivity, walkability) are correlated with physical activity. Less studied but more modifiable microscale elements of the environment (eg, crosswalks) may also affect physical activity, but short audit measures of microscale elements are needed to promote wider use. This study evaluated the relation of a 15-item neighborhood environment audit tool with a full version of the tool to assess neighborhood design on physical activity in 4 age groups.
From the 120-item Microscale Audit of Pedestrian Streetscapes (MAPS) measure of street design, sidewalks, and street crossings, we developed the 15-item version (MAPS-Mini) on the basis of associations with physical activity and attribute modifiability. As a sample of a likely walking route, MAPS-Mini was conducted on a 0.25-mile route from participant residences toward the nearest nonresidential destination for children (n = 758), adolescents (n = 897), younger adults (n = 1,655), and older adults (n = 367). Active transportation and leisure physical activity were measured with age-appropriate surveys, and accelerometers provided objective physical activity measures. Mixed-model regressions were conducted for each MAPS item and a total environment score, adjusted for demographics, participant clustering, and macrolevel walkability.
Total scores of MAPS-Mini and the 120-item MAPS correlated at r = .85. Total microscale environment scores were significantly related to active transportation in all age groups. Items related to active transport in 3 age groups were presence of sidewalks, curb cuts, street lights, benches, and buffer between street and sidewalk. The total score was related to leisure physical activity and accelerometer measures only in children.
The MAPS-Mini environment measure is short enough to be practical for use by community groups and planning agencies and is a valid substitute for the full version that is 8 times longer.
PMCID: PMC4561538  PMID: 26334713
6.  Self-Monitoring as a Mediator of Weight Loss in the SMART Randomized Clinical Trial 
International journal of behavioral medicine  2013;20(4):10.1007/s12529-012-9259-9.
Integral components of behavioral weight-loss treatment include self-monitoring of diet and physical activity along with feedback to participants regarding their behaviors. While providing feedback has been associated with weight loss, no studies have examined the impact of feedback frequency on weight loss, or the mediating role of self-monitoring adherence in this relationship.
This study examined the effect of participant feedback frequency on weight loss and determined if this effect was mediated by adherence to self-monitoring in a behavioral weight-loss trial conducted in the United States.
Participants (N=210) were randomly assigned to one of three self-monitoring methods with either no daily feedback messages or daily feedback messages: 1) paper diary (PD)- no daily feedback, 2) personal digital assistant (PDA)- no daily feedback, and 3) PDA- daily, tailored feedback messages (PDA+FB). The Sobel test via bootstrapping examined the direct effect of feedback frequency on weight loss and the indirect effect through self-monitoring adherence.
Receiving daily feedback messages significantly increased participants’ self-monitoring adherence. A significant effect of feedback frequency on weight loss was noted; however, after adjusting for self-monitoring adherence, the effect of feedback frequency on weight loss was no longer significant. Feedback frequency had a significant indirect effect on weight loss through self-monitoring adherence.
Self-monitoring adherence mediated the effect of feedback frequency on weight loss. Increasing the frequency with which participants receive feedback could enhance self-monitoring adherence, a critical component of behavioral weight-loss treatment.
PMCID: PMC3529986  PMID: 22936524
self-monitoring; mediation; adherence; feedback; weight loss; obesity
7.  Randomized Trial of Tailored Skin Cancer Prevention for Children: The Project SCAPE Family Study 
Journal of health communication  2013;18(11):10.1080/10810730.2013.778361.
This study evaluated a tailored intervention to promote sun protection in parents and their children, hypothesizing that the tailored intervention would lead to improved skin cancer prevention behaviors compared to generic materials. Families were recruited through schools and community centers and were included if there was one child in Grades 1–3 at moderate to high risk for skin cancer. Participants were randomized into one of two intervention groups: a tailored intervention, in which they received personalized skin cancer education through the mail; or a control group who received generic skin cancer information materials. Both pre- and post-intervention, parents completed questionnaires about their and their children’s skin cancer risk and prevention knowledge and behaviors. Parents also completed 4-day sun exposure and protection diaries for their child and themselves. Tailored group participants demonstrated significantly greater positive changes in prevention behavior after the intervention, including children’s use of sunscreen, shirts, and hats, and parents’ use of shade, and skin examinations. Effect sizes were small and perceived benefits and social norms mediated intervention effects. Findings from this study support the efficacy of focusing tailored communications to families in order to change skin cancer prevention practices in young children.
PMCID: PMC3815976  PMID: 23806094
8.  Psychosocial Assessments for HIV+ African Adolescents: Establishing Construct Validity and Exploring Under-Appreciated Correlates of Adherence 
PLoS ONE  2014;9(10):e109302.
Study Objectives
Psychosocial factors such as outcome expectancy, perceived stigma, socio-emotional support, consideration of future consequences, and psychological reactance likely influence adolescent adherence to antiretroviral treatments. Culturally-adapted and validated tools for measuring these factors in African adolescents are lacking. We aimed to identify culturally-specific factors of importance to establishing local construct validity in Botswana.
Using in-depth interviews of 34 HIV+ adolescents, we explored how the psychosocial factors listed above are perceived in this cultural context. We evaluated six scales that have been validated in other contexts. We also probed for additional factors that the adolescents considered important to their HIV medication adherence. Analyses were conducted with an analytic framework approach using NVivo9 software.
While the construct validity of some Western-derived assessment tools was confirmed, other tools were poorly representative of their constructs in this cultural context. Tools chosen to evaluate HIV-related outcome expectancy and perceived stigma were well-understood and relevant to the adolescents. Feedback from the adolescents suggested that tools to measure all other constructs need major modifications to obtain construct validity in Botswana. The scale regarding future consequences was poorly understood and contained several items that lacked relevance for the Batswana adolescents. They thought psychological reactance played an important role in adherence, but did not relate well to many components of the reactance scale. Measurement of socio-emotional support needs to focus on the adolescent-parent relationship, rather than peer-support in this cultural context. Denial of being HIV-infected was an unexpectedly common theme. Ambivalence about taking medicines was also expressed.
In-depth interviews of Batswana adolescents confirmed the construct validity of some Western-developed psychosocial assessment tools, but demonstrated limitations in others. Previously underappreciated factors related to HIV medication adherence, such as denial and ambivalence, should be further explored.
PMCID: PMC4184864  PMID: 25279938
9.  A Mixed Methods Study of Parental Vaccine Decision Making and Parent-Provider Trust 
Academic pediatrics  2013;13(5):481-488.
To describe parental vaccine decision making behaviors and characterize trust in physician advice among parents with varying childhood vaccination behaviors.
Between 2008 and 2011, a mixed methods study was conducted with parents of children aged <4 years who were members of Kaiser Permanente Colorado health plan. Seven focus groups were conducted with vaccine hesitant parents. Based on findings from the focus groups, a survey was developed, pilot tested and mailed to a stratified sample of 854 parents who accepted (n=500), delayed (n=227), or refused (n=127) vaccinations for one of their children. Survey results were analyzed using chi-square tests and multivariable logistic regression.
Several themes emerged from the focus groups, including: 1) the vaccine decision making process begins prenatally, 2) vaccine decision making is an evolving process, and 3) there is overall trust in the pediatrician, but a lack of trust in the information they provided about vaccines. The survey response rate was 52% (n=443). Parents who refused or delayed vaccines were 2-times more likely to report that they began thinking about vaccines before their child was born, and 8-times more likely to report that they constantly re-evaluate their vaccine decisions than parents who accepted all vaccines. While parents tended to report trusting their pediatrician’s advice on nutrition, behavior and the physical examination, they did not believe their pediatrician provided balanced information on both the benefits and risks of vaccination.
These results have implications for future interventions to address parental vaccination concerns. Such interventions may be more effective if they are applied early (during pregnancy), often (pregnancy through infancy), and cover both the risks and benefits of vaccination.
PMCID: PMC3767928  PMID: 24011751
immunization; vaccine refusal; vaccine decision making; mixed methods
10.  A scan statistic for identifying optimal risk windows in vaccine safety studies using self-controlled case series design 
Statistics in medicine  2013;32(19):3290-3299.
In examining the association between vaccines and rare adverse events after vaccination in post-licensure observational studies, it is challenging to define appropriate risk windows because pre-licensure randomized clinical trials provide little insight on the timing of specific adverse events. Past vaccine safety studies have often used pre-specified risk windows based on prior publications, biological understanding of the vaccine, and expert opinion. Recently, a data driven approach was developed to identify appropriate risk windows for vaccine safety studies that use the self-controlled case series design. This approach employs both the maximum incidence rate ratio and the linear relation between the estimated incidence rate ratio and the inverse of average person time at risk, given a specified risk window. In this paper, we present a scan statistic that can identify appropriate risk windows in vaccine safety studies using the self-controlled case series design while taking into account the dependence of time intervals within an individual and while adjusting for time-varying covariates such as age and seasonality. This approach uses the maximum likelihood ratio test based on fixed effects models, which has been used for analyzing data from self-controlled case series design in addition to conditional Poisson models.
PMCID: PMC4004030  PMID: 23303643
self-controlled case series; adverse events after vaccination; fixed effects model; scan statistics; maximum likelihood ratio test
11.  Sialic Acid Metabolic Engineering: A Potential Strategy for the Neuroblastoma Therapy 
PLoS ONE  2014;9(8):e105403.
Sialic acids (Sia) represent negative-charged terminal sugars on most glycoproteins and glycolipids on the cell surface of vertebrates. Aberrant expression of tumor associated sialylated carbohydrate epitopes significantly increases during onset of cancer. Since Sia contribute towards cell migration ( =  metastasis) and to chemo- and radiation resistance. Modulation of cellular Sia concentration and composition poses a challenge especially for neuroblastoma therapy, due to the high heterogeneity and therapeutic resistance of these cells. Here we propose that Metabolic Sia Engineering (MSE) is an effective strategy to reduce neuroblastoma progression and metastasis.
Human neuroblastoma SH-SY5Y cells were treated with synthetic Sia precursors N-propanoyl mannosamine (ManNProp) or N-pentanoyl mannosamine (ManNPent). Total and Polysialic acids (PolySia) were investigated by high performance liquid chromatography. Cell surface polySia were examined by flow-cytometry. Sia precursors treated cells were examined for the migration, invasion and sensitivity towards anticancer drugs and radiation treatment.
Treatment of SH-SY5Y cells with ManNProp or ManNPent (referred as MSE) reduced their cell surface sialylation significantly. We found complete absence of polysialylation after treatment of SH-SY5Y cells with ManNPent. Loss of polysialylation results in a reduction of migration and invasion ability of these cells. Furthermore, radiation of Sia-engineered cells completely abolished their migration. In addition, MSE increases the cytotoxicity of anti-cancer drugs, such as 5-fluorouracil or cisplatin.
Metabolic Sia Engineering (MSE) of neuroblastoma cells using modified Sia precursors reduces their sialylation, metastatic potential and increases their sensitivity towards radiation or chemotherapeutics. Therefore, MSE may serve as an effective method to treat neuroblastoma.
PMCID: PMC4141789  PMID: 25148252
12.  Patterns of Care and Persistence After Incident Elevated Blood Pressure 
Pediatrics  2013;132(2):e349-e355.
Screening for hypertension in children occurs during routine care. When blood pressure (BP) is elevated in the hypertensive range, a repeat measurement within 1 to 2 weeks is recommended. The objective was to assess patterns of care after an incident elevated BP, including timing of repeat BP measurement and likelihood of persistently elevated BP.
This retrospective study was conducted in 3 health care organizations. All children aged 3 through 17 years with an incident elevated BP at an outpatient visit during 2007 through 2010 were identified. Within this group, we assessed the proportion who had a repeat BP measured within 1 month of their incident elevated BP and the proportion who subsequently met the definition of hypertension. Multivariate analyses were used to identify factors associated with follow-up BP within 1 month of initial elevated BP.
Among 72 625 children and adolescents in the population, 6108 (8.4%) had an incident elevated BP during the study period. Among 6108 with an incident elevated BP, 20.9% had a repeat BP measured within 1 month. In multivariate analyses, having a follow-up BP within 1 month was not significantly more likely among individuals with obesity or stage 2 systolic elevation. Among 6108 individuals with an incident elevated BP, 84 (1.4%) had a second and third consecutive elevated BP within 12 months.
Whereas >8% of children and adolescents had an incident elevated BP, the great majority of BPs were not repeated within 1 month. However, relatively few individuals subsequently met the definition of hypertension.
PMCID: PMC3727670  PMID: 23821694
child; adolescent; hypertension; blood pressure; screening; electronic health records
13.  Pre-consent education about research processes improved African Americans’ willingness to participate in clinical research 
Journal of clinical epidemiology  2011;64(8):872-877.
To determine whether pre-consent education about research processes and protections affects African-Americans’ willingness to participate.
This study examined the willingness of 192 African-American outpatients (stratified by age, gender, and education) to participate in a hypothetical clinical study under varying consent conditions: Phase I participants underwent a typical informed consent process and were asked to indicate whether they would be willing to participate in the hypothetical clinical study and the reasons for their decision; their responses were used to develop a pre-consent educational DVD. Phase II participants viewed the DVD prior to the consent process. We compared the proportion of those who stated they were willing to participate in the clinical study using Fisher’s exact tests, and used qualitative methods to analyze open-ended responses.
When the consent process included education about research processes and protections, significantly more patients reported willingness to participate in the hypothetical clinical study (43% vs. 27%; p=0.002). Patients receiving pre-consent education were significantly less likely to cite mistrust, fear of side effects, lack of perceived benefits, and privacy as reasons for not participating.
Pre-consent education may improve the willingness of African-Americans to participate in clinical research and may address important concerns about research participation.
PMCID: PMC4108901  PMID: 21330104
clinical trial; consent; HIPAA; minority groups; patient participation
14.  Microstructural Changes in the Striatum and Their Impact on Motor and Neuropsychological Performance in Patients with Multiple Sclerosis 
PLoS ONE  2014;9(7):e101199.
Grey matter (GM) damage is a clinically relevant feature of multiple sclerosis (MS) that has been previously assessed with diffusion tensor imaging (DTI). Fractional anisotropy (FA) of the basal ganglia and thalamus might be increased in MS patients, and correlates with disability scores. Despite the established role of the striatum and thalamus in motor control, mood and cognition, the impact of DTI changes within these structures on motor and neuropsychological performance has not yet been specifically addressed in MS. We investigated DTI metrics of deep GM nuclei and their potential association with mobility and neuropsychological function. DTI metrics from 3T MRI were assessed in the caudate, putamen, and thalamus of 30 MS patients and 10 controls. Sixteen of the patients underwent neuropsychological testing. FA of the caudate and putamen was higher in MS patients compared to controls. Caudate FA correlated with Expanded Disability Status Scale score, Ambulation Index, and severity of depressive symptomatology. Putamen and thalamus FA correlated with deficits in memory tests. In contrast, cerebral white matter (WM) lesion burden showed no significant correlation with any of the disability, mobility and psychometric parameters. Our findings support evidence of FA changes in the basal ganglia in MS patients, as well as deep GM involvement in disabling features of MS, including mobility and cognitive impairment. Deep GM FA appears to be a more sensitive correlate of disability than WM lesion burden.
PMCID: PMC4105540  PMID: 25047083
15.  The impact of HIPAA authorization on willingness to participate in clinical research 
Annals of epidemiology  2007;17(11):899-905.
This study systematically examines the impact of inclusion of HIPAA authorization on the willingness of African Americans of diverse sociodemographic characteristics to participate in a clinical research study and explores reasons for non-participation.
For a purposive sample of 384 African American outpatients at 4 metropolitan primary care clinics from August 2005 through May 2006, willingness to participate in a hypothetical clinical research study of an antihypertensive medication under one of two experimental conditions was compared. Interviewees were randomly assigned to undergo informed consent alone (control group) or informed consent with HIPAA authorization (HIPAA group). They were asked whether they would participate and reasons for their decision.
A smaller proportion of interviewees in the HIPAA group were willing to enroll in the study (27% vs. 39%; p=.02), with an adjusted odds ratio = 0.56 (95% confidence interval: 0.36 – 0.91). Those in the HIPAA group were more likely to give reasons related to privacy (p<.001), poor understanding of the form (p=.01), and mistrust or fear of research (p=0.04) for non-participation.
The inclusion of HIPAA authorization within the informed consent process may adversely affect the willingness of African Americans to participate in clinical research and may raise concerns about privacy, understanding the forms, and mistrust or fear of research.
PMCID: PMC4096152  PMID: 17689261
clinical trial; consent form; HIPAA; minority groups; patient participation
16.  Children's Objective Physical Activity by Location: Why the Neighborhood Matters 
Pediatric exercise science  2013;25(3):468-486.
Knowledge of where children are active may lead to more informed policies about how and where to intervene and improve physical activity. This study examined where children aged 6–11 were physically active using time-stamped accelerometer data and parent-reported place logs and assessed the association of physical-activity location variation with demographic factors. Children spent most time and did most physical activity at home and school. Although neighborhood time was limited, this time was more proportionally active than time in other locations (e.g., active 42.1% of time in neighborhood vs. 18.1% of time at home). Children with any neighborhood-based physical activity had higher average total physical activity. Policies and environments that encourage children to spend time outdoors in their neighborhoods could result in higher overall physical activity.
PMCID: PMC4074079  PMID: 23877357
17.  Treatment Satisfaction in Multiple Sclerosis 
Background: Disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) are associated with inconvenient methods of administration, significant side effects, and low adherence rates. This study was undertaken to compare treatment satisfaction in MS patients treated with interferon beta-1a intramuscular (IFNβ-1a IM), interferon beta-1a subcutaneous (IFNβ-1a SC), glatiramer acetate (GA), and natalizumab (NTZ), and to examine the associations between treatment satisfaction ratings and adherence to therapy.
Methods: Two hundred twenty-six treated MS patients completed the Treatment Satisfaction Questionnaire for Medicine. Multivariable models were used to compare treatment satisfaction across groups.
Results: There were no statistically significant differences in overall treatment satisfaction. The NTZ group reported greater satisfaction with the ability of the medication to treat or prevent MS than the IFNβ-1a IM group. The NTZ group also reported higher overall convenience scores than the IFNβ-1a IM group and greater satisfaction with ease of use of the medication than the interferon and GA groups. Patients in the IFNβ-1a IM group reported less satisfaction with ease of planning when to use the medication than those in the other groups. Convenience was associated with adherence in IFNβ-1a SC- and GA-treated patients, with lower convenience scores associated with lower adherence.
Conclusions: These results may be useful to MS patients and health-care providers facing decisions about DMT use.
PMCID: PMC4106393  PMID: 25061430
18.  Use of Fixed Effects Models to Analyze Self-Controlled Case Series Data in Vaccine Safety Studies 
Conditional Poisson models have been used to analyze vaccine safety data from self-controlled case series (SCCS) design. In this paper, we derived the likelihood function of fixed effects models in analyzing SCCS data and showed that the likelihoods from fixed effects models and conditional Poisson models were proportional. Thus, the maximum likelihood estimates (MLEs) of time-varying variables including vaccination effect from fixed effects model and conditional Poisson model were equal. We performed a simulation study to compare empirical type I errors, means and standard errors of vaccination effect coefficient, and empirical powers among conditional Poisson models, fixed effects models, and generalized estimating equations (GEE), which has been commonly used for analyzing longitudinal data. Simulation study showed that both fixed effect models and conditional Poisson models generated the same estimates and standard errors for time-varying variables while GEE approach produced different results for some data sets. We also analyzed SCCS data from a vaccine safety study examining the association between measles mumps-rubella (MMR) vaccination and idiopathic thrombocytopenic purpura (ITP). In analyzing MMR-ITP data, likelihood-based statistical tests were employed to test the impact of time-invariant variable on vaccination effect. In addition a complex semi-parametric model was fitted by simply treating unique event days as indicator variables in the fixed effects model. We conclude that theoretically fixed effects models provide identical MLEs as conditional Poisson models. Because fixed effect models are likelihood based, they have potentials to address methodological issues in vaccine safety studies such as how to identify optimal risk window and how to analyze SCCS data with misclassification of adverse events
PMCID: PMC3976179  PMID: 24707443
Self-controlled case series; Adverse events after immunization; Fixed effects model; Longitudinal data; Conditional Poisson model
Cancer causes & control : CCC  2013;24(4):695-704.
Recognition of the complex, multidimensional relationship between excess adiposity and cancer control outcomes has motivated the scientific community to seek new research models and paradigms.
The National Cancer Institute developed an innovative concept to establish a centers grant mechanism in nutrition, energetics, and physical activity; referred to as the Transdisciplinary Research on Energetics and Cancer (TREC) Initiative. This paper gives an overview of the 2011-2016 TREC Collaborative Network and the 15 research projects being conducted at the Centers.
Four academic institutions were awarded TREC center grants in 2011: Harvard University, University of California San Diego, University of Pennsylvania, and Washington University in St. Louis. The Fred Hutchinson Cancer Research Center is the Coordination Center. The TREC research portfolio includes 3 animal studies, 3 cohort studies, 4 randomized clinical trials, 1 cross-sectional study, and 2 modeling studies. Disciplines represented by TREC investigators include basic science, endocrinology, epidemiology, biostatistics, behavior, medicine, nutrition, physical activity, genetics, engineering, health economics, and computer science. Approximately 41,000 participants will be involved in these studies, including children, healthy adults, and breast and prostate cancer survivors. Outcomes include biomarkers of cancer risk, changes in weight and physical activity, persistent adverse treatment effects (e.g., lymphedema, urinary and sexual function), and breast and prostate cancer mortality.
The NIH Science of Team Science group will evaluate the value-added by this collaborative science. However, the most important outcome will be whether this transdisciplinary initiative improves the health of Americans at risk for cancer as well as cancer survivors.
PMCID: PMC3602225  PMID: 23378138
energetics; obesity; diet; physical activity; cancer; transdisciplinary
20.  Melanoma Genetic Testing, Counseling, and Adherence to Skin Cancer Prevention and Detection Behaviors 
Little is known about the impact of knowledge of CDKN2A and MC1R genotype on melanoma prevention behaviors like sun avoidance and skin examination in the context of familial melanoma.
73 adults with a family history of melanoma were randomly assigned to be offered individualized CDKN2A and MC1R genotyping results in the context of a genetic counseling session, or the standard practice of not being offered counseling or disclosure of genotyping results. Mixed effects or longitudinal logistic models were used to determine whether the intervention affected change in sun protection habits, skin examinations and perception and beliefs related to melanoma risk, prevention, and genetic counseling.
All participants in the intervention group who attended genetic counseling sessions chose to receive their test results. From baseline to follow-up, participants in the intervention group reported an increase in the frequency of skin self-examinations compared to a slight decrease in the control group (p=0.002). Participants in the intervention group reported a smaller decrease in frequency of wearing a shirt with long sleeves than did participants in the control group (p =0.047). No effect of the intervention was noted for other outcomes.
Feedback of CDKN2A and MC1R genotype among families without known pathogenic CDKN2A mutations does not appear to decrease sun protection behaviors.
While disclosure of CDKN2A and MC1R genotype did not have negative effects on prevention, the benefits of communicating this information remain unclear. The small number of families who tested positive for CDKN2A mutations in this study is a limitation.
PMCID: PMC3617083  PMID: 23392000
skin cancer; genetic testing; sun exposure; sun protection; surveys
21.  National Trends in Pharmaceutical Opioid Related Overdose Deaths Compared to other Substance Related Overdose Deaths: 1999-2009 
Drug and alcohol dependence  2013;131(3):263-270.
Pharmaceutical opioid related deaths have increased. This study aimed to place pharmaceutical opioid overdose deaths within the context of heroin, cocaine, psychostimulants, and pharmaceutical sedative hypnotics, examine demographic trends, and describe common combinations of substances involved in opioid related deaths.
We reviewed deaths among 15-64 year olds in the US from 1999-2009 using death certificate data available through the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) Database. We identified International Classification of Disease-10 codes describing accidental overdose deaths, including poisonings related to stimulants, pharmaceutical drugs, and heroin. We used crude and age adjusted death rates (deaths/100,000 person years [p-y] and 95% confidence interval [CI] and multivariable Poisson regression models, yielding incident rate ratios (IRRs), for analysis.
The age adjusted death rate related to pharmaceutical opioids increased almost 4-fold from 1999 to 2009 (1.54/100,000 p-y [95% CI 1.49-1.60] to 6.05/100,000 p-y [95% CI 5.95-6.16; p<0.001). From 1999 to 2009, pharmaceutical opioids were responsible for the highest relative increase in overdose death rates (IRR 4.22, 95% CI 3.03-5.87) followed by sedative hypnotics (IRR 3.53, 95% CI 2.11-5.90). Heroin related overdose death rates increased from 2007 to 2009 (1.05/100,000 persons [95% CI 1.00-1.09] to 1.43/100,000 persons [95% CI 1.38-1.48; p<0.001). From 2005-2009 the combination of pharmaceutical opioids and benzodiazepines was the most common cause of polysubstance overdose deaths (1.27/100,000 p-y (95% CI 1.25-1.30).
Strategies, such as wider implementation of naloxone, expanded access to treatment, and development of new interventions are needed to curb the pharmaceutical opioid overdose epidemic.
PMCID: PMC3935414  PMID: 23294765
Overdose; poisoning; pharmaceutical opioids; stimulants; heroin; mortality
22.  Attitudes and barriers towards participation in an acupuncture trial among breast cancer patients: a survey study 
As breast cancer patients increasingly use complementary and alternative medicine (CAM), clinical trials are needed to guide appropriate clinical use. We sought to identify socio-demographic, clinical and psychological factors related to willingness to participate (WTP) and to determine barriers to participation in an acupuncture clinical trial among breast cancer patients.
We conducted a cross-sectional survey study among post-menopausal women with stage I-III breast cancer on aromatase inhibitors at an urban academic cancer center.
Of the 300 participants (92% response rate), 148 (49.8%) reported WTP in an acupuncture clinical trial. Higher education (p = 0.001), increased acupuncture expectancy (p < 0.001), and previous radiation therapy (p = 0.004) were significantly associated with WTP. Travel difficulty (p = 0.002), concern with experimentation (p = 0.013), and lack of interest in acupuncture (p < 0.001) were significant barriers to WTP. Barriers differed significantly by socio-demographic factors with white people more likely to endorse travel difficulty (p = 0.018) and non-white people more likely to report concern with experimentation (p = 0.024). Older patients and those with lower education were more likely to report concern with experimentation and lack of interest in acupuncture (p < 0.05).
Although nearly half of the respondents reported WTP, significant barriers to participation exist and differ among subgroups. Research addressing these barriers is needed to ensure effective accrual and improve the representation of individuals from diverse backgrounds.
PMCID: PMC3893614  PMID: 24400734
Acupuncture; Breast neoplasm; Clinical trial; Aromatase inhibitors/*adverse effects; Musculoskeletal; Joint pain; Attitudes; Barriers
23.  Objective and Self-Reported Factors Associated With Food-Environment Perceptions and Fruit-And-Vegetable Consumption: A Multilevel Analysis 
Few studies have assessed how people’s perceptions of their neighborhood environment compare with objective measures or how self-reported and objective neighborhood measures relate to consumption of fruits and vegetables.
A telephone survey of 4,399 residents of Philadelphia, Pennsylvania, provided data on individuals, their households, their neighborhoods (self-defined), their food-environment perceptions, and their fruit-and-vegetable consumption. Other data on neighborhoods (census tracts) or “extended neighborhoods” (census tracts plus 1-quarter–mile buffers) came from the US Census Bureau, the Philadelphia Police Department, the Southeastern Pennsylvania Transportation Authority, and the federal Supplemental Nutrition Assistance Program. Mixed-effects multilevel logistic regression models examined associations between food-environment perceptions, fruit-and-vegetable consumption, and individual, household, and neighborhood characteristics.
Perceptions of neighborhood food environments (supermarket accessibility, produce availability, and grocery quality) were strongly associated with each other but not consistently or significantly associated with objective neighborhood measures or self-reported fruit-and-vegetable consumption. We found racial and educational disparities in fruit-and-vegetable consumption, even after adjusting for food-environment perceptions and individual, household, and neighborhood characteristics. Having a supermarket in the extended neighborhood was associated with better perceived supermarket access (adjusted odds ratio for having a conventional supermarket, 2.04 [95% CI, 1.68–2.46]; adjusted odds ratio for having a limited-assortment supermarket, 1.28 [95% CI, 1.02–1.59]) but not increased fruit-and-vegetable consumption. Models showed some counterintuitive associations with neighborhood crime and public transportation.
We found limited association between objective and self-reported neighborhood measures. Sociodemographic differences in individual fruit-and-vegetable consumption were evident regardless of neighborhood environment. Adding supermarkets to urban neighborhoods might improve residents’ perceptions of supermarket accessibility but might not increase their fruit-and-vegetable consumption.
PMCID: PMC3970773  PMID: 24674635
24.  A Pragmatic Framework for Single-site and Multisite Data Quality Assessment in Electronic Health Record-based Clinical Research 
Medical care  2012;50(0):10.1097/MLR.0b013e318257dd67.
Answers to clinical and public health research questions increasingly require aggregated data from multiple sites. Data from electronic health records and other clinical sources are useful for such studies, but require stringent quality assessment. Data quality assessment is particularly important in multisite studies to distinguish true variations in care from data quality problems.
We propose a “fit-for-use” conceptual model for data quality assessment and a process model for planning and conducting single-site and multisite data quality assessments. These approaches are illustrated using examples from prior multisite studies.
Critical components of multisite data quality assessment include: thoughtful prioritization of variables and data quality dimensions for assessment; development and use of standardized approaches to data quality assessment that can improve data utility over time; iterative cycles of assessment within and between sites; targeting assessment toward data domains known to be vulnerable to quality problems; and detailed documentation of the rationale and outcomes of data quality assessments to inform data users. The assessment process requires constant communication between site-level data providers, data coordinating centers, and principal investigators.
A conceptually based and systematically executed approach to data quality assessment is essential to achieve the potential of the electronic revolution in health care. High-quality data allow “learning health care organizations” to analyze and act on their own information, to compare their outcomes to peers, and to address critical scientific questions from the population perspective.
PMCID: PMC3833692  PMID: 22692254
data quality; data quality assessment; single-site studies; multisite studies
25.  Nutrition-Labeling Regulation Impacts on Restaurant Environments 
Recent attempts to improve the healthfulness of away-from-home eating include regulations requiring restaurants to post nutrition information. The impact of such regulations on restaurant environments is unknown.
To examine changes in restaurant environments from before to after nutrition-labeling regulation in a newly regulated county versus a nonregulated county.
Using the Nutrition Environment Measures Surveys–Restaurant version audit, environments within the same quick-service chain restaurants were evaluated in King County (regulated) before and 6 and 18 months after regulation enforcement and in Multnomah County (nonregulated) restaurants over a 6-month period. Data were collected in 2008–2010 and analyses conducted in 2011.
Overall availability of healthy options and facilitation of healthy eating did not differentially increase in King County versus Multnomah County restaurants aside from the substantial increase in onsite nutrition information posting in King County restaurants required by the new regulation. Barriers to healthful eating decreased in King County relative to Multnomah County restaurants, particularly in food-oriented establishments. King County restaurants demonstrated modest increases in signage that promotes healthy eating, although the frequency of such promotion remained low, and the availability of reduced portions decreased in these restaurants. The healthfulness of children’s menus improved modestly over time, but not differentially by county.
A restaurant nutrition-labeling regulation was accompanied by some, but not uniform, improvements in other aspects of restaurant environments in the regulated compared to the nonregulated county. Additional opportunities exist for improving the healthfulness of awayfrom- home eating beyond menu labeling.
PMCID: PMC3479434  PMID: 23079173

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