Publications by authors named "Neha Trivedi"

39 Publications

Communication research at the National Cancer Institute, 2013-2019: a grant portfolio analysis.

Cancer Causes Control 2021 Jul 27. Epub 2021 Jul 27.

Health Communication and Informatics Research Branch, Division of Cancer Control and Population Sciences, 9609 Medical Center Drive, National Cancer Institute, Rockville, MD, 20850, USA.

Purpose: To analyze communication-focused grants funded by the National Cancer Institute (NCI) between fiscal years 2013 and 2019 to provide insight into the characteristics of funded projects and identify promising areas for future research.

Methods: iSearch, a portfolio analysis tool, was queried to identify communication-related grants funded by NCI. Abstracts and specific aims were coded for key study characteristics. 344 unique competing grants with a substantial communication component were included in the final analysis. SAS version 9.4 was used to calculate code frequencies.

Results: Most communication grants focused on cancer prevention (n = 197), with fewer targeting diagnosis, treatment, survivorship, or end-of-life. Tobacco product use was the most frequently addressed topic (n = 128). Most grants targeted or measured outcomes at the individual (n = 332) or interpersonal level (n = 127). Cancer patients/survivors (n = 101) and healthcare providers (n = 63) were often the population of focus, while caregivers or those at increased risk for cancer received less attention. Studies were often based in healthcare settings (n = 125); few studies were based in schools or worksites. Many grants employed randomized controlled trials (n = 168), but more novel methods, like optimization trials, were uncommon.

Conclusion: NCI's support of health communication research covers a diverse array of topics, populations, and methods. However, the current analysis also points to several promising opportunities for future research, including efforts focused on communication at later stages of the cancer control continuum and at multiple levels of influence, as well as studies that take advantage of a greater diversity of settings and leverage novel methodological approaches.
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http://dx.doi.org/10.1007/s10552-021-01481-7DOI Listing
July 2021

Degradation studies of pendimethalin by indigenous soil bacterium Pseudomonas strain PD1 using spectrophotometric scanning and FTIR.

Arch Microbiol 2021 Sep 19;203(7):4499-4507. Epub 2021 Jun 19.

Department of Biochemistry, College of Basic Science and Humanities, Govind Ballabh Pant University of Agriculture and Technology, Pantnagar, Uttarakhand, 263145, India.

In this study pendimethalin degrading indigenous soil bacterium was isolated from rice field (supplemented with pendimethalin) and identified as, Pseudomonas strain PD1 on the basis of 16S rRNA phylogenetic analysis. Biodegradation of pendimethalin by this strain was evaluated by spectrophotometric scanning and FTIR analysis of degraded compounds in minimal salt media. Decrease in concentration of pendimethalin at λ (430 nm) under spectrophotometric scanning is a measurement of time taken by bacterium strain PD1 to degrade pendimethalin. Degraded products were further analyzed by comparing stretching and bending pattern of chemical groups attached to compounds using FTIR spectroscopy. FTIR profile represented disappearance of nitrate group in degraded product by bacterium strain PD1 in minimal salt medium. Molecular docking of pendimethalin on nitro-reductase was done to suggest first enzyme of pathway used by bacterium strain PD1 to degrade pendimethalin. Analysis on degradation by strain PD1 shows that newly isolated strain PD1 can degrade 77.05% of pendimethalin at 50 mgL concentration in 30 h incubation under room temperature. Thus, the study here shed a light on degradation potential of Pseudomonas.
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http://dx.doi.org/10.1007/s00203-021-02439-8DOI Listing
September 2021

Factors Associated with Cancer Message Believability: a Mixed Methods Study on Simulated Facebook Posts.

J Cancer Educ 2021 Jun 19. Epub 2021 Jun 19.

Behavioral Research Program, Health Communication and Informatics Research Branch, National Cancer Institute, 9609 Medical Center Drive, 3E624, Bethesda, MD, 20892, USA.

The ability to share and obtain health information on social media (SM) places higher burden on individuals to evaluate the believability of such health messages given the growing nature of misinformation circulating on SM. Message features (i.e., format, veracity), message source, and an individual's health literacy all play significant roles in how a person evaluates health messages on SM. This study assesses how message features and SM users' health literacy predict assessment of message believability and time spent looking at simulated Facebook messages. SM users (N = 53) participated in a mixed methods experimental study, using eye-tracking technology, to measure relative time and message believability. Measures included individual health literacy, message format (narrative/non-narrative), and information veracity (evidence-based/non-evidence-based). Results showed individuals with adequate health literacy rated evidence-based posts as more believable than non-evidence-based posts. Additionally, individuals with limited health literacy spent more relative time on the source compared to individuals with adequate health literacy. Public health and health communication efforts should focus on addressing myths and misinformation found on SM. Additionally, the source of message may be equally important when evaluating messages on SM, and strategies should identify reliable sources to prevent limited health literate individuals from falling prey to misinformation.
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http://dx.doi.org/10.1007/s13187-021-02054-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213533PMC
June 2021

Using Social Media for Health: National Data from HINTS 2019.

J Health Commun 2021 03 15;26(3):184-193. Epub 2021 Apr 15.

Behavioral Research Program, Health Communication and Informatics Research Branch, National Cancer Institute, Rockville, Maryland, USA.

Social media (SM) have fundamentally changed the way we exchange information, including how we communicate about health. The goal of this study was to describe current prevalence and predictors of SM use by analyzing nationally representative data from the 2019 Health Information National Trends Survey (HINTS). Multivariate logistic regression models examined the odds of engaging in four SM activities: visiting social networking sites, sharing health information on SM, participating in online support groups, and watching health-related videos. In 2019, approximately 86% of Internet users reported engaging in at least one SM activity. Younger age and female gender were associated with higher likelihood of engaging in all SM activities. No significant ethnic/racial disparities were observed for most SM activities, but Hispanics were found to be more likely to report watching health-related videos. Additionally, those with regular health care access were more likely to participate in online support groups. Previous HINTS survey cycles were also used to examine change in SM use over time, showing that general SM use has increased substantially since 2007, but the use of SM for health-related purposes has not increased to the same extent. The dynamic and evolving nature of SM makes systematic assessment vital. Knowledge of current SM use patterns could make health communication efforts more effective and equitable.
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http://dx.doi.org/10.1080/10810730.2021.1903627DOI Listing
March 2021

Predictors of Patient-Centered Communication among U.S. Adults: Analysis of the 2017-2018 Health Information National Trends Survey (HINTS).

J Health Commun 2021 01 1;26(1):57-64. Epub 2021 Mar 1.

Behavioral Research Program, Health Communication and Informatics Research Branch, National Cancer Institute, Rockville, MD USA.

An essential component of patient-centered care is the communication between patients and their providers, which can affect patients' health outcomes A cancer care model, developed by Epstein and Street, includes a multi-dimensional patient-centered communication (PCC) framework with six functions: foster healing relationships, exchange information, respond to emotions, manage uncertainty, make decisions, and enable patient self-management. Seven domains that describe the functions were included on the Health Information National Trends Survey (HINTS) to assess PCC. We examined the association between sociodemographic and health-related factors and PCC as well as how U.S. adults, by different age groups, ranked different domains of PCC.Nationally representative data (n = 5,738) from 2017 to 2018 HINTS were merged to examine predictors of PCC among U.S. adults. Weighted statistics describe the study sample and prevalence for ratings of PCC domains. A multivariate linear regression model was computed to assess associations among predictors and PCC.Participants rated their communication with doctors in the last year with an overall mean of 80 out of 100. Older age, those reporting excellent health, and those with higher confidence in taking care of one's health predicted better PCC. Individuals who reported being non-Hispanic Asian and having lower household income were associated with poorer communication. Participants' lowest rating of PCC concentrated on providers dealing with their emotional needs.Findings suggest that many patients do not feel that their providers adequately manage, communicate, nor respond to their emotional needs. Future efforts should enhance interpersonal exchanges among sub-populations who report poorer communication with providers during clinical visits.
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http://dx.doi.org/10.1080/10810730.2021.1878400DOI Listing
January 2021

Barriers to accessing online medical records in the United States.

Am J Manag Care 2021 01;27(1):33-40

Health Communication and Informatics Research Branch, Behavioral Research Program, National Cancer Institute, 9609 Medical Center Dr, 3E624, Bethesda, MD 20892. Email:

Objectives: Patients' access to and use of online medical records (OMRs) can facilitate better management of their health and health care. However, health care disparities continue to exist. This study aimed to (1) determine the prevalence and predictors of individuals being offered access to OMRs, (2) identify predictors of individuals accessing their OMR, and (3) describe barriers to accessing one's OMR.

Study Design: Secondary analyses of cross-sectional data from Health Information National Trends Survey 5, cycles 1 and 2 (n = 6670).

Methods: Multivariable logistic regression analyses were used to examine the association between sociodemographic and health care-related factors on being offered access to OMRs, accessing OMRs, and cited reasons for not accessing OMRs.

Results: In 2017-2018, 54% of US adults reported having been offered access to OMRs, and among those offered, 57% reported accessing their records. The groups who were less likely to be offered OMRs included men, middle-aged adults, members of racial/ethnic minority groups, individuals with lower education and household incomes, those who do not use the internet, and those living in rural areas. Respondents who were less likely to access their OMRs despite being offered included individuals with lower education and household incomes and rural residents. Among the 43% who did not access their records, the primary reason for not accessing was their preference to speak to their provider directly.

Conclusions: Sociodemographic and health care-related factors are associated with variation in use of OMRs. To realize the intended value of OMR use for patients, it is important to address barriers to OMR access and integrate OMRs into patient-provider communication and clinical care.
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http://dx.doi.org/10.37765/ajmc.2021.88575DOI Listing
January 2021

Prevalence and Correlates of Family Cancer History Knowledge and Communication Among US Adults.

Prev Chronic Dis 2020 11 19;17:E146. Epub 2020 Nov 19.

Health Communication and Informatics Research Branch, National Cancer Institute, Bethesda, Maryland.

Introduction: Knowing one's family cancer history (FCH) plays an important role in cancer prevention. Communicating health histories with relatives can increase awareness about familial cancer risk and aid health care providers in personalizing cancer prevention recommendations.

Methods: This study used data from the National Cancer Institute's 2018 Health Information National Trends Survey. We calculated frequencies and weighted population estimates for key FCH communication variables. Multivariable logistic regression models estimated associations between sociodemographic characteristics and FCH communication.

Results: Findings provide the first nationally representative estimates of FCH communication. Less than one-third (31.1%) of the population reported knowing FCH very well, 70.0% had discussed FCH with at least 1 biological relative, 39.0% had discussed FCH with a health care provider, and 22.2% reported being completely confident in completing FCH on medical forms. Findings also identified key demographic factors, including sex, household income, education level, and race and ethnicity, associated with these FCH measures among the US adult population.

Conclusion: Results can be used to target and tailor FCH communication interventions for patients, families, and providers.
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http://dx.doi.org/10.5888/pcd17.200257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735478PMC
November 2020

Health Literacy Research Funded by the NIH for Disease Prevention.

Health Lit Res Pract 2020 11;4(4):e212-e223

Background: Advancing health literacy is a fundamental step toward achieving population health. To that end, the National Institutes of Health (NIH) funded research to increase scientific understanding of how health literacy can reduce disparities and enhance the health of the United States.

Objective: This study identified and evaluated NIH-funded health literacy research focusing on disease prevention.

Methods: New R01, R03, and R21 research project grants awarded from fiscal year (FY) 2004 to FY 2017 studying health literacy and disease prevention were identified. Study characteristics, including the role of health literacy, how health literacy was measured, populations studied, and study design, were coded for each grant. Administrative grant data were obtained from the NIH's internal database. Research impact was assessed using the relative citation ratio (RCR).

Key Results: There were 192 grants studying health literacy and disease prevention awarded by 18 NIH institutes and centers from FY 2004 to FY 2017, covering a wide variety of health conditions including cancer (26.0%), infectious diseases (13.5%), nutrition (8.3%), drug/alcohol use (7.8%), and cardiovascular disease (6.3%). Most grants studied the health literacy skills of patients (88%), with a few studies assessing the health literacy practices of health care providers (2.1%) or systems (1%). There was good representation of populations with traditionally low levels of health literacy, including Black/African American participants (30.2%), Hispanic/Latinx participants (28.6%), older adults (37%), and people with low income (20.8%). The scientific articles generated by these grants were more than twice (RCR = 2.18) as influential on the field as similar articles.

Conclusions: The NIH provided support for a wide array of prevention-focused health literacy research. The value of this research is highlighted by the number of funding institutes and centers, the diversity of populations and health conditions studied, and the effect these grants had on the field. Future research should move beyond patient-level health literacy to health literacy practices of health care systems and providers. [HLRP: Health Literacy Research and Practice. 2020, 4(4):e212-e223.] PLAIN LANGUAGE SUMMARY: This study describes health literacy research funded by the National Institutes of Health that focused on disease prevention. These grants sought to prevent a variety of health conditions, but health literacy research over the past 14 years continued to concentrate on the capacity of patients despite increased attention on the health literacy practices of health care providers and systems.
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http://dx.doi.org/10.3928/24748307-20200928-01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330440PMC
November 2020

Universal SARS-Cov-2 Screening in Women Admitted for Delivery in a Large Managed Care Organization.

Am J Perinatol 2020 09 3;37(11):1110-1114. Epub 2020 Jul 3.

Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has created a need for data regarding the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnant women. After implementing universal screening for COVID-19 in women admitted for delivery, we sought to describe the characteristics of COVID-19 in this large cohort of women.

Study Design: An observational study of women admitted to labor and delivery units in Kaiser Permanente Southern California (KPSC) hospitals between April 6 and May 11, 2020 who were universally offered testing for SARS-CoV-2 infection ( = 3,963). Hospital inpatient and outpatient physician encounter, and laboratory records were used to ascertain universal testing levels, test results, and medical and obstetrical histories. The prevalence of SARS-CoV-2 infection was estimated from the number of women who tested positive during labor per 100 women delivered.

Results: Of women delivered during the study period, 3,923 (99.0%) underwent SARS-CoV-2 testing. A total of 17 (0.43%; 95% confidence interval: 0.23-0.63%) women tested positive, and none of them were symptomatic on admission. There was no difference in terms of characteristics between SARS-CoV-2 positive and negative tested women. One woman developed a headache attributed to COVID-19 3 days postpartum. No neonates had a positive test at 24 hours of life.

Conclusion: The findings suggest that in pregnant women admitted for delivery between April 6 and May 11, 2020 in this large integrated health care system in Southern California, prevalence of SARS-CoV-2 test positive was very low and all patients were asymptomatic on admission.

Key Points: · The prevalence of SARS-CoV-2 infection in a large diverse cohort of term pregnant women was 0.43%.. · 99% of women accepted SARS-CoV-2 screening on admission to labor and delivery.. · All women with positive test results were asymptomatic at the time of testing..
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http://dx.doi.org/10.1055/s-0040-1714060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516390PMC
September 2020

Re-Prioritizing Digital Health and Health Literacy in to Affect Health Equity.

Health Commun 2021 Sep 30;36(10):1155-1162. Epub 2020 Apr 30.

Center for Health Literacy, School of Public Health, University of Maryland.

The U.S. health objective-setting process has taken place in an inequitable social structure with significant implications for health literacy, health equity, and population health. The draft 2030 objectives have greatly reduced the number of digital health and health literacy objectives, meaning our national agenda is poised to capture only a fraction of what will evolve in digital and health literacy between 2020 and 2030. This paper synthesizes two decades of Healthy People data on health literacy and digital health objectives, highlights the digital health and health literacy trends and disparities that persist and proposes remedies to ensure that health literacy and digital health issues receive the attention they deserve in the next decade. These remedies can inform policies, research, and interventions that touch health communication and digital health issues.
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http://dx.doi.org/10.1080/10410236.2020.1748828DOI Listing
September 2021

How do social media users process cancer prevention messages on Facebook? An eye-tracking study.

Patient Educ Couns 2020 06 28;103(6):1161-1167. Epub 2020 Jan 28.

George Mason University, 4400 University Dr., MS 3D6, Fairfax, VA 22030, United States.

Objective: The quality of cancer-related information on social media (SM) is mixed, and exposure to inaccurate information may negatively affect knowledge, attitudes, and behaviors. This study examines SM users' attention to simulated Facebook posts related to cancer and identifies message features associated with increased attention.

Methods: SM users (N = 53) participated in a mixed methods experimental study using eye-tracking technology, whereby participants' dwell time on message components was measured. Stimuli conditions included message format (narrative/non-narrative), information veracity, source (organization/individual), and cancer topic (HPV vaccine and sunscreen safety).

Results: Pixel-size adjusted analyses revealed that average dwell time was longer on posts attributed to individuals and on narrative-based posts. The source of the message received nearly the same amount of dwell time as the text. Dwell time on other message components did not significantly differ by condition.

Conclusion: This study found that the source of a message attracted substantial attention, whereas other features were not associated with attention. The study illustrates how communication research can help us understand the processing of ubiquitous cancer-related messages on SM.

Practical Implications: Health communication practitioners should consider message features that garner attention when developing efforts to facilitate the exchange of evidence-based information and to mitigate the harms of misinformation.
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http://dx.doi.org/10.1016/j.pec.2020.01.013DOI Listing
June 2020

Systematic review of barriers and facilitators to clinical trial enrollment among adolescents and young adults with cancer: Identifying opportunities for intervention.

Cancer 2020 03 23;126(5):949-957. Epub 2019 Dec 23.

Department of Pediatrics, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Adolescents and young adults (AYAs) are underrepresented in cancer clinical trials (CCTs). Limited trial enrollment slows progress in improving survival rates and prevents the collection of valuable biospecimens. A systematic literature review was conducted to assess barriers and facilitators to AYA enrollment in CCTs and to identify opportunities to improve enrollment. The PubMed MEDLINE, Web of Science, Scopus, and PsycINFO databases were searched to identify studies relevant to AYA CCT enrollment. Eligibility criteria included the qualitative and/or quantitative evaluation of barriers and facilitators to AYA enrollment. One hundred fifty-five unique publications were identified; 13 were included in the final analysis. Barriers to AYA enrollment in CCTs included a lack of existing trials applicable to the patient population, limited access to available CCTs, and a lack of physician awareness of relevant trials. Facilitators of enrollment included optimizing the research infrastructure, improving the awareness of available CCTs among providers, and enhancing communication about CCTs between providers and patients. In conclusion, the limited available research reports institution- and patient-level barriers and facilitators to AYA CCT enrollment. Because of persistent disparities in AYA enrollment, there is an urgent need to further identify the barriers and facilitators to AYA CCT enrollment to determine actionable areas for intervention.
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http://dx.doi.org/10.1002/cncr.32675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029803PMC
March 2020

Communication and Control: Hearing the Voices of Low-Income African American Adults to Improve Relationships with Healthcare Providers.

Health Commun 2020 11 16;35(13):1633-1642. Epub 2019 Aug 16.

Department of Communication, University of Maryland.

Patient-provider relationships can either impede or encourage patient utilization of healthcare services and adherence to treatment. Given the significant health disparities found among low-income African Americans, it is imperative to understand this population's experiences with healthcare providers and how to improve their patient-provider relationships in order to increase successful treatment outcomes. Relationship management is a well-tested theory that examines factors that improve outcomes between organizations and their publics. This exploratory study uses relationship management theory to understand how African Americans who are medically underserved perceive the quality of their relationships with healthcare providers. Focus groups were held with low-income African American adults. Findings reveal that communication is key to improving trust, but other characteristics needed for a quality relationship were lacking, particularly perceived commitment, which impedes better healthcare. The low-income, medically underserved context influenced participant perceptions of factors such as commitment, but participants also expressed efficacy in feeling in control of healthcare situations, which may help them maintain quality relationships. This study offers theoretical elaboration as well as practical suggestions for how providers may wish to address an important population of patients through communication.
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http://dx.doi.org/10.1080/10410236.2019.1654177DOI Listing
November 2020

Awareness of Palliative Care among a Nationally Representative Sample of U.S. Adults.

J Palliat Med 2019 12 30;22(12):1578-1582. Epub 2019 Apr 30.

Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland.

Palliative care can alleviate symptom burden, reduce psychosocial distress, and improve quality of life for patients suffering from serious or life-threatening illnesses. However, the extent to which U.S. adults are aware of or understand the goals and benefits of palliative care is not well understood. Public awareness of palliative care is necessary to change norms and create demand, and as such, limited awareness may be a significant barrier to palliative care uptake. An assessment of current palliative care awareness in the United States is needed to inform the health care sector's improving palliative care communication and delivery. To examine the prevalence of palliative care awareness among a nationally-representative sample of U.S. adults and to identify sociodemographic and health-related characteristics associated with palliative care awareness. Weighted data from the Health Information National Trends Survey (HINTS 5, Cycle 2 [2018],  = 3445) were used to produce frequencies of the characteristics, and associations with palliative care awareness were determined through multiple logistic regression. An estimated 71% of U.S. adults reported having never heard of palliative care. Older individuals, those with higher educational attainment, women, and whites (vs. nonwhites) had greater odds of palliative care awareness. These data suggest there is limited awareness of palliative care in the United States, despite its documented benefits. Addressing this awareness gap is a priority to change norms around using palliative care services. Community- and population-based interventions are necessary to raise awareness and inform the public about palliative care.
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http://dx.doi.org/10.1089/jpm.2018.0656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998043PMC
December 2019

Sonographic detection of an infected maternal urachal cyst during pregnancy.

J Clin Ultrasound 2018 Jun 5;46(5):355-357. Epub 2017 Oct 5.

Department of OBGYN, Division of Maternal Fetal Medicine, Kaiser Permanente San Diego Medical Center, San Diego, California.

Infection of a maternal urachal cyst during pregnancy is rare; Sonography is an important diagnostic tool that can help minimize maternal and fetal complications. We describe the case of a 35-year-old multiparous woman presenting in the third trimester with 2 weeks of fever, abdominal pain, and urinary symptoms. Imaging showed a 5-cm complex anterior midline mass, found intraoperatively to be eroding into the uterus. Sonographic imaging aided in the diagnosis and management of the urachal cyst, and antepartum sonographic measurements of the lower uterine segment helped to counsel regarding a trial of labor. Following treatment, the patient stabilized and had an uncomplicated vaginal delivery.
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http://dx.doi.org/10.1002/jcu.22540DOI Listing
June 2018

Cell Phone Use While Driving: Prospective Association with Emerging Adult Use.

Accid Anal Prev 2017 Sep 20;106:450-455. Epub 2017 Jul 20.

Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Secondary task engagement such as cell phone use while driving is a common behavior among adolescents and emerging adults. Texting and other distracting cell phone use in this population contributes to the high rate of fatal car crashes. Peer engagement in similar risky driving behaviors, such as texting, could socially influence driver phone use behavior. The present study investigates the prospective association between peer and emerging adult texting while driving the first year after high school. Surveys were conducted with a national sample of emerging adults and their nominated peers. Binomial logistic regression analyses, adjusting for gender, race/ethnicity, parental education, and family affluence, showed that participants (n=212) with peers (n=675) who reported frequently texting while driving, were significantly more likely to text while driving the following year (odds ratio, 3.01; 95% CI, 1.19-7.59; P=0.05). The findings are consistent with the idea that peer texting behavior influences the prevalence of texting while driving among emerging adults.
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http://dx.doi.org/10.1016/j.aap.2017.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610622PMC
September 2017

Switch in Site of Inhibition: A Strategy for Structure-Based Discovery of Human Topoisomerase IIα Catalytic Inhibitors.

ACS Med Chem Lett 2015 Apr 23;6(4):481-5. Epub 2015 Feb 23.

School of Biotechnology, KIIT University , Campus-11, Patia, Bhubaneswar, Orissa 751024, India.

A study of structure-based modulation of known ligands of hTopoIIα, an important enzyme involved in DNA processes, coupled with synthesis and in vitro assays led to the establishment of a strategy of rational switch in mode of inhibition of the enzyme's catalytic cycle. 6-Arylated derivatives of known imidazopyridine ligands were found to be selective inhibitors of hTopoIIα, while not showing TopoI inhibition and DNA binding. Interestingly, while the parent imidazopyridines acted as ATP-competitive inhibitors, arylated derivatives inhibited DNA cleavage similar to merbarone, indicating a switch in mode of inhibition from ATP-hydrolysis to the DNA-cleavage stage of catalytic cycle of the enzyme. The 6-aryl-imidazopyridines were relatively more cytotoxic than etoposide in cancer cells and less toxic to normal cells. Such unprecedented strategy will encourage research on "choice-based change" in target-specific mode of action for rapid drug discovery.
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http://dx.doi.org/10.1021/acsmedchemlett.5b00040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416441PMC
April 2015

Matched miRNA and mRNA signatures from an hESC-based in vitro model of pancreatic differentiation reveal novel regulatory interactions.

J Cell Sci 2013 Sep 26;126(Pt 17):3848-61. Epub 2013 Jun 26.

Department of Reproductive Medicine, University of California, San Diego, California, USA.

The differentiation of human pluripotent stem cells (hPSCs) to insulin-expressing beta islet-like cells is a promising in vitro model system for studying the molecular signaling pathways underlying beta cell differentiation, as well as a potential source of cells for the treatment of type 1 diabetes. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate many biological processes, including cellular differentiation. We studied the miRNA and mRNA expression profiles of hPSCs at five stages of in vitro differentiation along the pancreatic beta cell lineage (definitive endoderm, primitive gut tube, posterior foregut, pancreatic progenitor and hormone-expressing endocrine cells) in the context of samples of primary human fetal pancreas and purified adult islet cells using microarray analysis. Bioinformatic analysis of the resulting data identified a unique miRNA signature in differentiated beta islet cells, and predicted the effects of key miRNAs on mRNA expression. Many of the predicted miRNA-mRNA interactions involved mRNAs known to play key roles in the epithelial-mesenchymal transition process and pancreatic differentiation. We validated a subset of the predictions using qRT-PCR, luciferase reporter assays and western blotting, including the known interaction between miR-200 and ZEB2 (involved in epithelial-mesenchymal transition) and the novel interaction between miR-200 and SOX17 (a key transcription factor in specification of definitive endoderm). In addition, we found that miR-30d and let-7e, two miRNAs induced during differentiation, regulated the expression of RFX6, a transcription factor that directs pancreatic islet formation. These findings suggest that precise control of target mRNA expression by miRNAs ensures proper lineage specification during pancreatic development.
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http://dx.doi.org/10.1242/jcs.123570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757328PMC
September 2013

Two-dimensional sonographic cine imaging improves confidence in the initial evaluation of the fetal heart.

J Ultrasound Med 2013 Jun;32(6):963-71

Departments of Radiology, University of California, San Diego, California USA.

Objectives: Initial screening sonography of the fetal heart with static images is often inadequate, resulting in repeated imaging or failure to detect abnormalities. We hypothesized that the addition of short cine clips would reduce the need for repeated imaging.

Methods: Two-dimensional (2D) static sonograms and short 2D cine clips of the 4-chamber view and left and right ventricular outflow tracts were obtained from 342 patients with gestational ages of greater than 16 weeks. A diagnostic radiologist and a perinatologist retrospectively reviewed the static and cine images independently and graded them as normal, abnormal, or suboptimal.

Results: A statistically significant increase in the number of structures called normal was seen when 2D cine clips were added to static imaging for both observers (P < .05); the radiologist called 86.5% normal with combined static and cine images versus 61.9% with static images alone, whereas the perinatologist recorded 68.1% as normal versus 58.8%, respectively. The radiologist called 77.8% of structures normal with cine images only versus 61.9% with static images only (P < .001), whereas the perinatologist called fewer structures normal with cine images alone (38.9%) versus static images alone (58.8%). The use of cine loops alone resulted in no significant increase in the ability to clear the heart as normal. The maternal body mass index was inversely associated with the ability to clear structures when 2D cine images were added to static images (P < .05).

Conclusions: The addition of 2D cine clips to standard 2D static imaging of the fetal heart significantly improves the number of structures cleared as normal. Two-dimensional cine clips are easily obtained, add little time to a study, and require minimal archival space.
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http://dx.doi.org/10.7863/ultra.32.6.963DOI Listing
June 2013

Modeling the closed and open state conformations of the GABA(A) ion channel--plausible structural insights for channel gating.

J Chem Inf Model 2012 Nov 12;52(11):2958-69. Epub 2012 Nov 12.

Structural Biology and Bioinformatics Division, CSIR - Indian Institute of Chemical Biology, Kolkata -700 032, India.

Recent disclosure of high resolution crystal structures of Gloeobacter violaceus (GLIC) in open state and Erwinia chrysanthemii (ELIC) in closed state provides newer avenues to advance our knowledge and understanding of the physiologically and pharmacologically important ionotropic GABA(A) ion channel. The present modeling study envisions understanding the complex molecular transitions involved in ionic conductance, which were not evident in earlier disclosed homology models. In particular, emphasis was put on understanding the structural basis of gating, gating transition from the closed to the open state on an atomic scale. Homology modeling of two different physiological states of GABA(A) was carried out using their respective templates. The ability of induced fit docking in breaking the critical inter residue salt bridge (Glu155β(2) and Arg207β(2)) upon endogenous GABA docking reflects the perceived side chain rearrangements that occur at the orthosteric site and consolidate the quality of the model. Biophysical calculations like electrostatic mapping, pore radius calculation, ion solvation profile, and normal-mode analysis (NMA) were undertaken to address pertinent questions like the following: How the change in state of the ion channel alters the electrostatic environment across the lumen; How accessible is the Cl(-) ion in the open state and closed state; What structural changes regulate channel gating. A "Twist to Turn" global motion evinced at the quaternary level accompanied by tilting and rotation of the M2 helices along the membrane normal rationalizes the structural transition involved in gating. This perceived global motion hints toward a conserved gating mechanism among pLGIC. To paraphrase, this modeling study proves to be a reliable framework for understanding the structure function relationship of the hitherto unresolved GABA(A) ion channel. The modeled structures presented herein not only reveal the structurally distinct conformational states of the GABA(A) ion channel but also explain the biophysical difference between the respective states.
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http://dx.doi.org/10.1021/ci300189aDOI Listing
November 2012

Inviting patients to read their doctors' notes: a quasi-experimental study and a look ahead.

Ann Intern Med 2012 Oct;157(7):461-70

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

Background: Little information exists about what primary care physicians (PCPs) and patients experience if patients are invited to read their doctors' office notes.

Objective: To evaluate the effect on doctors and patients of facilitating patient access to visit notes over secure Internet portals.

Design: Quasi-experimental trial of PCPs and patient volunteers in a year-long program that provided patients with electronic links to their doctors' notes.

Setting: Primary care practices at Beth Israel Deaconess Medical Center (BIDMC) in Massachusetts, Geisinger Health System (GHS) in Pennsylvania, and Harborview Medical Center (HMC) in Washington.

Participants: 105 PCPs and 13,564 of their patients who had at least 1 completed note available during the intervention period.

Measurements: Portal use and electronic messaging by patients and surveys focusing on participants' perceptions of behaviors, benefits, and negative consequences.

Results: 11,155 [corrected] of 13,564 patients with visit notes available opened at least 1 note (84% at BIDMC, 82% [corrected] at GHS, and 47% at HMC). Of 5219 [corrected] patients who opened at least 1 note and completed a postintervention survey, 77% to 59% [corrected] across the 3 sites reported that open notes helped them feel more in control of their care; 60% to 78% of those taking medications reported increased medication adherence; 26% to 36% had privacy concerns; 1% to 8% reported that the notes caused confusion, worry, or offense; and 20% to 42% reported sharing notes with others. The volume of electronic messages from patients did not change. After the intervention, few doctors reported longer visits (0% to 5%) or more time addressing patients' questions outside of visits (0% to 8%), with practice size having little effect; 3% to 36% of doctors reported changing documentation content; and 0% to 21% reported taking more time writing notes. Looking ahead, 59% to 62% of patients believed that they should be able to add comments to a doctor's note. One out of 3 patients believed that they should be able to approve the notes' contents, but 85% to 96% of doctors did not agree. At the end of the experimental period, 99% of patients wanted open notes to continue and no doctor elected to stop.

Limitations: Only 3 geographic areas were represented, and most participants were experienced in using portals. Doctors volunteering to participate and patients using portals and completing surveys may tend to offer favorable feedback, and the response rate of the patient surveys (41%) may further limit generalizability.

Conclusion: Patients accessed visit notes frequently, a large majority reported clinically relevant benefits and minimal concerns, and virtually all patients wanted the practice to continue. With doctors experiencing no more than a modest effect on their work lives, open notes seem worthy of widespread adoption.

Primary Funding Source: The Robert Wood Johnson Foundation, the Drane Family Fund, the Richard and Florence Koplow Charitable Foundation, and the National Cancer Institute.
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http://dx.doi.org/10.7326/0003-4819-157-7-201210020-00002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908866PMC
October 2012

Placental histologic criteria for diagnosis of cord accident: sensitivity and specificity.

Pediatr Dev Pathol 2012 Jul-Aug;15(4):275-80. Epub 2012 Mar 8.

Department of Pathology, University of California San Diego, La Jolla, CA, USA.

"Cord accident" (compromised umbilical blood flow) as a cause of stillbirth is underreported, mainly due to a lack of diagnostic criteria. Based on fetal vascular pathology in the placenta, we have previously established histologic criteria for the diagnosis of cord accident. In the current study, we set out to test the sensitivity and specificity of these criteria by reviewing an independent set of stillbirth cases. Placental slides from 26 cases (in which cord accident was deemed the cause of death) and 62 controls (in which the cause of death was anything other than cord accident) were reviewed. The following histologic changes were noted: (1) dilated fetal vessels, (2) thrombosis in fetal vessels, and (3) avascular or near-avascular chorionic villi. "Minimal" criteria were defined as the presence of dilated and thrombosed fetal vessels, while the additional presence of focal or regional avascular or near-avascular villi satisfied the complete criteria. Of the 62 stillbirth controls with cause of death other than cord accident, 13 (21%) met the minimal criteria (specificity 79%) and only 4 (6%) met the complete criteria for cord accident (specificity 94%). In contrast, of the 26 cases with a cause of death related to cord accident, 16 met the minimal criteria (sensitivity 62%) and 12 met the complete criteria (sensitivity 46%). These histologic criteria identify cases of cord accident as a cause of stillbirth with very high specificity. This study confirms the utility of these criteria for diagnosis of cord accident and further stresses placental examination in evaluation of stillbirths.
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http://dx.doi.org/10.2350/11-12-1127-OA.1DOI Listing
November 2012

Congenital cardiac anomalies: prenatal readings versus neonatal outcomes.

J Ultrasound Med 2012 Mar;31(3):389-99

Department of Reproductive Medicine, Perinatal Division, University of California San Diego Medical Center, San Diego, La Jolla, CA 92037, USA.

Objective: The purpose of this study was to determine the variation between prenatal and postnatal diagnosis of congenital cardiac lesions diagnosed by both fetal center primary physicians and fetal pediatric cardiologists at a single tertiary referral center in the United States and evaluate why cases were misdiagnosed.

Methods: A retrospective review of all cardiac abnormalities identified prenatally by level II sonography at a tertiary referral fetal center between January 2006 and December 2008 was performed to include any patient with a fetal cardiac abnormality and with a documented autopsy or neonatal follow-up. Congenital heart disease diagnoses were classified as correct, incorrect, or incorrect but within the same spectrum of disease. Cases of correct diagnosis by primary physicians and pediatric cardiologists were compared.

Results: Sixty patients with fetal heart abnormalities were identified among 8894 patients who had level II sonography. The combined detection rate for fetal heart abnormalities for both primary physicians and pediatric cardiologists together was 81.7%. The detection rates of congenital heart disease were not statistically different between primary physicians and pediatric cardiologists: 77.9% (46 of 59) versus 85.0% (34 of 40; P = .3). The most common cardiac abnormalities misdiagnosed in our study population included pulmonic stenosis, ventricular septal defect, myxoma, truncus arteriosus, and coarctation of the aorta.

Conclusions: Congenital heart disease is misdiagnosed in tertiary care centers by both pediatric cardiologists and fetal imaging specialists. We believe that this occurrence is related to multiple factors, including evolution of congenital heart disease, maternal body habitus, associated congenital anomalies, decreased amniotic fluid volume, gestational age at evaluation, imaging techniques, and, most importantly, the experience of the sonographer.
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http://dx.doi.org/10.7863/jum.2012.31.3.389DOI Listing
March 2012

Predicting adverse outcomes following trauma in pregnancy.

J Reprod Med 2012 Jan-Feb;57(1-2):3-8

Department of Reproductive Medicine, University of California San Diego Medical Center, 92103, USA.

Objective: To identify variables predicting adverse maternal or fetal outcome following trauma and to establish a composite morbidity model to predict poor obstetrical outcomes.

Study Design: A retrospective study of pregnant women following major and minor trauma from a single institution from 1985-2007 was performed. Abstracted data included maternal demographics, Injury Severity Score (ISS), laboratory and radiology studies,fetal monitoring and delivery information. Linear algorithm and logistic regression analysis estimated predictors of adverse obstetrical outcomes. Accuracy of composite morbidity models was tested using receiver operating characteristic.

Results: A total of 292 pregnant trauma patients were analyzed. Forty-eight (13%) women had an ISS > or = 10. Adverse pregnancy outcomes occurred in 71 patients (24%). Predictors of poor outcomes included trauma in the third trimester, length of stay (LOS) >2 days, abdominal trauma, ISS >2 and a positive Kleihauer-Betke (KB) test. Composite morbidity models resulted in sensitivity and specificity ranging from 54.3% to 70.4% and 59.5% to 87.5%, respectively.

Conclusion: Predicting adverse perinatal outcomes following major trauma remains challenging. Composite morbidity models using a combination of third trimester trauma, LOS > 2 days, abdominal trauma, ISS >2 or a positive KB test improves identification of those at risk for adverse perinatal outcomes.
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February 2012
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