Publications by authors named "Hannah Park"

76 Publications

Stemless Total Shoulder Arthroplasty for a 4-Part Proximal Humerus Malunion and Post-traumatic Arthritis: A Case Report.

JBJS Case Connect 2021 04 22;11(2). Epub 2021 Apr 22.

The Division of Shoulder Surgery, Department of Orthopaedic Surgery, The Johns Hopkins University, Baltimore, Maryland.

Case: We present a 62-year-old left-hand-dominant woman with history of renal failure, osteoporosis, and 4-part proximal humerus fracture malunion with subsequent post-traumatic arthritis of the left glenohumeral joint. After conservative treatments failed to relieve her symptoms, the patient underwent stemless total shoulder arthroplasty (TSA) because of concerns that her proximal humerus could not accommodate a stemmed implant. At 2 and a half-years postoperative, the patient demonstrated significant improvement of symptoms without signs of radiographic loosening.

Conclusion: In the setting of proximal humerus malunion with post-traumatic arthritis, clinical improvement without implant loosening can be achieved with stemless TSA, even in the setting of compromised bone quality.
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http://dx.doi.org/10.2106/JBJS.CC.20.00902DOI Listing
April 2021

Impaired executive function exacerbates neural markers of posttraumatic stress disorder.

Psychol Med 2021 Apr 21:1-14. Epub 2021 Apr 21.

National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA.

Background: A major obstacle in understanding and treating posttraumatic stress disorder (PTSD) is its clinical and neurobiological heterogeneity. To address this barrier, the field has become increasingly interested in identifying subtypes of PTSD based on dysfunction in neural networks alongside cognitive impairments that may underlie the development and maintenance of symptoms. The current study aimed to determine if subtypes of PTSD, based on normative-based cognitive dysfunction across multiple domains, have unique neural network signatures.

Methods: In a sample of 271 veterans (90% male) that completed both neuropsychological testing and resting-state fMRI, two complementary, whole-brain functional connectivity analyses explored the link between brain functioning, PTSD symptoms, and cognition.

Results: At the network level, PTSD symptom severity was associated with reduced negative coupling between the limbic network (LN) and frontal-parietal control network (FPCN), driven specifically by the dorsolateral prefrontal cortex and amygdala Hubs of Dysfunction. Further, this relationship was uniquely moderated by executive function (EF). Specifically, those with PTSD and impaired EF had the strongest marker of LN-FPCN dysregulation, while those with above-average EF did not exhibit PTSD-related dysregulation of these networks.

Conclusion: These results suggest that poor executive functioning, alongside LN-FPCN dysregulation, may represent a neurocognitive subtype of PTSD.
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http://dx.doi.org/10.1017/S0033291721000842DOI Listing
April 2021

Factors Associated with Women's Unwillingness to Decrease Alcohol Intake to Decrease Breast Cancer Risk.

J Prim Care Community Health 2021 Jan-Dec;12:21501327211000211

University of California, Irvine School of Medicine, Irvine, CA, USA.

Objective: Alcohol intake is a known risk factor for breast cancer. National organizations recommend that women consume no more than one serving of alcohol per day, if at all; however, many women exceed this recommendation, and some are unwilling to decrease consumption. Our study sought to identify factors associated with women's unwillingness to decrease their alcohol intake to decrease their breast cancer risk.

Methods: 942 women in a screening mammography cohort were asked questions about their demographics, personal and family health history, lifestyle factors, and willingness/unwillingness to decrease alcohol intake to decrease their breast cancer risk. Univariate and multivariate analyzes of their responses were performed.

Results: 13.2% of women in our cohort indicated they were unwilling to decrease their alcohol intake to reduce their breast cancer risk. After adjusting for potential confounders, women who were 60 years and older were more than twice as unwilling to decrease their alcohol intake compared to their younger counterparts ( = .0002). Women who had an annual household income of more than $200,000 were 1.75 times more unwilling to decrease their alcohol intake compared to their less affluent counterparts ( = .033). Unwillingness was not significantly associated with race/ethnicity, education, having a first-degree family member with cancer, health perception, breast cancer risk perception, or BMI.

Conclusions: Levels of unwillingness to decrease alcohol intake differed by age and household income. An opportunity is present to potentially decrease breast cancer risk in the community by educating women, especially older and more affluent women, about alcohol as a risk factor for breast cancer and the importance of limiting one's alcohol intake.
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http://dx.doi.org/10.1177/21501327211000211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983428PMC
March 2021

Factors Associated with Women's Unwillingness to Decrease Alcohol Intake to Decrease Breast Cancer Risk.

J Prim Care Community Health 2021 Jan-Dec;12:21501327211000211

University of California, Irvine School of Medicine, Irvine, CA, USA.

Objective: Alcohol intake is a known risk factor for breast cancer. National organizations recommend that women consume no more than one serving of alcohol per day, if at all; however, many women exceed this recommendation, and some are unwilling to decrease consumption. Our study sought to identify factors associated with women's unwillingness to decrease their alcohol intake to decrease their breast cancer risk.

Methods: 942 women in a screening mammography cohort were asked questions about their demographics, personal and family health history, lifestyle factors, and willingness/unwillingness to decrease alcohol intake to decrease their breast cancer risk. Univariate and multivariate analyzes of their responses were performed.

Results: 13.2% of women in our cohort indicated they were unwilling to decrease their alcohol intake to reduce their breast cancer risk. After adjusting for potential confounders, women who were 60 years and older were more than twice as unwilling to decrease their alcohol intake compared to their younger counterparts ( = .0002). Women who had an annual household income of more than $200,000 were 1.75 times more unwilling to decrease their alcohol intake compared to their less affluent counterparts ( = .033). Unwillingness was not significantly associated with race/ethnicity, education, having a first-degree family member with cancer, health perception, breast cancer risk perception, or BMI.

Conclusions: Levels of unwillingness to decrease alcohol intake differed by age and household income. An opportunity is present to potentially decrease breast cancer risk in the community by educating women, especially older and more affluent women, about alcohol as a risk factor for breast cancer and the importance of limiting one's alcohol intake.
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http://dx.doi.org/10.1177/21501327211000211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983428PMC
March 2021

Breast Cancer Risk Prediction in Korean Women: Review and Perspectives on Personalized Breast Cancer Screening.

J Breast Cancer 2020 Aug 6;23(4):331-342. Epub 2020 Jul 6.

Department of Epidemiology, School of Medicine, University of California, Irvine, CA, USA.

Due to an increasing proportion of older individuals and the adoption of a westernized lifestyle, the incidence rate of breast cancer is expected to rapidly increase within the next 10 years in Korea. The National Cancer Screening Program (NCSP) of Korea recommends biennial breast cancer screening through mammography for women aged 40-69 years old and according to individual risk and preference for women above 70 years old. There is an ongoing debate on how to most effectively screen for breast cancer, with many proponents of personalized screening, or screening according to individual risk, for women under 70 years old as well. However, to accurately stratify women into risk categories, further study using more refined personalized characteristics, including potentially incorporating a polygenic risk score (PRS), may be needed. While most breast cancer risk prediction models were developed in Western countries, the Korean Breast Cancer Risk Assessment Tool (KoBCRAT) was developed in 2013, and several other risk models have been developed for Asian women specifically. This paper reviews these models compared to commonly used models developed using primarily Caucasian women, namely, the modified Gail, Breast Cancer Surveillance Consortium, Rosner and Colditz, and Tyrer-Cuzick models. In addition, this paper reviews studies in which PRS is included in risk prediction in Asian women. Finally, this paper discusses and explores strategies toward development and implementation of personalized screening for breast cancer in Korea.
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http://dx.doi.org/10.4048/jbc.2020.23.e40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462811PMC
August 2020

A Novel Pediatric Multisystem Inflammatory Syndrome During the COVID-19 Pandemic.

Pediatr Emerg Care 2020 Oct;36(10):500-504

From the Department of Emergency Medicine, NewYork-Presbyterian Queens, Queens, New York.

In late March and early April, New York City was an epicenter of the COVID-19 pandemic. Citizens were ordered to stay at home to flatten the curve. The adult population was affected with a severe respiratory illness as well as acute kidney injury, cardiomyopathy, arrhythmia, and thromboembolism. Although children were not affected in the same manner, weeks after the peak, reports from other countries emerged about cases of pediatric patients presenting with a novel inflammatory syndrome. We present 4 patients along with their emergency department course, so providers will have a better understanding of the identification and workup of these patients. Currently, it is unclear when this inflammatory syndrome develops in respect to a COVID-19 infection. The clinical features of this syndrome seem to overlap between Kawasaki disease, toxic shock syndrome, and myocarditis. All patients presenting to our emergency department had fever, variable rash, abdominal pain, vomiting, and/or diarrhea. Patients remained persistently tachycardic and febrile despite being given proper doses of antipyretics. Severity of presentations varied among the 4 cases. All 4 patients were found to have antibodies to COVID-19. All patients required admission, but 2 required the pediatric intensive care unit for cardiac and/or respiratory support or closer monitoring. Upon follow-up on our patients, it seems that most patients are recovering with treatment, and overall, there is a low reported mortality rate.
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http://dx.doi.org/10.1097/PEC.0000000000002229DOI Listing
October 2020

Organophosphate Pesticide Exposure and Breast Cancer Risk: A Rapid Review of Human, Animal, and Cell-Based Studies.

Int J Environ Res Public Health 2020 07 13;17(14). Epub 2020 Jul 13.

Department of Epidemiology, School of Medicine, University of California, Irvine, CA 92697, USA.

Background: Organophosphate pesticides (OPs) are one of the most commonly used classes of insecticides in the U.S., and metabolites of OPs have been detected in the urine of >75% of the U.S.

Population: While studies have shown that OP exposure is associated with risk of neurological diseases and some cancers, the relationship between OP exposure and breast cancer risk is not well understood.

Methods: The aim of this rapid review was to systematically evaluate published literature on the relationship between OP exposure and breast cancer risk, including both epidemiologic and laboratory studies. Twenty-seven full-text articles were reviewed by searching on Pubmed, EMBASE, and Cochrane databases.

Results: Some human studies showed that malathion, terbufos, and chlorpyrifos were positively associated with human breast cancer risk, and some laboratory studies demonstrated that malathion and chlorpyrifos have estrogenic potential and other cancer-promoting properties. However, the human studies were limited in number, mostly included agricultural settings in several geographical areas in the U.S., and did not address cumulative exposure.

Conclusions: Given the mixed results found in both human and laboratory studies, more research is needed to further examine the relationship between OP exposure and breast cancer risk, especially in humans in non-agricultural settings.
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http://dx.doi.org/10.3390/ijerph17145030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399930PMC
July 2020

Rationale, Study Design, and Cohort Characteristics for the Markers for Environmental Exposures (MEE) Study.

Int J Environ Res Public Health 2020 03 9;17(5). Epub 2020 Mar 9.

Department of Epidemiology, University of California, Irvine, CA 92697, USA.

Environmental factors have been linked to many diseases and health conditions, but reliable assessment of environmental exposures is challenging. Developing biomarkers of environmental exposures, rather than relying on self-report, will improve our ability to assess the association of such exposures with disease. Epigenetic markers, most notably DNA methylation, have been identified for some environmental exposures, but identification of markers for additional exposures is still needed. The rationale behind the Markers for Environmental Exposures (MEE) Study was to (1) identify biomarkers, especially epigenetic markers, of environmental exposures, such as pesticides, air/food/water contaminants, and industrial chemicals that are commonly encountered in the general population; and (2) support the study of potential relationships between environmental exposures and health and health-related factors. The MEE Study is a cross-sectional study with potential for record linkage and follow-up. The well-characterized cohort of 400 postmenopausal women has generated a repository of biospecimens, including blood, urine, and saliva samples. Paired data include an environmental exposures questionnaire, a breast health questionnaire, dietary recalls, and a food frequency questionnaire. This work describes the rationale, study design, and cohort characteristics of the MEE Study. In addition to our primary research goals, we hope that the data and biorepository generated by this study will serve as a resource for future studies and collaboration.
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http://dx.doi.org/10.3390/ijerph17051774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084413PMC
March 2020

A treatment-based algorithm for identification of diabetes type in the National Health and Nutrition Examination Survey.

Cardiovasc Endocrinol Metab 2020 Mar 21;9(1):9-16. Epub 2020 Feb 21.

Heart Disease Prevention Program, Division of Cardiology.

In epidemiology studies, identification of diabetes type (type 1 vs. type 2) among study participants with diabetes is important; however, conventional diabetes type identification approaches that include age at diabetes diagnosis as an initial criterion introduces biases. Using data from the National Health and Nutrition Examination Survey, we have developed a novel algorithm which does not include age at diagnosis to identify participants with self-reported diagnosed diabetes as having type 1 vs. type 2 diabetes.

Methods: A total of 5457 National Health and Nutrition Examination Survey participants between cycles 1999-2000 and 2015-2016 reported that a health professional had diagnosed them as having diabetes at a time other than during pregnancy and had complete information on diabetes-related questions. After developing an algorithm based on information regarding the treatment(s) they received, we classified these participants as having type 1 or type 2 diabetes.

Results: The treatment-based algorithm yielded a 6-94% split for type 1 and type 2 diabetes, which is consistent with reports from the Centers for Disease Control and other resources. Moreover, the demographics and clinical characteristics of the assigned type 1 and type 2 cases were consistent with contemporary epidemiologic findings.

Conclusion: Applying diabetes treatment information from the National Health and Nutrition Examination Survey, as formulated in our treatment-based algorithm, may better identify type 1 and type 2 diabetes cases and thus prevent the specific biases imposed by conventional approaches which include the age of diabetes diagnosis as an initial criterion for diabetes type classification.
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http://dx.doi.org/10.1097/XCE.0000000000000189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041875PMC
March 2020

Time-lapse technology for embryo culture and selection.

Ups J Med Sci 2020 May 25;125(2):77-84. Epub 2020 Feb 25.

Reproductive Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.

Culturing of human embryos in optimal conditions is crucial for a successful fertilisation (IVF) programme. In addition, the capacity to assess and rank embryos correctly for quality will allow for transfer of the potentially 'best' embryo first, thereby shortening the time to pregnancy, although not improving cumulative pregnancy and live birth rates. It will also encourage and facilitate the implementation of single embryo transfers, thereby increasing safety for mother and offspring. Time-lapse technology introduces the concept of stable culture conditions, in connection with the possibility of continuous viewing and documenting of the embryo throughout development. However, so far, even when embryo quality scoring is based on large datasets, or when using the time-lapse technology, the morphokinetic scores are still mainly based on subjective and intermittent annotations of morphology and timings. Also, the construction of powerful algorithms for widespread use is hampered by large variations in culture conditions between individual IVF laboratories. New methodology, involving machine learning, where every image from the time-lapse documentation is analysed by a computer programme, looking for patterns that link to outcome, may in the future provide a more accurate and non-biased embryo selection.
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http://dx.doi.org/10.1080/03009734.2020.1728444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720962PMC
May 2020

Epigenetic Biomarkers for Environmental Exposures and Personalized Breast Cancer Prevention.

Authors:
Hannah Lui Park

Int J Environ Res Public Health 2020 02 13;17(4). Epub 2020 Feb 13.

Department of Epidemiology, UC Irvine School of Medicine, Irvine, CA 92617, USA.

Environmental and lifestyle factors are believed to account for >80% of breast cancers; however, it is not well understood how and when these factors affect risk and which exposed individuals will actually develop the disease. While alcohol consumption, obesity, and hormone therapy are some known risk factors for breast cancer, other exposures associated with breast cancer risk have not yet been identified or well characterized. In this paper, it is proposed that the identification of blood epigenetic markers for personal, in utero, and ancestral environmental exposures can help researchers better understand known and potential relationships between exposures and breast cancer risk and may enable personalized prevention strategies.
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http://dx.doi.org/10.3390/ijerph17041181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068429PMC
February 2020

Expression of the BAD pathway is a marker of triple-negative status and poor outcome.

Sci Rep 2019 11 25;9(1):17496. Epub 2019 Nov 25.

Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.

Triple-negative breast cancer (TNBC) has few therapeutic targets, making nonspecific chemotherapy the main treatment. Therapies enhancing cancer cell sensitivity to cytotoxic agents could significantly improve patient outcomes. A BCL2-associated agonist of cell death (BAD) pathway gene expression signature (BPGES) was derived using principal component analysis (PCA) and evaluated for associations with the TNBC phenotype and clinical outcomes. Immunohistochemistry was used to determine the relative expression levels of phospho-BAD isoforms in tumour samples. Cell survival assays evaluated the effects of BAD pathway inhibition on chemo-sensitivity. BPGES score was associated with TNBC status and overall survival (OS) in breast cancer samples of the Moffitt Total Cancer Care dataset and The Cancer Genome Atlas (TCGA). TNBC tumours were enriched for the expression of phospho-BAD isoforms. Further, the BPGES was associated with TNBC status in breast cancer cell lines of the Cancer Cell Line Encyclopedia (CCLE). Targeted inhibition of kinases known to phosphorylate BAD protein resulted in increased sensitivity to platinum agents in TNBC cell lines compared to non-TNBC cell lines. The BAD pathway is associated with triple-negative status and OS. TNBC tumours were enriched for the expression of phosphorylated BAD protein compared to non-TNBC tumours. These findings suggest that the BAD pathway it is an important determinant of TNBC clinical outcomes.
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http://dx.doi.org/10.1038/s41598-019-53695-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877530PMC
November 2019

Rapid Generation of Somatic Mouse Mosaics with Locus-Specific, Stably Integrated Transgenic Elements.

Cell 2019 09;179(1):251-267.e24

Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Center for Neural Sciences in Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

In situ transgenesis methods such as viruses and electroporation can rapidly create somatic transgenic mice but lack control over copy number, zygosity, and locus specificity. Here we establish mosaic analysis by dual recombinase-mediated cassette exchange (MADR), which permits stable labeling of mutant cells expressing transgenic elements from precisely defined chromosomal loci. We provide a toolkit of MADR elements for combination labeling, inducible and reversible transgene manipulation, VCre recombinase expression, and transgenesis of human cells. Further, we demonstrate the versatility of MADR by creating glioma models with mixed reporter-identified zygosity or with "personalized" driver mutations from pediatric glioma. MADR is extensible to thousands of existing mouse lines, providing a flexible platform to democratize the generation of somatic mosaic mice. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.cell.2019.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934691PMC
September 2019

Mineralocorticoid receptor antagonist use after hospitalization of patients with heart failure and post-discharge outcomes: a single-center retrospective cohort study.

BMC Cardiovasc Disord 2019 08 9;19(1):194. Epub 2019 Aug 9.

Department of Medicine, New York University School of Medicine, 227 East 30th Street, New York, NY, 10016, USA.

Background: Mineralocorticoid receptor antagonists (MRA) are an underutilized therapy for heart failure with a reduced ejection fraction (HFrEF), but the current impact of hospitalization on MRA use is not well characterized. The objective of this study was to describe contemporary MRA prescription for heart failure patients before and after the full scope of hospitalizations and the association between MRA discharge prescription and post-hospitalization outcomes.

Methods: We conducted a retrospective cohort study at an academic hospital system in 2013-2016. Among 1500 included hospitalizations of 1009 unique patients with HFrEF and without MRA contraindication, the mean age was 71.9 ± 13.6 years and 443 (29.5%) were female. We compared MRA prescription before and after hospitalizations with McNemar's test and between patients with principal and secondary diagnoses of HFrEF with the chi-square test, and association of MRA discharge prescription with 30-day and 180-day mortality and readmissions using generalized estimating equations.

Results: MRA prescriptions increased from 303 (20.2%) to 375 (25.0%) at discharge (+4.8%, p < 0.0001). More patients with principal diagnosis of HFrEF compared to those hospitalized for other reasons received MRA (34.9% versus 21.3%, p < 0.0001) and had them initiated (21.8% versus 9.7%, p < 0.0001). MRA prescription at discharge was not associated with mortality or readmission at 30 and 180 days, and there was no interaction with principal/secondary diagnosis.

Conclusions: Among hospitalized HFrEF patients, 75% did not receive MRA before or after hospitalization, and nearly 90% of eligible patients did not have MRA initiated. As we found no signal for short-term harm after discharge, hospitalization may represent an opportunity to initiate guideline-directed heart failure therapy.
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http://dx.doi.org/10.1186/s12872-019-1175-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688376PMC
August 2019

Effects of an mHealth intervention for community health workers on maternal and child nutrition and health service delivery in India: protocol for a quasi-experimental mixed-methods evaluation.

BMJ Open 2019 03 27;9(3):e025774. Epub 2019 Mar 27.

University of California San Fransisco, San Fransisco, USA.

Introduction: Millions of children in India still suffer from poor health and under-nutrition, despite substantial improvement over decades of public health programmes. The Anganwadi centres under the Integrated Child Development Scheme (ICDS) provide a range of health and nutrition services to pregnant women, children <6 years and their mothers. However, major gaps exist in ICDS service delivery. The government is currently strengthening ICDS through an mHealth intervention called Common Application Software (ICDS-CAS) installed on smart phones, with accompanying multilevel data dashboards. This system is intended to be a job aid for frontline workers, supervisors and managers, aims to ensure better service delivery and supervision, and enable real-time monitoring and data-based decision-making. However, there is little to no evidence on the effectiveness of such large-scale mHealth interventions integrated with public health programmes in resource-constrained settings on the service delivery and subsequent health and nutrition outcomes.

Methods And Analysis: This study uses a village-matched controlled design with repeated cross-sectional surveys to evaluate whether ICDS-CAS can enable more timely and appropriate services to pregnant women, children <12 months and their mothers, compared with the standard ICDS programme. The study will recruit approximately 1500 Anganwadi workers and 6000+ mother-child dyads from 400+ matched-pair villages in Bihar and Madhya Pradesh. The primary outcomes are the proportion of beneficiaries receiving (a) adequate number of home visits and (b) appropriate level of counselling by the Anganwadi workers. Secondary outcomes are related to improvements in other ICDS services, and knowledge and practices of the Anganwadi workers and beneficiaries.

Ethics And Dissemination: Ethical oversight is provided by the Committee for the Protection of Human Subjects at the University of California at Berkeley, and the Suraksha Independent Ethics Committee in India. The results will be published in peer-reviewed journals and analysis data will be made public.

Trial Registration Number: ISRCTN83902145.
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http://dx.doi.org/10.1136/bmjopen-2018-025774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6475202PMC
March 2019

Effective risk communication to promote behavioral change in patients at elevated risk for breast cancer based on the Health Belief Model.

Breast J 2018 11 6;24(6):1097-1098. Epub 2018 Aug 6.

Department of Epidemiology, School of Medicine, University of California, Irvine, California.

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http://dx.doi.org/10.1111/tbj.13086DOI Listing
November 2018

Secondary overtriage of pediatric neurosurgical trauma at a Level I pediatric trauma center.

J Neurosurg Pediatr 2018 Oct 29;22(4):375-383. Epub 2018 Jun 29.

2Shriners Hospitals for Children-Philadelphia, Philadelphia, Pennsylvania.

The authors looked at all of the pediatric patients with a head injury who were transferred from other hospitals to their own over 12 years and tried to identify factors that would allow patients to stay closer to home at their local hospitals and not be transferred. Many patients with isolated, nondisplaced skull fractures or negative CT imaging likely could have avoided transfer. While hospitals should be cautious, this may help families stay closer to home.
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http://dx.doi.org/10.3171/2018.5.PEDS182DOI Listing
October 2018

Inducible Expression of GDNF in Transplanted iPSC-Derived Neural Progenitor Cells.

Stem Cell Reports 2018 06 26;10(6):1696-1704. Epub 2018 Apr 26.

Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address:

Trophic factor delivery to the brain using stem cell-derived neural progenitors is a powerful way to bypass the blood-brain barrier. Protection of diseased neurons using this technology is a promising therapy for neurodegenerative diseases. Glial cell line-derived neurotrophic factor (GDNF) has provided benefits to Parkinsonian patients and is being used in a clinical trial for amyotrophic lateral sclerosis. However, chronic trophic factor delivery prohibits dose adjustment or cessation if side effects develop. To address this, we engineered a doxycycline-regulated vector, allowing inducible and reversible expression of a therapeutic molecule. Human induced pluripotent stem cell (iPSC)-derived neural progenitors were stably transfected with the vector and transplanted into the adult mouse brain. Doxycycline can penetrate the graft, with addition and withdrawal providing inducible and reversible GDNF expression in vivo, over multiple cycles. Our findings provide proof of concept for combining gene and stem cell therapy for effective modulation of ectopic protein expression in transplanted cells.
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http://dx.doi.org/10.1016/j.stemcr.2018.03.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989694PMC
June 2018

Public Perceptions Regarding Use of Virtual Reality in Health Care: A Social Media Content Analysis Using Facebook.

J Med Internet Res 2017 12 19;19(12):e419. Epub 2017 Dec 19.

Cedars-Sinai Center for Outcomes Research and Education, Cedars-Sinai Medical Center, Los Angeles, CA, United States.

Background: Virtual reality (VR) technology provides an immersive environment that enables users to have modified experiences of reality. VR is increasingly used to manage patients with pain, disability, obesity, neurologic dysfunction, anxiety, and depression. However, public opinion regarding the use of VR in health care has not been explored. Understanding public opinion of VR is critical to ensuring effective implementation of this emerging technology.

Objective: This study aimed to examine public opinion about health care VR using social listening, a method that allows for the exploration of unfiltered views of topics discussed on social media and online forums.

Methods: In March 2016, NBC News produced a video depicting the use of VR for patient care. The video was repackaged by NowThis, a social media news website, and distributed on Facebook by Upworthy, a news aggregator, yielding 4.3 million views and 2401 comments. We used Microsoft Excel Power Query and ATLAS.ti software (version 7.5, Scientific Software Development) to analyze the comments using content analysis and categorized the comments around first-, second-, and third-order concepts. We determined self-identified gender from the user's Facebook page and performed sentiment analysis of the language to analyze whether the perception of VR differed by gender using a Pearson's chi-square test.

Results: Out of the 1614 analyzable comments, 1021 (63.26%) were attributed to female Facebook users, 572 (35.44%) to male users, and 21 (1.30%) to users of unknown gender. There were 1197 comments coded as expressing a positive perception about VR (74.16%), 251 coded as expressing a negative perception and/or concern (15.56%), and 560 coded as neutral (34.70%). Informants identified 20 use cases for VR in health care, including the use of VR for pain and stress reduction; bed-bound individuals; women during labor; and patients undergoing chemotherapy, dialysis, radiation, or imaging procedures. Negative comments expressed concerns about radiation, infection risk, motion sickness, and the ubiquity of and overall dependence on technology. There was a statistically significant association between the language valence of the Facebook post and the gender of the Facebook user; men were more likely to post negative perceptions about the use of VR for health care, whereas women were more likely to post positive perceptions (P<.001).

Conclusions: Most informants expressed positive perceptions about the use of VR in a wide range of health care settings. However, many expressed concerns that should be acknowledged and addressed as health care VR continues to evolve. Our results provide guidance in determining where further research on the use of VR in patient care is needed, and offer a formal opportunity for public opinion to shape the VR research agenda.
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http://dx.doi.org/10.2196/jmir.7467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5750416PMC
December 2017

Trends in Treatment Patterns and Clinical Outcomes in Young Women Diagnosed With Ductal Carcinoma In Situ.

Clin Breast Cancer 2018 04 10;18(2):e179-e185. Epub 2017 Aug 10.

Department of Epidemiology, University of California, Irvine, School of Medicine, Irvine, CA.

Background: Although it is known that the risk of a second breast cancer event among young women diagnosed with ductal carcinoma in situ (DCIS) is higher than in older women, the effect of current treatment options on long-term outcomes in this subgroup of women remains poorly defined. We aimed to evaluate national treatment trends and determine their effect on second breast cancer risk and overall survival among young women diagnosed with DCIS.

Materials And Methods: Surveillance, Epidemiology, and End Results data from 1998 to 2011 were used to analyze 3648 DCIS patients younger than age 40 years.

Results: Among all treatment options, breast-conserving surgery (BCS) with radiation therapy (BCS + RT) was the most prevalent (36.1%) followed by mastectomy (MTX) without contralateral prophylactic MTX (CPM; 25.8%), BCS alone (22.2%), and MTX with CPM (15.8%). Risk of a second ipsilateral event was > 5-fold and > 2-fold lower within 2 years and 5 years of initial DCIS diagnosis, respectively, in women who received BCS + RT compared with BCS alone; and overall survival was 3-fold higher in women who received BCS + RT. However, MTX with or without CPM did not show an increase in overall survival compared with BCS + RT. In addition, although the percentage of young women who receive MTX with CPM has increased in recent years, MTX with CPM did not show an increased benefit in survival compared with MTX without CPM.

Conclusion: The results of our study suggest that more aggressive treatments do not offer survival benefits over BCS + RT; thus, clinical treatment options in young women with DCIS should be carefully considered.
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http://dx.doi.org/10.1016/j.clbc.2017.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817367PMC
April 2018

Early Identification of Patients With Acute Decompensated Heart Failure.

J Card Fail 2018 06 5;24(6):357-362. Epub 2017 Sep 5.

Department of Medicine, New York Univeristy School of Medicine, New York, New York.

Background: Interventions to reduce readmissions after acute heart failure hospitalization require early identification of patients. The purpose of this study was to develop and test accuracies of various approaches to identify patients with acute decompensated heart failure (ADHF) with the use of data derived from the electronic health record.

Methods And Results: We included 37,229 hospitalizations of adult patients at a single hospital during 2013-2015. We developed 4 algorithms to identify hospitalization with a principal discharge diagnosis of ADHF: 1) presence of 1 of 3 clinical characteristics, 2) logistic regression of 31 structured data elements, 3) machine learning with unstructured data, and 4) machine learning with the use of both structured and unstructured data. In data validation, algorithm 1 had a sensitivity of 0.98 and positive predictive value (PPV) of 0.14 for ADHF. Algorithm 2 had an area under the receiver operating characteristic curve (AUC) of 0.96, and both machine learning algorithms had AUCs of 0.99. Based on a brief survey of 3 providers who perform chart review for ADHF, we estimated that providers spent 8.6 minutes per chart review; using this this parameter, we estimated that providers would spend 61.4, 57.3, 28.7, and 25.3 minutes on secondary chart review for each case of ADHF if initial screening were done with algorithms 1, 2, 3, and 4, respectively.

Conclusions: Machine learning algorithms with unstructured notes had the best performance for identification of ADHF and can improve provider efficiency for delivery of quality improvement interventions.
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http://dx.doi.org/10.1016/j.cardfail.2017.08.458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837903PMC
June 2018

Arrested Development: Infantile Hemangioma and the Stem Cell Teratogenic Hypothesis.

Lymphat Res Biol 2017 06 18;15(2):153-165. Epub 2017 May 18.

4 Department of Medicine, New York University School of Medicine , New York, New York.

Background: Early-life programming is defined by the adaptive changes made by the fetus in response to an adverse in utero environment. Infantile hemangioma (IH), a vascular anomaly, is the most common tumor of infancy. Here we take IH as the tumor model to propose the stem cell teratogenic hypothesis of tumorigenesis and the potential involvement of the immune system.

Objectives: Teratogenic agents include chemicals, heavy metals, pathogens, and ionizing radiation. To investigate the etiology and pathogenesis of IH, we hypothesized that they result from a teratogenic mechanism. Immature, incompletely differentiated, dysregulated progenitor cells (multipotential stem cells) are arrested in development with vasculogenic, angiogenic, and tumorigenic potential due to exposure to teratogenic agents such as extrinsic factors that disrupt intrinsic factors via molecular mimicry. During the critical period of immunological tolerance, environmental exposure to immunotoxic agents may harness the teratogenic potential in the developing embryo or fetus and modify the early-life programming algorithm by altering normal fetal development, causing malformations, and inducing tumorigenesis. Specifically, exposure to environmental agents may interfere with physiological signaling pathways and contribute to the generation of IH, by several mechanisms.

Discussion: An adverse in utero environment no longer serves as a sustainable environment for proper embryogenesis and normal development. Targeted disruption of stem cells by extrinsic factors can alter the genetic program.

Conclusions: This article offers new perspectives to stimulate discussion, explore novel experimental approaches (such as immunotoxicity/vasculotoxicity assays and novel isogenic models), and to address the questions raised to convert the hypotheses into nontoxic, noninvasive treatments.
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http://dx.doi.org/10.1089/lrb.2016.0030DOI Listing
June 2017

Lethal Giant Lineage Tracing: Mutating Locally, Acting Globally.

Neuron 2017 May;94(3):417-420

Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA. Electronic address:

The generation of neurons and glia from radial glia progenitors is critical to proper neocortical development but the mechanisms regulating their deterministic production are unclear. In this issue of Neuron, Beattie et al. (2017) use elegant MADM-based lineage tracing to demonstrate cell-intrinsic and global functions for Lgl1 during neocortical development.
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http://dx.doi.org/10.1016/j.neuron.2017.04.030DOI Listing
May 2017

System Changes to Implement the Joint Commission Tobacco Treatment (TOB) Performance Measures for Improving the Treatment of Tobacco Use Among Hospitalized Patients.

Jt Comm J Qual Patient Saf 2017 05 30;43(5):234-240. Epub 2017 Mar 30.

Background: In 2012 The Joint Commission implemented new Tobacco Treatment (TOB) performance measures for hospitals. A study evaluated the impact of a hospital-based electronic health record (EHR) intervention on adherence to the revised TOB measures.

Methods: The study was conducted in two acute care hospitals in New York City. Data abstracted from the EHR were analyzed retrospectively from 4,871 smokers discharged between December 2012 and March 2015 to evaluate the impact of two interventions: an order set to prompt clinicians to prescribe pharmacotherapy and a nurse-delivered counseling module that automatically populated the nursing care plan for all smokers. The study estimated the relative odds of a patient being prescribed medication and/or receiving smoking cessation counseling in the intervention period compared to the baseline time period.

Results: There was a modest increase in medication orders (odds ratio [OR], 1.35). In contrast, rates of counseling increased 10-fold (OR, 10.54). Patients admitted through surgery were less likely to receive both counseling and medication compared with the medicine service.

Conclusion: Hospitalization presents an important opportunity to engage smokers in treatment for primary and secondary prevention of tobacco-related illnesses. EHRs can be leveraged to facilitate integration of TOB measure requirements into routine inpatient care; however, the smaller effect on prescribing patterns suggests limitations in this approach alone in changing clinician behavior to meet this measure. The success of the nurse-focused EHR-driven intervention suggests an effective tool for integrating the cessation counseling component of the new measures and the importance of nursing's role in achieving the Joint Commission measure targets.
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http://dx.doi.org/10.1016/j.jcjq.2017.02.008DOI Listing
May 2017

Ets Factors Regulate Neural Stem Cell Depletion and Gliogenesis in Ras Pathway Glioma.

Cell Rep 2016 12;17(12):3407

Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

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http://dx.doi.org/10.1016/j.celrep.2016.12.026DOI Listing
December 2016

Racial and Ethnic Differences in Heart Failure Readmissions and Mortality in a Large Municipal Healthcare System.

JACC Heart Fail 2016 11 6;4(11):885-893. Epub 2016 Jul 6.

Department of Medicine, New York University School of Medicine, New York, New York; Department of Population Health, New York University School of Medicine, New York, New York. Electronic address:

Objectives: This study sought to determine whether racial and ethnic differences exist among patients with similar access to care. We examined outcomes after heart failure hospitalization within a large municipal health system.

Background: Racial and ethnic disparities in heart failure outcomes are present in administrative data, and one explanation is differential access to care.

Methods: We performed a retrospective cohort study of 8,532 hospitalizations of adults with heart failure at 11 hospitals in New York City from 2007 to 2010. Primary exposure was ethnicity and race, and outcomes were 30- and 90-day readmission and 30-day and 1-year mortality rates. Generalized estimating equations were used to test for associations between ethnicity and race and outcomes with covariate adjustment.

Results: Of the number of hospitalizations included, 4,305 (51%) were for blacks, 2,449 (29%) were for Hispanics, 1,494 (18%) were for whites, and 284 (3%) were for Asians. Compared to whites, blacks and Asians had lower 1-year mortality, with adjusted odds ratios (aORs) of 0.75 (95% confidence interval [CI]: 0.59 to 0.94) and 0.57 (95% CI: 0.38 to 0.85), respectively, and rates for Hispanics were not significantly different (aOR: 0.81; 95% CI: 0.64 to 1.03). Hispanics had higher odds of readmission than whites (aOR: 1.27; 95% CI: 1.03 to 1.57) at 30 (aOR: 1.40; 95% CI: 1.15 to 1.70) and 90 days. Blacks had higher odds of readmission than whites at 90 days (aOR:1.21; 95% CI: 1.01 to 1.47).

Conclusions: Racial and ethnic differences in outcomes after heart failure hospitalization were present within a large municipal health system. Access to a municipal health system may not be sufficient to eliminate disparities in heart failure outcomes.
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http://dx.doi.org/10.1016/j.jchf.2016.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097004PMC
November 2016

Does "Decision Fatigue" Impact Manuscript Acceptance? An Analysis of Editorial Decisions by the American Journal of Gastroenterology.

Am J Gastroenterol 2016 Nov 11;111(11):1511-1512. Epub 2016 Oct 11.

Division of Health Services Research, Cedars-Sinai Medical Center, Los Angeles, California, USA.

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http://dx.doi.org/10.1038/ajg.2016.452DOI Listing
November 2016

First Metatarsal Head and Medial Eminence Widths with and Without Hallux Valgus.

J Am Podiatr Med Assoc 2016 Sep;106(5):323-327

Background: Resection of the medial eminence in hallux valgus surgery is common. True hypertrophy of the medial eminence in hallux valgus is debated. No studies have compared metatarsal head width in patients with hallux valgus and control patients.

Methods: We reviewed 43 radiographs with hallux valgus and 27 without hallux valgus. We measured medial eminence width, first metatarsal head width, and first metatarsal shaft width in patients with and without radiographic hallux valgus.

Results: Medial eminence width was 1.12 mm larger in patients with hallux valgus (P < .0001). Metatarsal head width was 2.81 mm larger in patients with hallux valgus (P < .001). Metatarsal shaft width showed no significant difference (P = .63).

Conclusions: Metatarsal head width and medial eminence width are significantly larger on anteroposterior weightbearing radiographs in patients with hallux valgus. However, frontal plane rotation of the first metatarsal likely accounts for this difference.
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http://dx.doi.org/10.7547/15-038DOI Listing
September 2016

Comparison of Approaches for Heart Failure Case Identification From Electronic Health Record Data.

JAMA Cardiol 2016 Dec;1(9):1014-1020

Department of Computer Science, New York University, New York.

Importance: Accurate, real-time case identification is needed to target interventions to improve quality and outcomes for hospitalized patients with heart failure. Problem lists may be useful for case identification but are often inaccurate or incomplete. Machine-learning approaches may improve accuracy of identification but can be limited by complexity of implementation.

Objective: To develop algorithms that use readily available clinical data to identify patients with heart failure while in the hospital.

Design, Setting, And Participants: We performed a retrospective study of hospitalizations at an academic medical center. Hospitalizations for patients 18 years or older who were admitted after January 1, 2013, and discharged before February 28, 2015, were included. From a random 75% sample of hospitalizations, we developed 5 algorithms for heart failure identification using electronic health record data: (1) heart failure on problem list; (2) presence of at least 1 of 3 characteristics: heart failure on problem list, inpatient loop diuretic, or brain natriuretic peptide level of 500 pg/mL or higher; (3) logistic regression of 30 clinically relevant structured data elements; (4) machine-learning approach using unstructured notes; and (5) machine-learning approach using structured and unstructured data.

Main Outcomes And Measures: Heart failure diagnosis based on discharge diagnosis and physician review of sampled medical records.

Results: A total of 47 119 hospitalizations were included in this study (mean [SD] age, 60.9 [18.15] years; 23 952 female [50.8%], 5258 black/African American [11.2%], and 3667 Hispanic/Latino [7.8%] patients). Of these hospitalizations, 6549 (13.9%) had a discharge diagnosis of heart failure. Inclusion of heart failure on the problem list (algorithm 1) had a sensitivity of 0.40 and a positive predictive value (PPV) of 0.96 for heart failure identification. Algorithm 2 improved sensitivity to 0.77 at the expense of a PPV of 0.64. Algorithms 3, 4, and 5 had areas under the receiver operating characteristic curves of 0.953, 0.969, and 0.974, respectively. With a PPV of 0.9, these algorithms had associated sensitivities of 0.68, 0.77, and 0.83, respectively.

Conclusions And Relevance: The problem list is insufficient for real-time identification of hospitalized patients with heart failure. The high predictive accuracy of machine learning using free text demonstrates that support of such analytics in future electronic health record systems can improve cohort identification.
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http://dx.doi.org/10.1001/jamacardio.2016.3236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289894PMC
December 2016