Publications by authors named "Arriel Benis"

26 Publications

  • Page 1 of 1

Reasons for Taking the COVID-19 Vaccine by US Social Media Users.

Vaccines (Basel) 2021 Mar 29;9(4). Epub 2021 Mar 29.

School of Medicine, Ariel University, Ariel 40700, Israel.

Political and public health leaders promoting COVID-19 vaccination should identify the most relevant criteria driving the vaccination decision. Social media is increasingly used as a source of vaccination data and as a powerful communication tool to increase vaccination. In December 2020, we performed a cross-sectional social media-based survey addressing personal sentiments toward COVID-19 vaccination in the USA. Our primary research objective is to identify socio-demographic characteristics and the reasons for the 1644 survey participants' attitudes regarding vaccination. We present clear evidence that, contrary to the prevailing public perceptions, young audiences using social media have mostly a positive attitude towards COVID-19 vaccination (81.5%). These younger individuals want to protect their families and their relatives (96.7%); they see vaccination as an act of civic responsibility (91.9%) and express strong confidence in their healthcare providers (87.7%). Another critical factor is the younger population's fear of personal COVID-19 infection (88.2%); moreover, the greater the number of children the participants have, the greater is their intent to get the COVID-19 vaccine. These results enable a practical public-messaging pathway to reinforce vaccination campaigns addressing the younger population.
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http://dx.doi.org/10.3390/vaccines9040315DOI Listing
March 2021

An Early Stage Researcher's Primer on Systems Medicine Terminology.

Netw Syst Med 2021 Feb 25;4(1):2-50. Epub 2021 Feb 25.

Faculty of Health, Medicine & Life Science, Maastricht University, Maastricht, The Netherlands.

Systems Medicine is a novel approach to medicine, that is, an interdisciplinary field that considers the human body as a system, composed of multiple parts and of complex relationships at multiple levels, and further integrated into an environment. Exploring Systems Medicine implies understanding and combining concepts coming from diametral different fields, including medicine, biology, statistics, modeling and simulation, and data science. Such heterogeneity leads to semantic issues, which may slow down implementation and fruitful interaction between these highly diverse fields. In this review, we collect and explain more than100 terms related to Systems Medicine. These include both modeling and data science terms and basic systems medicine terms, along with some synthetic definitions, examples of applications, and lists of relevant references. This glossary aims at being a first aid kit for the Systems Medicine researcher facing an unfamiliar term, where he/she can get a first understanding of them, and, more importantly, examples and references for digging into the topic.
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http://dx.doi.org/10.1089/nsm.2020.0003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919422PMC
February 2021

Social Media Engagement and Influenza Vaccination During the COVID-19 Pandemic: Cross-sectional Survey Study.

J Med Internet Res 2021 03 16;23(3):e25977. Epub 2021 Mar 16.

Adelson School of Medicine, Ariel University, Ariel, Israel.

Background: Vaccines are one of the most important achievements of modern medicine. However, their acceptance is only partial, with vaccine hesitancy and refusal representing a major health threat. Influenza vaccines have low compliance since repeated, annual vaccination is required. Influenza vaccines stimulate discussions both in the real world and online. Social media is currently a significant source of health and medical information. Elucidating the association between social media engagement and influenza vaccination is important and may be applicable to other vaccines, including ones against COVID-19.

Objective: The goal of this study is to characterize profiles of social media engagement regarding the influenza vaccine and their association with knowledge and compliance in order to support improvement of future web-associated vaccination campaigns.

Methods: A weblink to an online survey in Hebrew was disseminated over social media and messaging platforms. The survey answers were collected during April 2020. Anonymous and volunteer participants aged 21 years and over answered 30 questions related to sociodemographics; social media usage; influenza- and vaccine-related knowledge and behavior; health-related information searching, its reliability, and its influence; and COVID-19-related information searching. A univariate descriptive data analysis was performed, followed by multivariate analysis via building a decision tree to define the most important attributes associated with vaccination compliance.

Results: A total of 213 subjects responded to the survey, of whom 207 were included in the analysis; the majority of the respondents were female, were aged 21 to 40 years, had 1 to 2 children, lived in central Israel, were secular Israeli natives, had higher education, and had a salary close to the national average. Most respondents (128/207, 61.8%) were not vaccinated against influenza in 2019 and used social media. Participants that used social media were younger, secular, and living in high-density agglomerations and had lower influenza vaccination rates. The perceived influence and reliability of the information on social media about COVID-19 were generally similar to those perceptions about influenza.

Conclusions: Using social media is negatively linked to compliance with seasonal influenza vaccination in this study. A high proportion of noncompliant individuals can lead to increased consumption of health care services and can, therefore, overload these health services. This is particularly crucial with a concomitant outbreak, such as COVID-19. Health care professionals should use improved and targeted health communication campaigns with the aid of experts in social media. Targeted communication, based on sociodemographic factors and personalized social media usage, might increase influenza vaccination rates and compliance with other vaccines as well.
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http://dx.doi.org/10.2196/25977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968480PMC
March 2021

One Digital Health: A Unified Framework for Future Health Ecosystems.

J Med Internet Res 2021 02 5;23(2):e22189. Epub 2021 Feb 5.

Faculty of Medicine, Institute for Health and Society, University of Oslo, Oslo, Norway.

One Digital Health is a proposed unified structure. The conceptual framework of the One Digital Health Steering Wheel is built around two keys (ie, One Health and digital health), three perspectives (ie, individual health and well-being, population and society, and ecosystem), and five dimensions (ie, citizens' engagement, education, environment, human and veterinary health care, and Healthcare Industry 4.0). One Digital Health aims to digitally transform future health ecosystems, by implementing a systemic health and life sciences approach that takes into account broad digital technology perspectives on human health, animal health, and the management of the surrounding environment. This approach allows for the examination of how future generations of health informaticians can address the intrinsic complexity of novel health and care scenarios in digitally transformed health ecosystems. In the emerging hybrid landscape, citizens and their health data have been called to play a central role in the management of individual-level and population-level perspective data. The main challenges of One Digital Health include facilitating and improving interactions between One Health and digital health communities, to allow for efficient interactions and the delivery of near-real-time, data-driven contributions in systems medicine and systems ecology. However, digital health literacy; the capacity to understand and engage in health prevention activities; self-management; and collaboration in the prevention, control, and alleviation of potential problems are necessary in systemic, ecosystem-driven public health and data science research. Therefore, people in a healthy One Digital Health ecosystem must use an active and forceful approach to prevent and manage health crises and disasters, such as the COVID-19 pandemic.
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http://dx.doi.org/10.2196/22189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886486PMC
February 2021

Statin Therapy for Primary Prevention in the Elderly and Its Association with New-Onset Diabetes, Cardiovascular Events, and All-Cause Mortality.

Am J Med 2020 Nov 17. Epub 2020 Nov 17.

Clalit Health Services, Tel-Aviv, Israel; Department of Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, Ill.

Purpose: This study assessed associations of the use of statins for primary prevention with cardiovascular outcomes among adults ages ≥70 years.

Methods: In a retrospective population-based cohort study, new users of statins without cardiovascular disease or diabetes mellitus were stratified by ages ≥70 years and <70 years. Using a time-dependent approach, adherence to statins was evaluated according to the proportion of days covered: <25%, 25%-50%, 50%-75%, and ≥75%. We assessed associations of statin therapy with increased risk of new-onset diabetes mellitus and with decreased risks of major adverse cardiovascular events and all-cause mortality.

Results: Of 42,767 new users of statins, 5970 (14%) were ages ≥70 years. The incident rates of major adverse cardiovascular events, all-cause mortality, and new-onset diabetes mellitus in the highest to lowest proportion of days covered categories were 16.9%, 16.7%, and 9.4% and 6.3%, 1.7%, and 9.4%, respectively. For the older group, the adjusted hazard ratios of major adverse cardiovascular events and mortality were significantly decreased for the highest adherence group (proportion of days covered ≥75%): 0.71 (0.57-0.88) and 0.68 (0.54-0.84), respectively. The respective hazard ratios were less favorable for the younger group: 0.80 (0.68-0.93) and 0.74 (0.58-1.03). The risk of new-onset diabetes mellitus was increased for the younger but not the older group.

Conclusions: Statin use for primary prevention was associated with cardiovascular benefit in adults ages ≥70 years without a significant risk for the development of diabetes. These data may support the use of statin therapy for primary prevention in the elderly.
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http://dx.doi.org/10.1016/j.amjmed.2020.09.058DOI Listing
November 2020

Network and Systems Medicine: Position Paper of the European Collaboration on Science and Technology Action on Open Multiscale Systems Medicine.

Netw Syst Med 2020 6;3(1):67-90. Epub 2020 Jul 6.

Department of Pharmacology and Personalised Medicine, Faculty of Health, Medicine and Life Science, MeHNS, Maastricht University, The Netherlands.

Network and systems medicine has rapidly evolved over the past decade, thanks to computational and integrative tools, which stem in part from systems biology. However, major challenges and hurdles are still present regarding validation and translation into clinical application and decision making for precision medicine. In this context, the Collaboration on Science and Technology Action on Open Multiscale Systems Medicine (OpenMultiMed) reviewed the available advanced technologies for multidimensional data generation and integration in an open-science approach as well as key clinical applications of network and systems medicine and the main issues and opportunities for the future. The development of multi-omic approaches as well as new digital tools provides a unique opportunity to explore complex biological systems and networks at different scales. Moreover, the application of findable, applicable, interoperable, and reusable principles and the adoption of standards increases data availability and sharing for multiscale integration and interpretation. These innovations have led to the first clinical applications of network and systems medicine, particularly in the field of personalized therapy and drug dosing. Enlarging network and systems medicine application would now imply to increase patient engagement and health care providers as well as to educate the novel generations of medical doctors and biomedical researchers to shift the current organ- and symptom-based medical concepts toward network- and systems-based ones for more precise diagnoses, interventions, and ideally prevention. In this dynamic setting, the health care system will also have to evolve, if not revolutionize, in terms of organization and management.
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http://dx.doi.org/10.1089/nsm.2020.0004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500076PMC
July 2020

Communication Behavior Changes Between Patients With Diabetes and Healthcare Providers Over 9 Years: Retrospective Cohort Study.

J Med Internet Res 2020 08 11;22(8):e17186. Epub 2020 Aug 11.

Faculty of Sciences, Holon Institute of Technology, Holon, Israel.

Background: Health organizations and patients interact over different communication channels and are harnessing digital communications for this purpose. Assisting health organizations to improve, adapt, and introduce new patient-health care practitioner communication channels (such as patient portals, mobile apps, and text messaging) enhances health care services access.

Objective: This retrospective data study aims to assist health care administrators and policy makers to improve and personalize communication between patients and health care professionals by expanding the capabilities of current communication channels and introducing new ones. Our main hypothesis is that patient follow-up and clinical outcomes are influenced by their preferred communication channels with the health care organization.

Methods: This study analyzes data stored in electronic medical records and logs documenting access to various communication channels between patients and a health organization (Clalit Health Services, Israel). Data were collected between 2008 and 2016 from records of 311,168 patients diagnosed with diabetes, aged 21 years and over, members of Clalit at least since 2007, and still alive in 2016. The analysis consisted of characterizing the use profiles of communication channels over time and used clustering for discretization purposes and patient profile building and then a hierarchical clustering and heatmaps to visualize the different communication profiles.

Results: A total of 13 profiles of patients were identified and characterized. We have shown how the communication channels provided by the health organization influence the communication behavior of patients. We observed how different patients respond differently to technological means of communication and change or don't change their communication patterns with the health care organization based on the communication channels available to them.

Conclusions: Identifying the channels of communication within the health organization and which are preferred by each patient creates an opportunity to convey messages adapted to the patient in the most appropriate way. The greater the likelihood that the therapeutic message is received by the patient, the greater the patient's response and proactiveness to the treatment will be.

International Registered Report Identifier (irrid): RR2-10.2196/10734.
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http://dx.doi.org/10.2196/17186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448191PMC
August 2020

The EFMI Working Group "Healthcare Informatics for Interregional Cooperation": An Evolving Strategy for Building Cooperation Bridges.

Stud Health Technol Inform 2019 Aug;264:1907-1908

Department of Automation and Applied Informatics, Politehnica University Timisoara, Timisoara, Romania.

The Working Group "Health Informatics for Interregional Cooperation" (WG HIIC) of the European Federation for Medical Informatics (EFMI) is dedicated to develop, to implement and to disseminate a strategy for promoting exchange of information, knowledge and experiences all around the world and more particularly, between Health Informatics arena players in the different European continent regions.
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http://dx.doi.org/10.3233/SHTI190707DOI Listing
August 2019

A Multi-Lingual Dictionary for Health Informatics as an International Cooperation Pillar.

Stud Health Technol Inform 2019 Jul;262:31-34

Department of Biomedical Informatics, Rouen University Hospital, France.

Even if, English is generally used for international communication, it is essential to keep in mind that research is running at the local level by local teams generally communicating in their local/national language. Bearing these in mind, the "European Federation for Medical Informatics Working Group on Health Informatics for Inter-regional Cooperation" has as one of its objectives, to develop a multilingual dictionary focusing on Health Informatics as a collaboration tool allowing improving international and more particularly European cooperation. This dictionary is implemented as a part of HeTOP (Health Terminology/Ontology Portal) which is currently integrating more than 70 terminologies and ontologies in 32 languages. The EFMI Dictionary main aims are helping medical librarians, translators, academic and industrial researchers understanding better one another and supporting students self-learning.
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http://dx.doi.org/10.3233/SHTI190009DOI Listing
July 2019

A Social Networks Data Historian Supporting Research in Emergency & Disaster Medicine and Management.

Stud Health Technol Inform 2019 ;258:231-232

Faculty of Technology Management, Holon Institute of Technology - HIT, Israel.

The aim of this initial research is to show that data and information collected from Internet Social Networks support the understanding of individual and collective behaviors which can help emergencies and disasters managers to mitigate and to improve preparedness programs for future similar events and to make more suitable decisions.
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August 2019

Incident gout and chronic Kidney Disease: healthcare utilization and survival.

BMC Rheumatol 2019 19;3:11. Epub 2019 Mar 19.

Clalit Research Institute, Zamenhoff 42, Floor - 1, 6435331 Tel Aviv, Israel.

Background: Uncontrolled gout can cause significant joint and organ damage and has been associated with impairments in quality of life and high economic cost. Gout has also been associated with other comorbid diseases, such as chronic kidney disease. The current study explored if healthcare resource utilization (HRU) and survival differs between patients with incident gout in the presence or absence of chronic kidney disease (CKD).

Methods: Clalit Health Services (CHS) data were used to conduct a retrospective population-based cohort study of incident gout between 1/1/2006-31/12/2009. Incident cases of gout were identified and stratified by CKD status and by age group (< 55 and 55+ years). CKD status was defined as a pre-existing diagnosis of chronic kidney disease, chronic renal failure, kidney transplantation, or dialysis at index date. Demographic and clinical characteristics, as well as healthcare resource use, were reported.

Results: A total of 12,940 incident adult gout patients, with ( = 8286) and without ( = 4654) CKD, were followed for 55,206 person-years. Higher rates of HRU were observed for gout patients with CKD than without. Total annual hospital admissions for patients with gout and CKD were at least 3 times higher for adults < 55 (mean = 0.51 vs 0.13) and approximately 1.5 times higher for adults 55+ (mean = 0.46 vs 0.29) without CKD. Healthcare utilization rates from year 1 to year 5 remained similar for gout patients < 55 years irrespective of CKD status, however varied according to healthcare utilization by CKD status for gout patients 55+ years. The 5-year all-cause mortality was higher among those with CKD compared to those without CKD for both age groups (HR = 1.65; 95% CI 1.01-2.71; HR = 1.50; 95% CI 1.37-1.65).

Conclusions: The current study suggests important differences exist in patient characteristics and outcomes among patients with gout and CKD. Healthcare utilization differed between sub-populations, age and comorbidities, over the study period and the 5-year mortality risk was higher for gout patients with CKD, regardless of age. Future work should explore factors associated with these outcomes and barriers to gout control in order to enhance patient management among this high-risk subgroup.
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http://dx.doi.org/10.1186/s41927-019-0060-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425669PMC
March 2019

Population-based cohort of 500 patients with Gaucher disease in Israel.

BMJ Open 2019 01 21;9(1):e024251. Epub 2019 Jan 21.

Clalit Research Institute, Clalit Health Services, Tel Aviv, Israel.

Objective: To characterise a population-based cohort of patients with Gaucher disease (GD) in Israel relative to the general population and describe sociodemographic and clinical differences by disease severity (ie, enzyme replacement therapy [ERT] use).

Design: A cross-sectional study was conducted.

Setting: Data from the Clalit Health Services electronic health record (EHR) database were used.

Participants: The study population included all patients in the Clalit EHR database identified as having GD as of 30 June 2014.

Results: A total of 500 patients with GD were identified and assessed. The majority were ≥18 years of age (90.6%), female (54.0%), Jewish (93.6%) and 34.8% had high socioeconomic status, compared with 19.0% in the general Clalit population. Over half of patients with GD with available data (51.0%) were overweight/obese and 63.5% had a Charlson Comorbidity Index ≥1, compared with 46.6% and 30.4%, respectively, in the general Clalit population. The majority of patients with GD had a history of anaemia (69.6%) or thrombocytopaenia (62.0%), 40.4% had a history of bone events and 22.2% had a history of cancer. Overall, 41.2% had received ERT.

Conclusions: Establishing a population-based cohort of patients with GD is essential to understanding disease progression and management. In this study, we highlight the need for physicians to monitor patients with GD regardless of their ERT status.
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http://dx.doi.org/10.1136/bmjopen-2018-024251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347887PMC
January 2019

Patterns of Patients' Interactions With a Health Care Organization and Their Impacts on Health Quality Measurements: Protocol for a Retrospective Cohort Study.

JMIR Res Protoc 2018 Nov 7;7(11):e10734. Epub 2018 Nov 7.

Clalit Community Division, Clalit Health Services, Tel-Aviv, Israel.

Background: Data collected by health care organizations consist of medical information and documentation of interactions with patients through different communication channels. This enables the health care organization to measure various features of its performance such as activity, efficiency, adherence to a treatment, and different quality indicators. This information can be linked to sociodemographic, clinical, and communication data with the health care providers and administrative teams. Analyzing all these measurements together may provide insights into the different types of patient behaviors or more accurately to the different types of interactions patients have with the health care organizations.

Objective: The primary aim of this study is to characterize usage profiles of the available communication channels with the health care organization. The main objective is to suggest new ways to encourage the usage of the most appropriate communication channel based on the patient's profile. The first hypothesis is that the patient's follow-up and clinical outcomes are influenced by the patient's preferred communication channels with the health care organization. The second hypothesis is that the adoption of newly introduced communication channels between the patient and the health care organization is influenced by the patient's sociodemographic or clinical profile. The third hypothesis is that the introduction of a new communication channel influences the usage of existing communication channels.

Methods: All relevant data will be extracted from the Clalit Health Services data warehouse, the largest health care management organization in Israel. Data analysis process will use data mining approach as a process of discovering new knowledge and dealing with processing data extracted with statistical methods, machine learning algorithms, and information visualization tools. More specifically, we will mainly use the k-means clustering algorithm for discretization purposes and patients' profile building, a hierarchical clustering algorithm, and heat maps for generating a visualization of the different communication profiles. In addition, patients' interviews will be conducted to complement the information drawn from the data analysis phase with the aim of suggesting ways to optimize existing communication flows.

Results: The project was funded in 2016. Data analysis is currently under way and the results are expected to be submitted for publication in 2019. Identification of patient profiles will allow the health care organization to improve its accessibility to patients and their engagement, which in turn will achieve a better treatment adherence, quality of care, and patient experience.

Conclusions: Defining solutions to increase patient accessibility to health care organization by matching the communication channels to the patient's profile and to change the health care organization's communication with the patient to a highly proactive one will increase the patient's engagement according to his or her profile.

International Registered Report Identifier (irrid): RR1-10.2196/10734.
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http://dx.doi.org/10.2196/10734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249502PMC
November 2018

Healthcare Informatics Project-Based Learning: An Example of a Technology Management Graduation Project Focusing on Veterinary Medicine.

Authors:
Arriel Benis

Stud Health Technol Inform 2018 ;255:267-271

Faculty of Technology Management, Holon Institute of Technology - HIT, Israel.

Teaching Healthcare Informatics using Project-Based Learning focuses students on active and inquiry-based learning and allows them to gain some knowledge and skills in the field. From the perspective of Technology Management, which is at the cross-road of Sciences, Engineering and Business Administration studies, Healthcare Informatics is an interesting application domain for developing both innovation and management capabilities. However, the specificities of Healthcare Informatics (standards, methodologies, human- or animal-focused information) require an additional involvement from the students to deliver projects that fit real-world needs and constraints. In this paper, we initially define the Technology Management field and describe how it is related to Healthcare Informatics, then we introduce Project-Based Learning and finally we present an example of a graduation project that focuses on Veterinary Medicine.
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August 2019

Administrative health databases for addressing emerging issues in adults with CHD: a systematic review.

Cardiol Young 2018 Jun 29;28(6):844-853. Epub 2018 Apr 29.

1INSERM-UMRS 1138 Team 22,Cordeliers Research Center,Paris Descartes University,Paris,France.

The need for population-based studies of adults with CHD has motivated the growing use of secondary analyses of administrative health data in a variety of jurisdictions worldwide. We aimed at systematically reviewing all studies using administrative health data sources for adult CHD research from 2006 to 2016. Using PubMed and Embase (1 January, 2006 to 1 January, 2016), we identified 2217 abstracts, from which 59 studies were included in this review. These comprised 12 different data sources from six countries. Of these, 55% originated in the United States of America, 28% in Canada, and 17% in Europe and Asia. No study was published before 2007, after which the number of publications grew exponentially. In all, 41% of the studies were cross-sectional and 25% were retrospective cohort studies with a wide variation in the availability of patient-level compared with hospitalisation-level episodes of care; 58% of studies from eight different data sources linked administrative data at a patient level; and 37% of studies reported validation procedures. Assessing resource utilisation and temporal trends of relevant epidemiological and outcome end points were the most reported objectives. The median impact factor of publication journals was 4.04, with an interquartile range of 3.15, 7.44. Although not designed for research purposes, administrative health databases have become powerful data sources for studying adult CHD populations because of their large sample sizes, comprehensive records, and long observation periods, providing a useful tool to further develop quality of care improvement programmes. Data linkage with electronic records will become important in obtaining more granular life-long adult CHD data. The health services nature of the data optimises the impact on policy and public health.
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http://dx.doi.org/10.1017/S1047951118000446DOI Listing
June 2018

Risk and Disaster Management: From Planning and Expertise to Smart, Intelligent, and Adaptive Systems.

Stud Health Technol Inform 2018 ;247:286-290

Holon Institute of Technology - HIT, Israel.

"Disaster" means some surprising and misfortunate event. Its definition is broad and relates to complex environments. Medical Informatics approaches, methodologies and systems are used as a part of Disaster and Emergency Management systems. At the Holon Institute of Technology - HIT, Israel, in 2016 a National R&D Center: AFRAN was established to study the disaster's reduction aspects. The Center's designation is to investigate and produce new approaches, methodologies and to offer recommendations in the fields of disaster mitigation, preparedness, response and recovery and to disseminate disaster's knowledge. Adjoint to the Center a "Smart, Intelligent, and Adaptive Systems" laboratory (SIAS) was established with the goal to study the applications of Information and Communication Technologies (ICT) and Artificial Intelligence (AI) to Risk and Disaster Management (RDM). In this paper, we are redefining the concept of Disaster, pointing-out how ICT, AI, in the Big Data era, are central players in the RDM game. In addition we show the merit of the Center and lab combination to the benefit of the performed research projects.
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June 2018

DisEpi: Compact Visualization as a Tool for Applied Epidemiological Research.

Stud Health Technol Inform 2017 ;244:38-42

Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel-Aviv, Israel.

Outcomes research and evidence-based medical practice is being positively impacted by proliferation of healthcare databases. Modern epidemiologic studies require complex data comprehension. A new tool, DisEpi, facilitates visual exploration of epidemiological data supporting Public Health Knowledge Discovery. It provides domain-experts a compact visualization of information at the population level. In this study, DisEpi is applied to Attention-Deficit/Hyperactivity Disorder (ADHD) patients within Clalit Health Services, analyzing the socio-demographic and ADHD filled prescription data between 2006 and 2016 of 1,605,800 children aged 6 to 17 years. DisEpi's goals facilitate the identification of (1) Links between attributes and/or events, (2) Changes in these relationships over time, and (3) Clusters of population attributes for similar trends. DisEpi combines hierarchical clustering graphics and a heatmap where color shades reflect disease time-trends. In the ADHD context, DisEpi allowed the domain-expert to visually analyze a snapshot summary of data mining results. Accordingly, the domain-expert was able to efficiently identify that: (1) Relatively younger children and particularly youngest children in class are treated more often, (2) Medication incidence increased between 2006 and 2011 but then stabilized, and (3) Progression rates of medication incidence is different for each of the 3 main discovered clusters (aka: profiles) of treated children. DisEpi delivered results similar to those previously published which used classical statistical approaches. DisEpi requires minimal preparation and fewer iterations, generating results in a user-friendly format for the domain-expert. DisEpi will be wrapped as a package containing the end-to-end discovery process. Optionally, it may provide automated annotation using calendar events (such as policy changes or media interests), which can improve discovery efficiency, interpretation, and policy implementation.
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June 2018

Identification and Description of Healthcare Customer Communication Patterns Among Individuals with Diabetes in Clalit Health Services: A Retrospective Database Study.

Stud Health Technol Inform 2017 ;244:18-22

Clalit Research Institute, Chief Medical Office, Clalit Health Services, Tel-Aviv, Israel.

HMOs record medical data and their interactions with patients. Using this data we strive to identify sub-populations of healthcare customers based on their communication patterns and characterize these sub-populations by their socio-demographic, medical, treatment effectiveness, and treatment adherence profiles. This work will be used to develop tools and interventions aimed at improving patient care. The process included: (1) Extracting socio-demographic, clinical, laboratory, and communication data of 309,460 patients with diabetes in 2015, aged 32+ years, having 7+ years of the disease treated by Clalit Healthcare Services; (2) Reducing dimensions of continuous variables; (3) Finding the K communication-patterns clusters; (4) Building a hierarchical clustering and its associated heatmap to summarize the discovered clusters; (5) Analyzing the clusters found; (6) Validating results epidemiologically. Such a process supports understanding different communication-channel usage and the implementation of personalized services focusing on patients' needs and preferences.
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June 2018

Obesity or smoking: Which factor contributes more to the incidence of myocardial infarction? Authors' Reply.

Eur J Intern Med 2016 10 4;34:e25-e26. Epub 2016 Jul 4.

Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel.

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http://dx.doi.org/10.1016/j.ejim.2016.06.025DOI Listing
October 2016

Obesity or smoking: Which factor contributes more to the incidence of myocardial infarction?

Eur J Intern Med 2016 Jul 14;32:43-6. Epub 2016 Apr 14.

Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel.

Objective: Comparing the contributions of smoking and obesity to the risk of myocardial infarction (MI) can help prioritize behavioral modifications. The objective of this study was to determine the relative risk of smoking, obesity and the joint burden on the risk of MI.

Methods: This is a retrospective cohort study of data accessed from electronic medical records of the largest health care organization in Israel. The study population included all 738,380 members of Clalit Health Services, with at least one smoking status and one BMI assessment recorded in 2009 or 2010, aged 40-74years, who were MI-free before 2009. Obesity was defined as BMI >30kg/m(2). New and primary MI between January 1 and December 31, 2011 were recorded.

Results: Rates of MI were: 0.18% for non-obese never smokers, 0.25% for obese never smokers, 0.40% for non-obese past smokers, 0.50% for obese past smokers, 0.53% for non-obese current smokers and 0.66% for obese current smokers. Among non-obese individuals, past smokers and current smokers had a greater risk of MI than did never smokers, after adjusting for age, gender and socioeconomic position (OR, 1.45; 95% CI, 1.23-1.70 and OR, 2.35; 95% CI, 2.10-2.63, respectively). The burden of obesity increased the risk of MI for never smokers but the burden of obesity did not elevate the risk of MI when combined with current or past smoking groups, after adjusting for comorbidities.

Conclusions: Past and, more so, current smoking confers greater risk for MI than obesity.
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http://dx.doi.org/10.1016/j.ejim.2016.03.029DOI Listing
July 2016

Stimulant use for ADHD and relative age in class among children in Israel.

Pharmacoepidemiol Drug Saf 2016 06 29;25(6):652-60. Epub 2016 Jan 29.

Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

Background: Diagnosis of children with attention-deficit/hyperactivity disorder (ADHD) is increasing. The present study sought to identify characteristics and medication treatment patterns of children with ADHD and compare them by relative age in class, sex, ethnicity, family size, sibling order, and other socioeconomic status, as well as find trends in disparity of pharmacotherapy.

Methods: This study was based on data from 1 013 149 Clalit Health Services members aged 6-17 years during 2006-2011. Centrally acting sympathomimetic drug purchases were compared according to children's estimated relative age in class; youngest third (born August to November), middle third (born April to July), and oldest third (born December to March). Treatment trends were determined and compared according to sociodemographic and family-related factors.

Results: The overall prevalence of stimulant use in the population was 2.6% in 2006 and 4.9% in 2011. The annual incidence of stimulant use increased from 0.75% to 1.36%, rising more sharply among children in the older age groups (≥12) than among younger ones. Moreover, the youngest third of children in class was more likely to use medication than the oldest third (risk ratio (RR) 1.17, confidence interval (CI) 1.12-1.23) or the middle third (RR 1.06, CI 1.01-1.11). Of the different ethnic sectors, incidence of stimulant use was highest among general Jewish (1.8% in 2011) and lowest among Arabs (0.37% in 2011).

Conclusions: The use of stimulant medication is growing among children in Israel. Although the overall use does not exceed the estimated prevalence of ADHD among children, the appropriateness of prescribing to the Israeli pediatric population, especially to the youngest children in class, may be questionable. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pds.3962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889495PMC
June 2016

Dynamics of circulating hypoxia-mediated miRNAs and tumor response in patients with high-grade glioma treated with bevacizumab.

J Neurosurg 2016 10 22;125(4):1008-1015. Epub 2016 Jan 22.

Leslie and Michael Gaffin Center for Neuro-Oncology and Department of Neurology, The Agnes Ginges Center for Human Neurogenetics.

OBJECTIVE Bevacizumab is an antiangiogenic agent under investigation for use in patients with high-grade glioma. It produces a high rate of radiological response; however, this response should be interpreted with caution because it may reflect normalization of the tumor vasculature and not necessarily a true antitumor effect. The authors previously demonstrated that 4 hypoxia-mediated microRNAs (miRNA)-miR-210, miR-21, miR-10b, and miR-196b-are upregulated in glioma as compared with normal brain tissue. The authors hypothesized that the regulation and expression of these miRNAs would be altered in response to bevacizumab treatment. The object of this study was to perform longitudinal monitoring of circulating miRNA levels in patients undergoing bevacizumab treatment and to correlate it with tumor response. METHODS A total of 120 serum samples from 28 patients with high-grade glioma were prospectively collected prior to bevacizumab (n = 15) or temozolomide (TMZ; n = 13) treatment and then longitudinally during treatment. Quantification of the 4 miRNAs was evaluated by real-time polymerase chain reaction using total RNA extracted from the serum. At each time point, tumor response was assessed by Response Assessment in Neuro-Oncology criteria and by performing MRI using fluid attenuated inversion recovery (FLAIR) and contrast-enhanced images. RESULTS As compared with pretreatment levels, high levels of miR-10b and miR-21 were observed in the majority of patients throughout the bevacizumab treatment period. miR-10b and miR-21 levels correlated negatively and significantly with changes in enhancing tumor diameters (r = -0.648, p < 0.0001) in the bevacizumab group but not in the TMZ group. FLAIR images and the RANO assessment did not correlate with the sum quantification of these miRNAs in either group. CONCLUSIONS Circulating levels of miR-10b and miR-21 probably reflect the antiangiogenic effect of therapy, but their role as biomarkers for tumor response remains uncertain and requires further investigation.
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http://dx.doi.org/10.3171/2015.8.JNS15437DOI Listing
October 2016

Sex-specific prediction of interferon beta therapy response in relapsing-remitting multiple sclerosis.

J Clin Neurosci 2015 Jun 14;22(6):986-9. Epub 2015 Apr 14.

Department of Neurology, The Agnes-Ginges Center for Neurogenetics, Hadassah-Hebrew University Hospital, Ein-Kerem, P.O. Box 12000, Jerusalem 91120, Israel. Electronic address:

Multiple sclerosis (MS) is a demyelinating disorder predominantly affecting young people. Currently, interferon beta (IFNβ) is a common treatment for MS. Despite a large effort in recent years, valid biomarkers with predictive value for clinical outcome and response to therapy are lacking. In order to identify predictive biomarkers of response to IFNβ therapy in relapsing-remitting MS patients, we analyzed expression of 526 immune-related genes with the nCounter Analysis System (NanoString Technologies, Seattle, WA, USA) on total RNA extracted from peripheral blood mononuclear cells of 30 relapsing-remitting MS patients. We used a Wilcoxon signed-rank test to find an association between certain gene expression profiles and clinical responses to IFNβ. We compared the expression profile of patients who responded to IFNβ treatment (n=16) and non-responsive IFNβ patients (n=14). The analysis revealed that the expression of eight genes could differentiate between responsive and non-responsive men (p⩽0.005). This differentiation was not evident in women. We analyzed results from an additional cohort of 47 treated and untreated patients to validate the results and explore whether this eight gene cluster could also predict treatment response. Analysis of the validation cohort demonstrated that three out of the eight genes remained significant in only the treated men (p⩽0.05). Our findings could be used as a basis for establishing a routine test for objective prediction of IFNβ treatment response in male MS patients.
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http://dx.doi.org/10.1016/j.jocn.2014.11.027DOI Listing
June 2015

Cathepsin S, a novel biomarker of adiposity: relevance to atherogenesis.

FASEB J 2005 Sep 28;19(11):1540-2. Epub 2005 Jun 28.

INSERM Avenir, Paris, France.

The molecular mechanisms by which obesity increases the risk of cardiovascular diseases are poorly understood. The purpose of this study was to identify candidate biomarkers overexpressed in adipose tissue of obese subjects that could link expanded fat mass to atherosclerosis. We compared gene expression profile in subcutaneous adipose tissue (scWAT) of 28 obese and 11 lean subjects using microarray technology. This analysis identified 240 genes significantly overexpressed in scWAT of obese subjects. The genes were then ranked according to the correlation between gene expression and body mass index (BMI). In this list, the elastolytic cysteine protease cathepsin S was among the highly correlated genes. RT-PCR and Western blotting confirmed the increase in cathepsin S mRNA (P=0.006) and protein (P<0.05) in obese scWAT. The circulating concentrations of cathepsin S were also significantly higher in obese than in nonobese subjects (P<0.0001). Both cathepsin S mRNA in scWAT and circulating levels were positively correlated with BMI, body fat, and plasma triglyceride levels. In addition, we show that the proinflammatory factors, lipopolysaccharide, interleukin-1beta, and tumor necrosis factor-alpha increase cathepsin S secretion in human scWAT explants. This study identifies cathepsin S as a novel marker of adiposity. Since this enzyme has been implicated in the development of atherosclerotic lesions, we propose that cathepsin S represents a molecular link between obesity and atherosclerosis.
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http://dx.doi.org/10.1096/fj.05-3673fjeDOI Listing
September 2005

Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects.

FASEB J 2004 Nov;18(14):1657-69

INSERM Avenir Paris 6 University, EA 3502, Nutrition Department, AP/HP, Hôtel-Dieu, Paris, France.

Adipose tissue produces inflammation and immunity molecules suspected to be involved in obesity-related complications. The pattern of expression and the nutritional regulation of these molecules in humans are poorly understood. We analyzed the gene expression profiles of subcutaneous white adipose tissue from 29 obese subjects during very low calorie diet (VLCD) using cDNA microarray and reverse transcription quantitative PCR. The patterns of expression were compared with that of 17 non-obese subjects. We determined whether the regulated genes were expressed in adipocytes or stromavascular fraction cells. Gene expression profiling identified 100 inflammation-related transcripts that are regulated in obese individuals when eating a 28 day VLCD but not a 2 day VLCD. Cluster analysis showed that the pattern of gene expression in obese subjects after 28 day VLCD was closer to the profile of lean subjects than to the pattern of obese subjects before VLCD. Weight loss improves the inflammatory profile of obese subjects through a decrease of proinflammatory factors and an increase of anti-inflammatory molecules. The genes are expressed mostly in the stromavascular fraction of adipose tissue, which is shown to contain numerous macrophages. The beneficial effect of weight loss on obesity-related complications may be associated with the modification of the inflammatory profile in adipose tissue.
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http://dx.doi.org/10.1096/fj.04-2204comDOI Listing
November 2004

In vivo epinephrine-mediated regulation of gene expression in human skeletal muscle.

J Clin Endocrinol Metab 2004 May;89(5):2000-14

Unité de Recherches sur les Obésités, Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 586, Institut Louis Bugnard, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, 31403 Toulouse, France.

The stress hormone epinephrine produces major physiological effects on skeletal muscle. Here we determined skeletal muscle mRNA expression profiles before and during a 6-h epinephrine infusion performed in nine young men. Stringent statistical analysis of data obtained using 43000 cDNA element microarrays showed that 1206 and 474 genes were up- and down-regulated, respectively. Microarray data were validated using reverse transcription quantitative PCR. Gene classification was performed through data mining of Gene Ontology annotations, cluster analysis of regulated genes among 14 human tissues, and correlation analysis of mRNA and clinical parameter variations. Evidence of an autoregulatory control was provided by the regulation of key genes of the cAMP-dependent transcription pathway. Genes with known functional cAMP response elements were regulated by the hormone. The impact on metabolism was illustrated by coordinated regulations of genes involved in carbohydrate and protein metabolisms. Epinephrine had a profound effect on genes involved in immunity and inflammatory response, a previously unappreciated aspect of catecholamine action. Information on 526 mRNAs corresponded to genes of unknown function. These data define the molecular signatures of epinephrine action in human skeletal muscle. They may contribute to the understanding of skeletal muscle alterations observed in pathological conditions characterized by sympathetic nervous system overdrive.
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http://dx.doi.org/10.1210/jc.2003-031733DOI Listing
May 2004