Abstract
Background: The purpose of this review was to examine and chart the “scope” of strategies reported in ED-SBIRT (emergency department-based screening, brief intervention and referral to treatment) studies that employ non–face-to-face (nFtF) modalities for high-risk alcohol use (i.e., risk for alcohol-related injury, medical condition, use disorder) and to identify research gaps in the scientific literature. Methods: The scoping review population included study participants with high-risk alcohol use patterns as well as study participants targeted for primary public health prevention (e.g., adolescent ED patients). Core concepts included SBIRT components among intervention studies that incorporated some form of nFtF modality (e.g., computer-assisted brief intervention). The context encompassed ED-based studies or trauma center studies, regardless of geographic location. After screening a total of 1526 unique references, reviewers independently assessed 58 full-text articles for eligibility. Results: A total of 30 full-text articles were included. Articles covered a period of 14 years (2003–2016) and 19 journal titles. Authors reported the use of a wide range of nFtF modalities across all 3 ED-SBIRT components: “screening” (e.g., computer tablet screening), “brief intervention” (e.g., text message–based brief interventions), and “referral to treatment” (e.g., computer-generated feedback with information about alcohol treatment services). The most frequently used nFtF modality was computerized screening and/or baseline assessment. The main results were mixed with respect to showing evidence of ED-SBIRT intervention effects. Conclusions: There is an opportunity for substance use disorder researchers to explore the specific needs of several populations (e.g., ED patients with co-occurring problems such as substance use disorder and violence victimization) and on several methodological issues (e.g., ED-SBIRT theory of change). Substance use disorder researchers should take the lead on establishing guidelines for the reporting of ED-SBIRT studies—including categorization schemes for various nFtF modalities. This would facilitate both secondary research (e.g., meta-analyses) and primary research design.
Keywords
Introduction
Screening, brief intervention, and referral to treatment (SBIRT) has been defined as “a comprehensive, integrated, public health approach to the delivery of early intervention and treatment services for persons with substance use disorders, as well as those who are at risk of developing these disorders.” 1 (pxx) The components of SBIRT involve rapid assessment of the patient's severity of substance use (“screening”); increasing the patient's awareness regarding substance use as well as their motivation to change behavior (“brief intervention”); and providing those identified as needing additional treatment with access to specialty care (“referral to treatment”). There exists a long history of SBIRT research and practice within emergency department settings (ED-SBIRT), with the first study being a controlled trial of 200 dependent drinkers at Massachusetts General Hospital in 1957. 2 , 3 Many authors have characterized the ED visit as a “teachable moment” when an individual patient might be especially amenable to change a health behavior such as high-risk alcohol use. 4 – 9 Recently, ED-SBIRT researchers have been testing the effects of non–face-to-face (nFtF) modalities—e.g., computer-guided brief intervention. To our knowledge, there is currently no review of the literature that catalogs the extent, range, and nature (i.e., scope) of strategies and outcomes in ED-SBIRT studies that employ nFtF modalities for high-risk alcohol use.
As the most commonly used drug in the United States, consequences of high-risk alcohol use persist as major short- and long-term detriments to both individual and population health. In 2015, the United States experienced the largest percent increase in motor vehicle crash fatalities in 50 years. 10 This included a significant increase in alcohol-impaired driving fatalities, with nearly one alcohol-impaired driving death occurring every 51 minutes. 11 Total charges of ED visits with all-listed alcohol-related diagnoses totaled more than $11 billion in 2010. 12 ED-SBIRT is one means of curbing these numbers and traditionally has been conducted by physicians, nurses, or other personnel engaging patients one-on-one, yet several clinical-setting barriers to broad implementation exist. 13 – 15 Included among the reported rationale for use of nFtF modalities in ED-SBIRT are lack of participation by ED staff or other personnel in traditional SBIRT; 4 – 7 , 9 , 16 – 19 greater likelihood of disclosing negative behaviors by patients; 4 , 7 , 9 , 17 , 19 reduced likelihood of interfering with patient care; 4 , 7 , 16 more freedom for participants to proceed with brief intervention components at their own pace; 4 , 7 , 9 less time required of study personnel (e.g., research assistants); 4 – 6 , 20 less resources required for training and monitoring of brief intervention delivery personnel (e.g., to ensure fidelity); 5 , 6 , 9 , 18 , 20 and the opportunity of providing a brief intervention that matches a patient's literacy level 17 and native language. 7 ,19
Understanding the scope of strategies and outcomes in ED-SBIRT studies that employ nFtF modalities for high-risk alcohol use is essential for improving evidence-based practice. In Figure 1, we depict one possible ordering of knowledge-synthesis methodologies. A narrative review can be characterized as a review of literature that is unsystematically searched with minimal data extraction, whereas evidence mapping may add a systematic search for evidence with tabular summaries of the findings of the studies. 21 Whereas systematic reviews are narrow in focus and designed around specific research questions, 22 , 23 scoping reviews are wider-ranging in describing the nature and extent of existing evidence. 24 A scoping review has been defined as an “aim to map rapidly the key concepts underpinning a research area and the main sources and types of evidence available, and can be undertaken as stand-alone projects in their own right, especially when an area is complex or has not been reviewed comprehensively before.” 25 Other reasons for conducting a scoping review are to clarify working definitions and to elucidate the conceptual boundaries of a topic, and the benefits include clarifying key concepts for consistency of use by others, identifying gaps in the evidence base, and informing future study designs by documenting the ways that prior studies have been conducted. 24 ,26

Possible ordering of knowledge-synthesis methodologies (adapted from Dijkers 21 ).
The primary objective of this scoping review was to examine and chart the extent, range, and nature of strategies reported in ED-SBIRT studies that employ nFtF modalities for high-risk alcohol use. Our secondary objective was to identify research gaps in the scientific literature specifically related to ED-SBIRT that employs nFtF modalities.
Review
We performed a scoping review in accordance with the methodology for Joanna Briggs Institute scoping reviews, 24 which draws upon two other influential scoping review frameworks. 26 , 27 Scoping review methods can be reported under the following rubrics: inclusion criteria, types of sources, screening strategy, and extraction of results.
We framed our scoping review question as follows: “What types of strategies have been reported in ED-SBIRT studies that employ nFtF modalities for high-risk alcohol use?” Sources were considered for inclusion in the scoping review based on this review question, the aforementioned goals of this investigation, and the PCC mnemonic: Population, Concepts, and Context. 24 Our population of interest included study participants with high-risk alcohol use patterns (i.e., secondary/tertiary public health prevention) as well as study participants targeted for primary public health prevention (e.g., adolescent ED patients). Core concepts included SBIRT components among intervention studies that incorporated at least one form of nFtF modality (e.g., self-administered computer assessment, telephone booster sessions, tailored mailings, etc.) for a purpose other than merely conducting SBIRT follow-up assessments. We excluded nonintervention studies as well as studies that did not incorporate (at a minimum) screening or brief assessment and brief intervention elements. The context encompassed ED-based studies or trauma center studies, regardless of geographic location. Articles had to be published in the English language, and the types of sources could not include lay publications or nonempirical works.
A senior medical librarian (DPH) searched for relevant articles in both PubMed (National Library of Medicine, National Institutes of Health [NLM/NIH]) and Scopus (Elsevier) to help determine the appropriate controlled vocabulary terms and synonymous free-text words necessary to capture the concepts of alcohol-related disorders, emergency medical services, and screening or intervention(s). Next, we used an iterative process to translate and refine the searches to create more comprehensive searches performed on multiple databases: PubMed (NLM/NIH), Ovid PsycINFO (1967 to July Week 2, 2016), Scopus (Elsevier), and CINAHL (EbscoHost). All searches were conducted on July 12, 2016, except for CINAHL, which was searched on July 18, 2016. The search strategies were filtered to include only articles written in English, but results were not limited by study design or year of publication. All search strategies are available from the corresponding author upon request. A flowchart per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines 28 is presented in Figure 2.

PRISMA flow diagram for screening and assessment of articles for potential inclusion in nFtF ED-SBIRT scoping review.
The final search retrieved a total of 1658 references, which were pooled in EndNote (Clarivate Analytics, Philadelphia, PA) and de-duplicated to 1526 references. This set was uploaded to Covidence review software (Covidence, Melbourne, Australia) for screening. Within Covidence, one reviewer (B.J.B.) screened the title and abstract of the 1526 de-duplicated records using the aforementioned inclusion/exclusion criteria. If no abstract was available and a decision could not be made otherwise, the reviewer searched online for additional information. We did not contact authors of primary studies for additional information at this stage.
After screening each record, 2 reviewers (F.E.V., B.J.B.) independently assessed the remaining 58 full-text articles for eligibility. The same inclusion/exclusion criteria as above were applied. Reasons for exclusion of full-text articles included wrong type of study design (n = 17), wrong type of study outcome (n = 8), wrong type of intervention (n = 2), and wrong type of patient population (n = 1). A total of 30 full-text articles were used for data extraction.
For included full-text articles, we extracted data into a Microsoft Excel spreadsheet (Microsoft, Redmond, WA). We extracted data on the following items to inform the scoping review question and objectives: authors; publication year; article title; publication name; article keywords; study funder(s); study objectives; study design; inclusion criteria; exclusion criteria; study setting; SBIRT description (general); subject identification methods; screening methods; baseline assessment methods; brief intervention methods; referral to treatment methods; nFtF modality(-ies); study arm(s); follow-up measures; randomization methods; study blinding; statistical analyses; sample size; subject characteristics; main findings; and (disclosed) limitations. Data coding and reduction was performed using IBM SPSS Statistics 24.29
The main features of the 30 articles identified among ED-SBIRT studies employing nFtF modalities for high-risk alcohol use are listed in Table 1. 4 – 9 , 16 – 20 , 30 – 48 Table 2 depicts the aggregated study characteristics of the 30 articles. The articles covered a period of 14 years (2003–2016) and 19 journal titles, with an apparent increasing trend in the frequency of articles over time (Figure 3). The greatest number of articles (n = 10; 33%) were published in journals categorized by InCite Journal Citation Reports (Thomson Reuters) as a “Substance Abuse” publication. The study objectives of most articles fell within the purview of ED-SBIRT for efficacy testing (70%), but some were focused more so on feasibility testing (20%). Articles tended to be based on more-traditional study designs (e.g., 2-group parallel randomized controlled trial [RCT]). Regarding inclusion criteria, more than one third of the articles (n = 12) reported results from studies focused on adolescents or young adults. 4 , 5 , 17 , 18 , 20 , 31 , 38 , 43 – 45 , 47 , 48 Two articles were based on studies restricted to female participants. 37 , 42 A total of 13 US-based articles (43%) were based on studies that deemed non–English-speaking patients to be ineligible. 7 , 20 , 30 , 32 , 37 , 39 , 40 , 42 – 45 , 47 , 48 All but 6 articles 9 , 16 , 33 , 35 , 36 , 46 originated from US-based studies.

Bivariate scatter plot for frequency of nFtF ED-SBIRT publications (y-axis) by year of publication (x-axis).
Data extracted from 30 articles retrieved during scoping review—Description of main study features.
Note. SS = statistically significant; NSS = not statistically significant.
ED-SBIRT study characteristics extracted from 30 articles retrieved during scoping review.
We performed geospatial visualization by US state for funding data as reported in NIH RePORTER by using Sci2, a modular toolset specifically designed for the study of science. 49 We also contacted lead authors to request confirmation of funding data as reported in NIH RePORTER or for actual funding amounts for studies not found in NIH RePORTER (US-based only). Figure 4 is a proportional symbol map of total funding amounts by US state. The greatest concentrations of funding were located in the Great Lakes and New England regions. We also attempted a temporal analysis using Sci2 software and applied Kleinberg's burst-detection algorithm 50 in order to identify sudden increases in the frequency of words contained within the 30 article titles as well as the author-designated keywords. The titles and keywords associated with these 30 articles were relatively homogenous over time (see supplementary material).

Geospatial visualization (proportional symbol map) for nFtF ED-SBIRT research funding by US state.
The ED-SBIRT strategies of the 30 journal articles identified during the scoping review are shown in Table 3. The intervention objectives of most articles fell within the purview of ED-SBIRT for selective prevention (n = 22; 73%). Among studies that reported the duration of subject recruitment (n = 28), the range was from 1 to 41 months (mean = 22 months). Regarding the identification of potential study participants, only 4 articles 30 , 40 , 47 , 48 originated from studies that made mention of probabilistic selection procedures (e.g., ED shifts selected at random). Authors reported the use of a variety of standardized alcohol screening questions, including the Alcohol Misuse Index (Amidx), 5 the Alcohol Frequency/Quantity (AFQ) Index, 5 the Alcohol Use Disorders Identification Test (AUDIT), 6 , 7 , 16 , 19 , 33 , 35 , 36 , 39 , 42 the AUDIT Consumption (AUDIT-C), 17 , 18 , 31 , 34 , 43 – 45 , 47 , 48 the time-line follow-back method (TLFB), 20 the TWEAK test, 37 the National Institute on Alcohol Abuse and Alcoholism (NIAAA) questions, 32 , 39 , 42 and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). 40 Whereas all articles reported both screening or assessment and brief intervention elements (see inclusion criteria above), less than two thirds of articles (18/30) 6 , 16 – 20 , 31 , 34 – 37 , 41 – 45 , 47 , 48 reported a “referral” component, all of which were considered passive referrals. Authors reported the use of a wide range of nFtF modalities across all 3 ED-SBIRT components: “screening” (e.g., computerized screening, 4 , 5 , 8 , 9 , 16 – 20 , 30 , 31 , 37 , 38 , 40 , 43 – 45 , 47 , 48 telephone screening 35 , 36 ), ”brief intervention” (e.g., computerized brief interventions, 4 , 5 , 17 – 19 , 31 , 33 , 41 , 47 , 48 bibliotherapy, 6 , 30 computer-generated feedback printouts, 9 , 16 , 19 telephone brief interventions, 7 , 39 , 40 telephone boosters, 7 , 20 , 32 – 34 , 38 – 40 , 42 mailed personalized feedback, 35 , 36 text message–based brief interventions, 43 – 45 brochures 38 ), and “referral” (e.g., computer-generated feedback with info about alcohol treatment services, 16 , 19 , 34 , 41 , 46 mailed personalized feedback with info about alcohol treatment services 35 , 36 ).
Data extracted from 30 articles retrieved during scoping review—SBIRT strategies.
The number of study “arms” ranged from 1 to 6 (Table 3) and included a variety of comparison groups: e.g., assessment only with/without provision of information on alcohol support services. Follow-up assessments were conducted using a range of modalities (e.g., computer-assisted telephone interviews) and time periods (e.g., weekly, 30 days, 6 weeks, 2 months, 3 months, 4 months, 6 months, 8 months, 9 months, 12 months). Follow-up measures were also wide-ranging: proximal outcomes (e.g., readiness to change); alcohol-use for the 30 days prior; number of days drinking; average weekly consumption; heavy episodic drinking; driving behavior; alcohol-related negative consequences; alcohol-related injuries; and seeking support, resources, or treatment for alcohol use disorder. Randomized allocation to study arms was most often reported as “block randomization,” and blinding was not reported (or not applicable) in approximately one third of the articles (11/30). With few exceptions, 17 , 18 , 31 , 38 , 43 – 45 when study subject characteristics were reported, males constituted most participants (i.e., in studies not restricted to female participants 37 , 42 ). Main results were mixed with respect to showing evidence of ED-SBIRT intervention effects (Table 1). Authors’ disclosed limitations tended to focus on selective recruitment time periods; missing out on subjects eligible for inclusion in the study; lack of blinding; differential loss to follow-up; limited statistical power; sole reliance on participant self-report (29/30 articles); ceiling (or floor) effects; and uncertain generalizability of results.
Conclusions
To our knowledge, this scoping review represents the first catalog of the extent, range, and nature (i.e., scope) of strategies and outcomes in ED-SBIRT studies that employed nFtF modalities for high-risk alcohol use. We extracted data from 30 full-text articles published in journals mostly classified as “Substance Abuse” or “Emergency Medicine” publications. In terms of study design, there is an opportunity for ED-SBIRT researchers to move beyond traditional designs (e.g., 2-arm RCTs) and explore other study designs (e.g., micro-randomized trials 51 ) and approaches (e.g., multiphase optimization strategy [MOST] 52 ). Regarding inclusion criteria, there may be an opportunity to explore ED-SBIRT for high-risk alcohol use among older patients. None of the studies reviewed here were focused on older adults, and some researchers have called for ED clinicians to help heavy-drinking older adults reduce their high-risk alcohol use. 53 Another area for future research is ED-SBIRT that focuses on the specific needs of female patients—a demographic group that, over the past generation, has exhibited unfavorable trends regarding increases in alcohol consumption 54 , 55 and alcohol-involved fatal crashes.56
To elaborate, only two of the articles reviewed here were focused on female participants—both of which had an emphasis on intimate partner violence (IPV). 37 , 42 Managers (e.g., hospital administrators, public health planners, policy makers) are not confronted with problems that are independent of each other, but with dynamic situations that consist of complex problems that interact with each other—i.e., “wicked problems” are those complex, ever-changing problems that are difficult to define and structure properly because they are messy, ambiguous, and reactive. 57 Such is the case with syndemics, which involve a set of enmeshed and mutually enhancing health problems that, working together in a context of harmful social and physical conditions, can significantly affect the overall disease burden and health status of a community. 58 Of particular concern for population health managers is the set of mutually enhancing epidemics of substance abuse, violence, and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), also referred to as the SAVA syndemic. 58 The SAVA syndemic is highly prevalent among impoverished urban women and potentially associated with poor HIV outcomes. 59 , 60 The most urgent concern for population health management of the SAVA syndemic among affected women and girls is early diagnosis and intervention as well as mental and physical rehabilitation to reduce damage caused by symptomatic disease (i.e., secondary/tertiary prevention). Although violence such as IPV and sexual assault is not restricted to female ED patients, emerging research suggests that SBIRT may reduce IPV and HIV risks for women; 60 however, integrated substance abuse, violence, and HIV/AIDS SBIRT models have not been adequately tested.
Additionally, but also related to the above, 13 articles reviewed here were based on studies that deemed non–English-speaking patients to be ineligible. There is an opportunity for additional investigation into ED-SBIRT for high-risk alcohol use among non–English-speaking patients. For example, one of the coauthors, Federico E. Vaca is the Principal Investigator of an active National Institutes of Health R01 study titled “Automated Bilingual-Computerized Alcohol Screening and Intervention (AB-CASI).” That study is an ED-based health information technology initiative that addresses the full spectrum of alcohol use disorders (from “at risk” to “dependence”) and their negative consequences in Latino ED patients. That study encompasses the rigorous testing of a brief intervention designed to facilitate alcohol use reduction and enhance engagement in specialized treatment initiation in Latino ED patients. AB-CASI is a tablet-delivered brief negotiation interview (BNI) encompassing branching logic and delivering motivational and personalized reflective statements. Provided in a busy clinical setting, AB-CASI embodies innovation where health information technology interfaces with disease prevention, health promotion, and clinical patient-oriented outcomes research. The purpose of the BNI is to assist patients to reduce/abstain from high-risk alcohol use. It combines techniques from motivational interviewing and behavioral contracting within a 5- to 10-minute SBIRT intervention for alcohol use. Moreover, only recently have emergency medicine researchers started to embrace technological interventions for co-occurring phenomena such as substance use disorder and intimate partner abuse. However, authors have reported favorable findings with respect to feasibility of computerized screening and advice for women with partner abuse and drug use histories. 61 ,62
In addition to future opportunities regarding the conduct of ED-SBIRT research with nFtF modalities, there exists opportunities to improve the reporting of such research. For instance, in terms of the “screening” component of ED-SBIRT, it would be beneficial for authors to clearly report the screening duration. This might help establish norms and set guidelines for what counts as “rapid assessment” of a patient's severity of substance use. Also, authors of the articles reviewed here reported the use of a wide range of nFtF modalities across all 3 ED-SBIRT components. Substance use disorder researchers should take the lead on establishing guidelines for the reporting of ED-SBIRT studies (e.g., Consolidated Standards of Reporting Trials (CONSORT) statement, STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines, STAndards for the Reporting of Diagnostic accuracy studies (STARD) guidelines)—including categorization schemes for various nFtF modalities. This would facilitate both secondary (e.g., meta-analyses) and primary (e.g., future study design) research. Similarly, ED-SBIRT authors would benefit from standardized guidelines about what counts as “referral to treatment.” Without such guidance, we cast a wide net in our scoping review about what counted as “referral to treatment”—everything from community brochures to social work consults. Recently, some authors have argued in favor of screening, treatment initiation, and referral (STIR) for substance use disorders.15
Also needed is research that develops the program theory—i.e., theory of how an intervention contributes to a chain of intermediate results and observed outcomes 63 —for how ED-SBIRT contributes to positive outcomes, in order to successfully translate ED-SBIRT from one context (e.g., substance use) to another (e.g., substance use and IPV victimization). A program theory can help answer many complex questions, including why an intervention was not successful and what changes should be made next time. For example, the primary way that motivational interviewing (MI) researchers try to describe the theory of MI is by evaluating which, if any, specific in-session patient verbal responses to an MI intervention are predictive of behavioral change. Although this has turned out to be a relatively useful approach from full-fledged MI psychotherapy, 64 it has not been as useful in the brief intervention (BI) space, perhaps owing to the substantially fewer patient statements made within a 5- to 10-minute intervention versus in multiple, hour-long therapy sessions. In fact, only one group has successfully tested their BI theory-of-change using a similar approach but with psychometrically sound adherence scales adapted for the brevity of BI. 65 , 66 A better understanding of ED-SBIRT's theory-of-change could help future researchers select from among the myriad outcome measures and follow-up periods uncovered here.
This scoping review shows the diverse extent, range, and nature of strategies and outcomes reported in ED-SBIRT studies that employ nFtF modalities for high-risk alcohol use. Our review has several potential limitations. For pragmatic reasons, we excluded sources not published in the English language. However, the purpose of this scoping review was to give an initial overview of the literature available. Additionally, only one screener reviewed the title and abstract of the 1526 de-duplicated records (Figure 2). However, we did share the list of 30 full-text articles used for data extraction with a group of highly experienced ED-SBIRT researchers to review for comprehensiveness. Another potential limitation is that we did not contact authors of primary studies for all potentially missing information. Thus, it is possible that some of the table cell entries recorded as “N/R” (not reported) may have been completed otherwise. Due to the substantial delay between submission of articles for peer review and actual publication, it is possible that we missed some articles that are under review or in press—not to mention articles that were rejected or never submitted for publication. Lastly, although the absence of a meta-analysis may be perceived as a limitation, determining the efficacy of interventions is not the purpose of a scoping review. 24 Moreover, the studies included here would be too heterogeneous to produce a single estimate of treatment effect.22
The above insights and recommendations could help the pragmatic aspects of ED-SBIRT and potentially optimize wider adoption and implementation where currently, despite support and published best-practice guidelines, the large majority (i.e., most) of EDs do not adhere to nor follow these guidelines—leaving patients’ undetected high-risk alcohol use unaddressed and patients set up for chronic alcohol use disorders and diseases and premature death and disability. In summary, nFtF modalities have become a compelling option over the past 15 years for improving ED-SBIRT, especially given the widespread ownership and usage of mobile phones, computers, tablets, and other technology among ED patients. 67 , 68 We believe that the above recommendations can be the start of an agenda for improving the conduct and reporting of ED-SBIRT research with nFtF modalities.
Funding
Effort on the manuscript by B.J.B. was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health (NIH) Loan Repayment Program (LRP) under award number L60MD009893-01. Effort on the manuscript by F.E.V. was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health, Office of the Director, National Institutes of Health (OD), Office of Behavioral and Social Sciences Research (OBSSR) under award number R01AA022083. The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Author contributions
B.J.B. conceived and designed the study, acquired the data, and analyzed and interpreted the data; led the drafting and revision of the article; and gave final approval of the version to be submitted. M.V.P. contributed to analysis and interpretation of data; participated in critical revision of the article for important intellectual content; and gave final approval of the version to be submitted. J.D.D. contributed to analysis and interpretation of data; participated in critical revision of the article for important intellectual content; and gave final approval of the version to be submitted. D.P.H. contributed to acquisition of data; participated in critical revision of the article for important intellectual content; and gave final approval of the version to be submitted. F.E.V. made substantial contributions to design of the study and analysis of data; contributed to the drafting and revision of the article; and gave final approval of the version to be submitted.
References
Supplementary Material
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