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. Author manuscript; available in PMC: 2024 Jan 1.
Published in final edited form as: Child Health Care. 2021 Oct 21;52(1):7–22. doi: 10.1080/02739615.2021.1984240

Family-based treatment for pediatric eating disorders: Evidence and guidance for delivering integrated interdisciplinary care

Sarah Forsberg 1, Sasha Gorrell 1, Erin C Accurso 1, Claire Trainor 2,3, Andrea Garber 4, Sara Buckelew 4, Daniel Le Grange 1,5
PMCID: PMC9817879  NIHMSID: NIHMS1746042  PMID: 36619528

Abstract

Eating disorders (EDs) are complex psychiatric diagnoses requiring specialized care. Family-based treatment (FBT) is the first-line treatment for adolescent anorexia nervosa and is also efficacious for other EDs. This study describes practice changes due to the implementation of an integrated interdisciplinary FBT-aligned treatment program for EDs at a large tertiary care hospital in the United States. We examined the feasibility and acceptability of implementation, barriers to implementation, and impact on providers’ roles over a one-year period. Practice changes came with shifts in roles, and were largely experienced as acceptable with good suitability. Barriers identified may inform future interdisciplinary implementation efforts.

Introduction

Eating disorders (EDs) are severe psychiatric disorders that affect 9% of the United States population (Deloitte Access Economics, 2020). Onset is typically in adolescence (Volpe et al., 2016) and is associated with serious medical complications and elevated suicide risk, leading to one of the highest mortality rates across psychiatric disorders (Schaumberg et al., 2017). Medical complications can lead to hospitalization, which is required for ≈20% of adolescents with anorexia nervosa (AN), and ≈40% of those are re-hospitalized within one year (Steinhausen et al., 2008). Data indicate that adolescents with atypical AN (AAN), who present at average or above-average BMI percentiles are just as medically compromised (Garber et al., 2019; Sawyer, et al., 2016). Early, effective treatment is particularly important for AN to minimize negative impacts on physical health and functioning, capitalize on higher recovery rates for adolescents than adults with longer duration of illness (Lock, 2015), and reduce the potential for a chronic course (Steinhausen, 2008) and premature death (Arcelus et al., 2011). While early treatment is critical across EDs, we will focus here on restrictive EDs (e.g., AN, AAN) among adolescents and young adults generally associated with greater medical acuity and often requiring more intensive interdisciplinary care.

Interdisciplinary services for AN and AAN frequently include medical monitoring, psychotherapy, and nutritional counseling (Joy et al., 2003). Established guidelines recommend close coordination of care both between provider disciplines and with caregivers when treating young people with EDs (Couturier et al., 2020; NICE, 2017). Family-based treatment (FBT), which empowers parents to interrupt ED behavior (Lock & Le Grange, 2015), is considered the first-line evidence-based treatment (EBT) approach for adolescents with EDs (Couturier et al., 2013; Lock & Le Grange, 2019). Several randomized clinical trials (RCTs) demonstrate the efficacy of FBT for AN (Agras et al., 2014; Le Grange et al., 2016; Lock et al., 2005, 2010), and bulimia nervosa (Le Grange et al., 2007; Le Grange et al., 2015), with preliminary evidence for treatment of AAN (Hughes et al., 2017) and avoidant restrictive food intake disorder (ARFID) (Fitzpatrick et al., 2015; Lock et al., 2019). Further, given that EDs are associated with a high cost burden (Agras et al., 2014; Van Hoeken, & Hoek, 2020), FBT has been shown to reduce associated costs to individuals and the medical system by up to 70% (Le et al., 2017; Lock et al., 2008).

FBT: History and Research Evidence

Historically, treatment for EDs such as AN deliberately excluded parents, as they were mistakenly implicated as a cause of the disorder (Le Grange et al., 2009; Le Grange & Eisler, 2009). A theoretical and evidence-based shift away from family responsibility in the etiology of EDs has created the opportunity for parents to participate in treatment, and to be seen as a vital resource in their child’s recovery (Le Grange et al., 2009). Accordingly, parents are now usually incorporated into treatment for adolescents with restrictive EDs, along with siblings and other family/caretakers who might be directly involved in the child’s care (Lock & Le Grange, 2019).

Manualized FBT has been systematically studied with eight RCTs, six of which have focused on AN, and provided a strong evidence base supporting the use of this approach for adolescents with this disorder. Comparing adolescents who received FBT v. individual adolescent-focused therapy (AFT), more patients receiving FBT had achieved full remission at 6- and 12-month follow-up (Lock et al., 2010). In another comparison of FBT for AN with systemic family therapy (SFT), adolescents receiving FBT gained weight significantly faster than those receiving SFT, and fewer participants in FBT were hospitalized (Agras et al., 2014). Other work has demonstrated that longer hospitalization is not required to enhance the overall effectiveness of FBT treatment for AN (Madden et al., 2015), and a short-term course of FBT may be as effective as a long-term course for some adolescents with AN (Lock et al., 2005).

As a departure from standard FBT, a separated format of FBT (parent-focused treatment [PFT]; Le Grange et al., 2016) or an augmented version with intensive parent coaching (Lock et al., 2015) has demonstrated greater suitability for adolescents within families with high expressed emotion or lower parental self-efficacy, respectively. As a further expansion of standard FBT, a short-term intensive family therapy (IFT) has been tested across sites (Marzola et al., 2015; Rockwell et al., 2011). With this IFT approach, families engage in a five-day, eight-hour/day treatment week, a format that may be particularly helpful for families with less access to specialty ED care, or as an option for treatment resistant cases (Knatz et al., 2015). A multi-family therapy (MFT) version of this week-long intensive approach has also demonstrated effectiveness in facilitating weight gain and reducing ED symptomology over extended follow-up (Marzola et al., 2015). Taken together, preliminary evidence suggests that short-term, intensive treatments—in both single and multi-family formats, may confer overall positive treatment outcomes. Across all currently tested formats, overall research evidence from systematic trials supports the use of FBT for AN, over and above other forms of therapy, and further suggests that continued examination of for whom, and in what format, FBT may be most effective, is warranted.

FBT Approach and General Principles

Along with the overarching belief that parents are a primary resource in their child’s recovery, FBT is characterized by agnosticism, a stance which discourages a focus on the cause of the ED. This approach reduces blame for the disorder on both the child as well as their parents and encourages all family members to work toward their shared treatment goals. FBT is structured in three Phases, with shifts in parental and patient responsibility and treatment focus in a developmentally sensitive manner as the Phases progress.

At the start of treatment (Phase 1), FBT galvanizes parental resources specifically toward weight restoration, and in the cessation of ED behaviors (e.g., restriction, purging). This early focus on weight progress derives from consistent evidence that gaining approximately 2.5 kg by the end of the first month of FBT is a robust predictor of positive prognosis (Accurso et al., 2014; Doyle et al., 2009; Hughes et al., 2019; Madden et al., 2015; Le Grange et al., 2013). FBT therapists serve as expert guides, supporting parents to wholly assume responsibility for supporting their child’s path through recovery. The therapist both directs parental instincts and skills, and helps them to override their concern that their efforts will erode familial relationships or exacerbate the illness.

As weight restoration is achieved and ED symptoms remit, less parental authority is typically required. In this stage of treatment (Phase 2), parents may gradually restore autonomy to the adolescent as is developmentally and culturally appropriate. The therapist consults with the parents in deciding when and in what manner they will allow the child to take increasing responsibility in their eating and exercise behavior. As the child returns to their full range of age-appropriate activities (Phase 3), the therapeutic focus then shifts to issues relevant to typical adolescent development (e.g., academic or social factors that had been impacted by the ED), and in preventing relapse.

Role of the Pediatrician and Dietitian

FBT is typically conducted with an interdisciplinary approach, involving a primary mental health provider (e.g., clinical psychologist, licensed clinical social worker), medical providers (i.e., pediatrician or adolescent medicine physician), nutrition experts (e.g., dietitians, nutritionists), and psychiatry providers, when indicated. Coordination and alignment between treatment providers is critical to support parental-empowerment and to ensure agreed-upon treatment goals. Tight coordination between mental health, medical, and nutrition providers includes regular consultation about shared clinical cases, and consistent messaging to the patient and family across the range of providers. Given the complexity of EDs and confusion that families often face in addressing their child’s symptoms, providers’ recommendations have the potential to enhance or undermine parental confidence. As such, guidelines for physicians (Katzman, et al., 2013) and dietitians (Lian et al., 2017) outline best practices to align interventions with FBT principles. For example, identifying an estimated weight for full ED recovery is achieved through collaboration with medical and nutrition experts using historic growth curves, information about vital signs, and cognitive features (i.e., the presence and severity of ED symptomology), and is communicated consistently across team members with necessary adjustments made as treatment proceeds.

FBT in Higher Levels of Care

Given that the medical acuity of this patient population may require more intensive services (inpatient medical monitoring and refeeding) or in some instances, residential or day treatment, consideration of the transition between levels of care is warranted. When hospitalization for medical management of common consequences of malnutrition like bradycardia, orthostatic tachycardia, hypotension and electrolyte abnormalities is required, patients are often admitted to generalist pediatric units, wherein training and specialization in the treatment of EDs is limited. Efforts to train multidisciplinary team members in principles of FBT has the potential to increase parental self-efficacy and improve treatment weight outcomes following discharge (early weight gain and rate of weight restoration at 6-months post hospitalization) (Matthews et al., 2019). Those engaged in FBT compared to traditional family therapy or individual therapy approaches also have lower rates of hospitalization during the course of treatment; thus, orienting families and preparing them to take an FBT approach upon discharge may reduce vulnerability for readmission in this medically acute subset of patients (Agras et al., 2014; Lock et al., 2010).

Although it is recommended that youth receive care in the least intensive treatment environment possible (NICE, 2017; Courtier et al., 2020), sometimes a higher level of care is indicated not only for reasons of medical acuity but also to address acute suicidality, complex psychiatric comorbidity and/or insufficient response to outpatient services. An FBT-informed approach has successfully been implemented in partial hospitalization (PHP) and intensive outpatient programs (IOP) with patients demonstrating significant improvements in weight and ED symptomology as well as lower rates of readmission (Huryk et al. 2020; Rienecke & Richmond, 2017).

Challenges with Implementation of FBT

Despite a strong evidence base and relative cost-effectiveness, implementation and dissemination of FBT into diverse settings has been fraught with challenges. Specifically, established barriers to implementing change in practice and adopting new protocols include limited resources (e.g., lack of training, supervision, financial and structural support) and motivational factors (e.g., perception of the suitability of the model, willingness to change aspects of practice) (Couturier et al., 2018). For some providers and caregivers, implementation of FBT requires a paradigm shift, whereby caregivers are not excluded from treatment, but instead viewed as consultants and experts on their child.

In one retrospective study, the process of implementing FBT at the Royal Children’s Hospital in Melbourne, Australia, revealed provider-reported challenges such as concerns about treatment suitability (i.e., which families were a match for FBT), reluctance to modify standard practice (i.e., taking a less prescriptive approach), adaptation to shifts in role definition (i.e., therapist became team lead), and differing views of treatment goals. As FBT was adopted, success was attributed to close communication between team members and the integration of services from assessment to treatment planning and delivery (Hughes et al., 2014). Another FBT implementation study delivered at four sites within the Ontario Provincial Network for Eating Disorders found barriers and facilitators were related to resources or lack thereof (e.g., time, adequate staffing, clinical infrastructure) and shifts in role definition and difficulties with communication (Couturier et al., 2018). Despite these challenges, integrated pediatric behavioral health models have demonstrated clinical benefits over standard of care, especially when applying well-established EBTs that are delivered collaboratively (Asarnow et al., 2015).

Implementation of an Interdisciplinary FBT Approach Into a Tertiary Care System

Below, we present commentary on an implementation effort at a large tertiary hospital, whereby providers from different disciplines (i.e., mental health, pediatric and adolescent medicine, and nutrition) were brought together to create a coordinated, FBT-based ED Program at the University of California, San Francisco (UCSF). Historically at UCSF (prior to 2015), young people with EDs were treated within the Adolescent Medicine Division in the Department of Pediatrics where they received medical monitoring and nutritional counseling. As needed, individuals were hospitalized for medical stabilization on a medical/surgical floor of the Children’s Hospital, where they were cared for by the adolescent medicine team. Mental health services were provided by a small group of clinicians in a general family therapy program, and the majority of patients were referred to community-based clinicians or intensive treatment programs with differing treatment paradigms.

Implementation of an integrated multi-disciplinary program (2015 onward) required onboarding of a new team of mental health providers, most of whom had prior expertise in FBT, as well as the training of a preexisting team of physicians, dietitians, social workers, and nurses in the FBT model. All providers had familiarity with the approach and some had received prior training in FBT. New hires and trainees (adolescent medicine fellows, clinical psychology interns and postdoctoral fellows) had varying backgrounds in the treatment of EDs and FBT and were provided with training suited to their educational needs. As behavioral health and medical services are now increasingly integrated (Heath et al., 2013), this program followed suit with the intention of fully aligning these services in a co-located setting. Central features of the highest level of integration are described as close collaboration in a transformed/merged practice, whereby there is a “blending and blurring of cultures”, and possibly a co-located model (Heath et al., 2013).

Efforts to establish the UCSF ED Program were informed by the belief that integration of care across disciplines would enhance patient outcomes. To this end, the program was structured to allow for close coordination, involving initial co-location of services requiring merging of administrative support in at least four key areas. One of these areas of increased coordination included streamlining referral processes. For example, an effort was made to improve patient experience by implementing a seamless system that could quickly refer families to needed consults with related specialists within the hospital system (e.g., cardiology; gastro-intestinal services) and within the more immediate team (e.g., psychiatry; nutrition services). The program also benefitted from establishing a centralized check-in and shared medical record system with features included in the electronic medical record that allowed for greater communication between care team members across hospital departments. Another critical area of increased coordination included introducing a weekly interdisciplinary case conference and administrative/research meeting which allowed for both regular ‘curb-side consults’ between specific team members, but also the opportunity to raise larger program-wide concerns for discussion that might impact patient care. Finally, implementation efforts included establishing an integrated half-day assessment process that incorporated psychiatric, medical, nutrition, and social work evaluations. This schedule provided a maximally comprehensive level of assessment across all treatment services, establishing both a standardized level of care, and the potential to improve patient experience by consolidating the number of appointments they may have needed to schedule across services. Initial structures were broadly designed to improve patient care by promoting shared decision-making, and clear role delineation. These systems were established over several months and the initial team of mental health clinicians was hired between August and November 2015, with integrated patient care beginning in January 2016.

Evaluation of Program Changes: Model and Outcomes

Program Treatment Model

Prior to the delivery of integrated services, providers all received training in FBT; all mental health clinicians also had a background or received training in Cognitive Behavioral Therapy for Eating Disorders (CBT-E) and Adolescent Focused Therapy (AFT) for AN, which were used either with young adults living independently (CBT-E), or in rare instances, adolescents who were unable to engage in FBT for a variety of reasons (e.g., family preference, previous failed attempts at FBT, perceived contraindication such as child abuse).

In addition to psychiatric and medical evaluation and follow-up, the integrated team at UCSF included a formal nutrition assessment for every patient (including assessment of degree of malnutrition and calculation of treatment goal weight) as well as social work, who provided education to families and connected them with resources, and eventually, a nursing coordinator was hired to support communication with nursing staff and improvements in workflow and procedures.

Patient enrollment in outpatient services would typically be facilitated in one of three ways: (i) referrals made by outpatient Adolescent Medicine providers to the Eating Disorders Program with a request for psychological evaluation, diagnostic assessment and/or treatment recommendations; (ii) referrals to the outpatient Eating Disorders Program for psychotherapy services following discharge from the affiliated medical stabilization inpatient unit; and (iii) calls placed to the Eating Disorders Program clinic by concerned families or community providers and hospital systems. A majority of youth in this treatment population meet criteria for restrictive spectrum EDs (e.g., AN, AAN OSFED, ARFID) with a smaller proportion of individuals with binge-eating disorder and bulimia nervosa. A typical course of outpatient FBT spans 9–12 months. With clinical judgment, all efforts are generally made to keep the patient ‘in their life,’ and not in a higher level of care, and for some, referrals for continued care for psychiatric comorbidities may follow discharge from ED treatment.

To contextualize the impact of implementation of the interdisciplinary, FBT-informed program, a mixed-method approach was used to survey treatment providers who were delivering care, assessing select established barriers and facilitators to successful implementation surrounding changes in practice, role definition, and perception of the feasibility and acceptability of an integrated and FBT-informed program (Proctor et al., 2011). Details of the study design (selected assessment items and methods and results) can be found in supplemental online materials, Appendix A and B.

Discussion

While program evaluation was exploratory in nature, it highlights potential challenges that are likely to arise in the implementation of an integrated ED program that provides FBT as a first-line treatment for adolescent EDs. It also underscores the perceived value of devoting resources towards building an evidence-based interdisciplinary program, in spite of these challenges. Mixed method results are discussed below, relative to the identified aims which were to capture provider perception of the feasibility, acceptability, and suitability of the integrated, multi-disciplinary FBT-focused programming.

Feasibility

Providers reported somewhat limited availability of resources to support the formation of such a program including support for budgetary needs, facilities, staffing and training. Perception of availability of these resources did not change over the year-long study period, which is unsurprising given that many of the resources dedicated to forming the program were provided at its inception. Despite relatively low quantitative ratings, very few providers noted barriers to resources in their qualitative feedback. Further, while perceived limitations in resources could have discouraged providers from implementing changes, or impacted confidence therein, providers expressed a high degree of personal support for practice changes to improve patient care. Providers reported an increased perception/experience of shifts in their role as the integrated program was implemented. Generally, these changes were experienced as beneficial - in many cases providers reported an ability to focus their work to be in line with their training background. At the same time, the transition was not without challenges, and early on, some expressed a desire for greater role definition. Prior to implementation, without the established mental health team, providers from other disciplines had been accustomed to providing additional support to families (e.g., more intensive nutrition counseling, “pseudo” therapy sessions). By the third and final survey administration, providers most frequently described their role with clarity, which did not occur at earlier timepoints, suggesting potential adaptation to earlier changes.

Acceptability

Providers expressed a belief that implementing an integrated program would enhance patient outcomes, indicating a very high degree of acceptability. There was high ‘readiness for change’ at the initial assessment, indicating that change was acceptable. Unexpectedly, space constraints resulted in separation of services just prior to the administration of the survey at time two when medical, nutritional and social work services were moved across the city from psychiatric services. Provider response to this separation suggested an overwhelming desire for a return to co-located services, as benefits to patient care, efficiency, and team communication were noted. These findings are consistent with recommendations whereby shared space and systems are foundational to true integration.

Suitability

At each timepoint, providers estimated that roughly 70% of patients were receiving appropriate care in the current model, and approximately 20% would benefit from a higher level of care. Given the psychiatric and medical acuity of patients presenting to the program, these figures indicate relatively good suitability of the program (i.e., treatment provided within the program was deemed suitable for more than 85% of patients who were appropriate for outpatient care). Although the modest sample did not allow for examination of any differences across disciplines, these numbers remained consistent across timepoints, and recommendations for additional services across all timepoints included a desire for a psychiatrist to support medication management for significant comorbidities, an intensive family therapy program, parent groups, and a specific protocol for ARFID cases, all of which have been put in place as the program has grown. Alignment with FBT principles was reflected in the current study via an item that identified the degree to which providers believe that parents are equipped to bring about their child’s recovery. This question reflects a central tenet of FBT, namely parental empowerment. One might expect that if providers were not in agreement with this item, their faith in the efficacy of the treatment and fidelity to the model would be diminished. At initial evaluation, providers reported agreement with the notion that parents are well-positioned to help their child recover in the home-setting, and that as providers, FBT fit well with their overall treatment approach. Further, spanning across disciplines, team members felt supported by one another and were in alignment in goals for patient care.

Implications for Practice

Taken together, we have highlighted how an integrated and multidisciplinary FBT-based approach to treating patients with restrictive EDs was largely found to be a feasible, acceptable, and suitable model of care. In practice, this integrated model may require some degree of time and resources (both practical and financial) to bring about, particularly if the needed components of care (e.g., all members of a multi-disciplinary team) are not already in place or readily available. However, due to the complexity and medical acuity of these disorders, it is critically necessary to establish an integrated multi-disciplinary approach to treatment as our standard of practice. Outpatient treatment is appropriate for most adolescents with restrictive EDs, and it is strongly recommended that youth receive care in the least intensive treatment environment possible (NICE, 2017; Courtier et al., 2020). However, given that some patients will require a higher level of care at some point in their illness (e.g., to address medical instability), in the current text, we have also described how this integrated model may improve treatment effectiveness across transitions in care. Although future research is indicated to further evaluate uptake of this integrated model and its impact on patient outcomes, current evidence suggests that this approach to clinical practice is one towards which all efforts should be made.

Lessons Learned and Future Directions

This was an exploratory, naturalistic evaluation of programming and interpretation of findings may be limited by natural evolutions of the service as it grew (i.e. changes in personnel, shifts in role, the separation of space). Provider experience of programmatic changes may have varied by discipline, given the mental health team was hired with the explicit goal of implementing an integrated and FBT-informed program. In contrast, there may have been more mixed feelings, and the most dramatic experience of change among the team members who had provided services prior to the advent of implementation. While factors unique to this program (e.g., urban location) may make generalization to other institutions or practice groups more challenging, the shared investment in working across department lines to create such a program is critical to successful implementation, and was reflected in the high degree of readiness for change and belief in the value of these changes. Presumably, without a high degree of motivation, implementation would not have been as successful. While patient outcomes were not examined alongside provider experiences, it is unlikely that providers would have expressed as much confidence in FBT and capacity to support the majority of patients in the program, had they not seen a positive impact on the patient population. In fact, when asked to provide concluding comments about their experience, several commented that the integrated program enhanced patient care (i.e., better outcomes, improved access to care).

Despite some of the challenges associated with measuring implementation efforts, the lessons learned here point to many positive aspects of delivering integrated and FBT-informed services to young patients with EDs. The changes were widely experienced as beneficial, and providers felt they were valuable despite reported growing pains and barriers. There appeared to be a general commitment across disciplines to continue to enhance care by improving team alignment in messaging, and in improving team communication and role delineation. Establishing structures for communication is especially important, and in this case was likely complicated by a physical separation of departments. Efforts to streamline and improve communication included holding a weekly interdisciplinary case conference, modifying documentation templates to improve clarity, and establishing structures for ongoing communication through the electronic medical record. As the capacity of the team grew, additional services were developed to meet the needs of the perceived small subset of patients who did not appear to respond to FBT, including establishing an intensive family therapy program, parent and caregiver groups, and protocols for ARFID treatment. Efforts were also made on the medical inpatient unit to prepare families for FBT upon discharge, and providers across disciplines modified practices to enhance parent empowerment. Changes in language (i.e., emphasizing parental strengths, involving parents in shared decision-making when appropriate) and practice (i.e., encouraging parents to be present for meals and snacks on the inpatient service, educating nursing and support staff on EDs and FBT), were made over time to bring the broader system in line with the approach.

Unfortunately, only patients with private insurance or those who could afford to self-pay were able to access integrated care across settings. Patients with public insurance were unable to access mental health services (with the exception on the medical stabilization program), which reflects a broader systemic challenge. Youth with EDs are poorly served by publicly-funded services, and policy reform is urgently needed to increase access to evidence-based treatment and improve outcomes for this population in particular (Accurso et al., in press). Future efforts are underway to evaluate the effectiveness of the treatment model, which may shed additional light on whether provider perception is an accurate reflection of outcomes and associated clinical needs. While each system of care will inevitably bring to bear its own set of barriers and facilitators to implementation efforts such as this one, the integration of disciplines, systems, and alignment of treatment philosophy is feasible, perceived as acceptable and beneficial to young people with EDs, and may inspire confidence in replicating similar models in other settings.

Supplementary Material

Appendix A and B

Acknowledgments

Funding

Drs. Accurso and Gorrell are supported by the National Institutes of Mental Health (K23 MH120347 and K23 MH126201, respectively). Dr. Accurso is also supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number KL2 TR001870. Dr. Garber is supported by the National Institutes of Child Health and Human Development (R01 HD082166) and in part by the Maternal Child Health Bureau (T71 MC00003).

Footnotes

Conflict of Interest Statement

Financial Disclosure: Dr. Le Grange receives royalties from Guilford Press and Routledge for books on family-based treatment and is co-director of the Training Institute for Child and Adolescent Eating Disorders, LLC, which trains professionals in FBT and other treatment modalities. Dr. Forsberg receives royalties from Routledge Press for a book on supervision in FBT.

On behalf of all identified authors, we wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Data Availability Statement

The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

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Supplementary Materials

Appendix A and B
NIHMS1746042-supplement-Appendix_A_and_B.docx (27.9KB, docx)

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