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. 2024 Jul 25;44(12):NP852–NP861. doi: 10.1093/asj/sjae168

BREAST-Q Analysis of Reduction Mammaplasty: Do Postoperative Complications of Breast Reduction Surgery Negatively Affect Patient Satisfaction?

John B Park 1, Oluwaseun D Adebagbo 1, Benjamin Rahmani 1, Daniela Lee 1, Matthew Prospero 1, Shreyas Puducheri 1, Amy Chen 1, Micaela Tobin 1, Mohammed Yamin 1, Ashley N Boustany 1, Bernard T Lee 1, Samuel J Lin 1, Ryan P Cauley 1,
PMCID: PMC11565859  PMID: 39052922

Abstract

Background

Reduction mammaplasty can provide symptomatic relief to patients suffering from macromastia; however, complications such as dehiscence are common. It is unknown if the presence of complications affects patient-reported outcomes.

Objectives

The aim of this study was to determine the risk factors for the development of complications, and to examine the correlation between postoperative complications and patient-reported outcomes in reduction mammaplasty.

Methods

A single-center retrospective chart review was undertaken of patients who received reduction mammaplasties (CPT 19318), performed by 13 surgeons, between January 2017 and February 2023. Breast cancer cases and oncoplastic reconstructions were excluded. Patients with >1 complication were grouped into the complications cohort. Satisfaction was assessed by administering the BREAST-Q survey.

Results

A total of 661 patients were included for analysis, 131 of whom developed at least 1 complication. Patients in the group with complications had significantly higher average ages and BMIs, and a higher likelihood of hypertension and diabetes (P < .01). Among 180 BREAST-Q responders, 41 had at least 1 complication. There were no significant differences between the 2 groups (complications vs no complications) across survey outcomes. Although obese patients were more likely to develop infection and require revisions (P < .01), no significant differences in subgroup analysis of patient-reported outcomes focusing on obese patients were observed.

Conclusions

Obesity, hypertension, and diabetes were associated with postoperative complications of reduction mammaplasty. Patients with complications had similar postoperative BREAST-Q satisfaction to patients without complications. Although risk optimization is critical, patients and surgeons should be reassured that satisfaction may be achieved even in the event of a complication.

Level of Evidence: 3

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Reduction mammaplasty is a common surgical intervention that has been shown to improve quality of life and may also lead to improvements in weight loss, physical activity, and eating behaviors.1-4 Common complications after reduction mammaplasty include wound dehiscence, seroma, asymmetry, sensory changes, and fat necrosis.5 Because complications may be more likely in patients with risk factors such as greater resection weight, obesity, current smoking status, and diabetes, considering the effects of surgical risks on long-term outcomes continues to be vital.6 Despite the overall generally high success and satisfaction rate of reduction mammaplasty, some surgeons take a more conservative approach to patient selection when assessing the risk of postoperative complications.7 Thresholds for BMI have remained a barrier to access for medically indicated patients despite more recent literature re-examining the association between obesity and increased complication rate. Although some studies have demonstrated that higher BMI may be associated with greater risk, others have shown comparable clinical outcomes between obese and nonobese individuals.3,8-13 Additionally, the higher prevalence of obesity in non-White patients and those with public insurance make arbitrary BMI thresholds an additional contributor to disparities in healthcare.14,15

When individuals do experience a complication after elective surgery, it is unclear if the development of complications affects long-term patient outcomes. Nuzzi et al found that in juvenile patients undergoing breast reduction surgery, the presence of complications did not appear to affect overall patient satisfaction.16 Nevertheless, the complication rate was low given the young age of the patient cohort. In another small study of obese individuals, long-term outcomes were comparable between patients who developed complications and those who did not; however, this result was restricted to the obese population, and no validated patient-reported outcome measures (PROMs) were used to measure outcomes from the patients’ perspectives.17 Thus far, there have been no large studies in the literature examining the effect in adults of complication development on validated long-term patient-reported outcomes (PROs) in reduction mammaplasty. The aims of the present study are twofold: (1) to determine independent risk factors for the development of complications; and (2) to examine the correlation between postoperative complications and long-term validated PROs in adult patients undergoing reduction mammaplasty.

METHODS

Study Population and Variables of Interest

The study was approved by the Beth Israel Deaconess Medical Center IRB (protocol number 2019P000819, version 17). A single-center retrospective study was undertaken of patients who received reduction mammaplasty, defined as Current Procedural Terminology code 19318, performed by 13 surgeons, between January 2017 and February 2023. Patients with a medical history of breast cancer or a surgical history of breast reduction and breast reconstruction were excluded from the analysis. Preoperative, perioperative, and postoperative variables of interest were collected through retrospective review of electronic medical records. The data were imported into Research Electronic Data Capture (REDCap) software hosted at our institution. REDCap is a secure, web-based platform designed to support data capture for research studies, providing an intuitive interface for data capture, automated export procedures, and data integration and interoperability with external sources.18

Patient Reported Outcomes (PROs)

Patients who met the inclusion criteria and had reachable contact information were asked to complete the 9 categories of the postoperative BREAST-Q version 2.0 Reduction/Mastopexy questionnaire, provided under license from Memorial Sloan Kettering Cancer Center and the University of British Columbia. A maximum of 5 call attempts were made to request survey completion between July 2023 and September 2023. For patients who completed 50% or greater of the questionnaire, the missing responses were substituted with the category's mean value according to the recommendation of the BREAST-Q protocol. Survey responses with less than 50% completed were excluded. BREAST-Q raw scores were converted according to BREAST-Q conversion table scores based on the findings from Rasch analysis.

Statistical Analysis

Patients with at least 1 identifiable postoperative complication (including hematoma, seroma, wound dehiscence, infection, and standing cone deformities requiring correction) were grouped into the complications cohort. Those who did not experience any complications after breast reduction surgery were grouped into the complication-free cohort. All analyses were performed using JMP Pro 17.0. Normally distributed, continuous data are reported as means with standard deviations, and a paired t-test was used to compare the 2 groups. Categorical variables are reported as frequencies with percentages, and a chi-squared test was used to compare the 2 groups. Multivariable logistic regression analysis was performed with covariate adjustment using the propensity score to evaluate the effect of wound complications on patient-reported unsatisfaction with outcome. The propensity score was estimated from a pruned forward selection logistic regression model, optimized for the corrected Akaike information criterion. Potential predictors of wound complication risk included age, gender, race, Hispanic ethnicity, superior/inferior pedicle type, Wise/non-Wise incision pattern, BMI, obese status, historic smoking status, current smoking status, hypertension (HTN), diabetes, hyperlipidemia (HLD), chronic obstructive pulmonary disorder (COPD), breast cup size, and degree of ptosis. Significance was set at P ≤ .05.

RESULTS

Patient Demographics and Preoperative Variables

Of the total of 631 patients included, 124 (19.7%) had at least 1 postoperative complication following surgery (Table 1). The age of patients included in the study ranged from 16 to 75 years. Patients in the complications cohort were on average significantly older (40.78 vs 37.79 years, P = .03) and more obese (BMI 32.61 vs 30.90 kg/m2, P < .01). A total of 121 patients (97.58%) in the complications cohort, and 496 patients (97.83%) in the complication-free cohort were female. No differences were seen between the 2 groups in terms of gender, race, and ethnicity. There was a trend towards active tobacco usage in the complications group (12.10% vs 6.31%, P = .09). The complications cohort had a significantly greater proportion of patients with HTN (27.42% vs 14.20%, P < .01) and diabetes (8.87% vs 2.76%, P < .01). There were no other differences in preoperative variables including presence of HLD, history of COPD, breast cup sizes, and degree of breast ptosis.

Table 1.

Patient Demographics and Preoperative Variables

Complications (N = 124) Complication-free (N = 507) P
Age (years) 40.78 [14.14] 37.79 [13.34] .03
BMI (kg/m2) 32.61 [5.77] 30.90 [6.00] <.01
Gender
 Female 121 (97.58) 496 (97.83) .62
 Nonbinary 1 (0.81) 7 (1.38)
 Othera 2 (1.61) 4 (0.79)
Race
 White 75 (60.48) 273 (53.85) .49
 Black or African American 28 (22.58) 133 (26.23)
 Asian 3 (2.42) 11 (2.17)
 American Indian or Alaska Native 0 (0) 1 (0.2)
 Native Hawaiian or Pacific Islander 0 (0) 2 (0.39)
 Mixed 0 (0) 5 (0.99)
 Other 3 (2.42) 4 (0.79)
 Unknown 15 (12.10) 78 (15.38)
Hispanic
 Hispanic 18 (14.52) 73 (14.40) .71
 Non-Hispanic 95 (76.61) 376 (74.16)
 Unknown 11 (8.87) 58 (11.44)
Smoking status
 Current 15 (12.10) 32 (6.31) .09
 Former 16 (12.90) 66 (13.02)
 Never 93 (75.00) 409 (80.67)
Past medical history
 Hypertension 34 (27.42) 72 (14.20) <.01
 Diabetes 11 (8.87) 14 (2.76) <.01
 Hyperlipidemia 12 (9.68) 30 (5.92) .13
 COPD 0 (0) 2 (0.39) .48
Breast cup size
 C 0 (0) 3 (0.59) .46
 D 13 (10.48) 70 (13.81)
 ≥E 107 (86.29) 409 (80.67)
 Unknown 4 (3.23) 25 (4.93)
Degree of ptosis
 Pseudoptosis 1 (0.81) 4 (0.79) .95
 Grade 1 1 (0.81) 6 (1.18)
 Grade 2 38 (30.65) 149 (29.39)
 Grade 3 77 (62.10) 327 (64.50)
 Unknown 7 (5.65) 20 (3.94)
Incision type
 Wise pattern 109 (87.90) 472 (93.28) .012
 Robertson 11 (8.87) 31 (6.13)
 Vertical 2 (1.61) 0 (0)
 Other 2 (1.61) 3 (0.59)

Values are mean [standard deviation] or n (%). COPD, chronic obstructive pulmonary disease. aOther genders include male, transgender male, and transgender female.

Complications and Interventions

In total 124 patients (19.7%) developed at least 1 complication after reduction mammaplasty, and there were a total of 171 incidences of complications (Table 2): 89 patients developed 1 complication, and 35 patients developed multiple (2 or more) complications after surgery. Seventeen patients developed major complications, which included hematoma, deep dehiscence, and infection requiring in-clinic debridement, incision and drainage, intravenous antibiotics, or intervention in the operating room. Minor complications, such as seroma, superficial dehiscence, standing cone deformity requiring correction, or infection resolving after outpatient oral antibiotic treatment, were noted in 154 patients. Complications requiring interventions are listed in Table 3. Most notably, 90% of hematoma cases required a procedure to drain the hematoma, and 71% of patients who developed seroma required 1 or more inpatient aspirations. Roughly half of the seroma aspirations were performed by interventional radiology. All but 1 of the wound dehiscences were resolved with dressing changes alone for an average of 5.11 weeks (median, 4.00 weeks). No patients from our cohort experienced significant morbidity or mortality after their breast reduction surgery.

Table 2.

Incidence of Complications

Complications N
Total number of patients with complications 124
Total number of incidence of complications 171
Number of complications per patient
 0 507 (80.3)
 1 89 (14.1)
 2 26 (4.1)
 3 7 (1.1)
 4 2 (0.3)
Major complicationsa
 Hematoma 10
 Infection 6
Dehiscence 1
 Total 17
Minor complicationsb
 Seroma 21
 Infection 68
 Dehiscence 45
 Standing cone deformity requiring correction 20
 Total 154

Values are n (%) or n. aMajor complications include hematoma, infection requiring in-clinic debridement, incision and drainage, intravenous antibiotics, or operating room intervention, and deep dehiscence. bMinor complications include seroma, infection only requiring outpatient oral antibiotics, and superficial dehiscence.

Table 3.

Complications of Reduction Mammaplasty Requiring Interventions

Complications N
Hematoma
 Incidence 10
 Required intervention 9 (90%)
 Inpatient drainage 5 (50%)
 Operating room intervention 5 (50%)
Seroma
 Incidence 21
 Required intervention 15 (71%)
 1 in-clinic aspiration 8 (38%)
 2 in-clinic aspirations 7 (33%)
 Aspiration by interventional radiology 8 (38%)
Infection
 Incidence 74
 Required treatment 68 (91.9%)
 Outpatient oral antibiotics 66 (89.2%)
 Inpatient intravenous antibiotics 2 (2.70%)
 In-clinic debridement or incision and drainage 4 (5.41%)
 Return to operating room 1 (1.4%)
Dehiscence
 Incidence 46
 Required treatment 31
 Wet-to-dry dressing 29
 Average weeks of wet-to-dry dressing 5
 Inpatient repair with sutures 1 (2.17%)
 Return to operating room 1 (2.17%)

Values are n or n (%).

Adjusted Risks of Complications and Creation of Propensity Score

We fitted a logistic regression model for all 631 patients who met the inclusion criteria to assess risk of complications. Patient risk factors for complications were selected with the pruned forward selection method, prioritizing variables based on the model corrected Akaike information criterion. Using this method, current tobacco smoking status, HTN, obesity status, and diabetes were included in our logistic regression model. Among those 4 factors, HTN (P < .01), obesity status (P = .044), and diabetes (P = .050) were identified as significantly contributing risk factors to complications, as determined by the Wald test. We then generated propensity scores with the regression model that were used to adjust for baseline covariate distributions.

PROs

There were 162 patients who completed the BREAST-Q questionnaire (25.7% survey response rate). Patients completed the survey on average 4.5 years after their breast reduction surgery. All 5 complications were comparable among BREAST-Q survey responders and nonresponders (Supplemental Table 1). Among the responders, 39 patients were in the complications group (Table 4). Among the 9 different categories in the BREAST-Q survey, there were no significant differences in 7 categories, namely, sexual well-being, physical well-being, breast satisfaction, nipple satisfaction, outcome satisfaction, information satisfaction, and medical team satisfaction. Although not significant, patients in the complications cohort reported trending significance of higher surgeon satisfaction scores (100 vs 92, P = .053). Lastly, patients in the complications group reported significantly higher psychosocial well-being scores compared with those in the complication-free group (81 vs 67.5, P = .04).

Table 4.

BREAST-Q Patient-Reported Outcomes Among Patients With Complications vs No Complications

BREAST-Q category Complications (N = 39) No complications (N = 123) P
Psychosocial Well-being 81 [59, 100] 67.5 [54, 84] .04
Sexual Well-being 60 [44, 82] 60 [50, 76] .70
Physical Well-being 77 [68, 90] 72 [62, 90] .22
Satisfaction with Breasts 68 [55, 89] 68 [53, 89] .97
Nipple Satisfaction 18 [14, 20] 19 [15, 20] .77
Outcome Satisfaction 86 [68, 100] 86 [63, 100] .29
Satisfaction with Information 77 [55, 100] 75 [56, 90] .68
Surgeon Satisfaction 100 [81, 100] 92 [64, 100] .053
Satisfaction with Medical Team 100 [92, 100] 100 [92, 100] .28

Values are median [interquartile range 25%, 75%].  

Patients were grouped into the “unsatisfied” cohort if their overall satisfaction score, measured by the BREAST-Q category Satisfaction with Outcome, was in the lowest quartile. We fitted a logistic regression model to evaluate the predictors of patient unsatisfaction, using complication status and propensity score as covariates. Our findings indicated that neither complication status nor the baseline covariates, represented by the propensity score, were significant predictors of patient unsatisfaction. This was confirmed by the likelihood ratio test and the Wald test, which both yielded P-values of .40 for complication status and 0.95 for the propensity score, respectively. When comparing between patients in the unsatisfied group and those who were satisfied or very satisfied, incidence of complications in hematoma, seroma, infection, dehiscence, and standing cone deformity requiring correction were all comparable (Table 5).

Table 5.

Effect of Complications by Satisfaction Scores

BREAST-Q category Unsatisfied
(N = 76)
Satisfied or very satisfied
(N = 86)
P
Hematoma 1 (1.32%) 0 (0%) .29
Seroma 3 (3.95%) 2 (2.35%) .56
Infection 9 (11.84%) 19 (22.35%) .08
Dehiscence 4 (5.26%) 5 (5.88%) .86
Standing Cone Deformity Requiring Correction 3 (3.95%) 5 (5.88%) .57

Values are n (%).

DISCUSSION

Reduction mammaplasty is one of the most common plastic surgery procedures and can profoundly and positively influence a patient's self-image and physical and emotional well-being.1,2 However, like all surgical procedures, it may be associated with potential risks. We found that obesity status, HTN, and diabetes were independently associated with the development of complications, which validates previous findings.5,19 Similar to previous studies, we noted that the majority of observed complications were minor, and no patients experienced significant morbidity or mortality after appropriate interventions. Most importantly, we confirmed that patients who experienced complications had comparable long-term satisfaction to patients who did not experience a complication, across multiple measures of the BREAST-Q PROMs. To our knowledge, this is the first study in which a validated PROM has been used to examine the association between complications and long-term patient satisfaction in adult breast reduction patients.

Benefits of Breast Reduction Surgery

Macromastia, or benign breast hypertrophy, can present with a variety of symptoms that impact patients’ quality of life, such as chronic pain in the chest, shoulders, back, and neck; neurological pain, such as migraine and neuropraxia of the upper limbs; and psychological distress, such as decreased social functioning and self-esteem.20-24 Although women with BMIs classified as Class I or II obesity represent a majority of patients requesting surgical treatment, any patient with symptoms unrelieved through nonsurgical interventions may benefit from reduction mammaplasty.25 Additional benefits include increased ability to exercise, psychosocial well-being, and improved quality of life.26-28 Although reduction mammaplasty has been primarily studied for its aesthetic and symptomatic benefits, there remains clinical controversy surrounding its role in weight management. Breast adipose tissue may have metabolic implications and its reduction through surgery could potentially influence metabolic parameters.29,30

Complications of Reduction Mammaplasty

Complication rates of breast reduction surgery vary between 4% and 54% depending on the types of complications measured.31 Wound dehiscence and wound infection are the most frequent clinical complications after reduction mammaplasty, especially at the T-junction.32 Small areas are self-limiting and may only require a conservative approach such as regular wound dressing changes, whereas larger and deeper dehiscence may require further procedures in the clinic or the operating room.33 Although superficial infections involving the skin or subcutaneous tissues are often localized and managed with topical or oral antibiotics targeting Gram-positive bacteria, deeper infections may require bedside incision and drainage, intravenous antibiotics, and/or a return to the operating room.34

Hematoma is another common complication seen following breast reduction surgery.35 Furthermore, retained hematomas can lead to aesthetic consequences such as nipple-areola complex (NAC) loss, warranting immediate exploration.36 Seromas are also common complications after breast reduction, and may lead to further sequelae of problems such as infection and delayed wound healing.37 Treatment of simple seromas may be observation and binding, but large or repeated seromas require a series of aspirations in the clinic or by interventionists. Some of the other complications of breast reduction include skin necrosis, NAC loss, breast asymmetry, standing cone deformity, and hypertrophic scars, some of which may also be treated with further procedures.

There is a lack of consensus concerning what constitutes major and minor complications of reduction mammaplasty.2,8,38,39 However, similar to Shah et al and Guemes et al, we adopted a distinction based on complication acuity and the likely need for intervention within a hospital setting: major complications were higher acuity whereas minor were lower acuity pursuant to standard clinical judgment and practice.2,38 Interestingly, Winter et al attempted to categorize complications following breast reduction utilizing the Clavien-Dindo classification, which groups complications depending on the intervention they require.31 Our study found that the vast majority of complications after breast reduction surgery were minor. Similar to previous studies, no patients in our cohort experienced complications resulting in long-term or severe morbidity and mortality.

Patient Comorbidities and Risk Factors

The identification of preoperative and operative risk factors for complications can present an opportunity for prevention.40-42 A better understanding of the risk factors independently associated with a poorer outcome in breast reduction surgery can allow for risk mitigation strategies.38,43-46 A systematic review found that obesity, diabetes, tobacco smoking, history of radiation therapy, and resection weight greater than 1000 grams were significantly associated with complications encompassing hematoma, seroma, wound dehiscence, infection, and nipple necrosis.5 Similarly, in our study, those who developed complications were more likely to have risk factors of obesity and diabetes. Although not a common theme in the literature, HTN was one of the factors seen in our patients with complications, possibly due to the correlation between HTN and obesity.47 Weight loss, glycemic control, and blood pressure monitoring are parameters that can be modified prior to surgery, and a collective effort with a multidisciplinary team including primary care physicians and anesthesia is crucial to achieving an optimal patient state.48

Many surgeons consider obesity as a contraindication for breast reduction surgery; multiple studies have reported a strong correlation between obesity and complications.32,49 However, this is an area of disagreement. Other practitioners advocate that obesity should be excluded as a threshold for surgery, arguing that the benefits have not been weighed against the disadvantages. For example, Setälä et al demonstrated in a multicenter study that although obesity has indeed an increased risk of local complications, the long-term health benefits that patients experience after breast reduction are far greater.8 Ultimately surgeons and patients should mutually consider the risk of complications for a given procedure and whether the long-term benefits and satisfaction outweigh such risks.

Association Between Complications and Long-term Patient Satisfaction

Although it is of the utmost importance to minimize complications through proper preoperative planning, it is not clear whether complications negatively affect long-term patient satisfaction, another surgical outcome measure. As described, it is well documented that reduction mammaplasty has a high rate of satisfaction.50-52 This has also been supported by literature demonstrating improved quality of life through various forms of PROs, including Short Form 36 (SF-36), Rosenberg Self-Esteem Scale (RSES), BREAST-Q, Breast-Related Symptoms Questionnaire (BRSQ), and numerous validated and individually designed questionnaires.50 However, only a few studies have investigated the impact that postoperative complications may have on patient satisfaction.

Nuzzi et al explored the relationship between complications and the difference between preoperative complications and satisfaction after procedure. Postoperative survey scores of patients showed a significant increase on all of their survey measures including SF-36, RSES, BRSQ, and Eating-Attitudes Test-26. More importantly, patients who eventually developed complications had significantly improved quality of life, measured by the difference between postoperative and preoperative survey scores—an improvement comparable to that seen in patients who did not experience any complications. However, the study only included young adolescent females who had an average age of 17.8 years at the time of surgery. Ngaage et al examined breast reduction mammaplasty satisfaction and its relationship with complications among high-BMI patients.17 They demonstrated that patients who reported having high satisfaction after breast reduction did not have the least number of complications; in other words, satisfaction was independent of complications. However, the authors used a novel, nonvalidated questionnaire and only had a small sample size of 70 patients with high BMI.

Our study confirms several points that were made in similar previous studies. Patients who developed complications did not report any significantly lower scores in all 9 domains of the BREAST-Q survey. Interestingly, we observed a trending significance in the complications cohort reporting higher scores for satisfaction with the surgeon. We speculate that this may be due to a greater frequency of encounters with the surgeon during treatment of complications; studies have shown that longer physician-patient interaction time and better communication improves overall patient satisfaction.53-55 Furthermore, our study's investigation of adult patient populations with a wide variety of demographic characteristics strengthens previous literature on the relationship between complications and patient satisfaction. In fact, the average age of our patient cohort is more reflective of the patient population who typically receives reduction mammaplasty.56-58 Given the larger sample size and the diversity of our patient population, our results further support the notion that postoperative complications do not adversely affect patient satisfaction for breast reduction surgery.

Limitations

Despite the important findings in our study, there are several limitations present. First, we did not have preoperative BREAST-Q measures to compare outcomes with. Without a baseline comparison, our results cannot support a conclusion of an association between change in satisfaction scores. In addition, per official BREAST-Q user guide instructions, missing scores were substituted with the category's mean values when at least 50% of the questions were scored. Furthermore, there are no distinctions present between the types of reduction mammaplasty. Although our data were institutional, the operating plastic surgeons have a range of experience. Nevertheless, all surgeons at our institution use standardized operative markings and techniques. There is also the possibility that PROs can be lower due to patient psychosocial history, such as depression, and this was not considered in our study.

CONCLUSIONS

Our findings indicate that despite the development of minor and major complications, with appropriate interventions, there is no correlation between postoperative complications and reduced long-term patient-reported satisfaction. Although we found no association between complications and postoperative BREAST-Q scores, this should be confirmed with prospective analysis. We aim to validate our findings by quantifying the change in preoperative and postoperative patient satisfaction in a future prospective study. Although it is important to discuss risk factors and potential complications for reduction mammaplasty, barriers to care for patients deemed high-risk may not be necessary to maintain a high level of patient satisfaction.

Supplemental Material

This article contains supplemental material located online at www.aestheticsurgeryjournal.com.

Supplementary Material

sjae168_Supplementary_Data

Disclosures

The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article.

Funding

Tufts University School of Medicine; Ms Adebagbo was supported by a T32 grant; the project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, award number T32TR004417. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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