United States

Background: Soft tissue sarcomas (STS) are malignant tumors that originate in soft tissues, managed with surgical resection as first-line treatment. Time to intervention (TTI) is crucial to the overall survival as metastases can develop in about 50% of STS patients. In the US, the median TTI is 22 days for STS patients, with longer TTI associated with poorer outcomes.1-3 While low-income public insurance and academic centers have individually been associated with increased TTI, no studies have investigated the combined impact of these factors.2,4-5 

Methods: We performed a single academic institution retrospective chart review of patients who underwent surgical STS resection between 2013 and 2023 with Medicaid or Medicare insurance. TTI was calculated from date of diagnosis to date of surgical resection. 

Result: Data was collected from 69 patients who underwent surgical STS resection; 20 patients were diagnosed and referred from outside hospitals, and 28 patients received preoperative radiation therapy (PRT). 90% of STS patients were diagnosed by biopsy and 10% by imaging. The most common STS diagnoses included “undifferentiated pleomorphic sarcoma” (25%) and “myxofibrosarcoma” (20%). Of the 41 patients that underwent STS surgical resection only, 56% had high grade (grade 2 or 3) STS and had a median TTI of 40 days. Among the PRT patients, 89% had high grade STS and median TTI of 104 days. 

Conclusion: The median TTI for surgical resection of STS in Medicare and Medicaid patients at a single academic institution was higher compared to the median TTI for STS in the US.

AMA Research Challenge 2024 

Increased Time to Intervention for Medicaid and Medicare Patients with
Localized Soft Tissue Sarcoma at a Single Academic Institution

**Welcome to EMNLP 2023!**

On behalf of the EMNLP 2023 Organizing Committee, I extend a warm and heartfelt welcome to all of you to the 2023 Conference on Empirical Methods in Natural Language Processing (EMNLP). It is with immense pleasure and excitement that we gather here in Singapore, a vibrant hub of innovation and technological advancement.

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EMNLP 2023

EMNLP 2023 took place in Singapore from Dec 6th to Dec 10th, 2023.

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Optimizing the ACS NSQIP Risk Calculator in Microsurgical Free Flap Breast Reconstruction

Background: Pre-operative risk indexes such as the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) have become increasingly popular for predicting patient-specific postoperative risks in plastic surgery. This study aimed to assess the accuracy of the ACS NSQIP tool in microsurgical breast reconstruction with subsequent analysis of the most significant patient-level risk variables that drive these predictions. 

Methods: A retrospective review of 98 microvascular free flap breast reconstructions performed between 2018-2022 was completed. 94 patients were included in the analysis. Univariate analysis between complication and non-complication groups was completed to identify significant differences in predictions. Receiver operating characteristic (ROC) curves on these predictions were subsequently completed to evaluate the accuracy of ACS NSQIP. Multivariate regression analysis was performed on pre-operative patient data utilized in the NSQIP risk calculator to identify any significant relationships between predictor variables and observed adverse postoperative events.

Results: Univariate analysis revealed the ACS NSQIP calculator most accurately predicted any complication (p=0.0432) and surgical site infection (p=0.0216) of the 12 outcomes analyzed by the authors. ACS NSQIP predicted “any” complications with a diagnostic accuracy of 63.1%, sensitivity of 61.3%, and specificity of 71.0%. It also predicted surgical site infection with a diagnostic accuracy of 71.6%, sensitivity of 57.1%, and specificity of 84.9%. Subsequent multivariate linear regression analysis of significant predictions revealed that non-white individuals were 6.68 times more likely to have any complication (95% CI 1.89-23.62; p=.003) and 6.38 times more likely to have a serious complication (95% CI 1.81-22.53; p=.004).

Conclusion: The NSQIP Risk Calculator was found to be significant in predicting “any complications” and “surgical site infections'' amongst our institution’s microsurgical breast reconstruction cohort, with minorities experiencing an approximate seven-fold increase in complications. Further analysis of the patient-level risk factors that drive these predictions may optimize the accuracy of this index and provide a powerful tool in pre-operative counseling by plastic surgeons.

Optimizing the ACS NSQIP Risk Calculator in Microsurgical Free Flap Breast
Reconstruction

Background
The Goldilocks mastectomy is a breast reconstruction technique that utilizes the remaining breast tissue post-mastectomy to create a new, smaller breast mound. For this reason, the Goldilocks technique is well-suited for patients with large, ptotic breasts. This procedure is often paired with free nipple grafting (FNG), a technique in which the nipple-areolar complex (NAC) is removed entirely and relocated as a skin graft. In cases where only one NAC can be preserved, the nipple can be split into halves and fashioned into two separate nipples prior to graft placement.

When FNG is employed in conjunction with Goldilocks mastectomy, it is often performed as a secondary procedure. However, the surgical risks and recovery time can be reduced when these procedures are performed concurrently. A single-stage operation can also allow for earlier radiation treatment or the avoidance of grafting on irradiated skin.

Case Presentation
Here, we present the successful application of FNG in conjunction with the Goldilocks mastectomy in a single-stage procedure. The patient was a 55-year-old female with bilateral, retropectoral breast implants who wore a DD size bra. After presentation with microcalcifications in the left breast and diagnosis of ductal carcinoma in situ, bilateral mastectomy was suggested. The patient requested a reconstructive procedure in which her implants could be removed while still preserving the shape and aesthetics of her breasts. Because cancer was present in the left NAC, only the right nipple could be preserved for grafting. Therefore, single-stage, bilateral Goldilocks mastectomy with nipple-splitting and subsequent FNG was suggested as a treatment option. The procedure was explained to the patient, and she was informed of the associated risks. She chose to proceed with surgery. The procedure was successfully performed using a single-stage approach. The patient did not suffer any complications and had good wound healing, which led to a pleasing cosmetic result and eliminated the need to return to the hospital for further treatment.

Discussion
The decision to perform FNG concurrently with a Goldilocks mastectomy provides several benefits. A FNG addresses the cosmetic impact of NAC removal, and the single-stage approach reduces overall recovery time, minimizes infection risk, and promotes a faster return to daily life. In this case, the patient’s desire for implant removal was accommodated while also providing total breast reconstruction in a single operation. The single-stage method helped to minimize postoperative complications and optimize the aesthetic outcome, ultimately yielding high patient satisfaction and improved quality of life.

Single-Stage Breast Reconstruction: The Application of Free Nipple Grafting in Goldilocks Mastectomy

Abstract Title 
Surgical Outcomes of Fresh Frozen Cartilage Use in Rhinoplasty: A Systematic Review 

Background 
Despite high satisfaction rates, rhinoplasty has a 5-15% revision rate, which is often complicated by insufficient cartilage. This challenge can be addressed with the use of cartilage grafts, including autologous cartilage and irradiated homologous costal cartilage. Recently, fresh frozen costal cartilage (FFCC) has emerged as a promising alternative, providing reduced donor site morbidity and preserved biomechanical properties. The purpose of this review is to systematically synthesize the existing literature on FFCC for rhinoplasty, focusing on surgical outcomes to inform clinicians and guide future research. 

Methods 
A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search input, “(fresh frozen) AND (rhinoplasty)” was utilized to identify relevant articles in six electronic databases: Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica Database, Google Scholar, PubMed, Scopus, and Web of Science. Database searching yielded 83 records. Three independent reviewers screened and assessed identified articles based on pre-established eligibility criteria. Eligible studies reported original patient outcomes of rhinoplasty utilizing FFCC and provided sufficient data regarding outcomes. Extracted data included study design, patient demographics, technical details, and surgical outcomes. 

Results 
A total of five studies were included in the review, and collectively encompassed data for a total of 766 patients (83.9% female, 16.1% male) who underwent rhinoplasty with FFCC. This included 72 primary rhinoplasties (9.4%) and 694 revision procedures (90.6%). Across the 766 patients, there were 13 cases (1.7%) of infection, nine cases (1.2%) of warping and seven cases (0.9%) of cartilage resorption. Of studies reporting cartilage graft displacement, there was only one case (0.1%). Additionally, the reoperation rate ranged from 0.5% to 16% with an average of 2.3% (n=18) across the studies. 

Conclusion 
With comparable outcomes and low complication and reoperation rates, FFCC represents a safe and reliable alternative to autologous rib grafts for rhinoplasty. However, given the novelty of this technique, additional studies with larger patient populations and long-term follow-up are needed to validate these findings.

Surgical Outcomes of Fresh Frozen Cartilage Use in Rhinoplasty: A Systematic Review​

Introduction: Interest has grown in transcutaneous osseointegrated (TOI) upper extremity prosthetics as an alternative to traditional socket prosthetics. As of 2023, no upper extremity TOI prosthetic have received FDA approval in the United States. This study examines demographics and postoperative outcomes in patients who have received upper extremity TOI prosthetics globally.
Methods: The PubMed, EMBASE, and Cochrane databases were queried for cases of upper limb TOI prosthetics with variations in terms for osseointegration, prosthetics, and upper extremity anatomy. Studies were included if demographic and outcome data on patients with at least one amputation and TOI prosthetic at any site of the upper limb were present. Studies that pertained only to endoprostheses or lower extremity TOI, had incomplete information on multiple patients, exclusively reported biomechanical or material data, or were in non-English languages were excluded. Site and etiology of limb loss, age, sex, history of infection at TOI site, and subsequent surgery on the site were recorded. Descriptive statistics were calculated. 
Results: The search returned 1,314 articles, of which 907 were screened after duplicate exclusion. Ultimately, 27 studies with 95 patients were analyzed. Patients were predominantly male (N=70, 73.6%) and age at prosthetic placement ranged from 10 to 68 years. The most common prosthetic sites were the thumb (N=33, 35.7%) and humerus (N=21, 22.1%). Eleven patients required secondary surgery; 10 were for hardware problems (e.g., loosening, breakage) and one was a soft tissue revision. Infections between surgery and first follow-up were reported in 11.5% of patients. Only 46.3% of studies explicitly discussed infection outcomes following TOI. 
Conclusion: TOI prosthetics have been used with some success internationally, but clinical data is limited and reports are inconsistent. Lack of approval in the U.S. has made analysis of outcomes difficult. While infection is a valid concern, implant hardware is a frequently reported cause of subsequent surgeries at TOI prosthetic sites. 


Transcutaneous Osseointegration for Upper Extremity: A Systematic Review of the Literature

Background: Peripheral nerve injuries present a major challenge due to limited functional and sensory recovery with current treatments. Human amniotic and umbilical cord membranes show promise in tissue regeneration but are limited by the quantity and variety of growth factors they release. This study evaluates the efficiency of umbilical cord and placental membranes as biological scaffolds for lysozyme delivery. The assessment includes investigating the binding capacity of double-walled microspheres (DWMS) loaded with lysozyme to the membranes and characterizing the subsequent lysozyme release kinetics.

Methods: Lysozyme, chosen for its similar properties to glial-derived neurotrophic factor (GDNF), was encapsulated in biodegradable poly lactic-co-glycolic acid (PLGA)/poly lactic acid (PLA) microspheres using a water-oil-water emulsion solvent evaporation technique. The binding capacity and release kinetics of lysozyme from DWMS bound to cryopreserved and lyophilized umbilical cord and placental membranes were assessed over 1, 6, and 24 hours, using the Bicinchoninic Acid assay.

Results: Our findings demonstrated that lysozyme-loaded DWMS bound similarly to both cryopreserved and lyophilized umbilical cord membranes. However, placental membranes soaked for 1 and 24 hours exhibited significantly higher lysozyme release (p<0.05) compared to non-loaded membranes. Notably, placental membranes soaked for 24 hours released 1.57 times more lysozyme than those soaked for 1 hour at the 72-hour mark. Furthermore, lysozyme release from both cryopreserved and lyophilized umbilical cord membranes was significantly greater after 6 and 24 hours of DWMS treatment compared to placental membranes (p<0.05). Cryopreserved umbilical cord membranes specifically showed a greater release than lyophilized membranes when assessed at these time points (p<0.05).

Conclusion: Placental membranes demonstrated superior efficacy as scaffolds for lysozyme-loaded DWMS delivery, particularly with longer incubation periods. Cryopreserved umbilical cord membranes were more effective than lyophilized ones, suggesting that preservation methods impact therapeutic potential. These findings highlight a novel approach for enhancing peripheral nerve regeneration through improved drug delivery systems.

Umbilical Cord & Placental Membranes as Biological Scaffolds for Drug Delivery in Nerve Regeneration

Using Digested and Lyophilized Bone Matrices for Enhanced Retention and Sustained Release of BMP-2 for Bone Regeneration
Background
Human recombinant bone morphogenetic protein 2 (rhBMP-2) is an FDA-approved growth factor that promotes bone formation but includes safety risks like inflammation and ectopic bone formation. Current research aims to enhance rhBMP-2 delivery strategies, as prolonged, controlled release improves bone healing and reduces side effects compared to short-term release. Currently, collagen sponges are often used for the delivery of rhBMP-2 but suffer from poor structural stability and inadequate release profiles. A previous study developed a sponge- like matrix from decellularized, demineralized, and enzymatically digested porcine bone, demonstrating biocompatibility and bone regeneration. In this study, we created a similar digested and lyophilized bone matrix (DLBM) while adding synthetic BMP2 (sBMP2) and stabilizing with glutaraldehyde (GL) crosslinking in the hopes of creating a safe and efficacious BMP2 delivery system.
Methods
The digested and lyophilized bone matrix (DLBM) was fabricated using established methods, with synthetic BMP2 peptide (sBMP2) infused and stabilized through glutaraldehyde (GL) crosslinking. This DLBM/BMP2/GL construct was compared to a DLBM/BMP2 scaffold without crosslinking. Over four weeks, we assessed in vitro degradation and BMP2 release of both constructs at various time points. The in vivo efficacy of the DLBM/BMP2/GL scaffold was evaluated using a non-healing tibial defect model in a rat model, analyzing bone growth via CT and histology after eight weeks.
Results
In vitro degradation experiments showed that the DLBM/BMP2/GL scaffold retained significantly more of its original mass (~40%) compared to the non-GL scaffold (~17%). Additionally, we found significantly higher retention of sBMP2 in the DLBM/BMP2/GL scaffold at all time points. CT analysis and histological examinations further indicated that the DLBM/BMP2/GL scaffold exhibited enhanced regenerative capability over the DLBM scaffold in vivo, demonstrating improved efficacy.

Conclusion
Our study underscores the potential of the DLBM/BMP2/GL scaffold as a promising platform for bone tissue engineering. We found that a sponge-like matrix, comprised of the digested and lyophilized bone matrix (DLBM) of pig bone, could effectively retain BMP2 peptide after chemical crosslinking using glutaraldehyde (DLBM/BMP2/GL). Further, we found a much more sustainable and controllable release profile of the BMP2 from the DLBM/BMP2/GL matrix when compared to the same BMP2-infused DLBM structure without any chemical crosslinking applied. Our in vivo evaluations demonstrate the improved biocompatibility, osteogenicity, and bone regenerative capacity of the DLBM/BMP2/GL scaffold compared to DLBM alone. Overall, our findings contribute to advancing innovative strategies for optimizing bone tissue engineering outcomes, thereby enhancing clinical efficacy and safety in bone repair and regeneration applications.

Using Digested and Lyophilized Bone Matrices for Enhanced Retention and Sustained Release of BMP-2 for Bone Regeneration

Background 
Vaginal rejuvenation refers to a variety of procedures that aim to improve genitourinary function or cosmetics. Local estrogen is the current standard of care to address complaints of vulvovaginal atrophy and vaginal laxity. However, energy-based treatments have become an emerging treatment option. Following an FDA statement in 2018 expressing concern over alleged lack of supporting evidence, laser and radiofrequency treatment of the vagina remains somewhat controversial.
Methods
The PubMed, EMBASE, and CENTRAL databases were queried for English-language studies published between November 2018 and June 2024 with terms associated with vaginal rejuvenation, including but not limited to, “vaginal” or “vagina” and “genitourinary syndrome of menopause” or “rejuvenation” or “vulvovaginal atrophy” or “vaginal atrophy”. Searches also included “laser” or “erbium-doped yttrium aluminum garnet” or “diode” or “carbon dioxide” or “CO2” or “radiofrequency” or “thermal”. 
Studies were included if they included at least one patient 18 years of age and older undergoing laser or radiofrequency therapy of the vagina for a specific vaginal or lower urinary complaint. Studies with purely cosmetic indications were excluded, as were studies with combined therapies, animal or cadaver models, or participants with active infectious or neoplastic pathology of the genitourinary system. Additionally, studies must have been available in full text and reported clinical outcome data, including standardized measures of patient reported outcomes and qualitative symptom data. Studies that did not explicitly report the presence or absence of adverse effects were excluded. 
Results
A total of 1374 studies were identified (EMBASE=792, PubMed=376, CENTRAL=206). 337 duplicates were excluded and 1059 studies were ultimately screened. 77 studies were included with a total number of 5,143 patients. 27 of these were randomized controlled trials, 40 were prospective interventional studies, and 10 were retrospective studies. A majority (79%) used laser treatment for vaginal rejuvenation. Indication for rejuvenation was stress urinary incontinence in 18 studies and genitourinary syndrome of menopause or its related symptoms in 
the remaining. 93.5% (N=72/77) of the studies reported improvements in patient-reported outcomes. Just under half (49.4%) of the studies reported at least minor or transient adverse effects of the treatment. These included vaginitis, leukorrhea, vaginal pain, dysuria, and urinary tract infection.
Conclusion 
Laser and radiofrequency treatment of the vagina has demonstrated improvement in patientreported outcomes for genitourinary symptoms associated with vaginal atrophy and urinary incontinence. Adverse effects of vaginal rejuvenation in the literature are minor, suggesting that this is a safe and effective option for patients with post-menopausal complaints requiring vaginal rejuvenation.

Vaginal Rejuvenation by Laser or Radiofrequency: A Systematic Review of the 
Literature

Background: Reduced sensation frequently occurs after reduction mammaplasty. However, the degree of sensation can vary among individuals. The aim of this study is to assess how body mass index (BMI) and weight of breast tissue excised during reduction mammaplasty affects postoperative sensation. 

Methods: Patients undergoing reduction mammaplasty with superomedial or superior pedicle and Wise pattern incisions were prospectively followed. One month after surgery, neurosensory testing was completed using a pressure-specified sensory device to record sensation on a scale from 0 to 100, where higher values indicate greater sensitivity. An average sensation score was calculated per breast from 9 breast regions. Patient demographics, BMI, and weight of breast tissue excised were recorded. Linear regression analysis was run to predict postoperative sensation from BMI, specimen weight, and ratio of BMI to specimen weight. Student t-test were used to detect differences between BMI groups (BMI <30 vs. BMI >30) and specimen weight (weight <1,000 g vs. weight >1,000 g). 

Results: Sensory testing was completed on 28 breasts in 14 patients. Multiple linear regression analysis revealed that specimen weight (t=-2.59, p=0.02) was a significant predictor of postoperative sensation, but BMI was not (t=-0.32, p=0.75). The ratio of BMI to specimen weight was also a significant predictor of postoperative sensation (t=2.65, p=0.01). Our result is robust to the normal assumption. Even using nonparametric Spearman’s coefficient test, the results remain significant. The Spearman’s Correlation coefficient was -0.46 for specimen weight (p=0.01) and 0.49 for ratio of BMI to specimen weight (p=0.01). A t-test revealed a significant difference in average postoperative sensation between patients with less than 1,000 g excised (68.39 ± 15.47) and 1,000 g or more excised (53.17 ± 18.93) (p=0.03). There was no difference between average postoperative sensation in obese (64.97 ± 16.74) and non-obese patients (60.28 ± 20.07) (p=0.51). 

Conclusions: This study revealed that specimen weight was a predictor for postoperative sensation, with more tissue excised resulting in worse sensation. The ratio of BMI to specimen weight was also found to be a significant predictor, suggesting that specimen weight is predictive of sensation irrespective of BMI. These parameters can guide preoperative counseling and may suggest a benefit for nerve reinnervation in certain groups that need a larger amount of breast tissue excised during reduction. Future work will investigate how BMI and specimen weight affect long-term sensation following mammaplasty.

Weighing In: Predicting Postoperative Sensation After Breast Reduction

INTRODUCTION: Loneliness is associated with increased morbidity and mortality and has been considered the latest global health epidemic. The COVID-19 pandemic has further exacerbated loneliness across all age groups, particularly older adults who are more vulnerable to the negative effects of quarantining and social distancing. This study aims to assess the relationship between loneliness, depression, and suicidality among older adults during the COVID-19 pandemic using data from the All of Us (AoU) Research Program. 

METHODS: We analyzed cross-sectional data from the National Institutes of Health AoU Research Program, a research initiative encompassing diverse US residents. We focused on older adults aged 65 (N=17,084) who completed a COVID-19-related survey administered between May 2020 and February 2021. Participants were divided into quartiles based on their UCLA Loneliness Scale Short Form-8 scores. Descriptive statistics and chi-square tests were employed for demographic analysis, and logistic regression models were used to test associations between loneliness quartiles and both depression (via Patient Health Questionnaire-9 [PHQ-9] score 10) and suicidal ideation (via PHQ-9 item 9 positive response). The models were adjusted for age, gender, race, ethnicity, education, marital status, employment status, housing status, health insurance status, and social support rating.

RESULTS: Among the 17,084 older adult participants (mean [SD] age of 72.0 [5.3]), 55.0% were female, 89.8% identified as White, 2.1% identified as Hispanic, 66.9% were married, 72.0% were college graduates, 70.3% were retired, 7.8% met the criteria for moderate-severe depression, and 3.5% endorsed experiencing suicidal ideation. Individuals in the highest quartile of loneliness were more likely to be younger, female, have lower social support, and lack of marital, educational, housing, or insurance status (all ps<0.05). Compared to individuals in the 1st quartile of loneliness, those in the 2nd, 3rd, and 4th (highest) quartile of loneliness had adjusted odds ratios (aORs) of 2.42 (95% confidence interval [CI]:1.57-3.77), 7.91 (95% CI: 5.29-11.82), and 39.50 (95% CI: 26.76-58.30), respectively, of meeting criteria for moderate-severe depression. Similarly, participants in the 2nd, 3rd, and 4th quartile of loneliness had greater odds of suicidal ideation (aORs of 3.73 (95% CI: 1.64-5.52), 12.31 (95% CI: 5.69-26.59), and 65.48 (95% CI: 30.85-138.97), respectively).

CONCLUSION: 
Older adults in the highest quartile of loneliness were nearly 40 and 65-times more likely to be depressed and suicidal, respectively, during the COVID-19 pandemic. To our knowledge, this is the largest US population-level investigation of its kind, and our findings underscore the need for targeted interventions to mitigate loneliness.

Dose-Dependent Association of Loneliness with Depression and Suicidal Ideation Among Older Adults During the COVID-19 Pandemic

Background: Extended-release (XL) bupropion hydrochloride (HCl) received FDA approval for Major Depressive Disorder (MDD) in 2003 and for Seasonal Affective Disorder (SAD) in 2006. XL bupropion hydrobromide (HBr) (Aplenzin®) received FDA approval in 2008 for both MDD and SAD following demonstration of pharmacokinetic bioequivalence to XL bupropion HCl. However, no human clinical efficacy trials of XL bupropion HBr have been completed and none comparing it to XL bupropion HCl. We wanted to compare equivalent FDA-approved dosing of XL bupropion HBr to generic XL bupropion HCl in patients with Treatment-Resistant Depression (TRD). There is only one FDA-approved oral TRD combination medication, fluoxetine-olanzapine, that carries cardiometabolic side effects and sedation, and one approved adjunctive nasal spray, esketamine, that requires 2-hour in-office monitoring limiting access. 
Methods: We obtained informed consent from each patient prior to conducting a de-identified retrospective chart review of 30 adults with TRD (18 females, 12 males) who directly switched from their maximally tolerated dose of generic XL bupropion HCl, due to inadequate response and/or side effects, to an equivalent dose of XL bupropion HBr. PHQ-9 scales were administered by a blinded rater. 
Results: Patients had a mean age of 38.7 +/- 14.7 years, failed a mean of 4 +/- 2 antidepressants, and had a mean baseline PHQ-9 score of 20.9 +/- 4.3 prior to taking a mean XL bupropion HCl dose of 300 mg/day (range 150‒450 mg/day) for a mean duration of 88.8 weeks (range 4‒480 weeks). After 2 weeks on a mean XL bupropion HBr dose of 348 mg/day (range 174‒522 mg/day), these patients demonstrated improvement in PHQ-9 scores from a mean of 15.3 +/- 5.3 on XL bupropion HCl to a mean of 6.4 +/- 5.0 on XL bupropion HBr (t = −8.63, p < 0.00001). The most commonly encountered side effects with generic XL bupropion HCl were insomnia (21 patients), anxiety (19 patients), and gastrointestinal upset (2 patients), which resolved on XL bupropion HBr except for residual insomnia (3 patients). 96.7% of patients (29 of 30) chose to continue on XL bupropion HBr rather than change back to generic XL bupropion HCl.
Conclusion: Adult patients suffering from TRD experience rapid and significant improvement in mood with greater tolerability when switching from generic XL bupropion HCl to an equivalent dose of XL bupropion HBr. A further double-blind study could enable the first FDA-approved oral monotherapy for TRD.

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