The Impact of Breast Implant Cohesivity on Rippling and Revision Procedures in 2-Stage Prepectoral Breast Reconstruction.

Background: Rippling remains one of the most common complications following prepectoral implant-based reconstruction (IBR). Objectives: The purpose of this study was to assess how implant cohesivity, a measure of elasticity and form stability, affects the incidence of rippling in prepectoral IBR. Methods: We performed a retrospective cohort study of 2-stage prepectoral IBR performed between January 2020 and June 2022 at the Brigham and Women's Hospital and Dana-Farber Cancer Institute, comparing outcomes in patients who received Allergan Natrelle least cohesive, moderately cohesive, and most cohesive silicone gel implants. Outcomes of interest were rippling and reoperation for fat grafting. Results: A total of 129 patients were identified, of whom 52 had the least cohesive implants, 24 had the moderately cohesive implants, and 53 patients had the most cohesive implants. The mean follow-up time was 463 (±220) days. A decreased incidence of rippling was seen with moderately cohesive (odds ratio [OR] 0.30, P < .05) and most cohesive (OR 0.39, P < .05) implants. Third stage reoperation for fat grafting was less frequent in patients with the most cohesive implant (OR 0.07, P < .05). In subgroup analyses, the patients with the most cohesive implant, who did not receive fat grafting at the time of initial implant placement, did not require reoperation for fat grafting (0%). Conclusions: The use of highly cohesive implants in prepectoral IBR is associated with decreased rippling and fewer reoperations for fat grafting.

Comparison of emotional and behavioral regulation between metopic and sagittal synostosis.

PURPOSE: Children with surgically corrected nonsyndromic craniosynostosis have been previously found to have neurocognitive and behavioral difficulties. Children with metopic synostosis have been described to have more difficulties than children with sagittal synostosis. This study aims to characterize the behavioral differences between children with metopic and sagittal synostosis. METHODS: Children with metopic and sagittal synostosis were recruited at school age. Parents completed four separated behavioral assessments: Conners-3 (evaluation of ADHD), Social Responsiveness Scale-2 (SRS-2: evaluation of autism), Behavior Rating Inventory of Executive Function-2 (BRIEF-2: evaluation of executive function), and Child Behavior Checklist (CBCL: evaluation of overall behavioral problems). Children underwent intelligence quotient (IQ) testing using the Wechsler Abbreviated Scale of Intelligence (WASI-II). RESULTS: There were 91 children (45 with metopic and 46 with sagittal synostosis). More children with metopic synostosis reported requiring supportive services (57.7% vs 34.7%, p = 0.02) and more reached or exceeded borderline clinical levels of two executive function subscales of the BRIEF-2 (emotion regulation index: 33.3% vs 17.4%, p = 0.05; global executive composite: 33.3% vs 17.4%, p = 0.05). Children with sagittal synostosis had higher scores on the rule-breaking and externalizing problem subscales of the CBCL. Increasing age at surgery was associated with worse executive function scores. CONCLUSIONS: A relationship between suture subtype and behavioral outcomes exists at school age. More children with metopic synostosis required social services indicating more overall difficulties. Children with metopic synostosis have more specific problems with executive function, while children with sagittal synostosis had more difficulties with externalizing behaviors.

Sports participation after craniosynostosis repair: the critical role of post-operative guidance in parental decision-making.

PURPOSE: Despite previous research supporting patient safety in sports after craniosynostosis surgery, parental anxiety remains high. This study sought to evaluate the role of healthcare providers in guiding patients and families through the decision-making process. METHODS: Parents of children with repaired craniosynostosis were asked to assess sports involvement and parental decision-making in children ages 6 and older. Questions were framed primarily on 5-point Likert scales. Sport categorizations were made in accordance with the American Academy of Pediatrics. Chi-squared, linear regression, and Pearson correlation tests were used to analyze associations between the questions. RESULTS: Forty-three complete parental responses were recorded. Mean ages at surgery and time of sports entry were 7.93 ± 4.73 months and 4.76 ± 2.14 years, respectively. Eighty-two percent of patients participated in a contact sport. Discussions with the primary surgeon were more impactful on parental decisions about sports participation than those with other healthcare providers (4.04 ± 1.20 vs. 2.69 ± 1.32). Furthermore, children whose parents consulted with the primary surgeon began participating in sports at a younger age (4.0 ± 1.0 vs. 5.8 ± 2.7 years, p = 0.034). The mean comfort level with contact sports (2.8 ± 1.4) was lower than that with limited-contact (3.8 ± 1.1, p = 0.0001) or non-contact (4.4 ± 1.3, p < 0.0001) sports. CONCLUSION: This study underscores the critical role that healthcare professionals, primarily surgeons, have in guiding families through the decision-making process regarding their children's participation in contact sports.

A diffusion tensor imaging comparison of white matter development in nonsyndromic craniosynostosis to neurotypical infants.

PURPOSE: Nonsyndromic craniosynostosis (NSC) is associated with neurocognitive deficits, and intervention at infancy is standard of care to limit the negative effects of NSC on brain development. In this study, diffusion tensor imaging (DTI) was implemented to investigate white matter microstructure in infants with NSC undergoing cranial vault remodeling, and a comparison was made with white matter development in neurotypical controls. METHODS: Infants presenting with NSC (n = 12) underwent DTI scans before and after cranial vault remodeling. Neurotypical infants (n = 5), age matched to NSC patients at preoperative scans, were compared to preoperative DTI scans. Pre- and postoperative NSC scans were compared in aggregate, and the sagittal synostosis (n = 8) patients were evaluated separately. Finally, neurotypical infants from the University of North Carolina/University of New Mexico Baby Connectome Project (BCP), who underwent DTI scans at timepoints matching the NSC pre- and postoperative DTI scans, were analyzed (n = 9). Trends over the same time period were compared between NSC and BCP scans. RESULTS: No significant differences were found between preoperative NSC scans and controls. White matter development was more limited in NSC patients than in BCP patients, with microstructural parameters of the corpus body and genu and inferior and superior longitudinal fasciculi consistently lagging behind developmental changes observed in healthy patients. CONCLUSION: Infant white matter development appears more limited in NSC patients undergoing cranial vault remodeling relative to that in neurotypical controls. Further investigation is needed to explore these differences and the specific effects of early surgical intervention.

Perceived Age and Gender Perception Using Facial Recognition Software Following Facial Feminization Surgery.

Measures of success for facial feminization surgery (FFS) have previously included improved rates of external gender perception as female and patient-reported outcome measures. In this study, we used artificial intelligence facial recognition software to objectively evaluate the effects of FFS on both perceived gender and age among male-to-female transgender patients, as well as their relationship with patient facial satisfaction. Standardized frontal preoperative and postoperative images of 27 transgender women undergoing FFS were analyzed by Amazon's AI facial recognition software to determine gender, femininity confidence score, and perceived age. Female gender-typing, improvement in gender-typing (preoperatively to postoperatively), and femininity confidence scores were analyzed. To assess patient satisfaction, FACE-Q modules were completed postoperatively. Preoperatively, FFS images were perceived as female 48.1% of the time, and postoperatively, this improved to 74.1% ( P =0.05). Femininity confidence scores improved from a mean score of 0.04 preoperatively to 0.39 postoperatively ( P =0.003). FFS was associated with a decrease in perceived age relative to the patient's true age (-2.4 y, P <0.001), with older patients experiencing greater reductions. Pearson correlation matrix found no significant relationship between improved female gender typing and patient facial satisfaction. Undergoing surgery at a younger age was associated with higher overall facial satisfaction ( r =-0.6, P =0.01). Transfeminine patients experienced improvements in satisfaction with facial appearance, perceived gender, and decreases in perceived age following FFS. Notably, patient satisfaction was not directly associated with improved AI-gender typing, suggesting that other factors may influence patient satisfaction.

Quantitative Analysis of Morphometric Changes in Feminization Rhinoplasty Utilizing a Standardized Forehead-Rhinoplasty Technique.

Background: Rhinoplasty is one of the most commonly performed facial gender-affirming surgeries (FGASs) for transgender females, but well-established morphometric parameters describing feminizing nasal changes do not exist. Objectives: Describe the author's technique for feminization rhinoplasty, analyze the changes in 3-dimensional nasal anthropomorphic parameters, and describe patient-reported outcomes. Methods: Three-dimensional photogrammetric evaluation was performed both preoperatively and postoperatively in transgender female patients who underwent FGAS. Measurements assessed included the nasofrontal angle, nasolabial angle, dorsal height, mid-dorsal width, alar width, nasal tip width, and tip projection. Patients were surveyed preoperatively and postoperatively using the FACE-Q Nose module. Paired t-tests were utilized to assess changes in postoperative measurements and FACE-Q Nose satisfaction scores. Results: Twenty patients underwent FGAS during the study period. The average time between surgery and postoperative 3-dimensional images was 13.6 ± 6.8 months. The nasofrontal angle increased by 8.2° (148.0 ± 7.4° to 156.1 ± 6.7°, P < .001) and tip projection increased by 0.017 (0.58 ± 0.03 to 0.60 ± 0.04, P < .01). Dorsal height, mid-dorsal width, and tip width all decreased significantly (P < .05). There were significant improvements in patients' "Satisfaction with Nose," "Satisfaction with Facial Appearance Overall," "Psychological Function," and "Social Function" on FACE-Q. One revision rhinoplasty was performed, and no documented surgical complications were reported. Conclusions: There were statistically significant changes in the nasofrontal angle, tip projection, dorsal height, mid-dorsal width, and tip width in patients receiving feminization rhinoplasty. These data may help surgeons with preoperative planning and intraoperative decision making.

An update on long-term mental health in eight face transplant recipients - A single center experience.

OBJECTIVE: Face transplantation is a groundbreaking and complex surgical intervention offering profound physical and psychological benefits to patients with severe facial disfigurements. This report provides an update on the long-term psychosocial outcome of eight face transplant recipients. METHOD: All transplant recipients were initially transplanted at Brigham and Women´s Hospital (Boston, USA) between 2011 and 2020 and are seen as outpatient patients at Yale New Haven Hospital (New Haven, USA). A mixed-methods approach was used to assess the psychological well-being of these patients. The Short-Form 12, Brief-COPE, EQ-VAS and CES-D were administered between October 2022 and October 2023. RESULTS: Older age of face transplant recipients was significantly and positively associated with better mental health and increased use of both emotional and instrumental support (Brief-COPE). The initial enhancement in patients' self-reported quality of life, as assessed by the EQVAS, declined on the EQ-VAS score at the last follow-up period. Similarly, an increase in depression score was observed (CES-D score) up through the last follow-up assessment. Both of the latter results, however, did not reach statistical significance. CONCLUSIONS: These results underscore the importance of ongoing psychological support throughout the long-term journey of recovery for face transplant recipients. They emphasized the need for a comprehensive, patient-centered approach that also addresses the complex psychological dimensions and contributes to our understanding of the mental health dynamics involved in face transplantation, underscoring the need for guidelines and continued research in this evolving field.

Economic Modeling Analysis of an Intensive GDMT Optimization Program in Hospitalized Heart Failure Patients.

BACKGROUND: The STRONG-HF trial (Safety, Tolerability and Efficacy of Up-Titration of Guideline-Directed Medical Therapies for Acute Heart Failure) demonstrated substantial reductions in the composite of mortality and morbidity over 6 months among hospitalized patients with heart failure (HF) who were randomized to intensive guideline-directed medical therapy (GDMT) optimization compared with usual care. Whether an intensive GDMT optimization program would be cost-effective for patients with HF with reduced ejection fraction is unknown. METHODS: Using a 2-state Markov model, we evaluated the effect of an intensive GDMT optimization program on hospitalized patients with HF with reduced ejection fraction. Two population models were created to simulate this intervention, a clinical trial model, based on the participants in the STRONG-HF trial, and a real-world model, based on the Get With The Guidelines-HF registry of patients admitted with worsening HF. We then modeled the effect of a 6-month intensive triple therapy GDMT optimization program comprised of cardiologists, clinical pharmacists, and registered nurses. Hazard ratios from the intervention arm of the STRONG-HF trial were applied to both population models to simulate clinical and financial outcomes of an intensive GDMT optimization program from a US health care sector perspective with a lifetime time horizon. Optimal quadruple GDMT use was also modeled. RESULTS: An intensive GDMT optimization program was extremely cost-effective with incremental cost-effectiveness ratios <$10 000 per quality-adjusted life-year in both models. Optimal quadruple GDMT implementation resulted in the most gains in life-years with incremental cost-effectiveness ratios of $60 000 and $54 000 in the clinical trial and real-world models, respectively. CONCLUSIONS: An intensive GDMT optimization program for patients hospitalized with HF with reduced ejection fraction would be cost-effective and result in substantial gains in clinical outcomes, especially with the use of optimal quadruple GDMT. Clinicians, payers, and policymakers should prioritize the creation of such programs.

Ear Molding Therapy of Congenital Ear Anomalies: Long-Term Aesthetic Outcomes and Caretaker Satisfaction.

INTRODUCTION: Ear molding is a safe, non-surgical approach to treat newborns with congenital ear anomalies. In this study, we aimed to investigate long-term aesthetic outcomes and caretaker satisfaction from ear molding therapy. METHODS: A retrospective chart review from 2018 to 2020 was conducted for infants who underwent ear molding treatment at our institution. Patient demographics and treatment related variables were collected. Caretakers were surveyed regarding their experience, expectations, and aesthetic outcome at 1 year (short-term) and 3 years (long-term) from treatment. Independent physicians evaluated treatment efficacy. Responses were converted to a Likert scale (1-5), with 5 representing most desirable. RESULTS: Overall, 38 of 42 patients participated in our long-term study (90%) for a total of 62 ears. Average follow-up was 3.31 ± 0.50 years after completion of treatment. Mean age at treatment was 23.2 ± 19.7 days with a mean treatment duration of 21.7 ± 7.7 days. Caretakers' satisfaction regarding auricular appearance remained high (short-term: 4.18 vs. long-term: 4.17, p = 0.54) and anticipated social distress decreased over time. Physician aesthetic evaluations were favorable between "somewhat effective" and "very effective" and remained consistent over time (short term: 3.46 vs. long-term: 3.31, p = 0.31). Furthermore, physician evaluations were higher for deformations than malformations (p = 0.04) and in children who began treatment by 30 days old (p = 0.04). CONCLUSION: Caretaker satisfaction from ear molding therapy remained high after long-term follow up, and social distress from the perception of their child's ears decreased with time. Physician aesthetic ratings confirmed efficacy, with better outcomes seen in deformations than in malformations. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Virtual Surgical Planning in Craniosynostosis Reduces Operative Time and Length of Stay for Cranial Vault Remodeling.

Cranial vault remodeling (CVR) with and without frontal orbital advancement remodels the skull in craniosynostosis. Virtual surgical planning (VSP) for preoperative planning has been previously shown to be effective in CVR. In this study, the authors aimed to evaluate the impact of VSP on operative and perioperative efficiency for craniosynostosis surgery. A retrospective chart review was conducted of patients with craniosynostosis who underwent CVR. Patient demographics, perioperative variables, use of VSP, and complications were obtained. Perioperative variables collected include operative time and length of stay. An independent t test was used to compare variables from patients who had surgery with VSP and patients who did not. Records were available for 126 patients with craniosynostosis who underwent CVR of whom 79 (62.7%) utilized VSP. There was no difference in average age at surgery (9.3±5.7 mo versus 13.2±31.1 mo, P =0.39). Surgeries planned using VSP demonstrated a decreased operative time of 1.3 hours (3.7±1.1 versus 5.0±1.1 h, P <0.001) and a shorter length of stay (3.9±1.3 versus 4.6±1.7 d, P =0.01). There were no differences in complication rates of dehiscence, infection, returns to the operating room, or 30-day readmission. These trends were similar among patients who underwent fronto-orbital advancement in addition to CVR. Virtual surgical planning was associated with decreased operative time and length of stay for patients with craniosynostosis and comparable complication rates. Virtual surgical planning is an effective tool for reducing anesthetic exposure time.

Relationship Between Paraoxonase-1 Genotype and Activity, and Major Adverse Cardiovascular Events and Malignancies in Patients With Rheumatoid Arthritis Receiving Tofacitinib.

OBJECTIVE: This posthoc analysis investigated the relationship between paraoxonase-1 (PON1) genotype and activity, and risk of major adverse cardiovascular events (MACE) and malignancies in clinical studies of tofacitinib in patients with rheumatoid arthritis (RA). METHODS: Data were pooled from 9 phase II/III studies and the associated long-term extension studies (all completed by October 2017). PON1 activities in plasma were measured using paraoxon (paraoxonase activity), dihydrocoumarin (lactonase activity), and phenylacetate (arylesterase activity) as substrates. PON1 Q192R genotype effect on baseline PON1 activity was assessed using linear regression for each study, with fixed-effects metaanalysis across studies. MACE and malignancy risk by time-varying enzyme activity was determined using Cox proportional hazards regression. RESULTS: The analysis included 1969 patients with RA. Compared with the QQ genotype, the RR genotype had a significant positive association with baseline paraoxonase activity and a significant negative association with baseline lactonase and arylesterase activity (all P < 0.001). Time-varying models demonstrated a significant association of increased paraoxonase activity over time with lower risk of MACE (P < 0.001) and malignancies (excluding nonmelanoma skin cancer [NMSC]; P ≤ 0.05), even after controlling for risk factors identified in univariate analysis and RA disease activity. A similar trend was observed for lactonase and arylesterase for MACE. CONCLUSION: Higher paraoxonase activity over time was associated with significantly reduced risk of future MACE and malignancies (excluding NMSC), but not NMSC, in patients with RA receiving tofacitinib. Further investigation of PON1 as a novel functional lipid biomarker of MACE/malignancy risk in patients with RA is warranted. (ClinicalTrials.gov: NCT01059864, NCT00550446, NCT00687193, NCT00960440, NCT00814307, NCT00856544, NCT00853385, NCT00847613, NCT01039688, NCT00413699, NCT00661661).

Assessing utilities for muscle-invasive bladder cancer-related health states.

OBJECTIVES: How patients value functional outcomes against oncologic outcomes during decision-making for muscular-invasive bladder cancer (MIBC) remains unclear. We sought to quantify individuals' preferences on a scale of 0 to 1, where 1 represents perfect health and 0 represents death. METHODS: Descriptions of 6 hypothetical health states were developed. These included: Neoadjuvant chemotherapy followed by radical cystectomy with ileal conduit (IC) or with neobladder reconstruction (NB), Transurethral resection and chemotherapy/radiation (CRT), CRT requiring salvage cystectomy (SC), Recurrent/metastatic bladder cancer after local therapy (RMBC), and Metastatic bladder cancer (MBC). Descriptions consisted of diagnosis, treatments, adverse effects, follow-up protocol, and prognosis and were reviewed for accuracy by expert panel. Included individuals were asked to evaluate states using the visual analog scale (VAS) and standard gamble (SG) methods. RESULTS: Fifty-four individuals were included for analysis. No score differences were observed between IC, NB, and CRT on VAS or SG. On VAS, SC (value = 0.429) was rated as significantly worse (P < 0.001) than NB (value = 0.582) and CRT (value = 0.565). However, this was not the case using the SG method. Both RMBC (VAS value = 0.178, SG value = 0.631) and MBC (VAS value = 0.169, SG value = 0.327) rated as significantly worse (P < 0.001) than the other states using both VAS and SG. CONCLUSIONS: Within this sample of the general population, preferences for local treatments including IC, NB, and CRT were not found to be significantly different. These values can be used to calculate quality-adjusted life expectancy in future cost-effectiveness analyses.

Cost communication in cosmetic and reconstructive breast surgery: Public perceptions in the United States.

BACKGROUND: There is a need to better understand the financial toxicity of surgery on patients. Recent data demonstrated that plastic surgeons seldom discuss out-of-pocket costs with patients. Not much is known regarding the public perceptions of out-of-pocket cost communication in reconstructive and cosmetic breast surgery. METHODS: A cross-sectional survey was administered to adult women in the United States from November 2021 to December 2021 using Amazon Mechanical Turk. Perceptions regarding cost communication in plastic surgery were gathered. Incomplete responses were excluded. Multivariable models were used to identify predictors of responses. RESULTS: There were 512 complete responses. Respondents had a mean age of 37.4 years. The majority strongly agreed or agreed that plastic surgeons should discuss out-of-pocket costs with patients undergoing implant-based breast reconstruction (85%), plastic surgeons should know the impact of surgery on patients' financial well-being (78%), and discussing costs was the most important aspect of the appointment (70%). Respondents who were unsure of their insurance status had lower odds of strongly agreeing or agreeing that surgeons should discuss out-of-pocket costs for autologous reconstruction (OR 0.12, CI 0.02-0.58, p = 0.01) and cosmetic breast augmentation (OR 0.14, CI 0.03-0.65, p = 0.01). Privately insured respondents had greater odds of strongly agreeing or agreeing to both, respectively (OR 2.21, CI 1.32-3.82, p < 0.01; OR 1.94, CI 1.17-3.31, p = 0.01) CONCLUSION: Many laywomen support the cost communication in plastic surgery and believe that plastic surgeons should know the impact of surgery on the patients' financial well-being, with variability among the sociodemographic groups. Plastic surgeons should strongly consider discussing costs with patients undergoing breast surgery.

Correlation between facial vascularized composite allotransplantation rejection and laboratory markers: Insights from a retrospective study of eight patients.

BACKGROUND: The field of facial vascularized composite allotransplantation (fVCA) is still new and a limited number of patients have undergone the procedure. This has led to a lack of understanding about the impact of fVCA rejection on standard laboratory markers (e.g., CBC, BMP, CRP) for the acute management of these patients. It is not clear if rejection elicits a systemic inflammatory response that influences common inflammatory markers such as WBC and CRP. A comprehensive understanding of changes in these markers could help in the management of fVCA patients in the acute setting. METHODS: The medical records of 8 fVCA patients with a total of 9 transplants were reviewed retrospectively, and data on standard laboratory values (CBC, BMP, LFTs, CRP) and vital signs were extracted. To examine the relationship between laboratory values and rejection status, linear mixed models were used to analyze the data, taking into account their longitudinal nature (repeated measures). RESULTS: A statistically significant relationship was found between the Banff grade of rejection and the relative number of basophils in the patient's blood during rejection (p = 0.005). In addition, in patients with clinical signs of rejection (e.g., facial erythema, edema) and skin biopsy showing Banff ≥ II, CRP was found to be significantly elevated (p = 0.03). The WBC count remained stable during rejection, and the relative number of neutrophils was lower at the time of rejection, indicating possible consumption at the site of rejection. CONCLUSION: During fVCA rejection, most standard laboratory parameters and vital signs appear to be stable. However, the levels of CRP and basophils were elevated during rejection, while the neutrophil count was lower. Leukocytosis can likely be used as a marker of microbial infection in fVCA patients, as WBC does not seem to increase at the time of allograft rejection.

Accelerated Cardiac Allograft Vasculopathy in an Orthotopic Heart Transplant Recipient with Prior COVID-19.

BACKGROUND Cardiac allograft vasculopathy (CAV) is a post-orthotopic heart transplant (OHT) complication driven by intimal smooth muscle proliferation and immune hyperactivity to donor heart tissue. Accelerated CAV leads to allograft failure within 1 year after receiving a normal angiogram result. Viruses can contribute to CAV development, but CAV after SARS-CoV-2 infection has not been reported to date. CASE REPORT A 48-year-old man, 5 years after OHT for non-ischemic cardiomyopathy, was admitted to the Cardiac Care Unit with 3 days of abdominal pain, dyspnea, and palpitations. His medical history included hyperlipidemia and insulin-dependent diabetes. He was compliant with all medications. Two months prior, he had a mild COVID-19 case. An echocardiogram and coronary angiogram 6 and 9 months prior, respectively, were unremarkable. Right and left heart catheterization demonstrated increased filling pressures, a cardiac index of 1.7 L/ml/m², and diffuse vasculopathy most severe in the LAD artery. Flow could not be restored despite repeated ballooning and intra-catheter adenosine. Empiric ionotropic support, daily high-dose methylprednisolone, and plasmapheresis were started. A few days later, the patient had cardiac arrest requiring venoarterial extracorporeal membranous oxygenation. Given CAV's irreversibility, re-transplantation was considered, but the patient had an episode of large-volume hemoptysis and remained clinically unstable for transplant. The patient died while on palliative care. CONCLUSIONS Our patient developed accelerated CAV 2 months after having COVID-19. While CAV has known associations with certain viruses, its incidence after SARS-CoV-2 infection is unknown. Further research is needed to determine if prior SARS-CoV-2 infection is a risk factor for development of CAV in OHT recipients.

Expanded access protocol (EAP) program for access to investigational products for amyotrophic lateral sclerosis (ALS).

INTRODUCTION/AIMS: Expanded access protocols (EAPs) are a Food and Drug Administration (FDA)-regulated pathway for granting access to investigational products (IPs) to individuals with serious diseases who are ineligible for clinical trials. There is limited information about the use of EAPs in amyotrophic lateral sclerosis (ALS); the aim of this report is to share the design, operational features, and costs of an EAP program for ALS. METHODS: The program was launched in 2018 at a single center. In alignment with FDA guidance, protocols were designed as individual (single participant) or intermediate size. Inclusion criteria were broad (e.g., no restrictions due to long disease duration or low vital capacity). Safety information was collected in all EAPs. Selected biomarkers were collected in nine of the EAPs. RESULTS: From July 2018 through February 2022, 17 EAPs were submitted for FDA and institutional review board (IRB) approval. The mean time from submission to approval from the FDA and IRB were 24 days and 37 days, respectively. A total of 164 participants were enrolled and, of these, 77 participants were still receiving IP as of February 2022. The mean duration of participation in an EAP was 12.6 mo. No drug-related serious adverse events were reported from any of the EAPs. Average site cost was $613.47 per participant per month, not including IP costs. CONCLUSION: EAPs provide a framework through which access to IP can be safely provided to people with ALS who do not qualify for clinical trials. Site resources are needed to launch and maintain these programs.

Cost-Effectiveness of Comprehensive Quadruple Therapy for Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is one of the most costly and deadly chronic disease states. The cost effectiveness of a comprehensive quadruple therapy regimen for HFrEF has not been studied. OBJECTIVES: The authors sought to determine the cost-effectiveness of quadruple therapy comprised of beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor-neprilysin inhibitors, and sodium glucose cotransporter-2 inhibitors vs regimens composed of only beta-blockers, angiotensin-converting enzyme inhibitors, and mineralocorticoid receptor antagonists (triple therapy), and angiotensin-converting enzyme inhibitors and beta-blockers (double therapy). METHODS: Using a 2-state Markov model, the authors performed a cost-effectiveness study using simulated populations of 1,000 patients with HFrEF based on the participants in the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) trial and compared them by treatment strategy (quadruple therapy vs triple and double therapy) from a United States health care system perspective. The authors also performed 10,000 probabilistic simulations. RESULTS: Treatment with quadruple therapy resulted in an increase of 1.73 and 2.87 life-years compared with triple therapy and double therapy, respectively, and an increase in quality-adjusted life-years of 1.12 and 1.85 years, respectively. The incremental cost-effectiveness ratios of quadruple therapy vs triple therapy and double therapy were $81,000 and $51,081, respectively. In 91.7% and 99.9% of probabilistic simulations quadruple therapy had an incremental cost-effectiveness ratio of <$150,000 compared with triple therapy and double therapy, respectively. CONCLUSIONS: At current pricing, the use of quadruple therapy in patients with HFrEF was cost effective compared with triple therapy and double therapy. These findings highlight the need for improved access and optimal implementation of comprehensive quadruple therapy in eligible patients with HFrEF.

Molecular Basis of Surgical Coaptation Techniques in Peripheral Nerve Injuries.

Peripheral nerve injuries requiring surgical repair affect over 100,000 individuals in the US annually. Three accepted methods of peripheral repair include end-to-end, end-to-side, and side-to-side neurorrhaphy, each with its own set of indications. While it remains important to understand the specific circumstances in which each method is employed, a deeper understanding of the molecular mechanisms underlying the repair can add to the surgeon's decision-making algorithm when considering each technique, as well as help decide nuances in technique such as the need for making epineurial versus perineurial windows, length and dept of the nerve window, and distance from target muscle. In addition, a thorough knowledge of individual factors that are active in a particular repair can help guide research into adjunct therapies. This paper serves to summarize the similarities and divergences of the three commonly used nerve repair strategies and the scope of molecular mechanisms and signal transduction pathways in nerve regeneration as well as to identify the gaps in knowledge that should be addressed if we are to improve clinical outcomes in our patients.

Augmenting Career Longevity: An Analysis of Ergonomics Training Among 134 Neurological Surgeons.

BACKGROUND: Work-related pain among neurosurgeons remains understudied, yet can have long-term consequences which affect operative efficiency and efficacy, career longevity, and life outside of work. OBJECTIVE: This study provides insight into the extent of pain experienced by neurosurgeons and the effect of ergonomics training on pain. METHODS: An online survey pertaining to ergonomics and pain was sent to all neurosurgeons on the Council of State Neurosurgical Societies (CSNS) email distribution list. Statistical comparisons of age groups against pain levels and ergonomics training against pain levels, as well as multivariate linear regression of demographics, training, and operating factors against pain levels were performed. RESULTS: One hundred and thirty-four neurosurgeons responded to the survey. The mean average severity of pain across respondents was 3.3/10 and the mean peak severity of pain was 5.1/10. Among the reported peak pain severity scores, neurosurgeons with 21-30 years of operating experience had significantly higher pain scores than those with 11-20 years of experience (mean 6.2 vs. 4.2; P < 0.05), while neurosurgeons with more than 30 years of experience had significantly less pain than those with 21-30 years of experience (mean 4.4 vs. 6.2, P = 0.005). Training in ergonomics did not significantly improve respondents' reported peak or mean pain severities (17.9% reported having ergonomics training). CONCLUSIONS: Ergonomics training did not appear to make a difference in neurosurgeons' pain severities. This may signify a need to optimize ergonomics pedagogy to achieve observable benefits.