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Dupilumab is a novel monoclonal antibody that recently received US Food and Drug Administration approval for the treatment of chronic rhinosinusitis with nasal polyps. Endoscopic sinus surgery (ESS) has been the mainstay of treatment for patients refractory to initial medical therapy. Data comparing the cost-effectiveness of these treatments are scarce. The objective of this study is to compare the cost-effectiveness of dupilumab and ESS treatment for patients with chronic rhinosinusitis with nasal polyps refractory to medical therapy.A cohort-style Markov decision tree economic evaluation with 10-year time horizon was performed. The two comparative treatment strategies were dupilumab therapy or ESS followed by postoperative maintenance therapy. Patients with response to treatment continued with either maintenance or dupilumab therapy; patients with no response underwent ESS. The primary outcome measure was incremental cost per quality-adjusted life-year calculated from Sino-Nasal Outcome Test (SNOT-22) scores. Sensitivity analyses were performed including discounting scenarios and a probabilistic sensitivity analysis.The dupilumab strategy cost $195,164 and produced 1.779 quality-adjusted life-years. The ESS strategy cost $20,549 and produced 1.526 quality-adjusted life-years. This implies an incremental cost of $691,691 for dupilumab for every 1-unit increase in quality-adjusted life-year compared with ESS. Probability sensitivity analysis indicated that ESS was more cost-effective than dupilumab in all iterations.While dupilumab and ESS may demonstrate similar clinical effectiveness, ESS remains the most cost-effective treatment option and should remain the standard of care for patients with chronic rhinosinusitis with nasal polyps refractory to medical therapy.

Objective: To determine in-hospital costs associated with performing an EEA to anterior skull base pathology and to identify drivers of cost variability for patients undergoing endoscopic anterior skull base surgery. Methods: All endoscopic anterior skull base surgeries performed over a period from January 1st, 2015 to October 24th, 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate analysis was performed using Stata software. Results: An EEA was associated with an average total in-hospital cost of $44 545. Compared to patients undergoing a transsphenoidal approach to pituitary tumor resection, EEA patients incurred higher in-hospital costs across all variables including a total cost increase of $15 921 (95% confidence interval $5720-26 122, P = .002). Univariate analysis of all endoscopic anterior skull base surgery patients showed a cost increase of $30 616 associated with post-operative cerebrospinal fluid (CSF) leak ($10 420-50 811, P = .004), $14 610 with post-operative diabetes insipidus (DI) ($4610-24 609, P = .004), and $11 522 with African-American patients relative to Caucasian patients ($3049-19 995, P = .008). Conclusions: Patients who undergo endoscopic EEA for resection of anterior skull base tumors typically incur greater in-hospital costs than patients undergoing a standard TSA. Post-operative complications such as CSF leak and DI, as well as ethnicity, are significant drivers of cost-variability.

Objective To determine the in-hospital cost implications of an endoscopic expanded endonasal approach (EEEA) for meningioma resection relative to the open transcranial approach. Methods All anterior skull base meningioma surgeries performed over a period from January 1st, 2015 to October 31th, 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate analysis was performed using R software. All cost data were converted into August 2021-equivalent dollar amounts using the United States Bureau of Labor Statistics consumer price index. Results Thirty-five patients met study criteria, including 27 patients undergoing an open transcranial approach and 8 undergoing an EEEA. Average length of stay for patients undergoing an open approach was 9.3 days compared to 5.6 within the EEEA group ( P = .126). The average total in-hospital cost of patient undergoing an EEEA was $35417.1 compared to $46406.9 among patients undergoing an open transcranial approach ( P = .168). On univariate analysis, the cost of an open transcranial approach relative to the EEEA was $10989.8 ( P = .411). Conclusions The open transcranial approach remained the dominant surgical approach to anterior skull base meningiomas over our study time period. However, despite limited patient numbers the EEEA was associated with decreased total in-hospital costs.

To determine the in-hospital cost implications of an expanded endoscopic endonasal approach (EEEA) for craniopharyngioma resection relative to the traditional open transcranial approach.All craniopharyngioma surgeries performed at a single institution over a period from January 1st 2001 to October 31th 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate regression analysis was performed using R software.Thirty-six patients met study criteria, including 22 undergoing an open approach and 14 undergoing an EEEA. There was a significantly longer average length of stay among patients undergoing open resection (21.5 vs. 10.6 days, p = 0.024). The average total in-hospital cost of a patient undergoing an EEEA was $58979.3 compared to $89142.3 for an open approach (p = 0.127). On univariate regression analysis, the total in-hospital cost for a patient undergoing an open approach relative to an EEEA was $30163.0 (p = 0.127). The open approach was exclusively performed from study onset until April 2010 (16 patients). From April 2010 to August 2013, 6 open approaches and 5 EEEA were performed. The EEEA has been exclusively performed from August 2013 until the conclusion of our study period (9 patients).There has been a shift toward surgical resection of craniopharyngioma via an EEEA approach for amenable tumors. Our study demonstrates that the EEEA has become the preferred surgical approach at our institution, and shows that the EEEA is associated with shorter postoperative length of stay and lower total in-hospital cost. Laryngoscope, 133:83-87, 2023.

Despite the evidence in support of the use of buprenorphine in the treatment of OUD and increasing ability of emergency medicine (EM) clinicians to prescribe it, emergency department (ED)-initiated buprenorphine is uncommon. Many EM clinicians lack training on how to manage acute opioid withdrawal or initiate treatment with buprenorphine. We developed a brief buprenorphine training program and assessed the impact of the training on subsequent buprenorphine initiation and knowledge retention.We conducted a pilot randomized control trial enrolling EM clinicians to receive either a 30-min didactic intervention about buprenorphine (standard arm) or the didactic plus weekly messaging and a monetary inducement to administer and report buprenorphine use (enhanced arm). All participants were incentivized to complete baseline, immediate post-didactic, and 90-day knowledge and attitude assessment surveys. Our objective was to achieve first time ED buprenorphine prescribing events in clinicians who had not previously prescribed buprenorphine in the ED and to improve EM-clinician knowledge and perceptions about ED-initiated buprenorphine. We also assessed whether the incentives and reminder messaging in the enhanced arm led to more clinicians administering buprenorphine than those in the standard arm following the training; we measured changes in knowledge of and attitudes toward ED-initiated buprenorphine.Of 104 EM clinicians enrolled, 51 were randomized to the standard arm and 53 to the enhanced arm. Clinical knowledge about buprenorphine improved for all clinicians immediately after the didactic intervention (difference 19.4%, 95% CI 14.4% to 24.5%). In the 90 days following the intervention, one-third (33%) of all participants reported administering buprenorphine for the first time. Clinicians administered buprenorphine more frequently in the enhanced arm compared to the standard arm (40% vs. 26.3%, p = 0.319), but the difference was not statistically significant. The post-session knowledge improvement was not sustained at 90 days in the enhanced (difference 9.6%, 95% CI - 0.37% to 19.5%) or in the standard arm (difference 3.7%, 95% CI - 5.8% to 13.2%). All the participants reported an increased ability to recognize patients with opioid withdrawal at 90 days (enhanced arm difference .55, 95% CI .01-1.09, standard arm difference .85 95% CI .34-1.37).A brief educational intervention targeting EM clinicians can be utilized to achieve first-time prescribing and improve knowledge around buprenorphine and opioid withdrawal. The use of weekly messaging and gain-framed incentivization conferred no additional benefit to the educational intervention alone. In order to further expand evidence-based ED treatment of OUD, focused initiatives that improve clinician competence with buprenorphine should be explored.ClinicalTrials.gov Identifier: NCT03821103.

Activation of estrogen receptor-alpha (ERalpha) by growth factors in the absence of estrogen is a well-documented phenomenon. To study further this process of ligand-independent receptor activation, COS-7 cells without ER were transfected with both ER and epidermal growth factor receptor (EGFR). In the absence of estrogen, epidermal growth factor (EGF) stimulated rapid tyrosine phosphorylation of ER in transfected COS-7 cells. Similarly, in MCF-7 breast cancer cells that have natural expression of ER and EGFR, EGF promoted acute phosphorylation of serine and tyrosine residues in ER, and a direct interaction between ER and EGFR after treatment with EGF was found. In confirmation of a direct interaction between ER and EGFR, activation of affinity-purified EGFR tyrosine kinase in vitro stimulated the phosphorylation of recombinant ER. The cross-communication between EGFR and ER appears to promote significant stimulation of cell proliferation and a reduction in the apoptotic loss of those cells that express both receptor signaling pathways. However, COS-7 cells transfected with both ER and EGFR show minimal stimulation of classical estrogen response element (ERE)-dependent transcriptional activity after stimulation by EGF ligand. This suggests that the proliferative and antiapoptotic activity of EGF-induced ER activation may be dissociated from ERE-dependent transcriptional activity of the ER.