Reduction in healthcare resource use through 24 months following sinus surgery with steroid-eluting implants in chronic rhinosinusitis patients with and without nasal polyps: a real-world study.

OBJECTIVE: To investigate the impact of steroid-eluting implants after endoscopic sinus surgery (ESS) on health care resource use (HCRU) in chronic rhinosinusitis patients with (CRSwNP) and without (CRSsNP) nasal polyps. METHODS: This retrospective, observational cohort study using real-world evidence data included adult patients with CRS who underwent ESS in 2015-2019 with at least 24 months of data before and after ESS. Patients who received implants were matched to patients who did not based on a propensity score developed using baseline characteristics and NP status. HCRU was compared between cohorts within each CRSwNP and CRSsNP subgroup using chi-square tests (binary variables). RESULTS: The implant cohort in the CRSwNP subgroup had fewer all-cause outpatient (90.0% vs. 93.9%, p < .001) and all-cause otolaryngology (64.3% vs. 76.4%, p < .001) visits as well as fewer endoscopy (40.5% vs. 47.4%, p = .005) and debridement (48.8% vs. 55.6%, p = .007) procedures than the non-implant cohort. The implant cohort in the CRSsNP subgroup had fewer all-cause outpatient (88.9% vs. 94.2%, p < .001) and all-cause otolaryngology (53.5% vs. 74.4%, p < .001) visits as well as fewer endoscopy (31.8% vs. 41.7%, p < .001) and debridement (36.7% vs. 53.4%, p <.001) procedures than the non-implant cohort. Revision sinus surgery was reduced in the implant cohort in both subgroups, and reached statistical significance in the CRSwNP subgroup (3.8% vs. 6.0%, p = .039) but not in the CRSsNP subgroup (3.6% vs. 4.2%, p = .539). CONCLUSIONS: Overall, patients receiving implants had lower HCRU for 24 months after sinus surgery independent of nasal polyp status, and revision surgery was reduced in CRSwNP patients. These findings provide additional evidence that long-term reductions in HCRU may be achieved with steroid-eluting implant use during sinus surgery.What is known on this topicPatients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a disproportionately higher burden of disease and consume greater healthcare resources than chronic rhinosinusitis patients without nasal polyps (CRSsNP).CRSwNP patients represent approximately 30% of CRS patients who undergo surgery, but their clinical course is disproportionally complicated by disease recurrence and revision surgery.Steroid-eluting sinus implants have been shown in clinical trials to improve short-term postoperative outcomes after endoscopic sinus surgery (ESS) in CRS patients in general.A recent real-world evidence study reported that steroid-eluting sinus implants following ESS were associated with a reduction in HCRU in CRS patients followed for 18 months, but the impact of implants on HCRU in CRSwNP and CRSsNP patients separately remains unknown. What this study addsIn this observational study, reduced HCRU was observed in CRSwNP and CRSsNP patients who receive steroid-eluting sinus implants.Use of implants in CRSwNP and CRSsNP patients was associated with a significant reduction in healthcare visits (all-cause outpatient, all-cause otolaryngology), and sinus procedures (endoscopy, debridement).Revision surgery was significantly reduced in the implant cohort of CRSwNP patients and trended lower in the implant cohort of CRSsNP patients.Use of implants had no significant impact on all-cause ER/urgent care visits or sinus-related imaging.

A phase 3 trial of mometasone furoate sinus implants for chronic sinusitis with recurrent nasal polyps.

BACKGROUND: Topical intranasal corticosteroid sprays (INCSs) are standard treatment for nasal polyps (NPs), but their efficacy is reduced by poor patient compliance and impaired access of drug to the sinus mucosa. A corticosteroid-eluting sinus implant was designed to address these limitations in patients with recurrent polyposis after sinus surgery by delivering 1350 µg of mometasone furoate (MF) directly to the ethmoid sinus mucosa over approximately 90 days. METHODS: A randomized, sham-controlled, double-blind trial was undertaken in 300 adults with refractory chronic rhinosinusitis with NPs (CRSwNP), who were candidates for repeat surgery. Eligible patients were randomized (2:1) and underwent in-office bilateral placement of 2 implants or a sham procedure. All patients used the MF INCS 200 µg once daily. Co-primary efficacy endpoints were the change from baseline in nasal obstruction/congestion score and bilateral polyp grade, as determined by an independent panel based on centralized, blinded videoendoscopy review. RESULTS: Patients treated with implants experienced significant reductions in both nasal obstruction/congestion score (p = 0.0074) and bilateral polyp grade (p = 0.0073) compared to controls. At day 90, implants were also associated with significant reductions in 4 of 5 prespecified secondary endpoints compared to control: proportion of patients still indicated for repeat sinus surgery (p = 0.0004), percent ethmoid sinus obstruction (p = 0.0007), nasal obstruction/congestion (p = 0.0248), and decreased sense of smell (p = 0.0470), but not facial pain/pressure (p = 0.9130). One patient experienced an implant-related serious adverse event (epistaxis). CONCLUSION: Significant improvements over a range of subjective and objective endpoints, including a reduction in the need for sinus surgery by 61%, suggest that MF sinus implants may play an important role in management of recurrent NP.

RESOLVE: bioabsorbable steroid-eluting sinus implants for in-office treatment of recurrent sinonasal polyposis after sinus surgery: 6-month outcomes from a randomized, controlled, blinded study.

BACKGROUND: Patients with recurrent sinonasal polyposis after endoscopic sinus surgery (ESS) have limited treatment options. Safety and efficacy were previously reported for a bioabsorbable sinus implant that elutes mometasone furoate for 3 months. Here we summarize longer-term outcomes. METHODS: A randomized, controlled, blinded study with 100 chronic rhinosinusitis with nasal polyps (CRSwNP) patients who failed medical treatment and were considered candidates for revision ESS. Treated patients (n = 57) underwent in-office implant placement. Control patients (n = 43) underwent a sham procedure. Endoscopic grading at 3 months by clinicians was corroborated by an independent review of randomized videoendoscopies by a panel of 3 sinus surgeons. Six-month follow-up included endoscopic grading and patient-reported outcomes. RESULTS: At 6 months, treated patients experienced significant improvement in Nasal Obstruction Symptom Evaluation (NOSE) score (p = 0.021) and >2-fold improvement in mean nasal obstruction/congestion score (-1.06 ± 1.4 vs -0.44 ± 1.4; p = 0.124). Endoscopically, treated patients experienced significant reduction in ethmoid sinus obstruction (p < 0.001) and bilateral polyp grade (p = 0.018) compared to controls. Panel review confirmed a significant reduction in ethmoid sinus obstruction (p = 0.010) and 2-fold improvement in bilateral polyp grade (p = 0.099), which reached statistical significance (p = 0.049) in a subset of 67 patients with baseline polyp burden ≥2 bilaterally. At 6 months, control patients were at 3.6 times higher risk of remaining indicated for ESS than treated patients. CONCLUSION: The symptomatic and endoscopic improvements observed confirm the efficacy of the steroid-eluting implant for in-office treatment of CRSwNP after ESS. These longer-term 6-month study results demonstrate that the steroid-eluting implant represents a durable, safe, and effective treatment strategy for this patient population.

RESOLVE: a randomized, controlled, blinded study of bioabsorbable steroid-eluting sinus implants for in-office treatment of recurrent sinonasal polyposis.

BACKGROUND: Patients with recurrent sinonasal polyposis after endoscopic sinus surgery (ESS) have limited treatment options. This study evaluated the safety and efficacy of a bioabsorbable steroid-eluting implant with 1350 µg of mometasone furoate for its ability to dilate obstructed ethmoid sinuses, reduce polyposis, and reestablish sinus patency. METHODS: This was a randomized, controlled, blinded study including 100 patients chronic rhinosinusitis with nasal polyposis (CRSwNP) refractory to medical therapy and considered candidates for revision ESS. Follow-up included endoscopic grading by investigators and patient-reported outcomes. RESULTS: Treated patients (n = 53; age as mean ± standard deviation [SD] 47.8 ± 12.6 years; 55% male) underwent in-office bilateral placement. Control patients (n = 47; age 51.6 ± 13.1 years; 66% male) underwent a sham procedure. At 3 months, treated patients experienced a significant reduction in bilateral polyp grade (p = 0.0269) and ethmoid sinus obstruction (p = 0.0001) compared to controls. Treated patients also experienced a 2-fold improvement in the mean nasal obstruction/congestion score (-1.33 ± 1.47 vs -0.67 ± 1.45; p = 0.1365). This improvement reached statistical significance (p = 0.025) in patients with greater polyp burden (grade ≥2 bilaterally; n = 74). At 3 months, 53% of treated patients compared to only 23% of controls were no longer indicated for repeat ESS. There was no serious adverse event or clinically significant increases in intraocular pressure or cataract formation. CONCLUSION: The symptomatic improvement and statistically significant reduction in polyp grade and ethmoid sinus obstruction supported the efficacy of the steroid-eluting implant for in-office treatment of CRS patient with recurrent polyposis after ESS. The study results demonstrated that the steroid-eluting implant represents a safe and effective alternative to current management for this patient population.

Steroid-eluting sinus implant for in-office treatment of recurrent polyposis: a pharmacokinetic study.

BACKGROUND: Long-term use of systemic glucocorticoid therapy has been associated with hypothalamic-pituitary-adrenal axis suppression and other systemic adverse events. This pharmacokinetic study evaluated the systemic safety and performance of a bioabsorbable sinus implant that gradually releases 1350 µg of mometasone furoate directly to the sinus mucosa. METHODS: A prospective, single-center study treating 5 adult patients with recurrent polyposis after bilateral total ethmoidectomy. Each patient received 2 steroid-releasing implants in-office under local/topical anesthesia. Plasma concentrations of mometasone furoate and cortisol were determined before placement and through 30-day follow-up, which also included endoscopic grading and patient-reported outcomes. RESULTS: Five patients (mean age 46.2 ± 9.2 standard deviation [SD] years; 60% male) underwent successful placement in all 10 ethmoid sinuses. There were no serious adverse events. The plasma concentrations of mometasone furoate were generally below the lower limit of quantification (LLOQ) of the assay (30 pg/mL). Cortisol concentrations at follow-up ranged from 3.9 to 5.7 mg/dL compared to 4.7 mg/dL at baseline. At 1 month, there was a significant improvement in bilateral polyp grade (p = 0.037), nasal obstruction score (p = 0.002), and 22-item Sino-Nasal Outcome Test (SNOT-22) (p = 0.010) compared to baseline. CONCLUSION: The reported 100% placement success, negligible systemic exposure to mometasone furoate released over time, lack of adrenal suppression, and the absence of serious adverse events suggest that the implant provides a valid and safe option for the in-office treatment of recurrent polyposis. Randomized, controlled, blinded clinical studies are underway to provide further evidence of safety and efficacy.

Two-year results of a feasibility study on antireflux transoral incisionless fundoplication using EsophyX.

BACKGROUND: A feasibility study (n = 19) evaluated the safety and initial efficacy of transoral incisionless fundoplication (TIF) for the treatment of gastroesophageal disease (GERD). The results at 1 year (n = 17) indicated that TIF was safe and had a significant effect on reducing GERD symptoms, proton pump inhibitor (PPI) usage, acid exposure, and small hiatal hernia. This study was designed to evaluate the long-term safety and durability of TIF. METHODS: Fourteen patients (50% female; median age, 34 years) completed the 2-year follow-up assessment tests. Three patients were excluded from the study after 1 year because two of them underwent retreatment and one was lost to follow-up. RESULTS: At 2 years, no adverse events related to TIF were reported. A >or=50% improvement in GERD-HRQL scores compared with those at baseline on PPIs was sustained by 64% of patients. TIF was effective in eliminating heartburn in 93% of patients and daily PPI therapy in 71% of patients. Significantly (p < 0.05) more patients were able to consume reflux-causing foods and maintain lifestyle activities without GERD symptoms compared with baseline on PPIs. Fundoplications were durable and maintained their geometric dimensions. TIF was effective in eliminating hiatal hernia in 60% of patients and esophagitis in 55% of patients. Global assessment of all outcomes in each patient revealed that 79% of patients experienced complete cure (29%) or remission (50%) of GERD at 2 years after TIF. CONCLUSION: The results at 2 years supported the long-term safety and durability of TIF and its sustained effect on the elimination of heartburn, esophagitis,

Antireflux transoral incisionless fundoplication using EsophyX: 12-month results of a prospective multicenter study.

BACKGROUND: A novel transoral incisionless fundoplication (TIF) procedure using the EsophyX system with SerosaFuse fasteners was designed to reconstruct a full-thickness valve at the gastroesophageal junction through tailored delivery of multiple fasteners during a single-device insertion. The safety and efficacy of TIF for treating gastroesophageal reflux disease (GERD) were evaluated in a prospective multicenter trial. METHODS: Patients (n = 86) with chronic GERD treated with proton pump inhibitors (PPIs) were enrolled. Exclusion criteria included an irreducible hiatal hernia > 2 cm. RESULTS: The TIF procedure (n = 84) reduced all hiatal hernias (n = 49) and constructed valves measuring 4 cm (2-6 cm) and 230 degrees (160 degrees -300 degrees ). Serious adverse events consisted of two esophageal perforations upon device insertion and one case of postoperative intraluminal bleeding. Other adverse events were mild and transient. At 12 months, aggregate (n = 79) and stratified Hill grade I tight (n = 21) results showed 73% and 86% of patients with >or=50% improvement in GERD health-related quality of life (HRQL) scores, 85% discontinuation of daily PPI use, and 81% complete cessation of PPIs; 37% and 48% normalization of esophageal acid exposure; 60% and 89% hiatal hernia reduction; and 62% and 80% esophagitis reduction, respectively. More than 50% of patients with Hill grade I tight valves had a normalized cardia circumference. Resting pressure of the lower esophageal sphincter (LES) was improved significantly (p < 0.001), by 53%. EsophyX-TIF cured GERD in 56% of patients based on their symptom reduction and PPI discontinuation. CONCLUSION: The 12-month results showed that EsophyX-TIF was safe and effective in improving quality of life and for reducing symptoms, PPI use, hiatal hernia, and esophagitis, as well as increasing the LES resting pressure and normalizing esophageal pH and cardia circumference in chronic GERD patients.

Trypsin gene expression by quantitative in situ hybridization in carnivorous and herbivorous prickleback fishes (Teleostei: Stichaeidae): ontogenetic, dietary, and phylogenetic effects.

We determined trypsin gene sequences and compared relative levels of trypsin gene expression as influenced by ontogeny, diet, and phylogeny in four related prickleback fish species. Of these species, Cebidichthys violaceus and Xiphister mucosus shift from carnivory to herbivory at approximately 45 mm standard length [SL], whereas Xiphister atropurpureus and Anoplarchus purpurescens remain carnivores. Pairwise sequence similarities among the four species were 77%-95% for the trypsin nucleotides and 69%-94% for the amino acids. Trypsin gene expression levels in small (30-40 mm SL) and larger (60-75 mm) wild-caught juveniles and larger (60-75 mm) juveniles raised on a high-protein artificial diet increased with ontogeny in all four species but in response to the diet only in the two carnivores. The indistinguishable expression levels in the sister taxa, X. mucosus and X. atropurpureus, represented the only apparent phylogenetic effect. Xiphister atropurpureus, however, increased both trypsin gene expression and enzymatic activity (the latter from a previous study) on the high-protein artificial diet, indicating transcriptional rather than posttranscriptional (shown in X. mucosus) regulation of the activity. This study provides evidence for genetically programmed upregulation of trypsin gene expression with ontogeny in both the carnivorous and herbivorous species but in response to the high-protein artificial diet only in the carnivores.

Storage and absorption in the digestive system of carnivorous and herbivorous prickleback fishes (Teleostei: Stichaeidae): ontogenetic, dietary, and phylogenetic effects.

The effects of ontogeny, diet, and phylogeny on glycogen storage levels and esterase and alkaline phosphatase activities in four related prickleback fishes were determined in situ using quantitative histochemistry. Of these species, Cebidichthys violaceus and Xiphister mucosus shift from carnivory to herbivory at approximately 45 mm standard length (SL), whereas Xiphister atropurpureus and Anoplarchus purpurescens remain carnivores. Comparisons between small (30-40 mm SL) and larger (60-75 mm SL) wild-caught juveniles showed that glycogen storage levels and alkaline phosphatase activity were unchanged with ontogeny. Comparisons between the larger wild-caught juveniles and juveniles of the same size that had been raised on a high-protein animal diet revealed that glycogen storage level and alkaline phosphatase activity increased in all species in response to this diet. Esterase activity also increased in response to the high-protein animal diet in all four species but increased with ontogeny only in C. violaceus, X. mucosus, and X. atropurpureus, in the xiphisterine clade, and not in A. purpurescens, in the adjacent alectriine clade. Xiphister mucosus and X. atropurpureus showed indistinguishable responses in esterase activity to ontogeny and diet despite their divergent natural diets. Overall, glycogen storage level and alkaline phosphatase activity responded primarily to diet, whereas esterase activity was also influenced by ontogeny and phylogeny and differed between intestinal regions among the species.