Efficacy and Safety of Ciprofloxacin Plus Fluocinolone in Otitis Media With Tympanostomy Tubes in Pediatric Patients: A Randomized Clinical Trial.

Importance: Acute otitis media with tympanostomy tubes (AOMT) in children commonly presents with otorrhea and negatively affects their daily activities. Objective: To evaluate the efficacy and safety of topical ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution relative to ciprofloxacin, 0.3%, otic solution alone and fluocinolone acetonide, 0.025%, otic solution alone in the treatment of AOMT in children. Design, Setting, and Participants: Two twin multicenter, randomized, double-blind clinical trials with identical designs were conducted from June 24, 2011, through June 23, 2014, at ear, nose, and throat pediatric practices, general practices, hospitals, and clinical research centers. The study population comprised 662 children (331 in each trial) with AOMT in at least 1 ear who presented with moderate or severe purulent otorrhea for 3 weeks or less. Data analyses were performed on an intention-to-treat basis. Interventions: Patients were randomly assigned to receive ciprofloxacin plus fluocinolone, ciprofloxacin alone, or fluocinolone alone twice daily for 7 days and were evaluated on days 1 (baseline), 3 to 5 (undergoing therapy), 8 to 10 (end of therapy), and 18 to 22 (test of cure). Main Outcomes and Measures: The primary efficacy measure was time to cessation of otorrhea. The principal secondary end point was sustained microbiological cure, defined as eradication or presumed eradication at end-of-therapy and test-of-cure visits. Results: A total of 662 children participating in the 2 studies were randomized to receive ciprofloxacin plus fluocinolone (n = 223), ciprofloxacin alone (n = 221), or fluocinolone alone (n = 218). The median age was 2.5 years (range, 0.6-12.7 years). The median time to cessation of otorrhea was 4.23 days (95% CI, 3.65-4.95 days) in patients receiving ciprofloxacin plus fluocinolone compared with 6.95 days (95% CI, 5.66-8.20 days) in those receiving ciprofloxacin and not estimable findings in those receiving fluocinolone alone (P < .001). The clinical cure rate at the test-of-cure visit was 80.6% in the ciprofloxacin plus fluocinolone group, 67.4% in the ciprofloxacin group (difference, 13.2%; 95% CI, 5.0%-21.4%; P = .002), and 47.6% in the fluocinolone group (difference, 33.0%; 95% CI, 24.0%-42.0%; P < .001). The sustained microbiological cure rate was 79.7% in the ciprofloxacin plus fluocinolone group vs 67.7% in the ciprofloxacin group (difference, 12.0%; 95% CI, 0.8%-23.0%; P = .04) and 37.6% in the fluocinolone group (difference, 42.1%; 95% CI, 29.3%-54.8%; P < .001). Only 7 (3.1%) of the patients receiving ciprofloxacin plus fluocinolone, 8 (3.6%) of the patients receiving ciprofloxacin, and 10 (4.7%) of the patients receiving fluocinolone presented with adverse events related to study medication. Conclusions and Relevance: The combination of ciprofloxacin plus fluocinolone is more effective than treatment with ciprofloxacin or fluocinolone alone for AOMT, and it is safe and well tolerated in children. Trial Registration: clinicaltrials.gov Identifiers: NCT01395966 and NCT01404611.

Tympanostomy tube placement in awake, unrestrained pediatric patients: A prospective, multicenter study.

OBJECTIVES: Tympanostomy tube (tube) placement is the most common pediatric otolaryngologic surgery in the United States. Most surgeries are performed in an operating-room setting under general anesthesia due to the lack of tolerable and reliable local anesthesia methods suitable for pediatric patients, and concerns regarding myringotomy procedures in a mobile child. This study evaluated the safety and efficacy of an iontophoresis system (IPS) to achieve local anesthesia in combination with a tube delivery system (TDS) for tube placement in pediatric patients in an office setting. METHODS: A prospective, single-arm study was conducted at 9 otolaryngology sites in the United States. Participants included pediatric patients aged 6 months to less than 22 years requiring tube placement. Patients were prepared for the procedure using behavioral support techniques and tube placement was attempted under local anesthesia using the IPS in conjunction with the TDS. No physical restraints were allowed and no anxiolytics, analgesics, or sedatives were permitted. Safety was assessed through the occurrence of adverse events and success rates for tube placement under local anesthesia were determined. Tolerability of the procedure was evaluated using the 5-point Wong-Baker FACES Pain Rating Scale and parental satisfaction was assessed using a postoperative survey. RESULTS: Seventy patients (127 ears) were enrolled in the study [mean (SD) age=7.0 (3.9) years]. No serious adverse events occurred in the 70 enrolled patients. Tube placement using the TDS was successful in 96.6% (114/118) of attempted ears. A single TDS was required in 105 ears, while more than 1 device was required in 9 ears. Of the 70 patients enrolled in study, 63 (90.0%) successfully received tubes in all indicated ears during their in-office visit. The mean (SD) change in pain score from pre-anesthesia to post-surgery was +0.9 (1.8). Favorable ratings for overall satisfaction with the in-office procedure were obtained from 96.9% (63/65) of respondents. Tube retention at 2 weeks was 99.1%. As only 15 patients were enrolled who were 3 years old or younger, the ability to generalize these results to younger patients is limited. CONCLUSIONS: In this study, use of the IPS and TDS technologies enabled safe, reliable, and tolerable placement of tubes in awake, unrestrained pediatric patients.

Steroid-eluting sinus implant for in-office treatment of recurrent nasal polyposis: a prospective, multicenter study.

BACKGROUND: Treatment options for chronic rhinosinusitis with recurrent polyposis (CRSwNP) after endoscopic sinus surgery (ESS) are limited, and include frequent use of systemic steroids and revision surgery. A bioabsorbable, steroid-eluting implant was studied for its ability to dilate sinuses obstructed by polyps and provide localized, controlled steroid delivery to reestablish sinus patency. This study assessed the initial feasibility, safety, and efficacy of steroid-eluting implants placed in the office setting in patients who were candidates for revision ESS. METHODS: Prospective, multicenter study enrolling 12 patients who had prior ESS but experienced recurrent polyposis refractory to medical therapy. Implants were placed bilaterally under topical anesthesia in-office. Follow-up through 6 months included endoscopic grading, patient-reported outcomes (22-item Sino-Nasal Outcomes Test [SNOT-22]) and need for revision ESS. RESULTS: Implants were successfully inserted in 21 of 24 (88%) ethmoid sinuses, resulting in 11 evaluable patients. No serious adverse events occurred. Within 1 month, mean bilateral polyp grade was reduced from 4.5 at baseline to 2.3 (p = 0.008) and sustained through 6 months (2.33; p = 0.008). Mean SNOT-22 score was significantly improved from 2.19 at baseline to 0.90 within 1 month (p = 0.001) and sustained to 6 months (1.03; p = 0.012). Sixty-four percent of patients were no longer revision ESS candidates at 6 months. CONCLUSION: The study provided initial clinical evidence of the feasibility, safety, and efficacy of in-office steroid-eluting implant placement in CRS patients with recurrent polyposis after ESS. Although further studies are needed, the results suggest this therapy may provide a safe and effective, office-based option for the treatment of obstructive polyposis.

Effect of steroid-releasing sinus implants on postoperative medical and surgical interventions: an efficacy meta-analysis.

BACKGROUND: Endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) can be compromised by postoperative inflammation, polyposis, and adhesions, often requiring subsequent interventions. A bioabsorbable, steroid-releasing sinus implant has been studied in 2 prospective, randomized clinical trials for its ability to preserve sinus patency and reduce medical and surgical interventions after ESS in patients with CRS. The objective of this study was to perform a meta-analysis of the efficacy results from the 2 trials. METHODS: The 2 prospective, randomized, double-blinded, multicenter trials enrolled a total of 143 patients utilizing an intrapatient control design. Postoperative day 30 videos were obtained for each patient, randomly ordered, and presented to an independent panel of 3 otolaryngologists for grading of efficacy endpoints. The need for postoperative interventions, formation of polyposis, and adhesions were assessed. Results from the 2 studies were then pooled. RESULTS: Implants were successfully placed in all 286 ethmoid sinuses. According to the grading done by the panel, drug-releasing implants reduced postoperative interventions by 35% (p = 0.0008), lysis of adhesions by 51% (p = 0.0016), and oral steroid need by 40% (p = 0.0023), compared to controls. The relative reduction in frank polyposis was 46% (p < 0.0001). CONCLUSION: Early postoperative healing is a predictor of longer-term success after sinus surgery. Evaluation of postoperative outcomes by a blinded independent panel demonstrates that steroid-releasing implants that provide a sustained release of corticosteroid improve surgical outcomes by reducing frank polyp formation, sinus adhesions, and middle turbinate lateralization. Steroid-releasing implants reduce the need for surgical intervention, and the need for oral steroid treatment.

A descriptive feasibility study to evaluate scheduled oral analgesic dosing at home for the management of postoperative pain in preschool children following tonsillectomy.

OBJECTIVES: The purpose of this study, in a sample of preschool children (ages 3-5 years; N = 47), was to evaluate the feasibility of scheduled analgesic dosing following outpatient tonsillectomy in order to optimize pain management. METHODS: Parents were instructed to give their child acetaminophen with hydrocodone (167 mg/5 mL) every 4 hours around the clock for the first 3 days following surgery. Parents recorded ratings of their child's pain with/without swallowing using the Faces, Legs, Activity, Cry, and Consolability (FLACC) behavioral pain scale, pain relief ratings, and severity of analgesic side effects in a home diary. Audiotaped interviews were conducted with parents to document descriptions of their experiences in managing their child's pain at home. RESULTS: Mean FLACC scores with/without swallowing were less than two at each measurement time and pain relief scores increased over time. Total analgesic dose decreased, and the number of missed doses increased over the first 3 days after surgery. Moderate-to-severe daytime sedation, nausea, vomiting, and constipation were reported by parents. DISCUSSION: Study results suggest that acetaminophen with hydrocodone is effective in relieving preschool children's pain following tonsillectomy and that parental adherence to a scheduled analgesic regimen decreases over time. Time-contingent dosing was associated with moderate to severe side effects and should be addressed in discharge teaching with parents. Findings provide insight into parents' perspective of pain management at home following tonsillectomy and methods for relieving their child's pain.

First clinic experience: patient selection and outcomes for ostial dilation for chronic rhinosinusitis.

BACKGROUND: To report outcomes for subjects undergoing balloon dilation in either the operating room (OR) or the clinic and define criteria to identify suitable candidates for local anesthesia procedures. METHODS: Subjects with medically refractory chronic rhinosinusitis (CRS) underwent de novo surgery via transantral balloon dilation of the maxillary sinus ostium and ethmoid infundibulum. Concomitant nasal or endoscopic sinus surgeries were contraindicated. Technical success, surgical parameters, and long-term outcomes were evaluated through 12-month follow-up. RESULTS: Seventy-one subjects underwent balloon dilation and 94% completed follow-up through 12 months. A total of 132 maxillary ostia were targeted for treatment and 129 were successfully dilated (98%). Almost one-half (33) of the procedures were performed in the OR under local anesthesia with intravenous sedation. Average balloon procedure times for unilateral and bilateral treatment were 28.3 ± 21.1 and 40.2 ± 17.7 minutes, respectively. Thirty-three ostial dilations in 19 subjects were attempted in the clinic. Each ostium was successfully accessed and ballooned under local anesthesia. Patient tolerance was very good with an average self-reported pain level of 2.7 (2 = hurts a little bit) out of 10. Each subject was discharged within 2 hours of the procedure and there was no postoperative bleeding. Symptomatic improvement of the clinic subgroup at 3, 6, and 12 months postprocedure was statistically significant (p ≤ 0.0012) and clinically meaningful and similar in magnitude to improvement seen across all subjects regardless of site of service. CONCLUSION: Transantral balloon dilation can be performed safely in the clinic and operative settings with symptom improvement sustained through 1 year.

Safety and efficacy of a novel bioabsorbable, steroid-eluting sinus stent.

BACKGROUND: Inflammation/polyp recurrence, adhesions, and middle turbinate lateralization are causes of suboptimal outcomes following sinus surgery and lead to increased rates of revision. A bioabsorbable, drug-eluting stent was evaluated for its ability to preserve sinus patency by providing controlled steroid delivery to the sinus mucosa. The study objective was to assess safety and efficacy of a steroid-eluting sinus stent when used following functional endoscopic sinus surgery (FESS) in patients with chronic rhinosinusitis (CRS). METHODS: Prospective, multicenter, randomized, double-blind clinical trial, enrolling 43 patients in 2 groups. One group (n = 38) used an intrapatient control design comparing drug-eluting to non-drug-eluting stents. The other group (n = 5) received bilateral drug-eluting stents to assess systemic safety. Endoscopic follow-up was performed for 60 days. Efficacy endpoints included assessment of inflammation, polyp formation, adhesions, and middle turbinate position. RESULTS: Stents were successfully deployed in all 86 sinuses. Compared to the control stent, the drug-eluting stent provided statistically significant reduction in inflammation at days 21 to 45 (p < 0.003), frequency of polyp formation (p = 0.0391), and frequency of significant adhesion (p = 0.0313). Reduced frequency of middle turbinate lateralization was also apparent though not statistically significant. No device-related adverse events occurred. Eluted steroid was unquantifiable systemically and there was no evidence of adrenal cortical suppression. CONCLUSION: This study demonstrates the safety and efficacy of a novel bioabsorbable, steroid-eluting stent for use in CRS patients. The steroid-eluting stent is effective in improving wound healing by preserving sinus patency, reducing inflammation, and minimizing adhesions via controlled local steroid delivery without measurable systemic exposure.

A randomized clinical trial of the efficacy of scheduled dosing of acetaminophen and hydrocodone for the management of postoperative pain in children after tonsillectomy.

OBJECTIVES: To determine the effectiveness of around-the-clock (ATC) analgesic administration, with or without nurse coaching, compared with standard care with as needed (PRN) dosing in children undergoing outpatient tonsillectomy. METHODS: Children 6 to 15 years of age were randomized to receive acetaminophen and hydrocodone (167 mg/2.5 mg/5 mL) for 3 days after surgery: Group A (N=39)-every 4 hours PRN, with standard postoperative instructions; Group B (N=34)-every 4 hours ATC, with standard postoperative instructions, without nurse coaching; and Group C (N=40)-every 4 hours ATC, with standard postoperative instructions, with coaching. Parents completed a medication log, and recorded the presence and severity of opioid-related adverse effects and children's reports of pain intensity using a 0 to 10 numeric rating scale. RESULTS: No differences were found in analgesic administration or pain intensity scores between the 2 ATC groups. Therefore, they were combined for comparison with the PRN group. Children in the ATC group received more analgesic than those in the PRN group (P<0.0001). Children in the PRN group had higher pain intensity scores compared to children in the ATC group, both at rest (P=0.017) and with swallowing (P=0.017). Pain intensity scores for both groups were higher in the morning compared with the evening (P<0.0001). With the exception of constipation, scheduled analgesic dosing did not increase the frequency or severity of opioid-related adverse effects. DISCUSSION: Scheduled dosing of acetaminophen and hydrocodone is more effective than PRN dosing in reducing pain intensity in children after tonsillectomy. Nurse coaching does not impact parent's adherence to ATC dosing.

Children's expectations of pain, perceptions of analgesic efficacy, and experiences with nonpharmacologic pain management strategies at home following tonsillectomy.

PURPOSE: To document children's (ages 6-15 years) descriptions of their pain management at home following tonsillectomy. DESIGN AND METHODS: Audio-taped interviews of 80 children were transcribed and coded. Data for each response category were tabulated. RESULTS: Children reported they had more pain after surgery than expected, the pain medicine helped to take their pain away, taking the pain medicine was associated with a negative response by some children, and cold liquids/food by mouth provided pain relief. PRACTICE IMPLICATIONS: Findings provide insight into children's perspective of pain management at home following tonsillectomy and methods for relieving their pain.

Time-contingent dosing of an opioid analgesic after tonsillectomy does not increase moderate-to-severe side effects in children.

As part of a randomized clinical trial that compared three different analgesic dosing regimens ( Sutters et al., 2004 ), the purpose of this study, in children who underwent tonsillectomy, was to determine whether around-the-clock (ATC) dosing of acetaminophen with codeine, compared with as-needed (PRN) dosing, increased the frequency of moderate-to-severe opioid-related side effects (i.e., daytime sedation, lightheadedness, nightmares, nausea, vomiting, and constipation) in the first 3 days after surgery. Because no differences were found in pain intensity scores and in the amount of analgesic administered between the two ATC groups (i.e., with and without coaching), for these analyses, the two groups were combined ( n = 52) and compared with the PRN group ( n = 28). Each side effect was recoded into a dichotomous response (i.e., 0 = did not have symptoms or had slight symptoms; 1 = symptoms that were moderate, severe, or very severe) to provide an adequate sample size in each cell for the statistical analyses. No differences were found in the frequency of moderate-to-severe side effects between the ATC and PRN groups at any of the postoperative assessments. The number of children who reported moderate-to-severe daytime sedation decreased over time in both the PRN ( p = .02) and ATC groups ( p = .01). Children in the ATC groups reported a statistically significant decrease over time in vomiting ( p = .001) and feeling lightheaded or dizzy ( p = .003), and a significant increase in constipation ( p = .018). Except for daytime sedation, changes, over time, in the frequency of moderate-to-severe side effects were not observed in the PRN group.

A randomized clinical trial of the effectiveness of a scheduled oral analgesic dosing regimen for the management of postoperative pain in children following tonsillectomy.

The purpose of this study was to determine whether around-the-clock (i.e. ATC) dosing of acetaminophen with codeine, with or without nurse coaching, compared to standard care with as needed (i.e. PRN) dosing: reduced children's reports of pain intensity with and without swallowing; increased pain relief, and increased analgesic consumption. Eighty children, 6-15 years, undergoing tonsillectomy were randomized to one of three treatment groups to receive acetaminophen with codeine (120 mg/12 mg/5 ml) for 3 days after surgery: PRN group (N = 28)-every 4 h PRN, with standard postoperative instructions, without nurse coaching; ATC group (N = 26)-every 4 h ATC, with standard postoperative instructions, without nurse coaching; and ATC+coaching group (N = 26)-every 4 h ATC, with standard postoperative instructions and nurse coaching. In all three groups, significant decreases were found over time in pain intensity scores at rest (P < 0.001) and with swallowing (P < 0.001). However, mean pain scores at rest and with swallowing were >3/10 until the fourth evening after tonsillectomy. Children in both ATC dosing groups received significantly greater amounts of acetaminophen and codeine than children in the PRN group (P < 0.003). No significant differences were found in the amount of analgesic administered between the ATC dosing groups with and without nurse coaching. No significant differences were found in the amount of nausea and vomiting among the three groups. Scheduled dosing of acetaminophen with codeine did not provide adequate pain relief for children following tonsillectomy. Nurse coaching does not increase parent's adherence with an ATC dosing schedule.

Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of granulation tissue in children with acute otitis media with otorrhea through tympanostomy tubes.

OBJECTIVE: Comparison of topical ciprofloxacin/dexamethasone otic suspension (CIP/DEX) to ofloxacin otic solution (OFL) for treatment of granulation tissue in children with AOMT. STUDY DESIGN: 599 children aged >/=6 months to 12 years with AOMT of up to 3 weeks' duration were enrolled. Patients received either CIP/DEX 4 drops twice daily for 7 days or OFL 5 drops twice daily for 10 days. Granulation tissue severity was graded at clinic visits on days 1, 3, 11, and 18. RESULTS: Granulation tissue was present in 90 of 599 AOMT patients (15.0%) at baseline. CIP/DEX treatment was superior to OFL for reduction of granulation tissue at the day 11 visit (81.3% compared with 56.1%, P = 0.0067) and the day 18 visit (91.7% compared with 73.2%, P = 0.0223). Both topical otic preparations are safe and well tolerated in pediatric patients. CONCLUSION: CIP/DEX was superior to OFL in the treatment of granulation tissue in children with AOMT.

Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of children with acute otitis media with otorrhea through tympanostomy tubes.

OBJECTIVE: To determine the efficacy and safety of topical ciprofloxacin/dexamethasone otic suspension compared with ofloxacin otic solution in the treatment of acute otitis media with otorrhea through tympanostomy tubes (AOMT) in pediatric patients. METHODS: This multicenter, prospective, randomized, observer-masked, parallel-group study was conducted at 39 sites in 599 children aged >or=6 months to 12 years with an AOMT episode of