Efficacy of Tympanostomy Tubes for Children With Recurrent Acute Otitis Media

An episode of AOM is considered a discrete occurrence if symptoms and signs persisted for, or recurred, >=17 days after the start of antimicrobial treatment. The rate is calculated by dividing the total # of occurrences by the total # of years of follow-up. Risk of recurrences was based on early age of onset of AOM; numerous and/or frequent previous AOM episodes; receipt of multiple courses of antibiotic; eligibility for enrollment first evident during warm-weather months; parental characterization of previous AOM episodes as severe; eligibility for enrollment despite nonexposure to other young children; moderate or marked tympanic membrane (TM) bulging with previous AOM episodes; most previous AOM episodes in both ears; and a high score on the Acute Otitis Media Severity of Symptom scale (with scores ranging from 0 to 10 and higher scores indicating greater severity of symptoms) during screening and/or at enrollment. Multiple imputation was used when follow-up was incomplete.

An episode of AOM is considered a discrete occurrence if symptoms and signs persisted for, or recurred, 17 or more days after the start of antimicrobial treatment. Children with at least 23 months of follow-up were considered to have completed the study.

Parents used the Acute Otitis Media Severity of Symptoms (AOM-SOS) scale (version 4.0) to rate each of 5 symptoms as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Total scores range from 0 to 10; higher scores indicate greater severity of symptoms. AOM episodes were categorized as likely severe if the parent described the child as having moderate or severe otalgia (a lot of ear tugging), temperature ≥39°C, or an AOM-SOS scale score >6 Day 1 of the episode. TF is defined as frequent AOM recurrences (2 in 3 months, 3 in 6 or 4 in 12); ≥3 likely severe AOM recurrences, receipt of ≥45 cumulative days of systemic antimicrobial treatment for AOM, otorrhea for ≥45 cumulative days or diarrhea associated with antimicrobial treatment for ≥30 cumulative days, respectively, in 12 months; persistent effusion for ≥12 successive months; TM perforation for ≥90 days; AOM related hospitalization; anesthesia reactions; and tubes in children randomized to nonsurgical management.

The time to the first episode of AOM is defined as the time, expressed in months, from randomization until the first episode of AOM.

The American Academy of Pediatrics clinical practice guideline concerning the management of AOM refers to children with "severe signs or symptoms" as those with "moderate or severe otalgia or otalgia for >= 48 hours or temperature 39°C (102.2°F) or higher." To simulate that definition, scores are used from the 5-item Acute Otitis Media Severity of Symptoms (AOM-SOS) scale (version 4.0) in which parents are asked to rate symptoms, as compared with the child's usual state, as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Total scores range from 0 to 10, with higher scores indicating greater severity of symptoms. AOM episodes are categorized as "probably severe" if the parent described the child as having had moderate or severe otalgia (a lot of ear tugging; i.e. a score of 2), temperature >=39°C, or an AOM-SOS scale score >6 on Day 1 of the episode. If not "probably severe", then the episode is categorized as "probably nonsevere".

The presence of either tympanic membrane bulging or tympanic membrane perforation with purulent otorrhea, in addition to documentation of symptoms, is required for each episode of AOM.

Adverse events, including tube-associated otorrhea, were collected from enrollment through the end of study. Each study visit included a review of adverse events. Any such event that occurred since the previous visit was recorded, including the date of onset and the date of resolution. For each child, the days per year of tube otorrhea is calculated by dividing the total number of days of tube otorrhea (based on dates of onset and resolution) by the total number of years of follow-up.

For a given child, if a day of follow-up coincides with a study visit, the status of the right and left TMs are recorded at the ear exam. If a day of follow-up does not coincide with a study visit the status of each TM is assumed to be the same as the status on the prior day. Scores are used from the 5-item Acute Otitis Media Severity of Symptoms (AOM-SOS) scale (version 4.0) in which parents are asked to rate symptoms, as compared with the child's usual state, as none, a little, or a lot, with corresponding scores of 0, 1, and 2. Total scores range from 0 to 10, with higher scores indicating greater severity of symptoms. Scores are recorded at study visits and on diaries. The total number of days with an intact TM and a AOM-SOS score greater than or equal to 1 is divided by the total number of years of follow-up to arrive at the days per year with AOM symptoms and an intact TM.

Systemic antibiotics include Amoxicillin-Clavulanate, Ceftriaxone, Cefdinir, Amoxicillin, Azithromycin, Clindamycin, Levofloxacin, Bactrim, Cefprozil, Omnicef and Trimethoprim-Sulfamethoxazole. The days per year, for each child, is calculated by dividing the total number of days the child receives systemic antimicrobials for AOM (based on the recorded start and stop dates) by the total number of years of follow-up.

PDD is defined as the occurrence of three or more watery stools on 1 day or two or more watery stools on each of 2 consecutive days. Adverse events, including PDD, were collected from enrollment through the end of study. Each study visit included a review of medication-related adverse events. Any such event that occurred since the previous visit was recorded.

Diaper dermatitis is defined as diaper rash necessitating administration of topical antifungal therapy. Adverse events, including diaper dermatitis, were collected from enrollment through the end of study. Each study visit included a review of medication-related adverse events. Any such event that occurred since the previous visit was recorded.

Adverse events, including tube-associated otorrhea, were collected from enrollment through the end of study. Each study visit included a review of adverse events. Any such event that occurred since the previous visit was recorded.

Throat specimens were obtained mainly from children older than 24 months of age. The penicillin-nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae and ß-lactamase-positive Haemophilus influenzae. Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of <0.1 μg/mL; intermediate as an MIC of 0.1 to 1μg/mL; and resistant as an MIC of >1 μg/mL.

Throat specimens were obtained mainly from children older than 24 months of age. The penicillin-nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (S. pn) and ß-lactamase-positive Haemophilus influenzae (H. flu). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of <0.1 μg/mL; intermediate as an MIC of 0.1 to 1μg/mL; and resistant as an MIC of >1 μg/mL.

Throat specimens were obtained mainly from children older than 24 months of age. The penicillin-nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (S. pm) and ß-lactamase-positive Haemophilus influenzae (H. flu). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of <0.1 μg/mL; intermediate as an MIC of 0.1 to 1μg/mL; and resistant as an MIC of >1 μg/mL.

Throat specimens were obtained mainly from children older than 24 months of age. The penicillin-nonsusceptible pathogens considered are penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae (S. pn) and ß-lactamase-positive Haemophilus influenzae (H. flu). Susceptibility to penicillin was defined as follows: susceptible as a minimum inhibitory concentration (MIC) of <0.1 μg/mL; intermediate as an MIC of 0.1 to 1μg/mL; and resistant as an MIC of >1 μg/mL.

At the end-of-study visit, parents were asked to rate their level of satisfaction with their child's assigned management using a 5-point scale with higher numbers indicating greater satisfaction, specifically 1 = very dissatisfied, 2 = somewhat dissatisfied, 3 = neither satisfied nor dissatisfied, 4 = somewhat satisfied, and 5 = very satisfied.

Health care encounters, indicators of medical resource use, were ascertained from parent reports. At scheduled study visits, every 8 weeks after randomization. and at interim sick study visits, parents were asked about encounters with healthcare providers, including hospitalizations and visits to emergency departments, urgent care, and primary care providers, since the previous study visit.

Occurrences of parent missing work due to child's illness, an indicator of non-medical resource use, was ascertained from parent reports at scheduled study visits, every 8 weeks after randomization, and at interim sick study visits.

Occurrences of the need for special childcare arrangements due to child's illness, an indicator of non-medical resource use, was ascertained from parent reports at scheduled study visits, every 8 weeks after randomization, and at interim sick study visits.

The OM-6 is a 6 item quality of life assessment addressing physical suffering, hearing loss, speech impairment, emotional distress, activity limitations and caregiver concerns. Responses are regarded on an ordinal scale ranging from 1 (no problem) to 7 (greatest problem). The average response, i.e., score, for these 6 items is calculated. The overall child's quality of life (QOL) score, also captured on the OM-6, is expressed on an ordinal response scale that ranges from 0 (worst quality of life) to 10 (best quality). A OM-6 is administered to the parent every 16 weeks after randomization and occasionally at sick visits.

The Caregiver Impact Questionnaire (CIQ) is a 6 item assessment addressing lack of sleep, absence from work or education, canceling of family activities, changing daily activities, feeling nervous and feeling helpless. Each of these responses is expanded to a continuous scale from 0 (no impact on caregiver) to 100 (greatest impact). The average response, i.e., score, for these 6 items is calculated. The overall caregiver's quality of life (QOL) score, also captured on the CIQ, is expressed on a ordinal response scale that ranges from 0 (worst quality of life) to 10 (best quality). The CIQ is administered to the parent every 16 weeks after randomization and occasionally at sick visits.

Total costs in US dollars were calculated by summing costs of lost wages, office visits, medical procedures, hospitalizations, and medications. Total QALDs were calculated by summing daily utility values. A utility value of 1.0 was assumed for days without AOM, otorrhea, or hospitalization. For days where these states were reported, published utility values associated with each state were used. To arrive at the final measure, total costs were divided by total utility values.

Total costs in US dollars were calculated by summing costs of lost wages, office visits, medical procedures, hospitalizations, and medications. Total QALDs were calculated by summing daily utility values. A utility value of 1.0 was assumed for days without AOM, otorrhea, or hospitalization. For days where these states were reported, published utility values associated with each state were used. To arrive at the final measure, total costs were divided by total utility values. The estimated risk of AOM at enrollment is described under both Baseline Characteristics and Outcome Measure #2.