Interventions for adult Eustachian tube dysfunction: A systematic review

Non-surgical

Non-surgical management strategies include:

• Active observation, which involves monitoring the symptoms to determine whether or not they naturally resolve.

• Supportive care, which includes advice about self-management such as to swallow, yawn, or chew to help equalise the pressure in the middle ear.

• Pressure equalisation methods, which is a technique whereby the Eustachian tube is reopened by raising the pressure in the nose. This can be achieved in several ways, including forced exhalation against a closed mouth and nose (Valsalva manoeuvre). Other methods include blowing up a balloon through each nostril, using an anaesthetic mask36 or the use of mechanical devices. 40,41 The aim is to introduce air into the middle ear, via the Eustachian tube, equalising the pressures and allowing better fluid drainage.

• Nasal douching, in which the nasal cavity is washed with a saline solution to flush out excess mucus and debris from the nose and sinuses. 42

• Decongestants, antihistamines, nasal or oral corticosteroids which are aimed at reducing nasal congestion and/or inflammation of the lining of the Eustachian tube.

• Antibiotics, for the treatment of rhinosinusitis.

• Simethicone, which is currently being investigated in adults to assess whether or not it can help to break up bubbles that may block the opening of the Eustachian tube in the back of the nose during a cold, allowing air to pass between the nose and middle ear. 43 This is not currently a management option used in the UK.

Surgical

We understand that, currently, the main surgical treatment in the UK is a pressure equalising tube (also known as tympanostomy tube, ventilation tube or grommet) which is inserted into the eardrum through a small incision. Pressure equalising tubes typically extrude after 6–9 months. Long-acting tubes are occasionally used, although these may be prone to crusting, infection, obstruction and permanent tympanic membrane perforation. This may be performed under either general or local anaesthesia. Newer surgical methods which are mainly used in the context of research include:

• Balloon dilatation (dilatation) of the Eustachian tube, a procedure which aims to dilate the Eustachian tube and improve its function. It consists of introducing a balloon catheter into the Eustachian tube through the nose, under transnasal endoscopic vision. The balloon is filled with saline. Pressure is maintained for approximately 2 minutes, following which the balloon is emptied and removed. The procedure has been performed experimentally under local and general anaesthesia.

• Transtubal application of fluids, an emerging approach for the application of fluids to the middle ear via the Eustachian tube. The transtubal application approach involves placing a nasal microendoscope within the Eustachian tube under local anaesthesia via its nasopharyngeal opening. Subsequently, fluids are applied through an additional working channel after microendoscopic evaluation. 44

• Eustachian tuboplasty, an emerging treatment in which a laser or rotary cutting tool is used to strip away enlarged mucous membranes and cartilage to clear obstruction to the Eustachian tube. Tuboplasty has been used in patients with chronic ETD as an alternative to pressure equalising tubes which may have extruded on numerous occasions. 23,32 The intervention has also been used for middle ear atelectasis or serous effusion. 45

There is no consensus on indications for treatment, or on the optimal timing of the interventions. Surgical interventions are generally (though not exclusively) used where ETD is resistant to other interventions. A step-up approach is usually adopted, from primary to secondary and tertiary care settings. Treatment choice is based on aetiology, severity and persistence of symptoms, as well as the degree of invasiveness of the treatment and surgical preference.

Population

Adults (≥ 18 years) with a clinical diagnosis of ETD were included. Given the current lack of consensus on diagnostic criteria for ETD, a strict definition of ETD was not applied and primary study definitions of ETD were accepted, provided that they were based on symptomatology and/or tests such as tympanometry or otoscopy. Studies of patients with known patulous Eustachian tube or nasopharyngeal tumours were excluded as these populations are distinct and are likely to require different management options. Studies with mixed populations of patients with and without ETD were included if separate outcome data were available for the population of interest. The intention was to include only studies of adults or where separate adult data were available.

At the study selection stage, only a single controlled study in adults with ETD was identified. Therefore, to allow a fuller mapping of the literature, the protocol was amended to include controlled studies including adults and children with no separate adult data, as well as controlled studies that did not explicitly state whether or not the whole study population were adults. For all such studies, the authors were contacted to clarify whether or not the population was indeed adults and/or to seek separate data on the adult population. Following this amendment, five additional comparative studies were included. This protocol amendment was not extended to uncontrolled studies of mixed populations, as this would have increased the risk of further uncertainty in the evidence.

Intervention

Interventions explicitly aimed at treating ETD in primary, secondary and tertiary care settings were eligible for inclusion. A list of eligible interventions and examples of specific treatments is provided in Table 1 .

Comparator

Any comparator (placebo, no intervention or another eligible treatment) was considered for inclusion.

Outcomes

There is currently no consensus regarding the most appropriate measure of treatment success. Change in severity and/or frequency of symptoms was classified as the primary outcome because of its relevance to patients. Other outcomes of interest included quality of life; improvement in middle ear function based on measurement tools such as tympanometry (reported as a categorical or continuous outcome); improvement in hearing based on audiometry (reported as a categorical or continuous outcome); tympanic membrane mobility; clearance of middle ear effusion; need for additional treatment, for example requirement for surgical procedure (including reintervention); early tube extrusion (for pressure equalising tubes); adverse events of interventions; and complications related to ETD (e.g. atelectasis).

Study design

Experimental trials (randomised and quasirandomised) as well as observational studies with a control group were included. Uncontrolled observational studies (e.g. case series) including at least 10 patients were also considered for interventions where no controlled studies were found.

Only English-language studies were included.

Patient characteristics

Four of the studies of non-surgical interventions reported data on a mixed adult/paediatric population. In the case of Gluth et al. ,52 the proportion of adults in the trial (63%) was reported and some separate data on the primary outcome were reported for the paediatric subgroup (aged 6 to 17 years), allowing results for adult patients to be calculated. 52 In the three other studies, the age ranges indicated that all patients were adolescents or adults, with age ranges of 14–66 years,24 12–75 years25 and 16–76 years. 41 In the fourth study, there was some uncertainty as to whether or not all patients were adults, but the mean age was 39.2 years, suggesting that, unless the range was very wide, the probability was that a majority of individuals were adults. 40

The mean ages of patients undergoing a surgical intervention ranged from 40 to 63 years and age ranges extended from 18 to 90 years where reported. The single controlled before-and-after study evaluating surgery had an age range of 21 to 56 years (mean age not reported). 51 All of the included studies which reported information on patient sex had approximately equal numbers of male and female patients.

There was notable variation in the inclusion criteria used by individual studies, and, consequently, in the characteristics of the patient populations. In particular, there was variation in the length of time patients were required to have had ETD symptoms, the severity of the symptoms and the previous treatments attempted. While two studies of surgical intervention required that patients had a history of 5 years of ETD symptoms,20,23 other studies required merely that patients experienced ongoing ETD symptoms following an aeroplane flight,41,54 while others specified that the symptoms be ‘chronic’18,56,61 or that participants were required to have a long history of symptoms. 21 Although the symptoms considered to be associated with ETD were specified as part of the inclusion criteria in many of the studies, ETD itself was rarely defined. None of the studies of pharmacological agents or mechanical devices specified a minimum duration of symptoms, although one required that symptoms be ‘persistent’. 40 Where symptoms were assessed and reported using a scale to quantify severity, it appeared that patients were in considerable discomfort at baseline. 40,55

Notably, three of the surgical studies included only patients with a diagnosis of otitis media with effusion with an aetiology indicating that ETD was responsible for the condition. 22,23,51 In these and four other studies, including two evaluations of pharmacological treatments, patients with a perforated tympanic membrane or current pressure equalisation tubes were included either as an identified subgroup or together with patients with an intact eardrum. 20,21,24,25

Previous treatment histories also varied widely both among and in some cases within studies. Poor reporting was an issue, particularly in the studies of pharmacological interventions. One study of a mechanical device reported previous therapies of nasal decongestants, non-steroidal anti-inflammatory drugs (NSAIDs), antihistamines and antibiotics,40 while the other did not report treatment history. 41 Of the studies of pharmacological interventions, two did not report treatment histories25,52 while the third noted only one previous pressure equalisation tube. 24

Where treatment histories were documented for surgical patients, they indicated considerable variation, with patients in some studies having failed multiple therapies including both medical and surgical interventions, while patients in others had no surgical history or no prior treatment history. In four studies of surgical intervention, failure of conservative or medical management was a criterion for enrolment in the study. 20,23,54,61 In four further surgical studies, repeated courses of medical therapy were documented for all patients. 56,60,63,83 Three studies required prior ventilation tubes. 22,23,61 One surgical study reported no prior treatments. 58 Within some studies, there was variation in the reported treatment histories, with three studies reporting prior surgeries in some but not all of the patients. 56,63,83 Three studies of surgical intervention did not report treatment histories18,21,62 and one noted only that most patients had had previous ETD treatment (Professor Maria Boboshko, St. Petersburg Pavlov State Medical University, 2012, personal communication). 51

There were also differences in the approach to comorbidities such as gastric reflux and rhinosinusitis. In five studies, the incidences of comorbidities were not reported. 18,55,58,62,63 Other studies documented substantial minorities of patients with these and related conditions,22,23,56,60,61 while some used their presence as an exclusion criterion. 20,21,54 One study of tuboplasty included only patients with a diagnosis of rhinosinusitis. 56

Interventions

As can be seen from Table 2 , the interventions represented in the review covered a range of pharmacological, surgical and mechanical devices.

Three studies, including two RCTs and one non-RCT, assessed pharmacological interventions. These were a nasal steroid spray,52 a topical administration of decongestant,25 and oral administration of a combination of antihistamine and ephedrine. 24

Two studies (one small RCT and one non-RCT) assessed pressure equalisation devices. 40,41

Surgical interventions assessed were various techniques for Eustachian tuboplasty, balloon dilatation, thermal or laser-assisted myringotomy, and laser coagulation of the Eustachian tube pharyngeal opening. One case series assessed dexamethasone administered via micro-wick following myringotomy. 61 Seven case series assessed forms of tuboplasty;20,21,23,54,56,62,63 three case series assessed balloon dilatation;18,22,55 and two assessed myringotomy. 58,60 For other interventions, a single retrospective controlled before-and-after study51 or case series were available. 61

Seven of the surgical studies reported that concomitant treatments were administered in addition to the intervention that was the focus of the assessment. These included a range of additional surgical interventions and/or pharmacological treatments. 20–23,55,56,61

The interventions assessed by the included studies did not include several methods which may be used in primary care, including active observation, supportive care, antibiotics, leukotriene receptor antagonists (LTRAs) or nasal douching. There were also no included studies assessing the most common surgical intervention for ETD: insertion of pressure equalisation tubes. For many of the eligible interventions, there was, therefore, no evidence which met the review inclusion criteria. For most interventions where evidence was available, there was no randomised and often no controlled evidence. The number of studies identified for each of the eligible interventions is reported in Table 3 , indicating where gaps in the evidence remain.

Outcomes

Eleven studies, comprising one of the three pharmacological studies,52 one of the two studies of mechanical devices40 and nine studies of 13 studies of surgical interventions,18,20,51,55,56,58,61–63 assessed the primary outcome. Of the studies which did assess symptoms, only four reported using a systematic method to quantify improvement or change in symptomatology. One used scales specific to the condition for which at least some information is available on reliability and validity (the ETDQ-7 and SNOT-22). 55 One used a symptom questionnaire which appeared to be a modified version of the ETDQ-7, and two used a visual analogue scale (VAS). 20,40,52

All other studies which reported symptom change restricted reporting to the number of patients reporting improvement in either global ETD symptoms,55,56,63 specific symptoms such as tinnitus or aural fullness51,58,61 or non-specific ‘improvement’18 or resolution of symptoms. 62

A considerable range of outcomes specified as relevant in the review protocol were assessed ( Table 4 ), although none of the studies reported quality of life, and early tube extrusion was not a relevant outcome as no studies of pressure equalisation tubes were included.

Hearing was assessed in seven of the studies of surgical interventions20,23,51,56,60,61,63 and in one of the mechanical device studies. 41 Various audiometry measures were reported, of which the most common was the average pure-tone threshold. 23,56,61,63 Air–bone gap was also commonly reported20,41,51,61 and one study also reported speech discrimination score,61 while another reported bone conduction in addition to air conduction. 20 One study reported only that a patient reported a change in hearing. 60

Most studies reported some measure of middle ear function but the measure used varied considerably. Conversion to a type A tympanogram was reported by one study of a mechanical device,41 one study of a pharmacological intervention52 and eight studies of surgical interventions. 18,20–23,51,54,55,61 Other measures of tympanometry were reported as alternative or additional outcomes. These included ‘improvement to normal or more normal tracing’56 and ‘improvement’. 63

Alternative measures of middle ear function which included outcomes related to pressure equalisation (e.g. tubotympanometry,40 Valsalva manoeuvre,20,21,23,25,84 passive opening pressure20,21,24) and measures based on the appearance of the middle ear on clinical examination22,23,55,57 were used. Multiple outcomes were reported by several studies for both middle ear function and hearing. 20,55,56,84

Two surgical studies reported on clearance of middle ear effusion. 23,51

All three of the pharmacological studies24,25,52 and one of the two studies of mechanical devices41 measured treatment success and provided a definition of successful treatment. Eight of the surgical studies measured treatment success; however, in three of these, the authors did not state how they defined treatment success. 18,51,62 Where provided, the definitions of treatment success varied widely and often included multiple criteria. For example, Gluth et al. defined treatment success as a normal (type A) tympanogram in both ears or as meeting this criterion and not requiring/using additional specified treatments during the study, and reported results according to both criteria. 52 In other studies, different definitions of success were used dependent on patient characteristics; for example, one case series required an improvement in tympanometry or hearing impairment as well as symptoms but an improvement only in symptoms for patients who had normal tympanometry and hearing at baseline. 55

Reporting of safety data was not consistent between studies and for the majority of studies there was insufficient information to establish how systematically the data were collected. Two of the three pharmacological studies reported adverse events information, and 11 of the studies of surgical interventions reported some information.

Finally, there were considerable differences in the length of follow-up, both between studies and within studies for different outcome measures. Where reported, length of follow-up ranged from the extremely short term (30 minutes or up to 3 hours), which may have very limited clinical relevance,24,25 to the more typical short term of between 1 and 8 weeks,40,41,52,54,55,58 and 1 to 2 years or longer in some of the studies assessing surgical interventions. 20,21,23,51 Length of follow-up was not clear in some studies, with assessments being noted as, for example, ‘post-operative’56 or ‘study completion’62 or only a mean duration of follow-up being reported. 18,61

Quality of non-surgical studies

Of the three studies reported as being randomised, Gluth et al. 52 was considered to be at low risk of bias. Jensen et al. 25 had an unclear risk of bias primarily due to multiple gaps in reporting. The third RCT, Alpini and Mattei,40 was considered at high risk of bias due to the lack of blinding of outcome assessors, personnel and participants ( Table 5 ). The two non-randomised studies24,41 were considered at high risk of bias due to the lack of randomisation and the lack of clarity around potential differences between groups at baseline (see Table 5 ).

Gluth et al. 52 was the only trial to describe appropriate randomisation methods and adequate allocation concealment methods. Three studies24,25,52 blinded their participants (placebo-controlled studies) but none clearly reported blinding study personnel, and therefore none of the studies were considered to have a low risk of performance bias (i.e. a risk of differences between groups in the care received or in exposure to factors other than the interventions). 48

Detection bias was unclear in all except two studies24,52 which clearly stated blinding outcome assessors. Attrition bias was considered low in all studies. Only Gluth et al. 52 reported sufficient data to rule out selective reporting of outcomes. Two trials25,52 reported a power calculation, but only Jensen et al. 25 reported sufficient power to detect a significant treatment effect. Follow-up duration was considered sufficient to detect a short-term impact in only two studies. 41,52 Further details are reported in Tables 5 and 6 .

Quality of surgical studies

The single controlled before-and-after study assessing a surgical intervention had adequately reported eligibility criteria, determined through author contact (Professor Maria Boboshko, St. Petersburg Pavlov State Medical University, 2012, personal communication), and had an adequate length of follow-up. 51 However, details of the intervention received by the control group were limited, and the representativeness of the sample and adequacy of participation rates were unclear ( Table 7 ).

The quality of the included case series was variable ( Table 8 ). Nine of the 13 studies were prospective and three reported consecutive recruitment of patients. 22,56,63 All except one study had adequately reported eligibility criteria and there was at least 80% follow-up from baseline in all except one study where this was not clear. 18 It was not clear in any study whether or not the patients assessed constituted a representative sample of those eligible. Even in studies using prospective and consecutive recruitment of patients, the fact that it was unclear whether or not patients were a representative sample meant that these case series, and the controlled before-and-after study, were still at high risk of selection bias, in which patients considered likely to demonstrate a good outcome were preferentially enrolled. This risk is increased for studies in which enrolment was not consecutive and particularly so where recruitment was not prospective. Only six studies used an appropriate statistical analysis with reporting of tests to assess the significance of differences between baseline and follow-up,20–23,54,56 and only four reported appropriate measures of variability such as standard deviations (SDs) for assessments at baseline and follow-up. 20,22,54,55

Six studies also reported both potential confounding and prognostic factors,20–23,55,56 while two reported confounding but not prognostic factors18,60 and one reported prognostic but not confounding factors. 54 Even an ideal case series is subject to the limitation that it is impossible to assess what the outcome would have been for patients had they not been given the intervention assessed. The lack of a control group means that it is unclear how much of the observed benefit(s) may be attributed to this therapy and how much may be a consequence of spontaneous recovery and/or regression to the mean. The natural history of ETD means that this is of particular relevance, as symptoms may be expected to change in intensity and frequency and, in some cases, to resolve without intervention.

In the case series included in this review, an additional consideration is the administration of concomitant therapy. The seven studies reporting confounding factors all documented additional treatments other than the intervention assessed. In some cases, all patients received additional surgical or pharmacological therapies, while in others a proportion of patients were given concomitant treatment according to perceived clinical need resulting from their ETD and/or comorbidity.

Study characteristics

The included studies evaluated a diverse range of interventions. Only single studies were identified for each intervention: there was one randomised placebo-controlled trial for each of a pressure equalisation method,40 nasal steroids52 and a topical decongestant,25 and a non-RCT of a combination of antihistamine and ephedrine24 and a politzerisation method. 41 A description of the interventions is provided in Table 2 . All the studies were small: the number of participants ranged from 20 to 91. Follow-up duration was short, ranging from 30 minutes up to 10 weeks after treatment initiation.

Only one study reported the setting and context in which interventions were delivered (by an ENT specialist in a private otology practice). 41 Antihistamine, ephedrine and topical decongestants were administered as a single dose. 24,25 None of the studies reported on treatment adherence and compliance. One trial reported on the use of concomitant treatments (antibiotics and/or oral decongestants) for 14 (15%) patients. 52 Although the requirement for participants to have ETD was clearly stated in all studies, the condition was not explicitly defined in any of them. Selection criteria varied across the studies. Two studies included patients with a perforated eardrum,24,25 while they were excluded from one. 52 Two studies excluded patients with comorbidities, such as craniofacial syndromes and cleft palate,52 active cholesteatoma, or upper respiratory tract infection. 25 Diagnostic methods of ETD varied. All studies used a combination of at least two diagnostic tools, with tympanometry being the most frequent. Further details on selection criteria are reported in Table 9 .

Where reported, baseline symptoms, related conditions and previous treatments varied between the studies. Three studies reported that the included participants had symptoms associated with ETD, such as fullness, ear pain, plugged sensation, popping sensation, dampened or loss of hearing. 40,41,52 However, only Alpini and Mattei reported an objective measurement of symptom severity at baseline (VAS score for fullness in the ear). 40 Gluth et al. used a non-validated symptoms questionnaire but the baseline results were not reported,52 and patients in Silman and Arick41 all reported ETD symptoms during aeroplane travel but the study did not report measuring their severity. None of the studies reported on the duration or persistence of ETD symptoms before treatment.

Three studies reported using tympanometry at baseline and found results indicating abnormal middle ear function in most evaluated ears. 24,41,52 Participants in Alpini and Mattei were reported to have residual middle ear effusion, although they showed normal audiometric and tympanometric results at baseline. 40 All patients in Jensen et al. 23 and about one-third of participants in Holmquist and Larsson had eardrum perforations. 24,25 Prevalence of eardrum perforations was not reported in the other studies. Two studies did not report any related conditions. 40,41

Only two studies reported on the use of previous treatments. 24,40 All patients in Alpini and Mattei had received pharmacological treatment for otitis media, such as nasal decongestants, NSAIDs, antihistamines and antibiotics. 40 Holmquist and Larsson was the only study to report on the number of patients who had had ventilation tubes placed. 24 Further details on patient characteristics are reported in Table 9 .

Results

The results from individual non-pharmacological studies are reported below, grouped by type of outcome. Given that there was only a single study for each intervention, a quantitative synthesis was not possible. Indeed, due to the poor reporting of results for most outcomes, it was not always possible to extract standard data such as baseline and follow-up values with associated SDs to allow calculation of the 95% CIs for the treatment effect.

Study characteristics

With the exception of Boboshko et al. ,51 all of the studies of surgical interventions were case series. Silverstein et al. (n = 11) used surgery to permit the topical application of steroids (see Table 2 ). 61 The other interventions assessed were procedural variations of laser Eustachian tuboplasty (seven studies, n = 182);20,21,23,54,56,62,63 balloon dilatation of the Eustachian tube (three studies, n = 103);18,22,55 and myringotomy (two studies; n = 121). 58,60 General anaesthesia was used in five studies,22,54–56,63 local in seven studies,18,20,21,51,58,60,61 a combination of the two in one study,23 and one study did not report which method was employed. 62

In most of the studies, all patients were described as having a diagnosis of ETD, although in two these patients were a defined subgroup for whom separate data were reported. 21,60 In three studies, the diagnosis was otitis media with effusion due to ETD;22,23,51 these patients would be expected to have a worse prognosis than those in other studies without otitis media with effusion. Three studies excluded patients with comorbidity such as allergies or reflux disease;20,21,54 conversely, one study required a diagnosis of rhinosinusitis severe enough to warrant surgery. 56 Some studies included patients with a perforated eardrum as a separate subgroup,20,21 while others did not report separate data for these patients, although they were identifiable from their baseline tympanometry. 22,23 Baseline tympanometry data are discussed together with the tympanometric response to therapy in Results, below.

Diagnostic methods varied between studies, but all (except one which did not report these) used more than one method. In all except two studies, the diagnostic process included tympanometry. Although the requirement for participants to have ETD was clearly stated by authors, as with the non-surgical studies, the condition was rarely defined. Most commonly, some of the symptoms characteristic of patients with a diagnosis of ETD such as otalgia during pressure change and aural fullness were cited,18,21,51,54–56,61,63 together with requirements for patients to have an abnormal tympanogram or abnormal appearance on clinical examination. 20,21,23,54–56,61,63 In some cases, ETD was cited as an inclusion criterion with no further information. 62 Full details of the range of criteria used are shown in Table 12 .

Patients in most of the studies had extensive histories of previous treatment for ETD and/or related conditions. These included multiple antibiotic and steroid treatments as well as previous aural and nasal surgeries (see Table 2 ). In five studies, failure of one or more medical therapies or previous surgical intervention (e.g. pressure equalisation tubes) was a criterion for inclusion in the study,20,22,23,54,61 while in nine studies, all patients had failed one or more previous treatment. 20,22,23,54–56,60,61,63

Results

Non-surgical interventions

Several pharmacological treatments and manual pressure equalisation devices were evaluated, but none of the interventions was evaluated by more than one study. Overall, the evidence from non surgical studies is weak due to the small number and size of the studies, as well as several important limitations, notably poor reporting of study design characteristics, patient characteristics and outcomes data, and limited follow-up duration. In particular, the clinical value of follow-up data at durations measured in minutes or hours is highly uncertain. This paucity of data precludes any definitive conclusions on the clinical effectiveness and safety of pharmacological or manual treatments for adult ETD. Only two of the studies reported measuring adverse events. Minor adverse events were reported in one study,52 and no events in the second. 25

One trial showed no evidence that a 6-week course of nasal steroids was effective at improving the severity and frequency of ETD symptoms among patients with otitis media with effusion and/or negative middle ear pressure by the end of the treatment. 52 This was the only study identified as having a low risk of bias, though even in this study there were limitations in how the outcome data were reported.

There were some data indicating improvement in middle ear function for patients with a history of chronic otitis media 30 minutes after receiving direct application of a topical decongestant on the pharyngeal opening of the Eustachian tube in a single RCT. 25 However, as pointed out by the authors, treatment only improved middle ear function when patients were subject to unphysiologically high pressure changes. The internal and external validity of this study are both unclear, notably due to multiple gaps in reporting of design characteristics and very short-term follow-up. This is also likely to be an unrealistic treatment for primary care; in secondary care, endoscopic guidance would be required.

One non-RCT found a significant improvement in middle ear function for patients receiving a single dose of antihistamine and ephedrine compared with placebo. However, the reliability of these findings is uncertain, notably due to a high risk of selection bias and very short follow-up duration (3 hours). 24

Two studies evaluated the use of two different manual pressure equalisation devices. 40,41 Both studies were small and subject to a high risk of bias. The RCT found that the self-administration of a manual device applying mild negative pressure to the external ear canal three times per day for 1 week was associated with a significant reduction in severity of fullness in the ear and middle ear function. 40 The non-RCT found a statistically significant difference in middle ear function (tympanometric peak pressure) and in hearing at 9 to 10 weeks’ follow-up which favoured the use of modified politzerisation twice-weekly for 6 weeks. 41 However, the difference in hearing reflected an unexplained deterioration in the control group rather than an improvement in those who received the intervention. Neither study reported data on adverse events of the interventions, making the safety of these interventions uncertain. In addition, this may be experienced as being an unpleasant treatment; however, adherence, compliance and patient experience of the treatment were not assessed. Therefore, it is unclear how feasible such a treatment would be in clinical practice.

Surgical interventions

As noted above, a variety of surgical interventions were evaluated. Eustachian tuboplasty and balloon dilatation were evaluated in multiple studies. Myringotomy was assessed in two studies. 58,60 The other surgical interventions, laser coagulation and myringotomy for direct application of topical steroids through a MicroWick tube, were each evaluated by a single study. 51,61 All studies had a high risk of bias. Any interpretation of data from case series is limited by the uncontrolled study designs: it is impossible to determine how much improvement in symptoms and other measures would have occurred in the absence of the intervention, especially in the case of a condition which may resolve naturally. Extensive use of cointerventions contributed to uncertainty.

Eustachian tuboplasty was the most commonly evaluated surgery (seven studies in 182 patients). 20,21,23,54,56,62,63 Where improvement in symptoms was evaluated, it was reported for a substantial proportion of patients at follow-up ranging from 2 to 37 months following surgery, though improvement was defined in a variety of ways. Four studies reported an improvement in hearing, although improvements were generally small with limited clinical significance. 20,23,56,63 Measures of middle ear function indicated low rates of conversion to type A tympanogram in the three studies that reported this outcome. 21,23,54 Tuboplasty may be considered a potentially promising intervention but there is insufficient evidence to demonstrate its effectiveness, or to determine either the details of the surgical technique which should be employed or the patients for whom it should be considered. As well as differences in the techniques used, there were wide variations between the patients in these studies, as well as differences in the outcomes reported and the measures used to assess outcomes. One study also employed sinus surgery in all patients,56 and concomitant interventions for some patients were reported in two other studies. 20,23

Three studies of balloon dilatation were identified (n = 107). 18,22,55 Two reported on symptoms at follow-up (12 weeks and mean 30 weeks); both showed high levels of improvement. 18,55 Tympanometric measurement of middle ear function was reported in all three studies, and all reported conversion to type A tracings, although follow-up duration varied significantly between the studies (from 6 weeks to 1 year). None of the studies reported data on hearing. Two of the studies reported that all or a majority of patients had additional surgery and a minority of patients in the third also had additional treatment. 22 The review findings are, therefore, in line with the NICE guidance which indicated some evidence of effectiveness but uncertainty as to its reliability. 30

Two studies assessing procedures for myringotomy were identified. 58,60 One small study reported efficacy in permitting patients to undergo hyperbaric oxygen therapy, while the other reported symptom alleviation in the subgroup of patients with an ETD diagnosis. The evidence base for topical application of steroids to the Eustachian tube and laser point coagulation each rested on a single study. 51,61

None of the interventions appeared to be associated with serious adverse effects, although minor complications of surgery were reported in a minority of patients in several studies. However, it was not clear that adverse events were systematically documented, and three surgical studies did not report any safety data. 58,62,63 None of the studies reported follow-up beyond a maximum of 10 weeks in non-surgical and 30 months in surgical studies; therefore, the long-term safety profile of the interventions is unknown.

In addition to the limitations arising from study design and use of cointerventions, multiple gaps in the reporting of the studies were identified (notably with regard to patient recruitment, patient characteristics, outcomes and statistical analyses) which limited the extent to which the results could be interpreted. None of the studies was conducted in the UK, which limits the extent to which the results can be interpreted in a NHS context. Therefore, while these studies suggested that there may be some benefits to surgical treatments of ETD, the quality and reliability of the available data are too limited to allow any conclusions to be drawn.

Gaps in the clinical effectiveness evidence

Studies of several relevant surgical and non-surgical interventions were not identified despite extensive searches. No studies were found of active observation (monitoring to determine whether or not the condition resolves naturally) or supportive care (advice on self-management strategies such as advice to swallow, yawn or chew). Participants in the control groups of the two studies evaluating pressure equalisation devices may have effectively been under active observation, although neither of the studies explicitly stated it. No evidence on the effectiveness of nasal douching, oral steroids, antibiotics, LTRAs and simethicone was found. An ongoing RCT of simethicone was identified, though this is not currently used in the UK. 43 No RCTs of surgical interventions were identified in the searches except for an ongoing RCT being conducted in the UK which aims to evaluate the effect of balloon dilatation of the Eustachian tube in adults with long-term ETD. 81

Differences in patient characteristics

There is a lack of consensus on how ETD should be defined, as well as on the aetiology of the condition. This lack of consensus was reflected in the considerable variation in inclusion criteria employed in the included studies, and, consequently, in the characteristics of the patients treated in these studies. The included studies, which required patients to have a clinical diagnosis of ETD, exhibited substantial variation in whether or how ETD was defined. Some studies simply reported that patients were required to have ETD, without further details. Even when precise symptoms that were considered necessary for a diagnosis of ETD were reported, the baseline severity and/or frequency of the symptoms were rarely quantified. It was, therefore, often unclear what the precise characteristics of the patient population were in relation to some or all of the criteria which may be considered to form part of the characterisation of ETD.

Studies also varied whether they required patients to have failed previous treatments or to have experienced symptoms for a particular duration. Studies of pharmacological interventions and mechanical devices did not specify duration of symptoms or that patients should have failed previous medical interventions, while several studies of surgical interventions required that patients should have failed multiple attempts at medical management and, in some cases, prior surgical intervention.

Another key difference between the non-surgical and surgical studies was that all except one of the non-surgical studies were conducted in mixed populations of adults and adolescents or children. In the fifth study, it was unclear whether or not this was also the case. 40 Unlike non-surgical interventions, studies of surgical interventions were available in exclusively adult populations.

Despite poor reporting of ETD history, it also appeared that, as might be anticipated, patients in the non-surgical studies might have had less serious or long-lasting ETD than those in the surgical studies. Within-study variation in these characteristics was also seen in several studies assessing surgical interventions. A minority of studies excluded patients with specified comorbidities, while other studies reported that some or all of the patients had these conditions (e.g. rhinosinusitis, allergies or reflux). In three of the surgical studies, it was clear that all patients had chronic otitis media with effusion related to ETD, and that their prognosis was consequently poorer than that of patients in other studies. Finally, there was variance in studies of all types of intervention with regard to whether or not an intact tympanic membrane was required, whether or not patients were required to have an abnormal otological examination, and whether or not an abnormal tympanogram was required. In several studies, poor reporting meant that it was unclear which baseline tests were employed and whether or not test results formed part of the inclusion criteria for the study.

Outcome assessment

Assessment methods were not well defined in most studies. This was a particular issue for the primary review outcome of patient reported symptoms. While a majority of the studies reported some information on this outcome, most of the studies, as with baseline assessment, reported only presence, remission or improvement of symptoms, rather than quantifying them using a validated scale. As with baseline assessment and/or inclusion criteria, some studies reported assessment of specific ETD symptoms, while others reported global improvement or improvement in unspecified symptoms. Owing to the level of symptoms experienced at baseline and follow-up being unclear, it was, therefore, also difficult to ascertain whether or not different studies were assessing comparable symptomatology. Exceptions to this were four studies, which all reported that they measured symptom severity before and after treatment using VASs or a form of the ETDQ-7. 20,40,52,55

Variability in the measure used was an issue for other outcomes, although to a lesser degree. Although data on middle ear function were reported by a majority of studies, a number of different tests were used to assess this, including tympanometry, ability to perform the Valsalva manoeuvre, and appearance on otological examination. Most studies which assessed hearing used a recognised measure such as pure-tone audiometry or air–bone gap.

Follow-up

Even where outcomes were consistently reported, a key issue was the variation between studies in duration of follow-up, which made the meaningful synthesis of data between the studies impossible. An extremely wide range in its duration was found. Two of the three studies of pharmacological agents had extremely short follow-up periods of 30 minutes and 1 to 4 hours. 24,25 These were too short for the data obtained to have any clinical relevance. Therefore, further work with appropriate longer-term assessment of efficacy and safety would be required to adequately assess these interventions. Follow-up in the third pharmacological study was reasonable, although relatively short term (6 weeks). 52 Follow-up in the two studies of mechanical devices was short (1 week)40 or unclear. 41

Follow-up in the studies of surgical interventions also varied considerably, from a few weeks to 2 years or longer. In some cases, mean duration of follow-up was reported, with or without an indication of the range of follow-up time, and data appeared to have been aggregated from patients assessed at different time points.

Conversely, some studies reported follow-up data for all or a majority of patients at multiple time points; in some cases, this appeared to demonstrate continuing improvement over time. This may represent a true accrual of higher levels of benefit from surgery over time, or it may be reflective of remission of symptoms due to the natural course of the condition. As all except one of the studies of surgery were uncontrolled studies, and the single controlled study reported very limited data on outcomes for the control group, it is not possible to determine the cause of the apparent improvement over time. Lack of adequate long-term follow-up is a serious concern in relation to surgical interventions such as tuboplasty, where the procedure may have ongoing implications for middle ear function. For some studies, this uncertainty is additional to the difficulty in determining the effect of the assessed intervention when cointerventions have also been administered.

Interventions and cointerventions

For the small number of interventions where there was more than one study, the details of the interventions varied; there were differences in the surgical technique or pressure applied in studies of tuboplasty and balloon dilatation, respectively. In addition to differences in the primary intervention, many of the studies of surgical interventions reported cointerventions administered concurrently with or subsequent to the intervention being assessed. 18,20–23,55,56,61 As many of these cointerventions were additional sinonasal or otological surgical procedures, it is not possible to determine whether the observed treatment benefits are attributable to the primary intervention or to one or more of the additional treatments. The majority of the surgical evidence base was impacted by the use of cointerventions.

In studies of pharmacological agents and devices, cointervention appeared to be less of an issue, with only the RCT of nasal steroids documenting use of additional pharmacological agents. 52 In this instance, the use of cointerventions was recorded and used to inform a secondary analysis of overall efficacy. The extremely short follow-up and laboratory-based design of the other two pharmacological studies means that use of cointerventions appears unlikely. However, because reporting of the other non-surgical studies was, in some cases, limited, it is difficult to be certain that participants did not use cointerventions in the studies of mechanical devices.

MEDLINE In-Process & Other Non-Indexed Citations and MEDLINE via OvidSP: http://ovidsp.ovid.com/

1946 to 4 October 2012.

Searched on 8 October 2012.

Records retrieved: 1345.

1. 1. Eustachian Tube/ (2702)

2. 2. ((eustachian or auditory or pharyngotympanic) adj3 tub$).ti,ab. (2960)

3. 3. (eustachian adj2 (canal or orifice$)).ti,ab. (67)

4. 4. (middle ear adj3 dysfunction$).ti,ab. (121)

5. 5. (middle ear adj3 pressure$).ti,ab. (823)

6. 6. or/1-5 (4399)

Line 6 captures terms for Eustachian tube

1. 7. exp Adrenal Cortex Hormones/ (322,423)

2. 8. exp Steroids/ (672,905)

3. 9. exp Anti-Inflammatory Agents/ (381,776)

4. 10. (adrenal cort$ adj2 hormone$).ti,ab. (864)

5. 11. (corticosteroid$ or cortico steroid$ or corticoid$).ti,ab. (75,248)

6. 12. steroid$.ti,ab. (171,724)

7. 13. glucocorticoid$.ti,ab. (48,091)

8. 14. (anti inflam$ or antiinflam$).ti,ab. (91,002)

9. 15. (fluticason$ or flixonase or flonase or flovent or cultivate or flixotide or atemur or axotide or beconase or cci 18781 or cci18781 or cutivat$ or flixovate or flunase or fluspiral or flutide or flutinase or flutivate or fluxonal or gr 18781 or gr18781 or zoflut).ti,ab,rn. (4575)

10. 16. (budeson$ or pulmicort or horacort or rhinocort or bidien or budecort or budicort or CCRIS 5230 or cortivent or entocort or micronyl or noex or preferid or respules or rhinosol or spirocort or symbicort or uceris).ti,ab,rn. (4372)

11. 17. (mometason$ or sch 32088 or nasonex or rinelon or elocon or allermax aqueous or asmanex or danitin or dermotasone or dermovel or ecural or elica or elocom or elocone or elocyn or elomet or elosalic or eloson or flumeta or mefurosan or metaspray or momate or mometAid or monovel or morecort or motaderm or nosorex or novasone or propel or rimelon or rivelon or uniclar).ti,ab,rn. (1512)

12. 18. (triamcinolone acetonide or tricinolon or cinonide or kenalog or azmacort or kenacort or acetospan or adcortyl A or allerNaze or aristocort or aristoderm or aristogel or CCRIS 5231 or coupe-A or flutex or flutone or kenalone or NSC 21916 or nasacort or omcilon A or oracort or oralone or polcortolon or rineton or solodelf or tramacin or tri-nasal or triacet$ or triacort or triam-Injekt or triamonide or trianex or triatex or triderm or triesence or trivaris or trymex or volon A).ti,ab,rn. (7767)

13. 19. (dexameth$ or adrenocot or aflucoson$ or alfalyl or Anaflogistico or Aphtasolon or arcodexan$ or artrosone or Auxiron or Azium or bidexol or Bisu DS or Calonat or CCRIS 7067 or cebedex or cetadexon or colofoam or corsona or Corsone or cortastat or cortidex$ or cortidron$ or Cortisumman or dacortina fuerte or dacortine fuerte or dalalone or danasone or Decacortin or decadeltoson$ or Decaderm or decadion or decadran or decadron$ or decaesadril or Decagel or decaject or Decalix or decameth or Decasone or decaspray or decasterolone or decdan or decilone or decofluor or Dectancyl or Dekacort or delladec or deltafluoren$ or Dergramin or Deronil).ti,ab,rn. (56,163)

14. 20. (desacort or desacortone or Desadrene or desalark or desameton$ or Deseronil or desigdron or dexa cortisyl or dexa dabrosan or dexa korti or Dexa Mamallet or dexa scherosan or dexa scherozon$ or Dexacort$ or Dexa-Cort$ or dexadabroson or dexadecadrol or Dexadeltone or dexadrol or Dexafarma or dexagel or dexagen or dexahelvacort or dexakorti or dexalien or dexalocal or Dexalona or dexame$ or Dexametasona or dexan or dexane or dexano or Dexapolcort or Dexapos or dexapot or Dexaprol or dexascheroson or Dexa-Scheroson or dexascherozon$ or Dexa-sine or Dexason$ or Dex-ide or Dexinolon or Dexinoral or dexionil or dexona or Dexone or dexpak or Dextelan).ti,ab,rn. (55,444)

15. 21. (dextrasone or Dezone or dibasona or Dinormon or doxamethasone or esacortene or exadion$ or firmalone or fluormethyl prednisolon$ or fluormethylprednisolon$ or Fluormone or Fluorocort or fluorodelta or Fortecortin or Gammacorte$ or grosodexon$ or hexadecadiol or hexadecadrol or hexadiol or hexadrol or Isopto Dex or isopto maxidex or isoptodex or isoptomaxidex or Lokalison F or Loverine or Luxazone or marvidione or maxidex or Mediamethasone or megacortin or mephameson$ or metasolon$ or methazon$ ion or methazonion$ or metisone lafi or mexasone or Mexidex or millicorten$ or Mymethasone or nisomethasona or novocort or NSC 34521 or nsc34521).ti,ab,rn. (74)

16. 22. (Ocu-trol or oftan-dexa or opticorten or opticortinol or oradexan or oradexon$ or orgadrone or Ozurdex or pidexon or Policort or Prednisolon F or prodexon$ or sanamethasone or santenson or santeson or sawasone or solurex or spoloven or sterasone or thilodexine or triamcimetil or vexamet or visumetazone or visumethazone or adrecort or Aeroseb or dexacen or isnacort or methylfluorprednisolone or posurdex).ti,ab,rn. (44)

17. 23. (beclomet$ or aerobec or afifon or Alanase or Aldecin$ or anceron or apo-beclomethasone or ascocortonyl or asmabec clickhaler or Atomase or atomide or beceze or Beclacin or beclamet or beclate or Beclazone or beclo asma or beclo AZU or beclo rhino or becloasma or beclocort or becloforte or beclojet or beclone or beclorhinol or beclosol or beclotaide or becloturmant or becloturmat or beclovent or becodisk$ or beconase or beconasol or becotide or belax or bemedrex).ti,ab,rn. (3437)

18. 24. (Benconase or bronchocort or bronconox or chf 1514 or chf1514 or Clenil or decomit or ecobec or Entyderma or filair or Inalone or junik or Korbutone or Menaderm or miflasone or nasobec aqueous or nexxair or nobec or orbec or prolair or propaderm or qvar or ratioallerg or respocort or rhinivict or Rhino Clenil or Rhinosol or rinaze or rynconox or sanasthmax or sanasthmyl or “sbn 024” or sbn024 or Sch 18020W or Turbinal or vancenase or vanceril or ventolair or viarex or viarin or Viaro or xiten). ti,ab,rn. (141)

19. 25. (betamethasone or betamethason or betnesol or bentelan or rinderon$ or celestone phosphate or beta corlan or beta methasone or betam-ophtal or diprospan or durabetason or etnesol or inflacor or linolosal or linosal or NSC 90616 or solucelestan).ti,ab,rn. (6266)

20. 26. (apo-flunisolide or inhacort or nasalide or ratio-flunisolide or rhinalar or RS-3999 or syntaris or aeroBid or nasarel or aerospan or bronalide or cyntaris or flunitec or flunisolid$ or gibiflu or locasyn or lokilan or lunibron-a or lunis or nisolid or rs3999 or sanergal or soluzione or synaclyn or val 679 or val679).ti,ab,rn. (355)

21. 27. (prednison$ or Adasone or ancortone or Apo-Prednisone or biocortone or Cartancyl or CCRIS 2646 or colisone or Cortan or Cortancyl or cortidelt or cortiprex or Cotone or Cutason or dacorten or Dacortin or de cortisyl or decortancyl or decortin$ or Decortisyl or Dehydrocortisone or dekortin or delitisone or dellacort or delta cortelan or delta Cortisone or delta dome or delta e or delta prenovis or delta-1-Cortisone or delta-1-Dehydrocortisone or deltacort$ or delta-dome or Deltasone or deltison$ or deltra or di adreson or diadreson or drazone or Econosone or Encorton$).ti,ab,rn. (43,824)

22. 28. (Enkortolon or enkorton or fernisone or Fiasone or hostacortin or HSDB 3168 or Incocortyl or insone or IN Sone or Juvason or Kortancyl or Liquid Pred or Lisacort or lodotra or Lodtra or me-korti or meprison or metacortandracin or Meticorten or meticortine or NCI-C04897 or nisona or Nizon or Novoprednisone or nsc 10023 or nsc10023 or Nurison or Orasone or orisane or Panafcort or Panasol or paracort or Parmenison or pehacort or precort or precortal).ti,ab,rn. (135)

23. 29. (Predni Tablinen or prednicen-m or prednicorm or Prednicort or prednicot or Prednidib or Prednilonga or Predniment or prednitone or Prednizon or Prednovister or Presone or pronison or Pronisone or pronizone or pulmison or Rectodelt or Retrocortine or servisone or SK-Prednisone or steerometz or Sterapred or Supercortil or U 6020 or Ultracorten$ or urtilone or Winpred or Wojtab or Zenadrid).ti,ab,rn. (50)

24. 30. (methylprednisolon$ or adlone-40 or adlone-80 or A-Methapred or Artisone-wyeth or Besonia or BRN 2340300 or dep medalone 80 or depmedalone or depoject-80 or Depo-Medrol or depopred or Dopomedrol or esametone or firmacort or HSDB 3127 or Lemod or Medesone or medixon or med-jec-40 or Medlone 21 or mednin or medralone 80 or medrate or Medrol or medrone or meprednisolone or mesopren or Metastab or methacort 40 or methacort 80 or methylcotol or methylcotolone or Methyleneprednisolone or methylpred dp or methylsterolone or metidrol).ti,ab,rn. (19,994)

25. 31. (Metilbetasone or Metilprednisolon$ or Metipred or metrisone or Metrocort or metycortin or metypred or metypresol or Metysolon or Moderin or neomedrone or Nirypan or Noretona or nsc 19987 or nsc19987 or Predni N Tablinen or prednol or Promacortine or Reactenol or Sieropresol or solomet or solu decortin or Solu-medrol or Summicort or Suprametil or U 7532 or U-67 590A or Urbason or Urbasone or Wyacort).ti,ab,rn. (195)

26. 32. (Prednisolon$ or adelcort or antisolon or antisolone or aprednislon or aprednislone or benisolon or benisolone or berisolon or berisolone or BRN 1354103 or Bubbli-Pred or caberdelta or capsoid or CCRIS 980 or co hydeltra or codelcortone or CO-Hydeltra or compresolon or Cordrol or cortadeltona or cortadeltone or cortalone or cortelinter or cortisolone or Cotogesic or cotolone or dacrotin or ecaprednil or decortril or dehydro cortex or dehydro hydrocortisone or dehydro hydrocortisone or dehydrocortex or dehydrocortisol or dehydrocortisole or dehydrohydrocortison).ti,ab,rn. (36,518)

27. 33. (dehydrohydrocortisone or delcortol or delta cortef or delta cortril or delta ef cortelan or delta f or delta hycortol or delta hydrocortisone or delta hydrocortisone or delta ophticor or delta stab or delta1 dehydrocortisol or delta1 dehydrohydrocortisone or delta1 hydrocortisone or deltacortef or delta-cortef or Deltacortenol or deltacortenolo or deltacortil or deltacortoil or deltacortril or deltaderm or delta-Ef-Cortelan or deltaglycortril or deltahycortol or deltahydrocortison or deltahydrocortisone or deltaophticor or deltasolone or deltastab or deltidrosol or deltisilone).ti,ab,rn. (750)

28. 34. (deltisolon or deltisolone or deltolasson or deltolassone or deltosona or deltosone or depo-predate or dermosolon or Derpo PD or Dexa-Cortidelt or hostacortin H or dhasolone or diadresone f or DiAdresonF or dicortol or domucortone or Donisolone or Dydeltrone or Eazolin D or encortelon or encortelone or encortolon or Erbacort or Erbasona or Estilsona or Fernisolone or glistelone or hefasolon or HSDB 3385 or hydeltra or hydeltrone or hydrelta or hydrocortancyl or hydrocortidelt or hydrodeltalone or hydrodeltisone or hydroretrocortin or hydroretrocortine or inflanefran).ti,ab,rn. (22)

29. 35. (insolone or K 1557 or keteocort or key-pred or lenisolone or Lentosone or leocortol or liquipred or lygal kopftinktur or mediasolone or meprisolon or meprisolone or metacortalon or metacortalone or metacortandralon or metacortandralone or metacortelone or meti derm or meticortelone or metiderm or meti derm or morlone or mydrapred or neo delta or nisolon or nisolone or nsc 9120 or nsc9120 or opredsone or Orapred or panafcortelone or panafort or paracortol or Paracotol or Pediapred or phlogex or PRDL or pre cortisyl).ti,ab,rn. (34)

30. 36. (preconin or precortalon or precortancyl or Precortilon or precortisyl or predacort 50 or predaject-50 or predalone 50 or predartrina or predartrine or Predate or predeltilone or predisole or predisyr or pred-ject-50 or predne dome or prednecort or prednedome or Predne-Dome or prednelan or predni coelin or predni h tablinen or Prednicen or prednicoelin or prednicortelone or prednifor drops or predni-helvacort or Predniliderm or predniment or predniretard or prednis or prednisil or prednivet or prednorsolon or prednorsolone or Predonin or Predonine or predorgasolona or predorgasolone).ti,ab,rn. (28,673)

31. 37. (prelon or prelone or prenilone or prenin or prenolone or preventan or prezolon or Rolisone or rubycort or scherisolon or scherisolona or serilone or solondo or solone or solupren or soluprene or spiricort or spolotane or Steran or sterane or sterolone or supercortisol or supercortizol or taracortelone or Ulacort or walesolone or wysolone).ti,ab,rn. (64)

32. 38. or/7-37 (1,058,233)

Line 38 captures terms for steroids

1. 39. 6 and 38 (106)

Line 39 combines terms for Eustachian tube and terms for steroids

1. 40. exp Nasal Decongestants/ (15,904)

2. 41. Imidazoles/ (38,412)

3. 42. Nasal Sprays/ (108)

4. 43. (xylometazolin$ or Balkis or Chlorohist-LA or Decongest or espa-rhin or Gelonasal or Idasal or Idril N or Nasan or Imidin or NasenGel or NasenTropfen or NasenSpray or Novorin or Otradrops or Otraspray or Otrivin or Otriven$ or Rapako or schnupfen endrine or Snup or stas or Amidrin or Neo-Synephrine II or Olynth or Otrivine or Rhinactin or ba 11391 or ba11391 or “brn 0180524” or brufasol or otrovin hcl or servilaryn or tixycold or xylometarzoline or xylometazonolin$ or xylomethazoline or xilometazolin$ or zylometazoline or otrix).ti,ab,rn. (464)

5. 44. (cirazolin$ or LD 3098).ti,ab,rn. (408)

6. 45. (naphazolin$ or Afazol Grin or AK Con or AKCon or Albalon or albasol or All Clear or allersol or alpha-Naphthylmethyl imidazoline or antan or benil or “BRN 0151864” or cefasan or Ciba 2020 or Clear Eyes or Clearine or coldan or Colirio Alfa or comfort eye drops or dazolin or degest 2 or derinox or Idril or imidin or minha or Miraclar or mirafrin or Nafazair or Nafazolin$ or naphacel ofteno or naphasal or Naphcon or naphozoline hydrochloride or naphtears or naphthazoline or naphthizine).ti,ab,rn. (665)

7. 46. (naphthyzin or nastizol or nazil ofteno or niazol or ocu-zoline or opcon or Optazine or Privin$ or Proculin or rhinantin or rhinazin or rhinoperd or rimidol or sanorin or sanotin or Siozwo or strictylon or Tele Stulln or TeleStulln or Vasoclear or Vasocon or Vasoconstrictor Pensa or VasoNit or vistalbalon or vistobalon).ti,ab,rn. (15,396)

8. 47. (Oxymetazolin$ or afrazine or afrin or atomol or bayfrin or “BRN 0886303” or dristan or drixine or duramist plus or H 990 or Hazol or HSDB 3143 or Iliadin or iliadine or Nafrine or nasivin or Navisin or Nezeril or nostrilla or ocuclear or Oximetazolin$ or Oxylazine or Oxymethazoline or Rhinofrenol or rhinolitan or rhinosan or sch 9384 or Sinerol or sinex long last or sinex or visine).ti,ab,rn. (991)

9. 48. (Phenylephrin$ or adrianol or af-taf or Ah-Chew or AI3-02402 or ak-dilate or albalon relief or alconefrin or almefrin or biomidrin or biomydrin or CCRIS 8464 or derizene or despec-sf or disneumon pernasal or dristan nasal mist or drosin or efrin-10 or efrisel or fenylephrine or HSDB 3383 or idrianol or isonefrine or isophrin or isopto frin or isoptofrin or l meta synephrine or lexatol or m synephrine or mesaton$ or meta sympathol or meta synephrine or metaoxedrin$).ti,ab,rn. (19,182)

10. 49. (Metasympatol or metasynephrine or Mezaton or m-Methylaminoethanolphenol or m-Oxedrine or m-Sympathol or m-Sympatol or m-Synephrine or mydfrin or nefrin-ofteno or Neo Synephrine or neofrin or neooxedrine or neophryn or neosynephrin or neosynephrine or neosynesin or neosynesine or ocu-phrin or oftan-metaoksedrin or op-isophrin or optistin or phenoptic or phenylefrine or phenylephedrine or prefrin or pupiletto forte or rectasol or rhinall 10 or slv 325 or slv325 or sucraphen or visadron or vistafrin or vistosan).ti,ab,rn. (212)

11. 50. (Phenylpropanolamin$ or acutrim or apodrine or apoephedrine or apophedrine or appedrine or BRN 3196918 or descon or Dexatrim or dexatrim or diet gard or dietac premeal or HSDB 6485 or kontexin or monydrin or Mucron or mydriatin or nobese or Norephedrine or NSC 9920 or phenyl propanolamine or phenylpropanolamide or PPA or pressedrine or procol or Prolamine or propadine or propadrine or Propagest or Rhindecon or Super Odrinex or trimolet).ti,ab,rn. (4543)

12. 51. (Pseudoephedrin$ or acunaso or afrinol or Besan or dimetapp or d-Isoephedrine or drixora or Ephedrine or HSDB 3177 or Isoephedrine or isofedrine or isophedrine or logicin plus or monofed or nasa-12 or novafed or otrinol or pseudo ephedrine or pseudo-12 or Pseudoefedrina or pseudono or Psi-ephedrin or repedrina or rhinalair or sch 4855 or sch4855 or sinumed or sinutab or subulin or Sudafed or sudomyl or sudosian or symptofed or tiptipot).ti,ab,rn. (5861)

13. 52. (Synephrin$ or Sympaethamin$ or Oxedrine or aetaphen or asthma spray spofa or pentedrine or vasoton or Analeptin or DL-Synephrine or Ethaphene or NSC 166285 or NSC 170956 or Parakorper or Parasympatol or S 38537-9 or Simpalon or Simpatol or Sympathol or Sympatol or Synefrin or Synthenate or p-Hydroxyphenylmethylaminoethanol or p-Methylaminoethanolphenol or p-Oxedrine or p-Synephrine).ti,ab,rn. (8094)

14. 53. (tetrahydrozolin$ or tetryzoline or Caltheon or Collyrium Fresh or Diabenyl T or Eye-Sine or Eye-Zine or Murine Plus or Murine Sore Eyes or Ophtalmin or Optazine Fresh or Optigene or Rhinopront or Tetra-Ide or Tetraclear or Tetrilin or Tyzine or Vasopos or Visine or Yxin or Vispring or Berberil N or “BRN 0011442” or HSDB 7471 or Tetrizolin$ or Tyzanol or clarine or insto or murine tears or murine-2 or nasan or nazane or nazine or necor tyzine or octilia or ophthalmin-n or opsil-a or optizoline or rhinoprout or stilla drops or visina or visolin).ti,ab,rn. (192)

15. 54. (brompheniramine or Bromfed or Lodrane or Dimetapp).ti,ab,rn. (354)

16. 55. (decongestant$ or decongestive$).ti,ab. (1474)

17. 56. ((nasal or nose) adj2 (spray$ or mist or aerosol$)).ti,ab. (2359)

18. 57. or/40-56 (92,301)

Line 57 captures terms for decongestants

1. 58. 6 and 57 (71)

Line 58 combines terms for Eustachian tube and terms for decongestants

1. 59. exp Histamine Antagonists/ (53989)

2. 60. (anti histamin$ or antihistamin$).ti,ab. (10,920)

3. 61. (histamine adj3 (antagonist$ or block$)).ti,ab. (5986)

4. 62. ((H1 or H2 or H3 or H4) adj2 (antagonist$ or block$)).ti,ab. (10,245)

5. 63. (acrivastin$ or semprex or semprex-D or benadryl or prolert or BW 825C or BW825C or BW A825C).ti,ab,rn. (365)

6. 64. (bilastine or bilaxten or f 96221 bm1 or f96221 bm1).ti,ab,rn. (35)

7. 65. (Cetirizin$ or acidrine or adezio or agelmin or Alercet or Alergex or Alerid or Alerlisin or Alertisin or alertop or alerviden or aletir or alled or Allergy relief or Alleroff or allertec or alltec or alzytec or Apo-Cetirizine or betarhin or cerazine or cerini or cerotec or cesta or Cetalerg or Ceterifug or cethis or Ceti TAD or Cetiderm or Cetidura or Cetil von ct or CetiLich or cetimin or cetin or Ceti-Puren or cetirax or Cetirigamma or cetirin or Cetirlan or cetizin or Cetriler or cetrimed or Cetrine or cetrizet or cetrizin or Cetryn or cetymin or Cetzine or Cezin or cistamine or deallergy or falergi or finallerg or Formistin or histazine or histica or Hitrizin or HSDB 7739).ti,ab,rn. (1453)

8. 66. (incidal-od or lergium or nosemin or nosmin or ozen or “P 071” or P071 or prixlae or razene or Reactine or Ressital or rhizin or risima or Riztec or ryvel or Ryzen or Salvalerg or sancotec or selitex or Setir or Setiral or setizin or simtec or Stopaler or Sun mark all day allergy or sutac or symitec or terizin or terzine or Topcare all day allergy or Triz or “UCB-P 071” or vick-zyrt or Virdos or Virlix or Voltric or Xero-sed or zenriz or zensil or zeran or zertine or Zetir or zicet or zinex or Ziptek or zirtec or Zirtek or Zirtin or zyllergy or zymed or zyrac or zyrazine or zyrcon or zyrlex or Zyrtec or Zyrtec-D or zyrtek or Zyrzine).ti,ab,rn. (1556)

9. 67. (desloratadine or clarinex or aerius or neoclarityn or azomyr or denosin or SCH 34117 or allex or aviant or claramax or dasselta or decarbethoxyloratadine or desalex or descarboethoxyloratadine or deslor or neoclaritine or sch34117 or supraler).ti,ab,rn. (465)

10. 68. (fexofenadine or allegra or telfast or Carboxyterfenadine or MDL 16455A or mdl 16455 or mdl16455).ti,ab,rn. (684)

11. 69. (levocetirizine or xusal or xyzal).ti,ab,rn. (251)

12. 70. (loratadin$ or aerotina or Alarin or Alavert or alerfast or alernitis or Alerpriv or alertadin or allerta or Allertidin or allertyn or allohex or ambrace or analergal or anhissen or anlos or ardin or Bactimicina allergy or Biloina or bonalerg or caradine or carin or civeran or clalodine or claratyne or clarid or Clarinase or Claritin or claritine or clarityn or clarityne or Clarium or cronitin or cronopen or curyken or demazin anti-allergy or ezasmin or ezede or finska or frenaler or fristamin or genadine or halodin or hislorex or histalor or histaloran or HSDB 3578 or j-tadine or klarihist or klinset or laredine or lergia or Lergy or lertamine or Lesidas or lindine or lisino or lisono or lobeta or lodain or lorabasics or loracert or loraclar or loraderm or loradex).ti,ab,rn. (3041)

13. 71. (Loradif or loradin or lorahist or loralerg or lora-lich or lorano or loranox or Loranox or Lorantis or lorastine or lora-tabs or loratadura or loratan or loratazine or loratidin or loratidine or loraton or loratrim or loratyne or Loraver or loreen or lorfast or lorihis or lorin or lorita or Loritine or lotadine or lotarin or lowadina or mosedin or noratin or notamin or Nularef or onemin or optimin or polaratyne or proactin or pylor or restamine or Rhinase or ridamin or rihest or rinityn or Rinomex or rityne or roletra or rotifar or Sanelor or Sch 29851 or Sch29851 or sensibit or Sinhistan Dy or sohotin or Tadine or Talorat Dy or tidilor or tirlor or Topcare or toradine or velodan or versal or voratadine or zeos).ti,ab,rn. (93)

14. 72. (mizolastin$ or zolistan or mistamine or mistalin or mizollen or zolim or mizolen or “SL 85 0324” or CCRIS 8410 or mkc 431 or sl 850324).ti,ab,rn. (115)

15. 73. (rupatadine or rupafin or UR 12592 or UR12592).ti,ab,rn. (70)

16. 74. (Chlorphenamin$ or 4-Chloropheniramine or ahiston or alerfin or alergical or alergidryl or alergitrat or alermine or aller or Aller-Chlor or Allerclor or allerfin or Allergican or Allergin or Allergisan or allergyl or allermin or allerphen or Alunex or analerg or anaphyl or Antagonate or antamin or apomin or barominic or cadistin or Carbinoxamide maleate or CCRIS 1418 or Chlo-Amine or chlometon or chlor trimeton or Chlor-100 or chloramate unicelles or chlorleate or Chlormene or chlorophenamine maleate or Chloropheniramine or Chlorophenylpyridamine or Chloropiril).ti,ab,rn. (4230)

17. 75. (Chloroprophenpyridamine or chloroton or Chlorpheniramin$ or chlorpheno or chlorphenon or Chlorpro or Chlorprophenpyridamine or chlorpyrimine or Chlorspan 12 or Chlortab-4 or chlortrimeton or Chlor-Trimeton or chlortripolon or Chlor-Tripolon or Clorfenamina or Clorfeniramina or cloro trimeton or cloroalergan or Cloropiril or clorotrimeton or Cloro-Trimeton or C-Meton or cohistan or com-trimeton or Dehist or dl-Chlorpheniramine maleate or Efidac 24).ti,ab,rn. (13,363)

18. 76. (clemastin$ or meclastin$ or neclastine or mecloprodin or tavist or tavegyl or HS 592 or HS592).ti,ab,rn. (463)

19. 77. (cyproheptadine or adekin or Antergan or antisemin or apeton 4 or astonin or BRN 1685976 or CCRIS 5232 or ciplactin or cipractin or ciproeptadine or Ciproheptadina or ciproral or ciprovit-a or cryoheptidine or crypoheptadine or cyheptine or cylat or cypraheptidine or cypro h or cyproatin or cyprogin or cyprohaptadi$ or cypromin or cyprono or cyprosian or cytadine or Dihexazin or Dronactin or Eiproheptadine or ennamax or glocyp or heptasan or HSDB 3048 or ifrasal or istam-far or klarivitina or kulinet or MK 141 or nuran or Periact$ or Peritol or petina or pilian or pronicy or sinapdin or trimetabol or Viternum).ti,ab,rn. (2968)

20. 78. (ketotifen$ or ketotiphen$ or zaditen or zaditor or BRN 3983897 or HC 20 511 or hc 20511 or HSDB 7283).ti,ab,rn. (1472)

21. 79. (Prometh$ or 3277 RP or A-91033 or adgan or Allerfen or allergan or Anergan 25 or Anergan 50 or antiallersin or antinaus 50 or Aprobit or Atosil or Avomine or baymethazine or Bonnox or “BRN 0088554” or Camergan or CCRIS 5873 or CCRIS 7056 or Closin or dimapp or Dimethylamino-isopropyl-phenthiazin or Diphergan or Diprasine or Diprazin$ or diprozin or Dorme or Duplamin or Eusedon Mono or fargan or Farganesse or Fellozine or fenazil or fenazine or Fenergan or Fenetazin$ or Frinova or Ganphen or Hibechin or hiberna or Histantil or Histargan or HL 8700 or HSDB 3173 or insomn-eze or Isophenergan or Isopromethazine or Kinetosin or lercigan or Lergigan or lergigan or “Lilly 01516” or Lilly 1516 or Metaryl or Mymethazine Fortis or NCI-C60673 or NSC 231688).ti,ab,rn. (4507)

22. 80. (NSC 30321 or Pelpica or pentazine or phargan or Phenadoz or Phenargan or Phencen or Phenergan or Phenerzine or phenoject-50 or Phensedyl or Pilothia or Pipolfen or Pipolphen$ or Plletia or pm 284 or Primine or Pro-50 or Proazamine or procit or promacot or Promantine or promazinamide or Prome or Promergan or Promesan or Promet or Prometazin or Prometazina or Prometh$ or Promezathine or Promine or Proneurin or Prorex or protazine or Prothazin or Prothiazine or prothazine or provigan or Provigan or Pyrethia or Pyrethiazine or Remsed or Romergan or rp 3277 or rp 3389 or Rumergan or sayomol or SKF 1498 or Soporil or tanidil or thiergan or V GAN or vallergine or WY 509 or Zipan-25 or Zipan-50).ti,ab,rn. (4091)

23. 81. or/59-80 (82,509)

Line 81 captures terms for anti-histamines

1. 82. 6 and 81 (45)

Line 82 combines terms for Eustachian tube and terms for anti-histamines

1. 83. Simethicone/ (270)

2. 84. (simethicone or Antifoam A or Antifoam AF or DC antifoam A or Disflatyl or Gas-X or gas relief or HSDB 3906 or Mylanta or mytab gas or Phazyme or Sab Simplex or Simeticone or dimethicone or digel or flatulex or infacol or lefax or minifom or mylicon or silain or Alka-Seltzer Anti-Gas or Colic Drops or Colicon or Degas or Gas Aide or Genasyme or Maalox Anti-Gas or Majorcon or Micon-80 or Mylaval or SonoRx or WindEze or Wind-Eze).ti,ab,rn. (513)

3. 85. 83 or 84 (513)

Line 84 captures terms for simethicone

1. 86. 6 and 85 (0)

Line 86 combines terms for Eustachian tube and terms for simethicone

1. 87. exp Nasal Lavage/ (960)

2. 88. Therapeutic Irrigation/ (14,655)

3. 89. ((nasal or nose) adj3 (douch$ or irrigat$ or lavage)).ti,ab. (1345)

4. 90. (saline adj3 (douch$ or irrigat$ or lavage)).ti,ab. (1689)

5. 91. or/87-90 (17,313)

Line 87 captures terms for nasal irrigation

1. 92. 6 and 91 (37)

Line 92 combines terms for Eustachian tube and terms for nasal irrigation

1. 93. Leukotriene Antagonists/ (2568)

2. 94. (leukotriene adj3 (antagonist$ or block$ or inhibitor$)).ti,ab. (2975)

3. 95. (montelukast or Singulair or Montelo-10 or montair or montek or montus or romilast or “MK 0476” or mk 476 or mk0476 or mk476 or l 706631 or l706631).ti,ab,rn. (1580)

4. 96. (zafirlukast or Accolate or accoleit or Olmoran or Aeronix or respix or vanticon or zafirst or zuvair or ICI 204,219 or ICI 204219).ti,ab,rn. (492)

5. 97. (pranlukast or azlaire or ultair or ONO 1078 or SB 205312 or SB205312 or ONO RS 411 or rs411 or rs 411).ti,ab,rn. (404)

6. 98. (zileuton$ or A 64077 or A64077 or Abbot 64077 or cgs 23622 or cgs23622 or Zyflo or Leutrol).ti,ab,rn. (518)

7. 99. or/93-98 (5395)

Line 99 captures terms for leukotriene antagonists

1. 100. 6 and 99 (0)

Line 100 combines terms for Eustachian tube and terms for leukotriene antagonists

1. 101. Chewing Gum/ (1895)

2. 102. Xylitol/ (1868)

3. 103. (Xylitol or BRN 1720523 or Eutrit or HSDB 7967 or Kannit or Klinit or NSC 25283 or Newtol or Xylite or Xylitol or Xyliton or xylit).ti,ab,rn. (2740)

4. 104. or/101-103 (4411)

Line 104 captures terms for xylitol

1. 105. 6 and 104 (0)

Line 105 combines terms for Eustachian tube and terms for xylitol

1. 106. exp Anti-Infective Agents/ (1,191,754)

2. 107. (anti bacterial$ or antibacterial$ or anti biotic$ or antibiotic$ or anti mycobacterial$ or antimycobacterial$ or bacteriocid$).ti,ab. (241,072)

3. 108. (anti infective$ or antiinfective$ or anti microbial$ or antimicrobial$ or microbicide$).ti,ab. (84764)

4. 109. (doxycyclin$ or adoxa or alpha-Doxycycline or amermycin or atrax or azudoxat or bactidox or banndoclin or basedillin or bassado or biocolyn or biodoxi or bmy 28689 or bmy28689 or bronmycin or bu 3839t or bu3839t or cloran or cyclidox or dentistar or deoxycycline or deoxymycin dispersal or deoxymykoin or deoxyoxytetracycline or desoxy oxytetracycline or desoxycycline or doinmycin or doryx or dosil or Dossiciclina or dotur or doxaciclin or doxacycline or doxat or doxatet or doxibiotic or Doxiciclina or doxicycline or doxilin or doximed or doximycin or doxin or doxine or doxi-sergo).ti,ab,rn. (11242)

5. 110. (Doxitard or Doxivetin or doxocycline or doxsig or doxy or doxy-1 or doxybiocin or doxy-caps or doxycen or doxychel or doxycin or doxycydine monohydrate or doxylag or doxylin or doxymycin or doxypuren or Doxy-Puren or Doxysol or doxytec or Doxytetracycline or doxytrim or dumoxin or duracycline or esdoxin or etidoxina or gewacyclin or gs 3065 or HSDB 3071 or hydramycin or ibralene or idocyclin or idocyklin or interdoxin or investin or Liviatin or longamycin or lydox or magdrin or medomycin or mespafin or mildox or miraclin or monodox or nordox or novum vibramycin).ti,ab,rn. (7033)

6. 111. (nsc 56228 or oracea or paldomycin or pernox gel or radox or remycin or respidox or Ronaxan or roximycin or serodoxy or servidoxine or servidoxyne or siadocin or siclidon or sigadoxin or spanor or supracyclin or supramycina or tenutan or tolexine or torymycin or tsurupioxin or unidox or veemycin or viadoxin or vibra$ or viradoxyl-n or wanmycin or zadorin).ti,ab,rn. (42,398)

7. 112. (amoxicil$ or a gram or abdimox or acilina or acimox or actimoxi or adbiotin or agerpen or agram or a-gram or alfamox or alfoxil or almodan or almorsan or alphamox or amagesen solutab or ameclina or amocillin or amoclen or amodex or amo-flamisan or amoflux or amohexal or amolin or amonex or amopen or Amopenixin or amophar ge or amosine or amoval or amoxa or amoxal or amoxapen or amoxaren or amoxcil or amoxcillin or amoxcin or Amoxi or amoxi-basan or Amoxicaps or amoxiclin or amoxicot or amoxidal or Amoxiden or amoxidin or amoxidrops or amoxihexal or amoxil$).ti,ab,rn. (19,750)

8. 113. (Amoxi-Mast or amoxipen or amoxipenil or amoxisol or amoxivan or amoxivet or Amoxivet or amoxy or Amoxycillin$ or amoxy-diolan or amoxypen or AMPC or ampliron or Ampy-Penyl or Anemolin or apo-amoxi or ardine or aroxin or Aspenil or azillin or bacihexal or bactamox or bactox ge or beamoxy or betamox or bimox or bintamox or biomox or biotamoxal or bioxidona or bioxyllin or BLP 1410 or bristamox or brl 2333 or brl2333 or broadmetz or cabermox or Cemoxin or cilamox or clamox or clamoxyl or clearamox or clonamox or coamoxin or damoxicil or D-Amoxicillin or Delacillin).ti,ab,rn. (4247)

9. 114. (dispermox or doxamil or draximox or edamox or Efpenix or erphamoxy or eupen or farconcil or fisamox or flemoxin or fluamoxina or foxolin or fullcilina or gexcil or gimalxina or glamox or glassatan or gomcillin or grinsul or grunamox or hamoxillin or hiconcil or hidramox or hipen or Histocillin or hosboral or HSDB 3204 or Hydroxyampicillin or ibamox or ibiamox or ikamoxil or imacillin or imaxilin or inamox or infectomycin or intermox or isimoxin or izoltil or julphamox or jutamox or kamoxin or ladoxillin or lamoxy or larocilin or larocin or larotid or macromox or magnimox or maxamox or maxcil).ti,ab,rn. (21)

10. 115. (medimox or meixil or Metafarma or metifarma or mopen or morgenxil or moxacin or Moxal$ or moxarin or Moxatag or moxilen or moxilin or moximar or moxitab or moxtid or moxylin or moxypen or moxyvit or neogram or novabritine or novamox or novamoxin or novenzymin or novoxil or NSC 277174 or nuvosyl or optium or ospamox or pamocil or pamoxicillin or pamoxin or panvilon or pasetocin or penamox or penbiosyn or pentyloxycillin or pharmoxyl or p-Hydroxyampicillin or piramox or polymox or pondnoxcill or rancil or ranmoxy or ranoxil or ranoxyl or Ro 10-8756).ti,ab,rn. (1540)

11. 116. (robamox or romoxil or ronemox or saltermox or sawacillin or sawamezin or Sawamox PM or servamox or shamoxil or sia-mox or sigamopen or silamox or sil-a-mox or simoxil or solpenox or sumox or superpeni or teramoxyl or tolodina or tormoxin or triafamox or triamoxil or trifamox or trimox or Unicillin or uro clamoxyl or uroclamoxyl or utimox or vastamox or velamox or Vetramox or vistrep or widecillin or winpen or wymox or Wymox or Wymox or xiltrop or zamocillin or zamox or zamoxil or zerrsox or zimox).ti,ab,rn. (14)

12. 117. (clarith$ or A 56268 or A56268 or abbotic or abbott 56268 or Adel or aeroxina or Astromen or bactirel or baxin filmtab or Biaxin or biclar or bicrolid or binoklar or bremon or carimycin or c-clarin or CCRIS 8833 or celex or clacin or clacine or clambiotic or clapharma or claribid or Claricide or claridar or clarimac or claripen or claritrol or Claritromicina or claroma or Clathromycin or clormicin).ti,ab,rn. (7366)

13. 118. (crixan or cylind or Cyllid or cyllind or dicupal or DRG-0099 or er 36469 or er36469 or gervaken or hecobac or Helas or heliclar or helitic or klacid or klacina or klaciped or klaribac or klaricid or Klarid or klaridex or klaridia or klarin or Klax or klerimed or kofron or lagur or Mabicrol or macladim or macladin or maclar or mavid or monozeclar or naxy or “TE 031” or TE031 or veclam or zeclar).ti,ab,rn. (101)

14. 119. (moxif$ or Actira or Avalox or avelon or Avelox or Avolex or BAY 12 8039 or BAY 128039 or bay128039 or CCRIS 8690 or Izilox or megaxin or moxeza or Octegra or Proflox or vigamox).ti,ab,rn. (2639)

15. 120. (Telithromycin or Ketek or RU 66647 or HMR 3647 or HMR3647 or levviax or ru 647 or ru 66647 or ru647 or ru66647).ti,ab,rn. (855)

16. 121. (azithromycin$ or Aritromicina or aruzilina or atizor or Azadose or azasite or azenil or azimin or azithral or Azitrocin or azitromax or Azitromicine or aziwok or azomyne or aztrin or Azythromycin or BRN 5387583 or CCRIS 1961 or cp 62933 or cp62933 or DRG-0104 or forcin or Goxal or Hemomycin or HSDB 7205 or inedol or isv 401 or isv401 or kromicin or macrozit or mezatrin or Misultina).ti,ab,rn. (5129)

17. 122. (Mixoterin or octavax or Setron or Sumamed or sunamed or Tobil or tobyl or Toraseptol or tromix or Trulimax or Ultreon or Vinzam or xithrone or xz 450 or xz450 or zaret or zarom or Zentavion or Zeto or zibramax or zifin or zimericina or zistic or Zithrax or Zithromax or zithrox or zitrim or zitrobifan or Zitromax or Zitrotek or Zmas or zmax or Z-Pak).ti,ab,rn. (401)

18. 123. or/106-122 (1,349,743)

Line 123 captures terms for antibiotics

1. 124. 6 and 123 (270)

Line 124 combines terms for Eustachian tube and terms for antibiotics

1. 125. Balloon Dilation/ (13,893)

2. 126. Dilatation/ (7905)

3. 127. Dilatation, Pathologic/ (8128)

4. 128. Catheterization/ (31,341)

5. 129. Catheterization, Peripheral/ (5862)

6. 130. catheter$.ti,ab. (142,557)

7. 131. dilat$.ti,ab. (101,802)

8. 132. (BET or BDET).ti,ab. (4975)

9. 133. tuboplast$.ti,ab. (182)

10. 134. exp Laser Therapy/ (46,697)

11. 135. exp Lasers/ (36,258)

12. 136. laser$.ti,ab. (163,455)

13. 137. LETP.ti,ab. (5)

14. 138. Middle Ear Ventilation/ (1984)

15. 139. (tympanostom$ or tympanotom$).ti,ab. (1435)

16. 140. grommet$.ti,ab. (453)

17. 141. ((ventilat$ or aerat$) adj4 ear$).ti,ab. (1472)

18. 142. ((ventilat$ or aerat$) adj4 tub$).ti,ab. (2404)

19. 143. (pressur$ adj3 tub$).ti,ab. (1460)

20. 144. ear tube$.ti,ab. (67)

21. 145. PE tube$.ti,ab. (43)

22. 146. T tube$.ti,ab. (2251)

23. 147. (transtubal or trans tubal).ti,ab. (60)

24. 148. (myringotom$ or myringocentesis).ti,ab. (1163)

25. 149. (paracentesis or tympanocentesis).ti,ab. (2556)

26. 150. ((eardrum$ or ear drum$ or tympan$) adj3 (punctur$ or tap$)).ti,ab. (23)

27. 151. or/125-150 (459,729)

Line 151 captures terms for types of surgery

1. 152. 6 and 151 (931)

Line 152 combines terms for Eustachian tube and terms for surgery

1. 153. Valsalva Maneuver/ (3361)

2. 154. Insufflation/ (1366)

3. 155. Yawning/ (533)

4. 156. Mastication/ (7711)

5. 157. Deglutition/ (6665)

6. 158. Watchful Waiting/ (561)

7. 159. valsalva$.ti,ab. (6721)

8. 160. (autoinflat$ or auto inflat$).ti,ab. (73)

9. 161. (insufflat$ or autoinsufflat$ or auto insufflat$).ti,ab. (5159)

10. 162. (inflat$ adj4 ear$).ti,ab. (117)

11. 163. Politzer$.ti,ab. (124)

12. 164. ((equalis$ or equaliz$ or normalis$ or normaliz$) adj5 pressure$).ti,ab. (3810)

13. 165. (yawn$ or swallow$ or chew$ or masticat$ or deglutition).ti,ab. (36,922)

14. 166. (watch$ adj2 wait$).ti,ab. (1809)

15. 167. (wait adj2 see).ti,ab. (873)

16. 168. (active$ adj2 observ$).ti,ab. (1012)

17. 169. conservative.ti,ab. (68,251)

18. 170. (management adj2 (decision$ or option$ or choice$)).ti,ab. (9031)

19. 171. (support$ adj4 (care or caring)).ti,ab. (19,380)

20. 172. ((standard or usual) adj3 care).ti,ab. (23,669)

21. 173. (advice or advis$).ti,ab. (69192)

22. 174. or/153-173 (247,702)

Line 174 captures terms for supportive care/advice

1. 175. 6 and 174 (603)

Line 175 combines terms for Eustachian tube and terms for supportive care/advice

1. 176. 39 or 58 or 82 or 86 or 92 or 100 or 105 or 124 or 152 or 175 (1562)

2. 177. exp animals/ not humans/ (3,791,654)

3. 178. 176 not 177 (1345)

Line 178 is the final set of records retrieved excluding animal studies

Bioscience Information Service Previews via Dialog: www.dialog.com/

1993–2012, September week 5.

Searched on 5 October 2012.

Records retrieved: 139.

Bioscience Information Service Previews via ISI Web of Knowledge: www.isinet.com/

1969–2008.

Search on 9 October 2012.

Records retrieved: 692.

Cochrane Central Register of Controlled Trials via Wiley: http://onlinelibrary.wiley.com/

Issue 9 of 12, September 2012.

Search date: 8 October 2012.

Records retrieved: 106.

ID Search

#1 MeSH descriptor: [Eustachian Tube] this term only

#2 ((eustachian or auditory or pharyngotympanic) near/3 tub*):ti,ab,kw

#3 (eustachian near/2 (canal or orifice*)):ti,ab,kw

#4 ((middle next ear) near/3 pressure*):ti,ab,kw

#5 ((middle next ear) near/3 dysfunction*):ti,ab,kw

#6 #1 or #2 or #3 or #4 or #5

Cochrane Database of Systematic Reviews via Wiley: http://onlinelibrary.wiley.com/

Issue 9 of 12, September 2012.

Search date: 8 October 2012.

Records retrieved: 2.

See above under CENTRAL for search strategy used.

Cumulative Index to Nursing and Allied Healthcare via EBSCO: www.EBSCO.com/

Inception to 28 September 2012.

Search date: 8 October 2012.

Records retrieved: 369.

Database of Abstracts of Reviews of Effect via Wiley: http://onlinelibrary.wiley.com/

Issue 3 of 4, July 2012.

Records retrieved: 0.

See above under CENTRAL for search strategy used.

Dissertation Abstracts via Dialog: www.dialog.com/

1861 to August 2012.

Searched on 5 October 2012.

Records retrieved: 53.

EMBASE via OvidSP: http://ovidsp.ovid.com/

1974 to week 5, October 2012.

Searched on 8 October 2012.

Records retrieved: 1849.

1. auditory tube/ (3102)

2. auditory tube dysfunction/ (736)

3. middle ear pressure/ (649)

4. ((eustachian or auditory or pharyngotympanic) adj3 tub$).ti,ab. (3590)

5. (eustachian adj2 (canal or orifice$)).ti,ab. (77)

6. (middle ear adj3 dysfunction$).ti,ab. (137)

7. (middle ear adj3 pressure$).ti,ab. (992)

8. or/1-7 (5666)

9. exp steroid/ (1,090,248)

10. exp antiinflammatory agent/ (1,120,613)

11. (adrenal cort$ adj2 hormone$).ti,ab. (864)

12. (corticosteroid$ or cortico steroid$ or corticoid$).ti,ab. (101,335)

13. steroid$.ti,ab. (217,679)

14. glucocorticoid$.ti,ab. (58,069)

15. (anti inflam$ or antiinflam$).ti,ab. (122,004)

16. (fluticason$ or flixonase or flonase or flovent or cultivate or flixotide or atemur or axotide or beconase or cci 18781 or cci18781 or cutivat$ or flixovate or flunase or fluspiral or flutide or flutinase or flutivate or fluxonal or gr 18781 or gr18781 or zoflut).ti,ab,rn. (12,301)

17. (budeson$ or pulmicort or horacort or rhinocort or bidien or budecort or budicort or CCRIS 5230 or cortivent or entocort or micronyl or noex or preferid or respules or rhinosol or spirocort or symbicort or uceris).ti,ab,rn. (14,488)

18. (mometason$ or sch 32088 or nasonex or rinelon or elocon or allermax aqueous or asmanex or danitin or dermotasone or dermovel or ecural or elica or elocom or elocone or elocyn or elomet or elosalic or eloson or flumeta or mefurosan or metaspray or momate or mometAid or monovel or morecort or motaderm or nosorex or novasone or propel or rimelon or rivelon or uniclar).ti,ab,rn. (4448)

19. (triamcinolone acetonide or tricinolon or cinonide or kenalog or azmacort or kenacort or acetospan or adcortyl A or allerNaze or aristocort or aristoderm or aristogel or CCRIS 5231 or coupe-A or flutex or flutone or kenalone or NSC 21916 or nasacort or omcilon A or oracort or oralone or polcortolon or rineton or solodelf or tramacin or tri-nasal or triacet$ or triacort or triam-Injekt or triamonide or trianex or triatex or triderm or triesence or trivaris or trymex or volon A).ti,ab,rn. (14,831)

20. (dexameth$ or adrenocot or aflucoson$ or alfalyl or Anaflogistico or Aphtasolon or arcodexan$ or artrosone or Auxiron or Azium or bidexol or Bisu DS or Calonat or CCRIS 7067 or cebedex or cetadexon or colofoam or corsona or Corsone or cortastat or cortidex$ or cortidron$ or Cortisumman or dacortina fuerte or dacortine fuerte or dalalone or danasone or Decacortin or decadeltoson$ or Decaderm or decadion or decadran or decadron$ or decaesadril or Decagel or decaject or Decalix or decameth or Decasone or decaspray or decasterolone or decdan or decilone or decofluor or Dectancyl or Dekacort or delladec or deltafluoren$ or Dergramin or Deronil).ti,ab,rn. (112,780)

21. (desacort or desacortone or Desadrene or desalark or desameton$ or Deseronil or desigdron or dexa cortisyl or dexa dabrosan or dexa korti or Dexa Mamallet or dexa scherosan or dexa scherozon$ or Dexacort$ or Dexa-Cort$ or dexadabroson or dexadecadrol or Dexadeltone or dexadrol or Dexafarma or dexagel or dexagen or dexahelvacort or dexakorti or dexalien or dexalocal or Dexalona or dexame$ or Dexametasona or dexan or dexane or dexano or Dexapolcort or Dexapos or dexapot or Dexaprol or dexascheroson or Dexa-Scheroson or dexascherozon$ or Dexa-sine or Dexason$ or Dex-ide or Dexinolon or Dexinoral or dexionil or dexona or Dexone or dexpak or Dextelan).ti,ab,rn. (112,287)

22. (dextrasone or Dezone or dibasona or Dinormon or doxamethasone or esacortene or exadion$ or firmalone or fluormethyl prednisolon$ or fluormethylprednisolon$ or Fluormone or Fluorocort or fluorodelta or Fortecortin or Gammacorte$ or grosodexon$ or hexadecadiol or hexadecadrol or hexadiol or hexadrol or Isopto Dex or isopto maxidex or isoptodex or isoptomaxidex or Lokalison F or Loverine or Luxazone or marvidione or maxidex or Mediamethasone or megacortin or mephameson$ or metasolon$ or methazon$ ion or methazonion$ or metisone lafi or mexasone or Mexidex or millicorten$ or Mymethasone or nisomethasona or novocort or NSC 34521 or nsc34521).ti,ab,rn. (86)

23. (Ocu-trol or oftan-dexa or opticorten or opticortinol or oradexan or oradexon$ or orgadrone or Ozurdex or pidexon or Policort or Prednisolon F or prodexon$ or sanamethasone or santenson or santeson or sawasone or solurex or spoloven or sterasone or thilodexine or triamcimetil or vexamet or visumetazone or visumethazone or adrecort or Aeroseb or dexacen or isnacort or methylfluorprednisolone or posurdex).ti,ab,rn. (49)

24. (beclomet$ or aerobec or afifon or Alanase or Aldecin$ or anceron or apo-beclomethasone or ascocortonyl or asmabec clickhaler or Atomase or atomide or beceze or Beclacin or beclamet or beclate or Beclazone or beclo asma or beclo AZU or beclo rhino or becloasma or beclocort or becloforte or beclojet or beclone or beclorhinol or beclosol or beclotaide or becloturmant or becloturmat or beclovent or becodisk$ or beconase or beconasol or becotide or belax or bemedrex).ti,ab,rn. (12,486)

25. (Benconase or bronchocort or bronconox or chf 1514 or chf1514 or Clenil or decomit or ecobec or Entyderma or filair or Inalone or junik or Korbutone or Menaderm or miflasone or nasobec aqueous or nexxair or nobec or orbec or prolair or propaderm or qvar or ratioallerg or respocort or rhinivict or Rhino Clenil or Rhinosol or rinaze or rynconox or sanasthmax or sanasthmyl or “sbn 024” or sbn024 or Sch 18020W or Turbinal or vancenase or vanceril or ventolair or viarex or viarin or Viaro or xiten).ti,ab,rn. (208)

26. (betamethasone or betamethason or betnesol or bentelan or rinderon$ or celestone phosphate or beta corlan or beta methasone or betam-ophtal or diprospan or durabetason or etnesol or inflacor or linolosal or linosal or NSC 90616 or solucelestan).ti,ab,rn. (14,841)

27. (apo-flunisolide or inhacort or nasalide or ratio-flunisolide or rhinalar or RS-3999 or syntaris or aeroBid or nasarel or aerospan or bronalide or cyntaris or flunitec or flunisolid$ or gibiflu or locasyn or lokilan or lunibron-a or lunis or nisolid or rs3999 or sanergal or soluzione or synaclyn or val 679 or val679).ti,ab,rn. (2227)

28. (prednison$ or Adasone or ancortone or Apo-Prednisone or biocortone or Cartancyl or CCRIS 2646 or colisone or Cortan or Cortancyl or cortidelt or cortiprex or Cotone or Cutason or dacorten or Dacortin or de cortisyl or decortancyl or decortin$ or Decortisyl or Dehydrocortisone or dekortin or delitisone or dellacort or delta cortelan or delta Cortisone or delta dome or delta e or delta prenovis or delta-1-Cortisone or delta-1-Dehydrocortisone or deltacort$ or delta-dome or Deltasone or deltison$ or deltra or di adreson or diadreson or drazone or Econosone or Encorton$).ti,ab,rn. (128,418)

29. (Enkortolon or enkorton or fernisone or Fiasone or hostacortin or HSDB 3168 or Incocortyl or insone or IN Sone or Juvason or Kortancyl or Liquid Pred or Lisacort or lodotra or Lodtra or me-korti or meprison or metacortandracin or Meticorten or meticortine or NCI-C04897 or nisona or Nizon or Novoprednisone or nsc 10023 or nsc10023 or Nurison or Orasone or orisane or Panafcort or Panasol or paracort or Parmenison or pehacort or precort or precortal).ti,ab,rn. (134)

30. (Predni Tablinen or prednicen-m or prednicorm or Prednicort or prednicot or Prednidib or Prednilonga or Predniment or prednitone or Prednizon or Prednovister or Presone or pronison or Pronisone or pronizone or pulmison or Rectodelt or Retrocortine or servisone or SK-Prednisone or steerometz or Sterapred or Supercortil or U 6020 or Ultracorten$ or urtilone or Winpred or Wojtab or Zenadrid).ti,ab,rn. (66)

31. (methylprednisolon$ or adlone-40 or adlone-80 or A-Methapred or Artisone-wyeth or Besonia or BRN 2340300 or dep medalone 80 or depmedalone or depoject-80 or Depo-Medrol or depopred or Dopomedrol or esametone or firmacort or HSDB 3127 or Lemod or Medesone or medixon or med-jec-40 or Medlone 21 or mednin or medralone 80 or medrate or Medrol or medrone or meprednisolone or mesopren or Metastab or methacort 40 or methacort 80 or methylcotol or methylcotolone or Methyleneprednisolone or methylpred dp or methylsterolone or metidrol).ti,ab,rn. (68,350)

32. (Metilbetasone or Metilprednisolon$ or Metipred or metrisone or Metrocort or metycortin or metypred or metypresol or Metysolon or Moderin or neomedrone or Nirypan or Noretona or nsc 19987 or nsc19987 or Predni N Tablinen or prednol or Promacortine or Reactenol or Sieropresol or solomet or solu decortin or Solu-medrol or Summicort or Suprametil or U 7532 or U-67 590A or Urbason or Urbasone or Wyacort).ti,ab,rn. (347)

33. (Prednisolon$ or adelcort or antisolon or antisolone or aprednislon or aprednislone or benisolon or benisolone or berisolon or berisolone or BRN 1354103 or Bubbli-Pred or caberdelta or capsoid or CCRIS 980 or co hydeltra or codelcortone or CO-Hydeltra or compresolon or Cordrol or cortadeltona or cortadeltone or cortalone or cortelinter or cortisolone or Cotogesic or cotolone or dacrotin or ecaprednil or decortril or dehydro cortex or dehydro hydrocortisone or dehydro hydrocortisone or dehydrocortex or dehydrocortisol or dehydrocortisole or dehydrohydrocortison).ti,ab,rn. (96,870)

34. (dehydrohydrocortisone or delcortol or delta cortef or delta cortril or delta ef cortelan or delta f or delta hycortol or delta hydrocortisone or delta hydrocortisone or delta ophticor or delta stab or delta1 dehydrocortisol or delta1 dehydrohydrocortisone or delta1 hydrocortisone or deltacortef or delta-cortef or Deltacortenol or deltacortenolo or deltacortil or deltacortoil or deltacortril or deltaderm or delta-Ef-Cortelan or deltaglycortril or deltahycortol or deltahydrocortison or deltahydrocortisone or deltaophticor or deltasolone or deltastab or deltidrosol or deltisilone).ti,ab,rn. (179)

35. (deltisolon or deltisolone or deltolasson or deltolassone or deltosona or deltosone or depo-predate or dermosolon or Derpo PD or Dexa-Cortidelt or hostacortin H or dhasolone or diadresone f or DiAdresonF or dicortol or domucortone or Donisolone or Dydeltrone or Eazolin D or encortelon or encortelone or encortolon or Erbacort or Erbasona or Estilsona or Fernisolone or glistelone or hefasolon or HSDB 3385 or hydeltra or hydeltrone or hydrelta or hydrocortancyl or hydrocortidelt or hydrodeltalone or hydrodeltisone or hydroretrocortin or hydroretrocortine or inflanefran).ti,ab,rn. (25)

36. (insolone or K 1557 or keteocort or key-pred or lenisolone or Lentosone or leocortol or liquipred or lygal kopftinktur or mediasolone or meprisolon or meprisolone or metacortalon or metacortalone or metacortandralon or metacortandralone or metacortelone or meti derm or meticortelone or metiderm or meti derm or morlone or mydrapred or neo delta or nisolon or nisolone or nsc 9120 or nsc9120 or opredsone or Orapred or panafcortelone or panafort or paracortol or Paracotol or Pediapred or phlogex or PRDL or pre cortisyl).ti,ab,rn. (62)

37. (preconin or precortalon or precortancyl or Precortilon or precortisyl or predacort 50 or predaject-50 or predalone 50 or predartrina or predartrine or Predate or predeltilone or predisole or predisyr or pred-ject-50 or predne dome or prednecort or prednedome or Predne-Dome or prednelan or predni coelin or predni h tablinen or Prednicen or prednicoelin or prednicortelone or prednifor drops or predni-helvacort or Predniliderm or predniment or predniretard or prednis or prednisil or prednivet or prednorsolon or prednorsolone or Predonin or Predonine or predorgasolona or predorgasolone).ti,ab,rn. (87,742)

38. (prelon or prelone or prenilone or prenin or prenolone or preventan or prezolon or Rolisone or rubycort or scherisolon or scherisolona or serilone or solondo or solone or solupren or soluprene or spiricort or spolotane or Steran or sterane or sterolone or supercortisol or supercortizol or taracortelone or Ulacort or walesolone or wysolone).ti,ab,rn. (89)

39. or/9-38 (1,806,878)

40. 8 and 39 (275)

41. exp decongestive agent/ (90,821)

42. cirazoline/ (666)

43. oxedrine/ (663)

44. (xylometazolin$ or Balkis or Chlorohist-LA or Decongest or espa-rhin or Gelonasal or Idasal or Idril N or Nasan or Imidin or NasenGel or NasenTropfen or NasenSpray or Novorin or Otradrops or Otraspray or Otrivin or Otriven$ or Rapako or schnupfen endrine or Snup or stas or Amidrin or Neo-Synephrine II or Olynth or Otrivine or Rhinactin or ba 11391 or ba11391 or “brn 0180524” or brufasol or otrovin hcl or servilaryn or tixycold or xylometarzoline or xylometazonolin$ or xylomethazoline or xilometazolin$ or zylometazoline or otrix).ti,ab,rn. (1340)

45. (cirazolin$ or LD 3098).ti,ab,rn. (728)

46. (naphazolin$ or Afazol Grin or AK Con or AKCon or Albalon or albasol or All Clear or allersol or alpha-Naphthylmethyl imidazoline or antan or benil or “BRN 0151864” or cefasan or Ciba 2020 or Clear Eyes or Clearine or coldan or Colirio Alfa or comfort eye drops or dazolin or degest 2 or derinox or Idril or imidin or minha or Miraclar or mirafrin or Nafazair or Nafazolin$ or naphacel ofteno or naphasal or Naphcon or naphozoline hydrochloride or naphtears or naphthazoline or naphthizine).ti,ab,rn. (1761)

47. (naphthyzin or nastizol or nazil ofteno or niazol or ocu-zoline or opcon or Optazine or Privin$ or Proculin or rhinantin or rhinazin or rhinoperd or rimidol or sanorin or sanotin or Siozwo or strictylon or Tele Stulln or TeleStulln or Vasoclear or Vasocon or Vasoconstrictor Pensa or VasoNit or vistalbalon or vistobalon).ti,ab,rn. (115)

48. (Oxymetazolin$ or afrazine or afrin or atomol or bayfrin or “BRN 0886303” or dristan or drixine or duramist plus or H 990 or Hazol or HSDB 3143 or Iliadin or iliadine or Nafrine or nasivin or Navisin or Nezeril or nostrilla or ocuclear or Oximetazolin$ or Oxylazine or Oxymethazoline or Rhinofrenol or rhinolitan or rhinosan or sch 9384 or Sinerol or sinex long last or sinex or visine).ti,ab,rn. (2646)

49. (Phenylephrin$ or adrianol or af-taf or Ah-Chew or AI3-02402 or ak-dilate or albalon relief or alconefrin or almefrin or biomidrin or biomydrin or CCRIS 8464 or derizene or despec-sf or disneumon pernasal or dristan nasal mist or drosin or efrin-10 or efrisel or fenylephrine or HSDB 3383 or idrianol or isonefrine or isophrin or isopto frin or isoptofrin or l meta synephrine or lexatol or m synephrine or mesaton$ or meta sympathol or meta synephrine or metaoxedrin$).ti,ab,rn. (31,213)

50. (Metasympatol or metasynephrine or Mezaton or m-Methylaminoethanolphenol or m-Oxedrine or m-Sympathol or m-Sympatol or m-Synephrine or mydfrin or nefrin-ofteno or Neo Synephrine or neofrin or neooxedrine or neophryn or neosynephrin or neosynephrine or neosynesin or neosynesine or ocu-phrin or oftan-metaoksedrin or op-isophrin or optistin or phenoptic or phenylefrine or phenylephedrine or prefrin or pupiletto forte or rectasol or rhinall 10 or slv 325 or slv325 or sucraphen or visadron or vistafrin or vistosan).ti,ab,rn. (243)

51. (Phenylpropanolamin$ or acutrim or apodrine or apoephedrine or apophedrine or appedrine or BRN 3196918 or descon or Dexatrim or dexatrim or diet gard or dietac premeal or HSDB 6485 or kontexin or monydrin or Mucron or mydriatin or nobese or Norephedrine or NSC 9920 or phenyl propanolamine or phenylpropanolamide or PPA or pressedrine or procol or Prolamine or propadine or propadrine or Propagest or Rhindecon or Super Odrinex or trimolet).ti,ab,rn. (7117)

52. (Pseudoephedrin$ or acunaso or afrinol or Besan or dimetapp or d-Isoephedrine or drixora or Ephedrine or HSDB 3177 or Isoephedrine or isofedrine or isophedrine or logicin plus or monofed or nasa-12 or novafed or otrinol or pseudo ephedrine or pseudo-12 or Pseudoefedrina or pseudono or Psi-ephedrin or repedrina or rhinalair or sch 4855 or sch4855 or sinumed or sinutab or subulin or Sudafed or sudomyl or sudosian or symptofed or tiptipot).ti,ab,rn. (15,192)

53. (Synephrin$ or Sympaethamin$ or Oxedrine or aetaphen or asthma spray spofa or pentedrine or vasoton or Analeptin or DL-Synephrine or Ethaphene or NSC 166285 or NSC 170956 or Parakorper or Parasympatol or S 38537-9 or Simpalon or Simpatol or Sympathol or Sympatol or Synefrin or Synthenate or p-Hydroxyphenylmethylaminoethanol or p-Methylaminoethanolphenol or p-Oxedrine or p-Synephrine).ti,ab,rn. (814)

54. (tetrahydrozolin$ or tetryzoline or Caltheon or Collyrium Fresh or Diabenyl T or Eye-Sine or Eye-Zine or Murine Plus or Murine Sore Eyes or Ophtalmin or Optazine Fresh or Optigene or Rhinopront or Tetra-Ide or Tetraclear or Tetrilin or Tyzine or Vasopos or Visine or Yxin or Vispring or Berberil N or “BRN 0011442” or HSDB 7471 or Tetrizolin$ or Tyzanol or clarine or insto or murine tears or murine-2 or nasan or nazane or nazine or necor tyzine or octilia or ophthalmin-n or opsil-a or optizoline or rhinoprout or stilla drops or visina or visolin).ti,ab,rn. (553)

55. (brompheniramine or Bromfed or Lodrane or Dimetapp).ti,ab,rn. (1081)

56. (decongestant$ or decongestive$).ti,ab. (1953)

57. ((nasal or nose) adj2 (spray$ or mist or aerosol$)).ti,ab. (3331)

58. or/41-57 (102,618)

59. 8 and 58 (156)

60. exp antihistaminic agent/ (164,435)

61. (anti histamin$ or antihistamin$).ti,ab. (15,317)

62. (histamine adj3 (antagonist$ or block$)).ti,ab. (8134)

63. ((H1 or H2 or H3 or H4) adj2 (antagonist$ or block$)).ti,ab. (15,633)

64. (acrivastin$ or semprex or semprex-D or benadryl or prolert or BW 825C or BW825C or BW A825C).ti,ab,rn. (736)

65. (bilastine or bilaxten or f 96221 bm1 or f96221 bm1).ti,ab,rn. (53)

66. (Cetirizin$ or acidrine or adezio or agelmin or Alercet or Alergex or Alerid or Alerlisin or Alertisin or alertop or alerviden or aletir or alled or Allergy relief or Alleroff or allertec or alltec or alzytec or Apo-Cetirizine or betarhin or cerazine or cerini or cerotec or cesta or Cetalerg or Ceterifug or cethis or Ceti TAD or Cetiderm or Cetidura or Cetil von ct or CetiLich or cetimin or cetin or Ceti-Puren or cetirax or Cetirigamma or cetirin or Cetirlan or cetizin or Cetriler or cetrimed or Cetrine or cetrizet or cetrizin or Cetryn or cetymin or Cetzine or Cezin or cistamine or deallergy or falergi or finallerg or Formistin or histazine or histica or Hitrizin or HSDB 7739).ti,ab,rn. (5508)

67. (incidal-od or lergium or nosemin or nosmin or ozen or “P 071” or P071 or prixlae or razene or Reactine or Ressital or rhizin or risima or Riztec or ryvel or Ryzen or Salvalerg or sancotec or selitex or Setir or Setiral or setizin or simtec or Stopaler or Sun mark all day allergy or sutac or symitec or terizin or terzine or Topcare all day allergy or Triz or “UCB-P 071” or vick-zyrt or Virdos or Virlix or Voltric or Xero-sed or zenriz or zensil or zeran or zertine or Zetir or zicet or zinex or Ziptek or zirtec or Zirtek or Zirtin or zyllergy or zymed or zyrac or zyrazine or zyrcon or zyrlex or Zyrtec or Zyrtec-D or zyrtek or Zyrzine).ti,ab,rn. (2383)

68. (desloratadine or clarinex or aerius or neoclarityn or azomyr or denosin or SCH 34117 or allex or aviant or claramax or dasselta or decarbethoxyloratadine or desalex or descarboethoxyloratadine or deslor or neoclaritine or sch34117 or supraler).ti,ab,rn. (1608)

69. (fexofenadine or allegra or telfast or Carboxyterfenadine or MDL 16455A or mdl 16455 or mdl16455).ti,ab,rn. (3008)

70. (levocetirizine or xusal or xyzal).ti,ab,rn. (1021)

71. (loratadin$ or aerotina or Alarin or Alavert or alerfast or alernitis or Alerpriv or alertadin or allerta or Allertidin or allertyn or allohex or ambrace or analergal or anhissen or anlos or ardin or Bactimicina allergy or Biloina or bonalerg or caradine or carin or civeran or clalodine or claratyne or clarid or Clarinase or Claritin or claritine or clarityn or clarityne or Clarium or cronitin or cronopen or curyken or demazin anti-allergy or ezasmin or ezede or finska or frenaler or fristamin or genadine or halodin or hislorex or histalor or histaloran or HSDB 3578 or j-tadine or klarihist or klinset or laredine or lergia or Lergy or lertamine or Lesidas or lindine or lisino or lisono or lobeta or lodain or lorabasics or loracert or loraclar or loraderm or loradex).ti,ab,rn. (15709)

72. (Loradif or loradin or lorahist or loralerg or lora-lich or lorano or loranox or Loranox or Lorantis or lorastine or lora-tabs or loratadura or loratan or loratazine or loratidin or loratidine or loraton or loratrim or loratyne or Loraver or loreen or lorfast or lorihis or lorin or lorita or Loritine or lotadine or lotarin or lowadina or mosedin or noratin or notamin or Nularef or onemin or optimin or polaratyne or proactin or pylor or restamine or Rhinase or ridamin or rihest or rinityn or Rinomex or rityne or roletra or rotifar or Sanelor or Sch 29851 or Sch29851 or sensibit or Sinhistan Dy or sohotin or Tadine or Talorat Dy or tidilor or tirlor or Topcare or toradine or velodan or versal or voratadine or zeos).ti,ab,rn. (171)

73. (mizolastin$ or zolistan or mistamine or mistalin or mizollen or zolim or mizolen or “SL 85 0324” or CCRIS 8410 or mkc 431 or sl 850324).ti,ab,rn. (666)

74. (rupatadine or rupafin or UR 12592 or UR12592).ti,ab,rn. (197)

75. (Chlorphenamin$ or 4-Chloropheniramine or ahiston or alerfin or alergical or alergidryl or alergitrat or alermine or aller or Aller-Chlor or Allerclor or allerfin or Allergican or Allergin or Allergisan or allergyl or allermin or allerphen or Alunex or analerg or anaphyl or Antagonate or antamin or apomin or barominic or cadistin or Carbinoxamide maleate or CCRIS 1418 or Chlo-Amine or chlometon or chlor trimeton or Chlor-100 or chloramate unicelles or chlorleate or Chlormene or chlorophenamine maleate or Chloropheniramine or Chlorophenylpyridamine or Chloropiril).ti,ab,rn. (238)

76. (Chloroprophenpyridamine or chloroton or Chlorpheniramin$ or chlorpheno or chlorphenon or Chlorpro or Chlorprophenpyridamine or chlorpyrimine or Chlorspan 12 or Chlortab-4 or chlortrimeton or Chlor-Trimeton or chlortripolon or Chlor-Tripolon or Clorfenamina or Clorfeniramina or cloro trimeton or cloroalergan or Cloropiril or clorotrimeton or Cloro-Trimeton or C-Meton or cohistan or com-trimeton or Dehist or dl-Chlorpheniramine maleate or Efidac 24).ti,ab,rn. (20392)

77. (clemastin$ or meclastin$ or neclastine or mecloprodin or tavist or tavegyl or HS 592 or HS592).ti,ab,rn. (2247)

78. (cyproheptadine or adekin or Antergan or antisemin or apeton 4 or astonin or BRN 1685976 or CCRIS 5232 or ciplactin or cipractin or ciproeptadine or Ciproheptadina or ciproral or ciprovit-a or cryoheptidine or crypoheptadine or cyheptine or cylat or cypraheptidine or cypro h or cyproatin or cyprogin or cyprohaptadi$ or cypromin or cyprono or cyprosian or cytadine or Dihexazin or Dronactin or Eiproheptadine or ennamax or glocyp or heptasan or HSDB 3048 or ifrasal or istam-far or klarivitina or kulinet or MK 141 or nuran or Periact$ or Peritol or petina or pilian or pronicy or sinapdin or trimetabol or Viternum).ti,ab,rn. (7695)

79. (ketotifen$ or ketotiphen$ or zaditen or zaditor or BRN 3983897 or HC 20 511 or hc 20511 or HSDB 7283).ti,ab,rn. (4419)

80. (Prometh$ or 3277 RP or A-91033 or adgan or Allerfen or allergan or Anergan 25 or Anergan 50 or antiallersin or antinaus 50 or Aprobit or Atosil or Avomine or baymethazine or Bonnox or “BRN 0088554” or Camergan or CCRIS 5873 or CCRIS 7056 or Closin or dimapp or Dimethylamino-isopropyl-phenthiazin or Diphergan or Diprasine or Diprazin$ or diprozin or Dorme or Duplamin or Eusedon Mono or fargan or Farganesse or Fellozine or fenazil or fenazine or Fenergan or Fenetazin$ or Frinova or Ganphen or Hibechin or hiberna or Histantil or Histargan or HL 8700 or HSDB 3173 or insomn-eze or Isophenergan or Isopromethazine or Kinetosin or lercigan or Lergigan or lergigan or “Lilly 01516” or Lilly 1516 or Metaryl or Mymethazine Fortis or NCI-C60673 or NSC 231688).ti,ab,rn. (13,784)

81. (NSC 30321 or Pelpica or pentazine or phargan or Phenadoz or Phenargan or Phencen or Phenergan or Phenerzine or phenoject-50 or Phensedyl or Pilothia or Pipolfen or Pipolphen$ or Plletia or pm 284 or Primine or Pro-50 or Proazamine or procit or promacot or Promantine or promazinamide or Prome or Promergan or Promesan or Promet or Prometazin or Prometazina or Prometh$ or Promezathine or Promine or Proneurin or Prorex or protazine or Prothazin or Prothiazine or prothazine or provigan or Provigan or Pyrethia or Pyrethiazine or Remsed or Romergan or rp 3277 or rp 3389 or Rumergan or sayomol or SKF 1498 or Soporil or tanidil or thiergan or V GAN or vallergine or WY 509 or Zipan-25 or Zipan-50).ti,ab,rn. (14,656)

82. or/60-81 (198,982)

83. 8 and 82 (104)

84. simethicone/ (777)

85. (simethicone or Antifoam A or Antifoam AF or DC antifoam A or Disflatyl or Gas-X or gas relief or HSDB 3906 or Mylanta or mytab gas or Phazyme or Sab Simplex or Simeticone or dimethicone or digel or flatulex or infacol or lefax or minifom or mylicon or silain or Alka-Seltzer Anti-Gas or Colic Drops or Colicon or Degas or Gas Aide or Genasyme or Maalox Anti-Gas or Majorcon or Micon-80 or Mylaval or SonoRx or WindEze or Wind-Eze).ti,ab,rn. (1463)

86. 84 or 85 (1463)

87. 8 and 86 (0)

88. nasal lavage/ (368)

89. lavage/ (12,033)

90. ((nasal or nose) adj3 (douch$ or irrigat$ or lavage)).ti,ab. (1664)

91. (saline adj3 (douch$ or irrigat$ or lavage)).ti,ab. (2156)

92. or/88-91 (15,123)

93. 8 and 92 (29)

94. exp leukotriene receptor blocking agent/ (13729)

95. zileuton/ (1886)

96. (leukotriene adj3 (antagonist$ or block$ or inhibitor$)).ti,ab. (3925)

97. (montelukast or Singulair or Montelo-10 or montair or montek or montus or romilast or “MK 0476” or mk 476 or mk0476 or mk476 or l 706631 or l706631).ti,ab,rn. (5838)

98. (zafirlukast or Accolate or accoleit or Olmoran or Aeronix or respix or vanticon or zafirst or zuvair or ICI 204,219 or ICI 204219).ti,ab,rn. (2326)

99. (pranlukast or azlaire or ultair or ONO 1078 or SB 205312 or SB205312 or ONO RS 411 or rs411 or rs 411).ti,ab,rn. (1096)

100. (zileuton$ or A 64077 or A64077 or Abbot 64077 or cgs 23622 or cgs23622 or Zyflo or Leutrol).ti,ab,rn. (1946)

101. or/94-100 (15,465)

102. 8 and 101 (6)

103. chewing gum/ (1934)

104. xylitol/ (3087)

105. (Xylitol or BRN 1720523 or Eutrit or HSDB 7967 or Kannit or Klinit or NSC 25283 or Newtol or Xylite or Xylitol or Xyliton or xylit).ti,ab,rn. (3767)

106. or/103-105 (5455)

107. 8 and 106 (3)

108. exp antiinfective agent/ (2,031,219)

109. (anti bacterial$ or antibacterial$ or anti biotic$ or antibiotic$ or anti mycobacterial$ or antimycobacterial$ or bacteriocid$).ti,ab. (312,266)

110. (anti infective$ or antiinfective$ or anti microbial$ or antimicrobial$ or microbicide$).ti,ab. (111,188)

111. (doxycyclin$ or adoxa or alpha-Doxycycline or amermycin or atrax or azudoxat or bactidox or banndoclin or basedillin or bassado or biocolyn or biodoxi or bmy 28689 or bmy28689 or bronmycin or bu 3839t or bu3839t or cloran or cyclidox or dentistar or deoxycycline or deoxymycin dispersal or deoxymykoin or deoxyoxytetracycline or desoxy oxytetracycline or desoxycycline or doinmycin or doryx or dosil or Dossiciclina or dotur or doxaciclin or doxacycline or doxat or doxatet or doxibiotic or Doxiciclina or doxicycline or doxilin or doximed or doximycin or doxin or doxine or doxi-sergo).ti,ab,rn. (34,826)

112. (Doxitard or Doxivetin or doxocycline or doxsig or doxy or doxy-1 or doxybiocin or doxy-caps or doxycen or doxychel or doxycin or doxycydine monohydrate or doxylag or doxylin or doxymycin or doxypuren or Doxy-Puren or Doxysol or doxytec or Doxytetracycline or doxytrim or dumoxin or duracycline or esdoxin or etidoxina or gewacyclin or gs 3065 or HSDB 3071 or hydramycin or ibralene or idocyclin or idocyklin or interdoxin or investin or Liviatin or longamycin or lydox or magdrin or medomycin or mespafin or mildox or miraclin or monodox or nordox or novum vibramycin).ti,ab,rn. (31,921)

113. (nsc 56228 or oracea or paldomycin or pernox gel or radox or remycin or respidox or Ronaxan or roximycin or serodoxy or servidoxine or servidoxyne or siadocin or siclidon or sigadoxin or spanor or supracyclin or supramycina or tenutan or tolexine or torymycin or tsurupioxin or unidox or veemycin or viadoxin or vibra$ or viradoxyl-n or wanmycin or zadorin).ti,ab,rn. (38,600)

114. (amoxicil$ or a gram or abdimox or acilina or acimox or actimoxi or adbiotin or agerpen or agram or a-gram or alfamox or alfoxil or almodan or almorsan or alphamox or amagesen solutab or ameclina or amocillin or amoclen or amodex or amo-flamisan or amoflux or amohexal or amolin or amonex or amopen or Amopenixin or amophar ge or amosine or amoval or amoxa or amoxal or amoxapen or amoxaren or amoxcil or amoxcillin or amoxcin or Amoxi or amoxi-basan or Amoxicaps or amoxiclin or amoxicot or amoxidal or Amoxiden or amoxidin or amoxidrops or amoxihexal or amoxil$).ti,ab,rn. (68,789)

115. (Amoxi-Mast or amoxipen or amoxipenil or amoxisol or amoxivan or amoxivet or Amoxivet or amoxy or Amoxycillin$ or amoxy-diolan or amoxypen or AMPC or ampliron or Ampy-Penyl or Anemolin or apo-amoxi or ardine or aroxin or Aspenil or azillin or bacihexal or bactamox or bactox ge or beamoxy or betamox or bimox or bintamox or biomox or biotamoxal or bioxidona or bioxyllin or BLP 1410 or bristamox or brl 2333 or brl2333 or broadmetz or cabermox or Cemoxin or cilamox or clamox or clamoxyl or clearamox or clonamox or coamoxin or damoxicil or D-Amoxicillin or Delacillin).ti,ab,rn. (5713)

116. (dispermox or doxamil or draximox or edamox or Efpenix or erphamoxy or eupen or farconcil or fisamox or flemoxin or fluamoxina or foxolin or fullcilina or gexcil or gimalxina or glamox or glassatan or gomcillin or grinsul or grunamox or hamoxillin or hiconcil or hidramox or hipen or Histocillin or hosboral or HSDB 3204 or Hydroxyampicillin or ibamox or ibiamox or ikamoxil or imacillin or imaxilin or inamox or infectomycin or intermox or isimoxin or izoltil or julphamox or jutamox or kamoxin or ladoxillin or lamoxy or larocilin or larocin or larotid or macromox or magnimox or maxamox or maxcil).ti,ab,rn. (27)

117. (medimox or meixil or Metafarma or metifarma or mopen or morgenxil or moxacin or Moxal$ or moxarin or Moxatag or moxilen or moxilin or moximar or moxitab or moxtid or moxylin or moxypen or moxyvit or neogram or novabritine or novamox or novamoxin or novenzymin or novoxil or NSC 277174 or nuvosyl or optium or ospamox or pamocil or pamoxicillin or pamoxin or panvilon or pasetocin or penamox or penbiosyn or pentyloxycillin or pharmoxyl or p-Hydroxyampicillin or piramox or polymox or pondnoxcill or rancil or ranmoxy or ranoxil or ranoxyl or Ro 10-8756).ti,ab,rn. (1384)

118. (robamox or romoxil or ronemox or saltermox or sawacillin or sawamezin or Sawamox PM or servamox or shamoxil or sia-mox or sigamopen or silamox or sil-a-mox or simoxil or solpenox or sumox or superpeni or teramoxyl or tolodina or tormoxin or triafamox or triamoxil or trifamox or trimox or Unicillin or uro clamoxyl or uroclamoxyl or utimox or vastamox or velamox or Vetramox or vistrep or widecillin or winpen or wymox or Wymox or Wymox or xiltrop or zamocillin or zamox or zamoxil or zerrsox or zimox).ti,ab,rn. (15)

119. (clarith$ or A 56268 or A56268 or abbotic or abbott 56268 or Adel or aeroxina or Astromen or bactirel or baxin filmtab or Biaxin or biclar or bicrolid or binoklar or bremon or carimycin or c-clarin or CCRIS 8833 or celex or clacin or clacine or clambiotic or clapharma or claribid or Claricide or claridar or clarimac or claripen or claritrol or Claritromicina or claroma or Clathromycin or clormicin).ti,ab,rn. (25,489)

120. (crixan or cylind or Cyllid or cyllind or dicupal or DRG-0099 or er 36469 or er36469 or gervaken or hecobac or Helas or heliclar or helitic or klacid or klacina or klaciped or klaribac or klaricid or Klarid or klaridex or klaridia or klarin or Klax or klerimed or kofron or lagur or Mabicrol or macladim or macladin or maclar or mavid or monozeclar or naxy or “TE 031” or TE031 or veclam or zeclar).ti,ab,rn. (453)

121. (moxif$ or Actira or Avalox or avelon or Avelox or Avolex or BAY 12 8039 or BAY 128039 or bay128039 or CCRIS 8690 or Izilox or megaxin or moxeza or Octegra or Proflox or vigamox).ti,ab,rn. (9503)

122. (Telithromycin or Ketek or RU 66647 or HMR 3647 or HMR3647 or levviax or ru 647 or ru 66647 or ru647 or ru66647).ti,ab,rn. (2482)

123. (azithromycin$ or Aritromicina or aruzilina or atizor or Azadose or azasite or azenil or azimin or azithral or Azitrocin or azitromax or Azitromicine or aziwok or azomyne or aztrin or Azythromycin or BRN 5387583 or CCRIS 1961 or cp 62933 or cp62933 or DRG-0104 or forcin or Goxal or Hemomycin or HSDB 7205 or inedol or isv 401 or isv401 or kromicin or macrozit or mezatrin or Misultina).ti,ab,rn. (19,937)

124. (Mixoterin or octavax or Setron or Sumamed or sunamed or Tobil or tobyl or Toraseptol or tromix or Trulimax or Ultreon or Vinzam or xithrone or xz 450 or xz450 or zaret or zarom or Zentavion or Zeto or zibramax or zifin or zimericina or zistic or Zithrax or Zithromax or zithrox or zitrim or zitrobifan or Zitromax or Zitrotek or Zmas or zmax or Z-Pak).ti,ab,rn. (323)

125. or/108-124 (2,169,770)

126. 8 and 125 (494)

127. balloon dilatation/ (11,320)

128. dilatation/ (4864)

129. catheterization/ (35,076)

130. catheter$.ti,ab. (187,758)

131. dilat$.ti,ab. (132,494)

132. (BET or BDET).ti,ab. (6346)

133. tuboplast$.ti,ab. (233)

134. low level laser therapy/ (9275)

135. exp laser/ (75,145)

136. laser$.ti,ab. (165,104)

137. LETP.ti,ab. (5)

138. middle ear ventilation/ (790)

139. tympanostomy tube/ (1727)

140. myringotomy/ (2339)

141. t tube/ (1399)

142. (tympanostom$ or tympanotom$).ti,ab. (1764)

143. grommet$.ti,ab. (562)

144. ((ventilat$ or aerat$) adj4 ear$).ti,ab. (1944)

145. ((ventilat$ or aerat$) adj4 tub$).ti,ab. (2986)

146. (pressur$ adj3 tub$).ti,ab. (1862)

147. ear tube$.ti,ab. (87)

148. PE tube$.ti,ab. (54)

149. T tube$.ti,ab. (2805)

150. (transtubal or trans tubal).ti,ab. (64)

151. (myringotom$ or myringocentesis).ti,ab. (1401)

152. (paracentesis or tympanocentesis).ti,ab. (3287)

153. ((eardrum$ or ear drum$ or tympan$) adj3 (punctur$ or tap$)).ti,ab. (30)

154. or/127-153 (528682)

155. 8 and 154 (1216)

156. Valsalva maneuver/ (5320)

157. aeration/ (7359)

158. yawning/ (1151)

159. mastication/ (11,913)

160. swallowing/ (11,936)

161. watchful waiting/ (968)

162. conservative treatment/ (36,164)

163. valsalva$.ti,ab. (8682)

164. (autoinflat$ or auto inflat$).ti,ab. (103)

165. (insufflat$ or autoinsufflat$ or auto insufflat$).ti,ab. (6602)

166. (inflat$ adj4 ear$).ti,ab. (126)

167. Politzer$.ti,ab. (157)

168. ((equalis$ or equaliz$ or normalis$ or normaliz$) adj5 pressure$).ti,ab. (4936)

169. (yawn$ or swallow$ or chew$ or masticat$ or deglutition).ti,ab. (44,916)

170. (watch$ adj2 wait$).ti,ab. (2449)

171. (wait adj2 see).ti,ab. (1164)

172. (active$ adj2 observ$).ti,ab. (1213)

173. conservative.ti,ab. (87,263)

174. (management adj2 (decision$ or option$ or choice$)).ti,ab. (11,653)

175. (support$ adj4 (care or caring)).ti,ab. (25,573)

176. ((standard or usual) adj3 care).ti,ab. (32,634)

177. (advice or advis$).ti,ab. (91,523)

178. or/156-177 (344,713)

179. 8 and 178 (763)

180. 40 or 59 or 83 or 87 or 93 or 102 or 107 or 126 or 155 or 179 (2115)

181. animal/ (1,804,242)

182. exp animal experiment/ (1,646,534)

183. Nonhuman/ (3,926,525)

184. (rat or rats or mouse or mice or hamster or hamsters or animal or animals or dog or dogs or cat or cats or bovine or sheep).ti,ab,sh. (4,762,757)

185. or/181-184 (6,743,001)

186. exp human/ (13,954,738)

187. human experiment/ (305422)

188. 186 or 187 (13,956,174)

189. 185 not (185 and 188) (5,304,415)

190. 180 not 189 (1849)

Health Technology Assessment database via Wiley: http://onlinelibrary.wiley.com/

Issue 3 of 4, July 2012.

Records retrieved: 0.

See above under CENTRAL for search strategy used.

Inside Conferences via Dialog: www.dialog.com/

1993 to October, week 4 2012.

Searched on 5 October 2012.

Records retrieved: 231.

Latin American and Caribbean Health Science: http://lilacs.bvsalud.org/en/

Search date: 8 October 2012.

Records retrieved: 158.

eustachian AND tub$ 48

auditory AND tub$ 82

pharyngotympanic AND tub$ 0

eustachian AND canal 2

eustachian AND orifice$ 0

middle AND ear AND dysfuntion$ 1

middle AND ear AND pressure$ 25

PASCAL via Dialog: www.dialog.com/

1973 to September, week 5 2012.

Searched on 5 October 2012.

Records retrieved: 1678.

Science Citation Index and Conference Proceedings Citation Index – Science via ISI Web of Knowledge: www.isinet.com/

Search date: 8 October 2012.

Records retrieved: 888.

Clinical Trials.gov: http://clinicaltrials.gov/

Search date: 15 October 2012.

Records retrieved: 40.

Eustachian AND (tube OR tubes OR tubal)

• 15 studies found for: Eustachian AND (tube OR tubes OR tubal)

auditory AND (tube OR tubes OR tubal)

• 3 studies found for: auditory AND (tube OR tubes OR tubal)

pharyngotympanic AND (tube OR tubes OR tubal)

• no studies found for: pharyngotympanic AND (tube OR tubes OR tubal)

pharyngotympanic

• no studies found for: pharyngotympanic

eustachian AND (canal OR canals)

• 2 studies found for: eustachian AND (canal OR canals)

Eustachian AND (orifice OR orifices)

• no studies found for: Eustachian AND (orifice OR orifices)

“middle ear “ AND (dysfunction OR dysfunctional)

• 6 studies found for: “middle ear “ AND (dysfunction OR dysfunctional)

“middle ear “ AND (pressure OR pressures)

• 14 studies found for: “middle ear “ AND (pressure OR pressures)

Current Controlled Trials: www.controlled-trials.com/

Search date: 15 October 2012.

Records retrieved: 88.

Search of all registers via the meta Register of Controlled Trials (mRCT).

Eustachian – 10 results.

auditory AND tube – 12 results.

auditory AND tubes – 7 results.

auditory and tubal – 10 results.

pharyngotympanic – 0 results.

middle ear AND dysfunction – 12 results.

middle ear AND dysfunctional – 0 results.

middle ear AND pressure – 34 results.

middle ear AND pressures – 3 results.

EU Clinical Trials Register: www.clinicaltrialsregister.eu/

Search date: 15 October 2012.

Records retrieved: 5.

Eustachian – 0 results.

Auditory AND tube – 3.

Auditory AND tubes – 2.

pharyngotympanic – 0.

“middle ear” AND dysfunction – 0 results.

“middle ear” AND dysfunctional – 0 results.

National Research Register Archive: www.nihr.ac.uk/Pages/NRRArchiveSearch.aspx

Search date: 15 October 2012.

Records retrieved: 0.

Searched using the all fields search option.

Eustachian – 0 results.

auditory AND tube – 0 results.

auditory AND tubes – 0 results.

auditory AND tubal – 0 results.

pharyngotympanic – 0 results.

middle ear – 0 results.

World Health Organization International Clinical Trials Registry Platform: www.who.int/ictrp/en/

Search date: 15 October 2012.

Records retrieved: 18.

Eustachian – 7 results.

auditory AND tub* – 1 result.

pharyngotympanic – 0 results.

middle ear AND dysfunction* – 2 results.

middlear ear AND pressure* – 8 results.

European Medicines Agency: www.ema.europa.eu/ema/

Search date: 1 November 2012

Site wide search for:

Eustachian – 1 result

middle ear dysfunction – 0 results

middle ear pressure – 0 results

US Food and Drug Administration: www.fda.gov/

Search date: 1 November 2012

'eustachian AND (tube OR tubes OR tubal OR canal OR orifice OR orifices)' in all of FDA and archived advisory committee and dockets information – 198 results.

“middle ear dysfunction” in all of FDA and archived advisory committee and dockets information – 5 results.

"middle ear pressure" in all of FDA and archived advisory committee and dockets information – 11 results.

Medicines and Healthcare products Regulatory Agency: www.mhra.gov.uk/

Search date: 5 November 2012.

Site wide search for:

Eustachian – 5 results.

“middle ear dysfunction” – 0 results.

“middle ear pressure” – 0 results.

Laser tuboplasty (one case series, five records)

Kujawski O. Laser Eustachian tuboplasty, L.E.T.P. Laryngorhinootologie 2000;79(Suppl.):S162.

Kujawski O. Laser Eustachian tuboplasty (LETP): an overview of four years of experience in endoscopic transnasal laser-assisted cartilaginous Eustachian tube surgery (LETP) for middle ear diseases. Skull Base Surg 2001;11(Suppl. 2):14.

Kujawski O, Fasel J, Romanowicz R. Laser Cartilaginous Eustachian Tuboplasty. In Oswal V, Remade M, editors. Principles and Practice of Lasers in Otorhinolaryngology and Head Neck Surgery. The Hague: Kugler Publications; 2002. pp. 295–9.

Kujawski OB, Poe DS. Laser Eustachian tuboplasty. Otol Neurotol 2004;25:1–8.

Poe D, Kujawaski O. Endoscopic Diagnosis and Surgery of Eustachian Tube Dysfunction. In Silverstein H, Rosenberg SI, Poe D, Jackson LE, editors. Minimally Invasive Otological Surgery. New York, NY: Thomson/Delmar Learning; 2003. pp. 51–69.

Balloon dilatation

Dalchow C, Muenscher A, Knecht R. Endoscopic dilatation of the Eustachian tube. Otolaryngol Head Neck Surg 2011;145:P93.

Bouginage

Tos M. Management of tubal function in reconstructive middle ear surgery. J Laryngol Otol 1980;94:25–30.

Eustachian tube prosthesis

Wright JW, Wright JW, Hicks GW. The Eustachian tube prosthesis revisited. Otolaryngology 1978;86:ORL-834–7.

Gold wire

Jahnke K, Lieberum B. A gold wire for temporary or permanent implantation in patients with Eustachian tube dysfunction. In Tos M, Thomsen J, Balle V, editors. Otitis Media Today. Proceedings of the Third Extraordinary Symposium on Recent Advances in Otitis Media, 1–5 June 1997, Copenhagen, Denmark. The Hague: Kugler Publications; 1999. pp. 619–21.

Myringoplasty

Gimenez F, Marco-Algarra J, Carbonell R, Morant A, Cano S. Prognostic factors in tympanoplasty: a statistical evaluation. Rev Laryngol Otol Rhinol 1993;114:335–7.

Ventilation tubes

Al-Swadi W, Karlsmose B, Gaihede M, Henriksen SD, Rosborg J. Long-term treatment of chronic Eustachian tube dysfunction by subannular ventilation tubes. Otol Neurotol 2005;26:301.

Elluru RG, Dhanda R, Neely JG, Goebel JA. Anterior subannular T-tube for prolonged middle ear ventilation during tympanoplasty: evaluation of efficacy and complications. Otol Neurotol 2001;22:761–5.

Gupta SC, Malhotra M, Singh M. Eustachian tube function after transmyringeal ventilation. Indian J Otolaryngol Head Neck Surg 2005;57:39–42.

Jahn AF. Middle ear ventilation with HydroxylVent tube: review of the initial series. Otolaryngol Head Neck Surg 1993;108:701–5.

Jensen MG, Jacobsen H, Gaihede ML, Rosborg J. Subannular ventilation tubes in treatment of chronic tubal dysfunction – results in 85 consecutive cases. In Huber A, Eiber A, editors. Middle Ear Mechanics in Research and Otology. Proceedings of the 4th International Symposium, 27–30 July 2006, Zurich, Switzerland. Singapore: World Scientific Publishing Company; 2007. pp. 46–52.

O’Hare T, Goebel JA. Anterior subannular T-tube for long-term middle ear ventilation during tympanoplasty. Am J Otol 1999;20:304–8.

Per-Lee JH. Long-term middle ear ventilation. Laryngoscope 1981;91:1063–73.

Rothera MP, Grant HR. Long-term ventilation of the middle ear using the Goode T-tube. J Laryngol Otol 1985;99:335–7.

Sajan JA, Hilton CW, Levine SC. Long-term outcomes and reliability of Jahn ventilating tube. Otolaryngol Head Neck Surg 2011;145(Suppl. 2):218.