[Structured ABEV Exercises for the Treatment of vestibular dysfunction]. / Strukturierte ABEV-Übungen zur Behandlung vestibulärer Funktionsstörungen.

INTRODUCTION: In addition to medication, the standard clinical treatment for vestibular vertigo primarily includes physical therapy in the form of regular exercises. Vertidisan is a future digital health application (DiGA) for structured dizziness therapy. Its content is multimodal and consists of Adaptive Balance and Eye Movements and Visual Stimulation (ABEV) exercises, which are expected to have an anti-vertigo effect through neural learning. METHODS: A cohort study with 104 patients with intra-individual control was conducted to examine the clinical efficacy of solely 16 ABEV exercises for the treatment of peripheral vestibulopathies which are also used digitally in the future DiGA Vertidisan. Using the short version vertigo symptom scale short form1 vertigo and related symptoms (VSS-sf1-VER) of the vertigo-specific and validated VSS rating scale (Vertigo Symptom Scale) as the primary outcome variable, the vertigo scores before therapy (time T0) were compared with the corresponding data at the end of a period of 12-16 weeks (time T1). RESULTS: Complete datasets on T0 and T1 were available for N=104 patients. The mean VSS-sf1-V score decreased from 3.80 (median 4, SD 0.47) to 0.92 (median 1, SD 1.19) from T0 to T1 (weeks 12-16). The result is statistically significant (p=0.001) and shows a high clinical effect size. CONCLUSION: In summary, the analysis of the dizziness score shows a statistically and clinically significant reduction in dizziness through the use of the 16 ABEV exercises.

[Structuring of inpatient case management to improve quality and cost-effectiveness of inpatient healthcare providers from a university hospital's point of view]. / Strukturierung des stationären Fallmanagements für die Verbesserung von Qualität und Wirtschaftlichkeit stationärer Gesundheitsdienstleister aus Sicht eines Universitätsklinikums.

OBJECTIVE: In hospitals, case management (CM) on hospital wards is essential for maintaining a high level of quality and efficiency of care. The present study examined how CM at the Point of Care (POC) can be optimized and which potentials exist. METHODS: The potentials for optimization of typical case management processes performed on hospital wards were analyzed using a structured interview guide. For this purpose, a field study was performed in 24 German hospital departments of tertiary care. Structured interviews were conducted with homogeneous focus groups. The results were evaluated using an extended Balanced Score Card approach and discussed afterwards with the focus groups. RESULTS: Above all, the process quality and safety of case management as well as ensuring the relevant documentation at the POC appears to offer significant potential for optimization. An essential approach to eventually realize the potential for optimization is the reduction of fragmentation of the micro-processes associated with the case management duties on inpatient wards. This homogenization of these activities ideally requires a new and interdisciplinary acting profession, the clinical case managers. CONCLUSION: The homogenization of the case management activities on hospital wards by clinical case managers has the potential and possibilities to relieve both medical and nursing staff of these activities, while improving the quality and efficiency of care for patients, staff and cross-sectoral healthcare provider at the same time.

Implantability of endaurally insertable active vibratory middle-ear implants - an anatomical study.

Background: Hearing loss is often treated with an acoustic hearing aid. However, distortion and insufficient gain may cause problems. Active non-acoustic vibratory middle-ear implants (AMEI) may contribute to solve this problem. We recently developed an AMEI which is to be implanted completely through the patient's external auditory canal. The device uses a light-emitting diode (LED) in the external auditory canal that stimulates a photovoltaic sensor, placed in the middle ear, through the intact tympanic membrane. This results in activation of a vibratory miniaturized piezoelectric displacement transducer (MDT) (actuator) coupled to the auditory organ. Aims/objectives: The aim of this study was to evaluate the anatomical implantability of the novel AMEI using an exclusively endaural approach. Materials and methods: The internal components of our AMEI were implanted into 39 human temporal bones. The surgical procedure and the optimal size and anatomical fitting were systematically evaluated. Results: We can show here that implantation of all components of this novel AMEI into anatomical specimens proves to be a quick and easy procedure, performed using an endaural approach. Conclusions and significance: The anatomical data of this study establish the basis for further technical development of our AMEI and other future implantable hearing systems.

A multidisciplinary systematic review of the treatment for chronic idiopathic tinnitus.

The majority of tinnitus patients are affected by chronic idiopathic tinnitus, and almost 60 different treatment modalities have been reported. The present study is a multidisciplinary systematic analysis of the evidence for the different forms of treatment for chronic tinnitus. The results are used to form the basis of an S3 guideline. A systematic search was carried out in PubMed and the Cochrane Library. The basis for presenting the level of evidence was the evidence classification of the Oxford Centre of Evidence-based Medicine. Whenever available, randomised controlled trials were given preference for discussing therapeutic issues. All systematic reviews and meta-analyses were assessed for their methodological quality, and effect size was taken into account. As the need for patient counselling is self-evident, specific tinnitus counselling should be performed. Due to the high level of evidence, validated tinnitus-specific, cognitive behavioural therapy is strongly recommended. In addition, auditory therapeutic measures can be recommended for the treatment of concomitant hearing loss and comorbidities; those should also be treated with drugs whenever appropriate. In particular, depression should be treated, with pharmacological support if necessary. If needed, psychiatric treatment should also be given on a case-by-case basis. With simultaneous deafness or hearing loss bordering on deafness, a CI can also be indicated. For auditory therapeutic measures, transcranial magnetic or direct current stimulation and specific forms of acoustic stimulation (noiser/masker, retraining therapy, music, and coordinated reset) for the treatment of chronic tinnitus the currently available evidence is not yet sufficient for supporting their recommendation.

Standardized tinnitus-specific individual cognitive-behavioral therapy: a controlled outcome study with 286 tinnitus patients.

BACKGROUND: Pharmacological treatment of tinnitus cannot be considered well established. Thus, reducing tinnitus severity through behavioral therapy is emerging as a key goal. METHODS: A total of 286 patients suffering from persistent and stable tinnitus for four months or longer participated in this controlled clinical multicenter study. The study investigated the efficacy and safety of a standardized treatment involving individual cognitive-behavioral therapy (CBT). Controls were 120 patients waiting to be treated. Therapy was standardized using manualized procedures within the setting of a specifically designed disease management program. The primary outcome measure was the tinnitus change score using an 8-point numeric verbal rating scale. Secondary outcome measures were tinnitus severity as determined by the tinnitus questionnaire score as well as the tinnitus loudness score and the tinnitus annoyance score using 6- and 8-point numeric verbal rating scales, respectively. Following a significant multivariate rank test, these four validated outcome measures were tested in the order given. RESULTS: The primary outcome measure, tinnitus change score, showed an efficacy of treatment with an odds ratio of 3.4 (95% confidence interval, 2.6-4.5). Of the treated patients, 84% showed a tinnitus change score improvement, but only 22% of controls did. The secondary outcome measures of tinnitus questionnaire score, loudness score, and annoyance score improved in the treatment group significantly more than in the control group. In the therapy group, the tinnitus questionnaire score was reduced by 50% from a median of 27 to 13.5; in the control group, no change in median tinnitus questionnaire score was observed. The multivariate endpoint of the primary and secondary outcome measures differed significantly (P < 0.0001) between treatment and control groups. The same was true when univariate scores were considered. CONCLUSIONS: A structured tinnitus-specific CBT using standardized tinnitus-specific interventions can be an effective individual therapy for the treatment of patients suffering from tinnitus for at least 4 months. The trial was registered at the ClinicalTrials.gov registry (ID: NCT 00719940).

Concept and evaluation of an endaurally insertable middle-ear implant.

A concept for a partially implantable hearing device, for which the power supply and signal transmission are provided by an optical transmission path, is evaluated. The actuator is designed to fit into the round-window niche and to couple directly to the round-window membrane. Implantable hearing aids can be a suitable solution in the case of severe hearing loss, where conventional hearing aids often fail. However, the surgical effort for an implantation is comparatively high. Therefore, the objective of our work was to provide a hearing system which combines reliable coupling to the auditory system with an easy implantation technique. The actuator was designed as a piezoelectric thin-film cantilever. The optical transmission path was realised using an infrared light-emitting diode combined with an active receiver circuit. For a voltage of 1V, the unloaded actuator presents displacement amplitudes of 1µm up to a stimulus frequency of 25kHz and forces up to 0.2mN. Proportionally larger forces can be achieved by stacking single actuators. The overall transmission loss from the electrical input of the light-emitting diode driver to the mechanical output of the unloaded actuator was less than 25dB at 1kHz and maximum output.

Risk factors for nasal malignancies in German men: the South-German Nasal cancer study.

BACKGROUND: There are few studies of the effects of nasal snuff and environmental factors on the risk of nasal cancer. This study aimed to investigate the impact of using nasal snuff and of other risk factors on the risk of nasal cancer in German men. METHODS: A population-based case-control study was conducted in the German Federal States of Bavaria and Baden-Württemberg. Tumor registries and ear, nose and throat departments provided access to patients born in 1926 or later. RESULTS: Telephone interviews were conducted with 427 cases (mean age 62.1 years) and 2.401 population-based controls (mean age 60.8 years). Ever-use of nasal snuff was associated with an odds ratio (OR) for nasal cancer of 1.45 (95% confidence interval [CI] 0.88-2.38) in the total study population, whereas OR in smokers was 2.01 (95% CI 1.00-4.02) and in never smokers was 1.10 (95% CI 0.43-2.80). The OR in ever-smokers vs. never-smokers was 1.60 (95% CI 1.24-2.07), with an OR of 1.06 (95% CI 1.05-1.07) per pack-year smoked, and the risk was significantly decreased after quitting smoking. Exposure to hardwood dust for at least 1 year resulted in an OR of 2.33 (95% CI 1.40-3.91) in the total population, which was further increased in never-smokers (OR 4.89, 95% CI 1.92-12.49) in analyses stratified by smoking status. The OR for nasal cancer after exposure to organic solvents for at least 1 year was 1.53 (1.17-2.01). Ever-use of nasal sprays/nasal lavage for at least 1 month rendered an OR of 1.59 (1.04-2.44). The OR after use of insecticides in homes was 1.48 (95% CI 1.04-2.11). CONCLUSIONS: Smoking and exposure to hardwood dust were confirmed as risk factors for nasal carcinoma. There is evidence that exposure to organic solvents, and in-house use of insecticides could represent novel risk factors. Exposure to asbestos and use of nasal snuff were risk factors in smokers only.

Conditions for highly efficient and reproducible round-window stimulation in humans.

Round-window stimulation is a new clinical approach for the application of active middle-ear implants. To investigate factors influencing the efficiency of round-window stimulation, experiments in 6 human temporal bones were performed with different actuator geometries and coupling conditions. The experiments show that the amplitude ratio between stapes and round-window actuator vibration is most efficient when using a 1.0-mm diameter rod with a 30° inclined tip geometry and an attached silicone pad. In this case, the amplitude ratio is 0.34 for frequencies up to 1.5 kHz and 0.27 for frequencies up to 20 kHz, with a standard deviation of only 4-6 dB at most frequencies. The analysis of data presented here and in a companion paper suggests that control of proper round-window membrane pretension as well as the inclined tip geometry are the major requirements for maximal performance.

Upper bounds for energy harvesting in the region of the human head.

This paper investigates different approaches for supplying power to implantable hearing systems via energy harvesting. Because of the specific nature of the problem, only energy harvesting in the region of the human head is considered. Upper bounds as well as more conservative estimations for harvesting mechanical, thermal, and electromagnetic energy are presented and discussed.

Controlled round-window stimulation in human temporal bones yielding reproducible and functionally relevant stapedial responses.

Stimulation of the round window (RW) has gained increasing clinical importance. Clinical, as well as human temporal bone and in-vivo animal studies show considerable variability. The influence of RW stimulation on the cochlea remains unclear. We designed a human temporal-bone study with controlled direct mechanical stimulation of the RW membrane to identify conditions for successful RW stimulation. Eight human temporal bones were stimulated on the RW by piezoelectric stack actuators with cylindrical aluminium rods of diameter 0.5 mm and with either flat or 30° inclined top surface. Using a dedicated two-stage positioning protocol for the actuator, we achieved highly reproducible measurements of the stimulus vibration at the RW and of the resultant vibration of the stapes footplate. The reverse transmission, characterized by the displacement ratio of the stapes-footplate relative to the actuator tip on the RW membrane, yielded an average displacement ratio of 0.089 up to 1.2 kHz when the actuator was coupled without angular misalignment to the RW membrane. The results suggest that 90-µm pretension of the RW membrane is essential for optimum and reproducible RW stimulation. The displacements are shown to be roughly consistent with the equal-volume displacement hypothesis under specific assumptions about the displacement mode of the RW membrane. It is further suggested that the large inter-patient variability in the effectiveness of RW stimulation might be due primarily to the success of coupling, rather than to the variability of functionally relevant anatomical parameters.

Accuracy of velocity distortion product otoacoustic emissions for estimating mechanically based hearing loss.

Distortion product otoacoustic emissions (DPOAEs) measured as vibration of the human eardrum have been successfully used to estimate hearing threshold. The estimates have proved more accurate than similar methods using sound-pressure DPOAEs. Nevertheless, the estimation accuracy of the new technique might have been influenced by endogenous noise, such as heart beat, breathing and swallowing. Here, we investigate in an animal model to what extent the accuracy of the threshold estimation technique using velocity-DPOAEs might be improved by reducing noise sources. Velocity-DPOAE I/O functions were measured in normal and hearing-impaired anaesthetized guinea pigs. Hearing loss was either conductive or induced by furosemide injection. The estimated distortion product threshold (EDPT) obtained by extrapolation of the I/O function to the abscissa was found to linearly correlate with the compound action potential threshold at the f(2) frequency, provided that furosemide data were excluded. The standard deviation of the linear regression fit was 6 dB as opposed to 8 dB in humans, suggesting that this accuracy should be achievable in humans with appropriate improvement of signal-to-noise ratio. For the furosemide animals, the CAP threshold relative to the regression line provided an estimate of the functional loss of the inner hair cell system. For mechanical losses in the middle ear and/or cochlear amplifier, DPOAEs measured as velocity of the umbo promise an accuracy of hearing threshold estimation comparable to classical audiometry.

Randomized, double blind, placebo controlled trial on the safety and efficacy of continuous intratympanic dexamethasone delivered via a round window catheter for severe to profound sudden idiopathic sensorineural hearing loss after failure of systemic therapy.

OBJECTIVES: To study the safety and efficacy of continuous intratympanic dexamethasone-phosphate (Dex-P) for severe to profound sudden idiopathic sensorineural hearing (ISSHL) or sudden idiopathic anacusis after failure of systemic therapy. STUDY DESIGN: Randomized, double-blind, placebo controlled multicenter trial. METHODS: Patients with ISSHL and insufficient recovery (mean 4PTA = 97 dB HL) after systemic high dose glucocorticoid therapy received either Dex-P (4 mg/ml) or placebo (NaCl 0.9%) continuously applied for 14 days into the round window niche via a temporarily implanted catheter. For ethical reasons, intratympanic treatment was continued with Dex-P in all patients for another 14 days after the placebo-controlled study period. According to a two-step adaptive study design an interim analysis was performed after inclusion of 23 patients. RESULTS: Intention-to-treat analysis for the primary outcome criterion (4PTA: 0.5-3 kHz) during the placebo controlled study period (14 days) showed an average hearing improvement in the treatment group of 13.9 dB (SD: 21.3) and in the placebo group of 5.4 dB (SD: 10.4). This difference in hearing improvement between the two groups (mean: 8.4 dB, SD: 17.0, 95% CI: -7.1-24.1) was statistically not significant (p = .26). Of the secondary outcome parameters, the largest benefit of local salvage therapy was found for maximum speech discrimination with an improvement of 24.4% (SD: 32.0) in the treatment and 4.5% (SD: 7.6) in the placebo group (p = 0.07). After a 3 month follow-up period (i.e. after all patients received intratympanic Dex-P) hearing improvement in the two groups was very similar. No serious adverse events were observed. Sample size calculation after the interim analysis resulted in stopping of the trial. CONCLUSIONS: The tendency toward better hearing improvement in the treatment group, the rather conservative inclusion criteria, the limited placebo-controlled observation period and the absence of serious adverse events supports further investigation local inner ear drug delivery as a first or second line treatment option for ISSHL.

Test-retest repeatability of distortion product otoacoustic emissions.

OBJECTIVES: Distortion product otoacoustic emissions (DPOAE) have become part of routine audiological diagnostics. The large scale of clinical DPOAE applications, such as screening of hearing in infants, objective estimation of hearing status, distinction between cochlear and retrocochlear origin of sensorineural hearing loss, exclusion of psychogenic hearing loss, monitoring of hearing during administration of ototoxic drugs, and others illustrates the significance of this audiological tool. In all diagnostic tests, knowledge about the procedure's test-retest repeatability is of crucial importance, to allow for distinction between measurement deviations and true physiological or pathological changes in monitoring over time. DESIGN: Measurements of DPOAE were performed in triplicate in 80 normally hearing ears of 40 subjects. Both immediate remeasurements with the ear probe left in place [single-fit mode (SF-mode)] and remeasurements after approximately 5 to 10 days [multiple-fit mode (MF-mode)] were included. DPOAE primary tone levels were varied in 5 dB steps from L2 = 60 to 20 dB SPL (L1 = L2 x 0.4 + 39 dB SPL) and within the frequency range f2 = 1 to 6 kHz. Repeatability of DPOAE was evaluated by the standard error of measurement (Sm), reliability (Cronbach alpha), absolute differences between measurements, 95% confidence intervals, and repeatability standard deviations. RESULTS: Sm averaged 0.67 dB over all frequencies and primary tone levels in the SF-mode, and 1.44 dB in the MF-mode, respectively. As expected, test-retest repeatability declined with decreasing primary tone levels; however, repeatability values were still mostly satisfactory with the lower primary tone levels. For the exemplary primary tone level combination of L1/L2 = 63/60 dB SPL, which is close to common clinical paradigms, the difference between two DPOAE measurements under the reported test conditions could be considered statistically significant (p = 0.05) if it exceeded 0.7 to 1.3 dB in the range 1 to 5 kHz and 2.3 dB for 6 kHz in the SF-mode, when compared with 1.8 to 2.7 dB for 1 to 5 kHz and 3.7 dB for 6 kHz in the MF-mode. Signal to noise ratio (SNR) did not seem to have a large influence on repeatability, as long as SNR was within 6 to 35 dB, which covers the range of most clinical DPOAE measurements. CONCLUSIONS: The DPOAE-test-retest study presented here is to our knowledge the first, which combines variation of primary tone levels, assessment of both SF- and MF-modes, and comparison of the two modalities within the same subjects. Although the measurements were conducted under practical conditions resembling the clinical setting, repeatability was generally good. The widely used minimum SNR of 6 dB seems to be a recommendable criterion when considering both practicability and measurement quality under clinical conditions. The current findings underline the suitability of DPOAE as a monitoring tool of cochlear status over time. The data are intended to assist the clinician and the scientist in the correct interpretation of DPOAE level changes in the test-retest situation.

Speech-in-noise intelligibility does not correlate with efferent olivocochlear reflex in humans with normal hearing.

CONCLUSION: According to the presented data, speech-in-noise intelligibility (SI) does not correlate with olivocochlear efferent activity - as measured by contralateral suppression (CS) of distortion product otoacoustic emissions (DPOAE) in humans with normal auditory threshold. OBJECTIVES: Literature data indicate a possible role of the medial olivocochlear efferents in speech intelligibility, especially in background noise. The objective of this study was to investigate this relationship. MATERIALS AND METHODS: SI was evaluated in three independent sessions by determining the ratio speech level/noise level, at which 50% of the words are understood (i.e. speech reception threshold, SRT). Efferent activity was inferred measuring CS of DPOAE, using two different paradigms with extensive variation of stimulus parameters and duplicate measurements. RESULTS: For optimum measurement of CS, the study was restricted to subjects (n =49) with valid DPOAE down to primary tone levels L1=47/L2 =20 dB SPL. Average SRT was -6.66 dB (-4.50 to -7.65 dB, SD 0.63 dB). CS increased with decreasing primary tone levels, with mean absolute CS values in the range of 0.6-6 dB SPL. Test-retest repeatability was good. Statistical evaluation revealed no significant relationship between SI and CS of DPOAE.

Hyposmotic stimulation-induced nitric oxide production in outer hair cells of the guinea pig cochlea.

Nitric oxide (NO) production during hyposmotic stimulation in outer hair cells (OHCs) of the guinea pig cochlea was investigated using the NO sensitive dye DAF-2. Simultaneous measurement of the cell length and NO production showed rapid hyposmotic-induced cell swelling to precede NO production in OHCs. Hyposmotic stimulation failed to induce NO production in the Ca2+-free solution. L-NG-nitroarginine methyl ester (L-NAME), a non-specific NO synthase inhibitor and gadolinium, a stretch-activated channel blocker inhibited the hyposmotic stimulation-induced NO production whereas suramin, a P2 receptor antagonist did not. S-nitroso-N-acetylpenicillamine (SNAP), a NO donor inhibited the hyposmotic stimulation-induced increase in the intracellular Ca2+ concentrations ([Ca2+]i) while L-NAME enhanced it. 1H-[1,2,4]oxadiazole[4,3a]quinoxalin-1-one, an inhibitor of guanylate cyclase and KT5823, an inhibitor of cGMP-dependent protein kinase (PKG) mimicked effects of L-NAME on the Ca2+ response. Transient receptor potential vanilloid 4 (TRPV4), an osmo- and mechanosensitive channel was expressed in the OHCs by means of immunohistochemistry. 4alpha-phorbol 12,13-didecanoate, a TRPV4 synthetic activator, induced NO production in OHCs. These results suggest that hyposmotic stimulation can induce NO production by the [Ca2+]i increase, which is presumably mediated by the activation of TRPV4 in OHCs. NO conversely inhibits the Ca2+ response via the NO-cGMP-PKG pathway by a feedback mechanism.

Hyposmotic stimulation-induced nitric oxide production in outer hair cells of the guinea pig cochlea.

Nitric oxide (NO) production during hyposmotic stimulation in outer hair cells (OHCs) of the guinea pig cochlea was investigated using the NO sensitive dye DAF-2. Simultaneous measurement of the cell length and NO production showed rapid hyposmotic-induced cell swelling to precede NO production in OHCs. Hyposmotic stimulation failed to induce NO production in the Ca(2+)-free solution. L-N(G)-nitroarginine methyl ester (L-NAME), a non-specific NO synthase inhibitor and gadolinium, a stretch-activated channel blocker inhibited the hyposmotic stimulation-induced NO production whereas suramin, a P2 receptor antagonist did not. S-nitroso-N-acetylpenicillamine (SNAP), a NO donor inhibited the hyposmotic stimulation-induced increase in the intracellular Ca(2+) concentrations ([Ca(2+)](i)) while L-NAME enhanced it. 1H-[1,2,4]oxadiazole[4,3a]quinoxalin-1-one, an inhibitor of guanylate cyclase and KT5823, an inhibitor of cGMP-dependent protein kinase (PKG) mimicked effects of L-NAME on the Ca(2+) response. Transient receptor potential vanilloid 4 (TRPV4), an osmo- and mechanosensitive channel was expressed in the OHCs by means of immunohistochemistry. 4alpha-phorbol 12,13-didecanoate, a TRPV4 synthetic activator, induced NO production in OHCs. These results suggest that hyposmotic stimulation can induce NO production by the [Ca(2+)](i) increase, which is presumably mediated by the activation of TRPV4 in OHCs. NO conversely inhibits the Ca(2+) response via the NO-cGMP-PKG pathway by a feedback mechanism.

Cochlear pharmacokinetics with local inner ear drug delivery using a three-dimensional finite-element computer model.

HYPOTHESIS: Cochlear fluid pharmacokinetics can be better represented by three-dimensional (3D) finite-element simulations of drug dispersal. BACKGROUND: Local drug deliveries to the round window membrane are increasingly being used to treat inner ear disorders. Crucial to the development of safe therapies is knowledge of drug distribution in the inner ear with different delivery methods. Computer simulations allow application protocols and drug delivery systems to be evaluated, and may permit animal studies to be extrapolated to the larger cochlea of the human. METHODS: A finite-element 3D model of the cochlea was constructed based on geometric dimensions of the guinea pig cochlea. Drug propagation along and between compartments was described by passive diffusion. To demonstrate the potential value of the model, methylprednisolone distribution in the cochlea was calculated for two clinically relevant application protocols using pharmacokinetic parameters derived from a prior one-dimensional (1D) model. In addition, a simplified geometry was used to compare results from 3D with 1D simulations. RESULTS: For the simplified geometry, calculated concentration profiles with distance were in excellent agreement between the 1D and the 3D models. Different drug delivery strategies produce very different concentration time courses, peak concentrations and basal-apical concentration gradients of drug. In addition, 3D computations demonstrate the existence of substantial gradients across the scalae in the basal turn. CONCLUSION: The 3D model clearly shows the presence of drug gradients across the basal scalae of guinea pigs, demonstrating the necessity of a 3D approach to predict drug movements across and between scalae with larger cross-sectional areas, such as the human, with accuracy. This is the first model to incorporate the volume of the spiral ligament and to calculate diffusion through this structure. Further development of the 3D model will have to incorporate a more accurate geometry of the entire inner ear and incorporate more of the specific processes that contribute to drug removal from the inner ear fluids. Appropriate computer models may assist in both drug and drug delivery system design and can thus accelerate the development of a rationale-based local drug delivery to the inner ear and its successful establishment in clinical practice.

Technical note on microcatheter implantation for local inner ear drug delivery: surgical technique and safety aspects.

HYPOTHESIS: Despite its invasiveness, the temporary implantation of a microcatheter into the middle ear cavity is an appropriately safe method for providing continuous drug delivery to the inner ear. BACKGROUND: For the application of drugs to the inner ear, different delivery strategies are available ranging from intratympanic injections to temporarily implanted microcatheters. It has recently been demonstrated that the choice of the drug delivery system influences the pharmacokinetics in the inner ear. If a continuous drug application over several weeks is required, a secure placement of the delivery device (i.e., the microcatheter) is necessary to guarantee efficient drug delivery and to avoid unwanted side effects. STUDY DESIGN: Retrospective chart review. MATERIALS AND METHODS: During 2000 to 2005, 25 patients with acute unilateral severe-to-profound hearing loss or anacusis and failure of systemic high-dose glucocorticoid and rheological therapy were offered an intratympanic delivery of glucocorticoids via a temporarily implanted catheter and an external pump for up to 4 weeks as a salvage treatment option. The standardized surgical implantation and fixation technique developed for the microcatheter were characterized by six elements: 1) a medial and a lateral tunnel connected by a groove in the posterior wall of the bony ear canal, 2) stabilization of the catheter with bone wax and soft tissue plugs in the tunnels, 3) an ear canal packing, 4) a series of fixating sutures along the catheter, 5) an adhesive dressing, and 6) additional tapes at the connecting line between pump and catheter. At the end of the implantation period, the catheter was removed by a second surgical procedure allowing for evaluation of the catheter position and the condition of the middle ear space. RESULTS: Adverse events included catheter dislocation, catheter obstruction, formation of mild granulation tissue in the middle ear cavity, tympanic membrane defects, and ear canal skin defects. With introduction of an improved implantation and fixation technique, the number of catheter dislocations could be significantly reduced. No complications were observed on long-term follow-up. CONCLUSION: If the pharmacokinetics or pharmacodynamics of a specific local inner ear therapy approach requires a continuous intratympanic drug application (e.g., to restore hearing in patients with severe or profound hearing loss), the temporary implantation of a microcatheter by a standardized surgical technique is a feasible and appropriately safe method for providing continuous drug delivery to the inner ear.