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Objectives: Medical overuse exposes patients to unnecessary risks of harm. It is an open question whether and how patients perceive the concept of medical overuse, its causes and negative consequences., Design: A qualitative study design, using elements of the Grounded Theory Approach by Strauss and Corbin., Setting: Between May 2017 and January 2020, we recruited participants and conducted face-to-face interviews in the participants' homes. Data collection took place in Bavaria, Germany., Participants: We recruited 16 participants (female=8, male=8) with various characteristics for the study. We used different strategies such as flyers in supermarkets, pharmacies, participants spreading information about the study or local multipliers (snowball sampling)., Results: The participants mostly defined medical overuse as too much being done but understood the concept superficially. During the interviews, most participants could describe examples of medical overuse. They named a variety of direct and indirect drivers with economic factors suspected to be the main driver. As a consequence of medical overuse, participants named the physical and emotional harm (eg, side effects of medication). They found it difficult to formulate concrete solutions. In general, they saw themselves more in a passive role than being responsible for bringing about change and solutions themselves. Medical overuse is a 'problem of the others'. The participants emphasised that health education is important in reducing medical overuse., Conclusions: Medical overuse was little discussed among participants, although many participants reported experiences of too much medicine. Health education and strengthening the patients' self-responsibility can play a vital role in reducing medical overuse., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: A small number of cochlear implant (CI) users experience facial nerve stimulation (FNS), which can manifest as facial twitching. In some patients, this can be resolved by adjusting the electrical stimulation parameters. However, for others, facial stimulation can significantly impair CI outcomes or even prevent its use. The exact mechanisms underlying FNS are unclear and may vary among patients., Design: Transimpedance measurements were used to assess lateral and longitudinal spread of current within 15 cochlea of nucleus CI recipients with FNS (13 unilateral recipients and 1 bilateral recipient). We compared the transimpedance measurements with programming parameters from clinical visits and pre- and postoperative temporal bone computed tomography (CT) scans to identify factors that may contribute to FNS in each CI ear., Results: In nine ears, transimpedance curves showed inflection, which suggests a localized current sink within the cochlea. This indicates a low-impedance pathway through which current exits the cochlea and stimulates the labyrinthine segment of the facial nerve canal. Electrodes near this current sink were disabled or underfit to minimize facial stimulation. In the other seven ears, current flow peaked toward the basal end of the cochlea, suggesting that current exits through the round window or other structures near the basal end of the cochlea, stimulating the tympanic segment of the facial nerve., Conclusions: Objective transimpedance measurements can be used to elucidate the mechanisms of FNS and to develop strategies for optimizing electrical stimulation parameters and speech coding to minimize or eliminate FNS in a small subset of CI users., Competing Interests: The authors do not have any conflict of interest to report., (Copyright © 2024, Otology & Neurotology, Inc.)

Aim: In Marfan syndrome, various cardiovascular pathologies, such as aortic dilatation and mitral valve pathologies, already occur in childhood and determine course of the disease. This study aimed to establish additional cardiovascular risk markers for severe Marfan phenotypes. We investigated tricuspid valve prolapse (TVP) and its predictive value for outcome of paediatric Marfan disease., Methods: In this retrospective, observational cohort study, we identified 130 paediatric Marfan patients (10.7 ± 4.8 years) with FBN1 variants. We divided patients into two groups based on TVP presence and performed a cross-sectional analysis to investigate the association of TVP with other cardiovascular, ocular and systemic pathologies, at first and last visit. A longitudinal analysis was performed with follow-up data., Results: At baseline, patients with TVP had higher incidence of aortic root dilatation (p = 0.013), mitral valve prolapse (p = 0.0001) and systemic manifestations (p = 0.025) than patients without TVP. At follow-up, previous presence of TVP predicted higher probability of aortic root dilatation (p = 0.002), mitral valve prolapse (p = 0.0001) and systemic manifestations (p = 0.002)., Conclusion: This shows that TVP is linked to both cardiac and extracardiac Marfan manifestations and TVP is an important marker for a disease severity in these children. Therefore, TVP should be assessed routinely using echocardiography in paediatric Marfan patients., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Objectives: To investigate the preservation of residual hearing in subjects who received the Nucleus Hybrid L24 cochlear implant. To investigate the performance benefits up to one year post-implantation in terms of speech recognition, sound quality, and quality of life., Design: Prospective, with sequential enrolment and within-subject comparisons. Post-operative performance using a Freedom Hybrid sound processor was compared with that of pre-operative hearing aids., Study Sample: Sixty-six adult hearing-impaired subjects with bilateral severe-to-profound high frequency hearing loss., Results: Group median increase in air-conduction thresholds in the implanted ear for test frequencies 125-1000 Hz was < 15 dB across the population; both immediately and one year post-operatively. Eighty-eight percent of subjects used the Hybrid processor at one year post-op. Sixty-five percent of subjects had significant gain in speech recognition in quiet, and 73% in noise (≥ 20 percentage points/2 dB SNR). Mean SSQ subscale scores were significantly improved (+ 1.2, + 1.3, + 1.8 points, p < 0.001), as was mean HUI3 score (+ 0.117, p < 0.01). Combining residual hearing with CI gave 22-26 %age points mean benefit in speech recognition scores over CI alone (p < 0.01)., Conclusions: Useful residual hearing was conserved in 88% of subjects. Speech perception was significantly improved over preoperative hearing aids, as was sound quality and quality of life.

The Nucleus CI24RE ‘Freedom' device offers higher stimulation rates and lower noise levels in action potential measurements (ECAPs) than previous devices. A study including ten European implant teams showed that the effect of changes in rate from 250 to 3500 pulses per second on tilt and curvature of the T and C profiles is insignificant. When changing rate one may change the levels at all electrodes by the same amount. Using an automated procedure ECAPs could be measured quickly and reliably at a noise level of only 1 microV, this did not result in improved correlations between the tilt and curvature parameters of the ECAP profiles and those of the T and C profiles. Average C levels appear to differ markedly among implant centers; a better assessment protocol is required. When increasing stimulus rate one should take into account that this requires higher pulse charges per second and more power consumption.

Patients with high-frequency deafness and/or substantial residual hearing across frequencies might benefit from combined electro-acoustic stimulation. The Hybrid-L electrode was designed to address the issues of both hearing conservation and effective electrical stimulation in those recipients. The electrode with 22 contacts should be inserted through the round window membrane, and covers approximately 270 degrees of the basal turn of the cochlear. This insertion length is equivalent to the one seen in many patients using the former Nucleus straight electrode. Twenty-four patients with low-frequency thresholds of 60 dB or better, up to 500 Hz, were implanted with a Hybrid-L device in a clinical trial at the Medical University of Hannover. Another group of 8 recipients with less residual hearing was included under extended inclusion criteria. Residual hearing was conserved in the majority of cases. One patient had a loss of more than 30 dB, but hearing partially recovered after 9 months. The median loss in all patients was 10 dB in both the Hybrid group and the extended group. Patients were able to use the residual hearing postoperatively to the same extent as preoperatively. In the Hybrid mode (cochlear implant + ipsilateral hearing aid), patients showed a significant improvement of 21% (p = 0.002) in speech understanding in quiet using the Freiburger Monosyllabic Word Test compared to the preoperative scores under aided conditions with their hearing aid. The Oldenburg Sentence Test in noise showed a remarkable average improvement of 10.2 dB (p < 0.001) compared to the preoperative hearing aid only mode. An additional improvement could be seen in the combined mode using an additional contralateral hearing aid. Recipients with a shorter duration of high-frequency hearing loss showed a larger benefit than those with a longer duration of hearing loss. Hearing conservation using the Hybrid-L electrode and a given surgical technique is possible with high probability in patients with high-frequency deafness or pantonal hearing loss. The use of the residual acoustic hearing offers specific advantages, especially for understanding speech in noise and for spatial hearing., ((c) 2009 S. Karger AG, Basel.)

Objectives: The first objective of the study was to determine whether there were any consistent differences in the electrophysiological spread of excitation (SOE) function, as measured using the electrically evoked compound action potential (ECAP), between dual and single electrode stimulation with the Nucleus Freedom cochlear implant system. Dual electrode stimulation is produced by electrically coupling two adjacent single electrodes. The second objective was to determine whether there were any relationships between the SOE functions and psychophysically measured pitch ranking of dual and single electrodes., Design: Nine adult cochlear implant subjects participated in the study. ECAPs for dual and single electrode stimulation were measured using the forward masking paradigm, as also used in the Neural Response Telemetry (NRT) software with the Nucleus implant. Research software was used to generate the dual and single electrode stimuli and record the ECAPs. Spread of excitations (SOEs) were measured on a dual electrode and the two adjacent single electrodes, at three positions on the array: apical, mid, and basal. Compared were the ECAP amplitudes at the peak of the SOE functions, the widths of the scaled SOE functions at the 75% point, and the electrode positions at the peak of the SOE function and at the 75%, 50%, and 25% points on apical and basal sides of the scaled functions. Pitch ranking was measured for the same sets of dual and single electrodes. A two-alternative forced choice procedure was used, with the electrodes in each set paired with each other as AB and BA pairs. The subject indicated which of the two stimuli had the higher pitch., Results: Dual electrode SOEs could be successfully obtained using the same methods as used to measure single electrode SOEs. The shapes of the dual and single electrodes SOEs were similar. There was a trend of a higher ECAP amplitude for the dual electrode at the peak of the SOE function, but this was only significant for two comparisons at the apical and basal positions. There were no significant differences in the SOE widths between dual and single electrodes. The electrodes at the peak of the SOE function and on the apical and basal sides of the function at the 75% position were, in most cases, tonotopically ordered. At the 50% and 25% positions, there were fewer significant differences between the dual and single electrodes The pitch ranking results showed that in 74% of cases, the single and dual electrodes at each position were successfully ranked in the expected tonotopic order. There were no statistically significant correlations between the pitch ranking results and the ordering of electrodes on the SOE functions., Conclusions: Dual electrode stimulation produced similar SOE functions as single electrode stimulation. A tonotopic ordering of electrodes at the peak of the SOE and on the sides of the functions was found, but this was not statistically related to the pitch ranking results., Summary: Electrophysiological spread of neural excitation (SOE) and pitch perception using dual and single electrodes was investigated in nine subjects using the Nucleus Freedom cochlear implant. Dual electrodes are produced by electrically coupling two adjacent single electrodes. The dual and single electrodes SOEs were similar in shape. Higher electrophysiological response amplitudes were generally found for the dual electrodes. There were no differences in SOE widths between dual and single electrodes. In three quarters of cases, dual and single electrodes were successfully pitch ranked in the expected tonotopic order. No significant relationships between pitch ranking and the SOE functions were found.

Four adult bilateral cochlear implant users, with good open-set sentence recognition, were tested with three different sound coding strategies for binaural speech unmasking and their ability to localize 100 and 500 Hz click trains in noise. Two of the strategies tested were envelope-based strategies that are clinically widely used. The third was a research strategy that additionally preserved fine-timing cues at low frequencies. Speech reception thresholds were determined in diotic noise for diotic and interaurally time-delayed speech using direct audio input to a bilateral research processor. Localization in noise was assessed in the free field. Overall results, for both speech and localization tests, were similar with all three strategies. None provided a binaural speech unmasking advantage due to the application of 700 micros interaural time delay to the speech signal, and localization results showed similar response patterns across strategies that were well accounted for by the use of broadband interaural level cues. The data from both experiments combined indicate that, in contrast to normal hearing, timing cues available from natural head-width delays do not offer binaural advantages with present methods of electrical stimulation, even when fine-timing cues are explicitly coded.

Cochlear recently released the Nucleus Freedom System which has been based on the Nucleus Research Platform 8. Both systems make use of the same implant, the CI24RE, which includes expanded total stimulation rates up to 32 kHz. In this study the performance of the ACE strategy at 500, 1200 and 3500 pps/channel was investigated using an ABC-CBA design. At the end of each period speech tests were performed. In the CBA phase the patients completed a comparative questionnaire to determine the subjective rate preference. Preliminary results in 13 recipients indicate no differences in for the ACE strategy at rates ranging from 500 pps to 3500 pps/channel.

Hypothesis: Perimodiolar intracochlear electrodes with contacts facing towards the modiolus have limited current flow towards the outer wall of the cochlea and therefore, may reduce the occurrence of facial nerve stimulation (FN) in cochlear implant subjects., Background: Facial nerve stimulation is a well-known complication in cochlear implant treatment especially in the group of subjects with otosclerosis. The possible explanation of this side effect is a change of the electrical properties of the otosclerotic bone leading to leakage current and resulting in facial nerve stimulation., Methods: Four CI subjects who had been implanted with a Nucleus Mini22 device with a Nucleus Straight electrode between 9 to 12 years ago suffered from severe FN stimulation. Electrode contacts had to be switched off so that they could only use 4, 11, 13, and 15 electrodes of their usual set of 22. The switch off resulted in deteriorating speech understanding over time. Therefore, all subjects were reimplanted with a Nucleus 24R device with a Contour electrode. Preoperatively, the threshold of FN stimulation was obtained on all electrodes subjectively. Intraoperatively, FN stimulation thresholds were measured objectively with both, the old and the new device and were compared. NRT and SRT thresholds were also obtained with the reimplanted device to assure effective electrical stimulation of the auditory nerve., Results: In all four cases the postoperative fitting demonstrated no FN stimulation on all electrodes up to maximum comfortable level. The insertion of the Contour electrode array was complete in three cases, in one case the array could only be inserted partially similarly to the situation before the reimplantation. Speech perception tests showed a significant improvement in all subjects with the new device., Conclusion: Electrodes with modiolar facing contacts and perimodiolar position like the Nucleus Contour electrode reduce the possibility of facial nerve stimulation significantly due to more focused electrical stimulation.

The efficiency of the photoinduced radical addition of tertiary amines to olefinic double bonds is significantly enhanced and the stereoselectivity is influenced when thiocarbonyl compounds are added to the reaction mixture.

Due to improved technology, cochlear implant (CI) candidacy has been widened towards patients with usable residual hearing in the low frequency range. These patients might benefit from additional acoustic amplification provided that residual hearing can be preserved with cochlear implantation. To provide a high probability of hearing preservation, a new electrode array was designed and developed at the Medizinische Hochschule Hannover. This 'Hybrid-L' electrode array has 22 electrodes spread over 15 mm with an overall insertion depth of 16 mm. The straight electrode with modiolus facing contacts is designed for a round window insertion. It shall provide the full range of the currently most advanced Nucleus CI system. A temporal bone study demonstrated the favorable insertion characteristics and minimized trauma to intracochlear structures. Compared to standard CI electrodes especially no basilar membrane perforation could be found. So far, 4 patients have been implanted and residual hearing could be preserved. One patient was fitted and showed a marked additional benefit from the electroacoustic stimulation compared to either acoustic or electrical stimulation alone. These results are very encouraging towards a concept of reliable hearing preservation with cochlear implantation., (Copyright (c) 2006 S. Karger AG, Basel.)

The purpose of this study was to evaluate the performance of the new features of the Nucleus Research Platform 8 (RP8), a system developed specifically for research purposes The RP8 consists of a research implant, a speech processor and a new NRT software (NRT v4), and includes comparisons of the different artefact-cancellation methods, NRT threshold, and recovery function measurements. The system has new artefact-suppression techniques and new diagnostic capabilities; their performance has been verified in animal experiments. In this study, NRT data were collected from 15 postlingually deafened adult cochlear implant patients intraoperatively and up to 6 months postoperatively after switch-on. The initial investigation in two clinics in Europe focused primarily on the enhanced NRT capabilities Results from the trial in two European clinics indicate that NRT measurements can be obtained with lower noise levels. A comparison of the different artefact-cancellation techniques showed that the forward-masking paradigm implemented in the Nucleus 3 system is still the method of choice. The focus of this report is on recovery function characteristics, which may give insight into auditory nerve fiber properties with regard to higher stimulation rates.

The gap junction protein connexin30 (Cx30) is expressed in a variety of tissues that include epithelial and mesenchymal structures of the inner ear. We generated Cx30 (Gjb6) deficient mice by deletion of the Cx30 coding region. Homozygous mutants (Cx30((-/-))) were born at the expected Mendelian frequency, developed normally and were fertile. However, they exhibit a severe constitutive hearing impairment. From the age of hearing onset, these mice lack the electrical potential difference between the endolymphatic and perilymphatic compartments of the cochlea, i.e. the endocochlear potential, which plays a key role in the high sensitivity of the mammalian auditory organ. In addition, after postnatal day 18, the cochlear sensory epithelium starts to degenerate by cell apoptosis. This degeneration process is likely to account for the concomitant decrease of the endolymphatic potassium concentration and the aggravation of the hearing loss in adult Cx30((-/-)) mice. The Cx30 ((-/-)) phenotype thus reveals the critical role of Cx30 both in generating the endocochlear potential and for survival of the auditory hair cells after the onset of hearing. The Cx30 deficient mice may represent a valuable model to study the mechanism of the hearing loss in human patients carrying a homozygous deletion of the CX30 gene (del Castillo et al., 2002, New Engl. J. Med., 346, 243-249).

Mutations in the human GJB3 gene that codes for Connexin31 (Cx31), a protein subunit of gap junction channels, have recently been reported to cause deafness and the skin disorder erythrokeratodermia variabilis. To study the function of this gene in mice, we generated animals with targeted replacement of the Cx31 gene (Gjb3) by a lacZ reporter gene. Although homozygous Cx31-deficient adult mice (Gjb3(-/-)) were found among the offspring of heterozygous Cx31-deficient parents (Gjb3(+/-)), 60% of the animals expected according to Mendelian inheritance were lost between ED 10.5 and 13.5. Placentas of Gjb3(-/-) embryos at ED 9.5 were smaller than controls as a result of severely reduced labyrinth and spongiotrophoblast size. From ED 10.5 onward, placentas of surviving Gjb3(-/-) embryos recovered progressively and reached normal size and morphology by ED 18.5. This corresponds to a time period in which another connexin isoform, Connexin43, is upregulated in spongiotrophoblast cells of Cx31-deficient and control placentas. No morphological or functional defects of skin or inner ear were observed in surviving adult Gjb3(-/-) mice. We conclude that Cx31 is essential for early placentation but can be compensated for by other connexins in the embryo proper and adult mouse., (Copyright 2001 Academic Press.)

The paper describes finite element related procedures for inverse localization of multiple sources in realistically shaped head models. Dipole sources are modeled by placing proper monopole sources on neighboring nodes. Lead field operators are established for dipole sources. Two different strategies for the solution of inverse problems, namely combinatorial optimization techniques and regularization methods are discussed and applied to visually evoked potentials, for which exemplary results are shown. Most of the procedures described are fully automatic and require only proper input preparation. The overall work for the example presented (from EEG recording to visual inspection of the results) can be performed in roughly a week, most of which is waiting time for the computation of the lead field matrix or inverse calculations on a standard and affordable engineering workstation.

The electric conductivities of different tissues are important parameters of the head model and their precise knowledge appears to be a prerequisite for the localization of electric sources within the brain. To estimate the error in source localization due to errors in assumed conductivity values, parameter variations on skull conductivities are examined. The skull conductivity was varied in a wide range and, in a second part of this paper, the effect of a nonhomogeneous skull conductivity was examined. An error in conductivity of lower than 20% appears to be acceptable for fine finite element head models with average discretization errors down to 3 mm. Nonhomogeneous skull conductivities, e.g., sutures, yield important mislocalizations especially in the vincinty of electrodes and should be modeled.

Interleukin 2 (IL-2) and interleukin 4 (IL-4) secreted by activated but not by resting mature T cells are pleiotropic cytokines affecting growth and differentiation of diverse cell types, such as T cells, B cells, and mast cells. There is little information about the molecular basis for the constitutive repression of IL-2 and IL-4 gene expression in unstimulated T cells. We investigated the possibility that wild-type (wt) p53, a nuclear tumor suppressor protein, might serve to repress IL-2 and IL-4 gene expression in murine E14 T lymphoma and in human Jurkat cells. We transiently cotransfected these cells with constitutive simian virus 40 (SV 40) early promoter expression plasmids overproducing wt or mutant murine p53 and with appropriate luciferase (luc) reporter plasmids containing the promoter elements of murine IL-2 and IL-4 genes to evaluate the effect of various p53 species on these promoters. Murine wt p53 derived from pSG5p53cD strongly repressed the IL-2 and IL-4 promoters in both cell lines induced by the phorbol ester TPA and the Ca2+ ionophore ionomycin but not, however, in uninduced cells. In similar transient transfection experiments with lymphoma cells, overexpression of deletion mutant species of murine p53 revealed that the N-terminal and C-terminal domains are crucial for inhibition of both IL-2 and IL-4 gene expression. These parts of p53 comprise the transactivation domain at the amino terminal side, which has previously also been shown to interact with the TATA-box binding-protein TBP and the carboxy-terminal oligomerization domain. Additionally, it was shown that a previously described inhibitory protein, the high-mobility-group protein HMG-I/Y, does not functionally interact with p53. Cotransfection of expression plasmids for both p53 and HMG-I/Y did not alter the extent of inhibition by the individual proteins. These data suggest that p53 can downmodulate both IL-2 and IL-4 gene expression and that both the transactivation and oligomerization domains of the tumor suppressor protein are essential for this transcriptional repression.

The onset of DNA replication is an important step within the life cycle of the human neurotropic polyomavirus JC. In this report, evidence that both the human and the murine tumor suppressor protein p53 strongly inhibit JCV DNA replication in vivo is presented. This inhibition is dose-dependent and not a secondary effect of a decreased expression of JCV large T-antigen in response to p53. Using deletion mutants of murine p53 and tumor-derived point mutations of human p53, the basis of the suppression of JCV DNA replication by p53 was dissected. Deletion of either the amino- or the carboxy-terminal domain of murine p53 did not interfere with the repression of JCV DNA replication. However, deletion of the highly conserved central region of p53 abolished the inhibitory effect on replication. The tumor-derived human mutant p53(His273) inhibited JCV DNA replication significantly, whereas another tumorigenic mutant, p53(His175), had no inhibitory effect Concomitantly, a direct protein-protein interaction between p53 and JCV large T-antigen was lost in mutants which did not affect JCV DNA replication. These results strongly suggest that p53 inhibits JCV DNA replication by interacting with JCV large T-antigen.

Three manual suture techniques (double-layer inverting, single-layer end-to-end, and continuous suture of the submucosa) were compared with anastomoses performed by stapling instruments (EEA, KZ 28) on the canine colon. The two manual techniques with exact end-to-end apposition led to primary wound-healing during the early postoperative period (3-20 days). There was no significant stenosis at the site of anastomosis five and ten months postoperatively. Inverting sutures as well as stapled anastomoses, however, showed delayed healing with considerable inflammatory reaction, resulting in marked stenosis after five to ten months.

Postoperative parenteral nutrition can only be optimally effective if the characteristics of post-traumatic metabolism are taken into account. Two main possibilities are discussed for the carbohydrate component of parenteral nutrition during this phase: glucose with high doses of insulin or non-glucose carbohydrates (sugar substitutes) possibly in a suitable combination with glucose. The risks as well as the technical and organisational problems involved in the use of them are discussed and the authors prefer the second of the two alternatives. Possible side effects of non-glucose carbohydrates are pointed out and it is shown how these can be avoided by observing dose guidelines. So far a combination of frucose : glucose : xylitol in a ratio of 2 : 1 :1 with a total dose of 0.50 g/kg/hour has been studied most thoroughly. This combination normalises the fat metabolism and improves glucose tolerance without requiring exogenous insulin. Experiences with this combination as well as individual non-glucose carbohydrates on operated patients have been given continuously for up to 7 days and in some cases even for several weeks. No side effects, no deviations from a steady state and no abnormal changes of the laboratory values occurred. The authors are of the opinion that non glucose carbohydrates are necessary if the facilities for frequent blood sugar controls are not available.