Out-of-Hospital cardiac arrest & SmartphonE RespOndErS trial (HEROES Trial): Methodology and study protocol of a pre-post-design trial of the effect of implementing a smartphone alerting system on survival in out-of-hospital cardiac arrest.

Background: Since 2021, international guidelines for cardiopulmonary resuscitation recommend the implementation of so-called "life-saving systems". These systems include smartphone alerting systems (SAS), which enable dispatch centres to alert first responders via smartphone applications, who are in proximity of a suspected out-of-hospital cardiac arrest (OHCA). However, the effect of SAS on survival remains unknown. Aim: The aim is to assess the rate of survival to hospital discharge in adult patients with OHCA not witnessed by emergency medical services (EMS): before and after SAS implementation. Design: Multicentre, prospective, observational, intention-to-treat, pre-post design clinical trial. Population: Adults (aged ≥ 18 years), OHCA not witnessed by EMS, no traumatic cause for cardiac arrest, cardiopulmonary resuscitation initiated or continued by EMS. Setting: Dispatch-centre-based. Outcomes: Primary: survival to hospital discharge. Secondary: time to first compression, rate of basic life support measures before EMS arrival, rate of patients with shockable rhythm at EMS arrival, Cerebral Performance Category at hospital discharge, and duration of hospital stay. Sample size: Assuming an absolute difference in survival rates to hospital discharge of 4% in the two groups (11% before implementation of the SAS versus 15% after) and 80% power, and a type 1 error rate of 0.05, the required sample size is N = 1,109 patients per group (at least N = 2,218 evaluated patients in total). Conclusions: The HEROES trial will investigate the effects of a SAS on the survival rate after OHCA. Trial registration: German Clinical Trials Register (DRKS, ID: DRKS00032920).

Short-Term Ambient Air Pollution and Urticaria in Guangzhou, China: Estimating the Association and Population Attributable Fraction.

Limited evidence is available regarding the association between acute exposure to ambient air pollutants and the risk of urticaria, even though the skin is an organ with direct contact with the external environment. This study utilized generalized additive models to investigate the association between particulate matter with an aerodynamic diameter smaller than 10 µm (PM10) and 2.5 µm (PM2.5), nitrogen dioxide (NO2) and sulfur dioxide (SO2), and daily outpatient visits for urticaria in Guangzhou, China from 2013 to 2017. We also estimated the attributable fraction of urticaria outpatient visits due to air pollution. A total of 216,648 outpatient visits due to urticaria occurred during the study period. All air pollutants were significantly associated with an increased excess risk of urticaria. Each 10 µg/m3 increase in PM2.5, PM10, NO2, and SO2 was associated with an increase of 1.23% (95% CI: 0.42%, 2.06%), 0.88% (95% CI: 0.28%, 1.49%), 3.09% (95% CI: 2.16%, 4.03%), and 2.82% (95% CI: 0.93%, 4.74%) in hospital visits for urticaria at lag05, respectively. It was estimated that 3.77% (95% CI: 1.26%, 6.38%), 1.91% (95% CI: 0.60%, 3.26%), 6.36% (95% CI: 4.38%, 8.41%), and 0.08% (95% CI: 0.03%, 0.14%) of urticaria outpatient visits were attributable to PM2.5, PM10, NO2, and SO2 using the World Health Organization's air quality guideline as the reference. Relatively stronger associations were observed during the cold season. This study indicates that short-term air pollution may play a significant role in outpatient visits for urticaria, and that such relationships could be modified by season.

Development of an Anticipatory Triage-Ranking Algorithm Using Dynamic Simulation of the Expected Time Course of Patients With Trauma: Modeling and Simulation Study.

BACKGROUND: In cases of terrorism, disasters, or mass casualty incidents, far-reaching life-and-death decisions about prioritizing patients are currently made using triage algorithms that focus solely on the patient's current health status rather than their prognosis, thus leaving a fatal gap of patients who are under- or overtriaged. OBJECTIVE: The aim of this proof-of-concept study is to demonstrate a novel approach for triage that no longer classifies patients into triage categories but ranks their urgency according to the anticipated survival time without intervention. Using this approach, we aim to improve the prioritization of casualties by respecting individual injury patterns and vital signs, survival likelihoods, and the availability of rescue resources. METHODS: We designed a mathematical model that allows dynamic simulation of the time course of a patient's vital parameters, depending on individual baseline vital signs and injury severity. The 2 variables were integrated using the well-established Revised Trauma Score (RTS) and the New Injury Severity Score (NISS). An artificial patient database of unique patients with trauma (N=82,277) was then generated and used for analysis of the time course modeling and triage classification. Comparative performance analysis of different triage algorithms was performed. In addition, we applied a sophisticated, state-of-the-art clustering method using the Gower distance to visualize patient cohorts at risk for mistriage. RESULTS: The proposed triage algorithm realistically modeled the time course of a patient's life, depending on injury severity and current vital parameters. Different casualties were ranked by their anticipated time course, reflecting their priority for treatment. Regarding the identification of patients at risk for mistriage, the model outperformed the Simple Triage And Rapid Treatment's triage algorithm but also exclusive stratification by the RTS or the NISS. Multidimensional analysis separated patients with similar patterns of injuries and vital parameters into clusters with different triage classifications. In this large-scale analysis, our algorithm confirmed the previously mentioned conclusions during simulation and descriptive analysis and underlined the significance of this novel approach to triage. CONCLUSIONS: The findings of this study suggest the feasibility and relevance of our model, which is unique in terms of its ranking system, prognosis outline, and time course anticipation. The proposed triage-ranking algorithm could offer an innovative triage method with a wide range of applications in prehospital, disaster, and emergency medicine, as well as simulation and research.

[Preparing for Pandemics]. / Vorbereitung auf eine Pandemie.

The current COVID-19 pandemic has contributed to millions of deaths globally and it is estimated that the hit to the global economy could reach more than twelve trillion US-dollars. Disease outbreaks have often pushed weak health systems to a breaking point, as witnessed during cholera, Ebola and Zika virus upsurges. The preparation of a plan involves the analysis of a scenario divided into the disaster cycle's four phases: preparation, response, recovery, and mitigation. Several levels of planning are recognised according to the goals to be reached: strategic plans are directed to define the organisational context and overall aims, operational plans with putting the strategy into place, tactical plans explain how resources will be allocated and managed, as well as provide essential instructions to the responders. The hospital surge capacity relies on the reorganisation of resources according to four categories: system, staff, stuff (supplies), and space. Each of these components needs to be analysed, implemented, and tested during the preparation phase to reduce the occurrence of a critical overrun of the response capabilities, as this will trigger the recourse of contingency plans. The response to pandemics must be associated with public health and social measures, as well as with initiatives to support the psycho-physical health of healthcare workers.

Virtual Reality for Emergency Medicine Training in Medical School: Prospective, Large-Cohort Implementation Study.

BACKGROUND: Virtual reality (VR)-based simulation is being increasingly used to train medical students in emergency medicine. However, because the usefulness of VR may depend on various factors, the best practices for implementing this technology in the medical school curriculum are yet to be determined. OBJECTIVE: The overall objective of our study was to assess the perceptions of a large cohort of students toward VR-based training and to identify the associations between these attitudes and individual factors, such as gender and age. METHODS: The authors implemented a voluntary, VR-based teaching session in the emergency medicine course at the Medical Faculty in Tübingen, Germany. Fourth-year medical students were invited to participate on a voluntary basis. Afterward, we asked the students about their perceptions, collected data on individual factors, and assessed the test scores achieved by them in the VR-based assessment scenarios. We used ordinal regression analysis and linear mixed-effects analysis to detect the impact of individual factors on the questionnaire answers. RESULTS: A total of 129 students participated in our study (mean age 24.7, SD 2.9 years; n=51, 39.8% male; n=77, 60.2% female). No student had previously used VR for learning, and only 4.7% (n=6) of the students had prior experience with VR. Most of the students agreed that VR can convey complex issues quickly (n=117, 91%), that VR is a useful addition to mannequin-based courses (n=114, 88%) or could even replace them (n=93, 72%), and that VR simulations should also be used for examinations (n=103, 80%). However, female students showed significantly less agreement with these statements. Most students perceived the VR scenario as realistic (n=69, 53%) and intuitive (n=62, 48%), with a relatively lower agreement for the latter among female respondents. We found high agreement among all participants (n=88, 69%) for immersion but strong disagreement (n=69, 54%) for empathy with the virtual patient. Only 3% (n=4) of the students felt confident regarding the medical content. Responses for the linguistic aspects of the scenario were largely mixed; however, most of the students were confident with the English language (not native) scenarios and disagreed that the scenario should be offered in their native language (female students agreed more strongly than male students). Most of the students would not have felt confident with the scenarios in a real-world context (n=69, 53%). Although physical symptoms during VR sessions were reported by 16% (n=21) of the respondents, this did not lead to the termination of the simulation. The regression analysis revealed that the final test scores were not influenced by gender, age, or prior experience in emergency medicine or with virtual reality. CONCLUSIONS: In this study, we observed a strong positive attitude in medical students toward VR-based teaching and assessment. However, this positivity was comparatively lower among female students, potentially indicating that gender differences need to be addressed when VR is implemented in the curriculum. Interestingly, gender, age, or prior experience did not influence the final test scores. Furthermore, confidence regarding the medical content was low, which suggests that the students may need further training in emergency medicine.

Presentation and evaluation of a modern course in disaster medicine and humanitarian assistance for medical students.

BACKGROUND: Disaster medicine is a component of the German medical education since 2003. Nevertheless, studies have shown some inconsistencies within the implementation of the national curriculum, and limits in the number of students trained over the years. Recently, the SARS-CoV-2 pandemic and other disasters have called attention to the importance of training medical students in disaster medicine on a coordinated basis. The aim of this study is to present and evaluate the disaster medicine and humanitarian assistance course, which was developed in the University of Tübingen, Germany. METHODS: The University Clinic for Anesthesiology and Intensive Care Medicine in Tübingen expanded the existing curriculum of undergraduate disaster medicine training with fundamentals of humanitarian medicine, integrating distance learning, interactive teaching and simulation sessions in a 40 h course for third-, fourth- and fifth- year medical students. This prospective and cross-sectional study evaluates the Disaster Medicine and Humanitarian Assistance course carried out over five semesters during the period between 2018 and 2020. Three survey tools were used to assess participants' previous experiences and interest in the field of disaster medicine, to compare the subjective and objective level of knowledge before and after training, and to evaluate the course quality. RESULTS: The total number of medical students attending the five courses was n = 102 of which n = 60 females (59%) and n = 42 males (41%). One hundred two students entered the mandatory knowledge assessment, with the rate of correct answers passing from 73.27% in the pre-test to 95.23% in the post-test (t [101] = 18.939, p < .001, d = 1.88). To determine the subjective perception of knowledge data were collected from 107 observations. Twenty-five did not complete the both questionnaires. Out of a remaining sample of 82 observations, the subjective perception of knowledge increased after the course (t [81] = 24.426, p < .001, d = 2.69), alongside with the interest in engaging in the field of disaster medicine (t [81] = 7.031, p < .001, d = .78). The 93.46% of the medical students (n = 100) graded the training received with an excellent overall score (1.01 out of 6). CONCLUSION: The study indicates a significant increase in students' understanding of disaster medicine using both subjective and objective measurements, as well as an increase interest in the field of disaster medicine and humanitarian assistance. Whereas former studies showed insufficient objective knowledge regarding disaster medical practices as well as subjective insecurities about their skills and knowledge to deal with disaster scenarios, the presented course seems to overcome these deficiencies preparing future physicians with the fundamentals of analysis and response to disasters. The development and successful implementation of this course is a first step towards fulfilling disaster medicine education requirements, appearing to address the deficiencies documented in previous studies. A possible adaptation with virtual reality approaches could expand access to a larger audience. Further effort must be made to develop also international training programs, which should be a mandatory component of medical schools' curricula.

Characteristics and Injury Patterns of Road Traffic Injuries in Urban and Rural Uganda-A Retrospective Medical Record Review Study in Two Hospitals.

In the ongoing Second Decade of Action for Road Safety, road traffic crashes pose a considerable threat especially in low-income countries. Uganda shows a vast burden of non-fatal injuries and resides at the top range of countries with the highest death rates due to unsafe roads. However, little is known about the differences in road traffic associated injuries between urban and rural areas and potential influence factors. Here, we used a cross-sectional study conducted by a retrospective medical record review from trauma cases admitted in 2016 to hospitals in rural and urban areas in Uganda. Injury severity scores were calculated and descriptive analysis was carried out while multivariate logistic regression was applied to assess significant covariates. According to the 1683 medical records reviewed, the mean age of trauma patients in the dataset under investigation was 30.8 years with 74% male. The trauma in-hospital mortality was 4% while prevalence of traumatic injuries is 56.4%. Motorcycle users (49.6%) and pedestrians (33.7%) were identified as the most vulnerable groups in both urban and rural setting while mild injuries of extremities (61.6%) and the head/neck-region (42.0%) were registered most. The frequency of road traffic injuries was homogenous in the urban and rural hospitals investigated in this study; interventions should therefore be intensified ubiquitously. The identification of significant differences in road traffic crash and injury characteristics provides the opportunity for specific programmes to decrease the socio-economic and health burden of unsafe roads. In addition to law enforcement and introduction of a Systems Thinking approach to road safety including infrastructural and educational concepts, the strengthening of trauma care and health resources is recommended.

Implementation of disaster medicine education in German medical schools - a nationwide survey.

Objectives: Floods, earthquakes and terror attacks in recent years emphasize the importance of disaster preparedness for the medical community. To best prepare doctors for providing optimal care in disaster situations, specific education and training should start at the medical school level. This study containes an online survey among German medical schools to evaluate the status quo of teaching disaster medicine and to reveal potential obstacles. Methods: The dean's offices of 36 German medical schools were contacted from April 2016 to May 2017. Via an e-mail link, recipients could anonymously and voluntarily access an online questionnaire (74 items, 42 with a four-point "Likert-like" scale, 12 yes/no questions and 20 with listed items to choose from). The answers were analyzed by descriptive statistics. Results: A total of 25 medical schools participated in the survey. Twenty respondents were in favor of expanding disaster medicine teaching at their institutions. Incorporating single topics ranging from triage (n=21) to accidents involving radioactive materials (n=4) into the curriculum varied widely. Only two schools had established a teaching coordinator for disaster medicine and only one e-learning course had been established. Twenty-one respondents regarded funding issues and 18 regarded organizational matters to be major hurdles in the future. Conclusion: Though most faculty representatives indicated that they favor expanding and implementing disaster medicine education, German medical schools still have a lot of room for enhancement in this field. The incorporation of e-learning tools could facilitate the expansion of disaster medicine teaching while simultaneously addressing the expressed concerns of the survey's participants and guarantee nationwide standardization.

One Step Closer towards a Reliable Tinnitus Pitch-Match Frequency Determination Using Repetitive Recursive Matching.

INTRODUCTION: The determination of the tinnitus pitch-match (PM) frequency is not straightforward but an important audiological assessment recommended for clinical and research purposes. We evaluated repetitive recursive matching using an iPod-based matching procedure as a method to estimate a patient's PM frequency without audiometric equipment. METHODS: One hundred and seventeen patients with chronic tonal tinnitus (uni- and bilateral tinnitus) measured their tinnitus in 10 sessions using a self-administered automated iPod-based procedure comprising a recursive 2 interval forced-choice test. RESULTS: Mean SD of the PM frequency of all participants across sessions was 0.41 octaves. The internal consistency measured by Cronbach's α was very high (0.8->0.95). As an example, 7 PMs obtained excellent internal consistency (α = 0.93). The exclusion of the first and/or second session led to more definite PMs with a decreased SD. Outliers were identified by PMs departing 2 SDs (i.e., 0.94 octaves) from the mean variability (n = 5). CONCLUSION: Repetitive recursive matching together with recommendations for the exclusion of initial and redundant sessions as well as outlier identification and treatment can enable a reliable estimation of the PM frequency.

Safety and Security in International Humanitarian Missions - Assessing the Stress Level of Responders in Critical Situations during a Realistic Full-Scale Training.

INTRODUCTION: Crises, wars, and disasters are remarkably increasing across the world. Responders are frequently tackled with an ever-greater number of challenges, and undoubtedly, they are physically and mentally affected during and after their missions, during which posttraumatic stress disorder (PTSD) is considered high-risk. To the authors' knowledge, no studies have addressed which type of incident has the greatest influence to trigger stress, and consequently, to cause PTSD for the responders after their missions. METHODS: A prospective longitudinal study was conducted with 69 participants of the "Safety and Security" course at the Federal Office for Civil Protection and Disaster Aid of the Federal Ministry of Interior Affairs (Berlin, Germany). The course is certified by the Hostile Environment Awareness Training (HEAT) guidelines of Europe's New Training Initiative for Civilian Crisis Management (ENTRi; Center for International Peace Operations; Berlin, Germany). Four incidents were evaluated: hostage-taking, carjacking, evacuation, and border-crossing. The participants completed the Positive and Negative Affect Schedule (PANAS) before and after each incident. For each incident, the delta of the PANAS scores was calculated. The differences between the described incidents, as well as the differences between novice and experienced responders, were evaluated. RESULTS: The hostage-taking incident had the greatest influence on the participants' temper, followed by carjacking and evacuation. Ultimately, the border-crossing event had the least effect on the responders. Novices were more affected by hostage-taking than experienced responders; however, no significant difference had been demonstrated between novices and experienced responders for the other evaluated incidents. CONCLUSION: Different incidents have big psychological impacts on humanitarian responders, in which consequences vary from short-term effects to PTSD. Therefore, humanitarian responders should be selected very carefully. They should also have more specific preparation for their missions. Mental after-care should be obligatory. Further studies are needed to understand and avoid reasons for the development of PTSD or other potential problems of responders.

Targeting Heterogeneous Findings in Neuronal Oscillations in Tinnitus: Analyzing MEG Novices and Mental Health Comorbidities.

Tinnitus is a prevalent phenomenon and bothersome for people affected by it. Its occurrence and maintenance have a clear neuroscientific tie and one aspect are differences in the neuronal oscillatory pattern, especially in auditory cortical areas. As studies in this field come to different results, the aim of this study was to analyze a large number of participants to achieve more stable results. Furthermore, we expanded our analysis to two variables of potential influence, namely being a novice to neuroscientific measurements and the exclusion of psychological comorbidities. Oscillatory brain activity of 88 subjects (46 with a chronic tinnitus percept, 42 without) measured in resting state by MEG was investigated. In the analysis based on the whole group, in sensor space increased activity in the delta frequency band was found in tinnitus patients. Analyzing the subgroup of novices, a significant difference in the theta band emerged additionally to the delta band difference (sensor space). Localizing the origin of the activity, we found a difference in theta and gamma band for the auditory regions for the whole group and the same significant difference in the subgroup of novices. However, no differences in oscillatory activity were observed between tinnitus and control groups once subjects with mental health comorbidity were excluded. Against the background of previous studies, the study at hand underlines the fragility of the results in the field of neuronal cortical oscillations in tinnitus. It supports the body of research arguing for low frequency oscillations and gamma band activity as markers associated with tinnitus.

Effects of red light running camera systems installation and then deactivation on intersection safety.

INTRODUCTION: The primary objective of this paper is to evaluate the safety impacts of red-light running camera (RLC) system installation and then deactivation at 48 intersections in Houston, Texas. The second objective is to evaluate the spillover effect at nearby non-treated intersections in Houston after the deactivation. METHODS: To accomplish study objectives, an Empirical Bayes (EB) before-after analysis was used. RESULTS: The results indicate statistically significant collision reductions on all red-light running (RLR) crash types (37 percent) as well as right-angle RLR crashes (47 percent) at the treated intersections after RLC activation. By way of comparison, the RLC deactivation analysis indicated that crashes increased by 20 percent for all RLR crash types and by 23 percent in right-angle RLR crashes at the formerly treated intersections. After deactivation, all severity RLR crashes increased more than expected at nearby non-treated intersections, which indicates the possibility of an adverse spillover effect. However, fatal/injury crashes associated with rear-end decreased after deactivation at both formerly treated and non-treated intersections, although those rear-end crashes account for smaller proportions when compared to all crash types/right-angle crashes. PRACTICAL APPLICATIONS: Overall, removing RLC treatments results in a negative reaction to the safety benefits that the treatment provides when it is in place and actively working and to the nearby intersections where the treatment has not been implemented. This study helps define the effects that RLCs have on safety at signalized intersections after installation and deactivation.

A multimodal dataset for various forms of distracted driving.

We describe a multimodal dataset acquired in a controlled experiment on a driving simulator. The set includes data for n=68 volunteers that drove the same highway under four different conditions: No distraction, cognitive distraction, emotional distraction, and sensorimotor distraction. The experiment closed with a special driving session, where all subjects experienced a startle stimulus in the form of unintended acceleration-half of them under a mixed distraction, and the other half in the absence of a distraction. During the experimental drives key response variables and several explanatory variables were continuously recorded. The response variables included speed, acceleration, brake force, steering, and lane position signals, while the explanatory variables included perinasal electrodermal activity (EDA), palm EDA, heart rate, breathing rate, and facial expression signals; biographical and psychometric covariates as well as eye tracking data were also obtained. This dataset enables research into driving behaviors under neatly abstracted distracting stressors, which account for many car crashes. The set can also be used in physiological channel benchmarking and multispectral face recognition.

Can vehicle longitudinal jerk be used to identify aggressive drivers? An examination using naturalistic driving data.

This paper investigated the characteristics of vehicle longitudinal jerk (change rate of acceleration with respect to time) by using vehicle sensor data from an existing naturalistic driving study. The main objective was to examine whether vehicle jerk contains useful information that could be potentially used to identify aggressive drivers. Initial investigation showed that there are unique characteristics of vehicle jerk in drivers' gas and brake pedal operations. Thus two jerk-based metrics were examined: (1) driver's frequency of using large positive jerk when pressing the gas pedal, and (2) driver's frequency of using large negative jerk when pressing the brake pedal. To validate the performance of the two metrics, drivers were firstly divided into an aggressive group and a normal group using three classification methods (1) traveling at excessive speed (speeding), (2) following too closely to a front vehicle (tailgating), and (3) their association with crashes or near-crashes in the dataset. The results show that those aggressive drivers defined using any of the three methods above were associated with significantly higher values of the two jerk-based metrics. Between the two metrics the frequency of using large negative jerk seems to have better performance in identifying aggressive drivers. A sensitivity analysis shows the findings were largely consistent with varying parameters in the analysis. The potential applications of this work include developing quantitative surrogate safety measures to identify aggressive drivers and aggressive driving, which could be potentially used to, for example, provide real-time or post-ride performance feedback to the drivers, or warn the surrounding drivers or vehicles using the connected vehicle technologies.

Self-Perception of Medical Students' Knowledge and Interest in Disaster Medicine: Nine Years After the Approval of the Curriculum in German Universities.

BACKGROUND: Following the recommendations of the World Association for Disaster and Emergency Medicine (WADEM; Madison, Wisconsin USA) to develop standards for training the undergraduates in disaster-relevant fields (2004), a German curriculum was approved in 2006. This paper aims to describe the level of training and interest of medical students nine years later. Problem The aim of this study was to assess the self-perception of medical students' knowledge and interest in disaster medicine nine years after the implementation of a standardized disaster medicine curriculum in German medical schools. METHODS: This prospective, cross-sectional, observational study was conducted with medical students in Germany using a web-based, purpose-designed questionnaire consisting of 27 mandatory and 11 optional questions. RESULTS: Nine hundred ninety-two students from 36 of 37 medical schools in Germany participated. More than one-half of medical students were aware of the field of disaster medicine. One hundred twenty-one students undertook training internally within their university and 307 undertook training externally at other institutions. Only a small content of the curriculum was taught. A difference in self-perception of knowledge between trained and untrained participants was found, despite the level of training being low in both groups. Participants were generally highly motivated to learn disaster medicine in a variety of institutions. CONCLUSION: German students are still largely not well educated regarding disaster medicine, despite their high motivation. The curriculum of 2006 was not implemented as originally planned and the number of trained students still remains low as the self-perception of knowledge. Currently, there is no clear and standardized training concept in place. A renewal in the agreement of implementation of the curriculum at medical schools should be targeted in order to follow the recommendation of WADEM. Wunderlich R Ragazzoni L Ingrassia PL Della Corte F Grundgeiger J Bickelmayer JW Domres B . Self-perception of medical students' knowledge and interest in disaster medicine: nine years after the approval of the curriculum in German universities. Prehosp Disaster Med. 2017;32(4):374-381.

Clinical trial on tonal tinnitus with tailor-made notched music training.

BACKGROUND: Tinnitus is a result of hyper-activity/hyper-synchrony of auditory neurons coding the tinnitus frequency, which has developed due to synchronous mass activity owing to the lack of inhibition. We assume that removal of exactly these frequencies from a complex auditory stimulus will cause the brain to reorganize around tonotopic regions coding the tinnitus frequency through inhibition-induced plasticity. Based on this assumption, a novel treatment for tonal tinnitus--tailor-made notched music training (TMNMT)--has been introduced and was tested in this clinical trial. METHODS: A randomized controlled trial in parallel group design was performed in a double-blinded manner. We included 100 participants with chronic, tonal tinnitus who listened to tailor-made notched music for two hours a day for three consecutive months. Our primary outcome measures were the Tinnitus Handicap Questionnaire and Visual Analog Scales measuring perceived tinnitus loudness, awareness, distress and handicap. Participants rated their tinnitus before and after the training as well as one month after cessation of the training. RESULTS: While no effect was found for the primary outcome measures, tinnitus distress, as measured by the Tinnitus Questionnaire, a secondary outcome measure, developed differently in the two groups. The treatment group showed higher distress scores while the placebo group revealed lower distress scores after the training. However, this effect did not reach significance in post-hoc analysis and disappeared at follow-up measurements. At follow-up, tinnitus loudness in the treatment group was significantly reduced as compared to the control group. Post hoc analysis, accounting for low reliability scores in the Visual Analog Scales, showed a significant reduction of the overall Visual Analog Scale mean score in the treatment group even at the post measurement. CONCLUSION: This is the first study on TMNMT that was planned and conducted following the CONSORT statement standards for clinical trials. The current work is one more step towards a final evaluation of TMNMT. Already after three months the effect of training with tailor-made notched music is observable in the most direct rating of tinnitus perception - the tinnitus loudness, while more global measures of tinnitus distress do not show relevant changes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN04840953; Trial registration date: 17.07.2013.

Modulatory Effects of Attention on Lateral Inhibition in the Human Auditory Cortex.

Reduced neural processing of a tone is observed when it is presented after a sound whose spectral range closely frames the frequency of the tone. This observation might be explained by the mechanism of lateral inhibition (LI) due to inhibitory interneurons in the auditory system. So far, several characteristics of bottom up influences on LI have been identified, while the influence of top-down processes such as directed attention on LI has not been investigated. Hence, the study at hand aims at investigating the modulatory effects of focused attention on LI in the human auditory cortex. In the magnetoencephalograph, we present two types of masking sounds (white noise vs. withe noise passing through a notch filter centered at a specific frequency), followed by a test tone with a frequency corresponding to the center-frequency of the notch filter. Simultaneously, subjects were presented with visual input on a screen. To modulate the focus of attention, subjects were instructed to concentrate either on the auditory input or the visual stimuli. More specific, on one half of the trials, subjects were instructed to detect small deviations in loudness in the masking sounds while on the other half of the trials subjects were asked to detect target stimuli on the screen. The results revealed a reduction in neural activation due to LI, which was larger during auditory compared to visual focused attention. Attentional modulations of LI were observed in two post-N1m time intervals. These findings underline the robustness of reduced neural activation due to LI in the auditory cortex and point towards the important role of attention on the modulation of this mechanism in more evaluative processing stages.

The Relevance of Interoception in Chronic Tinnitus: Analyzing Interoceptive Sensibility and Accuracy.

In order to better understand tinnitus and distress associated with tinnitus, psychological variables such as emotional and cognitive processing are a central element in theoretical models of this debilitating condition. Interoception, that is, the perception of internal processes, may be such a psychological factor relevant to tinnitus. Against this background, 20 participants suffering from chronic tinnitus and 20 matched healthy controls were tested with questionnaires, assessing interoceptive sensibility, and participated in two tasks, assessing interoceptive accuracy: the Schandry task, a heartbeat estimation assignment, and a skin conductance fluctuations perception task assessing the participants' ability to perceive phasic increases in sympathetic activation were used. To test stress reactivity, a construct tightly connected to tinnitus onset, we also included a stress induction. No differences between the groups were found for interoceptive accuracy and sensibility. However, the tinnitus group tended to overestimate the occurrence of phasic activation. Loudness of the tinnitus was associated with reduced interoceptive performance under stress. Our results indicate that interoceptive sensibility and accuracy do not play a significant role in tinnitus. However, tinnitus might be associated with a tendency to overestimate physical changes.

Impact of Spectral Notch Width on Neurophysiological Plasticity and Clinical Effectiveness of the Tailor-Made Notched Music Training.

Tinnitus, the ringing in the ears that is unrelated to any external source, causes a significant loss in quality of life, involving sleep disturbance and depression for 1 to 3% of the general population. While in the first place tinnitus may be triggered by damage to the inner ear cells, the neural generators of subjective tinnitus are located in central regions of the nervous system. A loss of lateral inhibition, tonotopical reorganization and a gain-increase in response to the sensory deprivation result in hypersensitivity and hyperactivity in certain regions of the auditory cortex. In the tailor-made notched music training (TMNMT) patients listen to music from which the frequency spectrum of the tinnitus has been removed. This evokes strong lateral inhibition from neurons tuned to adjacent frequencies onto the neurons involved in the tinnitus percept. A reduction of tinnitus loudness and tinnitus-related neural activity was achieved with TMNMT in previous studies. As the effect of lateral inhibition depends on the bandwidth of the notch, in the current study we altered the notch width to find the most effective notch width for TMNMT. We compared 1-octave notch width with ½-octave and »-octave. Participants chose their favorite music for the training that included three month of two hours daily listening. The outcome was measured by means of standardized questionnaires and magnetoencephalography. We found a general reduction of tinnitus distress in all administered tinnitus questionnaires after the training. Additionally, tinnitus-related neural activity was reduced after the training. Nevertheless, notch width did not have an influence on the behavioral or neural effects of TMNMT. This could be due to a non-linear resolution of lateral inhibition in high frequencies.

Enhancing inhibition-induced plasticity in tinnitus--spectral energy contrasts in tailor-made notched music matter.

Chronic tinnitus seems to be caused by reduced inhibition among frequency selective neurons in the auditory cortex. One possibility to reduce tinnitus perception is to induce inhibition onto over-activated neurons representing the tinnitus frequency via tailor-made notched music (TMNM). Since lateral inhibition is modifiable by spectral energy contrasts, the question arises if the effects of inhibition-induced plasticity can be enhanced by introducing increased spectral energy contrasts (ISEC) in TMNM. Eighteen participants suffering from chronic tonal tinnitus, pseudo randomly assigned to either a classical TMNM or an ISEC-TMNM group, listened to notched music for three hours on three consecutive days. The music was filtered for both groups by introducing a notch filter centered at the individual tinnitus frequency. For the ISEC-TMNM group a frequency bandwidth of 3/8 octaves on each side of the notch was amplified, additionally, by about 20 dB. Before and after each music exposure, participants rated their subjectively perceived tinnitus loudness on a visual analog scale. During the magnetoencephalographic recordings, participants were stimulated with either a reference tone of 500 Hz or a test tone with a carrier frequency representing the individual tinnitus pitch. Perceived tinnitus loudness was significantly reduced after TMNM exposure, though TMNM type did not influence the loudness ratings. Tinnitus related neural activity in the N1m time window and in the so called tinnitus network comprising temporal, parietal and frontal regions was reduced after TMNM exposure. The ISEC-TMNM group revealed even enhanced inhibition-induced plasticity in a temporal and a frontal cortical area. Overall, inhibition of tinnitus related neural activity could be strengthened in people affected with tinnitus by increasing spectral energy contrast in TMNM, confirming the concepts of inhibition-induced plasticity via TMNM and spectral energy contrasts.