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Background: Despite the high frequency of tinnitus and its impact on wellbeing, little is known about its economic burden, and, to our knowledge, no data are available on out-of-pocket (OOP) expenses. Methods: In 2022, a survey was conducted on OOP costs of tinnitus. We enrolled 679 participants with slight, moderate, and severe tinnitus in Italy, United Kingdom, Netherlands, Germany, and Spain. We estimated annual OOP expenses for tinnitus-related healthcare visits, treatments, medications, and alternative medicine practices. Prevalence of tinnitus in the general population, obtained from a representative survey we conducted in Europe in 2017–2018, was used to generalize costs for people with any tinnitus at the national level. Results: OOP expenses were 368€ (95% confidence intervals [CI], 78€–690€), 728€ (95% CI, 316€–1,288€), and 1,492€ (95% CI, 760€–2,688€) for slight, moderate, and severe tinnitus, respectively, with annual expenditure of 565€ for people with any tinnitus: 209€ for healthcare visits; 93€ for treatments; 16€ for drugs; 64€ for hearing supporting systems; and 183€ for acupuncture, homeopathy, and osteopathy. Individuals with slight, moderate, and severe tinnitus expressed a willingness to invest 1.6, 4.3, and 7.0 times their monthly income, respectively, to achieve complete relief from tinnitus. Conclusion: This study offers for the first time insights into the OOP expenses incurred by individuals with tinnitus. OOP expenses exhibited substantial variations based on severity status, accounting for more than 17 billion € in the countries considered. In terms of financial burden, these findings align tinnitus to the recognized leading disabilities, including back pain and migraine.

Abstract This perspective article explores how process mining can extract clinical insights from mobile health data and complement data-driven techniques like machine learning. Despite technological advances, challenges such as selection bias and the complex dynamics of health data require advanced approaches. Process mining focuses on analyzing temporal process patterns and provides complementary insights into health condition variability. The article highlights the potential of process mining for analyzing mHealth data and beyond.

Abstract The influence of naps on tinnitus was systematically assessed by exploring the frequency, clinical and demographic characteristics of this phenomenon. 9,724 data from two different tinnitus databases (Tinnitus Hub: n = 6115; Tinnitus Research Initiative (TRI): n = 3627) were included. After separate analysis of the databases, these results were then compared with each other. In the Tinnitus Hub survey database, a total of 31.1% reported an influence on tinnitus by taking a nap (26.9% in the TRI database), with much more frequent worsening after a nap than improvement (23.0% a little or a lot worse; TRI: 17.7% worse; 8.1% a little or a lot better; TRI: 9.2% better). The influence of napping on tinnitus was associated in both databases with other clinical features, such as the dependence of tinnitus on night quality, stress and somatosensory maneuvers. The present study confirms the clinical observation that more tinnitus sufferers report worsening after a nap than tinnitus sufferers reporting an improvement. It was consistently shown that tinnitus sufferers reporting nap-induced modulation of tinnitus also report more frequently an influence of night sleep on their tinnitus. Further clinical and polysomnographic research is warranted to better understand the interaction between sleep and tinnitus.

Objectives. The study aimed to assess the relationship of tinnitus with hyperacusis with cognitive impairment as indicated by the Montreal Cognitive Assessment (MoCA) tool. Methods. This multicenter cross-sectional study included individuals with chronic tinnitus from the “Unification of Treatments and Interventions for Tinnitus Patients” (UNITI) database. Participants were recruited from four different tertiary clinical centers located in Athens and Granada (Mediterranean group), as well as Berlin and Regensburg (German group). In total, 380 individuals with a diagnosis of non-pulsatile chronic tinnitus (permanent and constant tinnitus lasting more than 6 months) and no evidence of severe cognitive impairment (MoCA score >22) were enrolled. The evaluation utilized the following tools: MoCA, Tinnitus Handicap Inventory (THI), Hyperacusis Questionnaire (GÜF), Patient Health Questionnaire (PHQ-9), and the European School for Interdisciplinary Tinnitus Research Screening Questionnaire. Results. MoCA scores differed between German and Mediterranean individuals (P

ObjectivesWe aimed to evaluate the drug utilization of Ginkgo biloba extract (Gbe), systemic corticosteroids (CSs), and pentoxifylline (PTXF) for the treatment of acute tinnitus by analyzing electronic patient health record data. In addition, we assessed whether the different drug treatments were associated with different frequencies of repeat visits to ear, nose, and throat (ENT) doctors.MethodsThis retrospective cohort study used data from the IQVIA Disease Analyzer (DA) database. It included patients with an initial diagnosis of tinnitus between January 2005 and December 2021, treated by ENT specialists in Germany.ResultsOf 111,629 patients meeting all selection criteria, 51,205 received prescriptions of Gbe, 34,817 of systemic CSs, and 25,607 of PTXF. Gbe prescription was associated with significantly lower odds of a repeat consultation due to tinnitus compared to systemic CSs [odds ratio (OR) 0.91; 95% confidence interval (CI): 0.88–0.95] as well as PTXF (OR 0.74; 95% CI: 0.72–0.77). This association was significant in both men and women and in some age groups.ConclusionGbe is the most frequently ENT specialist-prescribed drug for the treatment of acute tinnitus. It is associated with a reduced likelihood of patients consulting their ENT specialist for tinnitus again compared to systemic CSs and PTXF.

IntroductionTreating major depressive disorder (MDD) with transcranial direct current stimulation (tDCS) devices at home has various logistic advantages compared to tDCS treatment in the clinic. However, preliminary (controlled) studies showed side effects such as skin lesions and difficulties in the implementation of home-based tDCS. Thus, more data are needed regarding the feasibility and possible disadvantages of home-based tDCS.MethodsTen outpatients (23–69 years) with an acute depressive episode were included for this one-arm feasibility study testing home-based tDCS. All patients self-administered prefrontal tDCS (2 mA, 20 min, anodal left, cathodal right) at home on 30 consecutive working days supported by video consultations. Correct implementation of the home-based treatment was analyzed with tDCS recordings. Feasibility was examined by treatment compliance. For additional analyses of effectiveness, three depression scores were used: Hamilton depression rating scale (HDRS-21), Major Depression Inventory (MDI), and the subscale depression of the Depression-Anxiety-Stress Scale (DASS). Furthermore, usability was measured with the user experience questionnaire (UEQ). Tolerability was analyzed by the number of reported adverse events (AEs).ResultsEight patients did not stick to the protocol. AEs were minimal. Four patients responded to the home treatment according to the MDI. Usability was judged positive by the patients.ConclusionsRegular video consultations or other safety concepts are recommended regardless of the number of video sessions actually conducted. Home-based tDCS seems to be safe and handy in our feasibility study, warranting further investigation.

Abstract Background Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient. Methods Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT. Discussion The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results. Trial registration ClinicalTrials.gov NCT04663828 . The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis.

Abstract Mobile applications have gained popularity in healthcare in recent years. These applications are an increasingly important pillar of public health care, as they open up new possibilities for data collection and can lead to new insights into various diseases and disorders thanks to modern data analysis approaches. In this context, Ecological Momentary Assessment (EMA) is a commonly used research method that aims to assess phenomena with a focus on ecological validity and to help both the user and the researcher observe these phenomena over time. One phenomenon that benefits from this capability is the chronic condition tinnitus. TrackYourTinnitus (TYT) is an EMA-based mobile crowdsensing platform designed to provide more insight into tinnitus by repeatedly assessing various dimensions of tinnitus, including perception (i.e., perceived presence). Because the presence of tinnitus is the dimension that is of great importance to chronic tinnitus patients and changes over time in many tinnitus patients, we seek to predict the presence of tinnitus based on the not directly related dimensions of mood, stress level, arousal, and concentration level that are captured in TYT. In this work, we analyzed a dataset of 45,935 responses to a harmonized EMA questionnaire using different machine learning techniques. In addition, we considered five different subgroups after consultation with clinicians to further validate our results. Finally, we were able to predict the presence of tinnitus with an accuracy of up to 78% and an AUC of up to 85.7%.

BackgroundHypersomnia poses major challenges to treatment providers given the limitations of available treatment options. In this context, the application of non-invasive brain stimulation techniques such as transcranial electrical stimulation (tES) may open up new avenues to effective treatment. Preliminary evidence suggests both acute and longer-lasting positive effects of transcranial direct current stimulation (tDCS) on vigilance and sleepiness in hypersomniac patients. Based on these findings, the present study sought to investigate short-term effects of single sessions of tDCS and transcranial random noise stimulation (tRNS) on sleepiness in persons suffering from hypersomnia.MethodsA sample of 29 patients suffering from narcolepsy or idiopathic hypersomnia (IH) was recruited from the Regensburg Sleep Disorder Center and underwent single sessions of tES (anodal tDCS, tRNS, sham) over the left and right dorsolateral prefrontal cortex on three consecutive days in a double-blind, sham-controlled, pseudorandomized crossover trial. The primary study endpoint was the mean reaction time measured by the Psychomotor Vigilance Task (PVT) before and directly after the daily tES sessions. Secondary endpoints were additional PVT outcome metrics as well as subjective outcome parameters (e.g., Karolinska Sleepiness Scale; KSS).ResultsThere were no significant treatment effects neither on objective (i.e., PVT) nor on subjective indicators of sleepiness.ConclusionWe could not demonstrate any clinically relevant effects of single sessions of tDCS or tRNS on objective or subjective measures of sleepiness in patients with hypersomnia. However, we cannot exclude that repeated sessions of tES may affect vigilance or sleepiness in hypersomniac patients.

Abstract Background Low frequency repetitive transcranial magnetic stimulation (rTMS) is commonly used to inhibit pathological hyperactivity of the auditory cortex in tinnitus. Novel and supposedly superior and faster inhibitory protocols such as continuous theta burst stimulation (cTBS) were examined as well, but so far there is not sufficient evidence for a treatment application in chronic tinnitus. rTMS effects in general are dependent on the brain state immediate before stimulation. This feasibility study was designed based on the concept to shift the pathological intrinsic brain state of tinnitus patients via acoustic stimulation (“activate”) and induce inhibitory effects via cTBS (“fire”). Methods Seven tinnitus patients with response in residual inhibition received 10 consecutive daily sessions of a combinatory treatment comprised of 3-minute acoustic stimulation with white noise followed by 600 pulses of cTBS over the left temporo-parietal cortex (activate & fire). A control group of 5 patients was treated parallel to the activate & fire data collection with 10 sessions á 3000 pulses of 1 Hz rTMS over the left temporo-parietal cortex. Results The activate & fire protocol was well tolerated except in one patient with tinnitus loudness increase. This patient was excluded from analyses. No statistical superiority of the activate & fire treatment approach in alleviating tinnitus-related symptoms was evident. Power calculations showed an effect size of 0.706 and a needed sample size of 66 for statistical significant group differences. On a descriptive level the activate & fire group demonstrated a stronger decrease in tinnitus-related symptoms. Conclusion The present feasibility study showed that combining acoustic stimulation with magnetic brain stimulation may be well-tolerable in the majority of patients and represents a promising treatment approach for tinnitus by hypothetically alter the intrinsic state prior to brain stimulation.

IntroductionObsessive-compulsive disorder (OCD) affects 2–3% of the global population, causing distress in many functioning levels. Standard treatments only lead to a partial recovery, and about 10% of the patients remain treatment-resistant. Deep brain stimulation offers a treatment option for severe, therapy-refractory OCD, with a reported response of about 60%. We report a comprehensive clinical, demographic, and treatment data for patients who were treated with DBS in our institution.MethodsWe offered DBS to patients with severe chronic treatment resistant OCD. Severity was defined as marked impairment in functioning and treatment resistance was defined as non-response to adequate trials of medications and psychotherapy. Between 2020 and 2022, 11 patients were implanted bilaterally in the bed nucleus of stria terminalis (BNST). Patients were evaluated with YBOCS, MADRS, GAF, CGI, and WHOQOL-BREF. We performed the ratings at baseline (before surgery), after implantation before the start of the stimulation, after reaching satisfactory stimulation parameters, and at follow-up visits 3, 6, 9, and 12 months after optimized stimulation.ResultsOne patient has retracted his consent to publish the results of his treatment, thus we are reporting the results of 10 patients (5 males, 5 females, mean age: 37 years). Out of our 10 patients, 6 have shown a clear response indicated by a YBOCS-reduction between 42 and 100 percent at last follow-up. One further patient experienced a subjectively dramatic effect on OCD symptoms, but opted afterwards to stop the stimulation. The other 3 patients showed a slight, non-significant improvement of YBOCS between 8.8 and 21.9%. The overall mean YBOCS decreased from 28.3 at baseline to 13.3 (53% reduction) at the last follow-up. The improvement of the OCD symptoms was also accompanied by an improvement of depressive symptoms, global functioning, and quality of life.ConclusionOur results suggest that BNST-DBS can be effective for treatment-resistant OCD patients, as indicated by a reduction in symptoms and an overall improvement in functioning. Despite the need for additional research to define the patients’ selection criteria, the most appropriate anatomical target, and the most effective stimulation parameters, improved patient access for this therapy should be established.

Abstract More than 10% of the population suffers from tinnitus, which is a phantom auditory condition that is coded within the brain. A new neuromodulation approach to treat tinnitus has emerged that combines sound with electrical stimulation of somatosensory pathways, supported by multiple animal studies demonstrating that bimodal stimulation can elicit extensive neural plasticity within the auditory brain. More recently, in a large-scale clinical trial, bimodal neuromodulation combining sound and tongue stimulation drove significant reductions in tinnitus symptom severity during the first 6 weeks of treatment, followed by diminishing improvements during the second 6 weeks of treatment. The primary objective of the large-scale randomized and double-blinded study presented in this paper was to determine if background wideband noise as used in the previous clinical trial was necessary for bimodal treatment efficacy. An additional objective was to determine if adjusting the parameter settings after 6 weeks of treatment could overcome treatment habituation effects observed in the previous study. The primary endpoint at 6-weeks involved within-arm and between-arm comparisons for two treatment arms with different bimodal neuromodulation settings based on two widely used and validated outcome instruments, Tinnitus Handicap Inventory and Tinnitus Functional Index. Both treatment arms exhibited a statistically significant reduction in tinnitus symptoms during the first 6-weeks, which was further reduced significantly during the second 6-weeks by changing the parameter settings (Cohen’s d effect size for full treatment period per arm and outcome measure ranged from − 0.7 to − 1.4). There were no significant differences between arms, in which tongue stimulation combined with only pure tones and without background wideband noise was sufficient to reduce tinnitus symptoms. These therapeutic effects were sustained up to 12 months after the treatment ended. The study included two additional exploratory arms, including one arm that presented only sound stimuli during the first 6 weeks of treatment and bimodal stimulation in the second 6 weeks of treatment. This arm revealed the criticality of combining tongue stimulation with sound for treatment efficacy. Overall, there were no treatment-related serious adverse events and a high compliance rate (83.8%) with 70.3% of participants indicating benefit. The discovery that adjusting stimulation parameters overcomes previously observed treatment habituation can be used to drive greater therapeutic effects and opens up new opportunities for optimizing stimuli and enhancing clinical outcomes for tinnitus patients with bimodal neuromodulation.

Abstract Background Tinnitus represents a relatively common condition in the global population accompanied by various comorbidities and severe burden in many cases. Nevertheless, there is currently no general treatment or cure, presumable due to the heterogeneity of tinnitus with its wide variety of etiologies and tinnitus phenotypes. Hence, most treatment studies merely demonstrated improvement in a subgroup of tinnitus patients. The majority of studies are characterized by small sample sizes, unstandardized treatments and assessments, or applications of interventions targeting only a single organ level. Combinatory treatment approaches, potentially targeting multiple systems as well as treatment personalization, might provide remedy and enhance treatment responses. The aim of the present study is to systematically examine established tinnitus therapies both alone and in combination in a large sample of tinnitus patients. Further, it wants to provide the basis for personalized treatment approaches by evaluating a specific decision support system developed as part of an EU-funded collaborative project (Unification of treatments and interventions for tinnitus patients; UNITI project). Methods/study design This is a multi-center parallel-arm randomized clinical trial conducted at five different clinical sites over the EU. The effect of four different tinnitus therapy approaches (sound therapy, structured counseling, hearing aids, cognitive behavioral therapy) applied over a time period of 12 weeks as a single or rather a combinatory treatment in a total number of 500 chronic tinnitus patients will be investigated. Assessments and interventions are harmonized over the involved clinical sites. The primary outcome measure focuses on the domain tinnitus distress assessed via the Tinnitus Handicap Inventory. Discussion Results and conclusions from the current study might not only provide an essential contribution to combinatory and personalized treatment approaches in tinnitus but could also provide more profound insights in the heterogeneity of tinnitus, representing an important step towards a cure for tinnitus. Trial registration ClinicalTrials.gov NCT04663828 . Registered on 11 December 2020.

Tinnitus affects a considerable part of the population and develops into a severe disorder in some sufferers. App-based interventions are able to provide low-threshold, cost-effective, and location-independent care for tinnitus patients. Therefore, we developed a smartphone app combining structured counseling with sound therapy and conducted a pilot study to evaluate treatment compliance and symptom improvement (trial registration: DRKS00030007). Outcome variables were Ecological Momentary Assessment (EMA) measured tinnitus distress and loudness and Tinnitus Handicap Inventory (THI) at baseline and final visit. A multiple-baseline design with a baseline phase (only EMA) followed by an intervention phase (EMA and intervention) was applied. 21 patients with chronic tinnitus (≥ 6 months) were included. Overall compliance differed between modules (EMA usage: 79% of days, structured counseling: 72%, sound therapy: 32%). The THI score improved from baseline to final visit indicating a large effect (Cohens d = 1.1). Tinnitus distress and loudness did not improve significantly from baseline phase to the end of intervention phase. However, 5 of 14 (36%) improved clinically meaningful in tinnitus distress (ΔDistress ≥ 10) and 13 of 18 (72%) in THI score (ΔTHI ≥ 7). The positive relationship between tinnitus distress and loudness weakened over the course of the study. A trend but no level effect for tinnitus distress could be demonstrated by a mixed effect model. The improvement in THI was strongly associated with the improvement scores in EMA of tinnitus distress (r = -0.75; 0.86). These results indicate that app-based structured counseling combined with sound therapy is feasible, has an impact on tinnitus symptoms and reduces distress for several patients. In addition, our data suggest that EMA could be used as a measurement tool to detect changes in tinnitus symptoms in clinical trials as has already been shown in other areas of mental health research. Author summary Tinnitus is the perception of a phantom sound which is generated in the brain. Many people are affected by tinnitus and some suffer severely. Management strategies can effectively reduce suffering of some patients. However, the access towards these treatments is limited due to long distances and lack of trained therapists. Therefore, there is increasing interest whether tinnitus management can be delivered via smartphone. In this study, we evaluated a smartphone application consisting of educational counseling and sound therapy with respect to treatment compliance and symptom improvement. We measured tinnitus symptoms at the beginning of baseline and at the end of intervention using clinical questionnaires, but also during the course of treatment using daily questions which were integrated in the mobile application. The app was used regularly by the patients (sound therapy: 32% of days, structured counseling: 72% of days; tinnitus assessment: 79% of days). Tinnitus handicap improved clinically meaningful for 13 of 18 patients, tinnitus distress for 5 of 14 and tinnitus loudness for 2 of 14. The correlation between tinnitus distress and loudness weakened during the study course. Thus, this study indicates that app-based tinnitus management has an impact on tinnitus symptoms and reduces suffering for several patients.

BackgroundChronic tinnitus is an increasing worldwide health concern, causing a significant burden to the health care system each year. The COVID-19 pandemic has seen a further increase in reported cases. For people with tinnitus, symptoms are exacerbated because of social isolation and the elevated levels of anxiety and depression caused by quarantines and lockdowns. Although it has been reported that patients with tinnitus can experience changes in cognitive capabilities, changes in adaptive learning via decision-making tasks for people with tinnitus have not yet been investigated. ObjectiveIn this study, we aim to assess state- and trait-related impairments in adaptive learning ability on probabilistic learning tasks among people with tinnitus. Given that performance in such tasks can be quantified through computational modeling methods using a small set of neural-informed model parameters, such approaches are promising in terms of the assessment of tinnitus severity. We will first examine baseline differences in the characterization of decision-making under uncertainty between healthy individuals and people with tinnitus in terms of differences in the parameters of computational models in a cross-sectional experiment. We will also investigate whether these computational markers, which capture characteristics of decision-making, can be used to understand the cognitive impact of tinnitus symptom fluctuations through a longitudinal experimental design. MethodsWe have developed a mobile app, AthenaCX, to deliver e-consent and baseline tinnitus and psychological assessments as well as regular ecological momentary assessments (EMAs) of perceived tinnitus loudness and a web-based aversive version of a probabilistic decision-making task, which can be triggered based on the participants’ responses to the EMA surveys. Computational models will be developed to fit participants’ choice data in the task, and cognitive parameters will be estimated to characterize participants’ current ability to adapt learning to the change of the simulated environment at each session when the task is triggered. Linear regression analysis will be conducted to evaluate the impacts of baseline tinnitus severity on adapting decision-making performance. Repeated measures linear regression analysis will be used to examine model-derived parameters of decision-making in measuring real-time perceived tinnitus loudness fluctuations. ResultsEthics approval was received in December 2020 from Dublin City University (DCUREC/2021/070). The implementation of the experiments, including both the surveys and the web-based decision-making task, has been prepared. Recruitment flyers have been shared with audiologists, and a video instruction has been created to illustrate to the participants how to participate in the experiment. We expect to finish data collection over 12 months and complete data analysis 6 months after this. The results are expected to be published in December 2023. ConclusionsWe believe that EMA with context-aware triggering can facilitate a deeper understanding of the effects of tinnitus symptom severity upon decision-making processes as measured outside of the laboratory. International Registered Report Identifier (IRRID)PRR1-10.2196/36583

Abstract Tinnitus is an auditory phantom perception in the absence of an external sound stimulation. People with tinnitus often report severe constraints in their daily life. Interestingly, indications exist on gender differences between women and men both in the symptom profile as well as in the response to specific tinnitus treatments. In this paper, data of the TrackYourTinnitus platform (TYT) were analyzed to investigate whether the gender of users can be predicted. In general, the TYT mobile Health crowdsensing platform was developed to demystify the daily and momentary variations of tinnitus symptoms over time. The goal of the presented investigation is a better understanding of gender-related differences in the symptom profiles of users from TYT. Based on two questionnaires of TYT, four machine learning based classifiers were trained and analyzed. With respect to the provided daily answers, the gender of TYT users can be predicted with an accuracy of 81.7%. In this context, worries, difficulties in concentration, and irritability towards the family are the three most important characteristics for predicting the gender. Note that in contrast to existing studies on TYT, daily answers to the worst symptom question were firstly investigated in more detail. It was found that results of this question significantly contribute to the prediction of the gender of TYT users. Overall, our findings indicate gender-related differences in tinnitus and tinnitus-related symptoms. Based on evidence that gender impacts the development of tinnitus, the gathered insights can be considered relevant and justify further investigations in this direction.

Background and aimCOVID-19 is a respiratory disease caused by the new coronavirus SARS-CoV-2, for which the first cases were reported in China, by December 2019. The spectrum of clinical presentations is wide, ranging from asymptomatic cases to a severe acute respiratory syndrome, sometimes with multiple systems involvement. Viral infections, including those related to respiratory virus, may cause hearing loss and, by extent, considering its pathophysiology, tinnitus. A systematic review on inner ear related symptoms in patients with COVID-19 reported 4.5% occurrence rate of tinnitus, with high variance of prevalence between the studies. Our aim is to further explore the relationship between COVID-19 and tinnitus. For this purpose we analyzed a sample of people who had suffered from a COVID-19 infection in the city of Volta Redonda, Brazil. In detail, we compared those with new onset tinnitus during or after the COVID-19 infection with those without tinnitus and those with tinnitus onset before the COVID-19 infection.MethodsFifty-seven patients over 18 years old and previously diagnosed with COVID-19 confirmed by a RT-PCR test were included. Patients were subdivided in three groups: no tinnitus (NT), tinnitus that already existed before COVID-19 (chronic tinnitus, CT) and tinnitus that arose during or after COVID-19 (post-COVID-19 tinnitus, PCT). Data concerning COVID-19 symptoms, drugs prescribed for COVID-19, tinnitus characteristics, comorbidities and other otological symptoms were collected. For all the patients, tonal audiometry and otoacoustic emissions were performed. Tinnitus patients fulfilled the Tinnitus Handicap Inventory (THI) and visual-analog scales (VAS) for loudness and distress. Patients with CT answered a simple question about the worsening of their tinnitus after COVID-19.ResultsPCT was reported by 19.3% of the patients, while 22.8% reported CT. No statistical difference was found between CT and PCT concerning hearing function, tinnitus characteristics and tinnitus distress. There was also no statistically significant difference between PCT and NT with respect to COVID-19 symptoms and pharmacological COVID-19 treatment. Patients with CT reported worsening of their tinnitus after COVID-19.ConclusionAs with other viral infections, inner ear symptoms may be associated with COVID-19. In our sample patients with tinnitus onset before COVID-19 and those with tinnitus onset during or after COVID-19 did not differ significantly in their clinical characteristics and their hearing function, suggesting that tinnitus occurring in the context of a COVID-19 infection is not related to a unique pathophysiological mechanism. The comparison of COVID-19 patients, who developed tinnitus with those who did not develop tinnitus did not reveal any differences in COVID-19 symptoms or COVID-19 treatment. Thus, there was no hint, that a specific expression of COVID-19 is closely related to post COVID-19 tinnitus onset. Although some drugs used to treat tinnitus are known to damage the inner ear cells (especially hydroxychloroquine), we did not see any relationship between the intake of these drugs and tinnitus onset, eventually due to the short prescription time and low doses. Among those patients who had tinnitus before COVID-19 30,8% reported worsening after COVID-19. Overall, tinnitus emerging in the context of a COVID-19 infection seems not to differ from tinnitus unrelated to COVID-19. For further exploring the relationship of tinnitus and COVID-19, large population based studies are warranted.

Objective: To investigate whether a four-week course of neuronavigated intermittent theta burst stimulation (iTBS) of the left dorsolateral prefrontal cortex is superior to the non-neuronavigated F3-EEG method of positioning. Methods: We conducted a single-center, two-arm, randomized and double-blinded study (clinicaltrials.gov NCT03953521). 37 inpatients with an at least moderate depressive episode were randomized to receive either neuronavigated or 10-20-EEG-system based F3 guided iTBS. Both groups received twenty week daily sessions of iTBS while continuing to receive standard-of-care treatment by their ward physicians. For navigated iTBS, we used magnetic resonance imaging to target the border between the anterior and middle third of the middle frontal gyrus considered to represent the left dorsolateral prefrontal cortex (lDLPFC).Differences in the treatment arms were blinded by completely mimicking the procedures of the respective other treatment group. Rating physicians were not involved in the treatment procedure.Primary outcome was defined as the change of the 21-item version of the Hamilton Depression Score (HAMD) from baseline to end of treatment at week 4. Secondary outcomes included HAMD score during the treatment, Patient Health Questionnaire-9, WHO Quality of Life-BREF and Clinical Global Impression. For primary outcome, we used a planned group comparison for the absolute change in the HAMD. For secondary outcome measures we calculated analyses of variance (ANOVAs) with the within-subjects factor time (primary: baseline vs. week 4; secondary: all visits) and the between-subjects factor group (navigated vs. F3 guided group). We also did planned contrasts between both groups for all variables and all treatment and follow-up visits with the aim not to oversee any group differences. For group contrasts we used Student T-tests for metric and chi-square tests for categorial variables. Significance threshold was set to 5% uncorrected for multiple comparisons. Results: Enrolment of 80 patients with interim analysis was planned. Interim analysis was performed after 37 patients (intention to treat). 6 patients dropped out, leaving 31 for analysis. With respect to primary outcome criteria, absolute change in the HAMD did not differ significantly between groups. In accordance, relative change and number of responders and remitters were not significantly different. Overall number of responders was 53% and of remitters was 60%. On a descriptive level, the results favor the clinical effects of the F3 group for the absolute and relative change in the HAMD and the number of responders. Number of remitters were exactly the same for both groups. Therefore, we decided to stop the trial due to the added burden of magnetic resonance imaging and neuronavigated treatment in relation to the effect. Secondary outcomes did also not differ significantly between groups. Patients did not differ in their baseline characteristics nor with respect to intake of medication during the trial period and all had access to the same therapeutic interventions. Conclusion: We noticed a high antidepressive effect of add-on iTBS treatment to standard inpatient treatment but failed to demonstrate a clinical superiority of neuronavigated localization. The non-navigated, F3 guided iTBS treatment used as a control group may be sophisticated enough to dilute potential added benefits, and the difference between the localization approaches is either negligible or too small to justify the additional efforts of navigation. The effects of concomitant treatment may mask effects, but our patient population reflects clinical reality in an inpatient setting. Further prospective studies are warranted to compare neuronavigated with surface-based approaches.

Abstract Little is known about the trajectory of tinnitus over time. This study addressed (1) how often tinnitus remitted in patients with chronic tinnitus; (2) how subjective reported tinnitus characteristics, such as loudness, laterality, and type and measures of burden, such as tinnitus distress, depression, and quality of life, changes over time; (3) how often tinnitus-specific treatments were undertaken and the prevalence of comorbidities, (4) if the number of treatments and comorbidities were associated to changes in tinnitus distress over time. Data from 388 patients with chronic tinnitus who visited a tertiary tinnitus clinic between 2012 and 2017 were interrogated via a mail survey in 2018. Tinnitus characteristics were measured with the Tinnitus Sample Case History Questionnaire and numeric rating scales; tinnitus distress with Tinnitus Handicap Inventory (THI) and the Tinnitus Questionnaire (TQ), depression with the Major Depression Inventory and Quality of life with the World Health Organisation Quality of Life BREF at both time points and the clinical global impression scale. Comorbidities experienced and undertaken treatments were assessed with an in-house survey. Three participants (0.8% of the sample) reported tinnitus remission between both assessments. A decrease in the THI and TQ, and numeric ratings for tinnitus severity, annoyance, unpleasantness, and discomfort was observed, but no differences in tinnitus characteristics, depression, quality of life or overall health status. 64% presented at least one comorbidity, and 88% sought at least on tinnitus-specific treatment. Common comorbidities were psychological and sleeping problems, and the most common interventions were going to the dentist, taking medications, and wearing hearing aids. Our results suggest that full remission of tinnitus is a rare condition, that tinnitus distress on average decreases over time, and that tinnitus characteristics, quality of life, and depression tend to remain unaltered. The high number of interventions and comorbidities displayed minimal association to the changes in tinnitus distress, highlighting the substantial and durable burden of tinnitus sufferers.

BackgroundTinnitus is a heterogeneous condition which may be associated with moderate to severe disability, but the reasons why only a subset of individuals is burdened by the condition are not fully clear. Ecological momentary assessment (EMA) allows a better understanding of tinnitus by capturing the fluctuations of tinnitus symptoms, such as distress and loudness, and psychological processes, such as emotional arousal, overall stress, mood, and concentration and how these variables interact over time. Whether any of those variables have an influence over the next day, that is, whether any of these variables are auto- or cross-correlated, is still unanswered.ObjectivesAssess whether behavioral and symptom-related data from tinnitus users from the TrackYourTinnitus (TYT) mobile app have an impact on tinnitus loudness and distress on subsequent days.MethodsAnonymized data was collected from 278 users of the iOS or Android TYT apps between 2014 and 2020. Tinnitus-related distress, tinnitus loudness, concentration level, mood, emotional arousal, and overall stress level were assessed using either a slider or the Wong-Baker Pain FACES scale via a daily survey. Three modeling strategies were used to investigate whether tinnitus loudness and distress are affected by previous days symptoms or psychological processes: auto- and cross correlations, regressions with elastic net regularization, and subgrouping within group iterative multiple model estimation (S-GIMME).ResultsNo autocorrelation or cross-correlation was observed at the group level between the variables assessed. However, application of the regression models with elastic net regularization identified individualized predictors of tinnitus loudness and distress for most participants, with the models including contemporaneous and lagged information from the previous day. S-GIMME corroborated these findings by identifying individualized predictors of tinnitus loudness and distress from the previous day.DiscussionWe showed that tinnitus loudness and tinnitus distress are affected by the contemporaneous and lagged dynamics of behavioral and emotional processes measured through EMA. These effects were seen at the group, and individual levels. The relevance EMA and the implications of the insights derived from it for tinnitus care are discussed, especially considering current trends toward the individualization of tinnitus care.

Summary: Background: Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time. Methods: Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated. Findings: In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 – 21,630) for MDs, 3,891 (3,020 - 4,905) for SUDs, and 89·1 (63·8 - 123·1) for self-harm. In terms of disability, anxiety contributed to 647·3 (432–912·3) YLDs, while in terms of premature death, self-harm contributed to 319·6 (248·9–412·8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14·9%;9·4-20·1) and drug use disorders (16·9%;8·9-26·3), and decreased in idiopathic developmental intellectual disability (–29·1%;23·8-38·5). YLLs decreased in self-harm (–27·9%;38·3-18·7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs. Interpretation: Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people. Funding: The Bill and Melinda Gates Foundation

Abstract Background A large proportion of admissions to psychiatric hospitals happen as emergency admissions and many of them occur out of core working hours (during the weekends, on public holidays and during night time). However, very little is known about what determines admission times and whether the information of admission time bears any relevance for the clinical course of the patients. In other words, do admission times correlate with diagnostic groups? Can accumulations of crises be detected regarding circadian or weekly rhythms? Can any differences between workdays and weekends/public holidays be detected? May it even be possible to use information on admission times as a predictor for clinical relevance and severity of the presented condition measured by the length of stay? Methods In the present manuscript we analyzed data derived from 37′705 admissions to the Psychiatric District Hospital of Regensburg located in the Southern part of Germany covering the years 2013 to 2018 with regard to ICD-10 diagnostic groups and admission times. The hospital provides 475 beds for in-patient treatment in all fields of clinical psychiatry including geriatrics and addiction medicine. Results Several core questions could be answered based on our analysis: 1st Our analysis confirms that there is a high percentage of unheralded admissions out of core time showing broad variation. 2nd In contrary to many psychiatrists’ misconceptions the time of admission has no relevant impact on the length of stay in the hospital. 3rd The predictive value of admission time regarding the allocation to ICD-10 diagnostic groups is low explaining only 1% of variability. Conclusions Taken together, our data reveal the enormous variation of admission times of psychiatric patients accounting for the need of adequate and consistent provision of personnel and spatial resources.

BackgroundChronic tinnitus is a clinically multidimensional phenomenon that entails audiological, psychological and somatosensory components. Previous research has demonstrated age and female gender as potential risk factors, although studies to this regard are heterogeneous. Moreover, whilst recent research has begun to identify clinical “phenotypes,” little is known about differences in patient population profiles at geographically separated and specialized treatment centers. Identifying such differences might prevent potential biases in joint randomized controlled trials (RCTs) and allow for population-specific treatment adaptations.MethodTwo German tinnitus treatment centers were compared regarding pre-treatment data distributions of their patient population bases. To identify overlapping as well as center-specific factors, juxtaposition-, similarity-, and meta-data-based methods were applied.ResultsBetween centers, significant differences emerged. One center demonstrated some predictive power of the patients of the other center with regard to questionnaire score after treatment, indicating similarities in treatment response across center populations. Furthermore, adherence to the completion of the questionnaires was found to be an important factor in predicting post-treatment data.DiscussionDifferential age and gender distributions per center should be considered as regards RCT design and individualized treatment planning.

Abstract Several studies emphasized the potential of single and multiple transcranial random noise stimulation (tRNS) sessions to interfere with auditory cortical activity and to reduce tinnitus loudness. It was the objective of the present study to evaluate the use of high-frequency (hf) tRNS in a one-arm pilot study in patients with chronic tinnitus. Therefore, 30 patients received 10 sessions of high frequency tRNS (100-640 Hz; 2 mA; 20 minutes) over the bilateral temporal cortex. All patients had received rTMS treatment for their tinnitus at least 3 months before tRNS. Primary outcome was treatment response (tinnitus questionnaire reduction of ≥5 points). The trial was registered at clinicaltrials.gov (NCT01965028). Eight patients (27%) responded to tRNS. Exactly the same number of patients had responded before to rTMS, but there were only two “double responders” for both treatments. None of the secondary outcomes (tinnitus numeric rating scales, depressivity, and quality of life) was significant when results were corrected for multiple comparisons. tRNS treatment was accompanied by tolerable side effects but resulted in temporal increases in tinnitus loudness in 20% of the cases (2 drop-outs). Our trial showed that hf-tRNS is feasible for daily treatment in chronic tinnitus. However, summarizing low treatment response, increase of tinnitus loudness in 20% of patients and missing of any significant secondary outcome, the use of hf-tRNS as a general treatment for chronic tinnitus cannot be recommended at this stage. Differences in treatment responders between tRNS and rTMS highlight the need for individualized treatment procedures.

Health systems worldwide are challenged by the coronavirus pandemic and all medical specialties have struggle to meet the conflicting requirements for virus containment on the one hand and treatment of other medical conditions on the other. This holds true also for psychiatry. Per se, psychiatric patients are highly vulnerable to suffer from social isolation and loneliness. As a result of the Covid-19 pandemic and lockdown measures, unfortunately, this vulnerability is even further increased. As a part of its pandemic risk management, the outpatient clinic of the Psychiatric District Hospital Regensburg launched an online blog as a means of assisting patients who were required to stay home. Aim of the blog was to stay by patients' side in those uncertain times by offering an online connection to their therapists, by providing important information about the pandemic situation, by offering some ideas on how to build a daily routine and how to meaningfully spend their time at home during the lockdown. We also aimed at involving patients as experts in their own affairs by inviting them to contribute to the blog's shape and content. As a result of coordinated team effort, it was possible to launch a blog within few days, and this was perceived helpful by many patients. Overall, however, patient involvement turned out to be a challenge requiring more attention in future work.

Little is known about the transition from acute tinnitus to chronic tinnitus. By means of this study, we are attempting to close this gap by presenting prospective pilot data of patients with acute tinnitus, followed by tracking their condition's trajectory over a period of 6 months. Forty-nine patients presenting with acute tinnitus (duration < 28 days) were recruited in two clinics. We recorded demographic and clinical tinnitus-related data as well as data on personality, health, treatments, and life-style, during patients' first appearance in the clinic and again three and 6 months thereafter. Standard audiograms were performed at the first and the second visit. Nine (18.4%) patients showed full remission of their tinnitus. These patients differed from patients with a chronic course of tinnitus by shorter tinnitus duration, lower fear-related hyperacusis, higher proportion of female gender, increased ear pressure, and lower levels of alcohol consumption. Among the patients with a chronification of tinnitus, there was no change in tinnitus characteristics. However, their tinnitus distress improved moderately over time. These preliminary data are in line with earlier studies that have shown that only a small proportion of those patients presenting in the clinic with acute tinnitus experience a full remission. The results of this study can be of service in deducing hypotheses for the transition from acute to chronic tinnitus and in developing designs for interventional studies.

The pandemic spread of the corona virus SARS-CoV-2 has even-handedly shattered national and international health systems and economies almost in an instant. As numbers of infections and COVID-19–related deaths rise from day to day, fears and uncertainties on how to deal with this unknown threat are extremely present both for individuals and societies as a whole. In this manuscript, we aim to exemplarily describe the bullet points concerning (a) the internal risk management, (b) the organizational and structural changes, and (c) the communicational strategies applied in a Psychiatric University Hospital in the Southern part of Germany. The authors are well aware about the fact that almost none of these considerations may be considered as evidence-based at the moment. However, the authors trust that these reflections and experiences may be useful as an orientation for similar risk constellations in other afflicted countries due to the temporal delay of the pandemic course.

Background: Preclinical studies recently showed that the mineralocorticoid antagonist spironolactone acts also as an antagonist of the NRG1-ERBB4 signaling pathway and improves schizophrenia-like behaviour in Nrg1 transgenic mouse model. As this signaling pathway is critically linked to the pathophysiology of schizophrenia, especially in the context of working-memory dysfunction, spironolactone may be a novel treatment option for patients with schizophrenia targeting cognitive impairments. Aims: To evaluate whether spironolactone added to an ongoing antipsychotic treatment improves cognitive functioning in schizophrenia. Methods: The add-on spironolactone for the treatment of schizophrenia trial (SPIRO-TREAT) is a multicenter randomized, placebo-controlled trial with three arms (spironolactone 100 mg, spironolactone 200 mg and placebo). Schizophrenia patients are treated for three weeks and then followed-up for additional nine weeks. As primary outcome, we investigate changes in working memory before and at the end of the intervention phase. We will randomize 90 patients. Eighty-one patients are intended to reach the primary endpoint measure at the end of the three-week intervention period. Secondary endpoints include other measures of cognition, psychopathology, safety measures and biological measures. Conclusions: SPIRO-TREAT is the first study evaluating the efficacy of the mineralocorticoid receptor antagonist spironolactone to improve cognitive impairments in schizophrenia patients targeting the NRG1-ERBB4 signaling pathway. With SPIRO-TREAT, we intend to investigate a novel treatment option for cognitive impairments in schizophrenia that goes beyond the established concepts of interfering with dopaminergic neurotransmission as key pathway in schizophrenia treatment. Clinical trial registration: International Clinical Trials Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2014-001968-35-DE Keywords: Schizophrenia, Cognitive impairment, Spironolactone, NRG1-ERBB4, Drug repositioning, Drug repurposing

Background: Past research highlighted the benefits of personalized repetitive transcranial magnetic stimulation (rTMS) for the treatment of chronic subjective tinnitus.Objective/Hypothesis: The objective was to investigate the feasibility of rTMS personalization by identifying individually optimal stimulation parameters in test sessions. Particularly, effectiveness and retest–reliability of different stimulation parameters were examined.Methods: Via electric-field guided rTMS, five patients were stimulated with different frequencies on three positions of the left and right superior temporal gyrus on 2 separate days. After each stimulation, the patients had to evaluate tinnitus loudness and discomfort of the used protocol.Results: Individualization of rTMS was possible in all five patients. Significant lower tinnitus loudness was found for 1 Hz stimulation. Positive correlations between 2 days were observed for hemisphere (left, right), position (mSTG, pSTG), and frequency (1, 10, 20 Hz). High-frequency stimulation produced high discomfort.Conclusion: Personalization of rTMS is considered as feasible. Consistency of parameter-specific tinnitus suppression is demonstrated.

The increasing prevalence of smart mobile devices (e.g., smartphones) enables the combined use of mobile crowdsensing (MCS) and ecological momentary assessments (EMA) in the healthcare domain. By correlating qualitative longitudinal and ecologically valid EMA assessment data sets with sensor measurements in mobile apps, new valuable insights about patients (e.g., humans who suffer from chronic diseases) can be gained. However, there are numerous conceptual, architectural and technical, as well as legal challenges when implementing a respective software solution. Therefore, the work at hand (1) identifies these challenges, (2) derives respective recommendations, and (3) proposes a reference architecture for a MCS-EMA-platform addressing the defined recommendations. The required insights to propose the reference architecture were gained in several large-scale mHealth crowdsensing studies running for many years and different healthcare questions. To mention only two examples, we are running crowdsensing studies on questions for the tinnitus chronic disorder or psychological stress. We consider the proposed reference architecture and the identified challenges and recommendations as a contribution in two respects. First, they enable other researchers to align our practical studies with a baseline setting that can satisfy the variously revealed insights. Second, they are a proper basis to better compare data that was gathered using MCS and EMA. In addition, the combined use of MCS and EMA increasingly requires suitable architectures and associated digital solutions for the healthcare domain.

Repetitive transcranial magnetic stimulation (rTMS) is effective in the treatment of depression. However, for the subset of patients with bipolar disorder, less data is available and overall strength of evidence is weaker than for its use in unipolar depression. A cohort of 505 patients (of which 46 had a diagnosis of bipolar disorder) with depression who were treated with rTMS were analyzed retrospectively with regards to their response to several weeks of treatment. Hamilton Depression Rating Scale (HDRS) was assessed as main outcome. Unipolar and bipolar patients with depression did not differ significantly in baseline demographic variables or severity of depression. Both groups did not differ significantly in their response to treatment as indicated by absolute and relative changes in the HDRS and response and remission rates. On HDRS subitem-analysis, bipolar patients showed superior amelioration of the symptom “paranoid symptoms” in a statistically significant manner. In conclusion, depressed patients with a diagnosis of bipolar disorder benefit from rTMS in a similar fashion as patients with unipolar depression in a naturalistic setting. rTMS might be more effective in reducing paranoia in bipolar than in unipolar patients.

Background: Personalization of repetitive transcranial magnetic stimulation (rTMS) for tinnitus might be capable to overcome the heterogeneity of treatment responses. The assessment of loudness changes after short rTMS protocols in test sessions has been proposed as a strategy to identify the best protocol for the daily treatment application. However, the therapeutic advantages of this approach are currently not clear. The present study was designed to further investigate the feasibility and clinical efficacy of personalized rTMS as compared to a standardized rTMS protocol used for tinnitus. Methods: RTMS personalization was conducted via test sessions and reliable, sham-superior responses respectively short-term reductions in tinnitus loudness following active rTMS protocols (1, 10, 20 Hz, each 200 pulses) applied over the left and right temporal cortex. Twenty pulses at a frequency of 0.1 Hz served as a control condition (sham). In case of a response, patients were randomly allocated to ten treatment sessions of either personalized rTMS (2000 pulses with the site and frequency producing the most pronounced loudness reduction during test sessions) or standard rTMS (1 Hz, 2000 pulses left temporal cortex). Those participants who did not show a response during the test sessions received the standard protocol as well. Results: The study was terminated prematurely after 22 patients (instead of 50 planned) as the number of test session responders was much lower than expected (27% instead of 50%). Statistical evaluation of changes in metric tinnitus variables and treatment responses indicated only numerical, but not statistical superiority for personalized rTMS compared to standard treatment. Conclusions: The current stage of investigation does not allow for a clear conclusion about the therapeutic advantages of personalized rTMS for tinnitus based on test session responses. The feasibility of this approach is primarily limited by the low test session response rate.

Recent digitization technologies empower mHealth users to conveniently record their Ecological Momentary Assessments (EMA) through web applications, smartphones, and wearable devices. These recordings can help clinicians understand how the users’ condition changes, but appropriate learning and visualization mechanisms are required for this purpose. We propose a web-based visual analytics tool, which processes clinical data as well as EMAs that were recorded through a mHealth application. The goals we pursue are (1) to predict the condition of the user in the near and the far future, while also identifying the clinical data that mostly contribute to EMA predictions, (2) to identify users with outlier EMA, and (3) to show to what extent the EMAs of a user are in line with or diverge from those users similar to him/her. We report our findings based on a pilot study on patient empowerment, involving tinnitus patients who recorded EMAs with the mHealth app TinnitusTips. To validate our method, we also derived synthetic data from the same pilot study. Based on this setting, results for different use cases are reported.

Background: Suicide is a major public health problem. About 90% of suicide victims have one or more major psychiatric disorder, with a reported 20-fold increased risk for suicide in patients with affective disorders in comparison with healthy subjects. Repetitive transcranial magnetic stimulation (rTMS) has been established as an effective alternative or adjunctive treatment option for patients with depressive disorders, but little is known about its effects on suicide risk.Objective: For the assessment of the effectiveness of rTMS on suicidal ideation and behaviors, we performed a retrospective analysis of a large sample of patients with depressive disorders, who were treated with rTMS.Methods: We analyzed the records of 711 TMS in- and out-patients with depressive affective disorders in a tertiary referral hospital between 2002 and 2017. Out of these patients we were able to collect Hamilton depression rating scale (HAMD) data of 332 patients (180 females, 152 males; age range 20 to 79 years; mean age 47.3 ± 12.3) for which we analyzed the change of suicidal ideation by using item 3 (suicidality) of HAMD.Results: Out of all 711 patients treated with rTMS for their depression, one patient (0.1%) committed suicide during the TMS treatment. In the statistical analysis of the subsample with 332 patients there was an overall amelioration of depressive symptoms accompanied by a significant decrease in the suicidality item with a medium effect size. Decrease in suicidality was not inferior to changes in other items as indicated by effect sizes. Forty-seven percent of patients showed an amelioration in suicidality, 41.3% of patients did not show a change in their suicidality’s scores, and 11.7% of patients showed an increase in suicidality’s scores from baseline to final rating. Correlation of item 3 (suicidality) and item 7 (drive) demonstrated a significant positive association, revealing improved drive with a parallel decreased suicidality.Conclusion: Based on the proposed data, there is no evidence that rTMS increases the risk for suicide during the course of the treatment. Conversely, rTMS tends to reduce suicidal ideation. Our findings call for further rTMS controlled studies using large sample sizes and specific suicidality assessment measures to obtain more conclusive results.

Introduction: Chronic tinnitus is a condition estimated to affect 10–15% of the population. No treatment has shown efficacy in randomized clinical trials to reliably and effectively suppress the phantom perceptions, and little is known why patients react differently to the same treatments. Tinnitus heterogeneity may play a central role in treatment response, but no study has tried to capture tinnitus heterogeneity in terms of treatment response.Research Goals: To test if the individualized treatment response can be predicted using personal, tinnitus, and treatment characteristics.Methods: A survey conducted by the web platform Tinnitus Hub collected data of 5017 tinnitus bearers. The participants reported which treatments they tried and the outcome of the given treatment. Demographic and tinnitus characteristics, alongside with treatment duration were used as predictors of treatment outcomes in both an univariate as well as a multivariate regression setup. First, simple linear regressions were used with each of the 13 predictors on all of 25 treatment outcomes to predict how much variance could be explained by each predictor individually. Then, all 13 predictors were added together in the elastic net regression to predict treatment outcomes.Results: Individual predictors from the linear regression models explained on average 2% of the variance of treatment outcome. “Duration of treatment” was the predictor that explained, on average, most of the variance, 6.8%. When combining all the predictors in the elastic net, the model could explain on average 16% of the deviance of treatment outcomes.Discussion: By demonstrating that different aspects predict response to various treatments, our results support the notion that tinnitus heterogeneity influences the observed variability in treatment response. Moreover, the data suggest the potential of personalized tinnitus treatment based on demographic and clinical characteristics.

Recent studies have compared tinnitus suppression, or residual inhibition, between amplitude- and frequency-modulated (AM) sounds and noises or pure tones (PT). Results are indicative, yet inconclusive, of stronger tinnitus suppression of modulated sounds especially near the tinnitus frequency. Systematic comparison of AM sounds at the tinnitus frequency has not yet been studied in depth. The current study therefore aims at further advancing this line of research by contrasting tinnitus suppression profiles of AM and PT sounds at the matched tinnitus frequency (i.e., 10 and 40 Hz AM vs. PT). Participants with chronic, tonal tinnitus (n = 29) underwent comprehensive psychometric, audiometric, tinnitus matching, and acoustic stimulation procedures. Stimuli were presented for 3 minutes in two loudness regimes (60 dB sensation level [SL], minimum masking level [MML] + 6 dB, control sound: SL −6 dB) and amplitude modulated with 0, 10, or 40 Hz. Tinnitus loudness suppression was measured after the stimulation every 30 seconds. In addition, stimuli were rated regarding their valence and arousal. Results demonstrate only trends for better tinnitus suppression for the 10 Hz modulation and presentation level of 60 dB SL compared with PT, whereas nonsignificant results are reported for 40 Hz and MML + 6 dB, respectively. Furthermore, the 10 Hz AM at 60 dB SL and the 40 Hz AM at MML + 6 dB (trend) stimuli were better tolerated as elicited by valence ratings. We conclude that 10 Hz AM sounds at the tinnitus frequency may be useful to further elucidate the phenomenon of residual inhibition.

Chronic subjective tinnitus is an auditory phantom phenomenon characterized by abnormal neuronal synchrony in the central auditory system. As shown computationally, acoustic coordinated reset (CR) neuromodulation causes a long-lasting desynchronization of pathological synchrony by downregulating abnormal synaptic connectivity. In a previous proof of concept study acoustic CR neuromodulation, employing stimulation tone patterns tailored to the dominant tinnitus frequency, was compared to noisy CR-like stimulation, a CR version significantly detuned by sparing the tinnitus-related pitch range and including substantial random variability of the tone spacing on the frequency axis. Both stimulation protocols caused an acute relief as measured with visual analogue scale scores for tinnitus loudness (VAS-L) and annoyance (VAS-A) in the stimulation-ON condition (i.e. 15min after stimulation onset), but only acoustic CR neuromodulation had sustained long-lasting therapeutic effects after 12weeks of treatment as assessed with VAS-L, VAS-A scores and a tinnitus questionnaire (TQ) in the stimulation-OFF condition (i.e. with patients being off stimulation for at least 2.5h). To understand the source of the long-lasting therapeutic effects, we here study whether acoustic CR neuromodulation has different electrophysiological effects on oscillatory brain activity as compared to noisy CR-like stimulation under stimulation-ON conditions and immediately after cessation of stimulation. To this end, we used a single-blind, single application, cross over design in 18 patients with chronic tonal subjective tinnitus and administered three different 16-minute stimulation protocols: acoustic CR neuromodulation, noisy CR-like stimulation and low frequency range (LFR) stimulation, a CR type stimulation with deliberately detuned pitch and repetition rate of stimulation tones, as control stimulation. We measured VAS-L and VAS-A scores together with spontaneous EEG activity pre-, during- and post-stimulation. Under stimulation-ON conditions acoustic CR neuromodulation and noisy CR-like stimulation had similar effects: a reduction of VAS-L and VAS-A scores together with a decrease of auditory delta power and an increase of auditory alpha and gamma power, without significant differences. In contrast, LFR stimulation had significantly weaker EEG effects and no significant clinical effects under stimulation-ON conditions. The distinguishing feature between acoustic CR neuromodulation and noisy CR-like stimulation were the electrophysiological after-effects.Acoustic CR neuromodulation caused the longest significant reduction of delta and gamma and increase of alpha power in the auditory cortex region. Noisy CR-like stimulation had weaker and LFR stimulation hardly any electrophysiological after-effects. This qualitative difference further supports the assertion that long-term effects of acoustic CR neuromodulation on tinnitus are mediated by a specific disruption of synchronous neural activity. Furthermore, our results indicate that acute electrophysiological after-effects might serve as a marker to further improve desynchronizing sound stimulation. Keywords: Alpha band activity, Coordinated reset neuromodulation, Delta band activity, Electroencephalography, Gamma band activity

Smart sensors and smartphones are becoming increasingly prevalent. Both can be used to gather environmental data (e.g., noise). Importantly, these devices can be connected to each other as well as to the Internet to collect large amounts of sensor data, which leads to many new opportunities. In particular, mobile crowdsensing techniques can be used to capture phenomena of common interest. Especially valuable insights can be gained if the collected data are additionally related to the time and place of the measurements. However, many technical solutions still use monolithic backends that are not capable of processing crowdsensing data in a flexible, efficient, and scalable manner. In this work, an architectural design was conceived with the goal to manage geospatial data in challenging crowdsensing healthcare scenarios. It will be shown how the proposed approach can be used to provide users with an interactive map of environmental noise, allowing tinnitus patients and other health-conscious people to avoid locations with harmful sound levels. Technically, the shown approach combines cloud-native applications with Big Data and stream processing concepts. In general, the presented architectural design shall serve as a foundation to implement practical and scalable crowdsensing platforms for various healthcare scenarios beyond the addressed use case.

Since somatic or somatosensory tinnitus (ST) was first described as a subtype of subjective tinnitus, where altered somatosensory afference from the cervical spine or temporomandibular area causes or changes a patient’s tinnitus perception, several studies in humans and animals have provided a neurophysiological explanation for this type of tinnitus. Due to a lack of unambiguous clinical tests, many authors and clinicians use their own criteria for diagnosing ST. This resulted in large differences in prevalence figures in different studies and limits the comparison of clinical trials on ST treatment. This study aimed to reach an international consensus on diagnostic criteria for ST among experts, scientists and clinicians using a Delphi survey and face-to-face consensus meeting strategy. Following recommended procedures to gain expert consensus, a two-round Delphi survey was delivered online, followed by an in-person consensus meeting. Experts agreed upon a set of criteria that strongly suggest ST. These criteria comprise items on somatosensory modulation, specific tinnitus characteristics, and symptoms that can accompany the tinnitus. None of these criteria have to be present in every single patient with ST, but in case they are present, they strongly suggest the presence of ST. Because of the international nature of the survey, we expect these criteria to gain wide acceptance in the research field and to serve as a guideline for clinicians across all disciplines. Criteria developed in this consensus paper should now allow further investigation of the extent of somatosensory influence in individual tinnitus patients and tinnitus populations.

In the recent years, there has been an increasing interest in the potential of internet- and smartphone-based technologies for the support of tinnitus patients. A broad spectrum of relevant approaches, some in the form of studies, others in the form of market products, have been mentioned in literature. They include auditory treatments, internet-based Cognitive Behavioral Therapy (iCBT), serious games, and questionnaires for tinnitus monitoring. The goal of this study is to highlight the role of existing internet-based and smart technologies for the advancement of tinnitus clinical practice: we consider contributions that refer to treatments and diagnostics, and we include contributions refering to self-help measures. We elaborate on the potential and challenges of such solutions and identify constraints associated to their deployment, such as the demand for familiarity with internet-based services and the need to re-design interactive services so that they fit on the small surface of a smartwatch.

While brain stimulation techniques have been examined as treatment options for chronic tinnitus for many years, they have recently been extended to multimodal treatment approaches. As chronic tinnitus is often accompanied by comorbid muscular tension in the neck and back, we performed a one-arm pilot study to explore the feasibility of a new multimodal treatment approach. In detail, repetitive peripheral magnetic stimulation (rPMS) of the back was performed before and after each session of repetitive transcranial magnetic stimulation (rTMS) of the brain. Data of 41 patients were analyzed, all of which were treated with ten sessions of rTMS of the left prefrontal and left temporoparietal cortex followed by rPMS of the neck and back muscles. Tinnitus severity was measured using the tinnitus questionnaire (TQ). Neck pain was assessed using the neck pain and disability scale (NPAD). The new treatment approach was feasible and well accepted by the majority of patients. However, the overall patient group did not improve significantly in either of the questionnaires. If patients were divided in different subgroups depending on whether they were suffering from neck pain or somatosensory tinnitus, explorative post-hoc tests suggested differential effects: patients with both neck pain and somatosensory tinnitus had better outcomes than patients without those conditions or with neck pain only. This was true for both the TQ and the NPAD. This effect was of transient nature though: the TQ score went back to its baseline level after a follow-up period of 12 weeks. Based on our results we recommend that in studies that investigate tinnitus treatments targeting somatosensory afferents patients should be stratified according to somatic co-morbidities and somatosensory influence on the tinnitus percept.Clinical trial registration: www.clinicaltrials.gov, NCT02306447.

Verbal episodic memory is one of the core cognitive functions affected in patients with schizophrenia (SZ). Although this verbal memory impairment in SZ is a well-known finding, our understanding about its underlying neurophysiological mechanisms is rather scarce. Here we address this issue by recording brain oscillations during a memory task in a sample of healthy controls and patients with SZ. Brain oscillations represent spectral fingerprints of specific neurocognitive operations and are therefore a promising tool to identify neurocognitive mechanisms that are affected by SZ. Healthy controls showed a prominent suppression of left prefrontal beta oscillatory activity during successful memory formation, which replicates several previous oscillatory memory studies. In contrast, patients failed to exhibit such a left prefrontal beta power suppression. Utilizing a new topographical pattern similarity approach, we further demonstrate that the degree of similarity between a patient's beta power decrease to that of the controls reliably predicted memory performance. This relationship between beta power decreases and memory was such that the patients' memory performance improved as they showed a more similar topographical beta desynchronization pattern compared to that of healthy controls. Together, these findings support left prefrontal beta desynchronization as the spectral fingerprint of verbal episodic memory formation, likely indicating deep semantic processing of verbal material. These findings also demonstrate that left prefrontal beta power suppression (or lack thereof) during memory encoding are a reliable biomarker for the observed encoding impairments in SZ in verbal memory.