Detecting Heterogeneity of Intervention Effects in Comparative Judgments.

Comparative measures such as paired comparisons and rankings are frequently used to evaluate health states and quality of life. The present article introduces log-linear Bradley-Terry (LLBT) models to evaluate intervention effectiveness when outcomes are measured as paired comparisons or rankings and presents a combination of the LLBT model and model-based recursive partitioning (MOB) to detect treatment effect heterogeneity. The MOB LLBT approach enables researchers to identify subgroups that differ in the preference order and in the effect an intervention has on choice behavior. Applicability of MOB LLBT models is demonstrated using an artificial data example with known data-generating mechanism and a real-world data example focusing on drug-harm perception among music festival visitors. In the artificial data example, the MOB LLBT model is able to adequately recover the "true" (population) model. In the real-world data example, the standard LLBT model confirms the existence of a situational willingness among festival visitors to trivialize drug harm when peer consumption behavior is made cognitively accessible. In addition, MOB LLBT results suggest that this trivialization effect is highly context-dependent and most pronounced for participants with low-to-moderate alcohol intoxication who also proactively contacted a substance counselor at the festival venue. Both data examples suggest that MOB LLBT models allow for more nuanced statements about the effectiveness of interventions. We provide R code examples to implement MOB LLBT models for paired comparisons, rankings, and rating (Likert-type) data.

Recovery from alcohol dependence: Do smoking indicators predict abstinence?

BACKGROUND AND OBJECTIVES: There is inconsistent evidence about the potential influence of smoking on recovery from alcohol dependence. Our study aimed at assessing the impact of smoking-behavior on relapse during a 12 months follow-up period following a detoxification in patients with Alcohol Use Disorder (AUD). METHODS: Three hundred Patients with AUD (74.9% smoking) were recruited from two inpatient detoxification units in psychiatric hospitals in Germany and their alcohol consumption was prospectively followed for 1 year. Data on different indicators of smoking behavior was gathered. Cox regression model was used to evaluate potential risk factors on time to relapse of alcohol consumption. Two hundred seventy-nine participants (n = 279) were included in the final analysis. RESULTS: Smoking increased the risk for alcohol relapse (hazard ratio = 3.962, 95% CI 1.582-9.921). However, this increased risk is slightly reduced with higher numbers of daily consumed cigarettes (hazard ratio per cigarette = .986, 95% CI .976-.995). CONCLUSION: Smoking reduced the probability of maintaining alcohol abstinence significantly, whereas higher number of cigarettes smoked daily diminished the increased risk of alcohol relapse in alcohol-dependent patients. SCIENTIFIC SIGNIFICANCE: Coordinated psychiatric and substance abuse interventions for different subgroups of patients with AUD in the post-acute treatment phase are necessary. Individualized treatment planning is especially important in smoking patients with AUD who are vulnerable for a relapse to alcohol drinking and for somatic complications. Our findings might support individualized treatment plans. (Am J Addict 2017;26:366-373).

Temoporfin improves efficacy of photodynamic therapy in advanced biliary tract carcinoma: A multicenter prospective phase II study.

UNLABELLED: Photodynamic therapy using porfimer (P-PDT) improves palliation and survival in nonresectable hilar bile duct cancer. Tumoricidal penetration depth of temoporfin-PDT (T-PDT) is twice that of P-PDT. In a single-arm phase II study we investigated the safety, efficacy, survival time, and adverse events of T-PDT compared with previous data on P-PDT. Twenty-nine patients (median 71 [range 47-88] years) with nonresectable hilar bile duct cancer were treated with T-PDT (median 1 [range 1-4] sessions) plus stenting and followed up every 3 months. The PDT was well tolerated. In patients with occluded segments at baseline (n=28) a reopening of a median of 3 (range 1-7) segments could be achieved: n=16 local response and n=11 stable local disease, one progressive disease. Cholestasis and performance significantly improved when impaired at baseline. Time to local tumor progression was a median of 6.5 (2.7-41.0) months. Overall survival time was a median of 15.4 (range 4.4-62.4) months. Patients died from tumor progression (55%), cholangitis (18%), pneumonia (7%), hemobilia (7%), esophagus variceal hemorrhage (3%), and vascular diseases (10%). Adverse events were cholangitis (n=4), liver abscess (n=2), cholecystitis (n=2), phototoxic skin (n=5), and injection site reactions (n=7). Compared to previous P-PDT, T-PDT shows prolonged time to local tumor progression (median 6.5 versus 4.3 months, P<0.01), fewer PDT treatments needed (median 1 versus 3, P<0.01), a higher 6-month survival rate (83% versus 70%, P<0.01), and a trend for longer overall median survival (15.4 versus 9.3 months, P=0.72) yet not significantly different. The risk of adverse events is not increased except for (avoidable) subcutaneous phototoxicity at the injection site. CONCLUSION: Temoporfin-PDT can safely be delivered to hilar bile duct cancer patients and results in prolonged patency of hilar bile ducts, a trend for longer survival time, and similar palliation as with P-PDT.

People with alcohol use disorders in specialized care in eight different European countries.

AIM: To provide a description of patients receiving alcohol treatment in eight different European countries, including the level of comorbidities and functional limitations. METHODS: Drinking behaviours, DSM-IV alcohol use disorder (AUD), mental and somatic comorbidities, disability and health services utilization of 1767 patients from various specialized treatment settings were assessed as representative for regions of eight European countries. Severity of alcohol dependence (AD) in terms of drinking level was compared with a large representative US sample. RESULTS: Patients in specialized care for AUDs showed high levels of consumption [average level of daily ethanol intake: 141.1 g, standard deviation (SD): 116.0 g], comorbidity [e.g. liver problems: 19.6%, 95% confidence interval (CI): 17.5-21.6%; depression: 43.2%, 95% CI: 40.7-45.8%; anxiety: 50.3%, 95% CI: 47.8-52.9%], disability and health services utilization (average number of nights spent in hospital(s) during the last 6 months: 8.8, SD: 19.5 nights). Severity of AD was similar to the US sample, but European men consumed on average more alcohol daily. CONCLUSIONS: High levels of consumption, somatic and mental comorbidities, disability and functional losses were found in this representative treatment sample, indicating that treatment was initiated only at severe stages of AUDs. Earlier initiation of treatment could help avoid some of the health and social burden.

Prevalence of and potential influencing factors for alcohol dependence in Europe.

Alcohol use disorders (AUDs), and alcohol dependence (AD) in particular, are prevalent and associated with a large burden of disability and mortality. The aim of this study was to estimate prevalence of AD in the European Union (EU), Iceland, Norway, and Switzerland for the year 2010, and to investigate potential influencing factors. The 1-year prevalence of AD in the EU was estimated at 3.4% among people 18-64 years of age in Europe (women 1.7%, men 5.2%), resulting in close to 11 million affected people. Taking into account all people of all ages, AD, abuse and harmful use resulted in an estimate of 23 million affected people. Prevalence of AD varied widely between European countries, and was significantly impacted by drinking cultures and social norms. Correlations with level of drinking and other drinking variables and with major known outcomes of heavy drinking, such as liver cirrhosis or injury, were moderate. These results suggest a need to rethink the definition of AUDs.

Burden of disease associated with alcohol use disorders in the United States.

BACKGROUND: Alcohol use disorders (AUD) have long been considered to be some of the most disabling mental disorders; however, empirical data on the burden of disease associated with AUD have been sparse. The objective of this article is to quantify the burden of disease (in disability-adjusted life years [DALYs] lost), deaths, years of life lost due to premature mortality (YLL), and years of life lost due to disability (YLD) associated with AUD for the United States in 2005. METHODS: Statistical modeling was based on epidemiological indicators derived from the National Epidemiologic Survey on Alcohol and Related Conditions. Formal consistency analyses were applied. Risk relations were taken from recent meta-analyses and the disability weights from the burden of disease study of the National Institutes of Health. Monte Carlo simulations were used to derive confidence intervals. All analyses were performed by sex and age. Sensitivity analyses were undertaken on key indicators. RESULTS: In the United States in 2005, 65,000 deaths, 1,152,000 YLL, 2,443,000 YLD, and 3,595,000 DALYs were associated with AUD. For individuals 18 years of age and older, AUD were associated with 3% of all deaths (5% for men and 1% for women), and 5% of all YLL (7% for men and 2% for women). The majority of the burden of disease associated with AUD stemmed from YLD, which accounted for 68% of DALYs associated with AUD (66% for men and 74% for women). The youngest age group had the largest proportion of DALYs associated with AUD stemming from YLD. CONCLUSIONS: Using data from a large representative survey (checked for consistency) and by combining these data with the best available evidence, we found that AUD were associated with a larger burden of disease than previously estimated. To reduce this disease burden, implementation of prevention interventions and expansion of treatment are necessary.

A Mobile-Based Preventive Intervention for Young, Arabic-Speaking Asylum Seekers During the COVID-19 Pandemic in Germany: Design and Implementation.

BACKGROUND: Most individuals seeking asylum in Germany live in collective housing and are thus exposed to a higher risk of contagion during the COVID-19 pandemic. OBJECTIVE: In this study, we aimed to test the feasibility and efficacy of a culture-sensitive approach combining mobile app-based interventions and a face-to-face group intervention to improve knowledge about COVID-19 and promote vaccination readiness among collectively accommodated Arabic-speaking adolescents and young adults. METHODS: We developed a mobile app that consisted of short video clips to explain the biological basis of COVID-19, demonstrate behavior to prevent transmission, and combat misconceptions and myths about vaccination. The explanations were provided in a YouTube-like interview setting by a native Arabic-speaking physician. Elements of gamification (quizzes and rewards for solving the test items) were also used. Consecutive videos and quizzes were presented over an intervention period of 6 weeks, and the group intervention was scheduled as an add-on for half of the participants in week 6. The manual of the group intervention was designed to provide actual behavioral planning based on the health action process approach. Sociodemographic information, mental health status, knowledge about COVID-19, and available vaccines were assessed using questionnaire-based interviews at baseline and after 6 weeks. Interpreters assisted with the interviews in all cases. RESULTS: Enrollment in the study proved to be very challenging. In addition, owing to tightened contact restrictions, face-to-face group interventions could not be conducted as planned. A total of 88 participants from 8 collective housing institutions were included in the study. A total of 65 participants completed the full-intake interview. Most participants (50/65, 77%) had already been vaccinated at study enrollment. They also claimed to comply with preventive measures to a very high extent (eg, "always wearing masks" was indicated by 43/65, 66% of participants), but practicing behavior that was not considered as effective against COVID-19 transmission was also frequently reported as a preventive measure (eg, mouth rinsing). By contrast, factual knowledge of COVID-19 was limited. Preoccupation with the information materials presented in the app steeply declined after study enrollment (eg, 12/61, 20% of participants watched the videos scheduled for week 3). Of the 61 participants, only 18 (30%) participants could be reached for the follow-up interviews. Their COVID-19 knowledge did not increase after the intervention period (P=.56). CONCLUSIONS: The results indicated that vaccine uptake was high and seemed to depend on organizational determinants for the target group. The current mobile app-based intervention demonstrated low feasibility, which might have been related to various obstacles faced during the delivery. Therefore, in the case of future pandemics, transmission prevention in a specific target group should rely more on structural aspects rather than sophisticated psychological interventions.

Social relationships as a major determinant in the valuation of health states.

PURPOSE: To empirically determine the impact of the capacity to sustain social relationships on valuing health states. METHODS: 68 clinical experts conducted a health state valuation exercise in five sites using pairwise comparison, ranking, and person trade-off as elicitation methods. 23,840 pairwise comparisons of a total of 379 health states were analyzed by conditional logistic regression. RESULTS: Social relationships had a clear monotonic association with perceived disability: the more limited the capacity to sustain social relationships, the more disabling the resulting health state valuations. The highest level of limitations with respect to social relationships was associated with slightly lower impact on health state valuations compared to the highest level of limitations in physical functioning. CONCLUSIONS: Social relationships showed an independent contribution to health state valuations and should be included in health state measures.

PeterPandemic: A Serious Game for Pandemic Management.

The COVID-19 situation shows that a deep understanding of how pandemics spread and how they can be managed is important in a multitude of domains. Various studies have shown that students benefit from game-based learning approaches. Therefore, we introduce the concept of a web-based serious game to teach students important aspects when dealing with pandemic situations.

Assessing Heterogeneity in Students' Visual Judgment: Model-Based Partitioning of Image Rankings.

Differences in the ability of students to judge images can be assessed by analyzing the individual preference order (ranking) of images. To gain insights into potential heterogeneity in judgement of visual abstraction among students, we combine Bradley-Terry preference modeling and model-based recursive partitioning. In an experiment a sample of 1,020 high-school students ranked five sets of images, three of which with respect to their level of visual abstraction. Additionally, 24 art experts and 25 novices were given the same task, while their eye movements were recorded. Results show that time spent on the task, the students' age, and self-reported interest in visual puzzles had significant influence on rankings. Fixation time of experts and novices revealed that both groups paid more attention to ambiguous images. The presented approach makes the underlying latent scale of visual judgments quantifiable.

How Do Art Skills Influence Visual Search? - Eye Movements Analyzed With Hidden Markov Models.

The results of two experiments are analyzed to find out how artistic expertise influences visual search. Experiment I comprised survey data of 1,065 students on self-reported visual memory skills and their ability to find three targets in four images of artwork. Experiment II comprised eye movement data of 50 Visual Literacy (VL) experts and non-experts whose eye movements during visual search were analyzed for nine images of artwork as an external validation of the assessment tasks performed in Sample I. No time constraint was set for completion of the visual search task. A latent profile analysis revealed four typical solution patterns for the students in Sample I, including a mainstream group, a group that completes easy images fast and difficult images slowly, a fast and erroneous group, and a slow working student group, depending on task completion time and on the probability of finding all three targets. Eidetic memory, performance in art education and visual imagination as self-reported visual skills have significant impact on latent class membership probability. We present a hidden Markov model (HMM) approach to uncover underlying regions of attraction that result from visual search eye-movement behavior in Experiment II. VL experts and non-experts did not significantly differ in task time and number of targets found but they did differ in their visual search process: compared to non-experts, experts showed greater precision in fixating specific prime and target regions, assessed through hidden state fixation overlap. Exploratory analysis of HMMs revealed differences between experts and non-experts in image locations of attraction (HMM states). Experts seem to focus their attention on smaller image parts whereas non-experts used wider parts of the image during their search. Differences between experts and non-experts depend on the relative saliency of targets embedded in images. HMMs can determine the effect of expertise on exploratory eye movements executed during visual search tasks. Further research on HMMs and art expertise is required to confirm exploratory results.

Exploring the Usability of the German COVID-19 Contact Tracing App in a Combined Eye Tracking and Retrospective Think Aloud Study.

In the course of the corona virus (COVID-19) pandemic, many digital solutions for mobile devices (e.g., apps) were presented in order to provide additional resources supporting the control of the pandemic. Contact tracing apps (i.e., identify persons who may have been in contact with a COVID-19 infected) constitute one of the most popular as well as promising solutions. However, as a prerequisite for an effective application, such apps highly depend on being used by large numbers of the population. Consequently, it is important that these apps offer a high usability for everyone. We therefore conducted an exploratory study to learn more about the usability of the German COVID-19 contact tracing app Corona-Warn-App (CWA). More specifically, N = 15 participants assessed the CWA, relying on a combined eye tracking and retrospective think aloud approach. The results indicate, on the one hand, that the CWA leaves a promising impression for pandemic control, as essential functions are easily recognized. However, on the other hand, issues were revealed (e.g., privacy policy) that could be addressed in future updates more properly.

Long-term follow-up of orally administered diacetylmorphine substitution treatment.

BACKGROUND: To assess the long-term course of the feasibility and safety of orally administered heroin [diacetylmorphine (DAM)] tablets in substitution treatment of severely addicted opioid users. DESIGN: Open-label, prospective cohort study with 2 non-randomly assigned treatment arms: DAM tablets only (n = 128) or DAM tablets combined with injected DAM and/or other opioids (n = 237). The average duration of the observation period was 62 months. Study endpoints were the time to discharge from treatment and the number of serious adverse events. RESULTS: Both patient groups had a higher than 70% retention rate after the first 48 months of treatment, with similar long-term retention rates (after 8 years both groups had retention over 50%). The physician-verified rate of serious adverse events was 0.01 events per application year among the exclusively oral substitution group (intention-to-treat analysis) during the last year of observation, and 0.005 events per application year in the other group. CONCLUSIONS: Because of their feasibility and safety over years, DAM tablets may be a valuable long-term therapeutic alternative.

The Relationship between Change of Direction Tests in Elite Youth Soccer Players.

Change of direction (COD) is a performance-limiting factor in team sports. However, there are no exact definitions describing which physical abilities limit COD performance in soccer. Nevertheless, different COD tests are used or have been recommended as being equally effective in the professional practice of measuring COD performance. Therefore, the aim of this study was to evaluate the relationship between different COD tests, and to test the independence and generalizability of these COD tests in soccer. As such, 27 elite youth soccer players were randomly recruited and were tested in different COD tests (i.e., Illinois agility test (IAT), T agility test (TT), 505 agility test (505), Gewandtheitslauf (GewT), triangle test (Tri-t), and square test (SQT)). Bivariate Pearson correlation analysis was used to assess the relationships between the COD tests. The Benjamini-Hochberg method was used to control for the false discovery rate of the study at 0.05. This investigation calculated explained variances of 10% to 55% between performances in the different COD tests. This suggested that the tests covered different aspects or task-specific characteristics of the COD. Therefore, coaches and sport scientists should review and select different tests with a logical validity, based on the requirement profiles of the corresponding sport.

Effect of Developmentally Adapted Cognitive Processing Therapy for Youth With Symptoms of Posttraumatic Stress Disorder After Childhood Sexual and Physical Abuse: A Randomized Clinical Trial.

Importance: Despite the high prevalence, evidence-based treatments for abuse-related posttraumatic stress disorder (PTSD) in adolescents have rarely been studied. Objective: To examine whether developmentally adapted cognitive processing therapy (D-CPT) is more effective than a wait-list condition with treatment advice (WL/TA) among adolescents with PTSD related to childhood abuse. Design, Setting, and Participants: This rater-blinded, multicenter, randomized clinical trial (stratified by center) enrolled treatment-seeking adolescents and young adults (aged 14-21 years) with childhood abuse-related PTSD at 3 university outpatient clinics in Germany from July 2013 to June 2015, with the last follow-up interview conducted by May 2016. Of 194 patients, 88 were eligible for randomization. Interventions: Participants received D-CPT or WL/TA. Cognitive processing therapy was enhanced by a motivational and alliance-building phase, by including emotion regulation and consideration of typical developmental tasks, and by higher session frequency in the trauma-focused core CPT phase. In WL/TA, participants received treatment advice with respective recommendations of clinicians and were offered D-CPT after 7 months. Main Outcomes and Measures: All outcomes were assessed before treatment (baseline), approximately 8 weeks after the start of treatment, after the end of treatment (posttreatment), and at the 3-month follow-up. The primary outcome, PTSD symptom severity, was assessed in clinical interview (Clinician-Administered PTSD Scale for Children and Adolescents for DSM-IV [CAPS-CA]). Secondary outcomes were self-reported PTSD severity, depression, borderline symptoms, behavior problems, and dissociation. Results: The 88 participants (75 [85%] female) had a mean age of 18.1 years (95% CI, 17.6-18.6 years). In the intention-to-treat analysis, the 44 participants receiving D-CPT (39 [89%] female) demonstrated greater improvement than the 44 WL/TA participants (36 [82%] female) in terms of PTSD severity (mean CAPS-CA scores, 24.7 [95% CI, 16.6-32.7] vs 47.5 [95% CI, 37.9-57.1]; Hedges g = 0.90). This difference was maintained through the follow-up (mean CAPS-CA scores, 25.9 [95% CI, 16.2-35.6] vs 47.3 [95% CI, 37.8-56.8]; Hedges g = 0.80). Treatment success was greatest during the trauma-focused core phase. The D-CPT participants also showed greater and stable improvement in all secondary outcomes, with between-groups effect sizes ranging from 0.65 to 1.08 at the posttreatment assessment (eg, for borderline symptoms, 14.1 [95% CI, 8.0-20.2] vs 32.0 [95% CI, 23.8-40.2]; Hedges g = 0.91). Conclusions and Relevance: Adolescents and young adults with abuse-related PTSD benefited more from D-CPT than from WL/TA. Treatment success was stable at the follow-up and generalized to borderline symptoms and other comorbidities. Trial Registration: German Clinical Trials Register identifier: DRKS00004787.

Modulation of human motor cortex excitability by quetiapine.

RATIONALE: Quetiapine is increasingly used for the treatment of patients with psychosis and bipolar disorder. However, the neurobiological mechanisms, which may account for the favourable risk/benefit profile of this drug, are not entirely understood. OBJECTIVES: Transcranial magnetic stimulation was used to investigate the effects of acute and repeated administration of quetiapine on cortical excitability in healthy volunteers. MATERIALS AND METHODS: Within a double-blind, placebo-controlled, randomized cross-over design motor threshold, intracortical inhibition, intracortical facilitation and cortical silent period were studied in 15 healthy volunteers before and after a single dose of placebo and 100 mg quetiapine. Additional measurements were performed after 5 days of daily intake of 100 mg quetiapine. RESULTS: We observed a significant prolongation of the cortical silent period after a single dose of quetiapine, whereas the placebo had no effects. After repeated administration, there was a trend towards CSP prolongation, which did not reach significance. However, plasma concentrations at this time point were relatively low, as measurements were performed 15 h after the last drug intake. Other parameters of cortical excitability remained unaffected. CONCLUSIONS: By lengthening CSP without affecting MT, ICI and ICF, quetiapine demonstrates a unique neurophysiological profile which differs distinctively from brain excitability profiles of typical antipsychotics such as haloperidol. Provided that the CSP prolongation reflects the antipsychotic potential of quetiapine, TMS may be developed as a tool to monitor neurobiological effects of quetiapine treatment in schizophrenic patients and to explore the efficacy of other antipsychotic drugs with a similar mode of action.

High-frequency priming stimulation does not enhance the effect of low-frequency rTMS in the treatment of tinnitus.

Based on its ability to reduce the excitability of the cortex locally, low-frequency repetitive transcranial magnetic stimulation (rTMS) has been investigated for the treatment of hyperexcitability disorders such as auditory hallucinations and tinnitus. Results are promising, but characterized by only moderate improvement and a high inter-individual variability. Experimental data from motor cortex stimulation in healthy subjects indicates that the depressant effect of low-frequency rTMS can be enhanced by high-frequency priming stimulation. Here we will investigate whether high-frequency priming also improves the therapeutic efficacy of low-frequency rTMS in a clinical application. 32 patients with chronic tinnitus were randomly assigned to either a standard protocol of low-frequency rTMS (110% motor threshold, 1 Hz, 2000 stimuli/day) or a stimulation protocol in which priming stimulation with 6 Hz (90% motor threshold, 960 stimuli) preceded low-frequency rTMS (110% motor threshold, 1 Hz, 1040 stimuli/day). Stimulation was applied over the left auditory cortex by using MRI-guided coil positioning. The treatment outcome was assessed with a standardized tinnitus questionnaire. There was no significant difference between the standard protocol and the protocol involving priming stimulation. Both stimulation protocols resulted in significant clinical improvement after 10 days of stimulation, as compared to baseline. Our data does not support an enhancing effect of higher frequency priming on low-frequency rTMS in the treatment of tinnitus.

Altered cortical excitability in subjectively electrosensitive patients: results of a pilot study.

OBJECTIVE: Hypersensitivity to electromagnetic fields is frequently claimed to be linked to a variety of unspecific somatic and/or neuropsychological complaints. Whereas provocation studies often failed to demonstrate a causal relationship between electromagnetic field exposure and symptom formation, neurophysiological examinations highlight baseline deviations in people claiming to be electrosensitive. METHODS: To elucidate a potential role of dysfunctional cortical regulations in mediating hypersensitivity to electromagnetic fields, cortical excitability parameters were measured by transcranial magnetic stimulation in subjectively electrosensitive patients (n=23) and two control groups (n=49) differing in their level of unspecific health complaints. RESULTS: Electrosensitive patients showed reduced intracortical facilitation as compared to both control groups, while motor thresholds and intracortical inhibition were unaffected. CONCLUSIONS: This pilot study gives additional evidence that altered central nervous system function may account for symptom manifestation in subjectively electrosensitive patients as has been postulated for several chronic multisymptom illnesses sharing a similar clustering of symptoms.

Pre-treatment anterior cingulate activity as a predictor of antidepressant response to repetitive transcranial magnetic stimulation (rTMS).

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation technique which has received increasing attention as an antidepressant treatment. However available studies are characterized by a substantial variability in response. We hypothesized that individual patients' characteristics might contribute to such heterogeneity. Therefore we investigated whether either alterations of regional cerebral blood flow (rCBF) or clinical characteristics may predict antidepressant response to rTMS. DESIGN: 24 patients with major depression and stable medication received high frequency (10 Hz) rTMS over the left dorsolateral prefrontal cortex (DLPFC) for two weeks as add-on treatment. ECD-Single photon emission computed tomographay (SPECT) imaging was performed 1 to 2 days before rTMS. SETTING: Tertial referral center RESULTS: After two weeks of rTMS a mean reduction of 30% of the initial Hamilton Depression Rating Score (HAMD) was observed. Using a multivariate regression model with simultaneous evaluation of the relative impact of a-priori chosen potential factors influencing treatment outcome, two variables, the pretreatment anterior cingulate rCBF and the former response to antidepressant agents proved significant. High pretreatment anterior cingulate activity and low treatment resistance to pharmacologic therapy were positive predictors for treatment response to rTMS. CONCLUSIONS: Pretreatment anterior cingulate activity seems to be a useful prognostic marker of rTMS treatment response, which is in line with other treatment strategies, like sleep deprivation, electroconvulsive therapy or antidepressant medication.

Different Patterns of Hearing Loss among Tinnitus Patients: A Latent Class Analysis of a Large Sample.

BACKGROUND: The heterogeneity of tinnitus is a major challenge for tinnitus research. Even if a complex interaction of many factors is involved in the etiology of tinnitus, hearing loss (HL) has been identified as the most relevant etiologic factor. Here, we used a data-driven approach to identify patterns of hearing function in a large sample of tinnitus patients presenting in a tinnitus clinic. METHODS: Data from 2,838 patients presenting at the Tinnitus Center of the University Regensburg between 2007 and 2014 have been analyzed. Standard audiometric data were frequency-wise categorized in four categories [a: normal hearing (0-20 dB HL); b: moderate HL (25-50 dB HL; representing outer hair cell loss); c: severe HL (>50 dB HL; representing outer and inner hair cell loss); d: no data available] and entered in a latent class analysis, a statistical method to find subtypes of cases in multivariate categorical data. To validate the clinical relevance of the identified latent classes, they were compared with respect to clinical and demographic characteristics of their members. RESULTS: The classification algorithm identified eight distinct latent classes with an excellent separation. Patient classes differed with respect to demographic (e.g., age, gender) and clinical characteristics (e.g., tinnitus location, tinnitus severity, gradual, or abrupt onset, etc.). DISCUSSION: Our results demonstrate that data-driven categorization of hearing function seems to be a promising approach for profiling tinnitus patients, as it revealed distinct subtypes that reflect prototypic forms of HL and that differ in several relevant clinical characteristics.