Limited Link of Common Blood Parameters with Tinnitus.

Background: Tinnitus severity is generally assessed by psychometric and audiological instruments. However, no objective measure exists to evaluate the subjective discomfort and suffering caused by this hearing phenomenon. The objective of this work was to determine the possible blood parameters for diagnostics and therapy. Methods: We measured tinnitus distress by using the Tinnitus Questionnaire (TQ) and collected tinnitus-related audiological measures, namely the hearing threshold (HT), tinnitus loudness (TL), and sensation level (SL, i.e., the tinnitus loudness/hearing threshold at a tinnitus frequency). Blood samples were taken from 200 outpatients of the Tinnitus Centre of the Charité, and 46 routine blood count parameters were examined. The possible interactions were determined by (robust) linear models. Results: Tinnitus distress and audiological measurements were largely uncorrelated but could partly be predicted by selected blood parameters. First, the erythrocyte counts predicted tinnitus distress to a small extent. Second, the levels of vitamin D3 explained about 6% of tinnitus loudness and, age-dependently, the hearing threshold variability. Last, the levels of uric acid explained about 5% of the sensation level variability. Conclusions: Tinnitus is a multidimensional phenomenon. The marginal influences of blood markers suggest the possible roles of inflammation and oxidative stress produced by psychological or somatic burdens. Clinically, a vitamin D substitution (in older patients) might have a hearing-protective effect.

The statistical analysis plan for the unification of treatments and interventions for tinnitus patients randomized clinical trial (UNITI-RCT).

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.

Hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness and distress in chronic tinnitus.

The role of stress and its neuroendocrine mediators in tinnitus is unclear. In this study, we measure cortisol as an indicator of hypothalamus-pituitary-adrenal (HPA) axis alterations and brain-derived neurotrophic factor (BDNF) as a marker of adaptive neuroplasticity in hair of chronic tinnitus patients to investigate relationships with tinnitus-related and psychological factors. Cross-sectional data from chronic tinnitus inpatients were analyzed. Data collection included hair sampling, pure tone audiometry, tinnitus pitch and loudness matching, and psychometric questionnaires. Elastic net regressions with n-fold cross-validation were performed for cortisol (N = 91) and BDNF (N = 87). For hair-cortisol (R2 = 0.10), the strongest effects were sampling in autumn and body-mass index (BMI) (positive), followed by tinnitus loudness (positive) and smoking (negative). For hair-BDNF (R2 = 0.28), the strongest effects were hearing aid use, shift work (positive), and tinnitus loudness (negative), followed by smoking, tinnitus-related distress (Tinnitus Questionnaire), number of experienced traumatic events (negative), and physical health-related quality of life (Short Form-12 Health Survey) (positive). These findings suggest that in chronic tinnitus patients, higher perceived tinnitus loudness is associated with higher hair-cortisol and lower hair-BDNF, and higher tinnitus-related distress with lower hair-BDNF. Regarding hair-BDNF, traumatic experiences appear to have additional stress-related effects, whereas hearing aid use and high physical health-related quality of life appear beneficial. Implications include the potential use of hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness or distress and the need for intensive future research into chronic stress-related HPA axis and neuroplasticity alterations in chronic tinnitus.

Psychological Treatment Effects Unrelated to Hair-Cortisol and Hair-BDNF Levels in Chronic Tinnitus.

BACKGROUND: Currently, there are no objective markers to measure treatment efficacy in chronic (distressing) tinnitus. This study explores whether stress-related biomarkers cortisol and brain-derived neurotrophic factor (BDNF) measured in hair samples of chronic tinnitus patients change after compact multimodal tinnitus-specific cognitive behavioral therapy. METHODS: In this longitudinal study, hair-cortisol and hair-BDNF levels, self-reported tinnitus-related distress (Tinnitus Questionnaire; TQ), and perceived stress (Perceived Stress Questionnaire; PSQ-20) were assessed before and 3 months after 5 days of treatment in N = 80 chronic tinnitus patients. Linear mixed-effects models with backward elimination were used to assess treatment-induced changes, and a cross-lagged panel model (structural equation model) was used for additional exploratory analysis of the temporal associations between TQ and hair-BDNF. RESULTS: At follow-up, a reduction in TQ (p < 0.001) and PSQ-20 scores (p = 0.045) was observed, which was not influenced by baseline hair-cortisol or hair-BDNF levels. No changes in biomarker levels were observed after treatment. The exploratory analysis tentatively suggests that a directional effect of baseline TQ scores on hair-BDNF levels at follow-up (trend; p = 0.070) was more likely than the opposite directional effect of baseline hair-BDNF levels on TQ scores at follow-up (n.s.). DISCUSSION: While the treatment effectively reduced tinnitus-related distress and perceived stress in chronic tinnitus patients, this effect was not mirrored in biological changes. However, the lack of changes in hair-cortisol and hair-BDNF levels might have been influenced by the treatment duration, follow-up interval, or confounding medical factors, and therefore must be interpreted with caution. The relationship between tinnitus-related distress and hair-BDNF levels should be explored further to obtain a better understanding of stress-related effects in chronic tinnitus.

Sex Differences in Comorbidity Combinations in the Swedish Population.

High comorbidity rates, especially mental-physical comorbidity, constitute an increasing health care burden, with women and men being differentially affected. To gain an overview of comorbidity rates stratified by sex across a range of different conditions, this study examines comorbidity patterns within and between cardiovascular, pulmonary, skin, endocrine, digestive, urogenital, musculoskeletal, neurological diseases, and psychiatric conditions. Self-report data from the LifeGene cohort of 31,825 participants from the general Swedish population (62.5% female, 18-84 years) were analyzed. Pairwise comorbidity rates of 54 self-reported conditions in women and men and adjusted odds ratios (ORs) for their comparison were calculated. Overall, the rate of pairwise disease combinations with significant comorbidity was higher in women than men (14.36% vs. 9.40%). Among psychiatric conditions, this rate was considerably high, with 41.76% in women and 39.01% in men. The highest percentages of elevated mental-physical comorbidity in women were found for musculoskeletal diseases (21.43%), digestive diseases (20.71%), and skin diseases (13.39%); in men, for musculoskeletal diseases (14.29%), neurological diseases (11.22%), and digestive diseases (10%). Implications include the need for integrating mental and physical health care services and a shift from a disease-centered to an individualized, patient-centered focus in clinical care.

Negative Associations of Stress and Anxiety Levels With Cytotoxic and Regulatory Natural Killer Cell Frequency in Chronic Tinnitus.

Background: Depression and anxiety are known to be associated with stress-induced changes in the immune system. Bothersome tinnitus can be related to stress and often co-occurs with depression and anxiety. This study investigates associations of psychological and audiological tinnitus-related factors with inflammatory parameters and immune cell subsets in chronic tinnitus patients as well as treatment-related effects. Methods: This longitudinal study of inpatients treated with compact multimodal tinnitus-specific cognitive behavioral therapy included four repeated measurement sessions: baseline (N = 41), treatment end, 7.8-week (N = 35), and 13.8-week follow-up (N = 34). Data collection included audiometric testing, blood sampling, and psychometric questionnaires: Tinnitus Handicap Inventory (THI), Perceived Stress Questionnaire (PSQ-20), and Hospital Anxiety Depression Scale (HADS). Flow cytometry was used to analyze immune cell subsets. Statistical analyses comprised correlation and network analysis (cross-sectional), and linear mixed effect models (longitudinal). Results: Bootstrapped network analysis showed negative averaged cross-sectional associations of cytotoxic natural killer (NKc) cell frequency (CD56 + CD16+) and PSQ-20 (-0.21 [-0.48, 0]) and of regulatory natural killer (NKreg) cell frequency (CD56 + CD16dim/-) and HADS anxiety (-0.14 [-0.38, 0]). No significant treatment effects were found. A negative predictive effect of baseline PSQ-20 scores (ß = -6.22 [-12.18, -0.26], p = 0.041) and a positive predictive effect of baseline ferritin levels (ß = 8.90 [2.76, 15.03], p = 0.004) on NKc cell frequency across the repeated measurement sessions were observed. Conclusion: We observed negative relationships between perceived stress levels and NKc cell frequency and between anxiety levels and NKreg cell frequency in chronic tinnitus patients. These exploratory results suggest stress-/anxiety-related immune alterations in bothersome tinnitus but need to be tested in further confirmatory studies with larger sample sizes. The potential of NK cells as biomarkers of emotional distress in chronic tinnitus should be further investigated.

Subjective hearing ability, physical and mental comorbidities in individuals with bothersome tinnitus in a Swedish population sample.

OBJECTIVE: This study investigates associations of subjective hearing ability, physical comorbidities, and mental comorbidities with bothersome (vs. non-bothersome) tinnitus and mediating effects between these influences. METHODS: The Swedish LifeGene cohort was used to sample cross-sectional survey data (collected 2009-2016) of 7615 participants with tinnitus, 697 (9.2%) of whom rated their tinnitus as bothersome. Associations between bothersome tinnitus and subjective hearing ability, physical and mental comorbidities were investigated by separate age- and gender-adjusted multiple logistic regression models. Interrelationships between these associations were investigated by logistic mediation models. RESULTS: Compared to non-bothersome tinnitus, bothersome tinnitus was associated with higher age, reduced subjective hearing ability, hearing-related difficulties in social situations, cardiovascular disease, chronic shoulder pain, thyroid disease, Ménière's disease, depression, anxiety syndrome, and social anxiety. Subjective hearing impairment or hearing-related difficulties mediated 13-36% of the effects of mental comorbidities on bothersome tinnitus. Depression or anxiety syndrome mediated 5-8% of most relationships between physical comorbidities and bothersome tinnitus. Depression, anxiety syndrome, or social anxiety mediated 2-4% of the effects of subjective hearing impairment or hearing-related difficulties on bothersome tinnitus. CONCLUSION: Psychological factors, subjective hearing impairment, and hearing-related difficulties in social situations play key roles in predicting bothersome (vs. non-bothersome) tinnitus in a large population sample. Psychological factors contribute to explaining the impact of physical comorbidities and hearing-related effects on bothersome tinnitus. This highlights their transdiagnostic importance for aggravating varied physical symptom clusters. Interventions to improve or prevent high tinnitus burden should be interdisciplinary/multimodal and target auditory, physical, and psychological factors.

Gender-Specific Risk Factors and Comorbidities of Bothersome Tinnitus.

OBJECTIVE: This study aims to identify gender-specific risk factors associated with the presence of bothersome tinnitus (compared with non-bothersome tinnitus), including sociodemographic and lifestyle factors, tinnitus-associated phenomena (hearing loss, traumatic experiences, sleep disturbances), and physical as well as mental comorbidities. METHODS: We conducted a cross-sectional study using survey data from the Swedish LifeGene cohort containing information on self-reported tinnitus (N = 7615). We (1) analyzed risk factor and comorbidity frequencies, (2) computed multivariate logistic regression models to identify predictors of bothersome tinnitus within both genders, and (3) moderated logistic regression models to compare effects between genders. RESULTS: (1) The majority of factors that differed in frequencies between bothersome and non-bothersome tinnitus were equal for both genders. Women with bothersome tinnitus specifically reported higher rates of cardiovascular disease, thyroid disease, epilepsy, fibromyalgia, and burnout, and men with bothersome tinnitus reported higher rates of alcohol consumption, Ménière's disease, anxiety syndrome, and panic (compared with non-bothersome tinnitus, respectively). (2) Across both genders, multivariate logistic regression analyses revealed significant associations between bothersome tinnitus and age, reduced hearing ability, hearing-related difficulties in social situations, and reduced sleep quality. In women, bothersome tinnitus was specifically associated with cardiovascular disease and epilepsy; in men, with lower education levels and anxiety syndrome. (3) Moderated logistic regression analyses revealed that the effects of low education and anxiety syndrome were present in men, but not in women, whereas the effects of age, reduced hearing ability and related difficulties, cardiovascular disease, epilepsy, and burnout were not gender specific. CONCLUSION: Irrespective of gender, bothersome tinnitus is associated with higher age, reduced hearing ability, hearing-related difficulties, cardiovascular disease, epilepsy, and burnout. Gender-specific effects comprise low levels of education and the presence of anxiety syndrome for men. These findings need to be interpreted with caution, yet they suggest the presence of gender-specific biopsychosocial influences in the emergence or maintenance of bothersome tinnitus. Future studies ought to investigate the underlying mechanisms of the observed relationships.

Antidepressant and neurocognitive effects of serial ketamine administration versus ECT in depressed patients.

BACKGROUND: While electroconvulsive therapy (ECT) is considered the gold standard for acute treatment of patients with otherwise treatment-resistant depression, ketamine has recently emerged as a fast-acting treatment alternative for these patients. Efficacy and onset of action are currently among the main factors that influence clinical decision making, however, the effect of these treatments on cognitive functions should also be a crucial point, given that cognitive impairment in depression is strongly related to disease burden and functional recovery. ECT is known to induce transient cognitive impairment, while little is known about ketamine's impact on cognition. This study therefore aims to compare ECT and serial ketamine administration not only with regard to their antidepressant efficacy but also to acute neurocognitive effects. METHODS: Fifty patients suffering from depression were treated with either serial ketamine infusions or ECT. Depression severity and cognitive functions were assessed before, during, and after treatment. RESULTS: ECT and ketamine administration were equally effective, however, the antidepressant effects of ketamine occurred faster. Ketamine improved neurocognitive functioning, especially attention and executive functions, whereas ECT was related to a small overall decrease in cognitive performance. CONCLUSIONS: Due to its pro-cognitive effects and faster antidepressant effect, serial ketamine administration might be a more favorable short-term treatment option than ECT. LIMITATIONS: As this research employed a naturalistic study design, patients were not systematically randomized, there was no control group and patients received concurrent and partially changing medications during treatment. CLINICAL TRIALS REGISTRATION: Functional and Metabolic Changes in the Course of Antidepressive Treatment, https://clinicaltrials.gov/ct2/show/NCT02099630, NCT02099630.

Anxiety during ketamine infusions is associated with negative treatment responses in major depressive disorder.

About 20 to 30 percent of patients with Major Depressive Disorder (MDD) do not respond to standard treatment and are considered treatment-resistant. The N-methyl-d-aspartate (NMDA) glutamate receptor antagonist ketamine has demonstrated rapid antidepressant effects in treatment-resistant MDD, but it is unknown whether its acute psychological effects are related to the later antidepressant effect. Therefore, we investigated the association between antidepressant responses to ketamine and the quality of ketamine-induced psychological experiences in MDD. A total of 31 patients (M = 49.5 ±â€¯11.2 years, 16 women) were treated with three ketamine infusions per week (0.5 mg/ kg over 40 min) administered for two consecutive weeks. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, after four and 24 h and at end of treatment. The 5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) was applied four hours after the first infusion to assess the subjective quality of acute psychological effects. Patients with a ≥ 50% MADRS reduction from baseline to end of treatment were considered as responders. After six infusions, 17 of 31 patients (55%) showed a response to ketamine treatment, while 14 patients (45%) had no response. Anxiety-related experiences induced by ketamine were significantly higher in non-responders. Percentage MADRS reduction after four hours and individual levels of ketamine-induced anxiety were predictive of a response at end of treatment. The study demonstrated the considerable impact of ketamine-induced anxiety on the antidepressant efficacy of ketamine. It underpins the importance of considering patients' subjective experiences and underlines the possibility of a phenotypic response predictor.

Percutaneous treatment of transplant renal artery stenosis in children.

Percutaneous treatment of renal artery stenosis (RAS) is an accepted procedure and numerous reports have been published. However, experience with its use in RAS in the transplanted kidney in children is scarce. Since 1994 we have diagnosed RAS in seven children with the use of Doppler ultrasonography (US), confirming it with percutaneous angiography (PAG). In six of the seven patients percutaneous transluminal angioplasty (PTA) was performed. In one patient a metallic stent was placed due to the extension of the arterial lesion, and a second stent was placed in another child when a re-stenosis was diagnosed 1 month after the PTA. All patients presented with hypertension (de novo or 30% increase over previous values). After ruling out acute rejection, calcineurin inhibitor toxicity, and urinary obstruction, US was performed and, when an increase in arterial flux velocity was registered, PAG was also performed. Six children showed an increase in serum creatinine (Cr) and proteinuria. Blood pressure decreased after the procedure and Cr returned to previous levels in all children. One of the grafts was lost due to chronic transplant rejection 7 years later. The other children have a functioning kidney. Although this is a small group of patients, the consistently good results and the lack of reported experience prompted us to communicate our preliminary observation.

Enfermedad renal crónica en la población general: importancia de la tasa de filtrado glomerular estimada absoluta / Chronic renal disease in the general population: importance of the absolute estimated glomerular filtration rate

Introducción: Evaluamos la Prevalencia de la Enfermedad Renal Crónica (ERC) en la población general y la asociación con factores de riesgo reconocidos. Determinamos la utilidad de la Tasa de Filtrado glomerular estimada absoluta(TFGea). Métodos: Utilizamos la fórmula MDRD-4 variables corregida por la superficie corporal del individuo evaluado. Se definió como “Probable ERC sin considerar la proteinuria” a la población con TFGea < 60 ml/m y “Probable ERC considerando proteinuria” a la anterior más la población con TFGea ≥ 60 ml/m que presenta proteinuria ≥ 30 mg/L. Regresión logística uni y multivariable para determinar asociación de TFGea < de 60 ml/m con factores comórbidos. Resultados: Se evaluaron 811 personas de edad promedio 52.5 ± 17.0 años. La Tasa de Probable ERC sin considerar a la proteinuria patológica es de 11.7% (IC95%:9.5-14.3) y de 15.8%(IC95%:13.2-18.8) considerándola. El grupo 3a(TFGea 45-59 ml/m) resultó el más frecuente: 9.9 % (IC95%:7.8-12.3). Los factores predictores significativosde TFGea <60 ml/m en el modelo multivariado son: la Mayor edad, la Litiasis Urinaria actual o pasada, el Sexo femenino y el Antecedente de Neoplasia. La TFGe relativa (ml/m/1.73m2) demostró una Tasa de Probable ERC sin considerar proteinuria de 12.8% (IC95%: 10.48-15.54), 1.1% más que la demostrada por la TFGea. Conclusiones: La Prevalencia de Probable ERC es alta en Santa Fe. La mayor edad, la Litiasis Urinaria actual o pasada, el Sexo femenino y el Antecedente de Neoplasia se asocian a TFGea < 60 ml/m. La TFGea permite reducir la Tasa de Probable ERC en el 1.1%.

Introduction: We assessed the prevalence of the Chronic Renal Disease (CRD) in the general population and the association with known risk factors. We determined the use of the absolute estimated glomerular filtration rate ( absolute eGFR) Methods: We used the MDRD formula with 4 variables corrected for body surface area of the examined individual. The population with absolute eGFR < 60 mL/min was defined as “Likely CRD regardless proteinuria” and the latter plus the population with absolute eGFR ≥ 60 mL/ min presenting proteinuria ≥ 30 mg/L was defined as “Likely CRD considering proteinuria”. Univariate and multivariate logistic regression to determine the association between absolute eGFR <60 mL/min with comorbid factors. Results: 811 individuals of an average age of 52.5 ± 17.0 years were examined. The rate of likely CRD without consideration of pathological proteinuria is 11.7% (95% CI:9.5 -14.3) while the rate considering this factor is 15.8% (95% CI:13.2 -18.8). The 3a group (absolute eGFR 45-59 mL/min) was the most frequent one: 9.9 % (95% CI:7.8 -12.3). The significant predictive factors for absolute eGFR <60 mL/min in the multivariate model are: older age, past or current urinary lithiasis, female gender and history of neoplasia. The relative eGFR (mL/min/1.73m2) showed a likely CRD rate without consideration of proteinuria of 12.8% (95% CI: 10.48 -15.54), 1.1% higher than observed for absolute eGFR. Conclusions: The prevalence of potential CRD is high in Santa Fe. The older age, either past or current urinary lithiasis, female gender and history of neoplasia are associated with absolute eGFR < 60 mL/min. Absolute eGFR helps to reduce the rate of likely CRD in 1.1%.

La comunidad terapéutica psicoanalítica como tratamiento de un paciente con el diagnóstico de esquizofrenia / Psychoanalitic terapeutic community as the treatment of a patient with schizophrenia diagnosis

En estre trabajo describimos el tratamiento psicoterapéutico institucional efectuado con un paciente diagnósticado como esquizofrénico. Enunciamos brevemente los basamentos teóricos tanto de la comunidad terapéutica como los del psicoanálisis del self. Se realiza una presentación del paciente y se muestra la evolución clínica del mismo en la comunidad terapéutica de Hospital de día, por medio de escenas dramáticas originadas y dirigidas por el paciente