Treatment-related hearing loss in weekly versus triweekly cisplatin chemoradiation for head and neck cancer.

PURPOSE: Cisplatin-induced hearing loss is a common side effect in patients treated with cisplatin-based chemoradiation (CRT) for head and neck squamous cell carcinoma. The extent of hearing loss after concurrent CRT was compared between triweekly (3 × 100 mg/m2) and weekly (7 × 40 mg/m2) cisplatin CRT. METHOD: This retrospective cohort study was conducted in the Antoni van Leeuwenhoek Hospital and included 129 patients with cisplatin-based CRT for head and neck cancer (72 treated in the triweekly and 57 in the weekly regimen). Baseline and follow-up pure tone audiometry was conducted to assess hearing loss. Clinically relevant hearing loss was defined as a decline upon treatment of ≥ 10 decibel at a pure tone average 1-2-4 kHz and/or 8-10-12.5 kHz. RESULTS: The incidence of clinically relevant cisplatin CRT induced hearing loss was 42% in the triweekly versus 19% in the weekly group (p < 0.01). The mean threshold shift at a pure tone average (PTA) 1-2-4 kHz was 9.0 decibel in the triweekly compared to 4.3 decibel in the weekly CRT group (p < 0.01). At PTA 8-10-12.5 kHz, the incidence of clinically relevant hearing loss was 75% in the triweekly compared to 74% in the weekly CRT group (p = 0.87). The mean threshold shift at PTA 8-10-12.5 kHz was 20.2 decibel versus 15.6 decibel, respectively (p = 0.07). CONCLUSION: Cisplatin-dose reduction to a weekly cisplatin CRT regimen for head and neck cancer may reduce the incidence of clinically relevant hearing loss at frequencies vital for speech perception.

Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.

BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSIONS: Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.

Contact lenses in paediatric aphakia in the Netherlands; A multicentre retrospective chart study.

PURPOSE: The main aim of this study was to evaluate the type, parameters, loss and complications of contact lenses (CLs) in the treatment of paediatric aphakia over a 10-year period. METHODS: This retrospective multicentre chart review included the files of aphakic CL wearers under the age of 9 years old that were treated between 2008 and 2018. Patients with traumatic aphakia and scarring of the cornea were excluded. The following data were collected; demographic data, cataract type (congenital or secondary), CL type, parameters and wearing time, reason for replacement and discontinuation of the CLs, visual acuity (VA), prophylactic use of antibiotics (ABs), and complications. RESULTS: Ninety-one aphakic children (132 eyes) were fitted with soft CLs. The median age of cataract extraction was 10.50 weeks (interquartile range (IQR) 7,15) in the congenital cataract group and 112 weeks (IQR 41,285) in the secondary cataract group. At the initial fitting a silicone elastomer CL was fitted in 86 % and a silicone hydrogel CL in 12 %, the remaining 2 % were mixed CL types. The median CL power at baseline was + 29 D (IQR 25,32) and after 3 years of wear the median power had shifted significantly to + 20 D (IQR 17,26), P < 0.001. A total of 1083 extra CL replacements were needed of which 414 in the first year of wear. Of these 414 replacements almost half (46 %;n = 191) were due to loss of the CL. Complications developed in 8 (9 %) cases and 7 (8 %) patients discontinued CL wear. CONCLUSION: This paper confirms that paediatric aphakia can be successfully treated with soft CLs with low rates of complications and discontinuation encountered. Unscheduled CL replacements due to loss are a concern, especially in the first year, and are straining for both the care giver and medical system. Attentive care and clear information is advised during the first year of CL wear.

[Prevalence and factors associated with benzodiazepine use in children and adult inpatients]. / Prevalentie van en factoren geassocieerd met benzodiazepinegebruik tijdens opname.

BACKGROUND: Given the growing focus on deprescribing, it is crucial to thoroughly evaluate our benzodiazepine prescribing practices considering the potential risks. AIM: To investigate the prevalence and predictors of benzodiazepine prescriptions during psychiatric hospitalization and as discharge medication. METHOD: This retrospective electronic patient file study included psychiatric admissions at the UMC Utrecht between 12/01/01 and 21/04/01. Descriptive statistics were used to evaluate prevalence of benzodiazepine prescriptions in youth and adults. Multivariate regression analyses were performed to predict factors associated with benzodiazepine prescriptions and dosage. RESULTS: In total, we analyzed data from 856 admissions of youth and 4002 admissions of adults. 36.0% of the youth were prescribed benzodiazepines during admission and 14.8% at discharge. Associated factors were age (OR: 1.38) and bipolar disorder (OR: 3.98). In adults, 69.7% were prescribed benzodiazepines during admission and 37.6% at discharge. Associated factors were length of hospital stay (OR: 1.01) and anxiety disorders (OR: 2.53). Male sex, age (resp. higher and lower), and a longer length of stay predicted benzodiazepine dosages for both youth (B = 3.48; 95% CI: 0.83-0.07) and adults (B = 2.17; 95% CI: -0.04-0.05). CONCLUSION: Benzodiazepines are frequently prescribed during inpatient stays and at discharge in youth and adults, offering opportunities for deprescribing.

The power of effective study design in animal experimentation: Exploring the statistical and ethical implications of asking multiple questions of a data set.

One of the chief advantages of using highly standardised biological models including model organisms is that multiple variables can be precisely controlled so that the variable of interest is more easily studied. However, such an approach often obscures effects in sub-populations resulting from natural population heterogeneity. Efforts to expand our fundamental understanding of multiple sub-populations are in progress. However, such stratified or personalised approaches require fundamental modifications of our usual study designs that should be implemented in Brain, Behavior and Immunity (BBI) research going forward. Here we explore the statistical feasibility of asking multiple questions (including incorporating sex) within the same experimental cohort using statistical simulations of real data. We illustrate and discuss the large explosion in sample numbers necessary to detect effects with appropriate power for every additional question posed using the same data set. This exploration highlights the strong likelihood of type II errors (false negatives) for standard data and type I errors when dealing with complex genomic data, where studies are too under-powered to appropriately test these interactions. We show this power may differ for males and females in high throughput data sets such as RNA sequencing. We offer a rationale for the use of alternative experimental and statistical strategies based on interdisciplinary insights and discuss the real-world implications of increasing the complexities of our experimental designs, and the implications of not attempting to alter our experimental designs going forward.

Combining automatic speech recognition with semantic natural language processing in schizophrenia.

Natural language processing (NLP) tools are increasingly used to quantify semantic anomalies in schizophrenia. Automatic speech recognition (ASR) technology, if robust enough, could significantly speed up the NLP research process. In this study, we assessed the performance of a state-of-the-art ASR tool and its impact on diagnostic classification accuracy based on a NLP model. We compared ASR to human transcripts quantitatively (Word Error Rate (WER)) and qualitatively by analyzing error type and position. Subsequently, we evaluated the impact of ASR on classification accuracy using semantic similarity measures. Two random forest classifiers were trained with similarity measures derived from automatic and manual transcriptions, and their performance was compared. The ASR tool had a mean WER of 30.4%. Pronouns and words in sentence-final position had the highest WERs. The classification accuracy was 76.7% (sensitivity 70%; specificity 86%) using automated transcriptions and 79.8% (sensitivity 75%; specificity 86%) for manual transcriptions. The difference in performance between the models was not significant. These findings demonstrate that using ASR for semantic analysis is associated with only a small decrease in accuracy in classifying schizophrenia, compared to manual transcripts. Thus, combining ASR technology with semantic NLP models qualifies as a robust and efficient method for diagnosing schizophrenia.

[Taal: een introductie]. / Taal: een introductie.

BACKGROUND: This special issue discusses the roles and functions of language in psychiatric practice from different perspectives. As an introduction, we discuss the phenomenon ‘language’ as an object of scientific investigation. AIM: To give a brief introduction to this theme issue. METHOD: After a terminological introduction and an outline of linguistics, we discuss some of the cognitive processes that enable humans to produce and interpret verbal utterances. RESULTS: The mental lexicon, the dictionary in our head, plays a central role in both language production and understanding. The starting point for language comprehension is recognizing basic form elements in the speech or sign stream (phonemes). Next, the perceiver must determine how words are related grammatically in order to deduce sentence meanings. We distinguish three successive steps in the production of language: conceptualizing, formulating and articulating. CONCLUSION: Production and understanding words and sentences rely on a complex interplay of cognitive processes. In communication, we use words and sentences to convey and recognize intentions. This requires close cooperation between interlocutors.

[Do doctors speak a different language? The case of 'patient' without an article]. / Spreken artsen een andere taal? Het geval van 'patiënt' zonder lidwoord.

BACKGROUND: In medical speech and writing, the article before ‘patient’ is often omitted, while this would be ungrammatical in Standard Dutch. AIM: To investigate how and when the article is omitted in medical Dutch. METHOD: An online questionnaire was distributed among individuals with a medical background. RESULTS: 85 respondents participated in this study. The participants showed a strong preference to omit the definite article (‘the’) befor the word ‘patient’ and related words. This phenomenon seemed independent of the function of the word in the sentence, or of the sentence construction. However, the indefinite article (‘a’) was not omitted in the same situations. CONCLUSION: Doctors speak a different language, namely a variety of Standard Dutch in which the omission of the definite article befor ‘patient’ is preferred. We conclude that this phenomenon can be explained by recognizing ‘patient’ as a substitute for the name of the patient.

[Automated speech analysis can distinguish frontotemporal dementia from depression: a pilot study]. / Geautomatiseerde spraakanalyse bij onderscheiden van frontotemporale dementie en depressie.

BACKGROUND: Differentiating the behavioural variant of frontotemporal dementia from a depression is challenging. Recent development of automated speech analyses might add to diagnostic. AIM: To investigate the value of automated speech analyses in differentiating bvFTD from a depressive disorder. METHOD: A semistructured interview was recorded in 15 patients with bvFTD, 15 patients with a depressive disorder and 15 healthy controls, which was transcribed and analysed. Acoustic and semantic values were extracted and classified using machine learning. RESULTS: Acoustic values showed an 80% accuracy for differentiating bvFTD from depressive disorder and semantic values showed an 70.8% accuracy. CONCLUSION: Acoustic as well as semantic values show significant differences between bvFTD and depressive disorder. In automated speech analyses researches should consider privacy matters as well as possible confounders like age, sex and ethnicity. This study should be repeated in a larger population.

[Recognizing depression through computational language analysis]. / Herkennen van depressie met computationele taalanalyse.

BACKGROUND: Currently, clinical practice lacks a usable biomarker for the detection and differentiation of depression. Such a biomarker may be found in speech, from which important information can be distilled using automated speech analysis. AIM: To provide an overview of the fast-developing field of automated speech analysis for depression. METHOD: We summarize the current literature on speech features in depression. RESULTS: Current computational models can detect depression with high accuracy, rendering them applicable for diagnostic tools based on automatic speech analysis. Such tools are developing at a fast rate. CONCLUSION: Some challenges are still in the way of clinical implementation. For example, results differ largely between studies due to much variation in methodology. Furthermore, privacy and ethical issues need to be addressed before tools can be used.

[Antipsychotic drugs for women: a narrative review and clinical guidelines]. / Antipsychotica voor vrouwen: overzicht van de literatuur en praktijkadviezen.

BACKGROUND: It has long been thought that women with a schizophrenia spectrum disorder have a more favorable course than men. However, this is not the case, even though they become ill later in life and are less likely to have comorbid drug abuse. Guidelines for prescribing antipsychotics are based on research with mostly male participants, and by following these guidelines we are doing our female patients a disservice. Gender and sex differences lead to differences in preferences, pharmacokinetics and pharmacodynamics. AIM: Providing an overview of antipsychotics for women with a schizophrenia spectrum disorder and discuss the consequences for practice. METHOD: A clinically oriented study of the literature. RESULTS: Women reach higher plasma levels than men when they receive the same dose of antipsychotic drugs (except for lurasidone and quetiapine). The effect of antipsychotics is also greater in women, because estrogens increase the brain’s dopamine sensitivity. This leads to higher risks of side effects. Clinical guidelines differ for women at different stages of life because estrogens greatly contribute to the sex differences seen in the efficacy and tolerability of antipsychotics. CONCLUSION: Clinicians should be aware that women should be treated differently with antipsychotics than men.

Ovarian cancer prevention by opportunistic salpingectomy is a new de facto standard in Germany.

PURPOSE: The most prevalent and aggressive subtype of epithelial ovarian carcinoma (EOC), high-grade serous carcinoma (HGSC), originates in many cases from the fallopian tubes. Because of poor prognosis and lack of effective screening for early detection, opportunistic salpingectomy (OS) for prevention of EOC is being implemented into clinical routine in several countries worldwide. Taking the opportunity of a gynecological surgery in women at average cancer risk, extramural fallopian tubes are completely resected preserving the ovaries with their infundibulopelvic blood supply. Until recently, only 13 of the 130 national partner societies of the International Federation of Obstetrics and Gynecology (FIGO) have published a statement on OS. This study aimed to analyze the acceptance of OS in Germany. METHODS: (1) Survey of German gynecologists in 2015 and 2022 by the Department of Gynecology of the Jena University Hospital in co-operation with the Department of Gynecology at Charité-University Medicine Berlin with support of NOGGO e. V. and AGO e. V. (2) Salpingectomy numbers in Germany for years 2005-2020 as retrieved from the Federal Statistical Office of Germany (Destatis). RESULTS: (1) Survey: Number of participants was 203 in 2015 and 166 in 2022, respectively. Nearly all respondents (2015: 92%, 2022: 98%) have already performed bilateral salpingectomy without oophorectomy in combination with benign hysterectomy with the intention to reduce the risk for malignant (2015: 96%, 2022: 97%) and benign (2015: 47%, 2022: 38%) disorders. Compared to 2015 (56.6%), considerably more survey participants performed OS in > 50% or in all cases in 2022 (89.0%). Recommendation of OS for all women with completed family planning at benign pelvic surgery was approved by 68% in 2015 and 74% in 2022. (2) Case number analysis: In 2020, four times more cases of salpingectomy were reported by German public hospitals compared to 2005 (n = 50,398 vs. n = 12,286). Of all inpatient hysterectomies in German hospitals in 2020, 45% were combined with salpingectomy, and more than 65% in women at the age of 35 to 49 years. CONCLUSION: Mounting scientific plausibility regarding involvement of fallopian tubes in the pathogenesis of EOC led to change of clinical acceptance of OS in many countries including in Germany. Case number data and widespread expert judgment demonstrate that OS has become a routine procedure in Germany and a de facto standard for primary prevention of EOC.

Retina-arrestin specific CD8+ T cells are not implicated in HLA-A29-positive birdshot chorioretinitis.

BACKGROUND: HLA-A29-positive birdshot chorioretinitis (BCR) is an inflammatory eye disorder that is generally assumed to be caused by an autoimmune response to HLA-A29-presented peptides from retinal arrestin (SAG), yet the epitopes recognized by CD8+ T cells from patients remain to be identified. OBJECTIVES: The identification of natural ligands of SAG presented by HLA-A29. To quantify CD8+ T cells reactive to antigenic SAG peptides presented by HLA-A29 in patients and controls. METHODS: We performed mass-spectrometry based immunopeptidomics of HLA-A29 of antigen-presenting cell lines from patients engineered to express SAG. MHC-I Dextramer technology was utilised to determine expansion of antigen-specific CD8+ T cells reactive to SAG peptides in complex with HLA-A29 in a cohort of BCR patients, HLA-A29-positive controls, and HLA-A29-negative controls. RESULTS: We report on the naturally presented antigenic SAG peptides identified by sequencing the HLA-A29 immunopeptidome of antigen-presenting cells of patients. We show that the N-terminally extended SAG peptide precursors can be trimmed in vitro by the antigen-processing aminopeptidases ERAP1 and ERAP2. Unexpectedly, no enhanced antigen engagement by CD8+ T cells upon stimulation with SAG peptides was observed in patients or HLA-A29-positive controls. Multiplexed HLA-A29-peptide dextramer profiling of a case-control cohort revealed that CD8+ T cells specific for these SAG peptides were neither detectable in peripheral blood nor in eye biopsies of patients. CONCLUSIONS: Collectively, these findings demonstrate that SAG is not a CD8+ T cell autoantigen and sharply contrast the paradigm in the pathogenesis of BCR. Therefore, the mechanism by which HLA-A29 is associated with BCR does not involve SAG.

Acoustic speech markers for schizophrenia-spectrum disorders: a diagnostic and symptom-recognition tool.

BACKGROUND: Clinicians routinely use impressions of speech as an element of mental status examination. In schizophrenia-spectrum disorders, descriptions of speech are used to assess the severity of psychotic symptoms. In the current study, we assessed the diagnostic value of acoustic speech parameters in schizophrenia-spectrum disorders, as well as its value in recognizing positive and negative symptoms. METHODS: Speech was obtained from 142 patients with a schizophrenia-spectrum disorder and 142 matched controls during a semi-structured interview on neutral topics. Patients were categorized as having predominantly positive or negative symptoms using the Positive and Negative Syndrome Scale (PANSS). Acoustic parameters were extracted with OpenSMILE, employing the extended Geneva Acoustic Minimalistic Parameter Set, which includes standardized analyses of pitch (F0), speech quality and pauses. Speech parameters were fed into a random forest algorithm with leave-ten-out cross-validation to assess their value for a schizophrenia-spectrum diagnosis, and PANSS subtype recognition. RESULTS: The machine-learning speech classifier attained an accuracy of 86.2% in classifying patients with a schizophrenia-spectrum disorder and controls on speech parameters alone. Patients with predominantly positive v. negative symptoms could be classified with an accuracy of 74.2%. CONCLUSIONS: Our results show that automatically extracted speech parameters can be used to accurately classify patients with a schizophrenia-spectrum disorder and healthy controls, as well as differentiate between patients with predominantly positive v. negatives symptoms. Thus, the field of speech technology has provided a standardized, powerful tool that has high potential for clinical applications in diagnosis and differentiation, given its ease of comparison and replication across samples.

Assessing coherence through linguistic connectives: Analysis of speech in patients with schizophrenia-spectrum disorders.

BACKGROUND: Incoherent speech is a core diagnostic symptom of schizophrenia-spectrum disorders (SSD) that can be studied using semantic space models. Since linguistic connectives signal relations between words, they and their surrounding words might represent linguistic loci to detect unusual coherence in speech. Therefore, we investigated whether connectives' measures are useful to assess incoherent speech in SSD. METHODS: Connectives and their surrounding words were extracted from transcripts of spontaneous speech of 50 SSD-patients and 50 control participants. Using word2vec, two different cosine similarities were calculated: those of connectives and their surrounding words (connectives-related similarity), and those of free-of-connectives words-chunks (non-connectives similarity). Differences between groups in proportion of five types of connectives were assessed using generalized logistic models, and connectives-related similarity was analyzed through non-parametric multivariate analysis of variance. These features were evaluated in classification tasks to differentiate between groups. RESULTS: SSD-patients used less contingency (e.g., because) (p = .008) and multiclass connectives (e.g., as) (p < .001) than control participants. SSD-patients had higher minimum similarity of multiclass (adj-p = .04) and temporality connectives (e.g., after) (adj-p < .001), narrower similarity-range of expansion (e.g., and) (adj-p = .002) and multiclass connectives (adj-p = .04), and lower maximum similarity of expansion connectives (adj-p = .005). Using connectives' features alone, SSD-patients and controls could be distinguished with 85 % accuracy. DISCUSSION: Our results show that SSD-speech can be distinguished from speech of control participants with high accuracy, based solely on connectives' features. We conclude that including connectives could strengthen computational models to categorize SSD.

[Improving care for women with schizophrenia-spectrum disorders]. / Vrouwen met schizofreniespectrum-stoornissen verdienen betere zorg.

Background   Women with a schizophrenia-spectrum disorder (SSD) have a better clinical profile than men at the start of their illness but lose this advantage within the first few years of living with SSD. There are benefits to be gained across different areas in the care currently offered to women with psychosis. Aim   To describe point of improvement in the care for women with SSD. Method   Review or relevant literature. Results   An important point for improvement is the early detection of female-specific signs of a first episode of psychosis, to shorten the duration of untreated psychosis, with prompt access to early intervention services. Special attention should be paid to sexual health, and to any history of childhood trauma. Antipsychotics clearly require dosing and prescription tailored to the female body, considering hormonal life phases such as menopause. Switching to prolactin-sparing medications can benefit both mental and somatic health. Finally, hormone replacement therapy should be considered for postmenopausal women. Conclusion   By providing female-specific care, women with SSD can live up to their full potential.

[Tapering of psychotropic drugs: current practice and needs of patients and their relatives]. / Deprescriptie van psychofarmaca; praktijk en behoeften van patiënten en naasten.

BACKGROUND: The prevalence of mental illness has remained stable in recent decades, yet the use of psychotropic drugs has increased. This trend suggests that psychotropic drugs are being prescribed with an unnecessary frequency. Internationally, there is growing attention for deprescribing. AIM: To investigate what experiences and needs patients and their loved ones/relatives have with regard to deprescribing of psychotropics. METHOD: An online questionnaire was distributed among members of the MIND mental health care panel, which consists of (former) patients with a psychiatric disorder and their loved ones. RESULTS: A total of 564 respondents took part in this survey. Most patients have phased out/stopped their psychotropic drugs (83.8%). This was usually done at the initiative of the patient (66.7%), in consultation with the practitioner (72.9%). The practitioner only took the initiative to deprescribe in 15.1% of the cases. In 68.6% tapering was not discussed at the start of psychotropic drug use. Patients did not experience willingness from practitioners in deprescribing, and would like to discuss deprescribing more often (79.5%). CONCLUSION: There is an undeniable demand among patients and near ones for more emphasis on deprescribing of psychotropic drugs. We advise to include this topic in the shared decision making process.

A data-driven linguistic characterization of hallucinated voices in clinical and non-clinical voice-hearers.

BACKGROUND: Auditory verbal hallucinations (AVHs) are heterogeneous regarding phenomenology and etiology. This has led to the proposal of AVHs subtypes. Distinguishing AVHs subtypes can inform AVHs neurocognitive models and also have implications for clinical practice. A scarcely studied source of heterogeneity relates to the AVHs linguistic characteristics. Therefore, in this study we investigate whether linguistic features distinguish AVHs subtypes, and whether linguistic AVH-subtypes are associated with phenomenology and voice-hearers' clinical status. METHODS: Twenty-one clinical and nineteen non-clinical voice-hearers participated in this study. Participants were instructed to repeat verbatim their AVHs just after experiencing them. AVH-repetitions were audio-recorded and transcribed. AVHs phenomenology was assessed using the Auditory Hallucinations Rating Scale of the Psychotic Symptom Rating Scales. Hierarchical clustering analyses without a priori group dichotomization were performed using quantitative measures of sixteen linguistic features to distinguish sets of AVHs. RESULTS: A two-AVHs-cluster solution best partitioned the data. AVHs-clusters significantly differed in linguistic features (p < .001); AVHs phenomenology (p < .001); and distribution of clinical voice-hearers (p < .001). The "expanded-AVHs" cluster was characterized by more determiners, more prepositions, longer utterances (all p < .01), and mainly contained non-clinical voice-hearers. The "compact-AVHs" cluster had fewer determiners and prepositions, shorter utterances (all p < .01), more negative content, higher degree of negativity (both p < .05), and predominantly came from clinical voice-hearers. DISCUSSION: Two voice-speech clusters were recognized, differing in syntactic-grammatical complexity and negative phenomenology. Our results suggest clinical voice-hearers often hear negative, "compact-voices", understandable under Broca's right hemisphere homologue and memory-based mechanisms. Conversely, non-clinical voice-hearers experience "expanded-voices", better accounted by inner speech AVHs models.