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Introduction: Dysarthria, a motor speech disorder caused by muscle weakness or paralysis, severely impacts speech intelligibility and quality of life. The condition is prevalent in motor speech disorders such as Parkinson's disease (PD), atypical parkinsonism such as progressive supranuclear palsy (PSP), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Improving intelligibility is not only an outcome that matters to patients but can also play a critical role as an endpoint in clinical research and drug development. This study validates a digital measure for speech intelligibility, the ki: SB-M intelligibility score, across various motor speech disorders and languages following the Digital Medicine Society (DiMe) V3 framework. Methods: The study used four datasets: healthy controls (HCs) and patients with PD, HD, PSP, and ALS from Czech, Colombian, and German populations. Participants' speech intelligibility was assessed using the ki: SB-M intelligibility score, which is derived from automatic speech recognition (ASR) systems. Verification with inter-ASR reliability and temporal consistency, analytical validation with correlations to gold standard clinical dysarthria scores in each disease, and clinical validation with group comparisons between HCs and patients were performed. Results: Verification showed good to excellent inter-rater reliability between ASR systems and fair to good consistency. Analytical validation revealed significant correlations between the SB-M intelligibility score and established clinical measures for speech impairments across all patient groups and languages. Clinical validation demonstrated significant differences in intelligibility scores between pathological groups and healthy controls, indicating the measure's discriminative capability. Discussion: The ki: SB-M intelligibility score is a reliable, valid, and clinically relevant tool for assessing speech intelligibility in motor speech disorders. It holds promise for improving clinical trials through automated, objective, and scalable assessments. Future studies should explore its utility in monitoring disease progression and therapeutic efficacy as well as add data from further dysarthrias to the validation.
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OBJECTIVE: To compare the success rates of medical management using a combined mifepristone and misoprostol protocol in cases of early pregnancy loss (EPL) between women who conceived without medical assistance and those who conceived through in vitro fertilization (IVF), after fresh or frozen embryo transfer, and evaluate for the predictive factors of success, time to first passage of tissue, and time to complete resolution of pregnancy. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): Women who presented with EPL below 13 weeks of gestation between June 2013 and July 2021 who were managed medically with mifepristone 200 mg orally and misoprostol 800 mcg vaginally were included in the study. INTERVENTION(S): Medical management with mifepristone and misoprostol; conception without medical assistance vs. post-IVF, after fresh or frozen embryo transfer. MAIN OUTCOME MEASURE(S): We evaluated overall success and performed subgroup analysis according to the mode of conception and compared fresh vs. frozen-thawed embryo transfers for IVF pregnancies. In all groups, we also calculated success according to gestational age and compared the time to first passage of tissue. The potential predictive factors of treatment success were analyzed. The side effects and complications of treatment were recorded. RESULT(S): A total of 930 women were included in the study, 99 (11%) of whom achieved pregnancy after IVF. The overall success of medical treatment was 89% with no statistically significant difference according to the mode of conception (89% vs. 89%) or type of transfer (fresh 89% vs. frozen 89%). Only lower gestational age by sonography was independently predictive of treatment success, showing a negative regression coefficient of ß = -0.333 and an odds ratio of 0.717. The mean time to first passage of tissue was 5.0 ± 2.1 hours. Altogether, 666 women (72%) showed pregnancy resolution on the day of medication administration, an additional 110 women at 1-week follow-up, and a further 74 women after ≥4 weeks on ultrasound. CONCLUSION(S): Medical management of EPL with mifepristone and misoprostol is a highly successful treatment option that results in completed abortion in a timely fashion in both pregnancies conceived without medical assistance and those conceived after IVF.
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Aborto Espontáneo , Transferencia de Embrión , Fertilización In Vitro , Mifepristona , Misoprostol , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Adulto , Mifepristona/administración & dosificación , Mifepristona/efectos adversos , Mifepristona/uso terapéutico , Fertilización In Vitro/métodos , Misoprostol/administración & dosificación , Misoprostol/efectos adversos , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Transferencia de Embrión/métodos , Resultado del Tratamiento , Abortivos no Esteroideos/administración & dosificación , Abortivos no Esteroideos/efectos adversos , Abortivos Esteroideos/administración & dosificación , Abortivos Esteroideos/efectos adversos , Administración OralRESUMEN
PURPOSE: If not eliminated by the immune system and persisting over years, oropharyngeal high-risk HPV infection can lead to cancer development in the oropharynx. HPV infection is very commonly found in the genital region and can serve as an HPV reservoir. In this study, we investigate whether women with a genital HPV infection are at a higher risk of harboring an undetected oropharyngeal HPV infection via genital-oropharyngeal transmission. METHODS: Women presenting for routine gynecological checkups were included in this study. All participants received an HPV brush test from the genital region as well as from the oropharynx. Additionally, probable risk factors for an HPV infection were assessed in a structured questionnaire. RESULTS: 142 women were included in this study. The rate of oropharyngeal HPV infection was low with 2/142 (1,4%) women positive for a low-risk HPV genotype. In the genital brush test, 54/142 (38%) women were tested HPV positive of which 41/142 (29%) were positive for a high-risk HPV genotype. CONCLUSIONS: The rate of an oropharyngeal HPV detection in our population was low with 2/142 women harboring a low-risk HPV infection.
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Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Femenino , Masculino , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Factores de Riesgo , Genitales , Papillomaviridae/genéticaRESUMEN
BACKGROUND: Previous research has shown that verbal memory accurately measures cognitive decline in the early phases of neurocognitive impairment. Automatic speech recognition from the verbal learning task (VLT) can potentially be used to differentiate between people with and without cognitive impairment. OBJECTIVE: Investigate whether automatic speech recognition (ASR) of the VLT is reliable and able to differentiate between subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODS: The VLT was recorded and processed via a mobile application. Following, verbal memory features were automatically extracted. The diagnostic performance of the automatically derived features was investigated by training machine learning classifiers to distinguish between participants with SCD versus MCI/dementia. RESULTS: The ICC for inter-rater reliability between the clinical and automatically derived features was 0.87 for the total immediate recall and 0.94 for the delayed recall. The full model including the total immediate recall, delayed recall, recognition count, and the novel verbal memory features had an AUC of 0.79 for distinguishing between participants with SCD versus MCI/dementia. The ten best differentiating VLT features correlated low to moderate with other cognitive tests such as logical memory tasks, semantic verbal fluency, and executive functioning. CONCLUSIONS: The VLT with automatically derived verbal memory features showed in general high agreement with the clinical scoring and distinguished well between SCD and MCI/dementia participants. This might be of added value in screening for cognitive impairment.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia , Humanos , Reproducibilidad de los Resultados , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Memoria , Recuerdo Mental , Pruebas Neuropsicológicas , Enfermedad de Alzheimer/psicología , Aprendizaje VerbalRESUMEN
Alzheimer's disease affects nearly three million people in France, and requires training for both healthcare professionals and caregivers. Our study underlines the value of supporting an adapted program based on mindfulness meditation, to reduce anxiety and stress for patients and their caregivers.
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Enfermedad de Alzheimer , Arteterapia , Meditación , Atención Plena , Humanos , Cuidadores , Enfermedad de Alzheimer/terapiaRESUMEN
Introduction: We studied the accuracy of the automatic speech recognition (ASR) software by comparing ASR scores with manual scores from a verbal learning test (VLT) and a semantic verbal fluency (SVF) task in a semiautomated phone assessment in a memory clinic population. Furthermore, we examined the differentiating value of these tests between participants with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). We also investigated whether the automatically calculated speech and linguistic features had an additional value compared to the commonly used total scores in a semiautomated phone assessment. Methods: We included 94 participants from the memory clinic of the Maastricht University Medical Center+ (SCD N = 56 and MCI N = 38). The test leader guided the participant through a semiautomated phone assessment. The VLT and SVF were audio recorded and processed via a mobile application. The recall count and speech and linguistic features were automatically extracted. The diagnostic groups were classified by training machine learning classifiers to differentiate SCD and MCI participants. Results: The intraclass correlation for inter-rater reliability between the manual and the ASR total word count was 0.89 (95% CI 0.09-0.97) for the VLT immediate recall, 0.94 (95% CI 0.68-0.98) for the VLT delayed recall, and 0.93 (95% CI 0.56-0.97) for the SVF. The full model including the total word count and speech and linguistic features had an area under the curve of 0.81 and 0.77 for the VLT immediate and delayed recall, respectively, and 0.61 for the SVF. Conclusion: There was a high agreement between the ASR and manual scores, keeping the broad confidence intervals in mind. The phone-based VLT was able to differentiate between SCD and MCI and can have opportunities for clinical trial screening.
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Introduction: The use of teleconsultations for mental health has drastically increased since 2020 due to the Covid19 pandemic. In the present paper, we aimed to analyze the advantages and disadvantages of teleconsultations for mental health compared to face-to-face consultations, and to provide recommendations in this domain. Methods: The recommendations were gathered using a Delphi methodology. The expert panel (N = 21) included professionals from the health and ICT domains. They answered questions via two rounds of web surveys, and then discussed the results in a plenary meeting. Some of the questions were also shared with non-experts (N = 104). Results: Both the experts and the non-experts with teleconsultation experience reported a general satisfaction concerning teleconsultations. A SWOT analysis revealed several strengths and opportunities of teleconsultations for mental health, but also several weaknesses and threats. The experts provided a set of practical recommendations for the preparation and organization of teleconsultations for mental health. Discussion: Teleconsultations for mental health have the potential to allow access to care for patients in remote and isolated areas. Thus, their use will unlikely be discontinued after the end of the pandemic. In this context, we suggest that the collaboration among clinicians, researchers, and interface designers is crucial to improve usability and user experience for both clinicians and patients. The importance of teaching teleconsultation skills and informing the public on the features of teleconsultations (e.g., data privacy/security) is also highlighted.
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Alzheimer's disease (AD) brings with it the need to think about the loss of autonomy caused by cognitive impairment, and how to manage it. In this context, adapted physical activity has been shown to benefit the overall quality of life of people suffering from the disease. In our study of thirteen patients with AD or related neurodegenerative diseases, we assessed the impact of physical activity on self-esteem and motivation, with patients taking part in group exercise sessions lasting twelve weeks, one hour a week.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Motivación , Calidad de Vida , Enfermedad de Alzheimer/psicología , Ejercicio FísicoRESUMEN
INTRODUCTION: Post-traumatic stress disorder (PTSD) symptoms in youth are influenced by parental anxiety and stress. When parents have high levels of stress or have developed PTSD themselves, children tend to show more anxiety symptoms. Parental stress can affect the severity of children's PTSD and lower the success of recovery. However, the influence of parental stress on the effectiveness of trauma-focused therapies (eye movement desensitisation and reprocessing and cognitive behavioural therapy) has not yet been investigated to our knowledge. Hence, we will measure parental stress (using both validated scales and vocal acoustic markers) and investigate how it influences children's PTSD recovery. METHOD AND ANALYSIS: Sixty children between the ages of 7 and 15 years who experienced type 1 trauma will be recruited at the Nice Pediatric Psychotrauma Center in France. We plan to measure stress using two different approaches. We will ask parents to answer validated scales of stress and mood in general. Stress will also be measured using vocal acoustic markers. Parents will be recorded while narrating their child's trauma and during the narrative of a positive and neutral recall of events. Child participants will have to complete anxiety, PTSD and depression scales before the beginning of the trauma-focused therapy and after 3 months of treatment.Linear mixed effects models and differential statistics, such as significance testing corrected for multiple testing, will be used to determine the validity of speech features for the proposed hypotheses. Repeated measures analysis of variance will be performed on the clinical scales scores according to parental stress. Correlations will be performed between clinical scales of parents and children according to time of assessment. ETHICS AND DISSEMINATION: This study was approved by the Committee for the Protection of Individuals of the University of Nice Sophia Antipolis (CERNI) on 21 February 2022, under the number CER2022-015.All participants will be informed that this is an observational study and their consent taken prior to the experiment. Participants will be informed that they can withdraw from the study at any time and that it would not affect the care provided. TRIAL REGISTRATION NUMBER: CER AVIS n° 2022-015.
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Trastornos por Estrés Postraumático , Voz , Adolescente , Niño , Humanos , Trastornos por Estrés Postraumático/terapia , Habla , Acústica , Padres , Estudios Observacionales como AsuntoRESUMEN
[This corrects the article DOI: 10.2196/37225.].
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BACKGROUND: Major depressive episode (MDE) is a common clinical syndrome. It can be found in different pathologies such as major depressive disorder (MDD), bipolar disorder (BD), posttraumatic stress disorder (PTSD), or even occur in the context of psychological trauma. However, only 1 syndrome is described in international classifications (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5]/International Classification of Diseases 11th Revision [ICD-11]), which do not take into account the underlying pathology at the origin of the MDE. Clinical interviews are currently the best source of information to obtain the etiological diagnosis of MDE. Nevertheless, it does not allow an early diagnosis and there are no objective measures of extracted clinical information. To remedy this, the use of digital tools and their correlation with clinical symptomatology could be useful. OBJECTIVE: We aimed to review the current application of digital tools for MDE diagnosis while highlighting shortcomings for further research. In addition, our work was focused on digital devices easy to use during clinical interview and mental health issues where depression is common. METHODS: We conducted a narrative review of the use of digital tools during clinical interviews for MDE by searching papers published in PubMed/MEDLINE, Web of Science, and Google Scholar databases since February 2010. The search was conducted from June to September 2021. Potentially relevant papers were then compared against a checklist for relevance and reviewed independently for inclusion, with focus on 4 allocated topics of (1) automated voice analysis, behavior analysis by (2) video and physiological measures, (3) heart rate variability (HRV), and (4) electrodermal activity (EDA). For this purpose, we were interested in 4 frequently found clinical conditions in which MDE can occur: (1) MDD, (2) BD, (3) PTSD, and (4) psychological trauma. RESULTS: A total of 74 relevant papers on the subject were qualitatively analyzed and the information was synthesized. Thus, a digital phenotype of MDE seems to emerge consisting of modifications in speech features (namely, temporal, prosodic, spectral, source, and formants) and in speech content, modifications in nonverbal behavior (head, hand, body and eyes movement, facial expressivity, and gaze), and a decrease in physiological measurements (HRV and EDA). We not only found similarities but also differences when MDE occurs in MDD, BD, PTSD, or psychological trauma. However, comparative studies were rare in BD or PTSD conditions, which does not allow us to identify clear and distinct digital phenotypes. CONCLUSIONS: Our search identified markers from several modalities that hold promise for helping with a more objective diagnosis of MDE. To validate their potential, further longitudinal and prospective studies are needed.
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OBJECTIVE: To investigate whether automatic analysis of the Semantic Verbal Fluency test (SVF) is reliable and can extract additional information that is of value for identifying neurocognitive disorders. In addition, the associations between the automatically derived speech and linguistic features and other cognitive domains were explored. METHOD: We included 135 participants from the memory clinic of the Maastricht University Medical Center+ (with Subjective Cognitive Decline [SCD; N = 69] and Mild Cognitive Impairment [MCI]/dementia [N = 66]). The SVF task (one minute, category animals) was recorded and processed via a mobile application, and speech and linguistic features were automatically extracted. The diagnostic performance of the automatically derived features was investigated by training machine learning classifiers to differentiate SCD and MCI/dementia participants. RESULTS: The intraclass correlation for interrater reliability between the clinical total score (golden standard) and automatically derived total word count was 0.84. The full model including the total word count and the automatically derived speech and linguistic features had an Area Under the Curve (AUC) of 0.85 for differentiating between people with SCD and MCI/dementia. The model with total word count only and the model with total word count corrected for age showed an AUC of 0.75 and 0.81, respectively. Semantic switching correlated moderately with memory as well as executive functioning. CONCLUSION: The one-minute SVF task with automatically derived speech and linguistic features was as reliable as the manual scoring and differentiated well between SCD and MCI/dementia. This can be considered as a valuable addition in the screening of neurocognitive disorders and in clinical practice.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia , Humanos , Habla , Reproducibilidad de los Resultados , Pruebas Neuropsicológicas , Lingüística , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Demencia/diagnóstico , Enfermedad de Alzheimer/psicologíaRESUMEN
BACKGROUND: Modern prodromal Alzheimer's disease (AD) clinical trials might extend outreach to a general population, causing high screen-out rates and thereby increasing study time and costs. Thus, screening tools that cost-effectively detect mild cognitive impairment (MCI) at scale are needed. OBJECTIVE: Develop a screening algorithm that can differentiate between healthy and MCI participants in different clinically relevant populations. METHODS: Two screening algorithms based on the remote ki:e speech biomarker for cognition (ki:e SB-C) were designed on a Dutch memory clinic cohort (Nâ=â121) and a Swedish birth cohort (Nâ=â404). MCI classification was each evaluated on the training cohort as well as on the unrelated validation cohort. RESULTS: The algorithms achieved a performance of AUC 0.73 and AUC 0.77 in the respective training cohorts and AUC 0.81 in the unseen validation cohorts. CONCLUSION: The results indicate that a ki:e SB-C based algorithm robustly detects MCI across different cohorts and languages, which has the potential to make current trials more efficient and improve future primary health care.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Habla , Enfermedad de Alzheimer/diagnóstico , Disfunción Cognitiva/diagnóstico , Aprendizaje Automático , Cognición , BiomarcadoresRESUMEN
Introduction: Digital cognitive assessments are gathering importance for the decentralized remote clinical trials of the future. Before including such assessments in clinical trials, they must be tested to confirm feasibility and acceptability with the intended participant group. This study presents usability and acceptability data from the Speech on the Phone Assessment (SPeAk) study. Methods: Participants (N = 68, mean age 70.43 years, 52.9% male) provided demographic data and completed baseline and 3-month follow-up phone based assessments. The baseline visit was administered by a trained researcher and included a spontaneous speech assessment and a brief cognitive battery (immediate and delayed recall, digit span, and verbal fluency). The follow-up visit repeated the cognitive battery which was administered by an automatic phone bot. Participants were randomized to receive their cognitive test results acer the final or acer each study visit. Participants completed acceptability questionnaires electronically acer each study visit. Results: There was excellent retention (98.5%), few technical issues (n = 5), and good interrater reliability. Participants rated the assessment as acceptable, confirming the ease of use of the technology and their comfort in completing cognitive tasks on the phone. Participants generally reported feeling happy to receive the results of their cognitive tests, and this disclosure did not cause participants to feel worried. Discussion: The results from this usability and acceptability analysis suggest that completing this brief battery of cognitive tests via a telephone call is both acceptable and feasible in a midlife-to-older adult population in the United Kingdom, living at risk for Alzheimer's disease.
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BACKGROUND: Automated speech analysis has gained increasing attention to help diagnosing depression. Most previous studies, however, focused on comparing speech in patients with major depressive disorder to that in healthy volunteers. An alternative may be to associate speech with depressive symptoms in a non-clinical sample as this may help to find early and sensitive markers in those at risk of depression. METHODS: We included n = 118 healthy young adults (mean age: 23.5 ± 3.7 years; 77% women) and asked them to talk about a positive and a negative event in their life. Then, we assessed the level of depressive symptoms with a self-report questionnaire, with scores ranging from 0-60. We transcribed speech data and extracted acoustic as well as linguistic features. Then, we tested whether individuals below or above the cut-off of clinically relevant depressive symptoms differed in speech features. Next, we predicted whether someone would be below or above that cut-off as well as the individual scores on the depression questionnaire. Since depression is associated with cognitive slowing or attentional deficits, we finally correlated depression scores with performance in the Trail Making Test. RESULTS: In our sample, n = 93 individuals scored below and n = 25 scored above cut-off for clinically relevant depressive symptoms. Most speech features did not differ significantly between both groups, but individuals above cut-off spoke more than those below that cut-off in the positive and the negative story. In addition, higher depression scores in that group were associated with slower completion time of the Trail Making Test. We were able to predict with 93% accuracy who would be below or above cut-off. In addition, we were able to predict the individual depression scores with low mean absolute error (3.90), with best performance achieved by a support vector machine. CONCLUSIONS: Our results indicate that even in a sample without a clinical diagnosis of depression, changes in speech relate to higher depression scores. This should be investigated in more detail in the future. In a longitudinal study, it may be tested whether speech features found in our study represent early and sensitive markers for subsequent depression in individuals at risk.
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Trastorno Depresivo Mayor , Adulto Joven , Humanos , Femenino , Adulto , Masculino , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Depresión/diagnóstico , Estudios Longitudinales , Habla , Encuestas y CuestionariosRESUMEN
Today, in rural isolated areas or so-called 'medical deserts', access to diagnosis and care is very limited. With the current pandemic crisis, now even more than ever, telemedicine platforms are gradually more employed for remote medical assessment. Only a few are tailored to comprehensive teleneuropsychological assessment of older adults. Hence, our study focuses on evaluating the feasibility of performing a remote neuropsychological assessment of older adults suffering from a cognitive complaint. 50 participants (aged 55 and older) were recruited at the local hospital of Digne-les-Bains, France. A brief neuropsychological assessment including a short clinical interview and several validated neuropsychological tests was administered in two conditions, once by Teleneuropsychology (TNP) and once by Face-to-Face (FTF) in a crossover design. Acceptability and user experience was assessed through questionnaires. Results show high agreement in most tests between the FTF and TNP conditions. The TNP was overall well accepted by the participants. However, differences in test performances were observed, which urges the need to validate TNP tests with broader samples with normative data.
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BACKGROUND: The optimal management of vulvar high-grade squamous intraepithelial lesions (vHSILs) is challenging. Surgery is the standard treatment, but recurrences are observed in half of patients. Medical treatment with imiquimod is an effective alternative, but the two modalities have not been compared in a randomised trial. The aim of this study was to compare the clinical effectiveness, histological response, human papillomavirus (HPV) clearance, acceptance, and psychosexual morbidity of primary imiquimod treatment versus surgical treatment in women with vHSIL. METHODS: This study was a multicentre, randomised, phase 3, non-inferiority clinical trial done by the Austrian Gynaecological Oncology group at six hospitals in Austria. We recruited female patients aged 18-90 years with histologically confirmed vHSIL with visible unifocal or multifocal lesions. Main exclusion criteria were clinical suspicion of invasion, a history of vulvar cancer or severe inflammatory dermatosis of the vulva, and any active treatment for vHSIL within the previous 3 months. Women with known immunodeficiency, who were pregnant, or who were lactating were excluded. Patients were randomly assigned (1:1) by block randomisation to imiquimod or surgery, and stratified by unifocal or multifocal disease. Treatment with imiquimod was self-administered in a slowly escalating dosage scheme up to three times per week for a period of 4-6 months. Surgery consisted of excision or ablation. Patients were assessed with vulvoscopy, vulvar biopsy, HPV tests, and patient-reported outcomes at baseline and after 6 months and 12 months. The primary endpoint was complete clinical response (CCR) at 6 months after local imiquimod treatment or one surgical intervention. Primary analysis was per protocol with a non-inferiority margin of 20%. This trial is registered at ClinicalTrials.gov, NCT01861535. FINDINGS: 110 patients with vHSIL (78% with unifocal vHSIL and 22% with multifocal vHSIL) were randomly assigned between June 7, 2013, and Jan 8, 2020. Clinical response to treatment could be assessed in 107 patients (54 in the imiquimod group and 53 in the surgery group), and 98 patients (46 in the imiquimod group and 52 in the surgery group) completed the study per protocol. 37 (80%) of 46 patients using imiquimod had CCR, compared with 41 (79%) of 52 patients after one surgical intervention, showing non-inferiority of the new treatment (difference in proportion -0·016, 95% CI -0·15 to -0·18; p=0·0056). Invasive disease was found in five patients at primary or secondary surgery, but not in patients with per-protocol imiquimod treatment. There was no significant difference in HPV clearance, adverse events, and treatment satisfaction between study groups. INTERPRETATION: Imiquimod is a safe, effective, and well accepted alternative to surgery for women with vHSIL and can be considered as first-line treatment. FUNDING: Austrian Science Fund and Austrian Gynaecological Oncology group.
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Infecciones por Papillomavirus , Lesiones Intraepiteliales Escamosas , Neoplasias de la Vulva , Femenino , Humanos , Imiquimod/uso terapéutico , Lactancia , Embarazo , Neoplasias de la Vulva/tratamiento farmacológico , Neoplasias de la Vulva/patología , Neoplasias de la Vulva/cirugíaRESUMEN
INTRODUCTION: Identifying cost-effective, non-invasive biomarkers of Alzheimer's disease (AD) is a clinical and research priority. Speech data are easy to collect, and studies suggest it can identify those with AD. We do not know if speech features can predict AD biomarkers in a preclinical population. METHODS AND ANALYSIS: The Speech on the Phone Assessment (SPeAk) study is a prospective observational study. SPeAk recruits participants aged 50 years and over who have previously completed studies with AD biomarker collection. Participants complete a baseline telephone assessment, including spontaneous speech and cognitive tests. A 3-month visit will repeat the cognitive tests with a conversational artificial intelligence bot. Participants complete acceptability questionnaires after each visit. Participants are randomised to receive their cognitive test results either after each visit or only after they have completed the study. We will combine SPeAK data with AD biomarker data collected in a previous study and analyse for correlations between extracted speech features and AD biomarkers. The outcome of this analysis will inform the development of an algorithm for prediction of AD risk based on speech features. ETHICS AND DISSEMINATION: This study has been approved by the Edinburgh Medical School Research Ethics Committee (REC reference 20-EMREC-007). All participants will provide informed consent before completing any study-related procedures, participants must have capacity to consent to participate in this study. Participants may find the tests, or receiving their scores, causes anxiety or stress. Previous exposure to similar tests may make this more familiar and reduce this anxiety. The study information will include signposting in case of distress. Study results will be disseminated to study participants, presented at conferences and published in a peer reviewed journal. No study participants will be identifiable in the study results.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Anciano , Enfermedad de Alzheimer/diagnóstico , Inteligencia Artificial , Biomarcadores/análisis , Humanos , Persona de Mediana Edad , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Habla , Encuestas y CuestionariosRESUMEN
Respiratory-digestive tract fistulas are fatal complications that occur in esophageal cancer treatment. Interdisciplinary treatment strategies are still evolving, especially in anatomical treatment stratification. Thus, this study aims to evaluate general therapeutic strategies for this rare condition. Medical records were reviewed for esophageal cancer-associated respiratory-digestive tract fistula patients treated between January 2008 and September 2021. Fistulas were classified according to being surgery- and tumor-associated. Treatment strategies, clinical success, and survival were analyzed. A total of 51 patients were identified: 28 had tumor-associated fistulas and 23 surgery-associated fistulas. Risk factors for fistula development such as radiation (OR = 0.290, p = 0.64) or stent implantation (OR = 1.917, p = 0.84) did not correlate with lack of symptom control for RDF patients. In contrast, advanced lymph node metastasis as another risk factor was associated with persistent symptoms after treatment for RDF patients (OR = 0.611, p = 0.01). Clinical success significantly correlated with bilateral fistula repair in surgery-associated fistulas (p = 0.01), while tumor-associated fistulas benefited the most from non-surgical (p = 0.04) or combined surgical and non-surgical intervention (p = 0.04) and a bilateral fistula repair (p = 0.02) in terms of overall survival. The therapeutic strategy should aim for bilateral fistula closure. A multidisciplinary, stepwise approach might have the best chance for restoration or symptom control with optimized overall survival in selected patients.
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In order to expand and exploit the useful properties of d6-iron(II) and d5-iron(III) complexes in potential magnetic, photophysical, or magnetooptical applications, crucial ligand-controlled parameters are the ligand field strength in a given coordination mode and the availability of suitable metal and ligand frontier orbitals for charge-transfer processes. The push-pull ligand 2,6-diguanidylpyridine (dgpy) features low-energy π* orbitals at the pyridine site and strongly electron-donating guanidinyl donors combined with the ability to form six-membered chelate rings for optimal metal-ligand orbital overlap. The electronic ground states of the pseudo-octahedral d6- and d5-complexes mer-[Fe(dgpy)2]2+, cis-fac-[Fe(dgpy)2]2+, and mer-[Fe(dgpy)2]3+ as well as their charge-transfer (CT) and metal-centered (MC) excited states are probed by variable temperature UV/vis absorption, NMR, EPR, and Mössbauer spectroscopy, magnetic susceptibility measurements at variable temperature as well as quantum chemical calculations.