Speech as a Biomarker: Opportunities, Interpretability, and Challenges

Purpose: Over the past decade, the signal processing and machine learning literature has demonstrated notable advancements in automated speech processing with the use of artificial intelligence for medical assessment and monitoring (e.g., depression, dementia, and Parkinson's disease, among others). Meanwhile, the clinical speech literature has identified several interpretable, theoretically motivated measures that are sensitive to abnormalities in the cognitive, linguistic, affective, motoric, and anatomical domains. Both fields have, thus, independently demonstrated the potential for speech to serve as an informative biomarker for detecting different psychiatric and physiological conditions. However, despite these parallel advancements, automated speech biomarkers have not been integrated into routine clinical practice to date. Conclusions: In this article, we present opportunities and challenges for adoption of speech as a biomarker in clinical practice and research. Toward clinical acceptance and adoption of speech-based digital biomarkers, we argue for the importance of several factors such as robustness, specificity, diversity, and physiological interpretability of speech analytics in clinical applications.

Ethanol Exposure During the Intravenous Administration of Chemotherapeutic Drugs: An Analysis of Clinical Practice and a Literature Review

PURPOSE: Injectable cytotoxics may be formulated with ethanol. This study sought to quantify the amount of ethanol exposure during chemotherapy infusions. MATERIALS AND METHODS: We first reviewed the antineoplastic drugs (Anatomical Therapeutic and Chemical code L01) and oncologic supportive care drugs (eg, antiemetics) currently available in France, to identify preparations containing ethanol. The amount of ethanol in the final chemotherapy preparation was calculated. Next, we performed a 2-year, single-center, retrospective analysis of injectable antineoplastic drug compounding in routine clinical practice in a French university medical center. Finally, we reviewed our results with regard to the literature data. RESULTS: Ten of the 60 cytotoxic products on the market contained ethanol at concentrations of up to 790 mg/mL, depending on the drug, formulation, and supplier. Several final preparations contained more than 3 g of ethanol per infusion (the maximum recommended by the European Medicines Agency); this was notably the case for gemcitabine, paclitaxel (up to 20 g ethanol per injection, for both), and etoposide (up to 50 g ethanol per infusion). The analysis of our compounding activity showed that 3,172 (4.99%) of the 63,613 chemotherapy preparations (notably paclitaxel) contained more than 3 g of ethanol. None of the oncologic supportive care drugs contained ethanol. CONCLUSION: Patients are exposed to ethanol during the infusion of antineoplastic drugs. With a view to better patient care, physicians and pharmacists should carefully evaluate the risk of ethanol exposure throughout the course of cytotoxic drug treatment.

Unlocking Access to Broad Molecular Profiling: Benefits, Barriers, and Policy Solutions

<b><i>Objectives:</i></b> “Personalized healthcare” is generating new approaches to disease management by considering inter-individual variability in genes, environment, and lifestyle. Technologies such as comprehensive genomic profiling (CGP) are drivers of this shift. Here, we address the significant hurdles to the equitable implementation of CGP into routine clinical practice. <b><i>Methods:</i></b> This article draws on published evidence on the value of genomic profiling, as well as interviews with nine academic and clinical experts from six different countries to validate findings and test policy proposals for reforms. <b><i>Results:</i></b> The potential benefits of CGP extend beyond direct patient outcomes, to healthcare systems with societal and economic impacts. Among key barriers impeding integration into routine clinical practice are the lack of infrastructure to ensure reliable clinical testing and the limited understanding of genomics among healthcare personnel. In addition, the absence of health economic evidence supporting broader use of CGP is creating concerns for payers regarding the systemic benefits and affordability of this technology. <b><i>Conclusion:</i></b> Policy proposals that aim to improve equitable patient access to CGP will need to consider new funding models, health technology assessment processes that capture both patient and systemic benefits, and appropriate regulatory standards to determine the quality of genomic profiling tests.

Romiplostim for Primary Immune Thrombocytopenia (ITP) in Routine Clinical Practice: Results from a Multicentre Observational Study in Germany

Introduction: The effectiveness and safety of romiplostim were evaluated by immune thrombocytopenia (ITP) phase (newly diagnosed/persistent/chronic) at romiplostim initiation. Methods: Post hoc analysis of a prospective, German, multicentre, observational study in adults with ITP who received ≥1 dose of romiplostim. Follow-up data were collected for ≤2 years. Outcomes included overall platelet response (≥1 platelet count ≥50 × 109/L at 2–24 weeks after romiplostim initiation) or durable platelet response (≥75% of measurements ≥50 x 109/L at 14–24 weeks), and adverse drug reactions (ADRs), evaluated by ITP phase. Results: Data from 96 patients were analysed (newly diagnosed, n=18; persistent, n=25; chronic, n=53). During the 2–24-week follow-up, overall platelet response was achieved in 100% (95% confidence interval [CI]: 81.5–100), 100% (86.3–100), and 96.2% (87.0–99.5) of patients with newly diagnosed, persistent, or chronic ITP, respectively; platelet responses were durable in 88.2% (63.6–98.5), 65.0% (40.8–84.6), and 69.4% (54.6–81.7) of patients. During the 2-year follow-up, ADRs occurred in 24.0–35.8% of patients across phases. Two patients with chronic ITP experienced bone marrow ADRs; no thrombotic ADRs occurred. Conclusion: Romiplostim was effective and well tolerated in patients with newly diagnosed, persistent, or chronic ITP in routine clinical practice.

Clinical Features, Histopathology and Differential Diagnosis of Sarcoidosis

Sarcoidosis is a chameleon disease of unknown etiology, characterized by the growth of non-necrotizing and non-caseating granulomas and manifesting with clinical pictures that vary on the basis of the organs that are mainly affected. Lungs and intrathoracic lymph nodes are the sites that are most often involved, but virtually no organ is spared from this disease. Histopathology is distinctive but not pathognomonic, since the findings can be found also in other granulomatous disorders. The knowledge of these findings is important because it could be helpful to differentiate sarcoidosis from the other granulomatous-related diseases. This review aims at illustrating the main clinical and histopathological findings that could help clinicians in their routine clinical practice.

Evaluation of Motor Complications in Parkinson’s Disease: Understanding the Perception Gap between Patients and Physicians

Background. Patients with Parkinson’s disease (PD) receiving levodopa treatment often report motor complications including wearing-off (WO), dyskinesia, and morning akinesia. As motor complications are associated with a decrease in patients’ quality of life (QoL), it is important to identify their occurrence and commence immediate management. This study investigated whether differences in the perception of motor complications exist between patients and their physicians in routine clinical practice. Methods. After an Internet-based screening survey, questionnaires were distributed to physicians and their patients in Japan. The 9-item Wearing-Off Questionnaire (WOQ-9) was used to objectively assess the presence of WO; patients with WOQ-9 scores ≥2 were considered to have WO. McNemar’s test was used to compare physician assessment versus WOQ-9 scores, patient self-awareness versus physician assessment, and patient self-awareness versus WOQ-9, separately. Morning akinesia and dyskinesia were assessed by both physician assessment and patient self-awareness with McNemar’s test. QoL was assessed using the 8-item Parkinson’s Disease Questionnaire (PDQ-8) with the Wilcoxon rank-sum test. Results. A total of 235 patients with PD and their 92 physicians participated in this survey. A significant discordance was observed between the WOQ-9 and physician assessment of WO (67.2% vs 46.0%; p < 0.0001 ). Furthermore, patient self-awareness of WO was 35.3% ( p = 0.0004 , vs physician). Morning akinesia (patient, 58.7%; physician, 48.9%; p = 0.0032 ), dyskinesia (patient, 34.0%; physician, 23.4%; p = 0.0006 ), and bodily discomfort (patient, 25.0; physician, 0.0; p = 0.0102 ) of QoL were underrecognized by physicians. Conclusions. This study investigated differences in the perception of WO between patients with PD and their physicians in routine clinical practice and highlighted that patients have a low awareness of the symptoms of WO compared with physician assessments and WOQ-9. Conversely, morning akinesia, dyskinesia, and bodily discomfort were underrecognized by physicians.