Innovative clinical trial designs, such as adaptive and Bayesian methodologies, have gained traction as solutions to the challenges of traditional trials, including their high costs and complex regulations. When they adhere to relevant ethical and regulatory requirements, these designs can improve efficiency, flexibility, and ethical standards. However, their application outside of oncology, particularly in fields such as neuroscience and rare diseases, remains underexplored. We analyzed data from ClinicalTrials.gov for interventional trials registered between 2005 and 2024. The trials were classified as innovative or traditional using a keyword-based algorithm. Therapeutic areas were identified using a large language model (LLM), with classification accuracy evaluated using a random sample of 2,000 trials. Of the 348,818 trials, 5827 were classified as innovative, with prevalence in neuroscience and rare diseases. These designs were predominantly observed in early-phase trials and pediatric research, with limited representation in elderly-focused or sex-specific studies. Innovative trial adoption has grown since 2011, spurred by regulatory advancements and increased funding from scientific networks and the National Institutes of Health. Survival analysis revealed that innovative trials tend to remain active for longer than traditional trials; however, this trend varies across different medical disciplines. LLM demonstrated a classification accuracy of 94.6% (95%CI = 93.6%-95.5%), supporting its utility for trial categorization. The rise in innovative clinical trial designs reflects a shift toward addressing complex challenges in neuroscience, rare diseases, and other therapeutic areas. Although these designs show promise in improving trial efficiency and patient outcomes, their success depends on rigorous planning and adherence to regulatory standards. Advancing LLM-based tools can further optimize clinical trial monitoring by tailoring research in trial settings and therapeutic fields.

Background: Palliative care is essential in intensive care, improving symptom control, quality of life, and reducing hospital stays without increasing mortality. However, early identification of patients who could benefit remains a major challenge. This study aimed to evaluate the NECesidades PALiativas (NECPAL) tool’s effectiveness in identifying ICU patients in Italy with PC needs. Methods: This prospective observational study was conducted from March 2024 to February 2025. Adult ICU patients (≥18 years), admitted for at least 24 h and meeting NECPAL eligibility criteria (e.g., cancer, COPD, heart failure, dementia, and frailty), were evaluated using the NECPAL tool. Results: A total of 85 patients were enrolled; 28 (32.9%) were classified as NECPAL-positive and 57 (67.1%) as NECPAL-negative. NECPAL-positive patients had a significantly higher ICU mortality rate (32.1%) compared to NECPAL-negative patients (1.8%) (p < 0.001). The median ICU length of stay was slightly longer for NECPAL-positive patients [11.0 days (IQR: 8.0–16.2)] versus NECPAL-negative patients [10.0 days (IQR: 5.0–14.0)], though not statistically significant. Multivariable Firth penalized logistic regression confirmed NECPAL positivity as an independent predictor of ICU mortality (OR 19.55; 95% CI: 3.06–124.93; p < 0.001). Conclusions: In this study, NECPAL identified about one-third of ICU patients as having palliative care needs, who also showed a higher mortality risk. Integration with ICU severity scores may improve early recognition of these needs, warranting validation in larger multicenter studies.

Background/Objectives: Alternative Tobacco and Nicotine Products (ATNPs) have gained widespread popularity. Although they are often promoted as lower-risk alternatives to traditional tobacco products, concerns remain regarding their association with risky behaviors among adolescents and young adults. This study examines the relationship between dietary and lifestyle habits and both ATNP use and intention to use ATNP among Italian participants in the MINERVA (My changINg lifEstyles our Research and eVeryone heAlth) international project. Methods: MINERVA is an observational, international, prospective cohort study. A study-specific questionnaire was administered to participants, who were recruited through informal snowball sampling. The questionnaire collected information on sociodemographic characteristics, lifestyle factors, dietary habits, and the use of both traditional tobacco products and ATNPs. Predictors of ATNP use and intention to use were assessed using logistic regression models. Results: Data from 7535 Italian participants were analyzed. Overall, 48% reported having ever used ATNP, and 14% of non-smokers and non-users expressed an intention to try these products. Significant predictors of ATNP use and intention to use included prior smoking, lower age, and having family members who smoke. Lifestyle factors such as frequent consumption of fast food, junk food, and alcoholic beverages were positively associated with both ATNP use and intention to use. Conversely, daily fruit and vegetable consumption was inversely associated with these outcomes. Conclusions: ATNP use and intention to use were associated with unhealthy dietary and lifestyle patterns. These findings highlight the importance of integrated public health strategies addressing substance use alongside broader lifestyle behaviors among adolescents and young adults.

Objective: This study examines how the choice of non-inferiority margins affects the clinical interpretation of interventional studies using the Santos et al. trial comparing high-flow nasal cannula (HFNC) with non-invasive ventilation (NIV) as a case example. We also demonstrate how Bayesian reanalysis improves interpretability by expressing non-inferiority margins on absolute and relative scales, quantifying posterior probabilities of non-inferiority and benefit, and translating these margins into patient-centred measures such as the Number Needed to Harm (NNH). Design: Secondary Bayesian reanalysis of a previously published randomised controlled trial. Setting: Multicentre paediatric intensive care units participating in the original Santos et al. study. Patients: Infants with acute bronchiolitis were randomised to receive either HFNC or NIV. Interventions: Respiratory support via HFNC or NIV. Main Outcome Measures: The primary endpoint was intubation, with the intubation rate reported as a descriptive summary statistic. We re-expressed the original non-inferiority margin on the Absolute Risk Reduction (ARR) and Odds Ratio (OR) scales, estimated Bayesian probabilities of non-inferiority and benefit, and derived patient-centred metrics such as the NNH. Results: The original analysis concluded non-inferiority using a fixed absolute margin. Our Bayesian reanalysis showed that this margin could correspond to a substantial relative tolerance when baseline risks are low; specifically, the 0.15 non-inferiority ARR margin might imply a doubling of the odds of intubation. When interpreted from a patient-centered perspective, this margin corresponds to an NNH of approximately 6.7. In other words, for every seven infants treated with HFNC instead of NIV, one additional child might require intubation who would not have needed it under standard care. Conclusions: Non-inferiority margins are typically derived through a combination of statistical evidence and clinical judgment. However, their interpretation may vary depending on the effect scale used, and this may not always be transparent in reporting. For this reason, integrating Bayesian methods and framing multiple noninferiority definitions improves the interpretability of trials.

Obstructive Sleep Apnea (OSA) is associated with several comorbidities, including renal dysfunction, which may improve with C-PAP therapy. Sleep fragmentation and nocturnal hypoxia in OSA have been hypothesized to contribute to carcinogenesis, particularly affecting hypoxia-sensitive urinary tract cells. The aim of the present study was to assess cancer prevalence in OSA patients and explore clinical profiles of those with urinary tract cancer. We retrospectively analyzed 50 OSA patients with cancer from the Vercelli Hospital Registry. Cancer diagnoses were collected at the time of OSA diagnosis, prior to C-PAP initiation. 70% of patients were male. Among OSA-cancer patients, 34% had urinary tract cancer (88% males, p<0.05), followed by breast (14%), colorectal (12%), lung (10%), laryngeal and skin (8%), intracranial (6%), hematologic and parotid (4%), and others (2%). 10% had multiple cancer sites. Hierarchical clustering revealed a distinct profile: urinary tract cancer associated with better respiratory indices, frequent hypertension and higher C-PAP compliance. Our findings show a higher prevalence of urinary tract cancer in male OSA patients, suggesting a possible link between OSA-related hypoxia and carcinogenesis. This supports increased clinical surveillance and further research into whether OSA is a modifiable cancer risk factor. PAP therapy may offer protective benefits.

Background: Obstructive sleep apnea (OSA) is recognized as a systemic disorder associated with several comorbidities, including renal dysfunction, which may improve with continuous positive airway pressure (C-PAP) therapy. Sleep fragmentation and nocturnal hypoxia characteristic of OSA have been implicated in carcinogenesis, particularly affecting hypoxia-sensitive urinary tract tissues. This study aimed to assess the prevalence of different cancer types among patients with concurrent OSA and malignancy and to characterize the clinical profiles of those with urinary tract cancer. Methods: We retrospectively analyzed 50 patients with both OSA and cancer from the Vercelli Hospital Registry. Cancer diagnoses were collected at the time of OSA diagnosis, prior to C-PAP initiation. Results: Among the cohort (70% males) of OSA-cancer patients, urinary tract cancers were the most frequent (34%), followed by breast (14%), colorectal (12%), lung (10%), laryngeal and skin (8%), intracranial (6%), hematologic and parotid (4%), and other cancers (2%); 10% had multiple cancer sites. Patients with urinary tract cancer were mainly male (88%, p = 0.0043) and displayed better respiratory indices, frequent hypertension, and higher C-PAP adherence. Conclusions: These findings suggest a possible link between OSA-related hypoxia and carcinogenesis in urinary tract tissues and support increased clinical surveillance and further research to determine potential protective effects of C-PAP therapy.