Clinical trials

The CAFIB trial is a multicenter, randomized, open-label, crossover clinical trial designed to determine whether habitual caffeine consumption in coffe adversely affects rate control in patients with permanent atrial fibrillation (AF). The rationale stems from the discrepancy between traditional clinical recommendations, which often advise patients with arrhythmias to avoid caffeine, and the growing body of evidence suggesting that moderate coffee consumption is not associated with an increased risk of AF and may even confer cardiovascular benefits. However, no randomized study has specifically investigated this issue in patients with permanent AF, a population in whom rate control remains the cornerstone of management. The primary hypothesis is that continued moderate caffeine consumption is non-inferior to caffeine abstinence regarding 24-hour mean heart rate control. Participants will be randomly assigned in a 1:1 ratio to one of two treatment sequences stratified according to baseline coffee intake (1 cup/day vs. \>1 cup/day). Owing to the nature of the intervention, the study is open-label; nevertheless, Holter recordings will be analyzed by blinded investigators, and the statistical analysis will also be performed blinded to treatment allocation to minimize bias. Eligible participants are adults with permanent AF diagnosed for more than three months, stable ventricular rate control (\<110 bpm at rest), unchanged rate-control medication for at least two months, and habitual coffee consumption of at least one caffeinated cup per day. Patients with advanced heart failure, recent major cardiovascular events, cognitive impairment, implanted cardiac pacing devices, or other conditions likely to interfere with study outcomes are excluded. The intervention compares two dietary strategies: continuation of regular caffeinated coffee consumption (at least one cup daily) versus complete caffeine abstinence, while allowing decaffeinated coffee. Energy drinks are prohibited in both groups, and participants assigned to abstinence are advised to avoid compensatory caffeine intake from other sources. No washout period is planned between crossover phases because caffeine has a biological half-life of less than 24 hours. Adherence will be assessed using caffeine consumption diaries and structured interviews at each study visit. The primary endpoint s the 24-hour mean heart rate measured by ambulatory Holter electrocardiography. Secondary endpoints include changes in mean HR from baseline, percentage of time with HR \>110 bpm or \<50 bpm, ventricular ectopic burden, symptom severity assessed using the modified EHRA classification, quality of life evaluated with the AFEQT questionnaire, circulating biomarkers of heart failure, adverse events, and changes in concomitant medical therapy. Patients will undergo three scheduled visits (baseline, 30 days, and 60 days), each including clinical assessment, ECG, 24-hour Holter monitoring, blood sampling, and quality-of-life questionnaires. Sample size calculation was based on detecting a clinically relevant difference of 5 bpm, assuming a standard deviation of 7 bpm, 80% statistical power, and a two-sided α of 0.05. After accounting for an anticipated 25% dropout rate and potential protocol deviations, a total of 50 patients (25 per treatment sequence) will be recruited. The primary analysis will follow the intention-to-treat principle, complemented by a per-protocol analysis. Statistical models will adjust for clinically relevant covariates, including age, sex, baseline heart rate, and concomitant rate-control therapy, while multivariable regression analyses will explore predictors of optimal heart rate control. The protocol acknowledges several limitations, including its open-label design, reliance on self-reported caffeine intake to assess adherence, interindividual variability in caffeine metabolism, and limited external validity to stable, habitual coffee consumers with permanent AF. Despite these limitations, CAFIB represents the first randomized trial specifically evaluating the impact of caffeine consumption on ventricular rate control in permanent AF.

An effective implementation of an exercise programme such as VIVIFRAIL, in an unsupervised mode, requires a careful consideration of the patient's motivational traits and state, and the adaptation of the interventions to the current stage in the behaviour change process, as critical countermeasures to fight against abandonment and lack of compliance. A computational ecosystem with motivational support, and functional and performance assessment for an autonomous exercise programme will improve the robust and prefrail community-dwelling older adults' independence and their physical and cognitive health, while reducing healthcare utilisation.

The intensive care units is of the main components of modern healthcare systems. Formally, its aim is to offer the critically ill health care fit to their needs; ensuring that this health care is appropriate, sustainable, ethical and respectful of their autonomy. Intensive medicine is a cross-sectional specialty that encompasses a broad spectrum of pathologies in their most severe condition, and specifically has as its foundation the practice of comprehensive care of the patient with organ dysfunction and susceptible to recovery. Although critically ill patients are a heterogeneous population, they have in common the need for a high level of care, often requiring the use of high technology, specific procedures for the support of organ dysfunction and the collaboration of other medical and surgical specialties for their management and treatment. Since their origins in the late 1950s, intensive care units have been adapting to the changes arising from the best scientific evidence. In the late 1990s and early 2000s, there were some successful clinical trials published that had tested alternative management strategies in the ICU. Mechanical ventilation is an intervention that defines the critical care specialty. Between 1970 and the 1990s, the management focused on normalizing arterial blood gas with aggressive mechanical ventilation. Over the ensuing decades, it became apparent that performing positive pressure ventilation worsened lung injury. The pivotal moment in the mechanical ventilation story would be the low versus high tidal volume trial. This trial shifted the focus away from normalizing gas exchange to reducing harm with mechanical ventilation. Further, it paved way for further trials testing ventilation interventions (PEEP strategy, prone position ventilation) and nonventilation interventions (neuromuscular blockade, corticosteroids, inhaled nitric oxide, extracorporeal gas exchange) in critically ill patients. That evidence-based intensive care medicine has undoubtedly had an influence on the outcome of critically ill patients, in general, and, particularly, of patients requiring mechanical ventilation. Temporal changes in mortality over the time have been scarcely reported for patients admitted to intensive care unit. Objective of this study is to estimate the changes over the time in several outcomes in the patients admitted to an 18-beds medical-surgical intensive care unit from 1991 (year of start of activity) to 2026