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BACKGROUND: Tailoring effective strategies for cancer pain management requires a careful analysis of multiple factors that influence pain phenomena and, ultimately, guide the therapy. While there is a wealth of research on automatic pain assessment (APA), its integration with clinical data remains inadequately explored. This study aimed to address the potential correlations between subjective and APA-derived objectives variables in a cohort of cancer patients. METHODS: A multidimensional statistical approach was employed. Demographic, clinical, and pain-related variables were examined. Objective measures included electrodermal activity (EDA) and electrocardiogram (ECG) signals. Sensitivity analysis, multiple factorial analysis (MFA), hierarchical clustering on principal components (HCPC), and multivariable regression were used for data analysis. RESULTS: The study analyzed data from 64 cancer patients. MFA revealed correlations between pain intensity, type, Eastern Cooperative Oncology Group Performance status (ECOG), opioids, and metastases. Clustering identified three distinct patient groups based on pain characteristics, treatments, and ECOG. Multivariable regression analysis showed associations between pain intensity, ECOG, type of breakthrough cancer pain, and opioid dosages. The analyses failed to find a correlation between subjective and objective pain variables. CONCLUSIONS: The reported pain perception is unrelated to the objective variables of APA. An in-depth investigation of APA is required to understand the variables to be studied, the operational modalities, and above all, strategies for appropriate integration with data obtained from self-reporting. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number (NCT04726228), registered 27 January 2021, https://classic. CLINICALTRIALS: gov/ct2/show/NCT04726228?term=nct04726228&draw=2&rank=1.
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Dolor en Cáncer , Dimensión del Dolor , Humanos , Masculino , Femenino , Dolor en Cáncer/diagnóstico , Persona de Mediana Edad , Dimensión del Dolor/métodos , Anciano , Adulto , Respuesta Galvánica de la Piel/fisiología , Electrocardiografía/métodos , Anciano de 80 o más Años , Manejo del Dolor/métodos , Manejo del Dolor/normas , Estudios de CohortesRESUMEN
Background and objectives: Healthcare-associated infections (HCAIs) pose a significant challenge, impacting patient safety and treatment effectiveness. This retrospective study investigates the correlation between pre-operative hospital stays and HCAIs in ICU cardiac surgery patients. Materials and methods: Medical records of 35 patients who died post-cardiac surgery in the ICU were analyzed, focusing on the duration of pre-operative hospitalization. Results: Prolonged pre-operative stays strongly correlate (r = 0.993) with increased HCAIs, indicating a critical risk factor. Conclusions: The duration of pre-operative hospital stays is pivotal in HCAI risk. Prospective multicenter studies are needed for validation, which is crucial for enhancing patient safety and treatment efficacy.
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INTRODUCTION: Cardiac arrest (CA) is the third leading cause of death, with persistently low survival rates despite medical advancements. This article evaluates the potential of emerging technologies to enhance CA management over the next decade, using predictions from the AI tools ChatGPT-4 and Gemini Advanced. METHODS: We conducted an exploratory literature review to envision the future of cardiopulmonary arrest (CA) management. Utilizing ChatGPT-4 and Gemini Advanced, we predicted implementation timelines for innovations in early recognition, CPR, defibrillation, and post-resuscitation care. We also consulted the AI to assess the consistency and reproducibility of the predictions. RESULTS: We extrapolate that healthcare may embrace new technologies, such as comprehensive monitoring of vital signs to activate the emergency system (wireless detectors, smart speakers, and wearable devices), use new innovative early CPR and early AED devices (robot CPR, wearable AEDs, and immersive reality), and post-resuscitation care monitoring (brain-computer interface). These technologies could enhance timely life-saving interventions for cardiac arrest. However, there are many ethical and practical challenges, particularly in maintaining patient privacy and equity. The two AI tools made different predictions, with a horizon for implementation ranging between three and eight years. CONCLUSION: Integrating advanced monitoring technologies and AI-driven tools offers hope in improving CA management. A balanced approach involving rigorous scientific validation and ethical oversight is necessary. Collaboration among technologists, medical professionals, ethicists, and policymakers is crucial to use these innovations ethically to reduce CA incidence and enhance outcomes. Further research is needed to enhance the reliability of AI predictive capabilities.
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Reanimación Cardiopulmonar , Paro Cardíaco , Humanos , Reanimación Cardiopulmonar/métodos , Reanimación Cardiopulmonar/instrumentación , Paro Cardíaco/terapia , Invenciones , Predicción , Inteligencia Artificial , DesfibriladoresRESUMEN
Aims: This study delves into the two-year opioid prescription trends in the Local Sanitary Agency Naples 3 South, Campania Region, Italy. The research aims to elucidate prescribing patterns, demographics, and dosage categories within a population representing 1.7% of the national total. Perspectives on artificial intelligence research are discussed. Methods: From the original dataset, spanning from January 2022 to October 2023, we processed multiple variables including demographic data, medications, dosages, drug consumption, and administration routes. The dispensing quantity was calculated as defined daily doses (DDD). Results: The analysis reveals a conservative approach to opioid therapy. In subjects under the age of 20, prescriptions accounted for 2.1% in 2022 and declined to 1.4% in 2023. The drug combination paracetamol/codeine was the most frequently prescribed, followed by tapentadol. Approximately two-thirds of the consumption pertains to oral formulations. Transdermal formulations were 15% (fentanyl 9.8%, buprenorphine 5.1%) in 2022; and 16.6% (fentanyl 10%, buprenorphine 6.6%) in 2023. These data were confirmed by the DDD analysis. The trend analysis demonstrated a significant reduction ( p < 0.001) in the number of prescribed opioids from 2022 to 2023 in adults (40-69 years). The study of rapid-onset opioids (ROOs), drugs specifically used for breakthrough cancer pain, showed higher dosage (>267 mcg) consumption among women, whereas a lower dosage (<133 mcg) was calculated for men. Fentanyl pectin nasal spray accounted for approximately one-fifth of all ROOs. Conclusion: Despite limitations, the study provides valuable insights into prescribing practices involving an important study population. The findings underscore the need for tailored approaches to prescribing practices, recognizing the complexities of pain management in different contexts. This research can contribute to the ongoing discourse on opioid use, advocating for innovative strategies that optimize therapeutic outcomes while mitigating potential risks.
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Isquemia Encefálica , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Isquemia Encefálica/prevención & control , Isquemia Encefálica/tratamiento farmacológicoRESUMEN
BACKGROUND: In the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies. METHODS: A panel of multidisciplinary experts defined clinical phenotypes, treatments and outcomes of greater interest in the field of adjunctive therapies for sepsis and septic shock. After an extensive systematic literature review, the appropriateness of each treatment for each clinical phenotype was determined using the modified RAND/UCLA appropriateness method. RESULTS: The consensus identified two distinct clinical phenotypes: patients with overwhelming shock and patients with immune paralysis. Six different adjunctive treatments were considered the most frequently used and promising: (i) corticosteroids, (ii) blood purification, (iii) immunoglobulins, (iv) granulocyte/monocyte colony-stimulating factor and (v) specific immune therapy (i.e. interferon-gamma, IL7 and AntiPD1). Agreement was achieved in 70% of the 25 clinical questions. CONCLUSIONS: Although clinical evidence is lacking, adjunctive therapies are often employed in the treatment of sepsis. To address this gap in knowledge, a panel of national experts has provided a structured consensus on the appropriate use of these treatments in clinical practice.
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Within the domain of Natural Language Processing (NLP), Large Language Models (LLMs) represent sophisticated models engineered to comprehend, generate, and manipulate text resembling human language on an extensive scale. They are transformer-based deep learning architectures, obtained through the scaling of model size, pretraining of corpora, and computational resources. The potential healthcare applications of these models primarily involve chatbots and interaction systems for clinical documentation management, and medical literature summarization (Biomedical NLP). The challenge in this field lies in the research for applications in diagnostic and clinical decision support, as well as patient triage. Therefore, LLMs can be used for multiple tasks within patient care, research, and education. Throughout 2023, there has been an escalation in the release of LLMs, some of which are applicable in the healthcare domain. This remarkable output is largely the effect of the customization of pre-trained models for applications like chatbots, virtual assistants, or any system requiring human-like conversational engagement. As healthcare professionals, we recognize the imperative to stay at the forefront of knowledge. However, keeping abreast of the rapid evolution of this technology is practically unattainable, and, above all, understanding its potential applications and limitations remains a subject of ongoing debate. Consequently, this article aims to provide a succinct overview of the recently released LLMs, emphasizing their potential use in the field of medicine. Perspectives for a more extensive range of safe and effective applications are also discussed. The upcoming evolutionary leap involves the transition from an AI-powered model primarily designed for answering medical questions to a more versatile and practical tool for healthcare providers such as generalist biomedical AI systems for multimodal-based calibrated decision-making processes. On the other hand, the development of more accurate virtual clinical partners could enhance patient engagement, offering personalized support, and improving chronic disease management.
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Comunicación , Lenguaje , Humanos , Documentación , Escolaridad , Suministros de Energía EléctricaRESUMEN
PURPOSE OF REVIEW: Increased public awareness of ethical issues in pain and palliative care, along with patient advocacy groups, put pressure on healthcare systems and professionals to address these concerns.Our aim is to review the ethics dilemmas concerning palliative care in ICU, artificial intelligence applications in pain therapy and palliative care, and the opioids epidemics. RECENT FINDINGS: In this focus review, we highlighted state of the art papers that were published in the last 18âmonths, on ethical issues in palliative care within the ICU, artificial intelligence trajectories, and how opioids epidemics has impacted pain management practices (see Visual Abstract). SUMMARY: Palliative care in the ICU should involve a multidisciplinary team, to mitigate patients suffering and futility. Providing spiritual support in the ICU is an important aspect of holistic patient care too.Increasingly sophisticated tools for diagnosing and treating pain, as those involving artificial intelligence, might favour disparities in access, cause informed consent problems, and surely, they need prudence and reproducibility.Pain clinicians worldwide continue to face the ethical dilemma of prescribing opioids for patients with chronic noncancer pain. Balancing the need for effective pain relief with the risk of opioid misuse, addiction, and overdose is a very controversial task.
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Analgésicos Opioides , Dolor Crónico , Humanos , Analgésicos Opioides/efectos adversos , Inteligencia Artificial , Reproducibilidad de los Resultados , Dolor Crónico/tratamiento farmacológico , Cuidados Paliativos/métodosRESUMEN
BACKGROUND: Despite being a useful strategy for providing respiratory support to patients with advanced or terminal illnesses, non-invasive ventilation (NIV) requires in-depth investigation in several key aspects. OBJECTIVES: This bibliometric analysis seeks to comprehensively examine the existing research on the subject. Its goal is to uncover valuable insights that can inform the prediction trajectory of studies, guide the implementation of corrective measures, and contribute to the improvement of research networks. METHODS: A comprehensive review of literature on NIV in the context of palliative care was conducted using the Web of Science core collection online database. The search utilized the key terms "non-invasive ventilation" and "palliative care" to identify the most relevant articles. All data were gathered on November 7, 2023. Relevant information from documents meeting the specified criteria was extracted, and Journal Citation Reports™ 2022 (Clarivate Analytics) served as the data source. The analysis employed literature analysis and knowledge visualization tools, specifically CiteScope (version 6.2.R4) and VOSviewer (version 1.6.20). RESULTS: A dataset with bibliometric findings from 192 items was analyzed. We found a consistent upward of the scientific output trend over time. Guidelines on amyotrophic lateral sclerosis management received the highest number of citations. Most documents were published in top-ranked journals. Less than one-third of the documents pertain to clinical studies, especially retrospective analyses (25%). Key topics such as "decision making", and "communication" were less addressed. CONCLUSIONS: Given the substantial clinical implications, further high-quality studies on this subject are recommended. Encouraging international collaborations is needed. Despite the growing volume of documents in the field, this bibliometric analysis indicates a decline in collaborative networks.
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INTRODUCTION: Nirmatrelvir/ritonavir (Paxlovid®) represent an oral antiviral therapy approved for the treatment of COVID-19. Extensive in vitro and in vivo studies have reported the promising activity of nirmatrelvir/ritonavir against numerous emerging viruses. This combination consists of nirmatrelvir, a protease reversible inhibitor of coronavirus 3CLpro mainly metabolized by cytochrome P450 (CYP)3A4, and ritonavir, an inhibitor of the CYP3A isoforms that enhances the efficacy of nirmatrelvir by fixing its suboptimal pharmacokinetic properties. AREAS COVERED: This review comprehensively examines the efficacy of nirmatrelvir/ritonavir through rigorous analysis of in vitro and in vivo studies. Moreover, it thoroughly assesses its safety, tolerability, pharmacokinetics, and antiviral efficacy against SARS-COV-2 infection, based on the main pre-authorization randomized controlled trials. EXPERT OPINION: Nirmatrelvir/ritonavir has a good tolerability profile. Its administration during the early stages of mild-to-moderate COVID-19 holds potential benefits, as it can help prevent the onset of an aberrant immune response that could lead to pulmonary and extra-pulmonary complications. However, its drug - drug interactions can be a factor limiting its use, at least in populations on some chronic therapies, along with the risk of infection relapse after treatment.
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COVID-19 , SARS-CoV-2 , Humanos , Ritonavir/efectos adversos , Tratamiento Farmacológico de COVID-19 , Antivirales/efectos adversosRESUMEN
Pain is an unpleasant sensory and emotional experience that affects every aspect of a patient's life and which may be treated through different pharmacological and non-pharmacological approaches. Analgesics are the drugs most commonly used to treat pain, and in specific situations, the use of opioids may be considered with caution. These drugs, in fact, do not always induce optimal analgesia in patients, and several problems are associated with their use. The purpose of this narrative review is to describe the pharmacological approaches currently used for the management of chronic pain. We review several aspects, from the pain-scale-based methods currently available to assess the type and intensity of pain, to the most frequently administered drugs (non-narcotic analgesics and narcotic analgesics), whose pharmacological characteristics are briefly reported. Overall, we attempt to provide an overview of different pharmacological treatments while also illustrating the relevant guidelines and indications. We then report the strategies that may be used to reduce problems related to opioid use. Specifically, we focus our attention on therapeutic drug monitoring (TDM), a tool that could help clinicians select the most suitable drug and dose to be used for each patient. The actual potential of using TDM to optimize and personalize opioid-based pain treatments is finally discussed based on recent scientific reports.
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The existing literature indicates that Globularia alypum L. (GA) influences inflammation and oxidative stress modulation in rats and in vitro. The present study aims to investigate the effects of this plant in patients with ulcerative colitis (UC) and normal controls. In our experiments, we pretreated colon biopsies from 46 UC patients and normal controls with GA leaves aqueous extract (GAAE) used at two concentrations (50 and 100 µg/mL) for 3 h, followed by Lipopolysaccharides (from Escherichia coli) stimulation. We analyzed the effects on inflammation by studying the cyclo-oxygenase-2, the intercellular adhesion molecule-1, the nuclear factor kappa B, and p38 mitogen-activated protein kinase expression. Moreover, we assessed the levels of interleukin 6, the superoxide dismutase activity, and nitric oxide release in the supernatant of cultures. Our data showed that GAAE influences UC patients and normal controls for most studied markers and enzymes. These results acknowledge, with some scientific evidence, the traditional belief in the anti-inflammatory properties of GA and represent the first demonstration of its effect in a human in vitro model of inflammatory conditions.
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Colitis Ulcerosa , Humanos , Ratas , Animales , Colitis Ulcerosa/metabolismo , Colon/metabolismo , FN-kappa B/metabolismo , Biopsia , Inflamación/metabolismoRESUMEN
Remdesivir (RDV) is a broad-spectrum antiviral drug, now approved by Regulatory Agencies for COVID-19 treatment. RDV is associated with improvements in clinical outcomes, but no conclusive studies have shown an effect in reducing mortality. This study aimed to carry out a systematic review with meta-analysis to investigate whether RDV can significantly modify the outcome of COVID-19 patients evaluating its effects on mortality, length of stay, time to clinical improvement and need for oxygen supplementation. No significant improvement in terms of survival in patients treated with standard therapy (ST)+RDV as compared to ST alone (P = 0.24) was found. The duration of oxygen support was significantly lower in patients treated with ST + RDV compared with ST alone (P = 0.03). Further investigations should be planned to assess the real impact of RDV in the management of COVID-19 patients.
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COVID-19 , Humanos , Tratamiento Farmacológico de COVID-19 , Antivirales/uso terapéuticoRESUMEN
The aim of this retrospective multicenter observational study is to test the feasibility and safety of a combined extracorporeal CO 2 removal (ECCO 2 R) plus renal replacement therapy (RRT) system to use an ultraprotective ventilator setting while maintaining (1) an effective support of renal function and (2) values of pH within the physiologic limits in a cohort of coronavirus infectious disease 2019 (COVID-19) patients. Among COVID-19 patients admitted to the intensive care unit of 9 participating hospitals, 27 patients with acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) requiring invasive mechanical ventilation undergoing ECCO 2 R-plus-RRT treatment were included in the analysis. The treatment allowed to reduce V T from 6.0 ± 0.6 mL/kg at baseline to 4.8 ± 0.8, 4.6 ± 1.0, and 4.3 ± 0.3 mL/kg, driving pressure (ΔP) from 19.8 ± 2.5 cm H 2 O to 14.8 ± 3.6, 14.38 ± 4.1 and 10.2 ± 1.6 cm H 2 O after 24 hours, 48 hours, and at discontinuation of ECCO 2 R-plus-RRT (T3), respectively ( p < 0.001). PaCO 2 and pH remained stable. Plasma creatinine decreased over the study period from 3.30 ± 1.27 to 1.90 ± 1.30 and 1.27 ± 0.90 mg/dL after 24 and 48 hours of treatment, respectively ( p < 0.01). No patient-related events associated with the extracorporeal system were reported. These data show that in patients with COVID-19-induced ARDS and AKI, ECCO 2 R-plus-RRT is effective in allowing ultraprotective ventilator settings while maintaining an effective support of renal function and values of pH within physiologic limits.
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Lesión Renal Aguda , COVID-19 , Enfermedades Transmisibles , Síndrome de Dificultad Respiratoria , Humanos , Respiración Artificial , COVID-19/complicaciones , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/complicaciones , Terapia de Reemplazo Renal , Enfermedades Transmisibles/complicaciones , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , PulmónRESUMEN
INTRODUCTION: Molnupiravir (MOV) is a broad-spectrum oral antiviral agent approved for the treatment of COVID-19. The results from in vitro and in vivo studies suggested MOV activity against many RNA viruses such as influenza virus and some alphaviruses agents of epidemic encephalitis. MOV is a prodrug metabolized into the ribonucleoside analog ß-D-N4-hydroxycytidine. It is incorporated into the viral RNA chain causing mutations impairing coding activity of the virus, thereby inhibiting viral replication. AREAS COVERED: This review analyzes the in vitro and in vivo studies that have highlighted the efficacy of MOV and the main pre-authorization randomized controlled trials evaluating its safety, tolerability, and pharmacokinetics, as well as its antiviral efficacy against SARS-COV-2 infection. EXPERT OPINION: MOV is an antiviral agent with an excellent tolerability profile with few drug-drug interactions. Treatment of mild-to-moderate COVID-19 can benefit from MOV administration in the precocious phases of the disease, prior to the trigger of an aberrant immune response responsible for the parenchymal damage to pulmonary and extrapulmonary tissues. However, its suspected mutagenic effect can be a factor limiting its use at least in selected populations and studies on its teratogen effects should be planned before it is authorized for use in the pediatric population or in pregnant women.
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COVID-19 , Niño , Femenino , Humanos , Embarazo , SARS-CoV-2 , Hidroxilaminas , Antivirales/efectos adversosRESUMEN
The Acute Respiratory Distress Syndrome (ARDS) is a common, devastating clinical pattern characterized by life-threatening respiratory failure. In ARDS there is an uncontrolled inflammatory response that results in alveolar damage, with the exudation of protein-rich pulmonary-edema fluid in the alveolar space. Although severe COVID-19 lung failure (CARDS) often meets diagnostic criteria of traditional ARDS, additional features have been reported, such as delayed onset, binary pulmonary compliant states, and hypercoagulable profile. Increased levels of Krebs von den Lungen 6 (KL-6, also known as MUC1) have been reported in both ARDS and CARDS. KL-6 is a transmembrane protein expressed on the apical membrane of most mucosal epithelial cells and it plays a critical role in lining the airway lumen. Abnormalities in mucus production contribute to severe pulmonary complications and death from respiratory failure in patients with diseases such as cystic fibrosis, chronic obstructive pulmonary disease, and acute lung injury due to viral pathogens. Nevertheless, it is not clear what role KL-6 plays in ARDS/CARDS pathophysiology. KL-6 may exert anti-inflammatory effects through the intracellular segment, as proven in animal models of ARDS, while its extracellular segment will enter the blood circulation through the alveolar space when the alveolar epithelial cells are damaged. Therefore, changes in plasma KL-6 levels may be useful in ARDS and CARDS phenotyping, and KL-6 might guide future clinical trials in 'personalized medicine' settings.
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Antimicrobial resistance represents a serious threat for global health, causing an unacceptable burden in terms of morbidity, mortality and healthcare costs. In particular, in 2017, carbapenem-resistant organisms were listed by the WHO among the group of pathogens for which novel treatment strategies are urgently needed. Fortunately, several drugs and combinations have been introduced in recent years to treat multi-drug-resistant (MDR) bacteria. However, a correct use of these molecules is needed to preserve their efficacy. In the present paper, we will provide an overview on the epidemiology and mechanisms of resistance of the most common MDR Gram-negative bacteria, proposing a treatment algorithm for the management of infections due to carbapenem-resistant bacteria based on the most recent clinical evidence.